Riboflavin 2',3',4',5'-tetraacetate (RFTA) is a classic enzyme-mimetic photocatalyst that has demonstrated excellent catalytic performance in various oxidation reactions. In this study, we found that RFTA, in the presence of visible light and oxygen, can promote the cleavage of C(sp3)-N bonds and achieve one-pot oxidative amidation to construct 3,4-dihydroisoquinolin-1(2H)-one, a heterocyclic core widely present in many bioactive molecules, with a yield of 72%. The reaction proceeds smoothly at room temperature and atmospheric pressure under 520 nm light irradiation using N-benzyl-1,2,3,4-tetrahydroisoquinoline as the substrate, without the need for precious metals, stoichiometric oxidants, or added bases, and is operationally simple. Preliminary mechanistic studies suggest that the reaction may first undergo single-electron transfer (SET), followed by a light-induced proton-coupled electron transfer (PCET) process, which cooperatively achieves the selective cleavage of the C(sp3)-N bond and the site-specific oxidation of the C(sp3)-H bond, thereby obtaining high chemical selectivity. Although this method still has certain limitations, we hope that this initial exploration can provide a useful supplement to the application of RFTA in biomimetic photocatalysis and offer a mild and practical new strategy for the synthesis of dihydroisoquinolinone skeletons with drug value.

Ligand-to-metal charge transfer (LMCT) photocatalysis has emerged as a transformative strategy in synthetic organic chemistry. This review summaries the synergistic integration of photoinduced LMCT processes with earth-abundant transition-metal catalysis, highlighting a sustainable paradigm that addresses longstanding challenges in organic synthesis. Unlike traditional photoredox systems that rely on expensive noble metal (such as ruthenium and iridium) complexes, LMCT photocatalysis utilizes complexes formed between organic ligands and first-row transition metals (iron, copper, cobalt, and lanthanide cerium), which generate reactive radical intermediates under mild conditions upon visible light irradiation. The combination of LMCT photocatalysis with transition-metal catalysis creates powerful dual platforms that enable challenging transformations by merging radical-generating capabilities with the coordination and bond-forming abilities of nickel, copper, cobalt, manganese, chromium, and titanium catalysts. These systems operate through sophisticated mechanisms where photogenerated radical species interact with transition metal centers to access novel reaction pathways inaccessible to either catalytic system alone. This review analyzes recent developments in dual LMCT/transitionmetal catalytic systems, examining their mechanisms, substrate scope, functional group compatibility, and synthetic utility. We highlight how these sustainable catalytic platforms have enabled challenging cross-coupling reactions, C-H functionalizations, and cascade transformations under remarkably mild conditions. Finally, we discuss current limitations and opportunities in this rapidly evolving field, with particular emphasis on expanding reaction scope, enhancing stereoselectivity, and advancing green chemistry principles.

ABSTRACT As one of the cornerstones of modern organic synthesis, the Tsuji–Trost reaction is fundamentally governed by the “hard–soft” characteristics of nucleophiles, which confine nitroalkanes as “soft” pronucleophiles to classical outer‐sphere substitution pathway. Here we report a palladium‐catalyzed fluoroallylic alkylation of secondary nitroalkanes with gem ‐difluorocyclopropanes that overturns this long standing reactivity paradigm by enabling their engagement through an inner‐sphere pathway. This strategy enables the switchable regiodivergence between linear and branched allylic nitroalkanes—an outcome unattainable under classical Tsuji–Trost conditions and unprecedented for secondary nitroalkanes. This method exhibits excellent functional‐group and heterocycle tolerance and is readily applicable to the late‐stage modification of structurally complex bioactive molecules. Moreover, its synthetic utility has been further highlighted by various downstream derivatizations of the resulting 2‐fluoroallylic α ‐tertiary nitroalkanes. DFT studies indicate that ligand‐controlled oxygen coordination to electrophilic fluoro‐π‐allyl–Pd intermediates enables an inner‐sphere 3,3'‐reductive elimination, thereby accounting for the excellent regioselectivity in C(sp 3 )–C(sp 3 ) bond formation.

We present a mild and efficient method for the arylation of N-H heteroarenes using a low-loading Pd/keYPhos catalyst (0.8 mol%). This approach employs inexpensive and structurally diverse aryl chlorides as electrophiles in reactions with indoles, pyrroles, and carbazole, enabling the construction of a wide range of N-arylated products. The method exhibits excellent functional group tolerance and is suitable for gram-scale synthesis. Furthermore, the relatively inert Ar-Cl bond allows for late-stage functionalization of pharmaceuticals and stepwise coupling reactions, providing a complementary strategy for the N-arylation of N-H heteroarenes.

A general method for accessing α,β-unsaturated ketones through visible-light or sunlight photoredox-catalyzed β-selective acylation of alkenes has been developed.

Objective:Mitophagy is a critical defense mechanism against metabolic dysfunction-associated steatotic liver disease. MRPL44, a mitochondrial ribosomal protein that regulates mitochondrial DNA-encoded gene expression, has not previously been linked to lipid metabolism. Methods:This study employed an oleic acid/palmitic acid induced HepG2 cell models and a high-fat diet fed mouse models, combined with lentivirus-mediated MRPL44 overexpression and mitophagy assays, to investigate the regulatory role of MRPL44 in the progression of metabolic dysfunction-associated steatotic liver disease. Results:Our findings demonstrated that MRPL44 alleviates lipid metabolic disorders induced by high-fat diet through the mitophagy pathway. Specifically, in oleic acid/palmitic acid-stimulated HepG2 cells, overexpression of MRPL44 reduced intracellular triglyceride accumulation and enhanced fatty acid oxidation. Moreover, liver-specific overexpression of MRPL44 in mice attenuated high-fat diet induced hepatic lipid deposition. Mechanistically, MRPL44 activated the BNIP3-dependent mitophagy pathway, promoted mitochondrial biogenesis, and mitigated mitochondrial damage, ultimately reducing lipid accumulation in hepatocytes. Conclusion:This study identifies MRPL44 as a novel regulator of lipid metabolism and a potential therapeutic target for metabolic dysfunction-associated steatotic liver disease.

A general method for accessing β-diketones through visible-light or sunlight photoredox-catalyzed radical acylation of enol silyl ethers has been developed.

Demethylation of N6-Methyladenosine (m6A) by fat mass and obesity-associated protein (FTO) occurs in the development of obesity and fatty liver disease. In this study, we synthesized FTO-degradation targeted chimera (FTO-DT), which exhibited excellent lipid-lowering activity at low concentration. At a concentration of 0.33 nM, the FTO-DT continuously and efficiently degraded FTO protein and reduced fat deposition. The FTO-DT improved energy metabolism and oxidative stress by increasing intracellular m6A levels, and further reduced fat deposition in hepatocytes, adipocytes, and mice fed a high-fat diet. The findings support the potential of FTO degradation by FTO-DT as a therapy for obesity and metabolic-associated fatty liver disease (MAFLD). This study provides a theoretical basis for the application of PROTACs in the treatment of metabolic disease and describes a novel approach for the development of drugs targeting metabolic disorders.

IMF (Intramuscular fat) content is a crucial indicator of meat quality in the livestock industry. However, the molecular mechanisms underlying IMF deposition remain unclear in pigs. In this study, we conducted RNC-seq (ribosome nascent-chain complex-bound RNA sequencing) and RNA-seq (RNA sequencing) analyses on the longissimus dorsi muscle of Duroc pigs (a lean breed) and Luchuan pigs (a fat breed) to uncover the genetic basis for the divergent IMF content. The results show that the overall translation level of Luchuan pigs is significantly higher than Duroc pigs, while there is no significant difference in the transcription level. Enzymes related to fatty acid synthesis and elongation, such as ACACA, FASN, and ELOVL5, are significantly up-regulated at the translation level, while enzymes associated with fatty acid degradation, namely ALDH1B1 and ALDH2, are significantly down-regulated. However, there is no significant difference in their transcription levels. qRT-PCR and Western Blotting experiments for ELOVL5 confirm the reliability of the sequencing results. Additionally, the translation initiation factor eIF4A1, known to positively regulate gene translation, displayed higher expression in Luchuan pigs rather than in Duroc pigs and the 5'UTR structural features of genes involved in translation up-regulation matched the mRNA selectivity of eIF4A1. In conclusion, these findings suggest the up-regulation of the eIF4A1 gene expression in Luchuan pigs may elevate the translation levels of genes related to lipid synthesis through translational regulation, further resulting in an increase in IMF content.

A step-economic method for C2-arylated azoles via Pd-catalyzed denitrative arylation of nitroarenes and azoles is reported. This protocol employs synthetically upstream nitroarenes as arylating reagents and proceeds through the selective cleavage of the C-NO2 and C-H bonds. Various nitroarenes and nitroheteroarenes were coupled with oxazoles, benzoxazoles, and methylbenzimidazoles, achieving yields of up to 95%. The method's utility is exemplified by its application in the synthesis of Flunoxaprofen. This strategy reduces synthetic steps and minimizes pollution, offering substantial cost-effectiveness and environmental benefits. Furthermore, the relatively inert C-NO2 bond in nitroarenes enables late-stage functionalization or stepwise coupling reactions, providing a complementary method for C2-arylation of azoles.

Metabolic-associated fatty liver disease (MAFLD), a major consequence of obesity and metabolic dysfunction, lacks effective treatments. The cAMP/PKA signaling pathway regulates lipid metabolism, and inhibition of its upstream target PDE4D alleviates MAFLD progression. Linarin, a natural flavonoid glycoside with hepatoprotective properties, remains underexplored for MAFLD mechanisms. To investigate linarin's therapeutic effects on high-fat diet (HFD)-induced MAFLD and elucidate its mechanisms, focusing on PDE4D inhibition and cAMP/PKA/CREB pathway activation. C57BL/6J mice were fed a normal diet (CON), high fat diet (HFD), HFD + 50 mg/kg linarin, and HFD + 100 mg/kg linarin. Oleic/palmitic acid-stimulated HepG2, Mouse primary cells and AML12 cells were used. In vitro, 25 μM linarin reduced intracellular triglycerides (TG), elevated ATP production, decreased ROS and MDA, and upregulated GSH and CAT. In vivo, 50 and 100 mg/kg linarin suppressed weight gain, reduced hepatic fat deposition, and improved insulin sensitivity and liver function. Mechanistically, linarin inhibits PDE4D activity, activates the cAMP/PKA/CREB pathway, and upregulates GPX4 expression. Linarin alleviates MAFLD by targeting PDE4D to activate the cAMP/PKA/CREB pathway, improving lipid metabolism, mitochondrial function, and oxidative stress. This study highlights the potential of natural compounds for metabolic disease intervention, providing a foundation for clinical translation.

N-arylated heterocycles are a significant class of core scaffolds in medicinal chemistry, materials science, and agrochemistry, highlighting their importance in various fields. The development of innovative methodologies for synthesizing these fundamental structures has been a central focus in organic synthesis. Over the past few decades, numerous approaches have been established to synthesize N-aryl heterocycles efficiently. Among these methods, the direct N-arylation of N-H heterocycles stands out as one of the most straightforward and robust strategies for accessing N-arylated heterocycles. This review provides a comprehensive review of the recent advances in the synthesis of N-arylated heterocycles, encompassing the relevant literature from the past decade. The review summarizes the N-arylation of N-H heterocycles using various catalytic systems, including palladium, nickel, copper, visible light-induced metal-catalyzed, and metal-free catalyzed methodologies. These advances highlighted the continuous evolution and optimization of synthetic strategies to create diverse and complex N-arylated heterocycles, which are pivotal for furthering research and development in multiple scientific domains.

A straightforward and efficient method has been developed for the transformation of aromatic CAr-H bond into CAr-NH2 via nickel-mediated C-H activation, eliminating the need for additional protection and deprotection steps. This strategy employs 8-aminoquinoline as a directing group and urea as the nitrogen source, a non-toxic, inexpensive, and stable bulk chemical. The reaction exhibits high selectivity, exclusively yielding mono-aminated primary aromatic amines. Furthermore, the protocol is tolerant of a wide range of substrates with various functional groups, producing the corresponding ortho-aminobenzamides in yields ranging from 38 % to 73 %. The preliminary results indicate the C-H bond cleavage is likely the rate-determining step in the reaction.

Decatungstate (DT) is a highly promising photocatalyst for dioxygen (O2)-based reactions but has hardly been applied in the photocatalytic degradation technology of dye. Here, we synthesized hydrophilic DT–SO3H salts by incorporating tetra-alkyl cations with sulfonic acid groups, aiming to enhance both the water solubility and catalytic efficiency of DT under visible light. Comprehensive characterization of DT–SO3H using ultraviolet–visible spectroscopy (UV–Vis), Fourier Transform Infrared Spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Photocurrent (PTC), and Electrochemical Impedance Spectroscopy (EIS) confirmed its improved properties. DT–SO3H demonstrated outstanding photocatalytic performance, achieving 90% degradation of methyl orange within 25 min under continuous visible light irradiation. This study presents a cost-effective and efficient method for degrading methyl orange, representing a significant advancement in the development of high-performance photocatalysts and opening new avenues for the study and application of photocatalytic dye degradation technologies.

Metabolic-associated fatty liver disease (MAFLD) has become increasingly widespread. The intestine is the primary site of lipid absorption and is important for the homeostasis of lipid metabolism. However, the mechanism underlying the participation of the intestinal tract in the development of MAFLD requires additional investigation. In this study, analysis of the single-cell transcriptome of intestinal tissue from cynomolgus monkeys found that hepatic leukemia factor (HLF) participated in the genetic regulation of intestinal lipid absorption. Results obtained from normal and intestine-specific Hlf-knockout mice confirmed that HLF alleviated intestinal barrier disorders by inhibiting peroxisome proliferator-activated receptor alpha (PPARα) expression. The HLF/PPARα axis alleviated MAFLD by mediating gut microbiota-derived extracellular vesicles (fEVs), thereby inhibiting hepatocyte ferroptosis. Lipidomics and functional experiments verified that taurochenodeoxycholic acid (TCDCA), a conjugated bile acid contained in the fEVs, had a key role in the process. In conclusion, intestinal HLF activity was mediated by fEVs and identified as a novel therapeutic target for MAFLD.

Background:Traumatic cerebral edema(TCE)is a life-threatening condition caused by excessive fluid accumulation in the brain,leading to elevated intracranial pressure and potential brain damage.Current treatments,including osmotic diuretics and antihypertensive medications,have limitations.Zhenwu Decoction,a traditional Chinese medicine formulation,has shown promise due to its multi-target pharmacological effects,including modulation of inflammation and regulation of aquaporins.Methods:Active components and targets of Zhenwu Decoction were identified using databases such as SymMap and TCMID.Protein-protein interaction networks and gene expression data related to toxic chemical exposure were analyzed through the GEO database and gene set enrichment analysis.Weighted gene co-expression network analysis(WGCNA)was used to identify TCE-associated gene modules.Molecular docking and in vivo validation using a traumatic brain injury model were conducted.Results:A total of 880 active components and 235 potential targets of Zhenwu Decoction were identified.Protein-protein interaction network analysis and WGCNA revealed key gene modules and inflammatory response-related DEGs.Molecular docking suggested lactiflorin and poricoic acid A as potential drug candidates targeting ATP2A2 and ATP2C1.Experimental results confirmed that Zhenwu Decoction improved TCE outcomes by upregulating these proteins.Conclusion:This study provides molecular evidence for the efficacy of Zhenwu Decoction in treating TCE,highlighting its mechanisms.The integration of WGCNA and molecular docking offers new insights into drug development and precision medicine for TCE.

The functionalization of the C-Cl bond in unactivated aryl chlorides under mild conditions presents a significant challenge. We disclose a general protocol for constructing both partially and entirely unsymmetrical tertiary phosphines through the Pd/keYPhos-catalyzed coupling of aryl chlorides with secondary phosphines under mild conditions. The reaction exhibits excellent functional group tolerance and broad substrate scopes. Furthermore, the rapid synthesis of ligands and luminescent compound sTPPs, alongside gram-scale systhesis, demonstrates the practical applicability of this method.

An efficient one-pot direct dihydroxylation of alkenes has been achieved. This reaction proceeds under transition-metal-free conditions and in water solution, producing the corresponding 1,2-diols in good to excellent yields. The discovery of an optimal pH environment is identified as a key factor in the current system, which ensures the generality and good functional group compatibility of this reaction. Moreover, the gram-scale dihydroxylation of alkenes was demonstrated and without significant decrease of the yield of product, making this protocol very practical.

BackgroundNardosinone, a major extract of Rhizoma nardostachyos, plays a vital role in sedation, neural stem cell proliferation, and protection of the heart muscle. However, the huge potential of nardosinone in regulating lipid metabolism and gut microbiota has not been reported, and its potential mechanism has not been studied.PurposeTo explore the regulation of nardosinone on liver lipid metabolism and gut microbiota.MethodsIn this study, the role of nardosinone in lipid metabolism was investigated in vitro and in vivo by adding it to mouse feed and HepG2 cell culture medium. And 16S rRNA gene sequencing was used to explore its regulatory effect on gut microbiota.ResultsResults showed that nardosinone could improve HFD-induced liver injury and abnormal lipid metabolism by promoting mitochondrial energy metabolism in hepatocytes, alleviating oxidative stress damage, and regulating the composition of the gut microbiota. Mechanistically, combined with network pharmacology and reverse docking analysis, it was predicted that CYP2D6 was the target of nardosinone, and the binding was verified by cellular thermal shift assay (CETSA).ConclusionsThis study highlights a novel mechanism function of nardosinone in regulating lipid metabolism and gut microbiota. It also predicts and validates CYP2D6 as a previously unknown regulatory target, which provides new possibilities for the application of nardosinone and the treatment of metabolic-associated fatty liver disease.

Decatungstate ((nBu4N)4W10O32, marked as DTs) and PMo12-nVn could be easily synthesized via polymerization in acidic aqueous solution. They can efficiently catalyze the oxidation of cyclohexane to afford cyclohexanone and cyclohexanol under visible light, affording about 30