IMperm: a fast and comprehensive IMmune Paired-End Reads Merger for sequencing data.

The adaptive immune receptor repertoire (AIRR), consisting of T- and B-cell receptors, is the core component of the immune system. The AIRR sequencing is commonly used in cancer immunotherapy and minimal residual disease (MRD) detection of leukemia and lymphoma. The AIRR is captured by primers and sequenced to yield paired-end (PE) reads. The PE reads could be merged into one sequence by the overlapped region between them. However, the wide range of AIRR data raises the difficulty, so a special tool is required. We developed a software package for IMmune PE reads merger of sequencing data, named IMperm. We used the k-mer-and-vote strategy to pin down the overlapped region rapidly. IMperm could handle all types of PE reads, eliminate adapter contamination and successfully merge low-quality and minor/non-overlapping reads. Compared with existing tools, IMperm performed better in both simulated and sequencing data. Notably, IMperm was well suited to processing the data of MRD detection in leukemia and lymphoma and detected 19 novel MRD clones in 14 patients with leukemia from previously published data. Additionally, IMperm can handle PE reads from other sources, and we demonstrated its effectiveness on two genomic and one cell-free deoxyribonucleic acid datasets. IMperm is implemented in the C programming language and consumes little runtime and memory. It is freely available at https://github.com/zhangwei2015/IMperm.

Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma.

Comprehensive identification of somatic structural variations (SVs) and understanding their mutational mechanisms in cancer might contribute to understanding biological differences and help to identify new therapeutic targets. Unfortunately, characterization of complex SVs across the whole genome and the mutational mechanisms underlying esophageal squamous cell carcinoma (ESCC) is largely unclear. To define a comprehensive catalog of somatic SVs, affected target genes, and their underlying mechanisms in ESCC, we re-analyzed whole-genome sequencing (WGS) data from 31 ESCCs using Meerkat algorithm to predict somatic SVs and Patchwork to determine copy-number changes. We found deletions and translocations with NHEJ and alt-EJ signature as the dominant SV types, and 16% of deletions were complex deletions. SVs frequently led to disruption of cancer-associated genes (e.g., CDKN2A and NOTCH1) with different mutational mechanisms. Moreover, chromothripsis, kataegis, and breakage-fusion-bridge (BFB) were identified as contributing to locally mis-arranged chromosomes that occurred in 55% of ESCCs. These genomic catastrophes led to amplification of oncogene through chromothripsis-derived double-minute chromosome formation (e.g., FGFR1 and LETM2) or BFB-affected chromosomes (e.g., CCND1, EGFR, ERBB2, MMPs, and MYC), with approximately 30% of ESCCs harboring BFB-derived CCND1 amplification. Furthermore, analyses of copy-number alterations reveal high frequency of whole-genome duplication (WGD) and recurrent focal amplification of CDCA7 that might act as a potential oncogene in ESCC. Our findings reveal molecular defects such as chromothripsis and BFB in malignant transformation of ESCCs and demonstrate diverse models of SVs-derived target genes in ESCCs. These genome-wide SV profiles and their underlying mechanisms provide preventive, diagnostic, and therapeutic implications for ESCCs.

The genomic dynamics during progression of lung adenocarcinomas.

Intra-tumor heterogeneity is a big barrier to precision medicine. To explore the underlying clonal diversity in lung adenocarcinomas, we selected nine individuals with whole-genome sequencing data from primary and matched metastatic tumors as a cohort for study. Similar global pattern of arm-level copy number changes and large variations of somatic single-nucleotide variant between the primary and metastasis are observed in the majority of cases. Importantly, we found breakage-fusion-bridge (BFB) cycles acting as an important mechanism for underlying cancer gene amplification, such as amplification of CDK4, CDKN3 and FGFR1 in early stage. We also identified recurrent focal amplification of gene CCNY derived from BFB in two metastatic tumors, but not in primary tumor. Clonal analysis of case 236T demonstrated that mutational processes are varying with tumor progression. Collectively, our data provide new insights into genetic diversity and potential therapeutic target in lung adenocarcinoma.

Stereoselective Electrophilic Chlorination of ß,ß-Disubstituted Enesulfinamides with Chloramine-T: Asymmetric Synthesis of Acyclic α,α-Disubstituted α-Chlorinated Carbonyl Surrogates.

Enamine and iminium ion-mediated asymmetric organocatalysis was not successful in achieving highly stereoselective α-chlorination of acyclic α,α-disubstituted carbonyls. To address this limitation, an alternative method was developed, which involved the use of geometry-defined persubstituted enesulfinamides to intercept the electrophilic chlorinating reagent. This approach enables the asymmetric construction of challenging acyclic α,α-disubstituted α-chlorinated ketimines with a high degree of stereoselectivity. The use of chloramine-T, a cost-effective and stable chlorine source rarely utilized in asymmetric electrophilic chlorination, plays a crucial role in achieving superior stereocontrol.

A data mining approach to analyze the role of biomacromolecules-based nanocomposites in sustainable packaging.

Recent decades have witnessed a surge in research interest in bio-nanocomposite-based packaging materials, but still, a lack of systematic analysis exists in this domain. Bio-based packaging materials pose a sustainable alternative to petroleum-based packaging materials. The current work employs bibliometric analysis to deliver a comprehensive outline on the role of bio nanocomposites in packaging. India, Iran, and China were revealed to be the top three nations actively engaged in this domain in total publications. Islamic Azad University in Iran and Universiti Putra Malaysia in Malaysia are among the world's best institutions in active research and publications in this field. The extensive collaboration between nations and institutions highlights the significance of a holistic approach towards bio-nanocomposite. The National Natural Science Foundation of China is the leading funding body in this field of research. Among authors, Jong whan Rhim secured the topmost citations (2234) in this domain (13 publications). Among journals, Carbohydrate Polymers secured the maximum citation count (4629) from 36 articles; the initial one was published in 2011. Bio nanocomposite is the most frequently used keyword. Researchers and policymakers focussing on sustainable packaging solutions will gain crucial insights on the current research status on packaging solutions using bio-nanocomposites from the conclusions.

Tourism Competitiveness Evaluation: Evidence From Mountain Tourism in China.

The evaluation of tourism competitiveness is an important tool for analyzing the potential of tourism in a specific context. Enshi Autonomous Prefecture (EAP) in China is selected as a case through which to explore the potential of mountain tourism and its competitiveness in the tourism industry. This study develops EAP's mountain tourism competitiveness model focusing on three criteria: core competitiveness of mountain tourism, the economic environment's competitiveness, and infrastructure competitiveness. Context-specific customized evaluation index has been applied to data collected from EAP Statistical Yearbook for 2005-2014. The study reveals that the value of EAP's mountain tourism core competitiveness, economic and environmental competitiveness, and infrastructure competitiveness are 84.292, 13.4, and 2.308%, respectively. When tourism core competitiveness is increased by one unit, EAP's mountain tourism competitiveness will increase by 0.84292 units. Similarly, when economic environment competitiveness is increased by one unit, EAP's mountain tourism competitiveness will increase by 0.134 units. EAP's mountain tourism competitiveness increases by 0.02308 units when infrastructure competitiveness increases by one unit. The major reasons for low levels of competitiveness were lack of awareness of the county authority, a low level of cooperation, and weak infrastructure. The recommendations from the study's findings are as follows. Firstly, the county authority should appropriately improve the relationship between competition and cooperation, maintaining cooperation in competition, and competition in cooperation. Secondly, the county authority should strengthen communication by establishing an effective coordinated mechanism. Thirdly, the county authority should improve the sense of cooperation and jointly develop the mountain tourism market. Fourthly, the county authority should improve the construction of tourism infrastructure and break down the barriers to tourism cooperation. The study's findings help develop a "win-win" cooperation mechanism within the competition and support the sustainable development of the mountain tourism industry while reducing poverty and promoting the revitalization of the mountains of China.

Preparation and thermal conductivity enhancement of a paraffin wax-based composite phase change material doped with garlic stem biochar microparticles.

The addition of thermally conductive nanomaterials is an effective strategy for increasing the thermal conductivity of phase change materials (PCMs). However, nanomaterials are expensive and may significantly reduce the latent heat capacity of PCMs. In this study, low-cost and eco-friendly biochar microparticles were prepared from garlic stems, a common food waste in Singapore. The thermal properties of paraffin wax (PW) doped with 1, 3, and 5 wt% garlic stem biochar (GSB) microparticles were investigated. The GSB microparticles prepared at 700 °C had three-dimensional porous and two-dimensional flake-like structures, which contributed to the formation of additional heat transfer pathways in the PW. The addition of 5 wt% GSB microparticles enhanced the thermal conductivity of PW by 27.3% and 7.2% in the solid and liquid phases, respectively. The T-history test revealed that the melting and solidification rates of PW improved by 90 and 115 s, respectively. The improved heat transfer performance was mainly ascribed to the high degree of graphitization and the interconnected porous carbon structure of the GSB microparticles. The phase change temperatures of PW were slightly changed upon the addition of GSB microparticles, and the latent heat capacity was only reduced by 6.1%. These results suggest that the GSB microparticles can be used as a potential alternative to other nanoadditives such as metal- and metal oxide-based nanoadditives.

Altered metabolome and microbiome features provide clues in understanding irritable bowel syndrome and depression comorbidity.

Irritable bowel syndrome (IBS) is one of the functional gastrointestinal disorders characterized by chronic and/or recurrent symptoms of abdominal pain and irregular defecation. Changed gut microbiota has been proposed to mediate IBS; however, contradictory results exist, and IBS-specific microbiota, metabolites, and their interactions remain poorly understood. To address this issue, we performed metabolomic and metagenomic profiling of stool and serum samples based on discovery (n = 330) and validation (n = 101) cohorts. Fecal metagenomic data showed moderate dysbiosis compared with other diseases, in contrast, serum metabolites showed significant differences with greater power to distinguish IBS patients from healthy controls. Specifically, 726 differentially abundant serum metabolites were identified, including a cluster of fatty acyl-CoAs enriched in IBS. We further identified 522 robust associations between differentially abundant gut bacteria and fecal metabolites, of which three species including Odoribacter splanchnicus, Escherichia coli, and Ruminococcus gnavus were strongly associated with the low abundance of dihydropteroic acid. Moreover, dysregulated tryptophan/serotonin metabolism was found to be correlated with the severity of IBS depression in both fecal and serum metabolomes, characterized by a shift in tryptophan metabolism towards kynurenine production. Collectively, our study revealed serum/fecal metabolome alterations and their relationship with gut microbiome, highlighted the massive alterations of serum metabolites, which empower to recognize IBS patients, suggested potential roles of metabolic dysregulation in IBS pathogenesis, and offered new clues to understand IBS depression comorbidity. Our study provided a valuable resource for future studies, and would facilitate potential clinical applications of IBS featured microbiota and/or metabolites.

Interaction of a weakly acidic dinitroaromatic with alkylamines: avoiding the Meisenheimer trap.

Polynitroaromatics are well-known to form anionic σ-complexes (Meisenheimer complexes). The formation of such complexes was assumed in the past to explain the blue color of solutions of 2,4-dinitrotoluene (DNT) and amines. However, this work shows that caution is warranted to avoid the hasty misidentification of Meisenheimer complexes. (1)H NMR spectra exhibit no significant shifts in the positions of the DNT protons, indicating that the majority of DNT species in solutions of DNT and amines retain their aromaticity. Density functional calculations on DNT-ethylamine complexes suggest that Meisenheimer complexes are sufficiently high in free energy so that they make up only a very small fraction of the full equilibrium population. While principal component analysis of the UV/vis spectra of the DNT-amine solutions reveals that only one absorbing species of significant concentration is formed, quantitative fits of Job's plots show that 1:1 association of DNT with the amines alone cannot explain the visible absorption spectra. Instead, the Job's plots can be accurately interpreted by deprotonation of DNT, with the amines acting as bases. The deprotonation equilibria lie far on the side of the unreacted DNT, preventing the detection by NMR of the deprotonated minority species that gives the solutions their strong blue color. The analysis of systems with DNT and n-butylamine, diethylamine, triethylamine, or benzylamine provides a consistent pK(a) of DNT in dimethyl sulfoxide of 15.3 ± 0.2.

Potential use of actigraphy to measure sleep in monkeys: comparison with behavioral analysis from videography.

Sleep is indispensable for human health, with sleep disorders initiating a cascade of negative consequences. As our closest phylogenetic relatives, non-human primates (NHPs) are invaluable for comparative sleep studies and exhibit tremendous potential for improving our understanding of human sleep and related disorders. Previous work on measuring sleep in NHPs has mostly used electroencephalography or videography. In this study, simultaneous videography and actigraphy were applied to observe sleep patterns in 10 cynomolgus monkeys ( Macaca fascicularis) over seven nights (12 h per night). The durations of wake, transitional sleep, and relaxed sleep were scored by analysis of animal behaviors from videography and actigraphy data, using the same behavioral criteria for each state, with findings then compared. Here, results indicated that actigraphy constituted a reliable approach for scoring the state of sleep in monkeys and showed a significant correlation with that scored by videography. Epoch-by-epoch analysis further indicated that actigraphy was more suitable for scoring the state of relaxed sleep, correctly identifying 97.57% of relaxed sleep in comparison with video analysis. Only 34 epochs (0.13%) and 611 epochs (2.30%) were differently interpreted as wake and transitional sleep compared with videography analysis. The present study validated the behavioral criteria and actigraphy methodology for scoring sleep, which can be considered as a useful and a complementary technique to electroencephalography and/or videography analysis for sleep studies in NHPs.