Role of gut microbiota in doxorubicin-induced cardiotoxicity: from pathogenesis to related interventions.

Doxorubicin (DOX) is a broad-spectrum and highly efficient anticancer agent, but its clinical implication is limited by lethal cardiotoxicity. Growing evidences have shown that alterations in intestinal microbial composition and function, namely dysbiosis, are closely linked to the progression of DOX-induced cardiotoxicity (DIC) through regulating the gut-microbiota-heart (GMH) axis. The role of gut microbiota and its metabolites in DIC, however, is largely unelucidated. Our review will focus on the potential mechanism between gut microbiota dysbiosis and DIC, so as to provide novel insights into the pathophysiology of DIC. Furthermore, we summarize the underlying interventions of microbial-targeted therapeutics in DIC, encompassing dietary interventions, fecal microbiota transplantation (FMT), probiotics, antibiotics, and natural phytochemicals. Given the emergence of microbial investigation in DIC, finally we aim to point out a novel direction for future research and clinical intervention of DIC, which may be helpful for the DIC patients.

MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.

Dynamin-related protein 1 (Drp1) is a crucial regulator of mitochondrial dynamics, the overactivation of which can lead to cardiovascular disease. Multiple distinct posttranscriptional modifications of Drp1 have been reported, among which S-nitrosylation was recently introduced. However, the detailed regulatory mechanism of S-nitrosylation of Drp1 (SNO-Drp1) in cardiac microvascular dysfunction in diabetes remains elusive. The present study revealed that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was consistently upregulated in diabetic cardiomyopathy (DCM) and promoted SNO-Drp1 in cardiac microvascular endothelial cells (CMECs), which in turn led to mitochondrial dysfunction and cardiac microvascular disorder. Further studies confirmed that MAP4K4 promoted SNO-Drp1 at human C644 (mouse C650) by inhibiting glutathione peroxidase 4 (GPX4) expression, through which MAP4K4 stimulated endothelial ferroptosis in diabetes. In contrast, inhibition of MAP4K4 via DMX-5804 significantly reduced endothelial ferroptosis, alleviated cardiac microvascular dysfunction and improved cardiac dysfunction in db/db mice by reducing SNO-Drp1. In parallel, the C650A mutation in mice abolished SNO-Drp1 and the role of Drp1 in promoting cardiac microvascular disorder and cardiac dysfunction. In conclusion, our findings demonstrate that MAP4K4 plays an important role in endothelial dysfunction in DCM and reveal that SNO-Drp1 and ferroptosis activation may act as downstream targets, representing potential therapeutic targets for DCM.

Global convergence in terrestrial gross primary production response to atmospheric vapor pressure deficit.

Atmospheric vapor pressure deficit (VPD) increases with climate warming and may limit plant growth. However, gross primary production (GPP) responses to VPD remain a mystery, offering a significant source of uncertainty in the estimation of global terrestrial ecosystems carbon dynamics. In this study, in-situ measurements, satellite-derived data, and Earth System Models (ESMs) simulations were analysed to show that the GPP of most ecosystems has a similar threshold in response to VPD: first increasing and then declining. When VPD exceeds these thresholds, atmospheric drought stress reduces soil moisture and stomatal conductance, thereby decreasing the productivity of terrestrial ecosystems. Current ESMs underscore CO2 fertilization effects but predict significant GPP decline in low-latitude ecosystems when VPD exceeds the thresholds. These results emphasize the impacts of climate warming on VPD and propose limitations to future ecosystems productivity caused by increased atmospheric water demand. Incorporating VPD, soil moisture, and canopy conductance interactions into ESMs enhances the prediction of terrestrial ecosystem responses to climate change.

A Composite Hydrogel Functionalized by Borosilicate Bioactive Glasses and VEGF for Critical-Size Bone Regeneration.

Critical-size bone defects pose a formidable challenge in clinical treatment, prompting extensive research efforts to address this problem. In this study, an inorganic-organic multifunctional composite hydrogel denoted as PLG-g-TA/VEGF/Sr-BGNPs is developed, engineered for the synergistic management of bone defects. The composite hydrogel demonstrated the capacity for mineralization, hydroxyapatite formation, and gradual release of essential functional ions and vascular endothelial growth factor (VEGF) and also maintained an alkaline microenvironment. The composite hydrogel promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as indicated by increased expression of osteogenesis-related genes and proteins in vitro. Moreover, the composite hydrogel significantly enhanced the tube-forming capability of human umbilical vein endothelial cells (HUVECs) and effectively inhibited the process of osteoblastic differentiation of nuclear factor kappa-B ligand (RANKL)-induced Raw264.7 cells and osteoclast bone resorption. After the implantation of the composite hydrogel into rat cranial bone defects, the expression of osteogenic and angiogenic biomarkers increased, substantiating its efficacy in promoting bone defect repair in vivo. The commendable attributes of the multifunctional composite hydrogel underscore its pivotal role in expediting hydrogel-associated bone growth and repairing critical bone defects, positioning it as a promising adjuvant therapy candidate for large-segment bone defects.

Effect of hydrothermal treatment on the rheological properties of xanthan gum.

In this study, the effect of hydrothermal treatment with different temperatures (120-180 °C) on the rheological properties of xanthan gum was evaluated. When the temperature of hydrothermal treatment was relatively low (120 °C), the rheological properties of the hydrothermally treated xanthan gum was similar to the untreated xanthan gum (pseudoplastic and solid-like/gel-like behavior). However, as the temperature of hydrothermal treatment was higher, the rheological properties of the hydrothermally treated xanthan gum changed greatly (e.g., a wider range of Newtonian plateaus in flow curves, existence of a critical frequency between the storage modulus (G') and the loss modulus (G") in the dynamic viscoelasticity measurement, variation of complex viscosity). Although the hydrothermal treatment showed little influence on the functional groups of xanthan gum, it altered the micromorphology of xanthan gum from uneven and rough lump-like to thinner and smoother flake-like. In addition, higher concentration (2 %) of hydrothermally treated xanthan gum made its viscosity close to that of the untreated xanthan gum (1 %). Besides, hydrothermal treatment also affected the effect of temperature and salt (CaCl2) adding on the rheological properties of xanthan gum. Overall, this study can provide some useful information on the rheological properties of xanthan gum after hydrothermal treatment.

Study on the Influence of Runner and Overflow Area Design on Flow-Fiber Coupling in a Multi-Cavity System.

Fiber-reinforced composites (FRPs) are characterized by their lightweight nature and superior mechanical characteristics, rendering them extensively utilized across various sectors such as aerospace and automotive industries. Nevertheless, the precise mechanisms governing the interaction between the fibers present in FRPs and the polymer melt during industrial processing, particularly the manipulation of the flow-fiber coupling effect, remain incompletely elucidated. Hence, this study introduces a geometrically symmetrical 1 × 4 multi-cavity mold system, where each cavity conforms to the ASTM D638 Type V standard specimen. The research utilizes theoretical simulation analysis and experimental validation to investigate the influence of runner and overflow design on the flow-fiber coupling effect. The findings indicate that the polymer melt, directed by a geometrically symmetrical runner, results in consistent fiber orientation within each mold cavity. Furthermore, in the context of simulation analysis, the inclusion of the flow-fiber coupling effect within the system results in elevated sprue pressure levels and an expanded core layer region in comparison to systems lacking this coupling effect. This observation aligns well with the existing literature on the subject. Moreover, analysis of fiber orientation in different flow field areas reveals that the addition of an overflow area alters the flow field, leading to a significant delay in the flow-fiber coupling effect. To demonstrate the impact of overflow area design on the flow-fiber effect, the integration of fiber orientation distribution analysis highlights a transformation in fiber arrangement from the flow direction to cross-flow and thickness directions near the end-of-fill region in the injected part. Additionally, examination of the geometric dimensions of the injected part reveals asymmetrical geometric shrinkage between upstream and downstream areas in the end-of-fill region, consistent with microscopic fiber orientation changes influenced by the delayed flow-fiber coupling effect guided by the overflow area. In brief, the introduction of the overflow area extends the duration in which the polymer melt exerts control in the flow direction, consequently prolonging the period in which the fiber orientation governs in the flow direction (A11). This leads to the impact of fiber orientation on the flow of the polymer melt, with the flow reciprocally affecting the fibers. Subsequently, the interaction between these two elements persists until a state of equilibrium is achieved, known as the flow-fiber coupling effect, which is delayed.

Cell therapies and its derivatives as immunomodulators in vascularized composite allotransplantation.

The adverse effects of traditional pharmaceutical immunosuppressive regimens have been a major obstacle to successful allograft survival in vascularized composite tissue allotransplantation (VCA) cases. Consequently, there is a pressing need to explore alternative approaches to reduce reliance on conventional immunotherapy. Cell therapy, encompassing immune-cell-based and stem-cell-based regimens, has emerged as a promising avenue of research. Immune cells can be categorized into two main systems: innate immunity and adaptive immunity. Innate immunity comprises tolerogenic dendritic cells, regulatory macrophages, and invariant natural killer T cells, while adaptive immunity includes T regulatory cells and B regulatory cells. Investigations are currently underway to assess the potential of these immune cell populations in inducing immune tolerance. Furthermore, mixed chimerism therapy, involving the transplantation of hematopoietic stem and progenitor cells and mesenchymal stem cells (MSC), shows promise in promoting allograft tolerance. Additionally, extracellular vesicles (EVs) derived from MSCs offer a novel avenue for extending allograft survival. This review provides a comprehensive summary of cutting-edge research on immune cell therapies, mixed chimerism therapies, and MSCs-derived EVs in the context of VCAs. Findings from preclinical and clinical studies demonstrate the tremendous potential of these alternative therapies in optimizing allograft survival in VCAs.

A Study on the Borehole Wall Stability Analysis and Slurry Ratio Optimization for Construction of Pile in Complex Marine Strata.

In order to address the issue of hole collapse, which frequently arises when boring piles are being constructed in intricate marine strata, this paper discusses the influence of the slurry ratio on the slurry performance as well as the mechanism of slurry wall protection. It performs this by means of theoretical analysis, laboratory ratio testing, engineering analogies, numerical simulation, and field testing. Our findings demonstrate that adding sodium polyacrylate and sodium carboxymethyl cellulose can enhance mud's viscosity, contribute to flocculation, and improve the connection between mud and soil layers. Refering similar engineering cases, three optimization schemes are proposed for achieving a mud ratio that offers wall protection in complex marine strata. Furthermore, the particle flow model of slurry viscous fluid is established. The collapse of holes in the sand layer is reflected in the uneven radial displacement of hole walls and the invasion of mud particles. Increasing the viscosity of mud gradually transforms the uneven radial deformation of pore walls in the sand layer into a uniform radial deformation, whereas increasing the proportion of mud significantly decreases the radial displacement of hole walls. Additionally, when the mud pressure in the hole is 300 kPa and 600 kPa, the wall protection effect is better, and there is no particle penetration by substances such as sand. It is found that a high mud pressure can promote the diffusion of mud particles into the sand layer, while low mud pressure cannot balance the pressure on deep soil. The results of the field tests show that the ratio of water-clay-bentonite-CMC-Na-sodium carbonate = 700:110:90:1.5:0.5 used (where the mass percentage of each material is 77.8% water, 12.2% clay, 10% bentonite, 0.16% CMC-Na, and 0.05% sodium carbonate) can effectively prevent hole collapse and reduce the thickness of the sand layer at the bottom of the hole by 50%.

Identification of Molecular Profile of Ear Fibroblasts Derived from Spindle-Transferred Holstein Cattle with Ooplasts from Taiwan Yellow Cattle under Heat Stress.

Global warming has a significant impact on the dairy farming industry, as heat stress causes reproductive endocrine imbalances and leads to substantial economic losses, particularly in tropical-subtropical regions. The Holstein breed, which is widely used for dairy production, is highly susceptible to heat stress, resulting in a dramatic reduction in milk production during hot seasons. However, previous studies have shown that cells of cows produced from reconstructed embryos containing cytoplasm (o) from Taiwan yellow cattle (Y) have improved thermotolerance despite their nuclei (n) being derived from heat-sensitive Holstein cattle (H). Using spindle transfer (ST) technology, we successfully produced ST-Yo-Hn cattle and proved that the thermotolerance of their ear fibroblasts is similar to that of Y and significantly better than that of H (p < 0.05). Despite these findings, the genes and molecules responsible for the different sensitivities of cells derived from ST-Yo-Hn and H cattle have not been extensively investigated. In the present study, ear fibroblasts from ST-Yo-Hn and H cattle were isolated, and differentially expressed protein and gene profiles were compared with or without heat stress (hs) (42 °C for 12 h). The results revealed that the relative protein expression levels of pro-apoptotic factors, including Caspase-3, -8, and -9, in the ear fibroblasts from the ST-Yo-Hn-hs group were significantly lower (p < 0.05) than those from the H-hs group. Conversely, the relative expression levels of anti-apoptotic factors, including GNA14 protein and the CRELD2 and PRKCQ genes, were significantly higher (p < 0.05) in the ear fibroblasts from the ST-Yo-Hn-hs group compared to those from the H-hs group. Analysis of oxidative phosphorylation-related factors revealed that the relative expression levels of the GPX1 gene and Complex-I, Complex-IV, CAT, and PGLS proteins were significantly higher (p < 0.05) in the ear fibroblasts from the ST-Yo-Hn-hs group compared to those from the H-hs group. Taken together, these findings suggest that ear fibroblasts from ST-Yo-Hn cattle have superior thermotolerance compared to those from H cattle due to their lower expression of pro-apoptotic factors and higher expression of oxidative phosphorylation and antioxidant factors. Moreover, this improved thermotolerance is attributed, at least partially, to the cytoplasm derived from more heat-tolerant Y cattle. Hence, using ST technology to produce more heat-tolerant H cattle containing Y cytoplasm could be a feasible approach to alleviate the negative impacts of heat stress on dairy cattle in tropical-subtropical regions.

CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation.

BACKGROUND: Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown. METHODS: In vitro molecular and cellular biological analyses on genetically modified endothelial cells, in vivo vascular biological analyses on genetically engineered mouse models, and in silico systems biology and bioinformatics analyses on CD151-related events. RESULTS: Endothelial ablation of Cd151 leads to pulmonary and cardiac inflammation, severe sepsis, and perilous COVID-19, and endothelial CD151 becomes downregulated in inflammation. Mechanistically, CD151 restrains endothelial release of proinflammatory molecules for less leukocyte infiltration. At the subcellular level, CD151 determines the integrity of multivesicular bodies/lysosomes and confines the production of exosomes that carry cytokines such as ANGPT2 (angiopoietin-2) and proteases such as cathepsin-D. At the molecular level, CD151 docks VCP (valosin-containing protein)/p97, which controls protein quality via mediating deubiquitination for proteolytic degradation, onto endolysosomes to facilitate VCP/p97 function. At the endolysosome membrane, CD151 links VCP/p97 to (1) IFITM3 (interferon-induced transmembrane protein 3), which regulates multivesicular body functions, to restrain IFITM3-mediated exosomal sorting, and (2) V-ATPase, which dictates endolysosome pH, to support functional assembly of V-ATPase. CONCLUSIONS: Distinct from its canonical function in strengthening cell adhesion at cell surface, CD151 maintains endolysosome function by sustaining VCP/p97-mediated protein unfolding and turnover. By supporting protein quality control and protein degradation, CD151 prevents proteins from (1) buildup in endolysosomes and (2) discharge through exosomes, to limit vascular inflammation. Also, our study conceptualizes that balance between degradation and discharge of proteins in endothelial cells determines vascular information. Thus, the IFITM3/V-ATPase-tetraspanin-VCP/p97 complexes on endolysosome, as a protein quality control and inflammation-inhibitory machinery, could be beneficial for therapeutic intervention against vascular inflammation.

Sediment record of heavy metals in Xincun Lagoon indicating anthropogenic impact over the last 200 years.

Anthropogenic metal pollution is a leading environmental problem in southern China, especially in remote regions where its impact remains poorly understood. This study investigates the historical variation of heavy metal pollution over the last 200 years using a sediment core from Xincun Lagoon, Hainan Island, South China. The temporal evolution of heavy metal pollution aligns with China's socioeconomic development. Prior to the 1950s, heavy metal concentrations were at geochemical background levels, reflecting China's agrarian status. Since the 1950s, the increased heavy metal accumulation may be attributed to intensified human activities linked to rapid urbanization and industrialization. Despite the increase in heavy metal enrichments since the 1950s, Xincun Lagoon currently faces a low ecological risk.

Immunization with a low dose of zymosan A confers resistance to depression-like behavior and neuroinflammatory responses in chronically stressed mice.

Stimulation of the innate immune system prior to stress exposure is a possible strategy to prevent depression under stressful conditions. Based on the innate immune system stimulating activities of zymosan A, we hypothesize that zymosan A may prevent the development of chronic stress-induced depression-like behavior. Our results showed that a single injection of zymosan A 1 day before stress exposure at a dose of 2 or 4 mg/kg, but not at a dose of 1 mg/kg, prevented the development of depression-like behaviors in mice treated with chronic social defeat stress (CSDS). The prophylactic effect of a single zymosan A injection (2 mg/kg) on CSDS-induced depression-like behaviors disappeared when the time interval between zymosan A and stress exposure was extended from 1 day or 5 days to 10 days, which was rescued by a second zymosan A injection 10 days after the first zymosan A injection and 4 days (4×, once daily) of zymosan A injections 10 days before stress exposure. Further analysis showed that a single zymosan A injection (2 mg/kg) 1 day before stress exposure could prevent the CSDS-induced increase in pro-inflammatory cytokines in the hippocampus and prefrontal cortex. Inhibition of the innate immune system by pretreatment with minocycline (40 mg/kg) abolished the preventive effect of zymosan A on CSDS-induced depression-like behaviors and CSDS-induced increase in pro-inflammatory cytokines in the brain. These results suggest that activation of the innate immune system triggered by zymosan A prevents the depression-like behaviors and neuroinflammatory responses in the brain induced by chronic stress.

NSC689857, an inhibitor of Skp2, produces antidepressant-like effects in mice.

We have previously reported that two inhibitors of an E3 ligase S-phase kinase-associated protein 2 (Skp2), SMIP004 and C1, have an antidepressant-like effect in non-stressed and chronically stressed mice. This prompted us to ask whether other Skp2 inhibitors could also have an antidepressant effect. Here, we used NSC689857, another Skp2 inhibitor, to investigate this hypothesis. The results showed that administration of NSC689857 (5 mg/kg) produced an antidepressant-like effect in a time-dependent manner in non-stressed male mice, which started 8 days after drug administration. Dose-dependent analysis showed that administration of 5 and 10 mg/kg, but not 1 mg/kg, of NSC689857 produced antidepressant-like effects in both non-stressed male and female mice. Administration of NSC689857 (5 mg/kg) also induced antidepressant-like effects in non-stressed male mice when administered three times within 24 h (24, 5, and 1 h before testing) but not when administered acutely (1 h before testing). In addition, NSC689857 and fluoxetine coadministration produced additive antidepressant-like effects in non-stressed male mice. These effects of NSC689857 were not associated with the changes in locomotor activity. Administration of NSC689857 (5 mg/kg) also attenuated depression-like behaviors in male mice induced by chronic social defeat stress, suggesting therapeutic potential of NSC689857 in depression. Overall, these results suggest that NSC689857 is capable of exerting antidepressant-like effects in both non-stressed and chronically stressed mice.

Patient privacy in AI-driven omics methods.

Artificial intelligence (AI) in omics analysis raises privacy threats to patients. Here, we briefly discuss risk factors to patient privacy in data sharing, model training, and release, as well as methods to safeguard and evaluate patient privacy in AI-driven omics methods.

Improving the Detection, Assessment, Management and Prevention of Delirium in Hospices (the DAMPen-D study): Feasibility study of a flexible and scalable implementation strategy to deliver guideline-adherent delirium care.

BACKGROUND: Delirium is a complex condition, stressful for all involved. Although highly prevalent in palliative care settings, it remains underdiagnosed and associated with poor outcomes. Guideline-adherent delirium care may improve its detection, assessment and management. AIM: To inform a future definitive study that tests whether an implementation strategy designed to improve guideline-adherent delirium care in palliative care settings improves patient outcomes (reduced proportion of in-patient days with delirium). DESIGN: With Patient Involvement members, we conducted a feasibility study to assess the acceptability of and engagement with the implementation strategy by hospice staff (intervention), and whether clinical record data collection of process (e.g. guideline-adherent delirium care) and clinical outcomes (evidence of delirium using a validated chart-based instrument;) pre- and 12-weeks post-implementation of the intervention would be possible. SETTING/PARTICIPANTS: In-patient admissions in three English hospices. RESULTS: Between June 2021 and December 2022, clinical record data were extracted from 300 consecutive admissions. Despite data collection during COVID-19, target clinical record data collection (n = 300) was achieved. Approximately two-thirds of patients had a delirium episode during in-patient stay at both timepoints. A 6% absolute reduction in proportion of delirium days in those with a delirium episode was observed. Post-implementation improvements in guideline-adherent metrics include: clinical delirium diagnosis 15%-28%; delirium risk assessment 0%-16%; screening on admission 7%-35%. CONCLUSIONS: Collection of data on delirium outcomes and guideline-adherence from clinical records is feasible. The signal of patient benefit supports formal evaluation in a large-scale study.

Anti-aging effect of peptides on Caenorhabditis elegans: a meta-analysis.

BACKGROUND: Recently, peptides have been studied in Caenorhabditis elegans for anti-aging research. Due to the lack of sufficient evidence, we conducted this meta-analysis focusing on the anti-aging effect of peptides in C. elegans to provide more convincing evidence. RESULTS: A literature search in PubMed, SCOUPUS, and Web of Science databases yielded 2879 articles. After removing duplicates and based on inclusion criteria and STAIR checklist quality assessment, nine articles were selected. Data extraction and analysis showed that, compared to the control group without peptide intervention, peptide supplementation significantly reduced nematode mortality risk [hazard ratio = 0.54, 95% confidence interval (CI) = 0.47, 0.62; P < 0.05], significantly increased the pharyngeal pumping rate [standardized mean difference (SMD) = 1.64, 95% CI = 0.87, 2.41; P < 0.05], bending frequency (SMD = 1.67, 95% CI = 1.16, 2.18; P < 0.05), and significantly decreased the accumulation of lipofuscin levels within nematodes (SMD = -4.48, 95% CI = -6.85, -2.12; P < 0.05). Additionally, subgroup analysis showed that doses ranging from 0.1 to 1 mg/mL (HR = 0.50, 95% CI = 0.38, 0.65; P < 0.05) displayed better anti-aging effects compared to other dose ranges. CONCLUSION: The findings suggest that peptides can significantly extend the lifespan of C. elegans under normal circumstances and improve three indicators of healthy life. More importantly, subgroup analysis revealed that a dosage of 0.1-1 mg/mL demonstrated superior anti-aging effects. This meta-analysis provides more convincing evidence that peptides can play an anti-aging role in C. elegans. © 2024 Society of Chemical Industry.

Discovery of novel Thymol-TPP antibiotics that eradicate MRSA persisters.

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains and the formation of non-growing, dormant "persisters" subsets help bacteria evade antibiotic treatment and enhance bacterial resistance, which poses a serious threat to human life and health. It is urgent to discover novel antibacterial therapies effective against MRSA persisters. Thymol is a common nutraceutical with weak antibacterial and antitumor activities. A series of Thymol triphenylphosphine (TPP) conjugates (TPP-Thy3) was designed and synthesized. These compounds showed significantly improved inhibitory activity against Gram-positive bacteria compared with Thymol. Among them, Thy3d displayed a low probability of resistance selection and showed excellent biocompatibility. Interestingly, Thy3d elicited a rapid killing effect of MRSA persisters (99.999%) at high concentration. Fluorescence experiments, electron microscopy, molecular dynamics simulation and bilayer experiment confirmed that Thy3d conjugates exerted potent antimicrobial activity by disrupting the integrity of the membrane of bacterial even the persister. Furthermore, Thy3d exhibited considerable efficacy in a mouse model of subcutaneous murine MRSA infection. In summary, TPP-Thy3 conjugates are a series of novel antibacterial agents and could serve as a new therapeutic strategy for combating antibiotic resistance.

Chemodivergence in Fluorine Source-Controlled Cascade Reaction of Aryne Precursors to Synthesize Pyrrolo[3,4-b]indoles and 3-Arylated Maleimides.

Reactions allowing chemodivergence prove to be attractive strategies in synthetic organic chemistry. We herein described a highly practical, transition-metal-free, highly regioselective and chemodivergent cascade reaction controlled by fluorine sources, which involved a [3 + 2] cycloaddition or C-arylation process between aryne precursors and 3-aminomaleimides. These two pathways led to a wide scope of structurally diverse pyrrolo[3,4-b]indoles (19 examples) and 3-arylated maleimides (25 examples) in good-to-excellent yields. Furthermore, the reaction could be scaled up, and several synthetic transformations were accomplished for the preparation of functionalized molecules and might provide new opportunities for the discovery of N-heterocyclic drugs.