A Pd‐catalyzed carbonylation reaction for the synthesis of fluoren‐9‐ones from 2‐halogenated biphenyls using phenyl formate as a carbon monoxide surrogate was achieved. The combined use of cesium ...carbonate and o‐anisic acid resulted in a remarkable rate enhancement, where the reaction was complete within 3 min in some cases. Mechanistic studies indicated that the turnover‐limiting step of the reaction was the C−H bond‐cleaving step or the oxidative addition step, depending on the substrate used.
Pd-catalyzed reductive carbonylation of aryl sulfonates using N-formylsaccharin as a carbon monoxide (CO) surrogate was developed. This external-CO-free carbonylation provides a safe and practical ...access to aldehydes from phenol derivatives. The reaction has a broad substrate scope, rendering it an attractive method for synthesizing aldehydes.
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•External-CO-free reductive carbonylation has been achieved.•Readily available aryl sulfonates can be used as substrates.•N-Formylsaccharin is a useful CO surrogate for the reaction.•Various functional groups are tolerated under the reaction conditions.
Palladium-catalyzed, hydroxy-group-directed C–H arylation of 1,1′-biphenyl-2-ols with chloroarenes was performed. The reaction showed a broad substrate scope and was successfully applied to ...pharmaceuticals containing a chloro group. Using 2-heteroarylphenols instead of 1,1′-biphenyl-2-ols also yielded the desired products. The arylated product was further transformed into a triphenylene derivative.
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•Synthesis of 2,3-disubstituted indoles bearing 2-hydroxyphenyl groups at the C3 positions has been achieved.•Readily available chlorophenols can be used as substrates.•Only the ...Pd–DHTP catalyst can effectively catalyze the desired reaction.•2-Chloro group of 2,4-dichlorophenol reacts selectively.
2,3-Disubstituted indoles bearing 2-hydroxyphenyl moieties at their C3 positions were synthesized from readily available 2-chlorophenols and alkynylanilines via aminopalladation/reductive elimination using Pd–dihydroxyterphenylphosphine catalyst. The catalyst accelerates the introduction of the 2-hydroxyphenyl group at the C3 position of the indole.
Background
Although colorectal cancer (CRC) is one of the most common causes of cancer mortality, early-stage detection improves survival rates dramatically. Because cancer impacts important ...metabolic pathways, the alteration of metabolite levels as a potential biomarker of early-stage cancer has been the focus of many studies. Here, we used CE-TOFMS, a novel and promising method with small injection volume and high resolution, to separate and detect ionic compounds based on the different migration rates of charged metabolites in order to detect metabolic biomarkers in patients with CRC.
Methods
A total of 56 patients with CRC (
n
= 14 each of Stages I-IV), 60 healthy controls, and 59 patients with colonic adenoma were included in this study. Metabolome analysis was conducted by CE-TOFMS on serum samples of patients and controls using the Advanced Scan package (Human Metabolome Technologies).
Results
We obtained 334 metabolites in the serum, of which 139 were identified as known substances. Among these 139 known metabolites, 16 were correlated with CRC stage by upregulation and 44 by downregulation, with benzoic acid (
r
= −0.649,
t
= 11.653,
p
= 6.07599E−24), octanoic acid (
r
= 0.557,
t
= 9.183,
p
= 7.9557E−17), decanoic acid (
r
= 0.539,
t
= 8.749,
p
= 1.24352E−15), and histidine (
r
= −0.513,
t
= 8.194,
p
= 3.90224E−14) exhibiting significant correlation.
Conclusions
To the best of our knowledge, this is the first report to determine the correlation between serum metabolites and CRC stage using CE-TOFMS. Our results show that benzoic acid exhibited excellent diagnostic power and could potentially serve as a novel disease biomarker for CRC diagnosis.
Blue laser imaging-bright (BLI-bright) has shown promise as a more useful tool for detection of early gastric cancer (EGC) than white-light imaging (WLI). However, the diagnostic performance of ...BLI-bright in the detection of EGC has not been investigated. We aimed to compare real-time detection rates of WLI with that of BLI-bright for EGC.
This was a prospective, randomized, controlled study in 2 Japanese academic centers. We investigated 629 patients undergoing follow-up endoscopy for atrophic gastritis with intestinal metaplasia or surveillance after endoscopic resection of EGC. Patients were randomly assigned to receive primary WLI followed by BLI-bright or primary BLI-bright followed by WLI. The real-time detection rates of EGC were compared between primary WLI and primary BLI-bright.
There were 298 patients in each group. The real-time detection rate of EGC with primary BLI-bright was significantly greater than that with primary WLI (93.1% vs 50.0%; P = .001). Primary BLI-bright had a significantly greater ability to detect EGCs in patients with a history of endoscopic resection for EGC, no Helicobacter pylori infection in the stomach after eradication therapy, lesions with an open-type atrophic border, lesions in the lower third of the stomach, depressed-type lesions, small lesions measuring <10 mm and 10 to 20 mm in diameter, reddish lesions, well-differentiated adenocarcinomas, and lesions with a depth of invasion of T1a.
BLI-bright has a higher real-time detection rate for EGC than WLI. BLI-bright should be performed during surveillance endoscopy in patients at high risk for EGC. (Clinical trial registration number: UMIN000011324.)
Proton pump inhibitors (PPIs) are widely used to treat gastro-esophageal reflux and prevent gastric ulcers, and have been considered as low risk. However, recent studies have identified possible ...associations between PPI use and gut microbiota, suggesting that PPIs use increases the risk of enteric infections, including Clostridium difficile infection. To investigate gut microbiota in Japanese PPIs users, we conducted 16S metagenomics analysis of fecal samples collected from PPI users and healthy adults. In total, 36 PPI users and 36 PPI non-users (as control subjects) matched by age and sex were recruited and fecal samples were obtained to analyze the gut microbiome using 16S rRNA gene sequencing. There were significant differences in the microbial structure between PPI non-users and PPI users. In contrast, the analysis of α-diversity revealed no significant differences between PPI non-users and PPI users. When comparing in genus level between these two groups, the genera Streptococcus was significantly abundant and the genera Faecalibacterium was significantly decreased in PPI users. Our findings indicate a probable association between PPI use and the alternation of microbiota. These alterations might provide a mechanism by which PPIs predispose enteric infection such as Clostridium difficile infection.
A practical Pd-catalyzed carbonylation of (hetero)aryl bromides using a crystalline carbon monoxide (CO) surrogate, 2,4,6-trichlorophenyl formate (TCPF), was developed. This reaction proceeds without ...the slow addition technique that was previously required and with a low catalyst loading (1 mol%). The utility of this Pd-catalyzed external-CO-free carbonylation using TCPF was demonstrated in the synthesis of a histone deacetylase inhibitor.
Background
Local recurrence after cold snare polypectomy (CSP) of colorectal polyps has not been well analyzed. In this study, we analyzed the characteristics of local recurrence.
Methods
We ...retrospectively reviewed consecutive lesions resected by CSP from 2014 to 2016 and lesions that were followed up at ≥ 10 months after CSP, were analyzed. Our indication for CSP was a benign tumor of < 15 mm in size. We analyzed local recurrence and its risk factors using multivariate analyses. In addition, we compared lesions of ≥ 10 mm and < 10 mm. Moreover, therapeutic methods for recurrence were analyzed.
Results
Finally, we analyzed 554 cases out of 820 consecutive cases. The mean polyp size was 5.3 ± 2.8 mm and the
en bloc
resection and histopathological complete resection rates were 99.3% and 70.2%, respectively. The overall recurrence rate was 1.9% (mean follow-up period: 13.0 ± 4.0 months). Significant differences were observed between 11 recurrent lesions and 543 lesions without recurrence regarding polyp size (8.0 ± 3.7 mm vs. 5.2 ± 2.7 mm,
p
< 0.001), rate of sessile-serrated polyp (27.3% vs. 3.0%,
p
< 0.001), and histopathological positive margin (45.4% vs. 3.7%,
p
= 0.019). Multivariate analyses showed that a histopathological positive margin was the only significant risk factor for local recurrence (OR 16.600, 95% CI 3.707–74.331,
p
< 0.001). Regarding the comparison between 74 lesions of ≥ 10 mm and 480 lesions of < 10 mm, significant differences were observed in the
en bloc
resection rate (93.2% vs. 100%,
p
< 0.001), high-grade dysplasia rate (8.1% vs. 0.8%,
p
< 0.001), and histopathological complete resection rate (54.0% vs. 72.7%,
p
= 0.001). The recurrence rates of these two groups were 5.4% and 1.4%, respectively (
p
= 0.069). All recurrent cases could be resected with repeat CSP.
Conclusions
The local recurrence rate after CSP for lesions of < 10 mm was 1.4%. CSP was not recommended for lesions of ≥ 10 mm due to high rates of recurrence and malignancy.
Retinoic acid-inducible gene I (RIG-I) plays a pivotal role in the regulation of cytokine production induced by pathogens. The RIG-I also augments the production of IFN and other cytokines via an ...amplification circuit. Because the production of cytokines is closely controlled, up- and down-regulation of RIG-I signaling also needs strict regulation. The mechanism of this regulation, however, remains elusive. Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production.
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