Adjuvant therapy provides no additional recurrence-free benefit for esophageal squamous cell carcinoma patients after neoadjuvant chemoimmunotherapy and surgery: a multi-center propensity score match study.

Purpose: The need for adjuvant therapy (AT) following neoadjuvant chemoimmunotherapy (nICT) and surgery in esophageal squamous cell cancer (ESCC) remains uncertain. This study aims to investigate whether AT offers additional benefits in terms of recurrence-free survival (RFS) for ESCC patients after nICT and surgery. Methods: Retrospective analysis was conducted between January 2019 and December 2022 from three centers. Eligible patients were divided into two groups: the AT group and the non-AT group. Survival analyses comparing different modalities of AT (including adjuvant chemotherapy and adjuvant chemoimmunotherapy) with non-AT were performed. The primary endpoint was RFS. Propensity score matching(PSM) was used to mitigate inter-group patient heterogeneity. Kaplan-Meier survival curves and Cox regression analysis were employed for recurrence-free survival analysis. Results: A total of 155 nICT patients were included, with 26 patients experiencing recurrence. According to Cox analysis, receipt of adjuvant therapy emerged as an independent risk factor(HR:2.621, 95%CI:[1.089,6.310], P=0.032), and there was statistically significant difference in the Kaplan-Meier survival curves between non-AT and receipt of AT in matched pairs (p=0.026). Stratified analysis revealed AT bring no survival benefit to patients with pathological complete response(p= 0.149) and residual tumor cell(p=0.062). Subgroup analysis showed no significant difference in recurrence-free survival between non-AT and adjuvant chemoimmunotherapy patients(P=0.108). However, patients receiving adjuvant chemotherapy exhibited poorer recurrence survival compared to non-AT patients (p= 0.016). Conclusion: In terms of recurrence-free survival for ESCC patients after nICT and surgery, the necessity of adjuvant therapy especially the adjuvant chemotherapy, can be mitigated.

Clinical Characteristics of Children Infected with SARS-CoV-2 Omicron (B.1.1.529) in China's Shanghai.

Introduction: The pandemic of SARS-CoV-2 brings great challenge and threats to humans worldwide. Multiple variants of SARS-CoV-2 tend to be epidemic, among which Omicron is highly infectious within China. The aim of this study was to analyze the clinical characteristics of children infected with SARS-CoV-2 variant B.1.1.529 (Omicron) in the Shanghai, China. Methods: We included 9378 pediatric patients diagnosed with Omicron and treated in the Shanghai International Convention and Exhibition Center between April 1, 2022 and May 31, 2022. We recorded and summarized the clinical characteristics, infectious conditions and biological features of the children infected with Omicron. Results: A total of 9355 paediatric patients were treated in isolation since Makeshift became available, including 5564 males (59.48%) and 3791 females (40.52%). More than half (55.56%) of the affected children were identified at premises screening. The number of symptomatic or asymptomatic patients was 4530 (48.42%) and 4825 (51.58%), respectively. Initial signs or symptoms in asymptomatic patients included fatigue (3582, 38.29%), cough (560, 5.99%), fever (242, 2.59%) and other (146, 1.56%). Age and number of vaccinations in paediatric patients were negatively associated with the number of days from positive to negative nucleic acid test results. Conclusion: Age and number of vaccinations were key factors influencing the conversion of nucleic acid test results in paediatric patients. Early childhood vaccination is encouraged to establish a complete immune barrier.

ß-C-H Allylation of Trialkylamines with Allenes Promoted by Synergistic Borane/Palladium Catalysis.

Functionalization of the C(sp3 )-H bonds of trialkylamines is challenging, especially for reactions at positions other than the α position. Herein, we report a method for ß-C(sp3 )-H allylation of trialkylamines. In these reactions, which involve synergistic borane/palladium catalysis, an enamine intermediate is first generated from the amine via α,ß-dehydrogenation promoted by B(C6 F5 )3 and a base, and then the enamine undergoes palladium-catalyzed reaction with an allene to give the allylation product. Because the hydride and the proton resulting from the initial dehydrogenation are ultimately shuttled to the product by B(C6 F5 )3 and the palladium catalyst, respectively, these reactions show excellent atom economy. The establishment of this method paves the way for future studies of C-H functionalization of trialkylamines by means of synergistic borane/transition-metal catalysis.

Selective and Functional-Group-Tolerant Photoalkylation of Imines by Energy-Transfer Photocatalysis.

Basic amines show broad bioactivity and remain a promising source of new medicines. The direct photoalkylation of imines offers a promising strategy for complex amines. However, the lack of efficient imine photoreactivity hinders this reaction and remains a fundamental limitation in organic photochemistry. We report an efficient photoalkylation of imines that provides primary amines directly without protecting or leaving groups. The transformation effects C-H addition across N-H imines under energy-transfer photocatalysis by a ketone. Our method is distinguished from organometallic, metal-catalyzed, and photoredox approaches to imine alkylation by its lack of protecting groups and its broad scope, which includes unactivated alkanes, protic substrates, basic amines, heterocycles, and ketone imines. We highlight this scope through the condensation and alkylation of two pharmaceutical ketones, providing complex amines succinctly. Our mechanistic analysis supports a three-step process, involving hydrogen-atom transfer to an imine triplet excited state, intersystem crossing, and radical recombination, with photocatalytic enhancement through energy transfer. We further show that N-H imines are more photoreactive than N-substituted imines, a distinction partially explained by sterics and side reactions. To fully explain this distinction, we introduce the thermodynamic parameter excited-state hydrogen-atom affinity, which is highly effective at predicting the photoreactivity of imines.

An anoikis-related gene signature for prediction of the prognosis in prostate cancer.

Purpose: This study presents a novel approach to predict postoperative biochemical recurrence (BCR) in prostate cancer (PCa) patients which involves constructing a signature based on anoikis-related genes (ARGs). Methods: In this study, we utilised data from TCGA-PARD and GEO databases to identify specific ARGs in prostate cancer. We established a signature of these ARGs using Cox regression analysis and evaluated their clinical predictive efficacy and immune-related status through various methods such as Kaplan-Meier survival analysis, subject work characteristics analysis, and CIBERSORT method. Our findings suggest that these ARGs may have potential as biomarkers for prostate cancer prognosis and treatment. To investigate the biological pathways of genes associated with anoikis, we utilised GSVA, GO, and KEGG. The expression of ARGs was confirmed by the HPA database. Furthermore, we conducted PPI analysis to identify the core network of ARGs in PCa. Results: Based on analysis of the TCGA database, a set of eight ARGs were identified as prognostic signature genes for prostate cancer. The reliability and validity of this signature were well verified in both the TCGA and GEO codifications. Using this signature, patients were classified into two groups based on their risk for developing BCR. There was a significant difference in BCR-free time between the high and low risk groups (P < 0.05).This signature serves as a dependable and unbiased prognostic factor for predicting biochemical recurrence (BCR) in prostate cancer (PCa) patients. It outperforms clinicopathological characteristics in terms of accuracy and reliability. PLK1 may play a potential regulatory role as a core gene in the development of prostate cancer. Conclusion: This signature suggests the potential role of ARGs in the development and progression of PCa and can effectively predict the risk of BCR in PCa patients after surgery. It also provides a basis for further research into the mechanism of ARGs in PCa and for the clinical management of patients with PCa.

C3-Cyanation of Pyridines: Constraints on Electrophiles and Determinants of Regioselectivity.

Methods for C-H cyanation of pyridines are rare. Here, we report a method for C3-selective cyanation of pyridines by a tandem process with the reaction of an in situ generated dihydropyridine with a cyano electrophile as the key step. The method is suitable for late-stage functionalization of pyridine drugs. The low reduction potential of the electrophile and effective transfer of the nitrile group were found to be essential for the success of this method. We studied the reaction mechanism in detail by means of control experiments and theoretical calculations and found that a combination of electronic and steric factors determined the regioselectivity of reactions involving C2-substituted pyridines.

Antibacterial angucyclinone and α-pyrone derivatives from desert-derived Nocardiopsis dassonvillei HDN 154151.

One new angucyclinone derivative, Kanglemycin N (1), and two new biogenetically related α-Pyrones, nocapyrones U-V (2-3), were isolated from a desert-derived Actinomycete Nocardiopsis dassonvillei HDN 154151. Their structures, including absolute configurations, were elucidated by extensive NMR, MS, and ECD analyses. Compound 1 exhibited potent antibacterial activity against Bacillus subtilis, Proteus sp., Vibrio Parahaemolyticus, Escherichia coli and Methicillin-resistant Staphylococcus aureus (MRSA) with MIC values ranging from 0.39 µM to 1.56 µM, and notably the effect of 1 against MRSA significantly exceeded the positive control ciprofloxacin. In addition, compound 1 also showed moderate cytotoxic activity against H69AR, MDA-MB-231, ASPC-1 and K562 cell lines, with IC50 values of 10.46, 8.78, 9.28 and 8.61 µM, respectively.

[miR-129 in the diagnosis, treatment and prediction of clinical prognosis of prostate cancer].

OBJECTIVE: To explore the value of miR-129 in the diagnosis, treatment and prediction of the clinical prognosis of PCa by observing the correlation between miR-129 and the progression of the malignancy. METHODS: This retrospective analysis included 310 male patients who visited the Department of Urology of the General Hospital of Eastern Theater Command from January 2014 to January 2022, 80 as normal healthy men, 80 with BPH, and the other 150 with PCa treated by radical prostatectomy without chemotherapy, radiotherapy or androgen-deprivation therapy. We determined the miR-129 expression in the serum and prostatic tissue of all the subjects by real-time quantitative PCR (RT-qPCR), performed pathological grading of the primary cancerous and pericancerous (≥ 3 cm from the focus) prostate tissues from the 150 PCa patients, collected the demographic and clinical data on all the subjects, and analyzed the correlation of their demographic data with the clinical parameters. We selected and transfected PC-3 and DU-145 cell lines with miR-129 precursor or miR-129 scramble, assessed the proliferation ability of each cell line and detected the expression levels of related proteins by cell proliferation assay and Western blot. RESULTS: The expression of miR-129 was significantly decreased in the serum of the PCa patients compared with that in the normal healthy men and BPH patients (P < 0.01), so was it in the PCa tissue in comparison with that in the pericancerous prostatic tissue (P < 0.01), and it was negatively correlated with the preoperative serum PSA level (P < 0.001), histological grade (P < 0.001), pathological stage (P < 0.001), Gleason score (P < 0.001), lymph node metastasis (P = 0.02), angiolymphatic invasion (P = 0.021) and biochemical recurrence (BCR) (P=0.001). Kaplan-Meier analysis showed a strong correlation of down-regulated miR-129 expression with a lower BCR-free survival rate, while multivariate survival analysis indicated that the expression of miR-129 was an independent prognostic indicator of BCR-free survival of the PCa patients (P < 0.001). Highly expressed miR-129 significantly inhibited the proliferation of PCa cells by regulating the expressions of cell cycle-regulatory proteins. CONCLUSION: The expression of miR-129 is significantly down-regulated in PCa tissues, which plays an important role in inhibiting the proliferation of PCa cells and tumor progression and improving BCR-free survival. Therefore, miR-129 can be considered as a new independent biomarker for the diagnosis, treatment and prediction of the clinical prognosis of PCa.

Oxidation-induced C-H amination leads to a new avenue to build C-N bonds.

In this work, we develop an oxidation-induced C-H functionalization strategy, which not only leads to a new avenue to build C-N bonds, but also leads to different site-selectivity compared with "classic directing-groups". The high selectivity of our new catalytic system originates from the heterogeneous electron-density distribution of the radical cation species which are induced by single electron transfer between the aromatics and oxidant-Cu(ii) species.

Coordination strategy-induced selective C-H amination of 8-aminoquinolines.

In this study, we broke through the directing function of the amide group. The coordination interaction between metal and directing-group enhanced the reactivity of the substrate. Using this strategy, we realized the selective amination of 8-aminoquinolines at the C5 position via employing azoles as the source of amine. Various kinds of 8-aminoquinolines and different substituted azoles were compatible to afford the corresponding C-N coupling products.