Sequential Dearomatization/Rearrangement of Quinazoline-Derived Azomethine Imines for the Synthesis of Nitrogen-Rich Three-Dimensional Cage-Like Molecules.

A sequential dearomatization/rearrangement reaction between quinazoline-derived azomethine imines and crotonate sulfonium salts has been developed to provide a series of three-dimensional cage-like molecules. The reaction involves two dearomatizations, two cyclizations, and two C-C bond and three C-N bond formations in one step. The new transformation has a broad substrate scope, does not require any added reagents, and proceeds under room temperature in a short time. A mechanistic rationale for the sequential dearomatization/rearrangement is also presented. Furthermore, the synthetic compounds are evaluated for their glucose control effect. Compounds 3aa and 3aj were found to be hyperglycemic, which might be lead compounds for treating hypoglycemia.

Single-cell transcriptome analysis upon ECM-remodeling meningioma cells.

Meningiomas are the most common tumours that primarily arise in the central nervous system, but their intratumoural heterogeneity has not yet been thoroughly studied. We aimed to investigate the transcriptome characteristics and biological properties of ECM-remodeling meningioma cells. Single-cell RNA sequencing (ScRNA-seq) data from meningioma samples were acquired and used for analyses. We conducted comprehensive bioinformatics analyses, including screening for differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) term enrichment analyses, Gene Set Enrichment Analysis (GSEA), protein-protein interaction (PPI) analysis, and copy number variation (CNV) analysis on single-cell sequencing data from meningiomas. Eighteen cell types, including six meningioma subtypes, were identified in the data. ECM-remodeling meningioma cells (MGCs) were mainly distributed in brain-tumour interface tissues. KEGG and GO enrichment analyses revealed that 908 DEGs were mainly related to cell adhesion, extracellular matrix organization, and ECM-receptor interaction. GSEA analysis demonstrated that homophilic cell adhesion via plasma membrane adhesion molecules was significantly enriched (NES = 2.375, P < 0.001). CNV analysis suggested that ECM-remodeling MGCs showed considerably lower average CNV scores. ECM-remodeling MGCs predominantly localized at the brain-tumour interface area and adhere stably to the basement membrane with a lower degree of malignancy. This study provides novel insights into the malignancy of meningiomas.

Genome assemblies of 11 bamboo species highlight diversification induced by dynamic subgenome dominance.

Polyploidy (genome duplication) is a pivotal force in evolution. However, the interactions between parental genomes in a polyploid nucleus, frequently involving subgenome dominance, are poorly understood. Here we showcase analyses of a bamboo system (Poaceae: Bambusoideae) comprising a series of lineages from diploid (herbaceous) to tetraploid and hexaploid (woody), with 11 chromosome-level de novo genome assemblies and 476 transcriptome samples. We find that woody bamboo subgenomes exhibit stunning karyotype stability, with parallel subgenome dominance in the two tetraploid clades and a gradual shift of dominance in the hexaploid clade. Allopolyploidization and subgenome dominance have shaped the evolution of tree-like lignified culms, rapid growth and synchronous flowering characteristic of woody bamboos as large grasses. Our work provides insights into genome dominance in a remarkable polyploid system, including its dependence on genomic context and its ability to switch which subgenomes are dominant over evolutionary time.

Repeated atrial arrhythmia induced by cochineal red poisoning: A case report.

BACKGROUND: Cochineal red is an organic compound widely used in food, cosmetics, pharmaceuticals, textiles, and other fields due to its excellent safety profile. Poisoning caused by eating foods containing cochineal red is rare, and repeated atrial arrhythmia due to cochineal red poisoning is even rarer. CASE SUMMARY: An 88-year-old Asian female patient was admitted to hospital due to a disturbance of consciousness. Twelve hours prior to presentation, the patient consumed 12 eggs containing cochineal red over a period of 2 h. At presentation, the patient was in a coma and had a score of 6 on the Glasgow Coma Scale (E2 + VT + M4). The patient's skin and mucous membranes were pink. Electrocardiography (ECG) revealed rapid atrial fibrillation without any signs of ischemia. We prescribed cedilan and fluid replacement for arrhythmia correction. Shortly after admission, the atrial fibrillation corrected to a normal sinus rhythm. On the day 2 of admission, the patient had a sudden atrial flutter accompanied by hemodynamic instability and rapidly declining arterial oxygen saturation between 85% and 90%. The sinus rhythm returned to normal after two electrical cardioversions. Six days after admission, the skin color of the patient returned to normal, and the ECG results were normal. The patient was transferred out of the intensive care unit and eventually discharged after 12 d in hospital. At the 2-mo follow-up visit, the patient was in good health with no recurrence of arrhythmia. CONCLUSION: Although cochineal red is a safe, natural food additive, excessive consumption or occupational exposure can induce cardiac arrhythmias.

How to use the Surveillance, Epidemiology, and End Results (SEER) data: research design and methodology.

In the United States (US), the Surveillance, Epidemiology, and End Results (SEER) program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data. This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field. Currently, the SEER program covers approximately half of the total cancer patients in the US. A growing number of clinical studies have applied the SEER database in various aspects. However, the intrinsic features of the SEER database, such as the huge data volume and complexity of data types, have hindered its application. In this review, we provided a systematic overview of the commonly used methodologies and study designs for retrospective epidemiological research in order to illustrate the application of the SEER database. Therefore, the goal of this review is to assist researchers in the selection of appropriate methods and study designs for enhancing the robustness and reliability of clinical studies by mining the SEER database.

Synthesis of 10-Membered Azecines through Pd-Catalyzed Formal [6+4] Cycloaddition and Their Transannular Reaction to Polycyclic Compounds.

Azecine fragments are frequently presented in natural products and bioactive compounds. However, minor efforts have been devoted to these 10-membered N-heterocycles, and their synthesis is still challenging. Reported herein is the first catalytic formal [6+4] cycloaddition for the synthesis of 10-membered azecines. Under palladium catalysis, the reaction of δ-vinylvalerolactones and benzofuran-derived azadienes proceeds smoothly to afford benzofuran-fused azecines with high diastereoselectivity in moderate to good yields. A unique transannular reaction of these 10-membered azecines for the construction of polycyclic compounds is also demonstrated.

The specific DNA methylation landscape in focal cortical dysplasia ILAE type 3D.

Focal Cortical Dysplasia (FCD) is a frequent cause of drug-resistant focal epilepsy in children and young adults. The international FCD classifications of 2011 and 2022 have identified several clinico-pathological subtypes, either occurring isolated, i.e., FCD ILAE Type 1 or 2, or in association with a principal cortical lesion, i.e., FCD Type 3. Here, we addressed the DNA methylation signature of a previously described new subtype of FCD 3D occurring in the occipital lobe of very young children and microscopically defined by neuronal cell loss in cortical layer 4. We studied the DNA methylation profile using 850 K BeadChip arrays in a retrospective cohort of 104 patients with FCD 1 A, 2 A, 2B, 3D, TLE without FCD, and 16 postmortem specimens without neurological disorders as controls, operated in China or Germany. DNA was extracted from formalin-fixed paraffin-embedded tissue blocks with microscopically confirmed lesions, and DNA methylation profiles were bioinformatically analyzed with a recently developed deep learning algorithm. Our results revealed a distinct position of FCD 3D in the DNA methylation map of common FCD subtypes, also different from non-FCD epilepsy surgery controls or non-epileptic postmortem controls. Within the FCD 3D cohort, the DNA methylation signature separated three histopathology subtypes, i.e., glial scarring around porencephalic cysts, loss of layer 4, and Rasmussen encephalitis. Differential methylation in FCD 3D with loss of layer 4 mapped explicitly to biological pathways related to neurodegeneration, biogenesis of the extracellular matrix (ECM) components, axon guidance, and regulation of the actin cytoskeleton. Our data suggest that DNA methylation signatures in cortical malformations are not only of diagnostic value but also phenotypically relevant, providing the molecular underpinnings of structural and histopathological features associated with epilepsy. Further studies will be necessary to confirm these results and clarify their functional relevance and epileptogenic potential in these difficult-to-treat children.

A Multilevel Analysis of Factors Influencing School Bullying in 15-Year-Old Students.

BACKGROUND: School bullying causes serious impacts on adolescents' physical and mental health. Few studies have explored the various factors influencing bullying by combining different levels of data. METHODS: Based on the database of four Chinese provinces and cities of the Program for International Student Assessment (PISA) in 2018, this study used a multilevel analysis model that combined school-level variables and student-level variables to explore the influencing factors of students being bullied. RESULTS: Students' gender, grade repetition, truancy and arriving late for class, economic, social, and cultural status (ESCS), teacher support, and parent support had significant explanatory power on school bullying on the student-level; on the school-level, school discipline atmosphere and competitive atmosphere among students had significant impacts on school bullying. CONCLUSIONS: Boys, students who have repeated grades, truancy and arriving late for class, and students with lower ESCS suffer from more severe school bullying. When developing school bullying interventions, teachers and parents should pay more attention to those students and provide more emotional support and encouragement to them. Meanwhile, students in schools with a lower discipline atmosphere and a higher level of competitive atmosphere experience greater levels of bullying, and schools should create more positive and friendly environments to prevent bullying events.

Orbital solitary fibrous tumours: clinicopathological characteristics and recurrence prediction.

BACKGROUND: SFTs are thought to have an unpredictable clinical course and currently have no recognized prognostic criterion. Our study aimed to determine the relationship between clinicopathological characteristics and the prognosis of patients with orbital SFTs. METHODS: The clinicopathological features of these patients were extracted from clinical records. The relationships between these features and prognosis were analysed. RESULTS: The positive rates of CD34, CD99, Blc2, and STAT6 expression were 90.3%, 90.3%, 83.9%, and 100%, respectively. The tumour recurrence rate was 38.7%. A higher recurrence rate was observed in patients with Ki67 index ≥ 5 (56.25% vs. 20%, P = 0.038). CONCLUSION: A Ki67 index ≥ 5 was an effective parameter for predicting tumour recurrence of orbital SFTs. Close follow-up is needed for these patients.

Effect of School Bullying on Students' Peer Cooperation: A Moderated Mediation Model.

BACKGROUND: Studies show that cooperative environments enhance student performance. However, school bullying can significantly undermine peer cooperation. There is limited research on how school bullying impacts peer cooperation and the mechanisms involved. METHODS: Using data from 15-year-old middle school students in four Chinese provinces and cities, as part of the 2018 Program for International Student Assessment (PISA), this study employs a moderated mediation model. It examines the negative effects of school bullying on peer cooperation, the mediating role of school belonging, and the moderating effects of teacher support and parents' support. RESULTS: School bullying negatively impacts peer cooperation. School belonging partially mediates this relationship. Teacher support moderates the effect of school bullying on school belonging, which in turn affects peer cooperation. Parents' support moderates the direct impact of school bullying on peer cooperation. CONCLUSION: School bullying reduces peer cooperation by diminishing students' sense of belonging in school. This effect is lessened with increased support from teachers and parents. The findings suggest that while social support is beneficial, it must be balanced and not excessive.

Intracellular alpha-fetoprotein mitigates hepatocyte apoptosis and necroptosis by inhibiting endoplasmic reticulum stress.

BACKGROUND: Endoplasmic reticulum (ER) stress contributes to the pathogenesis of chronic liver diseases, but how hepatocytes respond to ER stress has not been clarified. Alpha-fetoprotein (AFP) is secreted by hepatoma cells and elevated levels of serum AFP are associated with development of liver malignancies. AIM: To investigate whether and how AFP could regulate ER stress and hepatocyte injury. METHODS: The distribution of AFP and the degrees of ER stress in liver tissues and liver injury were characterized by histology, immunohistochemistry, and Western blot in biopsied human liver specimens, two mouse models of liver injury and a cellular model. The levels of AFP in sera and the supernatants of cultured cells were quantified by chemiluminescence. RESULTS: High levels of intracellular AFP were detected in liver tissues, particularly in the necrotic areas, from patients with chronic liver diseases and mice after carbon tetrachloride (CCl4) administration or induction of ER stress, but not from the controls. The induced intracellular AFP was accompanied by elevated activating transcription factor-6 (ATF6) expression and protein kinase R-like ER kinase (PERK) phosphorylation in mouse livers. ER stress induced AFP expression in LO2 cells and decreased their viability. ATF6, but not PERK, silencing mitigated the ER-stress-induced AFP expression in LO2 cells. Conversely, AFP silencing deteriorated the ER stress-mediated LO2 cell injury and CCl4 administration-induced liver damages by increasing levels of cleaved caspase-3, the C/enhancer binding protein homologous protein expression, mixed lineage kinase domain-like pseudokinase and PERK phosphorylation, but decreasing ATF6 expression. CONCLUSION: ER stress upregulated intra-hepatocyte AFP expression by activating ATF6 during the process of liver injury and intracellular AFP attenuated hepatocyte apoptosis and necroptosis by alleviating ER stress.

Zero-dimensional Hybrid Antimony Halide with Intrinsic Cyan Light Emission.

Recently, zero-dimensional (0D) hybrid metal halides have attracted intensive attention with wide applications in solid-state lighting and display diodes. Herein, by using a facile wet-chemistry method, we prepared one new 0D hybrid antimony halide of [HMHQ]2 SbCl5 ⋅ 2H2 O (MHQ=2-methyl-8-hydroxyquinoline) based on the discrete [SbCl5 ]2- unit. Remarkably, the bulk crystals of [HMHQ]2 SbCl5 ⋅ 2H2 O exhibit strong cyan light emission with a promising photoluminescence quantum yield (PLQY) of 18.92%. Systematical studies disclose that the cyan emission is mainly derived from the radiative recombination within conjugated organic cation. Benefiting from the promising luminescent performance, this 0D antimony halide can be utilized as an excellent down-conversion light emitting luminescent material to assemble white light-emitting diodes with high color rendering index (CRI) of 90.2.

Progress in traditional Chinese medicine and natural extracts for the treatment of lupus nephritis.

Lupus nephritis (LN) is an autoimmune disease with multiple system involvement and is also one of the most serious forms of organ damage in systemic lupus erythematosus (SLE), which is mainly caused by the formation and deposition of immune complexes in glomeruli. More than 50% of SLE patients have clinical manifestations of renal damage. At present, the treatment of lupus nephritis is mainly based on glucocorticoids and immunosuppressants. However, due to adverse drug reactions and frequent recurrence or aggravation after drug reduction or withdrawal, the prognosis remains poor; thus, it is still one of the most important causes of end-stage renal failure. Therefore, new treatment strategies are urgently needed. This article aims to review the application of traditional Chinese medicine and natural extracts in the treatment of lupus nephritis to provide the basic mechanisms of treatment and a new treatment strategy with clear effects and high safety performance.

The complete chloroplast genome of Casuarina cunninghamiana (Casuarinaceae).

Casuarina cunninghamiana Miq. naturally occurs in eastern Australia from New South Wales to north Queensland. After being introduced to China, it has become an important tree species of ecological shelter plantations in coastal areas of southern China. In this study, the complete chloroplast (cp) genome of C. cunninghamiana was sequenced and analyzed based on the Illumina NovaSeq 6000 platform. The cp genome of C. cunninghamiana was found to be 15,6129 bp in length, including a large single copy (LSC) region of 86,200 bp and a small single copy (SSC) region of 18,457 bp, which were separated by two inverted repeats (IRs) of 25,736 bp. The cp genome contains 132 genes, consisting of 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The overall GC content of the cp genome was 36.34%. The phylogenetic analyses indicated that C. cunninghamiana was closely related to C. glauca and C. equisetifolia and clustered with 4 Betulaceae species.

18F-FDG PET/CT metabolic parameters correlate with EIF2S2 expression status in colorectal cancer.

Background: We sought to investigate whether the expression of the gene EIF2S2 is related to 18F-FDG PET/CT metabolic parameters in patients with colorectal cancer (CRC). Materials and methods: The expression of EIF2S2 in CRC and its relationship with clinicopathological features were obtained through the ONCOMINE, UALCAN and GEPIA databases. EIF2S2 and GLUT1 expression were examined by immunohistochemistry in 42 CRC patients undergoing preoperative PET-CT examination. Spearman correlation analysis was used to assess the relationship between EIF2S2 and GLUT1 levels and clinical parameters. Correlation analysis between EIF2S2 and Reactome-Glycolysis signatures was performed using GEPIA2. We describe the effect of EIF2S2 knockdown on lactate production and the mRNA levels of glycolysis-related genes in human colon cancer SW480 cells. Results: Immunohistochemistry revealed an upregulation of EIF2S2 protein expression in tumor tissues of colorectal cancer patients, which is consistent with the significant upregulation of EIF2S2 transcript levels in the database. These colorectal cancer patients included 24 cases of colon cancer and 18 cases of rectal cancer, ranging in age from 31 to 78 years. The transcription was significantly related to histological subtypes and TP53 mutations (P <0.05). The value of SUVmax in CRC significantly correlated with the expression of EIF2S2 (rho = 0.462, P <0.01). Although SUVmax and SUVmean was not correlate with the expression of GLUT1 (P <0.05), a significant correlation was observed between the expression of GLUT1 and the volumetric PET parameters, such as MTV and TLG (P < 0.01). GLUT1 expression in CRC was positively correlated with EIF2S2 status (rho = 0.470, P <0.01). In SW480 cells, RNAi-mediated depletion of EIF2S2 inhibited lactic acid production (P <0.05) and SLC2A1, SLC2A3, SLC2A10, HK2, PKM2, LDHA mRNA level (P <0.01). Conclusions: Primary CRC FDG uptake is strongly associated with the overexpression of EIF2S2, and EIF2S2 may promote glycolysis in CRC by mediating GLUT1.

Synthesis of Indolo[2,1-a]benzazepinones through Rhodium-Catalyzed Cascade Reactions of 2-Arylindoles with Allyl Alcohols.

An efficient synthesis of indolo[2,1-a]benzazepinones through rhodium-catalyzed cascade reactions of 2-arylindoles with allyl alcohols has been developed. This work expands the scope of products that are available through C-H activation/intramolecular annulation reactions of 2-arylindoles in organic synthesis.

An aryl thiol-vinyl azide coupling reaction and a thiol-vinyl azide coupling/cyclization cascade: efficient synthesis of ß-ketosulfides and arene-fused 5-methylene-2-pyrrolidinone derivatives.

The addition reaction of thiol to vinyl azide has been extensively studied. Variously substituted aryl thiols are all viable for this coupling process. The scope of the other partner is successfully expanded from α-aryl vinyl azide to α-alkyl vinyl azide. A thiol-vinyl azide coupling/cyclization cascade is realized with substituted aryl vinyl azides carrying a 2-methoxycarbonyl group. The value of ß-ketosulfide products was demonstrated by its application in S-heterocycle synthesis.

Risk assessment model for heart failure in Chinese patients with Takayasu's arteritis.

OBJECTIVES: We aimed to construct and validate a risk assessment model to identify risk factors for heart failure (HF) in patients with Takayasu's arteritis (TAK). METHODS: Three hundred sixty-five patients with TAK were recruited in the East China Takayasu Arteritis Cohort from January 2012 to December 2019. Patients were assigned into training and validation sets following a 2:1 ratio according to the date of enrollment. Clinical characteristics were compared between heart failure (HF) and non-HF subgroups in the training set, and a risk assessment model for HF and its scoring algorithm was established based on logistic regression, which was tested in the validation set. RESULTS: Among total of 74 (20.27%) TAK patients exhibited HF, and 55 cases (74.32%) were in the training set. The risk factors for HF of TAK patients included onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension. We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients in the training set with the score ≥ 3 appeared to be associated with an increased risk of HF with an area under curve (AUC) of 0.88 and 0.90 in Model 1 and Model 2 respectively. The AUC reached to 0.88 and 0.89 in the validation set that proved the accuracy of the model. CONCLUSIONS: We presented a risk assessment model of HF in TAK, which may help clinicians alert the complication of HF in the patients with specifically cardiac impairments. Key Points • Heart failure was not rare in Chinese Takayasu's arteritis patients, and there were approximately 20% of patients with heart failure in ECTA cohort. • Cardiac involvements on echocardiography include pathological valvular and atrioventricular abnormalities. • The onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension were risk factors for heart failure in Takayasu's arteritis patients. • We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients with the risk assessment model score of ≥ 3 appeared to be associated with an increased risk of heart failure.