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In this study, we have described a novel reaction between 1,4-enynyl-3-ols and alkyl bromides. The reaction was carried out in the presence of Ag2O, following a free radical 1,2-alkynyl migration pathway, which was confirmed through control experiments. This methodology offers several advantages, including high efficiency and a wide range of applicable substrates.

Population genomic data could provide valuable information for conservation efforts; however, limited studies have been conducted to investigate the genetic status of threatened pheasants. Reeves's Pheasant (Syrmaticus reevesii) is facing population decline, attributed to increases in habitat loss. There is a knowledge gap in understanding the genomic status and genetic basis underlying the local adaptation of this threatened bird. Here, we used population genomic data to assess population structure, genetic diversity, inbreeding patterns, and genetic divergence. Furthermore, we identified candidate genes linked with adaptation across the current distribution of Reeves's Pheasant. The present study assembled the first de novo genome sequence of Reeves's Pheasant and annotated 19,458 genes. We also sequenced 30 individuals from three populations (Dabie Mountain, Shennongjia, Qinling Mountain) and found that there was clear population structure among those populations. By comparing with other threatened species, we found that Reeves's Pheasants have low genetic diversity. Runs of homozygosity suggest that the Shennongjia population has experienced serious inbreeding. The demographic history results indicated that three populations experienced several declines during the glacial period. Local adaptative analysis among the populations identified 241 candidate genes under directional selection. They are involved in a large variety of processes, including the immune response and pigmentation. Our results suggest that the three populations should be considered as three different conservation units. The current study provides genetic evidence for conserving the threatened Reeves's Pheasant and provides genomic resources for global biodiversity management.

Immunotherapy has been established as a standard in select molecular subgroups of treatment-refractory advanced gastric cancer. However, its role in resectable gastric cancer where perioperative systemic therapy is the standard remains unclear. We present a case of a man who was diagnosed with resectable gastric cancer that was microsatellite stable but programmed death-ligand 1 (PD-L1) and Epstein-Barr Virus (EBV)-positive. Given extenuating circumstances of the SARS-CoV-2 pandemic, preferences to limit exposure to the healthcare setting, and the unique tumor molecular features, neoadjuvant pembrolizumab and capecitabine was pursued after multidisciplinary discussion. He was able to achieve a complete response to this neoadjuvant regimen with no further signs of radiographic or pathologic disease on follow-up. We highlight a dramatic response to this novel approach that represents among the first cases to support a potentially viable neoadjuvant chemoimmunotherapy strategy to resectable gastric cancer. In select patients, perioperative immunotherapy-based therapy may constitute a promising strategy in resectable gastric cancer and warrants further investigation.

The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1+ myofibroblasts with prognostic values and potential biological significance. CST1+ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.

ObjectiveWhile oesophageal squamous cell carcinoma remains infrequent in Western populations, the incidence of oesophageal adenocarcinoma (EAC) has increased sixfold to eightfold over the past four decades. We aimed to characterise oesophageal cancer-specific and subtypes-specific gene regulation patterns and their upstream transcription factors (TFs).  DESIGN: To identify regulatory elements, we profiled fresh-frozen oesophageal normal samples, tumours and cell lines with chromatin immunoprecipitation sequencing (ChIP-Seq). Mathematical modelling was performed to establish (super)-enhancers landscapes and interconnected transcriptional circuitry formed by master TFs. Coregulation and cooperation between master TFs were investigated by ChIP-Seq, circularised chromosome conformation capture sequencing and luciferase assay. Biological functions of candidate factors were evaluated both in vitro and in vivo.ResultsWe found widespread and pervasive alterations of the (super)-enhancer reservoir in both subtypes of oesophageal cancer, leading to transcriptional activation of a myriad of novel oncogenes and signalling pathways, some of which may be exploited pharmacologically (eg, leukemia inhibitory factor (LIF) pathway). Focusing on EAC, we bioinformatically reconstructed and functionally validated an interconnected circuitry formed by four master TFs-ELF3, KLF5, GATA6 and EHF-which promoted each other's expression by interacting with each super-enhancer. Downstream, these master TFs occupied almost all EAC super-enhancers and cooperatively orchestrated EAC transcriptome. Each TF within the transcriptional circuitry was highly and specifically expressed in EAC and functionally promoted EAC cell proliferation and survival.ConclusionsBy establishing cancer-specific and subtype-specific features of the EAC epigenome, our findings promise to transform understanding of the transcriptional dysregulation and addiction of EAC, while providing molecular clues to develop novel therapeutic modalities against this malignancy.

SUMMARY: Cancer hallmarks rely on its specific transcriptional programs, which are dysregulated by multiple mechanisms, including genomic aberrations in the DNA regulatory regions. Genome-wide association studies have shown many variants are found within putative enhancer elements. To provide insights into the regulatory role of enhancer-associated non-coding variants in cancer epigenome, and to facilitate the identification of functional non-coding mutations, we present dbInDel, a database where we have comprehensively analyzed enhancer-associated insertion and deletion variants for both human and murine samples using ChIP-Seq data. Moreover, we provide the identification and visualization of upstream TF binding motifs in InDel-containing enhancers. Downstream target genes are also predicted and analyzed in the context of cancer biology. The dbInDel database promotes the investigation of functional contributions of non-coding variants in cancer epigenome. AVAILABILITY AND IMPLEMENTATION: The database, dbInDel, can be accessed from http://enhancer-indel.cam-su.org/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Background Maintaining brain health is an advanced goal of healthy ageing. As an important intervention to promote brain health and reduce the risk of cognitive impairment, physical activity is highly recommended in the WHO Guidelines on Risk Reduction of Cognitive Decline and Dementia. However, due to the lack of specific guidance on the types of exercise, amount of exercise and intervention methods, it is difficult to carry out physical activity in the community. Objective To construct a community-based physical activity intervention program to promote brain health in community-dwelling Chinese residents. Methods A draft of Community-based Physical Activity Intervention Program Promoting Brain Health (CPAIPPBH) was developed in December 2021 based on the evidence extracted from studies searched systematically after being screened and assessed in terms of quality by two researchers independently, and review results of our research group. Then from February to March 2022, the draft was revised in accordance with the results of a two-round email-based Delphi survey with 13 experts, and response rate, authority coefficient, Kendall's W, weight of each indicator, and the logical consistency of indicators at all levels were calculated, and finally the formal version was developed. Results Altogether, 26 out of the 8 943 searched studies were enrolled, from which 27 pieces of evidence were summarized, involving target group and principles of physical activity, type of physical activity, intensity and time of physical activity, effect and relevant evaluation of physical activity, and considerations for physical activity. The draft CPAIPPBH consisted of 6 primary indicators and 32 secondary indicators. The response rate, authority coefficient, and Kendall's W were 100.0%, 0.940, and 0.257 (χ2=123.386, P

The MADS-box (DAM) gene PpDAM6, which is related to dormancy, plays a key role in bud endodormancy release, and the expression of PpDAM6 decreases during endodormancy release. However, the interaction network that governs its regulation of the endodormancy release of flower buds in peach remains unclear. In this study, we used yeast two-hybrid (Y2H) assays to identify a mitogen-activated protein kinase, PpMAPK6, that interacts with PpDAM6 in a peach dormancy-associated SSHcDNA library. PpMAPK6 is primarily located in the nucleus, and Y2H and bimolecular fluorescence complementation (BiFC) assays verified that PpMAPK6 interacts with PpDAM6 by binding to the MADS-box domain of PpDAM6. Quantitative real-time PCR (qRT-PCR) analysis showed that the expression of PpMAPK6 was opposite that of PpDAM6 in the endodormancy release of three cultivars with different chilling requirements (Prunus persica ‘Chunjie’, Prunus persica var. nectarina ‘Zhongyou 5’, Prunus persica ‘Qingzhou peach’). In addition, abscisic acid (ABA) inhibited the expression of PpMAPK6 and promoted the expression of PpDAM6 in flower buds. The results indicated that PpMAPK6 might phosphorylate PpDAM6 to accelerate its degradation by interacting with PpDAM6. The expression of PpMAPK6 increased with decreasing ABA content during endodormancy release in peach flower buds, which in turn decreased the expression of PpDAM6 and promoted endodormancy release.

Abstract Background Numerous studies on myocardial ischemia/reperfusion (MI/R) injury have been undertaken in recent years. Hotspots and developmental trends in MI/R research are being rapidly updated. However, there has been no bibliometric analysis that systematically evaluates existing literature on MI/R injury. Our study explores developments in MI/R research over the past decade, and provides a reference for future research. Materials and methods Both experimental and clinical publications on MI/R injury from 2012 to 2021 were retrieved from the Web of Science Core Collection database. The CiteSpace and VOSviewer tools were used to perform a bibliometric analysis. Results A total of 8419 papers were analyzed. The number of annual publications demonstrated an overall upward trend, rising from 629 publications in 2012 to 1024 publications in 2021. China, the USA, Germany, England, and Italy were the top five contributors to MI/R studies. The Fourth Military Medical University in China contributed the most publications (188, 2.23%), while the University College London in England cooperated the most with relevant research institutions. Derek J Hausenloy (University College London), Derek M Yellon (University College London), and Gerd Heusch (University of Essen Medical School) were the top three most active and influential scholars according to the H-index. Among the top 10 journals with the most publications, Basic Research in Cardiology had the highest impact factors. The top three co-cited journals were Circulation, Circulation Research, and Cardiovascular Research. According to a co-cited reference analysis, MI/R research can be divided across 10 major subfields of mitophagy, cardioprotection, inflammation, remote ischemic preconditioning, long non-coding RNA, melatonin, postconditioning, mitochondria, microvascular obstruction, and ferroptosis. After 2018, the keywords with strongest citation bursts included extracellular vesicles, long non-coding RNA, cell proliferation, microRNA, mitochondrial quality control, mitophagy, biomarker, and mitochondrial biogenesis. Conclusions The present study reveals the influential authors, cooperating institutions, and main research foci in the field of MI/R injury in the past decade. The latest hotspots are a more in-depth insight into the molecular mechanisms underlying MI/R injury, such as mitochondrial quality control, non-coding RNAs, cell proliferation, and extracellular vesicles.

Umbilical hernia is a common type of extra-abdominal hernia in adults. However, chronic granulocytic leukemia in combination with cirrhotic ascites and renal insufficiency is less common. The patient reported here had both indications and contraindications for emergency surgery; therefore, the treatment options were subject to debate. We report the case of a man in his 60s who had a strangulated umbilical hernia, with overlying purple-colored infected and necrotic skin. The area was painful, but his bowel movements were normal. Patients underwent comprehensive conservative management, and remote follow-ups via telephone and video conferencing for a period of 60 days, during which the incarcerated contents of the hernia eventually retracted and his pain was relieved, such that there were no longer indications for emergency surgery. In addition, his skin infection disappeared and his quality of life improved, and therefore the treatment outcomes were good. Thus, we provide evidence that not all incarcerated umbilical hernias require emergency surgery, but may respond well to conservative treatment when the contents do not include intestinal loops or other critical organs.

ObjectiveThis study sought to investigate mental disorder and mortality risks and medical utilization among various long-term care (LTC) services and examine the associated factors.MethodsThis retrospective cohort study used data from the National Health Insurance Research Database of the entire population of Taiwan recorded between 2006 and 2017. A total of 41,407 patients using LTC (study group) were identified and propensity score–matched with 41,407 LTC nonusers (control group) at a ratio of 1:1 according to sex, age, salary-based premium, comorbidity index score, and urbanization level. Patients were divided into four groups according to LTC service type. The age distribution was as follows: 50–60 years (10.47%), 61–70 years (14.48%), 71–80 years (35.59%), and 81 years and older (39.45%). The mean age was 70.18 years and 53.57% of female participants were included. The major statistical methods were the Cox proportional hazards model and the general linear model (GLM).ResultsUsers of both institutional and inhome LTC services had the highest risk of mental disorder [adjusted hazard ratio (aHR) = 3.2]. The mean mortality rate in LTC nonusers was 46.2%, whereas that in LTC users was 90.4%, with the highest found among the users of both institutional and inhome LTC (90.6%). The institutional LTC users had the shortest survival time (4.1 years). According to the adjusted Cox model analysis, the odds of mortality was significantly higher among institutional LTC users than among inhome LTC users (aHR = 1.02). After the adjustment of covariates, adjusted GLM model results revealed that the annual medical expenditure per capita of LTC nonusers was NT$46,551, which was 1.6 times higher that of LTC users.ConclusionUsers of both institutional and inhome LTC services have higher risk of mental disorder, shorter survival time, and lower medical utilization.

LNK (SH2B3) is a key negative regulator of JAK-STAT signaling which has been extensively studied in malignant hematopoietic diseases. We found that LNK is significantly elevated in cutaneous melanoma; this elevation is correlated with hyperactive signaling of the RAS-RAF-MEK pathway. Elevated LNK enhances cell growth and survival in adverse conditions. Forced expression of LNK inhibits signaling by interferon-STAT1 and suppresses interferon (IFN) induced cell cycle arrest and cell apoptosis. In contrast, silencing LNK expression by either shRNA or CRISPR-Cas9 potentiates the killing effect of IFN. The IFN-LNK signaling is tightly regulated by a negative feedback mechanism; melanoma cells exposed to IFN upregulate expression of LNK to prevent overactivation of this signaling pathway. Our study reveals an unappreciated function of LNK in melanoma and highlights the critical role of the IFN-STAT1-LNK signaling axis in this potentially devastating disease. LNK may be further explored as a potential therapeutic target for melanoma immunotherapy.

Objective: The study aimed to develop the vegetable value of common vetch （CV） and explore the effects of salt solution on phenolic accumulation and antioxidant activity in CV sprouts. Methods: The effects of NaCl stress and supplemental CaCl2 on free and combined phenolic accumulation in CV sprouts were analysed by UPLC in comparison with pea sprouts, soybean sprouts and mung bean sprouts. The changes of key enzyme activities and gene relative expression levels of PAL, C4H and 4CL, antioxidant enzyme activities and antioxidant activities were investigated under NaCl and CaCl2 treatments. Results: The total phenolics increased from （10.63±0.40） mg GAE/g DW to （15.76±0.36） mg GAE/g DW with the co-treatment of NaCl and CaCl2. Sixteen phenolic acids were detected in CV sprouts. The content of Rutin increased from （22.50±0.49） mg/kg DW to （57.38± 0.87） mg/kg DW with the co-treatment, which was 79.69, 260.82, 5.89 times of pea sprout, soybea sprout and mung bean sprout respectively. Na+ increased enzyme activities of PAL, 4CL and C4H by increasing their relative gene expression levels. However, the co-treatment increased enzyme activities but their relative gene expression levels decreased or didn't change significantly. Conclusion: The co-treatment of NaCl and CaCl2 can enrich the phenolic content and enhance its antioxidant activity of CV sprouts.

Taming the electron transfer across metal–support interfaces appears to be an attractive yet challenging methodology to boost catalytic properties. Herein, we demonstrate a precise engineering strategy for the carbon surface chemistry of Pt/C catalysts—that is, for the electron-withdrawing/donating oxygen-containing groups on the carbon surface—to fine-tune the electrons of the supported metal nanoparticles. Taking the ammonia borane hydrolysis as an example, a combination of density functional theory (DFT) calculations, advanced characterizations, and kinetics and isotopic analyses reveals quantifiable relationships among the carbon surface chemistry, Pt charge state and binding energy, activation entropy/enthalpy, and resultant catalytic activity. After decoupling the influences of other factors, the Pt charge is unprecedentedly identified as an experimentally measurable descriptor of the Pt active site, contributing to a 15-fold increment in the hydrogen generation rate. Further incorporating the Pt charge with the number of Pt active sites, a mesokinetics model is proposed for the first time that can individually quantify the contributions of the electronic and geometric properties to precisely predict the catalytic performance. Our results demonstrate a potentially groundbreaking methodology to design and manipulate metal–carbon catalysts with desirable properties.

Structure–performance relationship is a complex issue in iron-catalyzed Fischer–Tropsch synthesis, and it is not easy to elucidate it by experimental investigations. First-principle calculation is a powerful method for explaining experimental results and guiding catalyst design. In this study, we investigated the reaction mechanisms of CH4 formation and C–C coupling on four χ-Fe5C2 surfaces and established the kinetic equations to compare the rates of CH4 formation and C1+C1 coupling reactions and determine the CH4/C2+ selectivity. The results show that the geometry of the χ-Fe5C2 surfaces has little effect on the formation rate of CH4; however, the C1+C1 coupling reactions are significantly affected by the surface geometry. The C1+C1 coupling reaction rates on the terraced-like (510) and (021) surfaces are much higher than those on the stepped-like (001) and (100) surfaces. Based on these results, we established a Brønsted–Evans–Polanyi (BEP) relationship between the effective barrier difference for CH4 formation and C1+C1 coupling (ΔEeff) and the adsorption energy of C+4H (ΔEC+4H) on χ-Fe5C2 surfaces. ΔEC+4H can be used as a descriptor for CH4/C2+ selectivity on different surfaces of χ-Fe5C2.

Background: Histone modification H3K27me3 plays a critical role in normal development and is associated with various diseases, including cancer. This modification forms large chromatin domains, known as Large Organized Chromatin Lysine Domains (LOCKs), which span several hundred kilobases. Result: In this study, we identify and categorize H3K27me3 LOCKs in 109 normal human samples, distinguishing between long and short LOCKs. Our findings reveal that long LOCKs are predominantly associated with developmental processes, while short LOCKs are enriched in poised promoters and are most associated with low gene expression. Further analysis of LOCKs in different DNA methylation contexts shows that long LOCKs are primarily located in partially methylated domains (PMDs), particularly in short-PMDs, where they are most likely responsible for the low expressions of oncogenes. We observe that in cancer cell lines, including those from esophageal and breast cancer, long LOCKs shift from short-PMDs to intermediate-PMDs and long-PMDs. Notably, a significant subset of tumor-associated long LOCKs in intermediate- and long-PMDs exhibit reduced H3K9me3 levels, suggesting that H3K27me3 compensates for the loss of H3K9me3 in tumors. Additionally, we find that genes upregulated in tumors following the loss of short LOCKs are typically poised promoter genes in normal cells, and their transcription is regulated by the ETS1 transcription factor. Conclusion: These results provide new insights into the role of H3K27me3 LOCKs in cancer and underscore their potential impact on epigenetic regulation and disease mechanisms. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the synergistic effects of high-intensity ultrasound (0, 5, 10, 15, and 20 min) in combination with L-lysine (15 mM) on improving the solubility and flavour adsorption capacity of myofibrillar proteins (MPs) in low-ion-strength media. The results revealed that the ultrasound treatment for 20 min or the addition of L-lysine (15 mM) significantly improved protein solubility (p < 0.05), with L-lysine (15 mM) showing a more pronounced effect (p < 0.05). The combination of ultrasound treatment and L-lysine further increased solubility, and the MPs treated with ultrasound at 20 min exhibited the best dispersion stability in water, which corresponded to the lowest turbidity, highest absolute zeta potential value, and thermal stability (p < 0.05). Based on the reactive and total sulfhydryl contents, Fourier transform infrared spectroscopy, and fluorescence spectroscopy analysis, the ultrasound treatment combined with L-lysine (15 mM) promoted the unfolding and depolymerization of MPs, resulting in a larger exposure of SH groups on the surface, aromatic amino acids in a polar environment, and a transition of protein conformation from α-helix to β-turn. Moreover, the combined treatment also increased the hydrophobic bonding sites, hydrogen-bonding sites, and electrostatic effects, thereby enhancing the adsorption capacity of MPs to bind kenone compounds. The findings from this study provide a theoretical basis for the production and flavour improvement of low-salt MP beverages and the utilisation of meat protein.

As the second most common malignant bone tumor in children and adolescents, Ewing sarcoma is initiated and exacerbated by a chimeric oncoprotein, most commonly, EWS-FLI1. In this study, we apply epigenomic analysis to characterize the transcription dysregulation in this cancer, focusing on the investigation of super-enhancer and its associated transcriptional regulatory mechanisms. We demonstrate that super-enhancer-associated transcripts are significantly enriched in EWS-FLI1 target genes, contribute to the aberrant transcriptional network of the disease, and mediate the exceptional sensitivity of Ewing sarcoma to transcriptional inhibition. Through integrative analysis, we identify MEIS1 as a super-enhancer-driven oncogene, which co-operates with EWS-FLI1 in transcriptional regulation, and plays a key pro-survival role in Ewing sarcoma. Moreover, APCDD1, another super-enhancer-associated gene, acting as a downstream target of both MEIS1 and EWS-FLI1, is also characterized as a novel tumor-promoting factor in this malignancy. These data delineate super-enhancer-mediated transcriptional deregulation in Ewing sarcoma, and uncover numerous candidate oncogenes which can be exploited for further understanding of the molecular pathogenesis for this disease.

Abstract Black‐headed penduline tit (Remiz macronyx) is a poorly known bird species mainly distributed in Iran, Turkmenistan, and Kazakhstan. The distribution of black‐headed penduline tit is disjointed and fragmented, and it occurs only along lakes or rivers surrounded by extensive reedbeds. Four subspecies of R. macronyx have been recognized (macronyx, neglectus, nigricans, and ssaposhnikowi). The ssaposhnikowi subspecies was previously known to occur only around lakes in southeastern Kazakhstan. In this study, we reported the first confirmed breeding record of R. m. ssaposhnikowi in the Nalati wetland, Ili, Xinjiang, China, extending the distribution range of the black‐headed penduline tit by 350 km to the east. We also obtained new information about the morphology and breeding behavior of R. m. ssaposhnikowi, which can be useful for the taxonomy of penduline tits, especially in distinguishing black‐headed penduline tits from Eurasian penduline tits (R. pendulinus).

To date, Cd remains a major contaminant in rice production. An in-depth exploration of the mechanism that causes genotypic differences in Cd enrichment in rice is necessary to develop strategies to regulate Cd enrichment in rice. Here, two rice cultivars (low grain Cd, ZZ143; and high grain Cd, YX409) displayed different transcriptomic profile patterns when subjected to 100μmol/L Cd stress. In fact, 18,721(9833 upregulated and 8888 downregulated) and 16,403 (8366 upregulated and 8037 downregulated) differentially expressed genes (DEGs) were found in ZZ143 and YX409, respectively. Gene ontology (GO) classification revealed 28 and 26 terms enriched in ZZ143 and YX409, respectively. ZZ143 had more enriched DEGs than YX409, primarily in cellular processes, metabolic processes, binding terms, catalytic activity, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that 21 and 24 pathways were significantly enriched in ZZ143 and YX409, respectively. Based on the DEGs, ZZ143 had a stronger ability for sulfur assimilation and Cys synthesis, whereas YX409 had a stronger ability to maintain cell wall stability. A series of DEGs involved in metabolic pathways, biosynthesis of secondary metabolites, plant hormone signal transduction pathways, and mitogen-activated protein kinase signaling pathways were identified, which maybe closely related to Cd resistance and the different Cd concentrations between cultivars. The above pathways and the greater number of identified DEGs in more than half of the GO terms and KEGG pathways suggest a higher absorption and stronger tolerance of the roots of ZZ143 than YX409 to Cd.

Abstract Fine constructing the chemical environment of the central metal is vital in developing efficient single‐atom catalysts (SACs). Herein, the atomically dispersed Cu on the N‐doped carbon is modulated by introducing CuP moiety to CuNC SAC. Through fine‐tuning with another heteroatom P, the Cu SAC shows the superior performance of ethylene oxychlorination. The Cu site activity of Cu‐NPC is four times higher than the P‐free Cu‐NC catalyst and 25 times higher than the Ce‐promoted CuCl2/Al2O3 catalyst in the long‐term test (>200 h). The selectivity of ethylene dichloride can be splendidly kept at ≈99%. Combined experimental and simulation studies provide a theoretical framework for the coordination of Cu, N, and P in the complex active center and its role in effectively catalyzing ethylene oxychlorination. It integrates the oxidation and chlorination reactions with superior catalytic performance and unrivaled ability of corrosive‐HCl resistance. The concept of fine constructing with another heteroatom is anticipated to provide with inspiration for rational catalyst design and expand the applications of carbon‐based SACs in heterogeneous catalysis.

BackgroundClonal VDJ rearrangement of B/T cell receptors (B/TCRs) occurring during B/T lymphocyte development has been used as a marker to track the clonality of B/T cell populations.MethodsWe systematically profiled the B/T cell receptor repertoire of 936 cancer cell lines across a variety of cancer types as well as 462 Epstein-Barr Virus (EBV) transformed normal B lymphocyte lines using RNA sequencing data.ResultsRearranged B/TCRs were readily detected in cell lines derived from lymphocytes, and subclonality or potential biclonality were found in a number of blood cancer cell lines. Clonal BCR/TCR rearrangements were detected in several blast phase CML lines and unexpectedly, one gastric cancer cell line (KE-97), reflecting a lymphoid origin of these cells. Notably, clonality was highly prevalent in EBV transformed B lymphocytes, suggesting either transformation only occurred in a few B cells or those with a growth advantage dominated the transformed population through clonal evolution.ConclusionsOur analysis reveals the complexity and heterogeneity of the BCR/TCR rearrangement repertoire and provides a unique insight into the clonality of lymphocyte derived cell lines.

Abstract Background Despite advanced treatments could inhibit progression of colorectal carcinoma (CRC), the recurrence and metastasis remain challenging issues. Accumulating evidences implicated that AVL9 played a vital role in human cancers, but it’s biological function and mechanism in CRC remain unclear. Aim To investigate the biological role and mechanism of AVL9 in colorectal carcinoma. Results AVL9 expression was significantly upregulated in tumor tissues than that in matched normal tissues both at mRNA and protein levels. High expression of AVL9 was closely correlated with M status, stages and poor prognosis of colorectal carcinoma (CRC) patients. Functionally, AVL9 overexpression promoted cell migration rather than cell proliferation in vitro, whereas AVL9 knockdown exhibited the contrary results. Mechanistically, AVL9 regulated EGFR expression, and knockdown of EGFR restrained AVL9-induced cell migration. Conclusion These findings demonstrated that AVL9 contributed to CRC cell migration by regulating EGFR expression, suggesting a potential biomarker and treatment target for CRC.

The microenvironment of oesophageal squamous cell carcinomas (ESCC) is heterogeneous and can strongly impact response to treatment. Here, the authors characterize the ESCC tumour microenvironment with single-cell RNA-seq, finding CST1 + myofibroblasts with potential biological and prognostic significance as well as immunosuppression signatures.

The Streptomyces cavourensis strain 2BA6PGT was isolated from sediment from the bottom of the salt lake Verkhnee Beloe (Buryatia, Russia). This strain's 7,651,223 bp complete genome has a high G + C content of 72.1% and consists of 7,069 coding sequences and 315 subsystems. The 16S ribosomal RNA of isolate 2BA6PGT was most closely related to Streptomyces cavourensis strain NBRC 13026T (98.91% identity), followed by Streptomyces bacillaris strain ATCC 15855T (95.36%), Streptomyces rhizosphaericola strain 1AS2cT (94.68%), and Streptomyces pluricolorescens strain JCM 4602T (86.75%). These comparisons were supported by pairwise comparisons using average nucleotide identity (ANI) and DNA-DNA hybridization analysis. This is the first complete genome reported on Streptomyces cavourensis isolated from sediment from the bottom of the salt lake Verkhnee Beloe. The complete genome sequence has been deposited at the NCBI GenBank with an accession number CP101140.

Spiribacter is the most abundant bacterial genus in the intermediate-salinity zones of hypersaline environments. However, Spiribacter strains are extremely difficult to isolate in pure culture. Therefore, the characteristics, genome features, and adaption mechanisms that allow Spiribacter strains to thrive in highly saline conditions are largely unknown. Here, we show that Spiribacter is predominant in brines from marine solar salterns and sulfate-type salt lakes with intermediate to saturated salinities. Using a high-salt medium, we isolated a novel strain, Spiribacter halobius E85T, which possesses a relatively large and distinct genome. The genome of strain E85T has a length of 4.17 Mbp, twice that of other Spiribacter species genomes and the largest described genome within the family Ectothiorhodospiraceae. Comparative genomic analyses indicate that approximately 50% of E85T genes are strain-specific, endowing functional differences in its metabolic capabilities, biosynthesis of compatible solutes, and transport and pumping of solutes into the cell from the environment. Hundreds of insertion sequences result in many pseudogenes and frequent gene fragment rearrangements in the E85T genome. Dozens of genomic islands, which show a significant preference for replication, recombination and repair, and cell motility and may have been gained from other bacterial species, are scattered in the genome. This study provides important insights into the general genetic basis for the abundance of Spiribacter in hypersaline environments and the strain-specific genome evolutionary strategies of strain E85T.

p63, more specifically its ΔNp63α isoform, plays essential roles in squamous cell carcinomas (SCCs), yet the mechanisms controlling its nuclear transport remain unknown. Nucleoporins (NUPs) are a family of proteins building nuclear pore complexes (NPC) and mediating nuclear transport across the nuclear envelope. Recent evidence suggests a cell type-specific function for certain NUPs; however, the significance of NUPs in SCC biology remains unknown. In this study, we show that nucleoporin 62 (NUP62) is highly expressed in stratified squamous epithelia and is further elevated in SCCs. Depletion of NUP62 inhibits proliferation and augments differentiation of SCC cells. The impaired ability to maintain the undifferentiated status is associated with defects in ΔNp63α nuclear transport. We further find that differentiation-inducible Rho kinase reduces the interaction between NUP62 and ΔNp63α by phosphorylation of phenylalanine-glycine regions of NUP62, attenuating ΔNp63α nuclear import. Our results characterize NUP62 as a gatekeeper for ΔNp63α and uncover its role in the control of cell fate through regulation of ΔNp63α nuclear transport in SCC.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. The exomes of more than 600 ESCCs have been sequenced in the past 4 years, and numerous key aberrations have been identified. Recently, researchers reported both inter- and intratumor heterogeneity. Although these are interesting observations, their clinical implications are unclear due to the limited number of samples profiled. Epigenomic alterations, such as changes in DNA methylation, histone acetylation, and RNA editing, also have been observed in ESCCs. However, it is not clear what proportion of ESCC cells carry these epigenomic aberrations or how they contribute to tumor development. We review the genomic and epigenomic characteristics of ESCCs, with a focus on emerging themes. We discuss their clinical implications and future research directions.

A molecular-level understanding of the electronic effects remains a grand challenge in heterogeneous catalysis. Here, the authors report an unconventional kinetics strategy for bridging the upscaling gap between the microscopic fingerprints of active sites and the macroscopic catalytic performance.

Abstract Background Divergence time estimation is fundamental to understanding many aspects of the evolution of organisms, such as character evolution, diversification, and biogeography. With the development of sequence technology, improved analytical methods, and knowledge of fossils for calibration, it is possible to obtain robust molecular dating results. However, while phylogenomic datasets show great promise in phylogenetic estimation, the best ways to leverage the large amounts of data for divergence time estimation has not been well explored. A potential solution is to focus on a subset of data for divergence time estimation, which can significantly reduce the computational burdens and avoid problems with data heterogeneity that may bias results. Results In this study, we obtained thousands of ultraconserved elements (UCEs) from 130 extant galliform taxa, including representatives of all genera, to determine the divergence times throughout galliform history. We tested the effects of different “gene shopping” schemes on divergence time estimation using a carefully, and previously validated, set of fossils. Our results found commonly used clock-like schemes may not be suitable for UCE dating (or other data types) where some loci have little information. We suggest use of partitioning (e.g., PartitionFinder) and selection of tree-like partitions may be good strategies to select a subset of data for divergence time estimation from UCEs. Our galliform time tree is largely consistent with other molecular clock studies of mitochondrial and nuclear loci. With our increased taxon sampling, a well-resolved topology, carefully vetted fossil calibrations, and suitable molecular dating methods, we obtained a high quality galliform time tree. Conclusions We provide a robust galliform backbone time tree that can be combined with more fossil records to further facilitate our understanding of the evolution of Galliformes and can be used as a resource for comparative and biogeographic studies in this group.

Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, particularly those involving epigenetic dysregulation, remain largely elusive, hampering clinical management of this malignancy. To identify novel druggable targets, we carried out an unbiased high-throughput chemical screening and observed that NPC cells were highly sensitive to inhibitors of cyclin-dependent kinases (CDK), especially THZ1, a covalent inhibitor of CDK7. THZ1 demonstrated pronounced antineoplastic activities both in vitro and in vivo An integrative analysis using both whole-transcriptome sequencing and chromatin immunoprecipitation sequencing pinpointed oncogenic transcriptional amplification mediated by super-enhancers (SE) as a key mechanism underlying the vulnerability of NPC cells to THZ1 treatment. Further characterization of SE-mediated networks identified many novel SE-associated oncogenic transcripts, such as BCAR1, F3, LDLR, TBC1D2, and the long noncoding RNA TP53TG1. These transcripts were highly and specifically expressed in NPC and functionally promoted NPC malignant phenotypes. Moreover, DNA-binding motif analysis within the SE segments suggest that several transcription factors (including ETS2, MAFK, and TEAD1) may help establish and maintain SE activity across the genome. Taken together, our data establish the landscape of SE-associated oncogenic transcriptional network in NPC, which can be exploited for the development of more effective therapeutic regimens for this disease. Cancer Res; 77(23); 6614-26. ©2017 AACR.

Relapsed acute lymphoblastic leukemia (ALL) is the leading cause of deaths of childhood cancer. Although relapse usually happens in the bone marrow, extramedullary relapse occasionally occurs including either the central nervous system or testis (

The circadian system regulates numerous physiological processes including immune responses. Here, we show that mice deficient of the circadian clock genes Cry1 and Cry2 [Cry double knockout (DKO)] develop an autoimmune phenotype including high serum IgG concentrations, serum antinuclear antibodies, and precipitation of IgG, IgM, and complement 3 in glomeruli and massive infiltration of leukocytes into the lungs and kidneys. Flow cytometry of lymphoid organs revealed decreased pre-B cell numbers and a higher percentage of mature recirculating B cells in the bone marrow, as well as increased numbers of B2 B cells in the peritoneal cavity of Cry DKO mice. The B cell receptor (BCR) proximal signaling pathway plays a critical role in autoimmunity regulation. Activation of Cry DKO splenic B cells elicited markedly enhanced tyrosine phosphorylation of cellular proteins compared with cells from control mice, suggesting that overactivation of the BCR-signaling pathway may contribute to the autoimmunity phenotype in the Cry DKO mice. In addition, the expression of C1q, the deficiency of which contributes to the pathogenesis of systemic lupus erythematosus, was significantly down-regulated in Cry DKO B cells. Our results suggest that B cell development, the BCR-signaling pathway, and C1q expression are regulated by circadian clock CRY proteins and that their dysregulation through loss of CRY contributes to autoimmunity.

B acute lymphoblastic leukemia (B-ALL) cells are distinctively vulnerable to endoplasmic reticulum (ER) stress. Recently, inhibition of p97 was shown to induce ER stress and subsequently cell death in solid tumors and in multiple myeloma. We investigated the role of a novel, orally available, p97 inhibitor (CB-5083; Cleave Biosciences) in B-ALL. CB-5083 induced a significant reduction in viability in 10 human B-ALL cell lines, harboring the most common fusion-genes involved in pediatric and adult B-ALL, with IC50s ranging from 0.34 to 0.76 μM. Moreover, CB-5083 significantly reduced the colony formation of OP1 and NALM6 cells. Early and strong induction of apoptosis was demonstrated in BALL1 and OP1 cells, together with a robust cleavage of PARP. CB-5083 induced ER stress, as documented through: 1) prominent expression of chaperones (GRP78, GRP94, PDI, DNAJC3, and DNAJB9); 2) increased activation of IRE1-alpha, as demonstrated by the splicing of XBP1; and 3) activation of PERK, which resulted in a significant overexpression of CHOP, and its downstream genes. CB-5083 reduced the viability also in GRP78-/-, GRP94-/-, and XBP1-/- cells, suggesting that none of these proteins alone was strictly required for CB-5083 activity. Moreover, we showed that the absence of XBP1 (XBP1-/-) increased the sensitivity to CB-5083, leading to the hypothesis that XBP1 splicing counteracts the activity of CB-5083, probably mitigating ER stress. Finally, vincristine was synergistic with CB-5083 in both BALL1 and OP1 cells. In summary, the targeting of p97 with CB-5083 is a novel promising therapeutic approach that should be further evaluated in B-ALL.

[This corrects the article DOI: 10.18632/oncotarget.7702.].