A novel ion exchange strategy has been developed to enable the asymmetric construction of axially chiral sulfone-containing styrenes. This approach provides a practical synthesis pathway for various axially chiral sulfone-containing styrenes with good yields, exceptional enantioselectivities, and nearly complete E/Z selectivities. Additionally, the reaction mechanism is elucidated in detail through density functional theory (DFT) calculations.
Tracheal stenosis is a rare but life-threatening disease in preterm infants. Misdiagnosis as congenital tracheal stenosis is common, making surgical management challenging. This report presents a case of a preterm infant with tracheal stenosis and congenital heart malformation treated with ECMO-assisted tracheal resection and end-to-end anastomosis. A male infant was born at 30 weeks of gestation with severe asphyxia, cardiac insufficiency, and pneumonia. Following failed medical treatment, fiberoptic bronchoscopy confirmed mid-tracheal to carinal stenosis. After a 2-week treatment course, ECMO-assisted tracheal resection and end-to-end anastomosis were performed successfully. This case confirms the feasibility of tracheal resection and end-to-end anastomosis in low-weight, preterm infants with tracheal stenosis born at 30 weeks gestation. The utilization of ECMO for oxygenation during surgery provides a clear surgical field and shorter operating time. Surgical intervention may be necessary for neonatal tracheal stenosis depending on the clinical presentation.
Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Adenocarcinoma of Lung/genetics , Cell Cycle , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Division , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Lung Neoplasms/genetics , Up-Regulation/genetics
Although more than 30 different types of neuropeptides have been identified in various cell types and circuits of the cerebellum, their unique functions in the cerebellum remain poorly understood. Given the nature of their diffuse distribution, peptidergic systems are generally assumed to exert a modulatory effect on the cerebellum via adaptively tuning neuronal excitability, synaptic transmission, and synaptic plasticity within cerebellar circuits. Moreover, cerebellar neuropeptides have also been revealed to be involved in the neurogenetic and developmental regulation of the developing cerebellum, including survival, migration, differentiation, and maturation of the Purkinje cells and granule cells in the cerebellar cortex. On the other hand, cerebellar neuropeptides hold a critical position in the pathophysiology and pathogenesis of many cerebellar-related motor and psychiatric disorders, such as cerebellar ataxias and autism. Over the past two decades, a growing body of evidence has indicated neuropeptides as potential therapeutic targets to ameliorate these diseases effectively. Therefore, this review focuses on eight cerebellar neuropeptides that have attracted more attention in recent years and have significant potential for clinical application associated with neurodegenerative and/or neuropsychiatric disorders, including brain-derived neurotrophic factor, corticotropin-releasing factor, angiotensin II, neuropeptide Y, orexin, thyrotropin-releasing hormone, oxytocin, and secretin, which may provide novel insights and a framework for our understanding of cerebellar-related disorders and have implications for novel treatments targeting neuropeptide systems.
Cerebellar Diseases , Neuropeptides , Humans , Cerebellum/metabolism , Purkinje Cells/metabolism , Neurons/metabolism , Cerebellar Cortex/metabolism , Neuropeptides/metabolism , Cerebellar Diseases/pathology
Aliphatic allylic amines are common in natural products and pharmaceuticals. The oxidative intermolecular amination of C(sp3)-H bonds represents one of the most straightforward strategies to construct these motifs. However, the utilization of widely internal alkenes with amines in this transformation remains a synthetic challenge due to the inefficient coordination of metals to internal alkenes and excessive coordination with aliphatic and aromatic amines, resulting in decreasing the reactivity of the catalyst. Here, we present a regioselective Cu-catalyzed oxidative allylic C(sp3)-H amination of internal olefins with azodiformates to these problems. A removable bidentate directing group is used to control the regiochemistry and stabilize the π-allyl-metal intermediate. Noteworthy is the dual role of azodiformates as both a nitrogen source and an electrophilic oxidant for the allylic C-H activation. This protocol features simple conditions, remarkable scope and functional group tolerance as evidenced by >40 examples and exhibits high regioselectivity and excellent E/Z selectivity.
The timing of mammalian diversification in relation to the Cretaceous-Paleogene (KPg) mass extinction continues to be a subject of substantial debate. Previous studies have either focused on limited taxonomic samples with available whole-genome data or relied on short sequence alignments coupled with extensive species samples. In the present study, we improved an existing dataset from the landmark study of Meredith et al. (2011) by filling in missing fragments and further generated another dataset containing 120 taxa and 98 exonic markers. Using these two datasets, we then constructed phylogenies for extant mammalian families, providing improved resolution of many conflicting relationships. Moreover, the timetrees generated, which were calibrated using appropriate molecular clock models and multiple fossil records, indicated that the interordinal diversification of placental mammals initiated before the Late Cretaceous period. Additionally, intraordinal diversification of both extant placental and marsupial lineages accelerated after the KPg boundary, supporting the hypothesis that the availability of numerous vacant ecological niches subsequent to the mass extinction event facilitated rapid diversification. Thus, our results support a scenario of placental radiation characterized by both basal cladogenesis and active interordinal divergences spanning from the Late Cretaceous into the Paleogene.
Marsupialia , Placenta , Humans , Female , Pregnancy , Animals , Phylogeny , Marsupialia/genetics , Sequence Alignment/veterinary , Mammals/genetics , Biological Evolution
Background: Lung adenocarcinoma (LUAD) has high morbidity and mortality. Current studies indicate nucleoporin 107 (NUP107) is involved in the construction of nuclear pore complex, and NUP107 overexpression contributes to the growth and development in most types of cancers, but its effect in LUAD has not been elucidated. Methods: Differences in NUP107 expression were investigated using the Cancer Genome Atlas (TCGA) and multiple Gene Expression Omnibus (GEO) data sets. Enrichment analysis were implemented to probe the NUP107 function. The association of NUP107 with the degree of immune cell infiltration was investigated by the TIMER database, single-sample gene set enrichment analysis (ssGSEA), and ESTIMATE. The association of NUP107 expression with tumor mutation burden (TMB), TP53, and immune checkpoint was analyzed. Single-cell RNA sequencing data were used to detect NUP107 expression in different cell clusters. Finally, we performed real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) to prove the difference of NUP107 expression. Results: NUP107 was overexpressed in LUAD and mainly expressed in cancer stem cell (CSC). Overexpression of NUP107 in LUAD suggested a poorer prognosis. Functional enrichment analysis pointed out that NUP107 was mainly linked to the regulation of cell cycle. Both immune cell infiltration and TMB were found to be in connection with NUP107. Cases in the group with high NUP107 expression had poorer immune infiltration, but had higher expression of immune checkpoints, TMB, and proportion of TP53 mutations. Conclusion: NUP107 is a sensitive diagnostic and prognostic factor for LUAD and may be involved in tumor progression through its effects on cell cycle and immune infiltration.
Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that can occur in various organs, including the lung. Surgical resection is usually the preferred treatment for localized IMT.A 6-year-old female was admitted to our hospital with complaints of "coughing and vomiting for 6 days". A chest CT scan revealed occlusion of the left main bronchus, segmental atelectasis of the left lower lung, and cystic low-density shadows along the bronchial pathway. Subsequent fiberoptic bronchoscopy confirmed the diagnosis of IMT through pathological biopsy. After excluding surgical contraindications, the patient underwent uniportal video-assisted thoracoscopic sleeve lobectomy for treatment. The patient had an uneventful postoperative course and was discharged four days after surgery. After one month, the patient received a follow-up examination and reported no significant discomfort. A chest CT scan revealed no postoperative complications.Our experience suggests that uniportal video-assisted thoracoscopic surgery may be a safe and effective approach for the treatment of pediatric patients with IMT requiring complex surgical procedures such as sleeve lobectomy and tracheoplasty.
An efficient palladium-catalyzed enantioselective direct N-alkylation of indoles using a novel type of axially chiral styrene-phosphine ligand SJTU-PHOS-1 was developed. This reaction demonstrated good functional group compatibility and a wide range scope of substrates in mild conditions. Moreover, the DFT calculations expounded the coordination mode of the metal catalyst and the axially chiral styrene-phosphine ligand in the enantioselectivity control.
An axially chiral styrene-based organocatalyst, featuring a combination of axially chiral styrene-based structure and a pyrrole ring, has been designed and synthesized. This catalyst demonstrates remarkable capabilities in producing a wide range of densely substituted spirooxindoles that feature an alkyne-substituted quaternary stereogenic center. These spirooxindoles are generated through mild cascade Michael/cyclization reactions, resulting in high conversion rates and exceptional enantioselectivity. Our catalytic model, based on experiments, X-ray structure analysis and DFT calculations suggests that chiral matched π-π interactions and multiple H-bonds between the organocatalyst and substrates play significant roles in controlling the stereoselectivity of the reaction.
Herein, we describe a stereoselective sulfa-Michael/aldol cyclization reaction promoted by a rationally designed novel axially chiral styrene-based organocatalyst. A variety of highly substituted tetrahydrothiophenes featuring an alkyne-substituted quaternary stereogenic center are obtained in good yields, excellent stereoselectivities, and exclusive trans selectivities. This process tolerates a broad range of alkynyl-substituted acrylamides under mind conditions. The utility of this approach is highlighted in its excellent asymmetric introduction, scalability, and attractive product diversification.
An asymmetric intramolecular hydroalkylation of unactivated internal olefins with tethered cyclic ketones was realized by the cooperative catalysis of a newly designed chiral amine (SPD-NH2 ) and PdII complex, providing straightforward access to either bridged or fused bicyclic systems containing three stereogenic centers with excellent enantioselectivity (up to 99 % ee) and diastereoselectivity (up to >20 : 1 dr). Notably, the bicyclic products could be conveniently transformed into a diverse range of key structures frequently found in bioactive terpenes, such as Δ6 -protoilludene, cracroson D, and vulgarisins. The steric hindrance between the Ar group of the SPD-NH2 catalyst and the branched chain of the substrate, hydrogen-bonding interactions between the N-H of the enamine motif and the C=O of the directing group MQ, and the counterion of the PdII complex were identified as key factors for excellent stereoinduction in this dual catalytic process by density functional theory calculations.
OBJECTIVE: To explore the relationship between Protein Phosphatase 1 Regulatory Inhibitor Subunit 14B (PPP1R14B) and the occurrence of lung adenocarcinoma (LUAD). METHOD: PPP1R14B expression was investigated using various databases, and its molecular functions and pathways were evaluated using Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Then, the correlation between tumor mutations and PPP1R14B expression was analyzed. Furthermore, the regulation network and expression pathway axes of PPP1R14B were constructed. The correlation analysis between PPP1R14B and immune cell infiltration was performed using deconvolution algorithm analysis and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining of the clinical samples were used for expression validation. RESULTS: PPP1R14B showed high expression in tumor tissue. PPP1R14B was associated with T and N stages and poor prognosis and was linked to the cell cycle, DNA repair, and low immune response. High PPP1R14B expression was associated with high tumor mutation rates. The upstream and downstream genes of PPP1R14B were identified, along with the construction of a protein-protein interaction network (PPI network) and the expression pathway axes of PPP1R14B. PPP1R14B expression was associated with poor immune cell infiltration and a negative correlation between PPP1R14B and mast cell and eosinophil infiltration. CONCLUSION: This study reveals high PPP1R14B expression in LUAD, its contribution to poor prognosis, molecular function, biological pathways, and impact on immune cell infiltration, and provides great insight into the role of PPP1R14B in LUAD tumorigenesis.
Owing to the unique biological functions, bacteria as biological materials have been widely used in biomedical field. With advances in biotechnology and nanotechnology, various bacteria-based bioactive materials were developed for cancer imaging and therapy. In this review, different types of bacteria-based bioactive materials and their construction strategies were summarized. The advantages and property-function relationship of bacteria-based bioactive materials were described. Representative researches of bacteria-based bioactive materials in cancer imaging and therapy were illustrated, revealing general ideas for their construction. Also, limitation and challenges of bacteria-based bioactive materials in cancer research were discussed.
Nanotechnology , Neoplasms , Humans , Nanotechnology/methods , Diagnostic Imaging , Bacteria
Utilization of Freon-type methanes as functional one-carbon synthons in the synthesis of various deuterated indoline alkaloids was demonstrated here. A series of halomethyl radicals were generated from electro-reductive C-X cleavage of Freon-type methanes and captured efficiently by acrylamides to provide various halogenated oxindoles via radical cyclization. This reaction features good functional group tolerance, and deuterium and fluorine atoms could be introduced facilely from Freon-type methanes. Further transformation of halogenated oxindoles enabled the synthesis of many (labeled) bioactive drug molecules and skeletons, such as deuterated (±)-physostigmine, deuterated (±)-esermethole and deuterated (±)-lansai B.
Alkaloids , Methane , Alkaloids/chemistry , Chlorofluorocarbons , Oxindoles , Stereoisomerism
A phosphoric acid catalyzed electrophilic thiocyanation of 3-aryl indoles, which provides an efficient and modular approach to SCN-containing 3-aryl indole compounds, was developed for the first time. A variety of 2-SCN-3-aryl indoles were obtained with moderate to excellent yields. Furthermore, catalytic asymmetric manner of this reaction was also studied. Using chiral phosphoric acid as the catalyst, axially chiral SCN-containing 3-aryl indoles were obtained in moderate to good yields with moderate enantioselectivity.
Indoles , Catalysis , Phosphoric Acids , Stereoisomerism
Primary tracheal tumors are seldom seen, and most of them are malignant. At present, the main treatment is surgical resection. It is rare to accomplish tracheal tumor resection and tracheoplasty via uniportalal thoracoscopy. In order both to maintain the patient's oxygen supply during surgery and to reduce the size of the surgical incision, we have innovatively integrated the ECMO-assisted and uniportal thoracoscopic techniques for the first time, perfectly achieving tracheal tumor resection and tracheoplasty. The intraoperative manipulation was only 180 min in duration. The patient returned to the intensive care unit and recovered smoothly after the surgery. The patient was discharged from the hospital 17 days after the operation. ECMO-assisted uniportal thoracoscopic tracheal resection and tracheoplasty provides a new idea and method for colleagues.
Enantioselective synthesis of axially chiral sulfur-containing biaryl derivatives through the electrophilic sulfenylation of biaryl phenols has been achieved for the first time. This catalytic asymmetric system, which involves sequential desymmetrization and kinetic resolution, is enabled by a combination of a novel 3,3'-disubstituted BINOL-derived selenide catalyst and an achiral sulfonic acid. Control experiments and computational studies suggest that multiple noncovalent interactions between the cocatalysts and substrate, especially a network of hydrogen bond interactions, play a crucial role in determining the enantioselectivity and reactivity.
Herein we disclose a highly efficient enantioselective para-C-H alkylation of aniline derivatives promoted by a base/Co/indeno-pybox ligand system. This methodology leads to the efficient construction of a series of enantioenriched aniline derivatives bearing all-carbon quaternary stereocenters. In addition, several special biologically or medicinally active indoles are facilely synthesized by our Co-catalyzed asymmetry synthesis method. Density functional theory calculations and experiment results suggest that the (acac)- anion of Co(acac)2 plays a very important role in chiral control during the nucleophilic reaction.
A highly regio- and diastereo-selective Brønsted acid-catalyzed tandem hydrothiolation/Friedel-Crafts reaction of linear 1,3-dienes has been developed for the first time, which provides a metal-free and atom-economic way of constructing thiochromane derivatives. Meanwhile, by changing the solvent, 4,3-addition hydrothiolation of 1,3-dienes was also discovered. The origin of the observed selectivity was explained by density functional theory calculations.
