Magnetization Transfer Prepared Gradient Echo MRI for CEST Imaging

Chemical exchange saturation transfer (CEST) is an emerging MRI contrast mechanism that is capable of noninvasively imaging dilute CEST agents and local properties such as pH and temperature, augmenting the routine MRI methods. However, the routine CEST MRI includes a long RF saturation pulse followed by fast image readout, which is associated with high specific absorption rate and limited spatial resolution. In addition, echo planar imaging (EPI)-based fast image readout is prone to image distortion, particularly severe at high field. To address these limitations, we evaluated magnetization transfer (MT) prepared gradient echo (GRE) MRI for CEST imaging. We proved the feasibility using numerical simulations and experiments in vitro and in vivo. Then we optimized the sequence by serially evaluating the effects of the number of saturation steps, MT saturation power (B1), GRE readout flip angle (FA), and repetition time (TR) upon the CEST MRI, and further demonstrated the endogenous amide proton CEST imaging in rats brains (n = 5) that underwent permanent middle cerebral artery occlusion. The CEST images can identify ischemic lesions in the first 3 hours after occlusion. In summary, our study demonstrated that the readily available MT-prepared GRE MRI, if optimized, is CEST-sensitive and remains promising for translational CEST imaging

Analysis on the Nutritional Components and Texture Characteristics of Prefabricated Grilled Fish with Different Fish Species

To explore the development value of different freshwater fish productions of prefabricated grilled fish and realize the diversified development of prefabricated grilled fish categories, an analysis was hereby carried out on the nutritional and textural characteristics of prefabricated grilled fish processed from six common freshwater fish. The results showed that there was no significant difference in the moisture and ash content (P>0.05), the protein content ranged from 21.87%~24.28%, and the fat content was low in all six types of grilled fish. Besides, the content of glutamic acid, aspartic acid and lysine was high, and that of the total essential amino acids ranged from 7.71~9.42 g/100 g. Among them, that of common carp and Wuchang fish was higher, followed by tilapia and grass carp, Wuchang fish, common carp and tilapia had a high fresh amino acid content. The ratio of the essential amino acids to the total amino acids of the six grilled fish was about 40%, which was a high-quality animal protein source. According to the amino acid score, the first limiting amino acid of all six grilled fish was methionine+cysteine, common carp had the highest essential amino acid index, followed by tilapia. Besides, a total of 22 fatty acids were detected in the six grilled fish species, which had a high proportion of unsaturated fatty acids. Tilapia and Wuchang fish contained high functional fatty acids with a high nutritional value, such as eicosapentaenoic acid and docosahexaenoic acid. Through the principal component analysis, the comprehensive score of nutritional indicators followed the order of tilapia>Wuchang fish>common carp>grass carp>crucian carp>pincer fish, while in terms of textural characteristics, the elasticity and chewiness of tilapia and Wuchang fish were significantly（P<0.05）higher than those of traditional common carp and grass carp, and the hardness was lower. In this case, it could be tentatively inferred that tilapia and Wuchang fish had a better muscle texture. As raw materials of grilled fish, all these six freshwater fish were excellent protein sources, reasonable amino acid composition and rich fatty acids, among which, tilapia and Wuchang fish produced prefabricated grilled fish with better nutrition and better taste. Overall, this study provides a theoretical basis for the development of grilled fish in multiple categories and the extension of the "breeding+processing" industry chain

Discordant Risk: Overweight and cardiometabolic risk in Chinese adults

Recent US work identifies “metabolically healthy overweight” and “metabolically at risk normal weight” individuals. Less is known for modernizing countries with recent increased obesity. Fasting blood samples, anthropometry and blood pressure from 8,233 adults aged 18–98 in the 2009 nationwide China Health and Nutrition Survey, were used to determine prevalence of overweight (Asian cut point, BMI≥23 kg/m2) and five risk factors [pre-diabetes/diabetes (HbA1c≥5.7%) inflammation (hsCRP ≥3 mg/L), pre-hypertension/hypertension (SBP/DBP≥130/85 mmHg), high triglycerides (≥150 mg/dL), low high-density lipoprotein cholesterol (70 years: 73%). Abdominal obesity was highly predictive of metabolic risk, irrespective of overweight (e.g., “metabolically at risk overweight” relative to “metabolically healthy normal weight” [men: Relative Risk Ratio (RRR) =39.06; 95% Confidence Interval (CI): 23.47, 65.00; women: RRR=22.26; 95% CI: 17.49, 28.33]). To conclude, a large proportion of Chinese adults have metabolic abnormalities. High hypertension risk with age, irrespective of obesity underlies the low prevalence of metabolically healthy overweight. Screening for cardiometabolic-related outcomes dependent upon overweight will likely miss a large portion of the Chinese at-risk population

Impact of alirocumab/evolocumab on lipoprotein (a) concentrations in patients with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized controlled trials

Introduction: Familial hypercholesterolaemia (FH) is a common hereditary genetic disorder, characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] concentrations, leading to atherosclerotic cardiovascular disease (ASCVD). Two types of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors — alirocumab and evolocumab — are efficient drugs in the treatment of FH, which can effectively reduce Lp(a) levels. Material and methods: Embase, MEDLINE, and PubMed up to November 2022 were searched for randomized clinical trials (RCTs) evaluating the effect of alirocumab/evolocumab and placebo treatment on plasma Lp(a) levels in FH. Statistics were analysed by Review Manager (RevMan 5.3) and Stata 15.1. Results: Eleven RCTs involved a total of 2408 participants. Alirocumab/evolocumab showed a significant efficacy in reducing Lp(a) [weighted mean difference (WMD): –20.10%, 95% confidence interval (CI): –25.59% to –14.61%] compared with placebo. In the drug type subgroup analyses, although the efficacy of evolocumab was slightly low (WMD: –19.98%, 95% CI: –25.23% to –14.73%), there was no difference with alirocumab (WMD: –20.54%, 95% CI: –30.07% to –11.02%). In the treatment duration subgroup analyses, the efficacy of the 12-week duration group (WMD: –17.61%, 95% CI: –23.84% to –11.38%) was lower than in the group of ≥ 24 weeks’ duration (WMD: –22.81%, 95% CI: –31.56% to –14.07%). In the participants’ characteristics subgroup analyses, the results showed that no differential effect of alirocumab/evolocumab therapy on plasma Lp(a) concentrations was observed (heterozygous FH [HeFH] WMD: –20.07%, 95% CI: –26.07% to –14.08%; homozygous FH [HoFH] WMD: –20.04%, 95% CI: –36.31% to –3.77%). Evaluation of all-cause adverse events (AEs) between alirocumab/evolocumab groups and placebo groups [relative risk (RR): 1.05, 95% CI: 0.98–1.12] implied no obvious difference between the 2 groups. Conclusions: Anti-PCSK9 drugs (alirocumab and evolocumab) may be effective as therapy for reducing serum Lp(a) levels in FH, and no differences were observed in treatment durations, participant characteristics, and other aspects of the 2 types of PCSk9 inhibitors. However, further experimental studies and RCTs are warranted to clarify the mechanism of PSCK9 inhibitors to lowering Lp(a) concentrations in FH

Characterization and Discrimination of Prefabricated Grilled Fish with Different Packaging Methods Using Non-targeted Metabolomics

To explore the metabolites differences of grilled fish in different packages, liquid chromatography-tandem mass spectrometry was used to analyze and compare the metabolite profile of prefabricated grilled fish in tray packaging, vacuum packaging and modified atmosphere packaging through non-targeted metabolomics. The results showed that 318 metabolites were identified under secondary mass spectrometry information in the prefabricated grilled fish with different packaging. In this study, 47 differential metabolites were identified, including 10 fatty acids, 10 nucleotides, 9 amino acids, 7 organic acids and derivatives, 3 benzene and derivatives, 2 alcohol amines, and 6 unconfirmed metabolites, based on the variable importance projection value (VIP, VIP>1) and P<0.05 of the orthogonal partial least squares discriminant analysis model. Clustering heat map analysis of the relative content of 47 different metabolites was performed and the results showed differences in the relative content of metabolites in three types of packages. The relative contents of multiple flavor amino acids and adenosine monophosphate (AMP) were significantly higher in the modified atmosphere packaging than in the conventional vacuum package and tray package. The results revealed that modified atmosphere packaging effectively preserved the umami flavor of grilled fish, offering a basis for the development of novel and effective packaging for grilled fish

Single cell transcriptome profiling reveals cutaneous immune microenvironment remodeling by photodynamic therapy in photoaged skin

BackgroundThe immune microenvironment plays a critical role in maintaining skin homeostasis, which is closely related to the dysfunction in photoaged skin such as autoimmunity and tumorigenesis. Several recent studies have demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in alleviating photoaging and skin cancer. However, the underlying immune mechanisms and the immune microenvironment change by ALA-PDT remain largely unknown.MethodsTo illustrate the effects of ALA-PDT on immune microenvironment in photoaged skin, single cell RNA sequencing (scRNA-seq) analysis of photoaged skin on the extensor side of the human forearm before and after ALA-PDT was performed. R-packages of Seurat, clusterProfiler, Monocle, CellChat were used for cell clustering, differentially expressed genes analysis, functional annotation, pseudotime analysis and cell-cell communication analysis. The gene sets related to specific functions were extracted from the MSigDB database, which were used to score the functions of immune cells in different states. We also compared our result with published scRNA-seq data of photoaged skin of the eyelids.ResultsThe increase score of cellular senescence, hypoxia and reactive oxygen species pathway in immune cells and the decrease of immune receptor activity function and proportion of naive T cells were found in skin photoaging. Moreover, the function of T cell ribosomal synthesis was also impaired or down regulated and function of G2M checkpoint was up regulated. However, ALA-PDT showed promising results in reversing these effects, as it improved the above functions of T cells. The ratio of M1/M2 and percentage of Langerhans cells also decreased with photoaging and increased after ALA-PDT. Additionally, ALA-PDT restored the antigen presentation and migration function of dendritic cells and enhanced cell-cell communication among immune cells. These effects were observed to last for 6 months.ConclusionALA-PDT has potential to rejuvenate immune cells, partially reversed immunosenescence and improved the immunosuppressive state, ultimately remodelling the immune microenvironment in photoaged skin. These results provide an important immunological basis for further exploring strategies to reverse skin photoaging, chronological aging and potentially systemic aging

Investigation of the Photothermal Performance of the Composite Scaffold Containing Light-Heat-Sensitive Nanomaterial SiO₂@Fe₃O₄

The objective of this investigation was to fabricate a photothermally responsive composite bone scaffold aimed at facilitating bone tissue regeneration and remedying bone defects via mild thermal stimulation. The photothermal-sensitive nanomaterial SiO2 coated Fe3O4 (SiO2@Fe3O4), synthesized through the hydrolysis–condensation process of tetraethyl orthosilicate (TEOS), displayed a uniform distribution of SiO2 coating, effectively preventing the aggregation of Fe3O4 particles within the scaffold matrix. The composite scaffold containing 5% mass fraction of photothermal-sensitive nanoparticles exhibited evenly dispersed microstructural porosity, a compressive strength of 5.722 MPa, and a water contact angle of 58.3°, satisfying the mechanical property requisites of cancellous bone while demonstrating notable hydrophilic characteristics. Upon exposure to near-infrared light at ambient temperature, the 5% composite scaffold underwent a temperature elevation of 3–6 °C within 40–45 s, attaining a temperature range (40–43 °C) conducive to fostering osteogenic differentiation. Experimental findings validated that the SiO2@Fe3O4/polyvinyl alcohol (PVA)/hydroxyapatite (HA)/polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) bone scaffold showcased outstanding mechanical and photothermal attributes, thereby presenting a pioneering avenue for advancing bone tissue cell proliferation and addressing bone defect rehabilitation

Numerical study on thermal-induced lubricant depletion in laser heat-assisted magnetic recording systems

This paper presents a numerical investigation of heat transfer and lubricant depletion on the hard disk in a heat-assisted magnetic recording (HAMR) system. The heat is induced by a laser pulse shooting down from a slider flying over the disk coated with a thin layer of lubricant. The main mechanisms to cause the lubricant depletion are examined by taking into account of effects associated with evaporation enthalpy, thermal induced surface tension and initial lubricant film thickness. The results show that the evaporation has a dominant effect at a lower evaporation enthalpy, while the thermocapillarity plays a main role at a higher evaporation enthalpy. The lubricant depletion is also found to be affected by the initial thickness of the lubricant film, mainly through the influence on the evaporation rather than on the thermocapillarity. In addition, the effect of lubricant accommodation coefficient on the evaporation has been addressed for the first time in the present study. It is found that a full accommodation assumption adopted in previous numerical studies may overestimate the actual evaporation rate, and a suitable value for the accommodation coefficient between 0 and 1 is required in the prediction in order to yield a good agreement between the simulation results and the experimental data

Numerical study on heat transfer and lubricant depletion in a heat assisted magnetic recording system with multilayer disk structure

Heat transfer and lubricant depletion in a HAMR system with multilayer disk substrate are numerically simulated in this study. Cases under two types of multilayer disk substrates with different materials on the top layer as well as different laser powers are examined. The results show the significant effects of the material property and the laser power. Compared with pure glass disk substrate, larger thermal conductivity of top-layer material in the multilayer disk substrate causes faster heat conduction and thus substantial reductions in the temperature increase and lubricant depletion on the top surface. Hence it is necessary and important to incorporate the real multilayer structure in modeling heat transfer and lubricant depletion in practical HAMR systems