Radical-triggered translocation of C-C double bond and functional group.

Multi-site functionalization of molecules provides a potent approach to accessing intricate compounds. However, simultaneous functionalization of the reactive site and the inert remote C(sp3)-H poses a formidable challenge, as chemical reactions conventionally occur at the most active site. In addition, achieving precise control over site selectivity for remote C(sp3)-H activation presents an additional hurdle. Here we report an alternative modular method for alkene difunctionalization, encompassing radical-triggered translocation of functional groups and remote C(sp3)-H desaturation via photo/cobalt dual catalysis. By systematically combining radical addition, functional group migration and cobalt-promoted hydrogen atom transfer, we successfully effectuate the translocation of the carbon-carbon double bond and another functional group with precise site selectivity and remarkable E/Z selectivity. This redox-neutral approach shows good compatibility with diverse fluoroalkyl and sulfonyl radical precursors, enabling the migration of benzoyloxy, acetoxy, formyl, cyano and heteroaryl groups. This protocol offers a resolution for the simultaneous transformation of manifold sites.

Cobalt-catalyzed conformationally restricted alkylarylation enables divergent access to Csp3-rich N-heterocycles.

Due to the intrinsic spatial orientation and structural novelty, Csp3-rich N-heterocycles have been recognized as increasingly sought-after scaffolds as compared to the aromatic ring-based moieties, which have generated considerable recent attention in drug discovery. Hence, we disclose a modular cobalt-catalyzed conformationally restricted alkylarylation strategy for the divergent access to Csp3-rich N-hetero(spiro)cycles. Herein, multiple effects, including radical rebound and conformational restriction, play critical roles in the stabilization of the stereospecific alkyl-cobalt-aryl intermediate. Under simple and mild reaction conditions, cobalt catalyst combines a range of polyfunctionalized cyclenyl bromides and organozinc pivalates to rapidly and reliably forge the architecturally complex Csp3-rich N-hetero(spiro)cycles (>70 examples, >20 : 1 dr), including but not limited to the [5,5]-, [5,6]-, [5,7]-, [5,12]-bicycles, tri- and tetracyclic N-heterocycles, as well as various novel N-heterospirocyclic scaffolds in one synthetic operation. Preliminary kinetic investigations suggested that the final reductive elimination might be the rate-determining step. Moreover, ample substrate scope, good functional group compatibility and facile derivatizations to the pharmaceutically active molecules show the potential applications of this technology to organic syntheses and drug discoveries in medicinal chemistry.

Metal-support interaction in supported Pt single-atom catalyst promotes lattice oxygen activation to achieve complete oxidation of acetone at low concentrations.

A precious metal catalyst with loaded Pt single atoms was prepared and used for the complete oxidation of C3H6O. Detailed results show that the T100 of the 1.5Pt SA/γ-Al2O3 catalyst in the oxidation process of acetone is 250 °C, the TOF of Pt is 1.09 × 10-2 s-1, and the catalyst exhibits good stability. Characterization reveals that the high dispersion of Pt single atoms and strong interaction with the carrier improve the redox properties of the catalyst, enhancing the adsorption and dissociation capability of gaseous oxygen. DFT calculations show that after the introduction of Pt, the oxygen vacancy formation energy on the catalyst surface is reduced to 1.2 eV, and PDOS calculations prove that electrons on Pt atoms can be quickly transferred to O atoms, increasing the number of electrons on the σp * bond and promoting the escape of lattice oxygen. In addition, in situ DRIFTS and adsorption experiments indicate that the C3H6O oxidation process follows the Mars-van Krevelen reaction mechanism, and CH2 =C(CH3)=O(ads), O* (O2-), formate, acetate, and carbonate are considered as the main intermediate species and/or transients in the reaction process. Particularly, the activation rate of O2 and the cleavage of the -C-C- bond are the main rate-determining steps in the oxidation of C3H6O. This work will further enhance the study of the oxidation mechanism of oxygenated volatile organic pollutants over loaded noble metal catalysts.

Benzvalene-like Carboranes: Genuine Rule Breakers and Good Kinetic Stability.

Substituents are widespread in chemistry, but it has remained quite difficult to reliably determine the thermodynamic and kinetic stabilities of substituted compounds, though they are key to helping establish a structural rule and synthetic viability, respectively. As an important class of valence isomers in the benzene family, benzvalene-like structures have been extensively studied in systems associated with electron-neutral (i.e., C, Si, Ge, Pb, and Sn) and electron-rich (e.g., P) skeletons. However, stable benzvalene-like examples associated with electron-deficient skeletons have been very limited, possibly due to the very complicated bonding patterns of electron-deficient elements. Here, we performed an extensive structural search at the density functional theory (DFT) and CBS-QB3 level for the well-known six-vertex dicarboranes (C2B4R6), one of the central families of boranes and carboranes chemistry. We unexpectedly found that all of the previously reported benzvalene-like structures III (C2B4R6) as the long-chased "rule breaker" examples of the Wade-Mingos rule (W-M rule) are not the lowest-lying structures. Promisingly, for the first time, we succeeded in identifying several substituted III as the genuine lowest-lying structures and thus true "rule breakers." Thus, "benzvalenes" present hitherto the fourth member of the lowest-lying structural patterns for the family of six-vertex dicarboranes. Moreover, the presently revealed good kinetic stability of III' (C2B4R2R'4) over a wide range of substituents promoted us to recommend a novel kind of synthesizable carboranes beyond the Wade-Mingos rule, i.e., "benzvalene-like carboranes" with all of the classical skeletal atoms.

[Quality identification of Aurantii Fructus Immaturus from different origins and their adulterants].

Aurantii Fructus Immaturus(AFI) is a traditional Chinese herbal medicine with multiple origins from Citrus aurantium and its legally cultivated variants. With advancements in agricultural biotechnology, many new cultivated varieties have sprung up,leading to an abundance of AFI adulterants and chaos in the herbal medicine markets. This study developed a specific identification method for AFI and its closely related adulterants by examining the appearance trait, content of extract, and multiple ingredients,involving indicators such as the ratio of pulp capsule to cross section diameter(Pc/Cs ratio), the content of extract, and the profile of 11 ingredients. The research finds that:(1) Pc/Cs ratio can conveniently identify adulterants such as Poncirus trifoliata, Ju, and Babagan from the genuine AFI.(2) The extract content can be used to identify adulterants originated from C. wilsonii with C. aurantium.(3) The contents of synephrine in all the samples were in accordance with the Chinese Pharmacopoeia except for the adulterants from P. trifoliata, C. wilsonii, C. aurantium 'Changshanhuyou' and orah mandarins. The synephrine content was high as 1. 40% in some C. sinensis varieties. The mass fraction of hesperidin was over 10. 00% in C. sinensis, while it was below 2. 50% in C. aurantium. C. aurantium contained high levels of naringin(3. 96%-15. 21%) and neo-hesperidin(9. 38%-21. 93%).(4) The compositions of adulterants from P. trifoliata and C. wilsonii were more similar to that of C. aurantium 'Daidai', but with significantly lower neo-hesperidin content(0. 03%-0. 14%) than that in C. aurantium, and they lacked hesperetin and tangeretin. C. maxima(originating from C. maxima) showed closer composition to Choucheng and hybrid originated from Citrus aurantium × Poncirus trifoliata, but had higher hesperidin content(3. 13%) than that in C. aurantium. Ju was closely related to C. sinensis and neither contained naringin nor neo-hesperidin. Hesperidins in Babagan and orah mandarins were similar to that in C. sinensis, with none containing rhoifolin. These quality indicators in combination can accurately distinguish between C. sinensis, C. aurantium, and their closely related adulterants(P. trifoliata, C. wilsonii, C. maxima, orah mandarins and C. reticulata), which are expected to provide a systematic method for quality control of AFI.

Performance studies of an ultrafast gamma Cherenkov imaging Screen based on Silica fibers array.

High-energy gamma rays produced in inertial confinement fusion (ICF) experiments are crucial for studying implosion dynamics. These gamma rays, characterized by their extremely short durations, represent the least disturbed products of fusion, preserving vital birth information. To detect such γ-rays, ultrafast radiation detectors with high time resolution are necessary. This study introduces a newly developed Cherenkov optical image screen designed for ultra-fast gamma-ray imaging. Composed of pure quartz fiber material, the imaging screen features a single fiber pixel size of 0.6 mm and a thickness of 3 cm. Theoretical investigations explore the luminous time response and efficiency of the Cherenkov optical imaging screen under gamma-ray irradiation. Experimental validation was conducted using a steady-state gamma-ray source with an average energy of 1.25 MeV. Results demonstrate that the image screen achieves a spatial resolution limit of 0.75 mm. The temporal response exhibits a full width at half maximum of less than 0.4 ns when excited by a high-energy electron beam with a single pulse duration of several picoseconds.

Natural products modulate phthalate-associated miRNAs and targets.

Phthalates are widespread and commonly used plasticizers that lead to adverse health effects. Several natural products provide a protective effect against phthalates. Moreover, microRNAs (miRNAs) are regulated by natural products and phthalates. Therefore, miRNAs' impacts and potential targets may underlie the mechanism of phthalates. However, the relationship between phthalate-modulated miRNAs and phthalate protectors derived from natural products is poorly understood and requires further supporting information. In this paper, we review the adverse effects and potential targets of phthalates on reproductive systems as well as cancer and non-cancer responses. Information on natural products that attenuate the adverse effects of phthalates is retrieved through a search of Google Scholar and the miRDB database. Moreover, information on miRNAs that are upregulated or downregulated in response to phthalates is collected, along with their potential targets. The interplay between phthalate-modulated miRNAs and natural products is established. Overall, this review proposes a straightforward pathway showing how phthalates modulate different miRNAs and targets and cause adverse effects, which are partly attenuated by several natural products, thereby providing a direction for investigating the natural product-miRNA-target axis against phthalate-induced effects.

Alterations in liver triglyceride profiles in CCl4-induced liver regeneration.

Lipid metabolism, particularly triglyceride (TG) metabolism, is crucial for liver regeneration. During the early phase of liver regeneration, the liver temporarily accumulates a substantial amount of TG-dominated lipids. However, the specific composition of the TG profile during this phase is not yet fully understood. Here, we showed that the TG molecular composition in the liver was significantly altered during liver regeneration following carbon tetrachloride (CCl4)-induced liver injury. Lipid accumulation in livers was observed as early as 12 hours after CCl4 treatment, with transient regeneration-associated steatosis (TRAS) lasting until 24 hours. Hepatocyte proliferation began only after liver lipid levels returned to baseline at 48 hours. Furthermore, the profile of TG species changed significantly during liver regeneration. During the TRAS period, the accumulated TGs in the liver were mainly long-chain triglycerides, with most of the fatty acids constituting these triglycerides having fewer than 20 carbon atoms. In the proliferation phase, the fatty acid composition of these triglycerides shifted from long-chain to ultra-long-chain fatty acids. Our results suggest a significant TRAS-related change in the TG lipid profile of the liver during liver regeneration.

Fine-tuning of IPA1 transactivation activity by E3 ligase IPI7-mediated non-proteolytic K29-ubiquitination during Magnaporthe oryzae infection.

The Ideal Plant Architecture 1 (IPA1) transcription factor promotes rice yield and immunity through phosphorylation at its amino acid residue Ser163 as a switch. Although phosphorylated IPA1 mimic, IPA1(S163D), directly targets the promoter of immune response gene WRKY45, it cannot activate its expression. Here, we identified a co-activator of IPA1(S163D), a RING-finger E3 ligase IPA1 interactor 7 (IPI7), which fine-tunes the transcriptional activity of IPA1 to timely promote plant immunity and simultaneously maintain growth for yield. IPI7 interacts with IPA1 and promotes K29-polyubiquitination of IPA1 in vitro and in vivo. However, the stability of IPA1 protein is not affected by IPI7-mediated ubiquitination. The IPI7-promoted K29-polyubiquitination of IPA1 is induced by Magnaporthe oryzae infection and required for phosphorylated IPA1 to transactivate WRKY45 expression for immune response but not for plain IPA1 to transactivate DENSE AND ERECT PANICLES 1 (DEP1) expression for panicle development. IPI7 knockout impairs IPA1-mediated immunity but not yield. Our study reveals that plants utilize non-proteolytic K29-ubiquitination as a response to pathogen infection to fine-tune IPA1 transactivation activity for promoting immunity.

[dvances in the diagnosis and treatment of necrozoospermia].

Necrozoospermia is a special type of asthenospermia, in which mass sperm death is commonly seen, with an incidence rate of 0.2%－0.4%. Studies on necrospermia are rarely reported. Its etiology is complicated, and its diagnosis and treatment are very difficult. This article focuses on the main etiological factors, pathophysiological mechanism, diagnostic methods and treatment strategies of necrospermia, aiming to provide some reference for andrologists and reproduction physicians, as well as a theoretical guidance for intracytoplasmic sperm injection (ICSI) in the treatment of the patients with necrospermia.

CytoCellDB: a comprehensive resource for exploring extrachromosomal DNA in cancer cell lines.

Recently, the cancer community has gained a heightened awareness of the roles of extrachromosomal DNA (ecDNA) in cancer proliferation, drug resistance and epigenetic remodeling. However, a hindrance to studying ecDNA is the lack of available cancer model systems that express ecDNA. Increasing our awareness of which model systems express ecDNA will advance our understanding of fundamental ecDNA biology and unlock a wealth of potential targeting strategies for ecDNA-driven cancers. To bridge this gap, we created CytoCellDB, a resource that provides karyotype annotations for cell lines within the Cancer Dependency Map (DepMap) and the Cancer Cell Line Encyclopedia (CCLE). We identify 139 cell lines that express ecDNA, a 200% increase from what is currently known. We expanded the total number of cancer cell lines with ecDNA annotations to 577, which is a 400% increase, covering 31% of cell lines in CCLE/DepMap. We experimentally validate several cell lines that we predict express ecDNA or homogeneous staining regions (HSRs). We demonstrate that CytoCellDB can be used to characterize aneuploidy alongside other molecular phenotypes, (gene essentialities, drug sensitivities, gene expression). We anticipate that CytoCellDB will advance cytogenomics research as well as provide insights into strategies for developing therapeutics that overcome ecDNA-driven drug resistance.

Effects of personalized music listening on post-stroke cognitive impairment: A randomized controlled trial.

BACKGROUND AND PURPOSE: Previous studies have suggested that music listening has the potential to positively affect cognitive functions and mood in individuals with post-stroke cognitive impairment (PSCI), with a preference for self-selected music likely to yield better outcomes. However, there is insufficient clinical evidence to suggest the use of music listening in routine rehabilitation care to treat PSCI. This randomized control trial (RCT) aims to investigate the effects of personalized music listening on mood improvement, activities of daily living (ADLs), and cognitive functions in individuals with PSCI. MATERIALS AND METHODS: A total of 34 patients with PSCI were randomly assigned to either the music group or the control group. Patients in the music group underwent a three-month personalized music-listening intervention. The intervention involved listening to a personalized playlist tailored to each individual's cultural, ethnic, and social background, life experiences, and personal music preferences. In contrast, the control group patients listened to white noise as a placebo. Cognitive function, neurological function, mood, and ADLs were assessed. RESULTS: After three months of treatment, the music group showed significantly higher Montreal Cognitive Assessment (MoCA) scores compared to the control group (p=0.027), particularly in the domains of delayed recall (p=0.019) and orientation (p=0.023). Moreover, the music group demonstrated significantly better scores in National Institutes of Health Stroke Scale (NIHSS) (p=0.008), Barthel Index (BI) (p=0.019), and Zarit Caregiver Burden Interview (ZBI) (p=0.008) compared to the control group. No effects were found on mood as measured by the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD). CONCLUSION: Personalized music listening promotes the recovery of cognitive and neurological functions, improves ADLs, and reduces caregiver burden in patients with PSCI.

KMT2D mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-induced regulatory T cell trafficking via FBXW7-NOTCH-MYC/TGF-ß1 axis.

Histone methyltransferase KMT2D is one of the most frequently mutated genes in diffuse large B-cell lymphoma (DLBCL) and has been identified as an important pathogenic factor and prognostic marker. However, the biological relevance of KMT2D mutations on tumor microenvironment remains to be determined. KMT2D mutations were assessed by whole-genome/exome sequencing (WGS/WES) in 334 patients and by targeted sequencing in 427 patients with newly diagnosed DLBCL. Among all 761 DLBCL patients, somatic mutations in KMT2D were observed in 143 (18.79%) patients and significantly associated with advanced Ann Arbor stage and MYC expression ≥ 40%, as well as inferior progression-free survival and overall survival. In B-lymphoma cells, the mutation or knockdown of KMT2D inhibited methylation of lysine 4 on histone H3 (H3K4), downregulated FBXW7 expression, activated NOTCH signaling pathway and downstream MYC/TGF-ß1, resulting in alterations of tumor-induced regulatory T cell trafficking. In B-lymphoma murine models established with subcutaneous injection of SU-DHL-4 cells, xenografted tumors bearing KMT2D mutation presented lower H3K4 methylation, higher regulatory T cell recruitment, thereby provoking rapid tumor growth compared with wild-type KMT2D via FBXW7-NOTCH-MYC/TGF-ß1 axis.

Tailoring photocatalysts to modulate oxidative potential of anilides enhances para-selective electrochemical hydroxylation.

Phenolic compounds have long captivated the interest of organic synthesis, particularly in their quest for selective hydroxylation of arenes using H2O as a hydroxyl source. However, the inherent high reactivity and low redox potential of phenols often lead to undesirable overoxidation byproducts. To address this challenge, herein, we develop an electrophotochemical approach, finetuning substrate oxidative potential and enabling para-selective hydroxylation of anilides. This method showcases versatility, accommodating a wide array of substrates, while revealing high regional selectivity and compatibility with diverse functional groups. Moreover, the protocol allows facile late-stage functionalization of biologically active molecules. Mechanistic investigations demonstrate the activation of anilides by the excited state photocatalyst, effectively decreasing their oxidative potential and enhancing regional selectivity during hydroxylation. By using this protocol, important drug molecules such as Paracetamol, Fenretinide, Practolol, and AM404 could be synthesized, demonstrating the applicability of this approach in drug synthesis and late-stage functionalization.

Key Lipoprotein Receptor Targeted Echinacoside-Liposomes Effective Against Parkinson's Disease in Mice Model.

Introduction: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment. Methods: We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model. Results: The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH. Conclusion: The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.

Unconventional Thermophotonic Charge Density Wave.

Charge-order states of broken symmetry, such as charge density wave (CDW), are able to induce exceptional physical properties, however, the precise understanding of the underlying physics is still elusive. Here, we combine fluctuational electrodynamics and density functional theory to reveal an unconventional thermophotonic effect in CDW-bearing TiSe_{2}, referred to as thermophotonic-CDW (tp-CDW). The interplay of plasmon polariton and CDW electron excitations give rise to an anomalous negative temperature dependency in thermal photons transport, offering an intuitive fingerprint for a transformation of the electron order. Additionally, the demonstrated nontrivial features of tp-CDW transition hold promise for a controllable manipulation of heat flow, which could be extensively utilized in various fields such as thermal science and electron dynamics, as well as in next-generation energy devices.

Anti-inflammatory and DNA Repair Effects of Astragaloside IV on PC12 Cells Damaged by Lipopolysaccharide.

OBJECTIVE: This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide (LPS) and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses. METHODS: PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25, 0.5, 0.75, 1, and 1.25 mg/mL for 24 h. Cell morphology was evaluated, and cell survival rates were calculated. A neurocyte inflammatory model was established with LPS treatment, which reached a 50% cell survival rate. PC12 cells were treated with 0.01, 0.1, 1, 10, or 100 µmol/L astragaloside IV for 24 h. The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments. NOS activity was detected by colorimetry; the expression levels of ERCC2, XRCC4, XRCC2, TNF-α, IL-1ß, TLR4, NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting. The differentially expressed genes (DEGs) between the groups were screened using a second-generation sequence (fold change>2, P<0.05) with the following KEGG enrichment analysis, RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells. RESULTS: The viability of PC12 cells was not altered by treatment with 0.01, 0.1, or 1 µmol/L astragaloside IV for 24 h (P>0.05). However, after treatment with 0.5, 0.75, 1, or 1.25 mg/mL LPS for 24 h, the viability steadily decreased (P<0.01). The mRNA and protein expression levels of ERCC2, XRCC4, XRCC2, TNF-α, IL-1ß, TLR4, NOS, and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h (P<0.01); however, these changes were reversed when PC12 cells were pretreated with 0.01, 0.1, or 1 µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h (P<0.05). Second-generation sequencing revealed that 1026 genes were upregulated, while 1287 genes were downregulated. The DEGs were associated with autophagy, TNF-α, interleukin-17, MAPK, P53, Toll-like receptor, and NOD-like receptor signaling pathways. Furthermore, PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2, CCL11, CCL7, MMP3, and MMP10, which are associated with the IL-17 pathway. RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results. CONCLUSION: LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage. astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.

Role of artificial intelligence in Crohn's disease intestinal strictures and fibrosis.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Intestinal fibrosis or stricture is one of the most prevalent complications in CD with a high recurrence rate. Manual examination of intestinal fibrosis or stricture by physicians may be biased or inefficient. A rapid development of artificial intelligence (AI) technique in recent years facilitates the detection of existing or possible intestinal fibrosis and stricture in CD through various modalities, including endoscopy, imaging examination, and serological biomarkers. We reviewed the articles on AI application in diagnosing intestinal fibrosis and stricture in CD during the past decade and categorized them into three aspects based on the detection methods, and found that AI helps accurate and expedient identification and prediction of intestinal fibrosis and stenosis in CD.

P62-autophagic pathway degrades SLC7A11 to regulate ferroptosis in doxorubicin-induced cardiotoxicity.

Doxorubicin-induced cardiotoxicity (DIC) poses a significant challenge, impeding its widespread application. Emerging evidence suggests the involvement of ferroptosis in the DIC. While the downregulation of SLC7A11 expression has been linked to the promotion of ferroptosis, the precise regulatory mechanism remains unclear. Recent studies, including our own, have highlighted abnormal levels of autophagy adapter protein P62 and autophagy in DIC development. Thus, our study aimed to further investigate the role of autophagy and ferroptosis in DIC, elucidating underlying molecular mechanisms across molecular, cellular, and whole-organ levels utilizing gene knockdown, immunoprecipitation, and mass spectrometry techniques. The results of our findings unveiled cardiomyocyte damage, heightened autophagy levels, and ferroptosis in DOX-treated mouse hearts. Notably, inhibition of autophagy levels attenuated DOX-induced ferroptosis. Mechanistically, we discovered that the autophagy adaptor protein P62 mediates the entry of SLC7A11 into the autophagic pathway for degradation. Furthermore, the addition of autophagy inhibitors (CQ or BAF) could elevate SLC7A11 and GPX4 protein expression, reduce the accumulation of Fe2+ and ROS in cardiomyocytes, and thus mitigate DOX-induced ferroptosis. In summary, our findings underscore the pivotal role of the P62-autophagy pathway in SLC7A11 degradation, modulating ferroptosis to exacerbate DIC. This finding offers significant insights into the underlying molecular mechanisms of DOX-induced ferroptosis and identifies new targets for reversing DIC.