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1.
Int J Cancer ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844851

RESUMO

Previous studies have suggested that gut microbiota plays a critical role in colorectal cancer (CRC). Although preliminary comparisons of the oral and gut microbiota between CRC and healthy control (HC) patients have been made, the association between microbiome abundance and host clinical factors has not been fully illustrated, especially oral health conditions. Matching samples of unstimulated saliva, cancer tissues or biopsies and stools were collected from 30 CRC and 30 HC patients from Shanghai Jiao Tong University affiliated Renji Hospital for 16S rRNA sequencing analysis. The diversity in salivary and mucosal microbiome, but not stool microbiome of CRC group, was significantly different from that of HC, as demonstrated by the Principal Component Analysis. Logistic regression analysis revealed that older age and higher oral hygiene index (OHI) were independent risk factors for CRC, with odds ratios and 95% confidence intervals of 1.159 (1.045-1.284) and 4.398 (1.328-14.567), respectively. Salivary Firmicutes to Bacteroides ratio in CRC was significantly higher than that in the HC group (P < 0.001), while the mucosal ratio was slightly decreased in CRC (P < 0.05). Salivary Rothia and Streptococcus levels were positively correlated with OHI, while Alloprevotella, Fusobacterium, Peptostreptoccus and Prevotella genera levels were negatively associated with OHI. NetShift analysis revealed that salivary Peptococcus, Centipeda and mucosal Subdoligranulum genus might act as key drivers during the process of carcinogenesis. In conclusion, the current study provides insights into the potential influence of host clinical factors on oral and gut microbiome composition and can be a guide for future studies.

2.
Nat Commun ; 12(1): 2187, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846346

RESUMO

The RNA-sensing pathway contributes to type I interferon (IFN) production induced by DNA damaging agents. However, the potential involvement of RNA sensors in DNA repair is unknown. Here, we found that retinoic acid-inducible gene I (RIG-I), a key cytosolic RNA sensor that recognizes RNA virus and initiates the MAVS-IRF3-type I IFN signaling cascade, is recruited to double-stranded breaks (DSBs) and suppresses non-homologous end joining (NHEJ). Mechanistically, RIG-I interacts with XRCC4, and the RIG-I/XRCC4 interaction impedes the formation of XRCC4/LIG4/XLF complex at DSBs. High expression of RIG-I compromises DNA repair and sensitizes cancer cells to irradiation treatment. In contrast, depletion of RIG-I renders cells resistant to irradiation in vitro and in vivo. In addition, this mechanism suggests a protective role of RIG-I in hindering retrovirus integration into the host genome by suppressing the NHEJ pathway. Reciprocally, XRCC4, while suppressed for its DNA repair function, has a critical role in RIG-I immune signaling through RIG-I interaction. XRCC4 promotes RIG-I signaling by enhancing oligomerization and ubiquitination of RIG-I, thereby suppressing RNA virus replication in host cells. In vivo, silencing XRCC4 in mouse lung promotes influenza virus replication in mice and these mice display faster body weight loss, poorer survival, and a greater degree of lung injury caused by influenza virus infection. This reciprocal regulation of RIG-I and XRCC4 reveals a new function of RIG-I in suppressing DNA repair and virus integration into the host genome, and meanwhile endues XRCC4 with a crucial role in potentiating innate immune response, thereby helping host to prevail in the battle against virus.

3.
Nucleic Acids Res ; 49(6): 3322-3337, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33704464

RESUMO

RPA is a critical factor for DNA replication and replication stress response. Surprisingly, we found that chromatin RPA stability is tightly regulated. We report that the GDP/GTP exchange factor DOCK7 acts as a critical replication stress regulator to promote RPA stability on chromatin. DOCK7 is phosphorylated by ATR and then recruited by MDC1 to the chromatin and replication fork during replication stress. DOCK7-mediated Rac1/Cdc42 activation leads to the activation of PAK1, which subsequently phosphorylates RPA1 at S135 and T180 to stabilize chromatin-loaded RPA1 and ensure proper replication stress response. Moreover, DOCK7 is overexpressed in ovarian cancer and depleting DOCK7 sensitizes cancer cells to camptothecin. Taken together, our results highlight a novel role for DOCK7 in regulation of the replication stress response and highlight potential therapeutic targets to overcome chemoresistance in cancer.

4.
J Insect Sci ; 21(2)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33693804

RESUMO

Diurnal temperature amplitude is known to have a large influence on insect life history. Population density affects intraspecific competition and many other aspects of insect life history. However, there is limited information on the interactive effects of these factors on insects. Here, we tested the interactive effects of three diurnal temperature amplitudes (22 ± 0°C, 22 ± 6°C, and 22 ± 12°C) and three population densities on the development, survival, longevity, and fecundity of the English grain aphid Sitobion avenae (Fabricius) (Homoptera: Aphididae). At a constant temperature, increasing population density reduced the growth and survival of early-instar nymphs, increased longevity, and reduced fecundity. At a low population density, increasing temperature amplitude inhibited nymph development. However, even at a high temperature amplitude, nymph survival rate was higher than expected, and reproduction was possible because the recovery of the lower night-temperatures eliminated thermal stress. Increasing the population density reduced, and even reversed, the negative effects of the wide temperature amplitude. This may reflect synergistic interactions between population density and wide temperature amplitude as these stressors each incur energetic costs. These findings emphasize the importance of temperature amplitude and population density for improving prediction accuracy and damage assessment during pest control modeling.


Assuntos
Afídeos , Densidade Demográfica , Temperatura , Animais , Afídeos/crescimento & desenvolvimento , Afídeos/fisiologia , Fertilidade , Estágios do Ciclo de Vida , Ninfa/crescimento & desenvolvimento , Reprodução
5.
Sci Total Environ ; 764: 142886, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33757247

RESUMO

During the outbreak of the coronavirus disease 2019 (COVID-19) in China in January and February 2020, production and living activities were drastically reduced to impede the spread of the virus, which also caused a strong reduction of the emission of primary pollutants. However, as a major species of secondary air pollutant, tropospheric ozone did not reduce synchronously, but instead rose in some region. Furthermore, higher concentrations of ozone may potentially promote the rates of COVID-19 infections, causing extra risk to human health. Thus, the variation of ozone should be evaluated widely. This paper presents ozone profiles and tropospheric ozone columns from ultraviolet radiances detected by TROPOospheric Monitoring Instrument (TROPOMI) onboard Sentinel 5 Precursor (S5P) satellite based on the principle of optimal estimation method. We compare our TROPOMI retrievals with global ozonesonde observations, Fourier Transform Spectrometry (FTS) observation at Hefei (117.17°E, 31.7°N) and Global Positioning System (GPS) ozonesonde sensor (GPSO3) ozonesonde profiles at Beijing (116.46°E, 39.80°N). The integrated Tropospheric Ozone Column (TOC) and Stratospheric Ozone Column (SOC) show excellent agreement with validation data. We use the retrieved TOC combining with tropospheric vertical column density (TVCD) of NO2 and HCHO from TROPOMI to assess the changes of tropospheric ozone during the outbreak of COVID-19 in China. Although NO2 TVCD decreased by 63%, the retrieved TOC over east China increase by 10% from the 20-day averaged before the lockdown on January 23, 2020 to 20-day averaged after it. Because the production of ozone in winter is controlled by volatile organic compounds (VOCs) indicated by monitored HCHO, which did not present evident change during the lockdown, the production of ozone did not decrease significantly. Besides, the decrease of NOx emission weakened the titration of ozone, causing an increase of ozone.


Assuntos
Poluentes Atmosféricos , Ozônio , Poluentes Atmosféricos/análise , Pequim , China/epidemiologia , Controle de Doenças Transmissíveis , Surtos de Doenças , Monitoramento Ambiental , Humanos , Ozônio/análise
6.
Sex Dev ; : 1-9, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33684916

RESUMO

Sexually dimorphic establishment of the reproductive tract system requires sex-specific regression of the Wolffian duct and Müllerian duct in the mesonephros. In an XX embryo, the Wolffian duct regresses under the control of the mesenchymal transcription factor COUP-TFII. To understand cellular and molecular actions underlying Wolffian duct regression, we performed transcriptomic analyses of XX mesonephroi with or without Coup-tfII and genome-wide analysis of COUP-TFII chromatin occupancy in XX mesonephroi. The integrative analysis of COUP-TFII genome-wide binding and transcriptomic analysis revealed the suppression of muscle differentiation and extracellular matrix genes by COUP-TFII and identified a group of potential transcriptional partners of COUP-TFII in the mesenchyme that potentially facilitate Wolffian duct regression. These findings provide insights into the molecular action of COUP-TFII in the Wolffian duct mesenchyme and identify a list of biologically relevant candidate genes and pathways for future functional analyses in sexual differentiation of reproductive tracts.

7.
Clin Transl Med ; 11(3): e341, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33784003

RESUMO

PARP inhibitors induce DNA lesions, the repair of which are highly dependent on homologous recombination (HR), and preferentially kill HR- deficient cancers. However, cancer cells have developed several mechanisms to transform HR and confer drug resistance to PARP inhibition. Therefore, there is a great clinical interest in exploring new therapies that induce HR deficiency (HRD), thereby sensitizing cancer cells to PARP inhibitors. Here, we found that GSK2578215A, a high-selective and effective leucine-rich repeat kinase 2 (LRRK2) inhibitor, or LRRK2 depletion suppresses HR preventing the recruitment of RAD51 to DNA damage sites through disruption of the interaction of RAD51 and BRCA2. Moreover, LRRK2 inhibition or depletion increases the susceptibility of ovarian cancer cells to Olaparib in vitro and in vivo. In clinical specimens, LRRK2 high expression is high related with advanced clinical characteristics and poor survival of ovarian cancer patients. All these findings indicate ovarian cancers expressing high levels of LRRK2 are more resistant to treatment potentially through promoting HR. Furthermore, combination treatment with an LRRK2 and PARP inhibitor may be a novel strategy to improve the effectiveness of LRRK2 expression ovarian cancers.

8.
J Med Chem ; 64(6): 3222-3233, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33724033

RESUMO

Several Conus-derived venom peptides are promising lead compounds for the management of neuropathic pain, with α-conotoxins being of particular interest. Modification of the interlocked disulfide framework of α-conotoxin Vc1.1 has been achieved using on-resin alkyne metathesis. Although introduction of a metabolically stable alkyne motif significantly disrupts backbone topography, the structural modification generates a potent and selective GABAB receptor agonist that inhibits Cav2.2 channels and exhibits dose-dependent reversal of mechanical allodynia in a behavioral rat model of neuropathic pain. The findings herein support the hypothesis that analgesia can be achieved via activation of GABABRs expressed in dorsal root ganglion (DRG) sensory neurons.

9.
BMC Biol ; 19(1): 42, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750361

RESUMO

BACKGROUND: Polyploidy has played a prominent role in the evolution of plants and many other eukaryotic lineages. However, how polyploid genomes adapt to the abrupt presence of two or more sets of chromosomes via genome regulation remains poorly understood. Here, we analyzed genome-wide histone modification and gene expression profiles in relation to domestication and ploidy transition in the A and B subgenomes of polyploid wheat. RESULTS: We found that epigenetic modification patterns by two typical euchromatin histone markers, H3K4me3 and H3K27me3, for the great majority of homoeologous triad genes in A and B subgenomes were highly conserved between wild and domesticated tetraploid wheats and remained stable in the process of ploidy transitions from hexaploid to extracted tetraploid and then back to resynthesized hexaploid. However, a subset of genes was differentially modified during tetraploid and hexaploid wheat domestication and in response to ploidy transitions, and these genes were enriched for particular gene ontology (GO) terms. The extracted tetraploid wheat manifested higher overall histone modification levels than its hexaploid donor, and which were reversible and restored to normal levels in the resynthesized hexaploid. Further, while H3K4me3 marks were distally distributed along each chromosome and significantly correlated with subgenome expression as expected, H3K27me3 marks showed only a weak distal bias and did not show a significant correlation with gene expression. CONCLUSIONS: Our results reveal overall high stability of histone modification patterns in the A and B subgenomes of polyploid wheat during domestication and in the process of ploidy transitions. However, modification levels of a subset of functionally relevant genes in the A and B genomes were trans-regulated by the D genome in hexaploid wheat.

10.
J Hazard Mater ; 415: 125690, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33773257

RESUMO

Heavy metal-containing wastewater can be treated by adsorption technology to obtain ultra-low concentration or high-quality treated effluent. Due to the constraints of the specific surface area, surface electrical structure and spatial effect of conventional adsorbents, it is often difficult to obtain adsorbents within high adsorption capacity. Graphene has characteristics of large specific surface area, small particle size, and high adsorption efficiency. It is considered as one of the research hotspots in recent years. However, despite graphene's unique properties, graphene-based adsorbents still have some drawbacks, i.e. graphene nanosheets are easier to be stacked with each other via π-π stacking and van der Waals interactions, which affect the site exposure, impede the rapid mass transport and limit its adsorption performance. Special strategy is needed to overcome its drawbacks. This work summarizes recent literatures on utilization of three strategies-surface functionalization regulation, morphology and structure control and material composite, to improve the adsorption properties of graphene-based adsorbent towards heavy metal removal. A brief summary, perspective on strategies to improving adsorption properties of graphene-based materials for heavy metal adsorption are also presented. Certainly, this review will be useful for designing and manufacturing of graphene-based nanomaterials for water treatment.

11.
Hum Gene Ther ; 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33678011

RESUMO

Lentiviral vectors are one of the most commonly used viral delivery systems for gene therapy. Vesicular stomatitis virus-G envelope glycoprotein- pseudotyped lentiviral vectors have been widely used in clinical studies for treatment of virus infections and genetic deficient diseases. However, the efficiency of lentiviral vector transduction has been long recognized as a limiting factor in clinical gene therapy application, especially in transducing hematopoietic stem cells. MARCH8, an E3 ubiquitin ligase, has been reported to target and down-regulate VSV G. Results in this study show that MARCH8 induces ubiquitination and lysosome degradation of VSV G. And knockout of MARCH8 in virus producing cells increases lentiviral vector transduction by elevating the level of VSV G protein. We then engineered VSV G mutant that has the lysine residues in the cytoplasmic domain substituted for arginine, and showed that this G mutant resists degradation by MARCH8, and allows the enhancement of transduction efficiency of lentiviral vector particles than the parental VSV G protein. This engineered VSV G mutant thus further advances the lentiviral vector system as a powerful tool in gene therapy.

12.
Foods ; 10(2)2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670310

RESUMO

To reveal the accumulation pattern of cyanogenic glycosides (amygdalin and prunasin) in bitter apricot kernels to further understand the metabolic mechanisms underlying differential accumulation during kernel development and ripening and explore the association between cyanogenic glycoside accumulation and the physical, chemical and biochemical indexes of fruits and kernels during fruit and kernel development, dynamic changes in physical characteristics (weight, moisture content, linear dimensions, derived parameters) and chemical and biochemical parameters (oil, amygdalin and prunasin contents, ß-glucosidase activity) of fruits and kernels from ten apricot (Prunus armeniaca L.) cultivars were systematically studied at 10 day intervals, from 20 days after flowering (DAF) until maturity. High variability in most of physical, chemical and biochemical parameters was found among the evaluated apricot cultivars and at different ripening stages. Kernel oil accumulation showed similar sigmoid patterns. Amygdalin and prunasin levels were undetectable in the sweet kernel cultivars throughout kernel development. During the early stages of apricot fruit development (before 50 DAF), the prunasin level in bitter kernels first increased, then decreased markedly; while the amygdalin level was present in quite small amounts and significantly lower than the prunasin level. From 50 to 70 DAF, prunasin further declined to zero; while amygdalin increased linearly and was significantly higher than the prunasin level, then decreased or increased slowly until full maturity. The cyanogenic glycoside accumulation pattern indicated a shift from a prunasin-dominated to an amygdalin-dominated state during bitter apricot kernel development and ripening. ß-glucosidase catabolic enzyme activity was high during kernel development and ripening in all tested apricot cultivars, indicating that ß-glucosidase was not important for amygdalin accumulation. Correlation analysis showed a positive correlation of kernel amygdalin content with fruit dimension parameters, kernel oil content and ß-glucosidase activity, but no or a weak positive correlation with kernel dimension parameters. Principal component analysis (PCA) showed that the variance accumulation contribution rate of the first three principal components totaled 84.56%, and not only revealed differences in amygdalin and prunasin contents and ß-glucosidase activity among cultivars, but also distinguished different developmental stages. The results can help us understand the metabolic mechanisms underlying differential cyanogenic glycoside accumulation in apricot kernels and provide a useful reference for breeding high- or low-amygdalin-content apricot cultivars and the agronomic management, intensive processing and exploitation of bitter apricot kernels.

13.
Nat Prod Res ; : 1-7, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648402

RESUMO

Two new pyrone derivatives, 2-(12S-hydroxypropyl)-3-hydroxy-methyl-6-hydroxy-7-methoxychromone (1), and (±)-pyrenocine S (5), together with five known compounds xanthoradone A (2), (+)-3,3',7,7',8,8'-hexahydroxy-5,5'-dimethyl-bianthra-quinone (3), butyrolactone-I (4), pyrenocine A (6), and (±)-pyrenocine E (7) were obtained from the mangrove endophytic fungus Aspergillus sydowii #2B. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction analysis and comparison data with of literatures. Compounds 2, 3, 4, 5, 6 and 7 showed cytotoxicities against prostate cancer VCaP cells with IC50 values of 4.19 ± 1.02, 33.36 ± 1.42, 1.92 ± 0.82, 20.06 ± 2.01, 7.92 ± 0.86, and 10.13 ± 0.88 µM respectively, while compound 1 showed no cytotoxic activity. Compounds 1, 3, 6, and 7 exhibited weak inhibition effects against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW 246.7 cells with IC50 values of 40.15, 28.69, 25.25 and 43.08 µM respectively.

14.
DNA Repair (Amst) ; 100: 103063, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33592542

RESUMO

The DNA replication stress-induced checkpoint activated through the TopBP1-ATR axis is important for maintaining genomic stability. However, the regulation of TopBP1 in DNA-damage responses remains unclear. In this study, we identify the deubiquitinating enzyme (DUB) USP13 as an important regulator of TopBP1. Mechanistically, USP13 binds to TopBP1 and stabilizes TopBP1 by deubiquitination. Depletion of USP13 impedes ATR activation and hypersensitizes cells to replication stress-inducing agents. Furthermore, high USP13 expression enhances the replication stress response, promotes cancer cell chemoresistance, and is correlated with poor prognosis of cancer patients. Overall, these findings suggest that USP13 is a novel deubiquitinating enzyme for TopBP1 and coordinates the replication stress response.

15.
Sleep Med ; 80: 244-259, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33610071

RESUMO

BACKGROUND: The efficacy of acupuncture for treating primary insomnia (PI) has been explored in several meta-analyses where the outcomes measures were based on subjective self-reported sleep rating scales. Sleep state misperception is common in PI and self-reports underestimate sleep duration and quality. No systematic reviews or meta-analyses have investigated the efficacy of acupuncture in improving objective sleep measures in PI. OBJECTIVE: To perform a systematic review to determine whether objective sleep parameters are improved by acupuncture in patients with PI. METHODS: Randomized controlled trials treating PI via verum-acupuncture versus sham-/placebo-acupuncture or waitlist control were searched for in English [MEDLINE (via PubMed), Sciverse ScienceDirect, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, Springer, EMBASE (Elsevier), Ebsco Medline, and PsycINFO (ProQuest)] and Chinese (SinoMed, CNKI, Wanfang and CQVIP) databases, from the dates of the databases' inception to January 2020. The parameters of polysomnography (PSG), actigraphy, or micromovement sensitive mattress/pillow sleep monitoring systems were considered as the primary outcome measures. Revman 5.3 and Stata 16.0 software were used to conduct the meta-analysis. Heterogeneity was examined by using I2 statistics and publication bias was assessed via Egger's test. RESULTS: Eleven studies involving 775 patients met the inclusion criteria. The results of meta-analysis suggested that acupuncture can increase total sleep time [MD = 55.29, 95%CI (29.16, 81.42), p < 0.01], increase sleep efficiency [MD = 8.96, 95%CI (3.97, 13.95), p < 0.01], decrease wake after sleep onset [MD = -49.54, 95%CI (-82.98, -16.09), p < 0.01], and reduce number of awakening times [MD = -6.29, 95%CI (-10.75, -1.82), p < 0.01] compared with either sham-/placebo-acupuncture or waitlist control. Subsequent analysis indicated a superior effect for verum-acupuncture in comparison with sham-/placebo-acupuncture or waitlist-control when the recommended lowest threshold dosage (12 sessions) was met. Despite positive outcomes, most studies reviewed were heterogeneous and at risk of bias due to methodological issues. CONCLUSIONS: Despite limited evidence, acupuncture was significantly associated with improvements in several objective sleep parameters (increases in total sleep time and sleep efficiency, and reductions in wake after sleep onset and number of awakening times) as well as subjective sleep quantity and quality in patients with PI. A minimum therapeutic threshold dosage (≥12 sessions) is recommended. Well-designed RCTs using PSG are required to clarify the influence of acupuncture on sleep architecture/structure and to promote better application of acupuncture as a treatment for PI.

16.
Plant Cell ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33594406

RESUMO

Wheat (Triticum aestivum) has a large allohexaploid genome. Subgenome-divergent regulation contributed to genome plasticity and the domestication of polyploid wheat. However, the specificity encoded in the wheat genome determining subgenome-divergent spatio-temporal regulation has been largely unexplored. The considerable size and complexity of the genome are major obstacles to dissecting the regulatory specificity. Here, we compared the epigenomes and transcriptomes from a large set of samples under diverse developmental and environmental conditions. Thousands of distal epigenetic regulatory elements (distal-epiREs) were specifically linked to their target promoters with coordinated epigenomic changes. We revealed that subgenome-divergent activity of homologous regulatory elements is affected by specific epigenetic signatures. Subgenome-divergent epiRE regulation of tissue specificity is associated with dynamic modulation of H3K27me3 mediated by Polycomb complex and demethylases. Furthermore, quantitative epigenomic approaches detected key stress responsive cis- and trans-acting factors validated by DNA Affinity Purification and sequencing, and demonstrated the coordinated interplay between epiRE sequence contexts, epigenetic factors, and transcription factors in regulating subgenome divergent transcriptional responses to external changes. Together, this study provides a wealth of resources for elucidating the epiRE regulomics and subgenome-divergent regulation in hexaploid wheat, and gives new clues for interpreting genetic and epigenetic interplay in regulating the benefits of polyploid wheat.

17.
BMC Cancer ; 21(1): 22, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402129

RESUMO

BACKGROUND: An accurate intraoperative prediction of lymph node metastatic risk can help surgeons in choosing precise surgical procedures. We aimed to develop and validate nomograms to intraoperatively predict patterns of regional lymph node (LN) metastasis in patients with esophageal cancer. METHODS: The prediction model was developed in a training cohort consisting of 487 patients diagnosed with esophageal cancer who underwent esophagectomy with complete LN dissection from January 2016 to December 2016. Univariate and multivariable logistic regression were used to identify independent risk factors that were incorporated into a prediction model and used to construct a nomogram. Contrast-enhanced computed tomography reported LN status and was an important comparative factor of clinical usefulness in a validation cohort. Nomogram performance was assessed in terms of calibration, discrimination, and clinical usefulness. An independent validation cohort comprised 206 consecutive patients from January 2017 to December 2017. RESULTS: Univariate analysis and multivariable logistic regression revealed three independent predictors of metastatic regional LNs, three independent predictors of continuous regional LNs, and two independent predictors of skipping regional LNs. Independent predictors were used to build three individualized prediction nomograms. The models showed good calibration and discrimination, with area under the curve (AUC) values of 0.737, 0.738, and 0.707. Application of the nomogram in the validation cohort yielded good calibration and discrimination, with AUC values of 0.728, 0.668, and 0.657. Decision curve analysis demonstrated that the three nomograms were clinically useful in the validation cohort. CONCLUSION: This study presents three nomograms that incorporate clinicopathologic factors, which can be used to facilitate the intraoperative prediction of metastatic regional LN patterns in patients with esophageal cancer.

18.
BMC Biol ; 19(1): 2, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419433

RESUMO

BACKGROUND: A robust molecular phylogeny is fundamental for developing a stable classification and providing a solid framework to understand patterns of diversification, historical biogeography, and character evolution. As the sixth largest angiosperm family, Lamiaceae, or the mint family, consitutes a major source of aromatic oil, wood, ornamentals, and culinary and medicinal herbs, making it an exceptionally important group ecologically, ethnobotanically, and floristically. The lack of a reliable phylogenetic framework for this family has thus far hindered broad-scale biogeographic studies and our comprehension of diversification. Although significant progress has been made towards clarifying Lamiaceae relationships during the past three decades, the resolution of a phylogenetic backbone at the tribal level has remained one of the greatest challenges due to limited availability of genetic data. RESULTS: We performed phylogenetic analyses of Lamiaceae to infer relationships at the tribal level using 79 protein-coding plastid genes from 175 accessions representing 170 taxa, 79 genera, and all 12 subfamilies. Both maximum likelihood and Bayesian analyses yielded a more robust phylogenetic hypothesis relative to previous studies and supported the monophyly of all 12 subfamilies, and a classification for 22 tribes, three of which are newly recognized in this study. As a consequence, we propose an updated phylogenetically informed tribal classification for Lamiaceae that is supplemented with a detailed summary of taxonomic history, generic and species diversity, morphology, synapomorphies, and distribution for each subfamily and tribe. CONCLUSIONS: Increased taxon sampling conjoined with phylogenetic analyses based on plastome sequences has provided robust support at both deep and shallow nodes and offers new insights into the phylogenetic relationships among tribes and subfamilies of Lamiaceae. This robust phylogenetic backbone of Lamiaceae will serve as a framework for future studies on mint classification, biogeography, character evolution, and diversification.

19.
Genome Biol ; 22(1): 26, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419466

RESUMO

BACKGROUND: Polyploidization and introgression are major events driving plant genome evolution and influencing crop breeding. However, the mechanisms underlying the higher-order chromatin organization of subgenomes and alien chromosomes are largely unknown. RESULTS: We probe the three-dimensional chromatin architecture of Aikang 58 (AK58), a widely cultivated allohexaploid wheat variety in China carrying the 1RS/1BL translocation chromosome. The regions involved in inter-chromosomal interactions, both within and between subgenomes, have highly similar sequences. Subgenome-specific territories tend to be connected by subgenome-dominant homologous transposable elements (TEs). The alien 1RS chromosomal arm, which was introgressed from rye and differs from its wheat counterpart, has relatively few inter-chromosome interactions with wheat chromosomes. An analysis of local chromatin structures reveals topologically associating domain (TAD)-like regions covering 52% of the AK58 genome, the boundaries of which are enriched with active genes, zinc-finger factor-binding motifs, CHH methylation, and 24-nt small RNAs. The chromatin loops are mostly localized around TAD boundaries, and the number of gene loops is positively associated with gene activity. CONCLUSIONS: The present study reveals the impact of the genetic sequence context on the higher-order chromatin structure and subgenome stability in hexaploid wheat. Specifically, we characterized the sequence homology-mediated inter-chromosome interactions and the non-canonical role of subgenome-biased TEs. Our findings may have profound implications for future investigations of the interplay between genetic sequences and higher-order structures and their consequences on polyploid genome evolution and introgression-based breeding of crop plants.

20.
J Glob Antimicrob Resist ; 24: 228-232, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33460841

RESUMO

OBJECTIVES: The aim of this study was to investigate the biological characteristics and effect of antibiotic treatment for different Mycoplasma pneumoniae isolates co-infecting the same patient. METHODS: Two throat swab specimens from a single patient, on the day of admission (Sp01) and discharge (Sp13), were liquid cultured and subcultured on agar medium to obtain M. pneumoniae monoclones. The 23S rRNA gene of 50 monoclones from specimens Sp01 and Sp13 were analysed. Real-time PCR assay was used for detection of mutations and genotyping. Two typical monoclones were isolated for antimicrobial susceptibility testing. RESULTS: Genotype 1 monoclones accounted for 70.8% (34/48) in Sp01 and 95.7% (44/46) in Sp13. All genotype 1 monoclones were of the 4-5-7-2 multilocus variable-number tandem-repeat analysis (MLVA) type, while all genotype 2 monoclones were 3-5-6-2 MLVA type. The genotype 1 monoclone, which harboured the A2063G mutation in 23S rRNA gene, was resistant to erythromycin and azithromycin in vitro, whilst genotype 2, which did not carry the mutation, was susceptible to macrolides. The proportion of macrolide-resistant M. pneumoniae monoclones in the specimen cultures collected rose from 70.8% to 95.7% at the time of discharge. CONCLUSION: This is the first report on the isolation of macrolide-resistant and -susceptible strains of M. pneumoniae from the same patient. After treatment, the proportion of macrolide-resistant M. pneumoniae increased, but the patient still carried viable macrolide-susceptible strains, meaning that the macrolide-susceptible strains did not disappear completely.

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