Comparative and pan-genomic analyses of the endophytic fungus Pezicula neosporulosa (Helotiales, Ascomycota) from needles of the relict fir, Abies beshanzuensis, showed expansions of carbohydrate ...metabolism and secondary metabolite biosynthetic genes characteristic for unrelated plant-beneficial helotialean, such as dark septate endophytes and ericoid mycorrhizal fungi. The current species within the relatively young Pliocene genus Pezicula are predominantly saprotrophic, while P. neosporulosa lacks such features. To understand the genomic background of this putatively convergent evolution, we performed population analyses of 77 P. neosporulosa isolates. This revealed a mosaic structure of a dozen non-recombining and highly genetically polymorphic subpopulations with a unique mating system structure. We found that one idiomorph of a probably duplicated mat1-2 gene was found in putatively heterothallic isolates, while the other co-occurred with mat1-1 locus suggesting homothallic reproduction for these strains. Moreover, 24 and 81 genes implicated in plant cell-wall degradation and secondary metabolite biosynthesis, respectively, showed signatures of the balancing selection. These findings highlight the evolutionary pattern of the two gene families for allowing the fungus a rapid adaptation towards endophytism and facilitating diverse symbiotic interactions.
A BINOLate-zinc complex prepared in situ from Et2Zn and 3,3‘-dibromo-1,1‘-bi-2-naphthol (3,3‘-Br2-BINOL) was found to be a highly efficient catalyst for the enantioselective hetero-Diels−Alder ...reaction of Danishefsky's diene and aldehydes to give 2-substituted 2,3-dihydro-4H-pyran-4-one in up to quantitative yield and 98% ee.
Correction for 'Enantioselective total synthesis of (−)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids' by Chuang-Chuang Li
...et al.
,
Chem. Sci.
, 2017,
8
, 4961-4966.
Here, we describe a concise, enantioselective, and scalable synthesis of (−)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and ...metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated 5 + 2 cycloaddition reaction. Notably, the synthesized colchicinoid
23
exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC
50
= ∼3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.
A highly concise, enantioselective synthesis of (−)-colchicine, the first syntheses of (+)-demecolcinone and metacolchicine, was reported.
A highly concise, enantioselective synthesis of (–)-colchicine, the first syntheses of (+)-demecolcinone and metacolchicine, was reported.
Here, we describe a concise, enantioselective, and scalable ...synthesis of (–)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated 5 + 2 cycloaddition reaction. Notably, the synthesized colchicinoid
23
exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC
50
= ∼3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.
Two positional isomers (regioisomers) through changing the substituted position of perylenetetracarboxylic diimide and benzanthrone moieties were designed and synthesized. These two regioisomers ...exhibit totally different aggregation behaviors. The
meta
(
bay
)-substituted product shows the aggregation-caused quenching feature as the fluorescence quantum yield in tetrahydrofuran-water mixtures is reduced by 80% with an increase in the water fraction of the medium from 0% to 60%. Interestingly, an aggregation-induced emission is observed for the
ortho
-substituted product as the fluorescence quantum yield is increased by nearly one order of magnitude with an increase in the water fraction. This fluorescence enhancement effect for the
ortho
-substituted product is because of the restriction of the intramolecular rotation between the perylene core and the benzanthrone substituent in the aggregated state. The
ortho
-substituted product also exhibits excellent two-photon absorption performance because the
ortho
-substitution retains the planarity of the perylene core and improves the intramolecular charge-transfer among the molecules. Moreover, the
ortho
-substituted product shows two-photon excited aggregation-induced emission, which has potential application in organic two-photon excited fluorescence imaging agents.
With
bay
- and
ortho
-substituted perylenetetracarboxylic diimide derivatives, one-photon and two-photon excited ACQ-to-AIE conversion is realized through simple positional isomerization.
Patients with COVID-19 frequently manifest adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality
. Browning of white adipose tissue and ...activation of brown adipose tissue are effective processes for energy expenditure
; however, mechanistic and functional links between SARS-CoV-2 infection and adipose thermogenesis have not been studied. In this study, we provide experimental evidence that SARS-CoV-2 infection augments adipose browning and non-shivering thermogenesis (NST), which contributes to adipose atrophy and body weight loss. In mouse and hamster models, SARS-CoV-2 infection activates brown adipose tissue and instigates a browning or beige phenotype of white adipose tissues, including augmented NST. This browning phenotype was also observed in post-mortem adipose tissue of four patients who died of COVID-19. Mechanistically, high levels of vascular endothelial growth factor (VEGF) in the adipose tissue induces adipose browning through vasculature-adipocyte interaction. Inhibition of VEGF blocks COVID-19-induced adipose tissue browning and NST and partially prevents infection-induced body weight loss. Our data suggest that the browning of adipose tissues induced by COVID-19 can contribute to adipose tissue atrophy and weight loss observed during infection. Inhibition of VEGF signaling may represent an effective approach for preventing and treating COVID-19-associated weight loss.
ObjectiveUnbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment ...but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments.DesignLiterature review, pooling analysis and correlation analysis.Data sourcesPubMed, from 1 January 2010 to 30 June 2017.Eligibility criteria for selecting studiesEligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments.ResultsOf 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29).ConclusionsNo systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.
We aimed to summarize the diagnostic accuracy of white light bronchoscopy (WLB) and advanced techniques for airway pre-cancerous lesions and early cancer, such as autofluorescence bronchoscopy (AFB), ...AFB combined with WLB (AFB + WLB) and narrow-band imaging (NBI) bronchoscopy.
We searched for eligible studies in seven electronic databases from their date of inception to Mar 20, 2015. In eligible studies, detected lesions should be confirmed by histopathology. We extracted and calculated the 2×2 data based on the pathological criteria of lung tumor, including high-grade lesions from moderate dysplasia (MOD) to invasive carcinoma (INV). Random-effect model was used to pool sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the receiver-operating characteristic curve (AUC).
In 53 eligible studies (39 WLB, 39 AFB, 17 AFB + WLB, 6 NBI), diagnostic performance for high-grade lesions was analyzed based on twelve studies (10 WLB, 7 AFB, 7 AFB + WLB, 1 NBI), involving with totally 2,880 patients and 8,830 biopsy specimens. The sensitivity, specificity, DOR and AUC of WLB were 51% (95% CI, 34-68%), 86% (95% CI, 73-84%), 6 (95% CI, 3-13) and 77% (95% CI, 73-81%). Those of AFB and AFB + WLB were 93% (95% CI, 77-98%) and 86% (95% CI, 75-97%), 52% (95% CI, 37-67%) and 71% (95% CI, 56-87%), 15 (95% CI, 4-57) and 16 (95% CI, 6-41), and 76% (95% CI, 72-79%) and 82% (95% CI, 78-85%), respectively. NBI presented 100% sensitivity and 43% specificity.
With higher sensitivity, advanced bronchoscopy could be valuable to avoid missed diagnosis. Combining strategy of AFB and WLB may contribute preferable diagnosis rather than their alone use for high-grade lesions. Studies of NBI warrants further investigation for precancerous lesions.
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