New Research: Enhanced protein–protein interaction network construction promoted by in vivo cross-linking with acid-cleavable click-chemistry enrichment: Chemical cross-linking coupled with mass spectrometry has emerged as a powerful strategy… https://t.co/tt8OpYyoJS#chemistry
Chemical cross linking coupled with mass spectrometry has emerged as a powerful strategy which enables global profiling of protein interactome with direct interaction interfaces in complex biological systems. The alkyne tagged enrichable cross linkers are preferred to improve the coverage of low abundance cross linked peptides, combined with click chemistry for biotin conjugation to allow the cross linked peptide enrichment. However, a systematic evaluation on the efficiency of click approaches (protein based or peptide based) and diverse cleavable click chemistry ligands (acid, reduction, and photo) for cross linked peptide enrichment and release is lacking. Herein, together with in vivo chemical cross linking by alkyne tagged cross linkers, we explored the click chemistry based enrichment approaches on protein and peptide levels with three cleavable click chemistry ligands, respectively. By comparison, the approach of protein based click chemistry conjugation with acid cleavable tags was demonstrated to permit the most cross linked peptide identification. The advancement of this strategy enhanced the proteome wide cross linking analysis, constructing a 5,518 protein–protein interaction network among 1,871 proteins with widely abundant distribution in cells. Therefore, all these results demonstrated the guideline value of our work for efficient cross linked peptide enrichment, thus facilitating the in depth profiling of protein interactome for functional analysis.
Some older adults with a persistent death wish without being severely ill report having had a death wish their whole lives (lifelong persistent death wish; L-PDW). Differentiating them from older adults without severe illness who developed a death wish later in life (persistent death wish, not lifelong; NL-PDW) can be relevant for the provision of adequate help and support. This study aims to gain insight into the characteristics, experiences, and needs of older adults with a L-PDW versus older adults with a NL-PDW and into the nature of their death wishes. In the Netherlands, in April 2019, a cross-sectional survey study was conducted among a large representative sample of 32,477 citizens aged 55 years and older. Respondents with a L-PDW (N = 50) were compared with respondents with a NL-PDW (N = 217) using descriptive statistics, Kruskal-Wallis tests, and Fisher's exact tests. Respondents with a L-PDW were relatively younger and less often had (step)children. They less often looked back on a good and satisfying life with many good memories and more often reported trauma. Older adults with a NL-PDW more often reported loss and bereavement. Overall, the groups showed a lot of similarities. Both groups reported a death wish diverse in nature, numerous health problems, and a variety of needs for help and support. Some of the differences we found between the groups might be particularly relevant for the provision of adequate help and support to older adults with a L-PDW (id est, their past and trauma) and to older adults with a NL-PDW (id est, their loss and bereavement). The heterogeneity of both groups and the diverse nature of their death wish indicate that careful assessment of the death wish, its background, and underlying needs is required to provide personalized help and support to older adults with a death wish.
We report ferroelectricity and piezoelectric energy harvesting by a discrete cyanoferrate hybrid. A Ferroelectric Aminophosphonium Cyanoferrate with a Large Electrostrictive Coefficient as Piezoelectric Nanogenerator https://t.co/o2HDnpaCbg
Hybrid materials possessing piezo‐ and ferroelectric properties emerge as excellent alternatives to conventional piezoceramics, due to their merits of facile synthesis, lightweight nature, ease of fabrication and mechanical flexibility. Inspired by the structural stability of aminophosphonium compounds, here we report the first A3BX6 type cyanometallate 3 (1), which shows a ferroelectric saturation polarization (Ps) of 3.71 μC cm‒2. Compound 1 exhibits a high electrostrictive coefficient (Q33) of 0.73 m4 C‒2, far exceeding those of piezoceramics (0.034−0.096 m4 C‒2). Piezoresponse force microscopy (PFM) analysis demonstrates the polarization switching and domain structure of 1 further confirming its ferroelectric nature. Furthermore, thermoplastic polyurethane (TPU) polymer composite films of 1 were prepared and employed as piezoelectric nanogenerators. Notably, the 15 wt % 1‐TPU device gave a maximum output voltage of 13.57 V and a power density of 6.03 μW cm‒2.
Viruses, Vol. 14, Pages 2570: Recent Information on Pan Genotypic Direct Acting Antiviral Agents for HCV in Chronic Kidney Disease Viruses doi: 10.3390/v14112570 Authors: Fabrizio Fabrizi Federica Tripodi Roberta Cerutti Luca Nardelli Carlo M. Alfieri Maria F. Donato Giuseppe Castellano Background : Hepatitis C virus (HCV) is still common in patients with chronic kidney disease. It has been recently discovered that chronic HCV is a risk factor for increased incidence of CKD in the adult general population. According to a systematic review with a meta analysis of clinical studies, pooling results of longitudinal studies (n = 2,299,134 unique patients) demonstrated an association between positive anti HCV serologic status and increased incidence of CKD; the summary estimate for adjusted HR across the surveys was 1.54 (95% CI, 1.26; 1.87), (p < 0.0001). The introduction of direct acting antiviral drugs (DAAs) has caused a paradigm shift in the management of HCV infection; recent guidelines recommend pan genotypic drugs (id est, drugs effective on all HCV genotypes) as the first choice therapy for HCV, and these promise to be effective and safe even in the context of chronic kidney disease. Aim: The purpose of this narrative review is to show the most important data on pan genotypic DAAs in advanced CKD (CKD stage 4/5). Method : We recruited studies by electronic databases and grey literature. Numerous key words (Hepatitis C AND Chronic kidney disease AND Pan genotypic agents, among others) were adopted. Result : The most important pan genotypic combinations for HCV in advanced CKD are glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL). Two clinical trials (EXPEDITION 4 and EXPEDITION 5) and some real world studies (n = 6) reported that GLE/PIB combinations in CKD stage 4/5 gave SVR12 rates ranging between 86 and 99%. We retrieved clinical trials (n = 1) and real life studies (n = 6) showing the performance of SOF/VEL; according to our pooled analysis, the summary estimate of SVR rate was 100% in studies adopting SOF/VEL antiviral combinations. The drop out rate (due to AEs) in patients on SOF/VEL ranged between 0 and 4.8%. Conclusions : Pan genotypic combinations, such as GLE/PIB and SOF/VEL, appear effective and safe for HCV in advanced CKD, even if a limited number of studies with small sample sizes currently exist on this issue. Studies are under way to assess whether successful antiviral therapy with DAAs will translate into better survival in patients with advanced CKD.
We present an approach to describing refactorings that abstracts away from particular refactorings to classes of similar transformations, and presents an implementation of these that works by substitution and subsequent rewriting. Substitution is language-independent under this approach, while the rewrites embody language-specific aspects. Intriguingly, it also goes back to work on API migration by Huiqing Li and the first author, and sets refactoring in that general context.
Agriculture, Vol. 12, Pages 1960: Experimental Characterization and Mathematical Modelling of Natural Drying of Apricots at Low Temperatures Agriculture doi: 10.3390/agriculture12111960 Authors: Can Hu Jie Li Qiaonan Yang Xiaokang Yi Hui Cheng Chao Xu Zhenhao Du To mitigate reduced apricot fruit quality due to mildew, browning and sand dust from natural drying under low temperatures and humidity, we determined the characteristics of three different methods of drying (via hanging) and further established their mathematical models. Various comparative analyses of natural drying by laying apricots in an area of the Gobi Desert, subjecting them to ventilated drying in an air drying house, and hanging them on trees were conducted. The least and most efficient methods were hanging on trees (302 h) and laying them in an area of the Gobi Desert (>192 h), respectively. The loss rate and the total sugar content were 5.26% and 70.16%, and up to 18.31% and 68.54% for fruits dried by ventilated drying in an air drying house and those hung on trees, respectively. Fruits dried by ventilated drying in an air drying house showed the least loss and the best comprehensive quality. Using experimental data from assessments of the drying methods, mathematical models were constructed and fitted to drying mathematical models of seven kinds of porous media. The Wang and Singh model had the best fitting degree, an error value of less than 0.05, and the regression that most accurately explained the drying mathematical model for apricots under natural conditions.
JCM, Vol. 11, Pages 6849: Clinical Application of Serum microRNAs in Atherosclerotic Coronary Artery Disease Journal of Clinical Medicine doi: 10.3390/jcm11226849 Authors: Anna Kabłak Ziembicka Rafał Badacz Tadeusz Przewłocki MicroRNAs (miRs) are promising diagnostic, prognostic and therapeutic biomolecules for atherosclerotic cardiovascular disease. Atherosclerotic occlusive disease concerns a large population of patients, carrying the highest incidence of fatal and non fatal adverse events, such as myocardial infarction, ischemic stroke, and limb ischemia, worldwide. Consistently, miRs are involved in regulation and pathogenesis of atherosclerotic coronary artery disease (CAD), acute coronary syndromes (ACS), both with ST segment (STEMI) and non ST segment elevation myocardial infarctions (NSTEMI), as well as cardiac remodeling and fibrosis following ACS. However, the genetic and molecular mechanisms underlying adverse outcomes in CAD are multifactorial, and sometimes difficult to interpret for clinicians. Therefore, in the present review paper we have focused on the clinical meaning and the interpretation of various miRs findings, and their potential application in routine clinical practice.
Nutrients, Vol. 14, Pages 4915: Modulation of Human Motor Cortical Excitability and Plasticity by Opuntia Ficus Indica Fruit Consumption: Evidence from a Preliminary Study through Non Invasive Brain Stimulation Nutrients doi: 10.3390/nu14224915 Authors: Giuditta Gambino Filippo Brighina Mario Allegra Maurizio Marrale Giorgio Collura Cesare Gagliardo Alessandro Attanzio Luisa Tesoriere Danila Di Majo Giuseppe Ferraro Pierangelo Sardo Giuseppe Giglia Indicaxanthin (IX) from Opuntia Ficus Indica (OFI) has been shown to exert numerous biological effects both in vitro and in vivo, such as antioxidant, anti inflammatory, neuro modulatory activity in rodent models. Our goal was to investigate the eventual neuro active role of orally assumed fruits containing high levels of IX at nutritionally relevant amounts in healthy subjects, exploring cortical excitability and plasticity in the human motor cortex (M1). To this purpose, we applied paired pulse transcranial magnetic stimulation and anodal transcranial direct current stimulation (a tDCS) in basal conditions and followed the consumption of yellow cactus pear fruits containing IX or white cactus pear fruits devoid of IX (placebo). Furthermore, resting state functional MRI (rs fMRI) preliminary acquisitions were performed before and after consumption of the same number of yellow fruits. Our data revealed that the consumption of IX containing fruits could specifically activate intracortical excitatory circuits, differently from the placebo controlled group. Furthermore, we found that following the ingestion of IX containing fruits, elevated network activity of glutamatergic intracortical circuits can homeostatically be restored to baseline levels following a tDCS stimulation. No significant differences were observed through rs fMRI acquisitions. These outcomes suggest that IX from OFI increases intracortical excitability of M1 and leads to homeostatic cortical plasticity responses.
IJMS, Vol. 23, Pages 14424: Transcriptome Analysis of Goat Mammary Gland Tissue Reveals the Adaptive Strategies and Molecular Mechanisms of Lactation and Involution International Journal of Molecular Sciences doi: 10.3390/ijms232214424 Authors: Rong Xuan Jianmin Wang Xiaodong Zhao Qing Li Yanyan Wang Shanfeng Du Qingling Duan Yanfei Guo Zhibin Ji Tianle Chao To understand how genes precisely regulate lactation physiological activity and the molecular genetic mechanisms underlying mammary gland involution, this study investigated the transcriptome characteristics of goat mammary gland tissues at the late gestation (LG), early lactation (EL), peak lactation (PL), late lactation (LL), dry period (DP), and involution (IN) stages. A total of 13,083 differentially expressed transcripts were identified by mutual comparison of mammary gland tissues at six developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesis, and metabolism make adaptive transcriptional changes to meet the needs of mammary lactation. Notably, platelet derived growth factor receptor beta (PDGFRB) was screened as a hub gene of the mammary gland developmental network, which is highly expressed during the DP and IN. Overexpression of PDGFRB in vitro could slow down the G1/S phase arrest of goat mammary epithelial cell cycle and promote cell proliferation by regulating the PI3K/Akt signaling pathway. In addition, PDGFRB overexpression can also affect the expression of genes related to apoptosis, matrix metalloproteinase family, and vascular development, which is beneficial to the remodeling of mammary gland tissue during involution. These findings provide new insights into the molecular mechanisms involved in lactation and mammary gland involution.
Foods, Vol. 11, Pages 3729: Hypoglycemic Activity of Self Assembled Gellan Gum Soybean Isolate Composite Hydrogel Embedded Active Substance Saponin Foods doi: 10.3390/foods11223729 Authors: Tao Wu Jinghuan Cheng Jinxuan Zhang Hongxi Zhao Wenjie Sui Qiaomei Zhu Yan Jin Min Zhang In order to avoid hemolysis caused by direct dietary of kidney tea saponin, complex gels based on gellan gum (GG) and soybean isolate protein (SPI) loaded with saponin were created in the present study by using a self assembly technique. Studies were conducted on the rheological characteristics, encapsulation effectiveness, molecular structure, microstructure, and hypoglycemic activity of GG/SPI saponin gels. Increasing the concentration of SPI helped to enhance the strength and energy storage modulus (G′) of the gels, and the incorporation of high acylated saponin allowed the whole gel to undergo sol-gel interconversion. The encapsulation efficiency showed that GG/SPI saponin was 84.52 ± 0.78% for saponin. Microstructural analysis results suggested that GG and SPI were bound by hydrogen bonds. The in vitro digestion results also indicated that saponin could be well retained in the stomach and subsequently released slowly in the intestine. In addition, the in vitro hypoglycemic activity results showed that the IC50 of encapsulated saponin against α glucosidase and α amylase were at 2.4790 mg/mL and 1.4317 mg/mL, respectively, and may be used to replace acarbose for hypoglycemia.
Biomedicines, Vol. 10, Pages 2983: Molecular Mechanisms Linking Empagliflozin to Renal Protection in the LLC PK1 Model of Diabetic Nephropathy Biomedicines doi: 10.3390/biomedicines10112983 Authors: Vjera Mihaljević Milorad Zjalić Tomislav Kizivat Tea Omanović Kolarić Martina Smolić Edi Rođak Marina Čović Lucija Kuna Robert Smolić Aleksandar Včev Ines Bilić Ćurčić Aims : Chronic diabetes complications, including diabetic nephropathy (DN), frequently result in end stage renal failure. This study investigated empagliflozin (SGLT2i) effects on collagen synthesis, oxidative stress, cell survival, and protein expression in an LLC PK1 model of DN. Method : Combinations of high glucose (HG) and increasing empagliflozin concentrations (100 nM and 500 nM), as well as combinations of HG, H2O2, and empagliflozin, were used for cell culture treatment. The cell viability, glutathione (tGSH), ECM expression, and TGF β1 concentration were measured. In addition, the protein expression of Akt, pAkt, GSK3, pGSK3, pSTAT3, and SMAD7 was determined. Result : The addition of both concentrations of empagliflozin to cells previously exposed to glucose and oxidative stress generally improved cell viability and increased GSH levels (p < 0.001, p < 0.05). In HG30/H2O2/Empa500 treated cells, significant increase in pSTAT3, pGSK3β, GSK3β, SMAD7, and pAKT levels (p < 0.001, p < 0.001, p < 0.05) was observed except for AKT. Lower drug concentrations did not affect the protein expression levels. Furthermore, empagliflozin treatment (100 nM and 500 nM) of HG30/H2O2 injured cells led to a decrease in TGF β1 levels (p < 0.001). In cells exposed to oxidative stress and hyperglycemia, collagen production remained unchanged. Conclusion : Renoprotective effects of empagliflozin, in this LLC PK1 cell model of DN, are mediated via activation of the Akt/GSK 3 signalling pathway, thus reducing oxidative stress induced damage, as well as enhanced SMAD7 expression leading to downregulation of TGF β1, one of the key mediators of inflammation and fibrosis.
Pia Fuertjes, Martin Bock, Lorenz von Grafenstein, Dennis Ueberschaer, Uwe Griebner, Thomas ElsaesserLow energy excitations can provide insight into the basic ultrafast nonequilibrium dynamics of condensed matter. High energy femtosecond ...
Molecules, Vol. 27, Pages 8067: Quantitation of Flavor Compounds in Refill Solutions for Electronic Cigarettes Using HS GCxIMS and Internal Standards Molecules doi: 10.3390/molecules27228067 Authors: Alexander L. R. M. Augustini Stefanie Sielemann Ursula Telgheder New regulations on the use of flavor compounds in tobaccoless electronic cigarettes require comprehensive analyses. Gas chromatography coupled ion mobility spectrometry is on the rise as an analytical technique for analyzing volatile organic compounds as it combines sensitivity, selectivity, and easy usage with a full range screening. A current challenge is the quantitative GCxIMS analysis. Non linear calibration methods are predominantly used. This work presents a new calibration method using linearization and its corresponding fit based on the relation between the reactant and analyte ions from the chemical ionization. The analysis of e liquids is used to compare the presented calibration with an established method based on a non linear Boltzmann fit. Since e liquids contain matrix compounds that have been shown to influence the analyte signals, the use of internal standards is introduced to reduce these effects in GCxIMS analysis directly. Different matrix mixtures were evaluated in the matrix matched calibration to improve the quantitation further. The systems detection and quantitation limits were determined using a separate linear calibration. A matrix matched calibration series of 29 volatile compounds with 12 levels were used to determine the concentration of these substances in a spiked, flavorless e liquid and a banana flavored e liquid, validating the quality of the different calibrations.
Applied Sciences, Vol. 12, Pages 11793: Chaos Applied Sciences doi: 10.3390/app122211793 Authors: Luigi Fortuna Arturo Buscarino The fascinating subject of chaos has been the focus of researchers and scientists from many fields over the last 40 years