Real-time monitoring of peptic and tryptic digestions of immunoglobulin G and the impact of dietary hydrocolloids on digestion.

Immunoglobulin G (IgG) exhibits potent antiviral, antibacterial, and immunological activities. The digestion process and bioavailability of IgG are often a concern. Dietary hydrocolloids are crucial for regulating healthy digestion and the bioavailability of protein as functional components.

Marchaetoglobins A-D: Four Cytochalasans with Proangiogenic Activity from the Marine-Sponge-Associated Fungus 162105.

Four new cytochalasans, marchaetoglobins A-D (), along with five known compounds (), were isolated from the marine-sponge-associated fungus 162105. Compounds represent examples of 19,20--chaetoglobosins, of which compound is the first furan-containing cytochalasan. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and electronic circular dichroism calculations.

Traditional Chinese Medicine Shi-Bi-Man ameliorates psoriasis via inhibiting IL-23/Th17 axis and CXCL16-mediated endothelial activation.

Background: Psoriasis is a chronic inflammatory genetic disease, mainly manifesting in the skin. Conventional therapies, such as glucocorticosteroids and corticosteroids, have adverse effects that limit drug use. Hence, it is imperative to identify a new therapeutic strategy that exhibits a favorable safety profile.

Molecular basis of an atypical dsDNA 5mC/6mA bifunctional dioxygenase CcTet from Coprinopsis cinerea in catalyzing dsDNA 5mC demethylation.

The eukaryotic epigenetic modifications 5-methyldeoxycytosine (5mC) and N6-methyldeoxyadenine (6mA) have indispensable regulatory roles in gene expression and embryonic development. We recently identified an atypical bifunctional dioxygenase CcTet from Coprinopsis cinerea that works on both 5mC and 6mA demethylation. The nonconserved residues Gly331 and Asp337 of CcTet facilitate 6mA accommodation, while D337F unexpectedly abolishes 5mC oxidation activity without interfering 6mA demethylation, indicating a prominent distinct but unclear 5mC oxidation mechanism to the conventional Tet enzymes.

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from , as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/-catenin pathway.

α-Acyloxylation of Ketones/Cyclic Ethers Mediated by Hypervalent Iodine(III) Reagents as Oxidants and Nucleophilic Sources.

This study describes a catalyst-free α-acyloxylation of ketones and a KBr-mediated α-acyloxylation of cyclic ethers. These conversions are effectively mediated by hypervalent iodine(III) reagents serving dual roles as the oxidant and nucleophilic source. Consequently, esters are produced directly in moderate to excellent yields.

The Molecular Basis of Human ALKBH3 Mediated RNA N -methyladenosine (m A) Demethylation.

N -methyladenosine (m A) is a prevalent post-transcriptional RNA modification, and the distribution and dynamics of the modification play key epitranscriptomic roles in cell development. At present, the human AlkB Fe(II)/α-ketoglutarate-dependent dioxygenase family member ALKBH3 is the only known mRNA m A demethylase, but its catalytic mechanism remains unclear. Here, we present the structures of ALKBH3-oligo crosslinked complexes obtained with the assistance of a synthetic antibody crystallization chaperone.

Access to Chromenopyrrolidines Enabled by Organophotocatalyzed [2 + 2 + 1] Annulation of Chromones with -Arylglycines.

A facile approach toward chromenopyrrolidines was achieved under mild conditions via organophotocatalyzed aerobic decarboxylative [2 + 2 + 1] annulation of chromones with -arylglycines, in which -arylglycines perform dual roles (i.e., radical precursor and methylene provider).

The Molecular Basis of Catalysis by SDR Family Members Ketoacyl-ACP Reductase FabG and Enoyl-ACP Reductase FabI in Type-II Fatty Acid Biosynthesis.

The short-chain dehydrogenase/reductase (SDR) superfamily members acyl-ACP reductases FabG and FabI are indispensable core enzymatic modules and catalytic orientation controllers in type-II fatty acid biosynthesis. Herein, we report their distinct substrate allosteric recognition and enantioselective reduction mechanisms. FabG achieves allosteric regulation of ACP and NADPH through ACP binding across two adjacent FabG monomers, while FabI follows an irreversible compulsory order of substrate binding in that NADH binding must precede that of ACP on a discrete FabI monomer.

Revealing the aging process of solid electrolyte interphase on SiO anode.

As one of the most promising alternatives to graphite negative electrodes, silicon oxide (SiO) has been hindered by its fast capacity fading. Solid electrolyte interphase (SEI) aging on silicon SiO has been recognized as the most critical yet least understood facet. Herein, leveraging 3D focused ion beam-scanning electron microscopy (FIB-SEM) tomographic imaging, we reveal an exceptionally characteristic SEI microstructure with an incompact inner region and a dense outer region, which overturns the prevailing belief that SEIs are homogeneous structure and reveals the SEI evolution process.

Lewis Base-Catalyzed Intramolecular Vinylogous Aldol Reaction and Chemoselective Syntheses of 3-Hydroxy-2,3-Disubstituted Dihydrobenzofurans and Indolines.

A Lewis base-catalyzed intramolecular vinylogous aldol reaction of -(allyloxy)phenyl ketoesters or -(allylamino)phenyl ketoesters has been developed. This reaction provides ready access to 3-hydroxy-2,3-disubstituted dihydrobenzofurans and indolines in high yields with excellent chemoselectivity and diastereoselectivity. An acid-promoted dehydration of such products further extends the utility of the reaction to the synthesis of 2-alkenyl benzofurans and indoles.

A decade update on the application of β-oxodithioesters in heterocyclic synthesis.

The diverse synthesis of heterocyclic compounds has always been one of the popular subjects of organic chemistry. To this end, great efforts have been devoted to developing new reagents and establishing new strategies and methods concerning efficiency, selectivity and sustainability. β-Oxodithioesters and their enol tautomers (, α-enolic dithioesters), as a class of simple and readily accessible sulfur-containing synthons, have been widely applied in the construction of various five- and six-membered heterocycles (, thiophenes, thiopyrans, thiazoles, pyridines and quinolines) and other useful open-chain frameworks.

Copper-Catalyzed Enantioconvergent Radical C(sp)-N Cross-Coupling of Activated Racemic Alkyl Halides with (Hetero)aromatic Amines under Ambient Conditions.

The enantioconvergent C(sp)-N cross-coupling of racemic alkyl halides with (hetero)aromatic amines represents an ideal means to afford enantioenriched -alkyl (hetero)aromatic amines yet has remained unexplored due to the catalyst poisoning specifically for strong-coordinating heteroaromatic amines. Here, we demonstrate a copper-catalyzed enantioconvergent radical C(sp)-N cross-coupling of activated racemic alkyl halides with (hetero)aromatic amines under ambient conditions. The key to success is the judicious selection of appropriate multidentate anionic ligands through readily fine-tuning both electronic and steric properties for the formation of a stable and rigid chelating Cu complex.

Catalyst-free inverse-electron-demand aza-Diels-Alder reaction of 4,4-dicyano-2-methylenebut-3-enoates and 1,3,5-triazinanes: access to polysubstituted tetrahydropyridines.

An inverse-electron-demand aza-Diels-Alder reaction between 4,4-dicyano-2-methylenebut-3-enoates and 1,3,5-triazinanes under catalyst-free and additive-free conditions was developed, which provided a highly convenient and straightforward method to construct a series of polyfunctionalized tetrahydropyridines in high yields. This strategy features numerous advantages, including high efficiency, good functional group tolerance, broad substrate scope, and environmentally friendly conditions.

Redox switching mechanism of the adenosine 5'-phosphosulfate kinase domain (APSK2) of human PAPS synthase 2.

Adenosine 5'-phosphosulfate kinase (APSK) catalyzes the rate-limiting biosynthetic step of the universal sulfuryl donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS). In higher eukaryotes, the APSK and ATP sulfurylase (ATPS) domains are fused in a single chain. Humans have two bifunctional PAPS synthetase isoforms: PAPSS1 with the APSK1 domain and PAPSS2 containing the APSK2 domain.

Divergent Total Syntheses of (-)-Daphnezomines A and B and (+)-Dapholdhamine B.

The daphnezomine A-type subfamily of Daphniphyllum alkaloids structurally features a unique aza-adamantane core skeleton and anticipates efficient strategies for completing their syntheses to thoroughly investigate their biological activities. Herein, divergent total syntheses of (-)-daphnezomines A and B and (+)-dapholdhamine B have been accomplished in 16-20 steps from a known epoxide via rapid construction of a common core intermediate. The present work features a Ti-mediated radical cyclization to establish the azabicyclo[3.

Fluorescent cellulose nanocrystals/waterborne polyurethane nanocomposites for anti-counterfeiting applications.

The development of eco-friendly anti-counterfeiting materials with high optical transparency and bright luminescence in the aggregate state is tremendously challenging. Herein, waterborne polyurethane/tetraphenylethylene-cellulose nanocrystal (WPU/TPE-CNC) nanocomposite aqueous solutions and films were prepared direct blending aggregation-induced emission (AIE) active fluorescent CNCs (TPE-CNCs) with WPU and then applied in the anti-counterfeiting field. TPE-CNCs are compatible with WPU and dispersed homogeneously in the nanocomposite aqueous solutions and films.

Purine metabolites promote ectopic new bone formation in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that mainly affects the axial skeleton, whose typical features are inflammatory back pain, bone structural damage and pathological new bone formation. The pathology of ectopic new bone formation is still little known. In this study, we found increased purine metabolites in plasma of patients with AS.

Adipokine chemerin overexpression in trophoblasts leads to dyslipidemia in pregnant mice: implications for preeclampsia.

Background: The adipokine chemerin regulates adipogenesis and the metabolic function of both adipocytes and liver. Chemerin is elevated in preeclamptic women, and overexpression of chemerin in placental trophoblasts induces preeclampsia-like symptoms in mice. Preeclampsia is known to be accompanied by dyslipidemia, albeit via unknown mechanisms.

New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs.

Recent advances in photochemical construction of aromatic C-P bonds C-hetero bond cleavage.

Photochemical synthesis is flourishing in recent years, which has provided new and efficient methods for aromatic C-P bond formation. This review summarises the recent advances in photochemical C-P bond cross-couplings in aromatics, enriching the synthetic methods of phosphorus containing compounds. Photosensitizer-catalyzed and photosensitizer-free reactions are reviewed.

Amorphous Solid Dispersions: Role of the Polymer and Its Importance in Physical Stability and In Vitro Performance.

Amorphous solid dispersions stabilized by one or more polymer(s) have been widely used for delivering amorphous drugs with poor water solubilities, and they have gained great market success. Polymer selection is important for preparing robust amorphous solid dispersions, and considerations should be given as to how the critical attributes of a polymer can enhance the physical stability, and the in vitro and in vivo performances of a drug. This article provides a comprehensive overview for recent developments in the understanding the role of polymers in amorphous solid dispersions from the aspects of nucleation, crystal growth, overall crystallization, miscibility, phase separation, dissolution, and supersaturation.

Asymmetric Total Synthesis of (+)-Alstonlarsine A.

The first asymmetric total synthesis of (+)-alstonlarsine A has been realized. The prominent features of the current synthesis include the following: (i) a Pd/self-adaptable ligand complex-catalyzed asymmetric allylic alkylation of 2-methyl-2-cyclopentenyl carbonate with 2-indolylsubstituted dimethyl malonate to establish the key stereocenter of C15, (ii) an intramolecular nitrile oxide-alkene [3 + 2] cycloaddition (INOC [3 + 2]) to construct the cyclohepta[]indole backbone with the installment of the requisite stereochemistry of the all-carbon quaternary center of C20, and (iii) a late-stage Pictet-Spengler reaction (IPSR) to rapidly assemble the core structure of (+)-alstonlarsine A.

Asymmetric Total Syntheses of Cephalotane-Type Diterpenoids Cephanolides A-D.

Cephanolides A-D are cephalotane-type diterpenoids featuring a novel 6/6/6/5 tetracyclic core embedded with a bridged δ-lactone. The asymmetric and divergent total syntheses of cephanolides A-D have been accomplished, proceeding in 11-14 steps from a known alcohol. The salient features of the present work include (i) a substrate-controlled diastereoselective intermolecular Diels-Alder reaction to form the 6-6 -fused rings, (ii) a palladium-catalyzed formal bimolecular [2 + 2 + 2] cycloaddition reaction via a partially intermolecular cascade reaction sequence involving multiple carbometalations to rapidly install the key tetracyclic skeleton, and (iii) lactonization and late-stage oxidative diversification to complete total syntheses of the four benzenoid cephanolides.

DNA-Mediated Assembly of Carbon Nanomaterials.

Carbon nanomaterials (CNMs) have attracted extensive attentions on account of their superior electrical, mechanical, optical, and biological properties. However, the dimensional limit and irregular arrangement have hampered their further application. It is necessary to find an easy, efficient and controllable way to assemble CNMs into well-ordered array.