•Bioactive compounds were extracted from byproduct Blueberry Wine Pomace.•Ultrasound-Assisted Extraction technique was optimized for phenolics and anthocyanins recovery.•Ultrasound-Assisted ...Extraction yielded more than Conventional Solvent Extraction.•HPLC–DAD–MS/MS showed that the two methods yielded the same anthocyanins.
Ultrasound-Assisted Extraction (UAE) of total anthocyanins (TA) and phenolics (TP) from Blueberry Wine Pomace (BWP) was optimized using Response Surface Methodology (RSM). A Box–Behnken design was used to predict that the optimized conditions were an extraction temperature of 61.03°C, a liquid–solid ratio of 21.70mL/g and a sonication time of 23.67min. Using the modeled optimized conditions, the predicted and experimental yields of TA and TP were within a 2% difference. The yields of TA and TP obtained through the optimized UAE method were higher than those using a Conventional Solvent Extraction (CSE) method. Seven anthocyanins, namely delphinidin-3-O-glucoside, delphindin-3-O-arabinoside, petunidin-3-O-glucoside, cyanidin-3-O-arabinoside, cyanidin-3-O-glucoside, malvidin-3-O-glucoside and malvidin-3-O-arabinoside, were found in the BWP extract from both the UAE and CSE methods.
(Hetero)arene reduction is one of the key avenues for synthesizing related cyclic alkenes and alkanes. While catalytic hydrogenation and Birch reduction are the two broadly utilized approaches for ...(hetero)arene reduction across academia and industry over the last century, both methods have encountered significant chemoselectivity challenges. We hereby introduce a highly chemoselective quinoline and isoquinoline reduction protocol operating through selective energy transfer (EnT) catalysis, which enables subsequent hydrogen atom transfer (HAT). The design of this protocol bypasses the conventional metric of reduction reaction, that is, the reductive potential, and instead relies on the triplet energies of the chemical moieties and the kinetic barriers of energy and hydrogen atom transfer events. Many reducing labile functional groups, which were incompatible with previous (hetero)arene reduction reactions, are retained in this reaction. We anticipate that this protocol will trigger the further advancement of chemoselective arene reduction and enable the current arene‐rich drug space to escape from flatland.
An alkene and a (hetero)arene, to be reduced or retained? In contrast to conventional processes, in the reported hydrogen atom transfer (HAT) protocol enabled by energy transfer (EnT) catalysis, the benzenoid ring of a quinoline is more easily reduced than an electron‐deficient alkene. Furthermore, many reducing labile moieties, such as aryl iodides, electron‐deficient alkynes, benzsulfamides, and benzyl ethers, are compatible with this method.
Soil acidification has always been a substantial eco-environmental problem restricting agricultural development in the red soil region of southern China. It is necessary to determine the dynamic ...change in soil pH in this area to formulate regional agricultural and environmental management measures. Yujiang County, a typical county with red soil acidification in southern China, was selected as the study area. Based on soil data from 1982, 2007, and 2018, the spatiotemporal variation characteristics and the latest changes in soil pH in the county were analyzed. The results show that the soil pH in Yujiang County decreased from 5.66 to 4.74 and then increased to 4.96 from 1982 to 2018, showing a trend of first decreasing and then increasing. According to the spatial distribution characteristics of soil pH, the low soil pH values in the three periods were mainly distributed in the northern mountainous areas with more forestland and dry land area and some southern hilly areas, while the paddy soil pH values in the middle low hilly areas were relatively higher. The soil pH decreased rapidly from 1982 to 2007, showing a large area of acidification. In 2007, the proportions of acidic (4.5 < pH < 5.5) and strongly acidic (pH < 4.5) soils increased by 67.37% and 10.6%, respectively, compared with that in 1982. However, from 2007 to 2018, the soil pH of the whole county increased, and the acidification trend was alleviated, which is of great significance to the regional red soil ecological environment. Through the analysis of the main factors affecting the change in soil pH, it was found that the sharp decline in soil pH in Yujiang County during 1982–2007 was mainly caused by acid rain and excessive nitrogen application. From 2007 to 2018, no significant reduction in nitrogen fertilizer in this area occurred, and although the increase in soil organic matter contributed to alleviating soil acidification, the analysis showed that the decrease in acid rain was the main reason for the rise in soil pH in Yujiang County. At the same time, notably, there is a large area of soil in the area that is still acidic, and effective control of soil acidification is still an important ecological and environmental issue in this area. In order to further improve the pH value of soil in red soil region, it is suggested that on the basis of continuous improvement of acid rain, in addition to increasing soil organic matter by returning straw to field and other measures, appropriate amount of lime or alkaline biochar can be applied to better improve the soil ecological environment in red soil hilly region.
Bacterial persister cells, a sub-population of dormant phenotypic variants highly tolerant to antibiotics, present a significant challenge for infection control. Investigating the mechanisms of ...antibiotic persistence is crucial for developing effective treatment strategies. Here, we found a significant association between tolerance frequency and previous infection history in bovine mastitis. Previous S. aureus infection led to S. aureus tolerance to killing by rifampicin in subsequent infection in vivo and in vitro. Actually, the activation of trained immunity contributed to rifampicin persistence of S. aureus in secondary infection, where it reduced the effectiveness of antibiotic treatment and increased disease severity. Mechanically, we found that S. aureus persistence was mediated by the accumulation of fumarate provoked by trained immunity. Combination therapy with metformin and rifampicin promoted eradication of persisters and improved the severity of recurrent S. aureus infection. These findings provide mechanistic insight into the relationship between trained immunity and S. aureus persistence, while providing proof of concept that trained immunity is a therapeutic target in recurrent bacterial infections involving persistent pathogens.
Chronic kidney disease (CKD) is associated with accelerated atherosclerosis progression and high incidence of cardiovascular events, hinting that atherosclerotic plaques in CKD may be vulnerable. ...However, its cause and mechanism remain obscure. Here, it is shown that apolipoprotein E‐deficient (ApoE−/−) mouse with CKD (CKD/ApoE−/− mouse) is a useful model for investigating the pathogenesis of plaque vulnerability, and premature senescence and phenotypic switching of vascular smooth muscle cells (VSMCs) contributes to CKD‐associated plaque vulnerability. Subsequently, VSMC phenotypes in patients with CKD and CKD/ApoE−/− mice are comprehensively investigated. Using multi‐omics analysis and targeted and VSMC‐specific gene knockout mice, VSMCs are identified as both type‐I‐interferon (IFN‐I)‐responsive and IFN‐I‐productive cells. Mechanistically, mitochondrial damage resulting from CKD‐induced oxidative stress primes the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway to trigger IFN‐I response in VSMCs. Enhanced IFN‐I response then induces VSMC premature senescence and phenotypic switching in an autocrine/paracrine manner, resulting in the loss of fibrous cap VSMCs and fibrous cap thinning. Conversely, blocking IFN‐I response remarkably attenuates CKD‐associated plaque vulnerability. These findings reveal that IFN‐I response in VSMCs through immune sensing of mitochondrial damage is essential for the pathogenesis of CKD‐associated plaque vulnerability. Mitigating IFN‐I response may hold promise for the treatment of CKD‐associated cardiovascular diseases.
Oxidative stress‐induced mitochondrial damage under chronic kidney disease (CKD) milieu primes the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway in vascular smooth muscle cells (VSMCs) to trigger type‐I‐interferon response, which induces VSMC premature senescence and phenotypic switching in an autocrine/paracrine manner and finally results in plaque vulnerability.
Tau aggregation in neurofibrillary tangles (NFTs) is closely associated with neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the molecular signatures that distinguish ...between aggregation-prone and aggregation-resistant cell states are unknown. We developed methods for the high-throughput isolation and transcriptome profiling of single somas with NFTs from the human AD brain, quantified the susceptibility of 20 neocortical subtypes for NFT formation and death, and identified both shared and cell-type-specific signatures. NFT-bearing neurons shared a marked upregulation of synaptic transmission-related genes, including a core set of 63 genes enriched for synaptic vesicle cycling. Oxidative phosphorylation and mitochondrial dysfunction were highly cell-type dependent. Apoptosis was only modestly enriched, and the susceptibilities of NFT-bearing and NFT-free neurons for death were highly similar. Our analysis suggests that NFTs represent cell-type-specific responses to stress and synaptic dysfunction. We provide a resource for biomarker discovery and the investigation of tau-dependent and tau-independent mechanisms of neurodegeneration.
In hypertrophic hearts, autophagic flux insufficiency is recognized as a key pathology leading to maladaptive cardiac remodeling and heart failure. This study aimed to illuminate the cardioprotective ...role and mechanisms of a new myokine and adipokine, irisin, in cardiac hypertrophy and remodeling. Adult male wild-type, mouse-FNDC5 (irisin-precursor)-knockout and FNDC5 transgenic mice received 4 weeks of transverse aortic constriction (TAC) alone or combined with intraperitoneal injection of chloroquine diphosphate (CQ). Endogenous FNDC5 ablation aggravated and exogenous FNDC5 overexpression attenuated the TAC-induced hypertrophic damage in the heart, which was comparable to the protection of irisin against cardiomyocyte hypertrophy induced by angiotensin II (Ang II) or phenylephrine (PE). Accumulated autophagosome and impaired autophagy flux occurred in the TAC-treated myocardium and Ang II- or PE-insulted cardiomyocytes. Irisin deficiency caused reduced autophagy and aggravated autophagy flux failure, whereas irisin overexpression or supplementation induced protective autophagy and improved autophagy flux, which were reversed by autophagy inhibitors Atg5 siRNA, 3-MA and CQ. Irisin boosted the activity of only AMPK but not Akt and MAPK family members in hypertrophic hearts and cultured cardiomyocytes and further activated ULK1 at Ser555 but not Ser757 and did not affect the mTOR-S6K axis. Blockage of AMPK and ULK1 with compund C and SBI-0206965, respectively, both abrogated irisin's protection against cardiomyocyte hypertrophic injury and reversed its induction of both autophagy and autophagy flux. Our results suggest that irisin protects against pressure overload-induced cardiac hypertrophy by inducing protective autophagy and autophagy flux via activating AMPK-ULK1 signaling.
•Irisin is highly expressed in mouse hearts.•FNDC5 deletion aggravated and FNDC5 overexpression ameliorated the left ventricle hypertrophy, remodeling, injury and dysfunction induced by pressure overload.•Irisin supplementation attenuated hypertrophy in Ang II– or phenylephrine-induced cardiomyocytes.•Irisin alleviated cardiomyocyte hypertrophy in vivo and in vitro by inducing beneficial autophagy and autophagy influx via AMPK-ULK1 signaling but independent of mTOR.
La0.7Ca0.3MnO3 nanoparticles doped with Sr (La0.7(Ca0.3-xSrx)MnO3, x = 0, 0.05, 0.10, 0.15, 0.20, 0.25, and 0.30) were prepared by sol–gel method. Their structural, electrical and magnetic properties ...were examined by various analytical methods. XRD (X-ray diffraction) showed a transition in phase from orthorhombic (space group of Pbnm) to rhombohedral (space group of R3̅c) at x = 0.10∼0.15. Cell volume continuously expanded as x increased due to larger radius of Sr2+ ion (1.31Å) compared to that of Ca2+ (1.18Å). This substitution accordingly led to changes in tolerance factor (τ). TEM images confirmed structural phase transition from Pbnm to R3̅c. Average particle sizes of samples with x = 0.05 and 0.25 were measured by TEM as 56nm and 45nm, respectively. Furthermore, a significant increase in Tc and Tp for LCSMO nanoparticles was observed as x rose from lower to higher values. The enhancement of double−exchange (DE) interactions was caused by larger radius of Sr2+ cation, which induced modifications in the Mn−O−Mn bond angles and Mn−O bond distance. This, in turn, boosted magnetic and electrical properties of the resulting nanoparticles. On the other hand, the effect of particle size and intrinsic characteristics was found responsible for approximate values of saturation magnetization. Finally, the increase in coercivity and the decrease in temperature coefficient of resistance (TCR%) were related to spin disordered surface layers of particles and scattering of electrons at grain boundaries, respectively.
Background
The contaminated output water from dental unit waterlines (DUWLs) is a potential risk to both patients and dental personnel who are frequently exposed to this water or aerosols.
Aim
The ...purpose was to evaluate the contamination level and prevalence of bacteria in the output water of DUWLs, and to identify key factors to provide technical support for formulating relevant policies.
Methods
We developed a special sampling connector designed for collecting dental handpiece output water and a measurement device to assess retraction of a dental chair unit (DCU). Output water from dental handpieces and air/water syringes were collected as representative of DUWLs. Water samples were tested with reference to China's national standard.
Findings
From 2012 to 2017, 318 DCUs were randomly selected from 64 hospitals in Tianjin, China. Of these DCUs, 78.93% had no disinfection to prevent DUWL contamination. Three‐hundred and forty‐three (56.14%) samples complied with the guidelines on DUWL output water. The highest concentration of bacteria was 1.8 × 106 colony‐forming units (CFUs)/mL. The three key factors of influence were as follows: daily or weekly disinfection of DUWLs; water supply source being hospital self‐made purified water or purchased purified bottled water; and DCU with a valid anti‐retraction valve. Potential infectious agents, including Bacillus cereus, Burkholderia cepacia and Pseudomonas aeruginosa, were isolated.
Conclusion
There was a high rate of contamination in DUWLs. This highlights the need to develop national standards. There is a need to disinfect the DUWLs periodically and use a cleaner source of water; more attention should be paid to the efficacy of DCU anti‐retraction valves.
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