The 4+3 annulation of aza‐o‐quinone methides and pyridinium 1,4‐zwitterionic thiolates has been developed for the one‐step synthesis of functionalized 2,3‐unsaturated 4,1‐benzothiazepines under mild ...and metal‐free conditions. The produced 4,1‐benzothiazepines can easily be converted into biologically interesting sulfoxides and sulfones via selective oxidization with m‐CPBA.
Hyperhomocysteinemia (Hhcy) may induce memory deficits with β‐amyloid (Aβ) accumulation and tau hyperphosphorylation. Simultaneous supplement of folate and vitamin B12 partially restored the plasma ...homocysteine level and attenuated tau hyperphosphorylation, Aβ accumulation and memory impairments induced by Hhcy. However, folate and vitamin B12 treatment have no effects on Hhcy which has the methylenetetrahydrofolate reductase genotype mutation. In this study, we investigated the effects of simultaneous supplement of betaine on Alzheimer‐like pathological changes and memory deficits in hyperhomocysteinemic rats after a 2‐week induction by vena caudalis injection of homocysteine (Hcy). We found that supplementation of betaine could ameliorate the Hcy‐induced memory deficits, enhance long‐term potentiation (LTP) and increase dendritic branches numbers and the density of the dendritic spines, with up‐regulation of NR1, NR2A, synaptotagmin, synaptophysin, and phosphorylated synapsin I protein levels. Supplementation of betaine also attenuated the Hcy‐induced tau hyperphosphorylation at multiple AD‐related sites through activation protein phosphatase‐2A (PP2A) with decreased inhibitory demethylated PP2AC at Leu309 and phosphorylated PP2AC at Tyr307. In addition, supplementation of betaine also decreased Aβ production with decreased presenilin‐1 protein levels. Our data suggest that betaine could be a promising candidate for arresting Hcy‐induced AD‐like pathological changes and memory deficits.
We have found that betaine can attenuate Hcy‐induced spatial memory deficits with possible mechanisms that may involve in the expresions or/and activations of several memory‐related proteins, and increase the dendritic branches and spine density in hippocampal CA1 region. It also attenuated AD‐like tau hyperphosphorylation by activation PP2A, and inhibited Aβ aggregation by decreasing PS‐1.
Atypical ductal hyperplasia (ADH) is an indication for excisional biopsy to rule out occult breast cancer. We analyzed pathological findings on excisional biopsy for ADH diagnosed in a high volume ...breast center equipped with digital tomosynthesis. Two hundred consecutive patients were diagnosed with ADH on core biopsy with radiographic concordance followed by excisional biopsy. On excisional biopsy, 33 patients (16.5%) were diagnosed with DCIS or invasive breast cancer. Patients with a concurrent diagnosis of papilloma had a higher risk of upstaging on both univariate and multivariate analysis (41.7% vs. 14.9%, p=0.015). No other statistically significant predictors of upgrading were identified (p>0.05).
Purpose
The management of biopsy proven atypical lobular hyperplasia (ALH) is controversial. Although upgrade rates are low, excisional biopsy is often performed to rule out occult breast cancer.
...Methods
In this study, we analyzed our experience with excisional biopsy for ALH diagnosed in the digital tomosynthesis era with radiographic concordance in the community hospital setting. This study included 93 consecutive patients diagnosed with pure ALH on core biopsy from January 2013–December 2017 who underwent subsequent excisional biopsy. Potential clinical, radiographic and pathologic predictors of upgrading were analyzed.
Results
At the time of excisional biopsy, five patients (5.4%) were upgraded to DCIS or invasive breast cancer. There was also a trend towards higher upgrade rates in patients with contralateral breast cancer (
p
= 0.06), biopsy performed by ultrasound or MRI (
p
= 0.07) and extensive ALH (
p
= 0.10). Other clinical, radiographic and pathologic variables were not predictive of upgrade rate (
p
> 0.1 for all).
Conclusion
Patients with pure ALH with radiographic concordance have a low risk of pathologic upgrading on excisional biopsy. Potential predictors of upgrade rate warrant further analysis in a larger dataset.
A novel class of chiral amphiphilic bifunctional thioureas based on a beyerane scaffold and each containing a primary amino group were designed and synthesized from the readily available natural ...product isosteviol. The thioureas were shown to be effective for catalyzing asymmetric Michael additions between isobutyraldehyde and nitroalkenes. The chiral thiourea 1a furnished S enantiomers, whereas 1b afforded R enantiomers, both with high yields (up to 92 %) and high to excellent enantioselectivities (up to 98 %). Furthermore, the reactions proceeded smoothly both in organic solvents and in water under mild conditions.
A novel class of chiral thioureas are highly effective organocatalysts of asymmetric Michael additions of isobutyraldehyde to nitroalkenes under mild conditions both in chloroform and in water. Both enantiomers of the corresponding adducts can be produced, with high to excellent yields and enantioselectivities.
A highly efficient domino aza-MIRC (Michael Induced Ring Closure) reaction between barbiturate-derived alkenes and N-alkoxy α-haloamides has been achieved in moderate to excellent yields. This ...reaction proceeds smoothly under mild conditions via a domino aza-Michael addition/intramolecular SN2 sequence, providing a practical tool in the synthesis of bioactive molecules spirobarbiturate-3-pyrrolidinones.
While progress has been made in information source localization, it has overlooked the prevalent friend and adversarial relationships in social networks. This paper addresses this gap by focusing on ...source localization in signed network models. Leveraging the topological characteristics of signed networks and transforming the propagation probability into effective distance, we propose an optimization method for observer selection. Additionally, by using the reverse propagation algorithm we present a method for information source localization in signed networks. Extensive experimental results demonstrate that a higher proportion of positive edges within signed networks contributes to more favorable source localization, and the higher the ratio of propagation rates between positive and negative edges, the more accurate the source localization becomes. Interestingly, this aligns with our observation that, in reality, the number of friends tends to be greater than the number of adversaries, and the likelihood of information propagation among friends is often higher than among adversaries. In addition, the source located at the periphery of the network is not easy to identify. Furthermore, our proposed observer selection method based on effective distance achieves higher operational efficiency and exhibits higher accuracy in information source localization, compared with three strategies for observer selection based on the classical full-order neighbor coverage.
The indication of retroperitoneal laparoscopic adrenalectomy (RLA) was extended with the retroperitoneal approach and has been wildly accepted and technologically matured. However, the management of ...large adrenal tumors via this approach still remains controversial. The aim of this study was to perform a comprehensive analysis on the minimally invasive surgical management of larger adrenal tumors.
A total of 78 patients with large adrenal tumors (> 5 cm) and 97 patients with smaller adrenal tumors (< 5 cm) were enrolled in this study. The patient characteristics were preferentially analyzed. The intra-operative and postoperative indicators were compared between those who underwent RLA and those who underwent transperitoneal laparoscopic adrenalectomy (TLA); the intra-operative and postoperative indicators were also compared between the large tumor group and smaller tumor group of those who underwent RLA. Furthermore, the analyses of partial RLA were focused on the perioperative indicators and follow-up results.
RLA was superior to TLA in terms of operation time (98.71 ± 32.30 min vs. 124.36 ± 34.62 min, respectively, P = 0.001), hospitalization duration (7.43 ± 2.82 days vs. 8.91 ± 3.40 days, respectively, P = 0.04), duration of drain (4.83 ± 0.37 days vs. 3.94 ± 2.21 days, respectively, P = 0.02), first oral intake (2.82 ± 0.71 days vs. 1.90 ± 0.83 days, respectively, P < 0.001) and time to ambulation (3.89 ± 1.64 days vs. 2.61 ± 1.42 days, respectively, P < 0.001). Further analyses of the RLA patients demonstrated that the larger tumor (> 5 cm) group showed superior results for the intraoperative indicators than the smaller tumor (< 5 cm) group (P < 0.05), while the results for the postoperative indicators between the two tumor size groups were similar (P > 0.05). Data confirmed that the partial resection method was superior to the total resection method from the perspective of the hormone supplement (0% vs. 48.15%, P = 0.002). The 2-year recurrence-free rates were 92.60 and 92.86% for the total and partial RLA resection methods, respectively (P = 0.97). The partial RLA resection method had a similar complete remission rate as the total RLA resection method (96.30% vs. 100%, respectively, P = 0.47).
Both RLA and TLA seem to provide similar effects for the surgical management of large adrenal tumors. However, partial RLA resection should be considered for the management of benign tumors to reduce the hormone supplement.
Patients with diabetes in the aging population are at high risk of Alzheimer's disease (AD), and reduction of sirtuin 1 (SIRT1) activity occurs simultaneously with the accumulation of ...hyperphosphorylated tau in the AD-affected brain. It is not clear, however, whether SIRT1 is a suitable molecular target for the treatment of AD. Here, we employed a rat model of brain insulin resistance with intracerebroventricular injection of streptozotocin (ICV-STZ; 3 mg/kg, twice with an interval of 48 h). The ICV-STZ-treated rats were administrated with resveratrol (RSV; SIRT1-specific activator) or a vehicle via intraperitoneal injection for 8 weeks (30 mg/kg, once per day). In ICV-STZ-treated rats, the levels of phosphorylated tau and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) at the hippocampi were increased significantly, whereas SIRT1 activity was decreased without change of its expression level. The capacity of spatial memory was also significantly lower in ICV-STZ-treated rats compared with age-matched control. RSV, a specific activator of SIRT1, which reversed the ICV-STZ-induced decrease in SIRT1 activity, increases in ERK1/2 phosphorylation, tau phosphorylation, and impairment of cognitive capability in rats. In conclusion, SIRT1 protects hippocampus neurons from tau hyperphosphorylation and prevents cognitive impairment induced by ICV-STZ brain insulin resistance with decreased hippocampus ERK1/2 activity.
A novel class of chiral multifunctional thioureas bearing a chiral lipophilic beyerane scaffold and a primary amino group were designed and prepared. The thioureas were proven to be effective for ...catalyzing the asymmetric Michael addition between isobutyraldehyde and maleimides with only 0.5
mol
% catalyst loading, and exhibited double asymmetric induction. Both of the catalysts afforded the corresponding adduct with high to excellent yields (up to 98%) and excellent enantioselectivities (up to 99%). Furthermore, this catalytic system can be used efficiently in large-scale reactions with the yields and enantioselectivities being maintained at the same level.
PDF
