A new artificial intelligence system for both stomach and small bowel capsule endoscopy.

BACKGROUND AND AIMS: Despite the benefits of artificial intelligence (AI) in small bowel (SB) capsule endoscopy (CE) image reading, information on its application in the stomach and SB CE is lacking. METHODS: In this multicenter, retrospective diagnostic study, gastric imaging data were added to the deep learning (DL)-based SmartScan (SS), which has been described previously. A total of 1,069 magnetically controlled gastrointestinal (GI) CE examinations (comprising 2,672,542 gastric images) were used in the training phase for recognizing gastric pathologies, producing a new AI algorithm named SS Plus. 342 fully automated, magnetically controlled CE (FAMCE) examinations were included in the validation phase. The performance of both senior and junior endoscopists with both the SS Plus-Assisted Reading (SSP-AR) and conventional reading (CR) modes was assessed. RESULTS: SS Plus was designed to recognize 5 types of gastric lesions and 17 types of SB lesions. SS Plus reduced the number of CE images required for review to 873.90 (1000) (median, IQR 814.50-1,000) versus 44,322.73 (42,393) (median, IQR 31,722.75-54,971.25) for CR. Furthermore, with SSP-AR, endoscopists took 9.54 min (8.51) (median, IQR 6.05-13.13) to complete the CE video reading. In the 342 CE videos, SS Plus identified 411 gastric and 422 SB lesions, whereas 400 gastric and 368 intestinal lesions were detected with CR. Moreover, junior endoscopists remarkably improved their CE image reading ability with SSP-AR. CONCLUSIONS: Our study shows that the newly upgraded DL-based algorithm SS Plus can detect GI lesions and help improve the diagnostic performance of junior endoscopists in interpreting CE videos.

Intergenerational or intragenerational learning? The relationship between interpersonal neural synchrony and older adult's learning acquisition.

OBJECTIVES: Lifelong learning facilitates active ageing, and intragenerational learning-the process by which older adults learn from their peers-is an effective means of achieving this goal. The present research aims to elucidate the mechanisms and differences between intergenerational and intragenerational learning models for older adults as evidenced by brain-to-brain synchrony. METHODS: Fifty-six instructor-learner dyads completed a study comparing intergenerational and intragenerational learning models, as well as task difficulty. The study utilized a block puzzle task and functional near-infrared spectroscopy (fNIRS) for hyperscanning. RESULTS: The instructor-learner dyads showed greater interpersonal neural synchrony (INS) and learning acquisition in the intragenerational learning model in the difficult task condition (t (54) = 3.49, p < 0.01), whereas the two learning models yielded similar results in the easy condition (t (54) = 1.96, p = 0.06). In addition, INS and self-efficacy mediated the association between learning models and learning acquisition in older adults (b = 0.14, SEM = 0.04, 95 % CI [0.01 0.16]). DISCUSSION: This study is the first to provide evidence of interbrain synchrony in an investigation of the intragenerational learning model in older adults. Our findings suggest that intra-learning is as effective as traditional inter-learning and may be more effective in certain contexts, such as difficult tasks. Encouraging intra-learning in community service or educational activities can effectively mitigate the challenge of limited volunteers and enhance learning acquisition among older adults.

N-Salicyloyl Tryptamine Derivatives as Potent Neuroinflammation Inhibitors by Constraining Microglia Activation via a STAT3 Pathway.

Neuroinflammation is an important factor that exacerbates neuronal death and abnormal synaptic function in neurodegenerative diseases (NDDs). Due to the complex pathogenesis and the presence of blood-brain barrier (BBB), no effective clinical drugs are currently available. Previous results showed that N-salicyloyl tryptamine derivatives had the potential to constrain the neuroinflammatory process. In this study, 30 new N-salicyloyl tryptamine derivatives were designed and synthesized to investigate a structure-activity relationship (SAR) for the indole ring of tryptamine in order to enhance their antineuroinflammatory effects. Among them, both in vitro and in vivo compound 18 exerted the best antineuroinflammatory effects by suppressing the activation of microglia, which is the culprit of neuroinflammation. The underlying mechanism of its antineuroinflammatory effect may be related to the inhibition of transcription, expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) that subsequently regulated downstream cyclooxygenase-2 (COX-2) expression and activity. With its excellent BBB permeability and pharmacokinetic properties, compound 18 exhibited significant neuroprotective effects in the hippocampal region of lipopolysaccharides (LPS)-induced mice than former N-salicyloyl tryptamine derivative L7. In conclusion, compound 18 has provided a new approach for the development of highly effective antineuroinflammatory therapeutic drugs targeting microglia activation.

SIRT6 positively regulates antiviral response in a bony fish, the Chinese perch Siniperca chuatsi.

SIRT6, a key member of the sirtuin family, plays a pivotal role in regulating a number of vital biological processes, including energy metabolism, oxidative stress, and immune system modulation. Nevertheless, the function of SIRT6 in bony fish, particularly in the context of antiviral immune response, remains largely unexplored. In this study, a sirt6 was cloned and characterized in a commercial fish, the Chinese perch (Siniperca chuatsi). The SIRT6 possesses conserved SIR2 domain with catalytic core region when compared with other vertebrates. Tissue distribution analysis indicated that sirt6 was expressed in all detected tissues, and the sirt6 was significantly induced following infection of infectious haemorrhagic syndrome virus (IHSV). The overexpression of SIRT6 resulted in significant upregulation of interferon-stimulated genes (ISGs), such as viperin, mx, isg15, irf3 and ifp35, and inhibited viral replication. It was further found that SIRT6 was located in nucleus and could enhance the expression of ISGs induced by type I and II IFNs. These findings may provide new information in relation with the function of SIRT6 in vertebrates, and with viral prevention strategy development in aquaculture.

Discovery of novel small molecules targeting the USP21/JAK2/STAT3 axis for the treatment of triple-negative breast cancer.

The deficiency in available targeted agents and frequency of chemoresistance are primary challenges in clinical management of triple-negative breast cancer (TNBC). The aberrant expression of USP21 and JAK2 represents a characterized mechanism of TNBC progression and resistance to paclitaxel (PTX). Despite its clear that high expression of USP21-mediated de-ubiquitination leads to increased levels of JAK2 protein, we lack regulator molecules to dissect the mechanisms that the interaction between USP21 and JAK2 contributes to the phenotype and resistance of TNBC. Here, we report a USP21/JAK2/STAT3 axis-targeting regulator 13c featuring a N-anthraniloyl tryptamine scaffold that showed excellent anti-TNBC potency and promising safety profile. Importantly, the therapeutic potential of using 13c in combination with PTX in PTX-resistant TNBC was demonstrated. This study showcases N-anthraniloyl tryptamine derivatives as a novel anti-TNBC chemotype with a pharmacological mode of action targeting the USP21/JAK2/STAT3 axis and provides a potential therapeutic target for the treatment of TNBC.

Lhx2 promotes axon regeneration of adult retinal ganglion cells and rescues neurodegeneration in mouse models of glaucoma.

The axons of retinal ganglion cells (RGCs) form the optic nerve, transmitting visual information from the eye to the brain. Damage or loss of RGCs and their axons is the leading cause of visual functional defects in traumatic injury and degenerative diseases such as glaucoma. However, there are no effective clinical treatments for nerve damage in these neurodegenerative diseases. Here, we report that LIM homeodomain transcription factor Lhx2 promotes RGC survival and axon regeneration in multiple animal models mimicking glaucoma disease. Furthermore, following N-methyl-D-aspartate (NMDA)-induced excitotoxicity damage of RGCs, Lhx2 mitigates the loss of visual signal transduction. Mechanistic analysis revealed that overexpression of Lhx2 supports axon regeneration by systematically regulating the transcription of regeneration-related genes and inhibiting transcription of Semaphorin 3C (Sema3C). Collectively, our studies identify a critical role of Lhx2 in promoting RGC survival and axon regeneration, providing a promising neural repair strategy for glaucomatous neurodegeneration.

The Autophagy-Related Protein ATG8 Orchestrates Asexual Development and AFB1 Biosynthesis in Aspergillus flavus.

Autophagy, a conserved cellular recycling process, plays a crucial role in maintaining homeostasis under stress conditions. It also regulates the development and virulence of numerous filamentous fungi. In this study, we investigated the specific function of ATG8, a reliable autophagic marker, in the opportunistic pathogen Aspergillus flavus. To investigate the role of atg8 in A. flavus, the deletion and complemented mutants of atg8 were generated according to the homologous recombination principle. Deletion of atg8 showed a significant decrease in conidiation, spore germination, and sclerotia formation compared to the WT and atg8C strains. Additionally, aflatoxin production was found severely impaired in the ∆atg8 mutant. The stress assays demonstrated that ATG8 was important for A. flavus response to oxidative stress. The fluorescence microscopy showed increased levels of reactive oxygen species in the ∆atg8 mutant cells, and the transcriptional result also indicated that genes related to the antioxidant system were significantly reduced in the ∆atg8 mutant. We further found that ATG8 participated in regulating the pathogenicity of A. flavus on crop seeds. These results revealed the biological role of ATG8 in A. flavus, which might provide a potential target for the control of A. flavus and AFB1 biosynthesis.

Effects of oral probiotics on inflammation and intestinal function in adult patients after appendectomy: Randomized controlled trial.

BACKGROUND: Appendectomy is an acute abdominal surgery that is often accompanied by severe abdominal inflammation. Oral probiotics are one of the postoperative treatments for rapid rehabilitation. However, there is a lack of prospective studies on this topic after appendectomy. AIM: To investigate whether the postoperative probiotics can modulate the inflammatory response and restore intestinal function in patients following appendectomy. METHODS: This was a prospective, randomized trial. A total of 60 emergency patients were randomly divided into a control group (n = 30) and a probiotic group (n = 30). Patients in the control group started to drink some water the first day after surgery, and those in the probiotic group were given water supplemented with Bacillus licheniformis capsules for 5 consecutive days postsurgery. The indices of inflammation and postoperative conditions were recorded, and the data were analyzed with RStudio 4.3.2 software. RESULTS: A total of 60 participants were included. Compared with those in the control group, the C-reactive protein (CRP), interleukin 6 and procalcitonin (PCT) levels were significantly lower in the probiotic group at 2 d after surgery (P = 2.224e-05, P = 0.037, and P = 0.002, respectively, all P < 0.05). This trend persisted at day 5 post-surgery, with CRP and PCT levels remaining significantly lower in the probiotic group (P = 0.001 and P = 0.043, both P < 0.05). Furthermore, probiotics resulted in a shorter time to first flatus and a greater percentage of gram-negative bacilli in the feces (P = 0.035, P = 0.028, both P < 0.05). CONCLUSION: Postoperative oral administration of probiotics may modulate the gut microbiota, benefit the recovery of the early inflammatory response, and subsequently enhance recovery after appendectomy.

Investigating the impact of ultrasound on the structural, physicochemical, and emulsifying characteristics of Dioscorin: Insights from experimental data and molecular dynamics simulation.

This study investigated the impact of ultrasound treatment on dioscorin, the primary storage protein found in yam tubers. Three key factors, namely ultrasound power, duration, and frequency, were focused on. The research revealed that ultrasound-induced cavitation effects disrupted non-covalent bonds, resulting in a reduction in α-helix and ß-sheet contents, decreased thermal stability, and a decrease in the apparent hydrodynamic diameter (Dh) of dioscorin. Additionally, previously hidden amino acid groups within the molecule became exposed on its surface, resulting in increased surface hydrophobicity (Ho) and zeta-potential. Under specific ultrasound conditions (200 W, 25 kHz, 30 min), Dh decreased while Ho increased, facilitating the adsorption of dioscorin molecules onto the oil-water interface. Molecular dynamics (MD) simulations showed that at lower frequencies and pressures, the structural flexibility of dioscorin's main chain atoms increased, leading to more significant fluctuations between amino acid residues. This transformation improved dioscorin's emulsifying properties and its oil-water interface affinity.

Transcription of NOD1 and NOD2 and their interaction with CARD9 and RIPK2 in IFN signaling in a perciform fish, the Chinese perch, Siniperca chuatsi.

NOD1 and NOD2 as two representative members of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family play important roles in antimicrobial immunity. However, transcription mechanism of nod1 and nod2 and their signal circle are less understood in teleost fish. In this study, with the cloning of card9 and ripk2 in Chinese perch, the interaction between NOD1, NOD2, and CARD9 and RIPK2 were revealed through coimmunoprecipitation and immunofluorescence assays. The overexpression of NOD1, NOD2, RIPK2 and CARD9 induced significantly the promoter activity of NF-κB, IFNh and IFNc. Furthermore, it was found that nod1 and nod2 were induced by poly(I:C), type I IFNs, RLR and even NOD1/NOD2 themselves through the ISRE site of their proximal promoters. It is thus indicated that nod1 and nod2 can be classified also as ISGs due to the presence of ISRE in their proximal promoter, and their expression can be mechanistically controlled through PRR pathway as well as through IFN signaling in antiviral immune response.

Subjective sleep more predictive of global cognitive function than objective sleep in older adults: A specification curve analysis.

OBJECTIVES: Sleep is associated with cognitive function in older adults. In the current study, we examined this relationship from subjective and objective perspectives, and determined the robustness and dimensional specificity of the associations using a comprehensive modelling approach. METHODS: Multiple dimensions of subjective (sleep quality and daytime sleepiness) and objective sleep (sleep stages, sleep parameters, sleep spindles, and slow oscillations), as well as subjectively reported and objectively measured cognitive function were collected from 55 older adults. Specification curve analysis was used to examine the robustness of correlations for the effects of sleep on cognitive function. RESULTS: Robust associations were found between sleep and objectively measured cognitive function, but not with subjective cognitive complaints. In addition, subjective sleep showed robust and consistent associations with global cognitive function, whereas objective sleep showed a more domain-specific association with episodic memory. Specifically, subjective sleep quality and daytime sleepiness correlated with global cognitive function, and objective sleep parameters correlated with episodic memory. CONCLUSIONS: Overall, associations between sleep and cognitive function in older adults depend on how they are measured and which specific dimensions of sleep and domains of cognitive function are considered. It highlights the importance of focusing on specific associations to ameliorate the detrimental effects of sleep disturbance on cognitive function in later life.

Unraveling the ecological mechanisms of Aluminum on microbial community succession in epiphytic biofilms on Vallisneria natans leaves: Novel insights from microbial interactions.

The extensive use of aluminum (Al) poses an escalating ecological risk to aquatic ecosystems. The epiphytic biofilm on submerged plant leaves plays a crucial role in the regulation nutrient cycling and energy flow within aquatic environments. Here, we conducted a mesocosm experiment aimed at elucidating the impact of different Al concentrations (0, 0.6, 1.2, 2.0 mg/L) on microbial communities in epiphytic biofilms on Vallisneria natans. At 1.2 mg/L, the highest biofilms thickness (101.94 µm) was observed. Al treatment at 2.0 mg/L significantly reduced bacterial diversity, while micro-eukaryotic diversity increased. Pseudomonadota and Bacteroidota decreased, whereas Cyanobacteriota increased at 1.2 mg/L and 2.0 mg/L. At 1.2 and 2.0 mg/L. Furthermore, Al at concentrations of 1.2 and 2.0 mg/L enhanced the bacterial network complexity, while micro-eukaryotic networks showed reduced complexity. An increase in positive correlations among microbial co-occurrence patterns from 49.51% (CK) to 57.05% (2.0 mg/L) was indicative of augmented microbial cooperation under Al stress. The shift in keystone taxa with increasing Al concentration pointed to alterations in the functional dynamics of microbial communities. Additionally, Al treatments induced antioxidant responses in V. natans, elevating leaf reactive oxygen species (ROS) content. This study highlights the critical need to control appropriate concentration Al concentrations to preserve microbial diversity, sustain ecological functions, and enhance lake remediation in aquatic ecosystems.

Adult pancreatoblastoma with atypical histological morphology combined with familial adenomatous polyposis: a rare case report.

Pancreatoblastoma (PB) is a rare malignant pancreatic epithelial tumor that mostly occurs in children and occasionally occurs in adults. The tumor has acinar cell differentiation and squamous corpuscles/squamous epithelial islands, which are frequently separated by fibrous bundles. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of numerous adenomatous polyps in the colon and rectum. Cases of pancreatoblastoma combined with familial adenomatous polyposis (FAP) are rarely reported. A review of a rare case of adult pancreatoblastoma with atypical histological morphology combined with familial adenomatous polyposis is presented herein. In this case, the patient was first diagnosed with familial adenomatous polyposis and subsequently found to have pancreatoblastoma 1 year and 3 months later. This suggests pancreatoblastoma may occur in patients with familial adenomatous polyposis or a family history of the condition, indicating a possible association between the two tumors. Therefore, pancreatoblastoma should be included in a differential diagnosis for FAP patients with a pancreatic mass. The final diagnosis of pancreatoblastoma depends on the pathological diagnosis. Acinar-like cells and squamous corpuscles/squamous epithelial cell islands under light microscopy are the key diagnostic points. This case report also can improve the awareness of clinicians, radiologists, and pathologists on the presence of rare tumor-adult pancreatoblastoma in patients with familial adenomatous polyposis.

Photoredox-catalyzed unsymmetrical diamination of alkenes for access to vicinal diamines.

A photoredox-catalyzed unsymmetrical diamination of alkenes by using N-aminopyridinium salts and nitriles as the amination reagents has been developed. Various vicinal diamines were obtained in moderate to excellent yields under mild reaction conditions. Furthermore, this protocol could be applied in the late-stage modification of pharmaceuticals and natural products. Preliminary mechanistic studies suggested that this methodology may undergo a radical pathway followed by a Ritter-type reaction.

Efficacy and safety of piecemeal submucosal tunneling endoscopic resection for giant esophageal leiomyoma.

BACKGROUND AND AIMS: Giant esophageal leiomyoma usually requires a thoracotomy or thoracoscopic surgery, which is more invasive than an endoscopic treatment. The purpose of this study is to evaluate the efficacy and safety of piecemeal submucosal tunneling endoscopic resection (P-STER) for giant leiomyoma originating from the muscularis propria (MP) layer of the esophagus. METHODS: This is a retrospective study. Patients with giant esophageal leiomyoma (transverse diameter ≥ 3 cm) who underwent P-STER were enrolled from November 2012 to May 2023. Clinical data and results were investigated. RESULTS: A total of 16 patients were enrolled for analysis. The lesion mean transverse diameter and longitudinal diameter were 4.22 ± 1.20 cm and 6.20 ± 1.57 cm, respectively. Our mean operation time was 195.38 ± 84.99 min. The mean number of piecemeal resected was 4.31 ± 2.36. An adverse event noted was an esophageal fistula that occurred in one case (6.25%) and was treated conservatively. The mean length of hospital stay was around 11.81 ± 7.30 days. The mean total hospitalization cost was U.S. dollars (USD) $5976.50 ± 2866.39. No recurrence or metastasis was found during the follow-up period. CONCLUSIONS: P-STER can be an effective and safe treatment for giant leiomyoma originating from the MP layer of the esophagus.

Structure-activity relationship study of 1,6-naphthyridinone derivatives as selective type II AXL inhibitors with potent antitumor efficacy.

The role of AXL in various oncogenic processes has made it an attractive target for cancer therapy. Currently, kinase selectivity profiles, especially circumventing MET inhibition, remain a scientific issue of great interest in the discovery of selective type II AXL inhibitors. Starting from a dual MET/AXL-targeted lead structure from our previous work, we optimized a 1,6-naphthyridinone series using molecular modeling-assisted compound design to improve AXL potency and selectivity over MET, resulting in the potent and selective type II AXL-targeted compound 25c. This showed excellent AXL inhibitory activity (IC50 = 1.1 nM) and 343-fold selectivity over the highly homologous kinase MET in biochemical assays. Moreover, compound 25c significantly inhibited AXL-driven cell proliferation, dose-dependently suppressed 4T1 cell migration and invasion, and induced apoptosis. Compound 25c also showed noticeable antitumor efficacy in a BaF3/TEL-AXL xenograft model at well-tolerated doses. Overall, this study presented a potent and selective type II AXL-targeted lead compound for further drug discovery.

Revealing the response characteristics of periphyton biomass and community structure to sulfamethoxazole exposure in aquaculture water: The perspective of microbial network relationships.

The widespread application of sulfonamide antibiotics in aquaculture has raised concerns about their adverse environmental impacts. Periphyton plays a crucial role in the aquatic ecosystem. In this study, we examined sulfamethoxazole (SMX) effects on the community structure and interactions of periphyton in simulated aquaculture water. Our findings indicated that the total biomass of periphyton decreased, while the biomass of periphytic algae and the secretion of extracellular polymeric substances (EPS) increased at 0.7 × 10-3 mg/L. Under higher SMX concentrations (5 mg/L and 10 mg/L), periphyton growth was severely inhibited, the microbial community structure of periphyton were sharply altered, characterized by the cyanobacteria growth suppression and decrease in the diversity index of community. Furthermore, elevated SMX concentrations (5 mg/L and 10 mg/L) increased the ratio of negative relationships from 45.4% to 49.4%, which suggested that high SMX concentrations promoted potential competition among microbes and disrupted the microbial food webs in periphyton. The absolute abundance of sul1 and sul2 genes in T2 and T3 groups were 2-3 orders of magnitude higher than those in control group after 30 days of SMX exposure, which elevated the risk of resistance gene enrichment and dissemination in the natural environment. The study contributes to our understanding of the detrimental effects of antibiotic pollution, which can induce changes in the structure and interaction relationship of microbial communities in aquaculture water.

UCHL-3 as a potential biomarker of ovarian cancer.

OBJECTIVE: This study explored promising prognostic and immune therapeutic candidate biomarkers for OC and determined the expression, prognostic value, and immune effects of UCHL3. METHODS: UCHL3 expression and clinical data were investigated using bioinformatic analysis. CCK8 and transwell assays were conducted to evaluate the impact of UCHL3 on proliferation and migration, and the effects of UCHL3 were further validated in a mouse model. Univariate and least absolute shrinkage and selection operator regression analyses were performed to construct a novel UCHL3-related prognostic risk model. Gene set enrichment analysis (GSEA) and immune analysis were performed to identify the significantly involved functions of UCHL3. Finally, bioinformatic analysis and immunohistochemistry were performed to explore the effect of UCHL3 on chemotherapy. RESULTS: UCHL3 expression was upregulated and associated with worse overall survival (OS) in OC. UCHL3 depletion repressed cell proliferation and migration both in vitro and in vivo. Furthermore, 237 genes were differentially expressed between the high and low UCHL3 expression groups. Subsequently, a UCHL3-related prognostic signature was built based on six prognostic genes (PI3, TFAP2B, MUC7, PSMA2, PIK3C2G, and NME1). Independent prognostic analysis suggested that age, tumor mutational burden, and RiskScore can be used as independent prognostic factors. The immune infiltration analysis and GSEA suggested that UCHL3 expression was related to the immune response. In addition, UCHL3 expression was higher in platinum-resistant OC patients than in platinum-sensitive patients. UCHL3 overexpression was associated with poorer OS. CONCLUSION: UCHL3 overexpression contributes to aggressive progression, poor survival, and chemoresistance in OC. Therefore, UCHL3 may be a candidate prognostic biomarker and potential target for controlling progression and platinum resistance in OC.

Salvirrane A-F, six undescribed nordrimane sesquiterpene derivatives from Salvia castanea Diels f. tomentosa Stib and their cytotoxic activities.

Six undescribed nordrimane sesquiterpene derivatives, salvirrane A-F (1-6), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Comprehensive spectral analysis and a quantum chemical calculation strategy were employed to determine their structures. These compounds represent four previously unreported nordrimane carbon skeletal types in Salvia genus, including 15-nor-drimane, 11,15-di-nor-drimane, 14,15-di-nor-drimane, and 11,14,15-tri-nor-drimane sesquiterpenes. All compounds were evaluated for their cytotoxic activities against several human cancer cell lines (A549, H460, Hep3B, MCF7, PC3, and HeLa). The results showed that 3 exhibited low activity against MCF7 cells (IC50,72.72 ± 6.95 µM) and moderate activity against HeLa cells (IC50, 9.80 ± 0.64 µM). Moreover, the EdU (5-ethynyl-2'-deoxyuridine) assay demonstrates that 3 displays dose-dependent efficacy in suppressing the proliferation of HeLa cells. Network pharmacology and molecular docking technology implied that 3 may potentially bind to Src (proto-oncogene tyrosine-protein kinase) to exert anti-proliferative activity.

A New Reaction Mode of 3-Halooxindoles: Acting as C-C-O Three-Atom Components for (3+3) Cycloaddition to Access Indolenine-Fused 2H-1,4-Oxathiines.

Herein, we report an unprecedented implementation of 3-halooxindoles as C-C-O three-atom components for (3+3) cycloaddition with pyridinium 1,4-zwitterionic thiolates, affording structurally diverse indolenine-fused 2H-1,4-oxathiines in moderate to high yields. A combined experimental and computational mechanistic study suggests that the reaction proceeds through addition of a S conjugate to the o-azaxylylene intermediate, followed by O-Michael addition and a sequential retro-Michael addition/pyridine extrusion pathway.