•Emulsions with different droplet sizes and compositions were prepared.•Long chain fatty acids and Coenzyme Q10 were encapsulated in droplets.•For digestible droplets, bioavailability increased with ...decreasing particle size.•The bioavailability of indigestible droplets was lower than digestible ones.
The influence of droplet size (d32=0.21, 0.70 or 2.2μm) and oil digestibility (corn oil versus mineral oil) on the bioavailability of a model long chain fatty acid (heptadecanoic acid) and lipophilic nutraceutical (Coenzyme Q10) was investigated using a rat feeding study. Initially, we showed that small droplets were digested more rapidly than large droplets using a simulated small intestinal model (pH stat), which was attributed to the greater surface area of lipid exposed to intestinal juices. The pH stat model also confirmed that emulsified corn oil was digestible, whereas emulsified mineral oil was indigestible. A rat feeding study showed that the bioavailability of the fatty acid and lipophilic nutraceutical in small intestinal tissues was highest when they were encapsulated within digestible oil droplets with the smallest size. This study provides important information for development of nanoemulsion-based delivery systems that increase oral bioavailability of lipophilic nutraceuticals.
Dynamic recrystallization (DRX) often takes place during hot deformation of metallic materials, which then exerts significant influence on the final microstructures and mechanical properties of the ...formed components. A considerable number of published papers related to DRX, however, suffer from non-negligible flaws originating from inappropriate experimental design. In this paper, the sources of these flaws are critically assessed, including the misinterpretation of DRX mechanisms, the strain localization on tested samples, the neglected post dynamic recrystallization and possible phase transformations which mask the real hot deformation microstructure. Solutions to eliminate or quantify these disturbing factors during DRX studies are suggested, yielding more accurate approaches to investigate DRX behaviour of metallic materials.
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•Common dynamic recrystallization (DRX) mechanisms are reviewed.•The disturbing effect of strain localization on DRX is discussed.•The neglected post DRX after hot deformation is examined.•The possible phase transformation during and after hot deformation is considered.
Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy ...workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses.
Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany.
Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells.
This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.
Strobilurin fungicides are used globally and have been detected in microgram per liter concentrations in aquatic environments. Here, we determined the potential toxicity of four commonly used ...strobilurins (azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin) on mitochondrial function and locomotor activity of larval zebrafish at an environmentally relevant level. As the mode of action of strobilurins in fungi is binding to cytochrome bc1 in mitochondrial complex III, we evaluated exposure effects on mitochondrial oxidative phosphorylation of zebrafish, by measuring oxygen consumption rates, mitochondria-related enzyme activities, and transcripts levels for genes associated with the electron transfer chain and citric acid cycle. We found that 50 nM pyraclostrobin and trifloxystrobin lowered basal respiration, oligomycin-induced ATP respiration, and maximal respiration of embryos. Dysfunction in mitochondrial bioenergetics was associated with changes in mitochondrial complex III activity and transcripts of oxidative respiration and stress-related genes. Lower activity of complex III, and reduced cytb mRNA levels were hypothesized to contribute to reduced electron supply to complex IV and V. Both coxI and atp6 were up-regulated, suggesting a compensatory response to impaired oxidative respiration. Cluster analysis indicated that strobilurin-induced oxidative stress and cytb transcript were related to impaired oxidative phosphorylation. We also assessed larval behavior responses, as reduced ATP can affect activity. We observed that pyraclostrobin and trifloxystrobin induced hypoactive responses in zebrafish. At 50 nM, azoxystrobin and kresoxim-methyl exerted no effects on mitochondrial function nor locomotion of zebrafish. Studies such as this are important for determining sublethal toxicity to these fungicides, as widespread detection of strobilurins in aquatic environments suggests there is a potential for adverse effects in aquatic organisms.
Safflower Injection is one kind of injections derived from traditional Chinese medicine. It is widely applied to treat cerebrovascular diseases such as acute cerebral infarction, stroke, coronary ...heart disease, and angiitis. However, most adverse reactions of Safflower Injection in clinic are caused by its quality problems. In this study, 10 batches of normal and 42 batches of abnormal Safflower Injections were obtained from the clinical practice. Their quality fluctuations were detected by chemical fingerprinting (CF, ultra-performance liquid chromatography tandem mass spectrometry) and bioassays including cell-based biological profile (CBP) assay and enzymatic assay. CF identified 33 compounds in the Safflower Injections, and scutellarin and kaempferol-3-O-rutinoside were identified to be the possible components responsible for clinical adverse reaction. In addition, 59.5% (25/42), 85.7% (36/42) and 38.1% (16/42) of abnormal samples could be identified by CF, CBP assay and enzymatic assay, respectively. Interestingly, further integration of the three methods could entirely identify all the abnormal samples. It indicated that it is advisable to integrate CF, CBP assay and enzymatic assay for developing quality standard of Safflower Injections.
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•Bioassays could differentiate abnormal samples that chemical detection could not.•100% identification of abnormal samples could be achieved by the integration method.•Novel integration of chemical fingerprinting and bioassay was established to promote quality control of Safflower Injection.
This study aimed to carry out a bibliometric analysis of primary ovarian insufficiency (POI) from 2010 to 2020 and to reveal the research status and hotspots in the future.
A total of 3087 articles ...and reviews related to POI published from 2010 to 2020 retrieved from the Web of Science Core Collection were used for bibliometric analysis. CiteSpace and VOSviewer were adopted to analyze countries and regions, organizations, authors, journals, keywords and co-cited references.
The number of publications about POI increased year by year. The USA produced the largest number of publications and the most influence in this field. The main research directions of POI can be roughly divided into four aspects according to the analysis of keywords and co-cited references: genetic research of POI; stem cell therapy for patients with POI; prediction of ovarian function; and fertility preservation of cancer patients. Genetic research and stem cell therapy may become research hotspots in the future.
This study might be the first bibliometric study to analyze publications of POI from multiple indicators, in order to provide new opinions for the research trends and possible hotspots of POI.
A 28 GHz 5-bit switch-type phase shifter (STPS) using 0.18 μm CMOS technology is presented for 5G mobile communication applications. Utilising a process variation insensitive transmission line-based ...bridged T-type topology for 11.25°, 22.5°, 45°, 90° 1-bit phase shifters and high-pass/low-pass network switched-path-type topology for 180° 1-bit phase shifter, the 5-bit STPS achieves ultra-low root mean square (RMS) phase error of 1.7° and low RMS amplitude error of 0.59 dB at 28 GHz with intrinsic digital phase-control mechanism. The measured insertion loss of all 32 states is 15 ± 1.5 dB at 28 GHz with zero dc consumption.
In this article, kinetics of neat poly(lactic acid) (PLA) and its blends with triphenyl phosphate (TPP) and/or talc crystallized isothermally in the temperature range of 113-128°C was analyzed by ...differential scanning calorimetry (DSC) and described by the Avrami equation. The results showed that the average value of Avrami exponents n is around 2.0 for neat PLA and the PLA/15TPP blend, and around 3.0 for the PLA/1.2Talc blend and the PLA/15TPP/1.2Talc blend. The crystallization rate constants k for neat PLA and its blends were increased in the following order: the PLA/15TPP blend, neat PLA, the PLA/15TPP/1.2Talc blend, and PLA/1.2Talc blend. The half-time of crystallization t₁/₂ was increased with an increase of crystallization temperature Tc and the presence of TPP, and was decreased sharply with the incorporation of talc. Further investigation into crystallization activation energy ΔEa of neat PLA and its blends with 15 wt % TPP and/or 1.2 wt % talc showed that the values of ΔEa were increased with the incorporation of TPP and/or talc compared to that of neat PLA. It was verified by wide angle X-ray diffraction (WAXD) that neat PLA and its blends with TPP and/or talc crystallized isothermally in the temperature range of 113-128°C, and all formed the α-form crystal after enough annealing time.
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