A strategy for decreasing the viscosity variation in the process of CO2 capture by amino-functionalized ionic liquids (ILs) through the formation of intramolecular hydrogen bond was reported. ...Different with the dramatic increase in viscosity during CO2 uptake by traditional amino-functionalized ILs, slight increase or even decrease in viscosity was achieved through introducing a N or O atom as hydrogen acceptor into amino-functionalized anion, which could stabilize the active hydrogen of produced carbamic acid. Quantum chemical calculations and spectroscopic investigations demonstrated that the formation of intramolecular hydrogen bond between introduced hydrogen acceptor and carbamic acid was the key to avoid the dramatic increase in viscosity during the capture of CO2 by these amino-functionalized ILs.
Grape seed procyanidins (GSPs), widely known for their beneficial health properties, fail to bring about the expected improvement in piglets' growth performance. The effects of dietary ...supplementation with GSPs on nutrient utilisation may be a critical influencing factor. Hence, the purpose of this study was to investigate the effects of dietary supplementation with GSPs on nutrient utilisation and gut function in weaned piglets. One hundred and twenty crossbred piglets were allocated randomly to four treatment groups, with three replicate pens per treatment and 10 piglets per pen. Each group was given one of the four dietary treatments: the basal diet (control group) or the basal diet with the addition of 50-, 100- or 150-mg/kg GSPs. The trial lasted 28 days. Faeces were collected from d 12 to 14 and from d 26 to 28 for measuring the coefficient of total tract apparent digestibility (CTTAD) of the nutrients. Blood samples were collected on d 14 and 28 for detecting the blood biochemical parameters. Two piglets per pen were slaughtered to collect the pancreas and intestinal digesta for evaluating the digestive enzyme activity and the coefficient of ileal apparent digestibility (CIAD) of the nutrients. On d 14 and 28, supplementation with 150-mg/kg GSPs significantly decreased the CTTAD of DM and CP in piglets. On d 14, GSPs supplementation at a concentration of 150 mg/kg led to a remarkable decrease in the CIAD of CP and gross energy (GE). On d 28, GSPs supplementation at a dose of 150 mg/kg generated a marked decline in the CIAD of DM, GE, CP and ether extract. Grape seed procyanidins supplementation at concentrations of 100 or 150 mg/kg inhibited the activities of lipase and amylase. In contrast, the jejunum mucosa maltase and sucrase activities increased due to the inclusion of GSPs at a concentration of 100 mg/kg in the piglet diet. Compared with the levels of the control group, the serum glucose and total protein levels were enhanced significantly by supplementation with GSPs at 100 mg/kg and reduced dramatically at 150 mg/kg. The serum diamine oxidase activity and endotoxin levels were decreased by GSPs supplementation in piglet diets. In conclusion, higher concentrations of GSPs in weaned piglet diets attenuated nutrient digestion and inhibited digestive enzyme activity; however, suitable concentrations of GSPs could promote brush-border enzyme activity, enhance serum glucose and total protein concentrations and decrease epithelial permeability.
To evaluate the association between sodium–glucose cotransporter-2 (SGLT2) inhibitors and risk of bone fractures in patients with type 2 diabetes mellitus (T2DM).
A systematic literature search ...conducted of PubMed, Embase, the Cochrane Library and Web of Science from inception up to 31 August 2018 identified all eligible randomized controlled trials (RCTs). The following data were extracted from each study: first author; year of publication; sample size; patient characteristics; study design; intervention drug; control drug; follow-up durations; and incident bone-fracture events. A meta-analysis was performed using Review Manager 5.3 software to calculate odds ratios (ORs) and 95% confidence intervals (CI) for dichotomous variables.
A total of 30 studies involving 23,372 patients with T2DM were included in our analysis. There were 387 incident bone-fracture cases (245 in the SGLT2 inhibitor group, 142 in the control group). Compared with patients who received placebo, those receiving SGLT2 inhibitor treatment had a pooled OR of bone fracture of 0.86 (95% CI: 0.70–1.06). Also, there was no evidence that individual SGLT2 inhibitors across different doses were associated with any increased risk of bone fracture. After stratification by follow-up duration, an SGLT2 inhibitor treatment period of ≤ 52 weeks appeared to have beneficial effects against bone fracture; however, when the treatment period exceeded 52 weeks, these beneficial effects for preventing bone fracture disappeared.
Our meta-analysis has indicated that SGLT2 inhibitors do not increase risk of bone fracture compared with placebo in patients with T2DM. However, these findings now need to be confirmed in well-designed RCT studies.
Undetectable or low-level hepatitis B virus (HBV) DNA and drug resistance mutations in patients may increase the risk of HBV transmission or cause active viral replication and other clinical ...problems. Here, we established a highly sensitive and practical method for HBV and drug resistance detection using a polymerase chain reaction (PCR) -based CRISPR-Cas13a detection system (referred to as PCR-CRISPR) and evaluated its detection capability using clinical samples.
Specific CRISPR RNAs (crRNAs) are designed for HBV DNA detection and YMDD (tyrosine-methionine-aspartate-aspartate) variant identification. The HBV DNA was detected in 312 serum samples for HBV diagnosis using quantification PCR (qPCR) and PCR-CRISPR. Additionally, 424 serum samples for YMDD testing were detected by qPCR, direct sequencing, and our assay.
Using PCR-CRISPR, one copy per test of HBV DNA was detected with HBV-1 crRNA in 15 min after PCR amplification. Consistent results with qPCR were observed for 302 samples, while the remaining 10 samples with low-level HBV DNA were detectable by PCR-CRISPR and droplet digital PCR but not by qPCR. PCR-CRISPR diagnosed all 412 drug-resistant samples detected by the YMDD detection qPCR kit and direct sequencing, as well as the other 12 drug-resistant samples with low-level HBV DNA undetectable by qPCR and direct sequencing.
We developed a novel PCR-CRISPR method for highly sensitive and specific detection of HBV DNA and drug resistance mutations. One copy per test for HBV DNA and YMDD drug resistance mutations could be detected. This method has wide application prospects for the early detection of HBV infection, drug resistance monitoring and treatment guidance.
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A strategy for improving the capture of CO2 was developed through the entropic effect by tuning the geometric construction of anion-functionalized ionic liquids. Several kinds of anion-functionalized ...ionic liquids with the amino group at the para or ortho position were designed and applied for the capture of CO2, which indicates that the former exhibited both higher capacity and lower enthalpy, resulting in the efficient and energy-saving CO2 capture. Viscosity measurements, spectroscopic investigations, and quantum chemical calculations showed that such a unique behavior originated from the entropic effect, which was induced by the intermolecular hydrogen bonding in these ionic liquids. The entropic control for gas separation developed by this work provides an efficient strategy to both increased capacity and reduced enthalpy.
Anthropogenic activities alter the underlying surface conditions and arrangements of landscape features in a drainage basin, interfering with the pollutant (e.g., dissolved nitrogen, phosphorus) ...transport network configuration and altering the hydrological response. Assessing the impact of anthropogenic activities on hydrological connectivity for natural-artificial catchment is critical to understand the hydrological-driven ecosystem processes, services and biodiversity. However, quantifying this impact at catchment scale remains challenging. In this study, a new framework was proposed to quantify the impact of anthropogenic activities on hydrological connectivity combined with graph theory and network analysis. This framework was exemplified in a natural-artificial catchment of the Yangtze River basin of China. Based on remote sensing and field-investigated data, three transport networks were constructed, including natural transport network (N1), ditch–road transport network (N2), and terrace–dominated transport network (N3), which reflected the different human intervention. The results showed that human intervention improved the connectivity of the nodes and enhanced the complexity of the catchment transport network structure. Anthropogenic activities significantly decreased the hydrological structural connectivity of the catchment. In particular, compared with the N1 network, the critical nodes for hydrological connectivity which were judged by connectivity indexes were reduced by 92.94% and 95.29% in the N2 and N3 network, respectively. Furthermore, the ditch–road construction had a greater impact than terraces in decreasing hydrological structural connectivity at catchment scale. This framework has proven effective in quantifying the hydrological connectivity analysis under different human intervention at the catchment scale and facilitates the improvement of catchment management strategies.
•A new framework was proposed to identify catchment hydrological connectivity.•Graph theory combined with network analysis were integrated into the framework.•Three transport networks were constructed to exemplify the framework.•Ditches, roads, and terraces significantly decreased hydrological connectivity.
It is accepted that amyloid β-derived diffusible ligands (ADDLs) have a prominent role in triggering the early cognitive deficits that constitute Alzheimer's disease (AD). However, there is still no ...effective treatment for preventing or reversing the progression of the disease. Targeting α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor trafficking and its regulation is a new strategy for AD early treatment. Here we investigate the effect and mechanism of L-Stepholidine (L-SPD), which elicits dopamine D1-type receptor agonistic activity, while acting as D2-type receptor antagonist on cognition and synaptic plasticity in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice, and hippocampal cultures or slices treated with ADDLs. L-SPD could improve the hippocampus-dependent memory, surface expression of glutamate receptor A (GluA1)-containing AMPA receptors and spine density in hippocampus of APP/PS1 transgenic mice. L-SPD not only rescued decreased phosphorylation and surface expression of GluA1 in hippocampal cultures but also protected the long-term potentiation in hippocampal slices induced by ADDLs. Protein kinase A (PKA) agonist Sp-cAMPS or D1-type receptor agonist SKF81297 had similar effects, whereas PKA antagonist Rp-cAMPS or D1-type receptor antagonist SCH23390 abolished the effect of L-SPD on GluA1 trafficking. This was mediated mainly by PKA, which could phosphorylate serine residue at 845 of the GluA1. L-SPD may be explored as a potential therapeutic drug for AD through a mechanism that improves AMPA receptor trafficking and synaptic plasticity via activating D1/PKA signaling pathway.
Temperature stability, one of the most important parameters of highly accurate MEMS accelerometers, is always calibrated by the temperature coefficients of performance, thus reducing the temperature ...coefficients has significance to acquire a higher stability of micro devices. This paper proposed an in-depth analytical study on the temperature coefficients of silicon resonant micro-accelerometer based on electrostatic rigidity. And an corresponding optimization method was introduced to reduce the influence of the temperature on the scale factor and improve the device stability over temperature. The results showed the temperature coefficient and the temperature sensitivity of the scale factor were 9Hz/g/°C and 1280ppm/°C, respectively, which are equal to 1.6% and 49% of the original values respectively.
Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate. However, most new chemical entities exhibit poor ...water solubility, and hence are exempt from such benefits. Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility, like other supersaturating systems, the problem of drug recrystallization has yet to be resolved, particularly within the dosage form. Here, we explored the potential of an emerging, non-leachable terpolymer nanoparticle (TPN) pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion (CRASD) beads comprising a poorly soluble drug (celecoxib) reservoir and insoluble polymer (ethylcellulose) membrane. Compared to conventional pore former, polyvinylpyrrolidone (PVP), TPN-containing membranes exhibited superior structural integrity, less crystal formation at the CRASD bead surface, and greater extent of celecoxib release. All-atom molecular dynamics analyses revealed that in the presence of TPN, intra-molecular bonding, crystal formation tendency, diffusion coefficient, and molecular flexibility of celecoxib were reduced, while intermolecular H-bonding was increased as compared to PVP. This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.
A new terpolymer nanoparticle pore former was found to inhibit internal recrystallization in controlled release amorphous solid dispersion beads of celecoxib via its nanoporous structure, non-leachability, and molecular interaction with the drug. Display omitted
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