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.

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.

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.

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.

Survival outcomes of neoadjuvant immunochemotherapy versus chemotherapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months. METHODS: This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS). RESULTS: Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171-0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145-0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar. CONCLUSION: This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety.

Characterization of a group of germacrene A synthases involved in the biosynthesis of ß-elemene from Atractylodis macrocephala.

ß-Elemene, an important component of the volatile oil of Atractylodis macrocephala, has been widely utilized as an antitumor drug for over 20 years. However, the germacrene A synthase (GAS) genes responsible for the biosynthesis of ß-elemene in A. macrocephala were previously unidentified. In this study, two new AmGASs were identified from the A. macrocephala transcriptome, demonstrating their capability to convert farnesyl pyrophosphate into germacrene A, which subsequently synthesizes ß-elemene through Cope rearrangement. Additionally, two highly catalytic AmGAS1 mutations, I307A and E392A, resulted in a 2.23-fold and 1.57-fold increase in ß-elemene synthesis, respectively. Furthermore, precursor supply and a fed-batch strategy were employed to enhance the precursor supply, resulting in ß-elemene yields of 7.3 mg/L and 33.3 mg/L, respectively. These findings identify a promising candidate GAS for ß-elemene biosynthesis and lay the foundation for further functional studies on terpene synthases in A. macrocephala.

Extraction, characterization and intestinal anti-inflammatory and anti-oxidative activities of polysaccharide from stems and leaves of Chuanminshen violaceum M. L. Sheh & R. H. Shan.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.

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.

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.

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 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.

Anti-HBV Activities of Cembranoids from the South China Sea Soft Coral Sinularia pedunculata and Their Structure Activity Relationship.

Hepatitis B Virus (HBV) infection is a global public health challenge that seriously endangers human health. Soft coral, as a major source of terpenoids, contains many structurally novel and highly bioactive compounds. In previous studies, it has been demonstrated that cembranoid-type diterpenoids showed significant anti-inflammatory and anti-colorectal cancer activities. In this study, cembranoids isolated from Sinularia pedunculata was found with anti-HBV activity for the first time. Among them, compound 6 showed significant anti-HBV activity with an IC50 value of 5.57 µM without cytotoxicity. We analysed the preliminary structure-activity relationship (SAR). Furthermore, it is demonstrated that compound 6 can accelerate the formation of capsid, inhibit HBeAg, HBV core particle DNA, HBV total RNA and pregenomic RNA in a dose dependent manner. We also confirmed the anti-HBV activity in HepG2-NTCP infection system. Finally, we find the anti-HBV mechanism of these compounds by inhibiting the ENI/Xp enhancer/promoter.

A Lesion-Fusion Neural Network for Multi-View Diabetic Retinopathy Grading.

As the most common complication of diabetes, diabetic retinopathy (DR) is one of the main causes of irreversible blindness. Automatic DR grading plays a crucial role in early diagnosis and intervention, reducing the risk of vision loss in people with diabetes. In these years, various deep-learning approaches for DR grading have been proposed. Most previous DR grading models are trained using the dataset of single-field fundus images, but the entire retina cannot be fully visualized in a single field of view. There are also problems of scattered location and great differences in the appearance of lesions in fundus images. To address the limitations caused by incomplete fundus features, and the difficulty in obtaining lesion information. This work introduces a novel multi-view DR grading framework, which solves the problem of incomplete fundus features by jointly learning fundus images from multiple fields of view. Furthermore, the proposed model combines multi-view inputs such as fundus images and lesion snapshots. It utilizes heterogeneous convolution blocks (HCB) and scalable self-attention classes (SSAC), which enhance the ability of the model to obtain lesion information. The experimental results show that our proposed method performs better than the benchmark methods on the large-scale dataset.

Oblique conformal anastomosis decreased the risks of cervical anastomotic leakage after totally minimally invasive esophagectomy.

OBJECTIVE: To investigate the effectiveness of the original oblique conformal anastomosis presented in this research in reducing the incidence of cervical anastomotic leak after performing totally minimally invasive esophagectomy (TMIE). METHODS: The esophagus and stomach of 27 fresh pigs, termed the esophagogastric model, were used to simulate human esophagogastric organs for this study's in vitro experimental objectives. Nine esophagogastric models of similar weight were divided into three groups. Esophagogastrostomy with circular-stapled end-to-side anastomosis was performed. A tension gauge was used to pull the anastomosis, and the tension at which anastomotic leakage occurred was recorded. Furthermore, a retrospective assessment of 539 patients who underwent TMIE was conducted to analyze the influencing factors of cervical anastomotic leakage. RESULTS: Experiments on the esophagogastric models showed a higher fracture strength of oblique conformal anastomosis than that of conventional anastomosis (F2,18 = 40.86, P < 0.05), which was associated with a lower incidence of cervical anastomotic leakage (X2 = 9.0260, P = 0.0027). Retrospective analysis of 539 esophageal cancer patients who underwent TMIE showed that in contrast to conventional anastomosis, oblique conformal anastomosis was an independent protective factor against cervical anastomotic leakage (P = 0.0462, OR = 0.5872, 95% CI = 0.3497-0.9993). CONCLUSION: Oblique conformation anastomosis was stronger and involved a more prominent reduced risk of cervical anastomotic leakage than conventional anastomosis after TMIE.

Gastric Cancer Mesenchymal Stem Cells Trigger Endothelial Cell Functional Changes to Promote Cancer Progression.

Our previous studies have highlighted the pivotal role of gastric cancer mesenchymal stem cells (GCMSCs) in tumor initiation, progression, and metastasis. In parallel, it is well-documented that endothelial cells (ECs) undergo functional alterations in response to challenging tumor microenvironment. This study aims to elucidate whether functional changes in ECs might be induced by GCMSCs and thus influence cancer progression. Cell proliferation was assessed through CCK-8 and colony formation assays, while cell migration and invasion capabilities were evaluated by wound-healing and Transwell assays. Immunohistochemistry was employed to examine protein distribution and expression levels. Additionally, quantitative analysis of protein and mRNA expression was carried out through Western blotting and qRT-PCR respectively, with gene knockdown achieved using siRNA. Our findings revealed that GCMSCs effectively stimulate cell proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs), both in vitro and in vivo. GCMSCs promote the migration and invasion of gastric cancer cells by inducing the expression of Slit2 in HUVECs. Notably, the inhibition of phosphorylated AKT partially mitigates the aforementioned effects. In conclusion, GCMSCs may exert regulatory control over Slit2 expression in ECs via the AKT signaling pathway, thereby inducing functional changes in ECs that promote tumor progression.

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.

NBS-Promoted Synthesis of Thiocyanated Aminomaleimides and Site-Selective Intramolecular Cyclization Access to 1,4-Benzothiazepines via S-CN Bond Cleavage.

A transition metal-free concise and efficient protocol for the synthesis of thiocyanated aminomaleimides and benzo[e][1,4]thiazepine derivatives has been developed. The method involves an initial α-C-H thiocyanation of aminomaleimides with KSCN and TEMPO-mediated tandem S-CN bond cleavage/intramolecular cyclization substitution processes, which enables the formation of seven-membered S/N-heterocycles. This synthetic strategy provides a reliable method for the synthesis of biologically interesting benzo[e][1,4]thiazepine derivatives by using KSCN as sulfur sources as well as expands the application of enaminones thiocyanation reactions in heterocycles synthesis.