Rapid, simple, and cost-effective diagnostics are needed to improve healthcare at the point of care (POC). However, the most widely used POC diagnostic, the lateral flow immunoassay (LFA), is ...∼1000-times less sensitive and has a smaller analytical range than laboratory tests, requiring a confirmatory test to establish truly negative results. Here, a rational and systematic strategy is used to design the LFA contrast label (i.e., gold nanoparticles) to improve the analytical sensitivity, analytical detection range, and antigen quantification of LFAs. Specifically, we discovered that the size (30, 60, or 100 nm) of the gold nanoparticles is a main contributor to the LFA analytical performance through both the degree of receptor interaction and the ultimate visual or thermal contrast signals. Using the optimal LFA design, we demonstrated the ability to improve the analytical sensitivity by 256-fold and expand the analytical detection range from 3 log10 to 6 log10 for diagnosing patients with inflammatory conditions by measuring C-reactive protein. This work demonstrates that, with appropriate design of the contrast label, a simple and commonly used diagnostic technology can compete with more expensive state-of-the-art laboratory tests.
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IJS, KILJ, NUK, PNG, UL, UM
Aims/hypothesis
Insulin resistance is a major pathophysiological defect in type 2 diabetes and obesity. Numerous experimental and clinical studies have provided evidence that sustained ...lipotoxicity-induced mitophagy deficiency can exacerbate insulin resistance, leading to a vicious cycle between mitophagy dysfunction and insulin resistance, and thereby the onset of type 2 diabetes. Emerging evidence suggests that exosomes (Exos) from M2 macrophages play an essential role in modulating metabolic homeostasis. However, how macrophages are affected by lipotoxicity and the role of lipotoxicity in promoting macrophage activation to the M1 state have not been determined. The objective of this study was to determine whether M1 macrophage-derived Exos polarised by lipopolysaccharide (LPS) + palmitic acid (PA)-induced lipotoxicity contribute to metabolic homeostasis and impact the development of insulin resistance in type 2 diabetes.
Methods
Lipotoxicity-polarised macrophage-derived M1 Exos were isolated from bone marrow (C57BL/6J mouse)-derived macrophages treated with LPS+PA. Exos were characterised by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Flow cytometry, H&E staining, quantitative real-time PCR, immunofluorescence, glucose uptake and output assays, confocal microscopy imaging, western blotting, GTTs and ITTs were conducted to investigate tissue inflammation, mitochondrial function and insulin resistance in vitro and in vivo. The roles of miR-27-3p and its target gene
Miro1
(also known as
Rhot1
, encoding mitochondrial rho GTPase 1) and relevant pathways were predicted and assessed in vitro and in vivo using specific miRNA mimic, miRNA inhibitor, miRNA antagomir and siRNA.
Results
miR-27-3p was highly expressed in M1 Exos and functioned as a
Miro1
-inactivating miRNA through the miR-27-3p–
Miro1
axis, leading to mitochondria fission rather than fusion as well as mitophagy impairment, resulting in NOD-like receptor 3 inflammatory activation and development of insulin resistance both in vivo and in vitro. Inactivation of miR-27-3p induced by M1 Exos prevented type 2 diabetes development in high-fat-diet-fed mice.
Conclusions/interpretation
These findings suggest that the miR-27-3p–
Miro1
axis, as a novel regulatory mechanism for mitophagy, could be considered as a new therapeutic target for lipotoxicity-related type 2 diabetes disease development.
Graphical Abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
An 8‐week feeding trial was conducted to evaluate the effects of fish meal (FM) replacement by rice protein concentrate (RPC) with supplementation of microcapsule lysine (ML) or crystalline lysine ...(CL) on growth performance, muscle development and flesh quality of blunt snout bream. Four isonitrogenous and isoenergetic diets were formulated, including FM diet (containing 50 g/kg FM), RPC diet (FM replaced by RPC), MRPC diet (FM replaced by RPC with ML supplementation) and CRPC diet (FM replaced by RPC with CL supplementation). Fish fed FM diet had significantly higher weight gain, feed efficiency, protein efficiency ratio and nitrogen and energy utilization than that of RPC group, but showed no statistical difference with other treatments. In addition, fish fed RPC diet showed higher muscle fibre frequency in the 20‐ to 50‐μm class but lower >50‐μm class and higher cooking loss than that of the other groups. Furthermore, no significant difference was found in whole‐body proximate compositions, frequency distribution of <20‐μm‐diameter fibres, texture, muscle content, collagen, pH 24 hr post‐mortem and sensory quality. The results showed that RPC supplemented with ML or CL could replace fishmeal without any adverse effects on growth performance and flesh quality for blunt snout bream.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
We present the analysis of the brightest flare that was recorded in the Insight-HMXT data set in a broad energy range (2–200 keV) from the microquasar GRS 1915+105 during an unusual ...low-luminosity state. This flare was detected by Insight-HXMT among a series of flares during 2019 June 2 UTC 16:37:06–20:11:36 with a 2–200 keV luminosity of 3.4–7.27 × 10
38
erg s
−1
. Basing on the broadband spectral analysis, we find that the flare spectrum shows different behaviors during bright and faint epochs. The spectrum of the flare can be fitted with a model dominated by a power-law component. Additional components show up in the bright epoch with a hard tail and in the faint epoch with an absorption line of ∼6.78 keV. The reflection component of the latter is consistent with an inner disk radius ∼five times larger than that of the former. These results on the giant flare during the “unusual” low-luminosity state of GRS 1915+105 may suggest that the source experiences a possible fast transition from a jet-dominated state to a wind-dominated state. We speculate that the evolving accretion disk and the large-scale magnetic field may play important roles in this peculiar huge flare.
Composting is an acceptable and economically feasible process for recycling agricultural biomass waste. The addition of external additives to adjust the process of composting has been attracted lots ...of research attention. To investigate the effects of external additives on nutrients transformation process of composting, a laboratory reactors scale co-composting based on swine manure and corn straw (CK) with the additives of phosphate (MP), calcium bentonite (CB) and biochar (BC) were performed for 30 days. The results showed the addition of phosphate and biochar could contribute to accelerating temperature rise and shorten the thermophilic phase. The germination index (GI) of MP and BC achieved 180% and 150%, respectively. The excitation-emission matrix (EEM) demonstrated the intensities of the peak C (humic acids) of the MP treatment was 829.5, and the PV,n/PIII,n value (9.59) of MP treatment was particularly higher compared to other three treatments according to the fluorescence regional integration (FRI) analysis. The Fourier Transform Infrared spectroscopy (FTIR) indicated the rate of decomposition of aliphatic C substances was higher than that of aromatic C substances. According to the X-ray diffraction (XRD) spectra results, characteristic peaks at both 16° and 22° were decreased, indicating cellulose and amorphous components were degraded. It further proved the formation of struvite component in MP treatment. Therefore, based on the maturity indicators, EEM and XRD results, phosphate is an efficient additive and recommended for swine manure and corn straw co-composting.
Display omitted
•Phosphate, Ca-bentonite and biochar promoted composting process.•The PV,n/PIII,n value indicated MP treatment promoted the maturity of composting.•Struvite XRD spectra confirmed MP treatment had a role in inhibiting nitrogen loss.•The decomposition rate of aliphatic C was higher than aromatic C.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper is concerned with the sliding mode control (SMC) of a continuous-time switched stochastic system. A sufficient condition for the existence of reduced-order sliding mode dynamics is derived ...and an explicit parametrization of the desired sliding surface is also given. Then, a sliding mode controller is then synthesized for reaching motion. Moreover, the observer-based SMC problem is also investigated. Some sufficient conditions are established for the existence and the solvability of the desired observer and the observer-based sliding mode controller is synthesized. Finally, numerical examples are provided to illustrate the effectiveness of the proposed theory.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Individuals with mild cognitive impairment (MCI) are at high risk for developing dementia. Physical exercise is a promising intervention for cognitive decline. Systematic reviews regarding the ...effects of physical exercise on cognitive and psychological outcomes among MCI patients are limited, and a systematic review exploring the effects of exercise modalities on the results has not been conducted. This study evaluated the effects of physical exercise on cognitive and psychological outcomes for MCI patients and attempted to identify which specific modality of exercise is more effective.
Systematic review and meta-analysis.
A systematic search of Medline, CINAHL, EMBASE, PsycINFO, SPORTDiscus, and the China National Knowledge Infrastructure was performed.
Two reviewers independently assessed the study quality using the Effective Public Health Practice Project Quality Assessment Tool. Meta-analysis was conducted when data were available, with further subgroup analyses for exercise types. A series of sensitivity analyses were conducted to explore the influence of study quality and control types on the primary outcome. A narrative analysis was performed when statistical synthesis was inappropriate.
Eleven studies met the inclusion criteria. The exercise interventions can be classified into three types: (a) aerobic exercise, (b) resistance exercise, and (c) multi-modal exercise. Results showed that physical exercise had beneficial effects for global cognition standard mean difference (SMD) = 0.30, 95% confidence interval (CI): 0.10–0.49, p = 0.002. Further subgroup analysis demonstrated that aerobic exercise programmes are consistently associated with medium effect size (SMD: 0.54–0.58). However, the effects of physical exercise on domain-specific cognitive function and psychological outcomes in MCI patients remain inconclusive. Results of sensitivity analysis indicated that types of control exert influence on the outcomes.
Physical exercise, aerobic exercise in particular, benefits global cognition in MCI patients. The evidence of physical exercise on domain-specific cognitive function and psychological outcomes remains unclear, more trials with rigorous study design are necessary to provide the evidence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation ...corresponding to a mutational "hotspot" in the human
gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (
= 2) or 8 weeks after systemic delivery (
= 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD.
The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this ...study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.
Abstract
We report the timing and spectral analyses of the type-II X-ray bursts from the rapid burster (MXB 1730–335) observed by the Hard X-ray Modulation Telescope (Insight-HXMT) and Swift/X-Ray ...Telescope (XRT). By stacking the long-duration bursts, we find for the first time that the hard X-rays are lagging behind the soft X-rays by 3 s. However, such a lag is not visible for the short-duration bursts, probably because of the poor statistics. For all bursts the energy spectrum is found to be nonthermal, thanks to the broadband coverage of Insight-HXMT. These findings provide new insights into the type-II bursts and require a temporally visible corona for possible interpretation.
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