We report an iron‐catalyzed divergent synthesis of alkylated indoles based on precise control of the activation sites on indoles through the selection of catalysts. Using indoles and styrenes as ...starting materials, 3,5‐di‐alkylated indoles could be prepared selectively and directly for the first time by treating with a catalytic amount of Fe(OTf)3 and 3‐alkylated indoles were achieved exclusively by adding a catalytic amount of γ‐cyclodextrin as the cocatalyst with Fe(OTf)3. This simple method was demonstrated with 52 examples with high yields and broad functional group compatibilities.
Anopheles sinensis is an important malaria vector in Southeast Asia. The widespread emergence of insecticide resistance in this mosquito species poses a serious threat to the efficacy of malaria ...control measures, particularly in China. Recently, the whole-genome sequencing and de novo assembly of An. sinensis (China strain) has been finished. A series of insecticide-resistant studies in An. sinensis have also been reported. There is a growing need to integrate these valuable data to provide a comprehensive database for further studies on insecticide-resistant management of An. sinensis.
A bioinformatics database named An. sinensis genome database (ASGDB) was built. In addition to being a searchable database of published An. sinensis genome sequences and annotation, ASGDB provides in-depth analytical platforms for further understanding of the genomic and genetic data, including visualization of genomic data, orthologous relationship analysis, GO analysis, pathway analysis, expression analysis and resistance-related gene analysis. Moreover, ASGDB provides a panoramic view of insecticide resistance studies in An. sinensis in China. In total, 551 insecticide-resistant phenotypic and genotypic reports on An. sinensis distributed in Chinese malaria-endemic areas since the mid-1980s have been collected, manually edited in the same format and integrated into OpenLayers map-based interface, which allows the international community to assess and exploit the high volume of scattered data much easier. The database has been given the URL: http://www.asgdb.org /.
ASGDB was built to help users mine data from the genome sequence of An. sinensis easily and effectively, especially with its advantages in insecticide resistance surveillance and control.
We conducted a meta-analysis to estimate the impact of different clinical and molecular characteristics on the efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) ...inhibitors. PubMed and Web of Science were searched for related trials. Eleven eligible studies, comprising 5,663 patients, were included in this meta-analysis. We found that the PD-1/PD-L1 inhibitor was associated with a 31% reduction in the risk of death (hazard ratio HR=0.69; 95% CI 0.64-0.74;
<0.00001) for patients with melanoma, non-small-cell lung cancer (NSCLC), urothelial carcinoma, head and neck carcinoma, and renal cell carcinoma. In subgroup analyses, all the patients with PD-L1-positive tumors had overall survival (OS) benefits from PD-1/PD-L1 inhibitors regardless of PD-L1 expression level, and a dose-effect relationship between the expression of PD-L1 and OS benefit from PD-1/PD-L1 inhibitors was observed. There was an OS improvement for patients with a smoking history (
<0.00001), but no OS benefit was observed for nonsmokers (
=0.28). In addition, first-line therapy had better OS than second-line or later treatment (
=0.02). No significant improvement of OS was observed (
=0.70) in patients aged ≥75 years. The relative treatment efficacy was similar according to sex (male vs female,
=0.60), performance status (0 vs ≥1,
=0.68), tumor histology (squamous NSCLC vs non-squamous NSCLC vs melanoma vs urothelial carcinoma vs head and neck carcinoma vs renal cell carcinoma,
=0.64), and treatment type (PD-1 inhibitor vs PD-L1 inhibitor,
=0.36). In conclusion, PD-L1-positive tumors, smoking history, and first-line treatment were potential factors for the efficacy of PD-1/PD-L1 inhibitors. Patients with higher PD-L1 expression might achieve greater OS benefits. In addition, sex, performance status, tumor histology, and treatment type could not predict the efficacy of this therapy. In contrast, patients aged >75 years and nonsmokers might not get OS benefits from this treatment. These results may improve treatment strategies and patient selection for PD-1/PD-L1 inhibitors.
The value of immune checkpoint inhibitor (ICI) combination therapy for patients with lung cancer remains unclear. We conducted a meta-analysis using PubMed, Embase, and ClinicalTrials.gov databases ...to identify eligible randomized controlled trials (RCTs) that might provide a reference for clinical practice. The selection criteria were defined according to the population, intervention, comparison, outcome and study design (PICOS) framework. In all, 12 RCTs with 5,989 patients were included in this meta-analysis. Our results showed that ICI combination therapy was significantly associated with the improvement of overall response rate (ORR) (RR =1.44 95% CI 1.19, 1.74,
=0.0002), progression-free survival (PFS) (HR =0.67 95% CI 0.59, 0.77,
<0.00001), and OS (HR =0.81 95% CI 0.70, 0.95,
=0.008) in lung cancer. In subgroup analyses, combination ICI therapy significantly prolonged OS in non-small-cell lung cancer (NSCLC) patients (HR =0.80 95% CI 0.73, 0.88,
<0.00001) but not in SCLC (HR =0.94 95% CI 0.82, 1.08,
=0.40) patients. Data suggested that PD-1 inhibitors had higher efficacy and safety profiles than PD-L1 and CTLA-4 inhibitors in combination ICI therapy for lung cancer patients. Furthermore, tolerability analysis revealed higher incidences of grade ≥3 AEs, fatigue, and increased transaminases from combination ICI therapy. In conclusion, our meta-analysis indicated that combination ICI therapy should be considered in clinical practice and future study designs for NSCLC patients. However, the current data do not support the large-scale clinical application of combination ICI therapy in SCLC patients.
Theranostics is a concept that integrated imaging and therapy. As an emerging field, it embraces multiple techniques to arrive at an individualized treatment purpose. Indocyanine green(ICG) is a near ...infrared dye that has been approved by Food and Drug Administration(FDA) in USA for the use in indicator-dilution studies in humans. ICG nanoparticles(NPs) have attracted much attention for its potential applications in cancer theranostics. This review focuses on the preparation, application of ICG NPs for in vivo imaging(fluorescent imaging and photoacoustic imaging) and therapeutics(photothermal therapy, photodynamic therapy and photoacoustic therapy), and future directions based on recent developments in these areas. It is hoped that this review might provide new impetus to understand ICG NPs for cancer theranostics.
This study was designed to analyze the effects of human epidermal growth factor receptor-2 (HER2) status on the prognosis of male breast cancer (MBC).
The SEER database was used to identify MBC ...patients diagnosed between 2010 and 2015. Patients were divided into HER2-negative and HER2-positive groups and chi-square test was used to compare the demographics. Propensity score matching (PSM) was used to remove confounding factors. The log-rank test was used to compare the overall survival (OS) and disease-specific survival (DSS) between the two groups. Univariate and multivariate Cox regression analyses were used to evaluate the effects of different variables on the prognosis of MBC patients. Subgroup analysis was conducted by using R software to explore the benefit of OS and DSS in the subgroup of MBC patients.
In the matched cohort, the log-rank test showed that there was a longer OS (
=0.044) in the HER2-negative group, and the 4-year OS rate in HER2-negative patients was significantly improved (
=0.008), but there was no difference in the DSS (
=0.408) and the 4-year DSS rates (
=0.198) between the two groups. Univariate and multivariate Cox regression also showed that the HER2 status did not independently associate with DSS (
=0.444). Subgroup analysis showed that HER2-negative patients experienced a longer OS in the subgroup of tumors 2-4 cm in size, no distant metastasis and who had received radiotherapy, but none of subgroup was found a significant difference in DSS between different HER2 status.
This study identified that HER2 status had a clear influence on OS in patients with MBC, and there was a longer OS and a higher 4-year OS rate in the HER2-negative group. In addition, we observed that HER2 status had no significant effect on DSS in patients with MBC.
The key activity to build semantic web is to build ontologies. But today, the theory and methodology of ontology construction is still far from ready. This paper proposed a theoretical framework for ...massive knowledge management- the knowledge domain framework （KDF）, and introduces an integrated development environment （IDE） named large-scale ontology development environment （LODE）, which implements the proposed theoretical framework. We also compared LODE with other popular ontology development environments in this paper. The practice of using LODE on management and development of agriculture ontologies shows that knowledge domain framework can handle the development activities of large scale ontologies. Application studies based on the described briefly. principle of knowledge domain framework and LODE was
Aim： The search for molecules whose bioactivities are similar to those of given compounds or to optimize the initial lead compounds from high throughput screening has attracted increasing interest in ...recent years. Our goal is to provide a publically searchable database of scaffolds out from a large collection of existing chemical molecules. Results： Although a number of in silico methods have emerged to facilitate this process, which has become known as ＂scaffold hopping＂ or ＂molecular hopping＂, there is an urgent need for a database system to provide such valuable data in the drug design field. Here we have systematically analyzed a collection of commercially available small molecule databases and a bioactive compound database to identify unique scaffolds and we have built apublically searchable database. The analysis of approximately 4 800 000 of these compounds identified 241 824 unique scaffolds, which are stored in a relational database （http：//202.127.30.184：8080/db.html）. Each entry in the database is associated with a molecular occurrence and includes its distribution of molecular properties, such as molecular weight, logP, hydrogen bond acceptor number, hydrogen bond donor number, rotatable bond number and ring number. More importantly, for scaffolds derived from the bioactive compounds database, it also contains the original compounds and their target information. Conclusion： This Web-based database system could help researchers in the fields of medicinal and organic chemistry to design novel molecules with properties similar to the original compounds, but built on novel scaffolds.
Small interfering RNA (siRNA) is an effective therapeutic to regulate the expression of target genes in vitro and in vivo. Constructing a siRNA delivery system with high serum stability, especially ...responsive to endogenous stimuli, remains technically challenging. Herein we develop anti-degradation Y-shaped backbone-rigidified triangular DNA bricks with sticky ends (sticky-YTDBs) and tile them onto a siRNA-packaged gold nanoparticle in a programmed fashion, forming a multi-functional three-dimensional (3D) DNA shell. After aptamers are arranged on the exterior surface, a biocompatible siRNA-encapsulated core/shell nanoparticle, siRNA/Ap-CS, is achieved. SiRNAs are internally encapsulated in a 3D DNA shell and are thus protected from enzymatic degradation by the outermost layer of YTDB. The siRNAs can be released by endogenous miRNA and execute gene silencing within tumor cells, causing cell apoptosis higher than Lipo3000/siRNA formulation. In vivo treatment shows that tumor growth is completely (100%) inhibited, demonstrating unique opportunities for next-generation anticancer-drug carriers for targeted cancer therapies.
Abstract
The origin of charge density waves (CDWs) in TiSe
$_{2}$$
2
has long been debated, mainly due to the difficulties in identifying the timescales of the excitonic pairing and electron–phonon ...coupling (EPC). Without a time-resolved and microscopic mechanism, one has to assume simultaneous appearance of CDW and periodic lattice distortions (PLD). Here, we accomplish a complete separation of ultrafast exciton and PLD dynamics and unravel their interplay in our real-time time-dependent density functional theory simulations. We find that laser pulses knock off the exciton order and induce a homogeneous bonding–antibonding transition in the initial 20 fs, then the weakened electronic order triggers ionic movements antiparallel to the original PLD. The EPC comes into play after the initial 20 fs, and the two processes mutually amplify each other leading to a complete inversion of CDW ordering. The self-amplified dynamics reproduces the evolution of band structures in agreement with photoemission experiments. Hence we resolve the key processes in the initial dynamics of CDWs that help elucidate the underlying mechanism.
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