Effect of Placental Transfusion on Long-Term Neurodevelopmental Outcomes in Premature Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The pathophysiology and the potential risks of placental transfusion (PT) differ substantially in preterm infants, necessitating specific studies in this population. This study aimed to evaluate the safety and efficacy of PT in preterm infants from the perspective of long-term neurodevelopmental outcomes. METHODS: We conducted a systematic literature search using placental transfusion, preterm infant, and its synonyms as search terms. Cochrane Central Register of Controlled Trials, Medline, and Embase were searched until March 07, 2023. Two reviewers independently identified, extracted relevant randomized controlled trials, and appraised the risk of bias. The extracted studies were included in the meta-analysis of long-term neurodevelopmental clinical outcomes using fixed-effects models. RESULTS: A total of 5612 articles were identified, and seven randomized controlled trials involving 2551 infants were included in our meta-analysis. Compared with immediate cord clamping (ICC), PT may not impact adverse neurodevelopment events. No clear evidence was found of a difference in the risk of neurodevelopmental impairment (risk ratio [RR]: 0.89, 95% confidence interval [CI]: 0.76 to 1.03, P = 0.13, I2 = 0). PT was not associated with the incidence of cerebral palsy (RR: 1.23, 95% CI: 0.59 to 2.57, P = 0.79, I2 = 0). Analyses showed no differences between the two interventions in cognitive, language, and motor domains of neurodevelopment. CONCLUSIONS: From the perspective of long-term neurodevelopment, PT at preterm birth may be as safe as ICC. Future studies should focus on standardized, high-quality clinical trials and individual participant data to optimize cord management strategies for preterm infants after birth.

Toripalimab plus capecitabine in the treatment of patients with residual nasopharyngeal carcinoma: a single-arm phase 2 trial.

Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.

AI-Based Risk Score from Tumour-Infiltrating Lymphocyte Predicts Locoregional-Free Survival in Nasopharyngeal Carcinoma.

BACKGROUND: Locoregional recurrence of nasopharyngeal carcinoma (NPC) occurs in 10% to 50% of cases following primary treatment. However, the current main prognostic markers for NPC, both stage and plasma Epstein-Barr virus DNA, are not sensitive to locoregional recurrence. METHODS: We gathered 385 whole-slide images (WSIs) from haematoxylin and eosin (H&E)-stained NPC sections (n = 367 cases), which were collected from Sun Yat-sen University Cancer Centre. We developed a deep learning algorithm to detect tumour nuclei and lymphocyte nuclei in WSIs, followed by density-based clustering to quantify the tumour-infiltrating lymphocytes (TILs) into 12 scores. The Random Survival Forest model was then trained on the TILs to generate risk score. RESULTS: Based on Kaplan-Meier analysis, the proposed methods were able to stratify low- and high-risk NPC cases in a validation set of locoregional recurrence with a statically significant result (p < 0.001). This finding was also found in distant metastasis-free survival (p < 0.001), progression-free survival (p < 0.001), and regional recurrence-free survival (p < 0.05). Furthermore, in both univariate analysis (HR: 1.58, CI: 1.13-2.19, p < 0.05) and multivariate analysis (HR:1.59, CI: 1.11-2.28, p < 0.05), we also found that our methods demonstrated a strong prognostic value for locoregional recurrence. CONCLUSION: The proposed novel digital markers could potentially be utilised to assist treatment decisions in cases of NPC.

A deep learning-based semiautomated workflow for triaging follow-up MR scans in treated nasopharyngeal carcinoma.

It is imperative to optimally utilize virtues and obviate defects of fully automated analysis and expert knowledge in new paradigms of healthcare. We present a deep learning-based semiautomated workflow (RAINMAN) with 12,809 follow-up scans among 2,172 patients with treated nasopharyngeal carcinoma from three centers (ChiCTR.org.cn, Chi-CTR2200056595). A boost of diagnostic performance and reduced workload was observed in RAINMAN compared with the original manual interpretations (internal vs. external: sensitivity, 2.5% [p = 0.500] vs. 3.2% [p = 0.031]; specificity, 2.9% [p < 0.001] vs. 0.3% [p = 0.302]; workload reduction, 79.3% vs. 76.2%). The workflow also yielded a triaging performance of 83.6%, with increases of 1.5% in sensitivity (p = 1.000) and 0.6%-1.3% (all p < 0.05) in specificity compared to three radiologists in the reader study. The semiautomated workflow shows its unique superiority in reducing radiologist's workload by eliminating negative scans while retaining the diagnostic performance of radiologists.

Development of a convenient and effective hypertension risk prediction model and exploration of the relationship between Serum Ferritin and Hypertension Risk: a study based on NHANES 2017-March 2020.

Background: Hypertension is a major public health problem, and its resulting other cardiovascular diseases are the leading cause of death worldwide. In this study, we constructed a convenient and high-performance hypertension risk prediction model to assist in clinical diagnosis and explore other important influencing factors. Methods: We included 8,073 people from NHANES (2017-March 2020), using their 120 features to form the original dataset. After data pre-processing, we removed several redundant features through LASSO regression and correlation analysis. Thirteen commonly used machine learning methods were used to construct prediction models, and then, the methods with better performance were coupled with recursive feature elimination to determine the optimal feature subset. After data balancing through SMOTE, we integrated these better-performing learners to construct a fusion model based for predicting hypertension risk on stacking strategy. In addition, to explore the relationship between serum ferritin and the risk of hypertension, we performed a univariate analysis and divided it into four level groups (Q1 to Q4) by quartiles, with the lowest level group (Q1) as the reference, and performed multiple logistic regression analysis and trend analysis. Results: The optimal feature subsets were: age, BMI, waist, SBP, DBP, Cre, UACR, serum ferritin, HbA1C, and doctors recommend reducing salt intake. Compared to other machine learning models, the constructed fusion model showed better predictive performance with precision, accuracy, recall, F1 value and AUC of 0.871, 0.873, 0.871, 0.869 and 0.966, respectively. For the analysis of the relationship between serum ferritin and hypertension, after controlling for all co-variates, OR and 95% CI from Q2 to Q4, compared to Q1, were 1.396 (1.176-1.658), 1.499 (1.254-1.791), and 1.645 (1.360-1.989), respectively, with P < 0.01 and P for trend <0.001. Conclusion: The hypertension risk prediction model developed in this study is efficient in predicting hypertension with only 10 low-cost and easily accessible features, which is cost-effective in assisting clinical diagnosis. We also found a trend correlation between serum ferritin levels and the risk of hypertension.

Hyphosphere microorganisms facilitate hyphal spreading and root colonization of plant symbiotic fungus in ammonium-enriched soil.

Anthropogenic nitrogen inputs lead to a high ammonium (NH4+)/nitrate (NO3-) ratio in the soil, which restricts hyphal spreading of soil fungi. Access of symbiotic fungi to roots is a prerequisite for plant-fungal interactions. Hyphosphere bacteria protect fungi from environmental stress, yet the impact of hyphosphere bacteria on adaptation of host fungi to NH4+-enriched conditions remains unclear. By developing soil microcosm assays, we report that a plant-symbiotic fungus, Phomopsis liquidambaris, harbors specific hyphosphere bacteria that facilitate hyphal spreading and assist in the root colonization in NH4+-enriched soil. Genetic manipulation, 16S rRNA gene analysis and coinoculation assays revealed that the genus Enterobacter was enriched in the hyphosphere of NH4+-sensitive wild-type compared to NH4+-preferring nitrite reductase-deficient strain. The representative Enterobacter sp. SZ2-promoted hyphal spreading is only evident in nonsterilized soil. We further identified an increased abundance and diversity of ammonia-oxidizing archaea (AOA) and a synchronously decreased NH4+:NO3- ratio following SZ2 inoculation. Microbial supplementation and inhibitor assays showed that AOA-mediated reduction in NH4+:NO3- ratio is responsible for SZ2-enhanced fungal adaptation to NH4+-enriched conditions. The Ph. liquidambaris-Enterobacter-AOA triple interaction promoted rice growth in NH4+-enriched soil. Our study reveals the essential role of hyphosphere microorganism-based hyphal spreading in plant-fungal symbiosis establishment within nitrogen-affected agroecosystems.

Widely targeted quantitative lipidomics and prognostic model reveal plasma lipid predictors for nasopharyngeal carcinoma.

BACKGROUND: Dysregulation of lipid metabolism is closely associated with cancer progression. The study aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC), based on lipidomics. METHODS: The plasma lipid profiles of 179 patients with locoregionally advanced NPC (LANPC) were measured and quantified using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set (P < 0.05). A deep survival method called DeepSurv was employed to develop a proposed model based on significant lipid species (P < 0.01) and clinical biomarkers to predict DMFS. Concordance index and receiver operating curve analyses were performed to assess model effectiveness. The study also explored the potential role of lipid alterations in the prognosis of NPC. RESULTS: Forty lipids were recognized as distant metastasis-associated (P < 0.05) by univariate Cox regression. The concordance indices of the proposed model were 0.764 (95% confidence interval (CI), 0.682-0.846) and 0.760 (95% CI, 0.649-0.871) in the training and validation sets, respectively. High-risk patients had poorer 5-year DMFS compared with low-risk patients (Hazard ratio, 26.18; 95% CI, 3.52-194.80; P < 0.0001). Moreover, the six lipids were significantly correlated with immunity- and inflammation-associated biomarkers and were mainly enriched in metabolic pathways. CONCLUSIONS: Widely targeted quantitative lipidomics reveals plasma lipid predictors for LANPC, the prognostic model based on that demonstrated superior performance in predicting metastasis in LANPC patients.

Incidence, consequences, and predictors of serious chemotherapy-induced thrombocytopenia in nasopharyngeal carcinoma.

OBJECTIVES: This study aimed to investigate the incidence, consequences, and predictors of serious chemotherapy-induced thrombocytopenia (CIT) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We retrospectively reviewed the clinical records of patients with NPC between 2013 and 2015. Multivariate Cox proportional hazards regression model and propensity score matching were used to estimate the effect of serious CIT on overall survival. Univariate and multivariate logistic regression analyses were applied to identify the predictors of serious CIT. RESULTS AND CONCLUSION: The incidence of serious CIT was 5.21% in patients with NPC. Patients who experienced serious thrombocytopenia had a worse long-term prognosis, while the difference in short-term survival rate was slight. Chemotherapy regimens of gemcitabine and platinum, 5-fluorouracil and platinum, taxane and platinum, serum potassium ion concentration, serum lactate dehydrogenase levels, platelet count, red blood cell count, and estimated glomerular filtration rate were predictors of serious CIT.

Tumor residue in patients with stage II-IVA nasopharyngeal carcinoma who received intensity-modulated radiation therapy: development and validation of a prediction nomogram integrating postradiotherapy plasma Epstein-Barr virus deoxyribonucleic acid, clinical stage, and radiotherapy dose.

BACKGROUND: To develop and validate a predictive nomogram for tumor residue 3-6 months after treatment based on postradiotherapy plasma Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA), clinical stage, and radiotherapy (RT) dose in patients with stage II-IVA nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: In this retrospective study, 1050 eligible patients with stage II-IVA NPC, who completed curative IMRT and underwent pretreatment and postradiotherapy (-7 to +28 days after IMRT) EBV DNA testing, were enrolled from 2012 to 2017. The prognostic value of the residue was explored using Cox regression analysis in patients (n=1050). A nomogram for predicting tumor residues after 3-6 months was developed using logistic regression analyses in the development cohort (n=736) and validated in an internal cohort (n=314). RESULTS: Tumor residue was an independent inferior prognostic factor for 5-year overall survival, progression-free survival, locoregional recurrence-free survival and distant metastasis-free survival (all P<0.001). A prediction nomogram based on postradiotherapy plasma EBV DNA level (0 vs. 1-499 vs. ≥500 copies/ml), clinical stage (II vs. III vs. IVA), and RT dose (68.00-69.96 vs. 70.00-74.00 Gy) estimated the probability of residue development. The nomogram showed better discrimination (area under the curve (AUC): 0.752) than either the clinical stage (0.659) or postradiotherapy EBV DNA level (0.627) alone in the development and validation cohorts (AUC: 0.728). CONCLUSIONS: We developed and validated a nomogram model integrating clinical characteristics at the end of IMRT for predicting whether tumor will residue or not after 3-6 months. Thus, high-risk NPC patients who might benefit from immediate additional intervention could be identified by the model, and the probability of residue can be reduced in the future.

Short-term efficacy and long-term survival of nasopharyngeal carcinoma patients with radiographically visible residual disease following observation or additional intervention: A real-world study in China.

Background: To explore the short- and long-term outcomes in patients with nasopharyngeal carcinoma (NPC) with magnetic resonance imaging (MRI)-detected residual disease at 3 months post-treatment who received intervention either promptly (0 month) or following observation (after an additional 3 months). Methods: A total of 272 patients with residual disease at 3 months post-treatment (observation [observation for additional 3 months]: 122, intervention [prompt intervention]: 150) were analyzed. Univariate and multivariate analyses were performed to examine the survival. Adverse events were analyzed in all patients. Results: Patients in the observation group had a lower 3-year overall survival (77.1% vs. 85.2%), progression-free survival (10.2% vs. 18.1%), and locoregional relapse-free survival (10.2% vs. 20.6%) (all p < .05), but not distant metastasis-free survival (83.8% vs. 78.4%, p = .189), whereas patients in the intervention group achieved higher complete remission (CR) rates (43.3% vs. 21.2%, p = .003). Patients who achieved CR after prompt intervention had a better survival rate than those who achieved observation-CR or non-CR (p < .001). Multivariate analyses revealed that a wait-and-see policy was an independent prognostic factor for impaired survival (p < .001). No significant differences of acute or late toxicities were observed between the two groups. Conclusions: Patients with NPC with MRI-detected residual disease 3 months post-radiotherapy should be encouraged to undergo prompt intervention rather than adopting a passive wait-and-see policy.

Identification of a differentiation-related prognostic nomogram based on single-cell RNA sequencing in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is a kidney cancer that is originated from the lined proximal convoluted tubule, and its major histological subtype is clear cell RCC (ccRCC). This study aimed to retrospectively analyze single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, to explore the correlation among the evolution of tumor microenvironment (TME), clinical outcomes, and potential immunotherapeutic responses in combination with bulk RNA-seq data from The Cancer Genome Atlas (TCGA) database, and to construct a differentiation-related genes (DRG)-based prognostic risk signature (PRS) and a nomogram to predict the prognosis of ccRCC patients. First, scRNA-seq data of ccRCC samples were systematically analyzed, and three subsets with distinct differentiation trajectories were identified. Then, ccRCC samples from TCGA database were divided into four DRG-based molecular subtypes, and it was revealed that the molecular subtypes were significantly correlated with prognosis, clinicopathological features, TME, and the expression levels of immune checkpoint genes (ICGs). A DRG-based PRS was constructed, and it was an independent prognostic factor, which could well predict the prognosis of ccRCC patients. Finally, we constructed a prognostic nomogram based on the PRS and clinicopathological characteristics, which exhibited a high accuracy and a robust predictive performance. This study highlighted the significance of trajectory differentiation of ccRCC cells and TME evolution in predicting clinical outcomes and potential immunotherapeutic responses of ccRCC patients, and the nomogram provided an intuitive and accurate method for predicting the prognosis of such patients.

Root endophyte differentially regulates plant response to NO3- and NH4+ nutrition by modulating N fluxes at the plant-fungal interface.

In the soil, plant roots associated with fungi often encounter uneven distribution of nitrate (NO3- )/ammonium (NH4+ ) patches, but the mechanism underlying N form-influenced plant-fungal interactions remains limited. We inoculated Arabidopsis with a root endophyte Phomopsis liquidambaris, and evaluated the effects of P. liquidambaris on plant performance under NO3- or NH4+ nutrition. Under NO3- nutrition, P. liquidambaris inoculation promoted seedling growth, whereas under NH4+ nutrition, P. liquidambaris suppressed seedling growth. Under high NH4+ conditions, fungus-colonized roots displayed increased NH4+ accumulation and NH4+ efflux, similar to the effect of ammonium stress caused by elevated NH4+ levels. Notably, this fungus excluded NH4+ during interactions with host roots, thereby leading to increased NH4+ levels at the plant-fungal interface under high NH4+ conditions. A nitrite reductase-deficient strain that excludes NO3- but absorbs NH4+ , decreased NH4+ levels in Arabidopsis shoots and rescued plant growth and nitrogen metabolism under high NH4+ levels. Transcriptomic analysis highlighted that P. liquidambaris had altered transcriptional responses associated with plant response to inorganic N forms. Our results demonstrate that fungus-regulated NO3- /NH4+ dynamics at the plant-fungal interface alters plant response to NO3- /NH4+ nutrition. This study highlights the essential functions of root endophytes in plant adaptation to soil nitrogen nutrients.

[Research progress in original species identification in industry chain of Rhei Radix et Rhizoma].

Rhei Radix et Rhizoma is a kind of commonly used Chinese medicinal materials. Due to the overharvesting, the wild resource is endangering. Large market demand caused severely adulterant of commercial Rhei Radix et Rhizoma medicinal materials and decoction pieces. This manuscript reviewed the advances of the original species authentication in the industrial chain of Rhei Radix et Rhizoma during the latest decade, including characteristics and microscopic features, phytochemical analysis on anthraquinones, and molecular authentication based on DNA barcoding. Accordingly, an original species authentication route for the industrial chain of Rhei Radix et Rhizoma was summarized:(1)the identification of seeds and seedlings by DNA barcoding;(2) the selection of high variable sites based on the chloroplast genome;(3)biomonitoring of the Rhei Radix et Rhizoma medicinal materials and decoction pieces by two-dimensional DNA barcode;(4)traceability of Chinese patent medicines by third-generation sequencing. In conclusion, the combination of molecular identification and traditional identification methods provides a new idea for the identification of the original species of Rhei Radix et Rhizoma in the industrial chain and a essential guidance for the research of drug safety and efficacy of Rhei Radix et Rhizoma.

Surgical outcomes of laparoscopic distal pancreatectomy in elderly and octogenarian patients: a single-center, comparative study.

BACKGROUND: Although recent reports have suggested the advantages of laparoscopic distal pancreatectomy (LDP), the potential benefits of this approach in elderly patients remain unclear. The aim of this study was to clarify the value of LDP in the elderly, in whom co-morbid diseases were generally more common. METHODS: Seventy elderly patients (≥ 70 years) and 264 non-elderly patients (40-69 years) who underwent LDP, and 48 elderly patients (≥ 70 years) who underwent open distal pancreatectomy (ODP) between May 2005 and May 2018 were studied. Demographics, intraoperative, and postoperative outcomes were compared. RESULTS: Comorbidity was more common in elderly patients than in non-elderly patients who underwent LDP (57.1 vs. 38.3%, p < 0.01). The intraoperative factors, postoperative complication rate, and length of hospital stay were comparable in these two groups. Elderly patients who underwent LDP had a significantly shorter operative time (185.5 vs. 208.0 min, p = 0.02), less blood loss (191.0 vs. 291.8 mL, p < 0.01), and reduced length of postoperative hospital stay (11.4 vs. 15.1 days, p < 0.01) than elderly patients who had ODP. The overall complication rate tended to be lower in LDP group than that in ODP group (20.0 vs. 33.3%, p = 0.07). CONCLUSION: LDP performed on the elderly is safe and feasible, leading to short-term outcomes similar to those of non-elderly patients. LDP could be an alternative to ODP in elderly patients, providing a lower rate of morbidity and favorable postoperative recovery and outcomes.

Catalyst-free [4 + 2] cyclization of para-quinone methide derivatives with homophthalic anhydrides.

The title reaction has been established, which offers a useful method for the construction of dihydrocoumarin frameworks in generally good chemical yields (up to 99%) and high diastereoselectivities (up to >95 : 5 dr). This reaction represents a good example of [4 + 2] cyclizations of para-quinone methide derivatives with electron-rich reaction partners under catalyst-free conditions.

Endophytic Pseudomonas induces metabolic flux changes that enhance medicinal sesquiterpenoid accumulation in Atractylodes lancea.

The bacterial endophyte Pseudomonas fluorescens ALEB7B significantly enhances photosynthate accumulations in Atractylodes lancea. These carbohydrates are preferentially used by the host plant to synthesize secondary metabolites, rather than to increase plant biomass accumulation. Mechanisms underlying the allocation of endophyte-increased carbohydrate in different plant metabolic processes are largely unknown. We have studied how P. fluorescens ALEB7B enhances photosynthate accumulation and how bacterial elicitors regulate metabolic flux and increase medicinal sesquiterpenoid formation in A. lancea using the sterile tissue culture plantlets. P. fluorescens ALEB7B enhances plant photosynthate accumulation by synthesizing and secreting indole-3-acetic acid, which has been demonstrated using high-performance liquid chromatography analysis. The increased endogenous indole-3-acetic acid promotes plant root development and then assimilation. Increased carbohydrates provide the material basis for the formations of terpenoid hydrocarbon scaffolds, which has been proved using gas chromatography analysis. Further, protein and polysaccharide elicitors secreted by P. fluorescens ALEB7B have been separated and purified from the bacterial fermentation broth, which have been applied to A. lancea plantlets. Both elicitors can stimulate the conversions of terpenoid hydrocarbon scaffolds to oxygenous sesquiterpenoids, the active medicinal ingredients in A. lancea, by triggering the oxidative burst in planta. Moreover, this study separates an ABC transporter substrate-binding protein from protein elicitors secreted by P. fluorescens ALEB7B with an ÄKTA Prime Plus Purifier System and firstly shows that this protein is essential to induce oxygenous sesquiterpenoid accumulation in A. lancea. This study provides new perspectives for mechanisms of medicinal oxygenous terpenoid synthesis, which has important reference values to the cultivation of medicinal plants that have terpenoids as their active ingredients, such as Artemisia annua and Taxus chinensis.

Synergistic-Catalysis-Enabled Reaction of 2-Indolymethanols with Oxonium Ylides for the Construction of 3-Indolyl-3-Alkoxy Oxindole Frameworks.

A synergistic-catalysis-enabled reaction of 2-indolymethanols with oxonium ylides has been established that makes use of a three-component reaction between 3-diazooxindoles, alcohols, and 2-indolymethanols under the cooperative catalysis of a metal complex and a Brønsted acid. This reaction has not only provided a new approach for the construction of 3-indolyl-3-alkoxy oxindole scaffolds by utilizing the C3-electrophilicity of an indole, but it is also the first example of a nucleophilic addition of a metal-associated ylide to 2-indolylmethanols. In addition, this reaction also includes a rarely reported trapping of onium ylides with aryl electrophiles.

Catalytic Asymmetric [2+3] Cyclizations of Azlactones with Azonaphthalenes.

The first catalytic asymmetric [2+3] cyclization of azlactones with azonaphthalenes has been established. This strategy allowed the synthesis of a variety of chiral isatin derivatives in generally good yields and excellent enantioselectivities (up to 99 % yield, 98 % ee). The developed reaction has not only established a catalytic enantioselective [2+3] cyclization using azlactones as two-carbon building blocks, but also enriches the chemistry of catalytic asymmetric cyclizations of azonaphthalenes. In addition, this protocol will provide a useful method for constructing enantioenriched 3,3'-disubstituted isatin-type frameworks.

Catalytic asymmetric chemodivergent arylative dearomatization of tryptophols.

The first catalytic asymmetric arylative dearomatization of tryptophols has been established. By using quinone imine ketals as aryl group surrogates and modulating the reaction conditions, the cascade reaction of tryptophols with quinone imine ketals in the presence of chiral phosphoric acid afforded two series of arylative dearomatization products with generally high yields (up to 99%), and excellent diastereo- and enantioselectivities (all > 95 : 5 dr, 90% to 99% ee) in a chemoselective manner.