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Exosomes derived from hepatocellular carcinoma (HCC) cells are nanovesicles and are involved in the occurrence and development of HCC, they also serve as important carriers and drug targets of nanodrug delivery systems. The external shape and internal structure of exosomes are important indexes of identification, and isolated intact morphology is crucial to biological function integrity. However, given their susceptibility to various influencing factors, the external shape and internal structure of exosomes derived from HCC cells remain incompletely studied. In this study, exosomes purified from HCC cells were isolated at different centrifugation speeds and examined via multiple electron microscopy (EM) techniques. The results demonstrate that exosomes possess a nearly spherical shape and bilipid membranous vesicle with a concave cavity structure containing electron-dense and coated vesicles, suggesting the possible existence of subpopulations of exosomes with specific functions. The exosomes isolated at ultracentrifugation (UC) speed (≥110,000×g) presented irregular and diverse external morphologies, indicating the effect on the integrity of the exosomes. Transforming growth factor signaling bioactive substances (TGF-β1, S100A8, and S100A9) can be found in exosomes by performing Western blotting, showing that the internal content is associated with metastasis of HCC. These findings show that EMelectron microscopy and UC speed can affect exosome characteristics, including external shape, internal structure, and content of bioactive substances. The electron-dense and coated vesicles that had been discovered in exosomes might become new additional morphological features, which could help to improve the interpretation of experimental results and widen our understanding of exosome morphology.
The narrow bandgap of Ag2S quantum dots was used to decorate TiO2 nanotube arrays (TiO2 NTAs) by the successive ionic layer adsorption and reaction (SILAR) method to enhance its photoelectrochemical performance. The micromorphology of the photoanode films prepared by the SILAR under different parameters (including different cycle times, capillary spot sample, and ultrasound-assisted) was systematically analyzed. The photoanode film Ag2S/TiO2 prepared by the SILAR under the ultrasound-assisted method shows Ag2S evenly distributed in TiO2 NTAs. At the same time, the corresponding photoabsorption range has been extended to the visible area, while the photocurrent density and photoconversion efficiency have been increased to ~1.8 mA/cm2 and 0.6%, respectively.
In this study, precipitate phase transformation behavior, microstructure, and properties of the Cu–1Cr–1Co–0.4Si (wt%) alloy were investigated. Precipitate phase transformation kinetic equations of the alloy under room temperature rolling (RTR) 90% deformation and aging at different temperatures (440–520 °C) were established. The alloy yielded excellent mechanical and electrical properties under RTR 90% deformation and aging at 440 °C for 1 h, and the corresponding hardness, yield strength (YS), ultimate tensile strength (UTS), elongation, and electrical conductivity were 181.6 HV, 573.6 MPa, 653.7 MPa, 7.3%, and 51.6% International Annealed Copper Standard, respectively. The precipitate phase transformation behavior determined the size and volume fraction of the precipitate phase fv, which played a key role in improving the YS. Impurity scattering caused by surplus Si atoms was mainly responsible for decreasing the electrical conductivity. Therefore, these results can provide a reliable theoretical guidance to prepare Cu–Cr–based alloys with high strength and high electrical conductivity.
Connexin 43 (CX43) is a component of gap junctions. The lack of functional CX43 induces oxidative stress, autophagy, and apoptosis in somatic cells. However, the role of CX43 in the early development of porcine embryos is still unknown. Thus, the aim of this study was to investigate the role of CX43, and its underlying molecular mechanisms, on the developmental competence of early porcine embryos. We performed CX43 knockdown by microinjecting dsRNA into parthenogenetically activated porcine parthenotes. The blastocyst development rate and the total number of cells in the blastocysts were significantly reduced by CX43 knockdown. Results from FITC-dextran assays showed that CX43 knockdown significantly increased membrane permeability. ZO-1 protein was obliterated in CX43 knockdown blastocysts. Mitochondrial membrane potential and ATP production were significantly reduced following CX43 knockdown. Reactive oxygen species (ROS) levels were significantly increased in the CX43 knockdown group compared to those in control embryos. Moreover, CX43 knockdown induced autophagy and apoptosis. Our findings indicate that CX43 is essential for the development and preimplantation of porcine embryos and maintains mitochondrial function, cell junction structure, and cell homeostasis by regulating membrane permeability, ROS generation, autophagy, and apoptosis in early embryos.
Recognizing the fact that the finite-time singularity of the Navier–Stokes equations is widely accepted as a key issue in fundamental fluid mechanics, and motivated by the recent model of Moffatt & Kimura (J. Fluid Mech., vol. 861, 2019a, pp. 930–967; J. Fluid Mech., vol. 870, 2019b, R1) on this issue, we have performed direct numerical simulation (DNS) for two colliding slender vortex rings of radius
. The separation between the two tipping points
and the scale of the core cross-section
are chosen as
; the vortex Reynolds number (
) ranges from 1000 to 4000. In contrast to the claim that the core remains compact and circular, there is notable core flattening and stripping, which further increases with
– akin to our previous finding in the standard anti-parallel vortex reconnection. Furthermore, the induced motion of bridges arrests the curvature growth and vortex stretching at the tipping points; consequently, the maximum vorticity grows with
substantially slower than the exponential scaling predicted by the model – implying that, for this configuration, even physical singularity is unlikely. Our simulations not only shed light on the longstanding question of finite-time singularities, but also further delineate the detailed mechanisms of reconnection. In particular, we show for the first time that the separation distance
before reconnection follows 1/2 scaling exactly – a significant DNS result.
C-reactive protein (CRP) and cardiac troponin I (cTnI) biomolecules represent the earliest enzymes that appear in the blood when a cardiac injury occurs. Real-time and selective detection of these biomarkers is essential for the prediction and detection of cardiovascular diseases at an early stage. Here we report on the label-free specific detection of both proteins at picomolar concentrations using fabricated nanowire-based biosensors. We demonstrate a novel functionalization technique based on the attachment of dibenzocyclooctyne (DBCO)-linked troponin-specific aptamers to azide-functionalized silicon (Si) nanowire (NW) surface. Due to the fast and reliable immobilization of cTnI-specific aptamers and CRP-specific antibodies on the Si NWs, the fabricated devices can rapidly detect target biomolecules demonstrating high sensitivity. We confirm the attachment of proteins to the surface of Si NWs by atomic force microscopy (AFM). Moreover, we demonstrate that nanowire structures of different sizes enable the detection of biomarkers in a wide concentration range (from 1 pg/ml to 1 µg/ml), corresponding to CRP and cTnI elevation levels during the early stage of disease formation.
Human milkfat is specially tailored to supply the developing infant with adequate and balanced nutrients. This study aimed to quantify the composition of fatty acids, tocopherols and carotenoids in human milk, with special emphasis on the lactational changes. Colostrum, transitional, and mature milk samples were collected longitudinally from the same 42 healthy, well-nourished Chinese mothers. Fatty acids were quantified by gas chromatography with carotenoids (carotenes and xanthophylls) and tocopherols (α-, γ-tocopherol) determined by high-performance liquid chromatography. Total fatty acids content increased from 15.09 g/L in colostrum to 32.57 g/L in mature milk with the percentages of DHA and ARA decreased. The ratio of n-6/n-3 PUFA and ARA/DHA remained constant during lactation at around 11:1 and 1.3:1, respectively. Both α-tocopherol and γ-tocopherol decreased over lactation with the ratio of α-/γ-tocopherol declined significantly from 7.21:1 to 4.21:1 (P < 0.001). Carotenoids all dropped from colostrum to mature milk as the less polar carotenes dropped by 88.67% while xanthophylls only dropped by 35.92%. Lutein predominated in both transitional and mature milk carotenoids (51.64~52.49%), while colostrum carotenoids were mainly composed of lycopene (32.83%) and β-carotene (30.78%). The concentrations of tocopherols and xanthophylls but not carotenes were positively associated with milk total fatty acids content. These results suggested that colostrum and mature milk contained divergent lipid profiles and selective transfer mechanisms related with polarity might be involved. The present outcomes provide new insights for future breastfeeding studies, which also add in scientific evidences for the design of both initial and follow-on infant formulas.
The association between milk consumption and metabolic syndrome remains inconclusive, and the data from Chinese populations are scarce. We conducted a cross-sectional study to investigate the association between milk consumption and metabolic syndrome and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 5149 participants were included in the final analysis. A logistic regression model was applied to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for the prevalence of metabolic syndrome and its components according to milk consumption. In addition, the results of our study were further meta-analyzed with other published observational studies to quantify the association between the highest versus lowest categories of milk consumption and metabolic syndrome and its components. There was no significant difference in the odds of having metabolic syndrome between milk consumers and non-milk consumers (OR 0.86, 95% CI 0.73, 1.01). However, milk consumers had lower odds of having elevated waist circumference (OR 0.78, 95% CI 0.67, 0.92), elevated triglyceride (OR 0.83, 95% CI 0.70, 0.99), and elevated blood pressure (OR 0.85, 95% CI 0.73, 0.99). When the results were pooled together with other published studies, higher milk consumption was inversely associated with the risk of metabolic syndrome (relative risk 0.80, 95% CI 0.72, 0.88) and its components (except elevated fasting blood glucose); however, these results should be treated with caution as high heterogeneity observed. In summary, the currently available evidence from observational studies suggests that higher milk consumption may be inversely associated with metabolic syndrome.
Freshwater habitats in China are potentially suitable for invasive alien turtle species and, consequently, raising turtles in aquaculture facilities and the trade in turtles this supplies pose risks to habitats and native wetland communities when exotic turtles escape or are released deliberately. Online trade (e-commerce) is making an increasing contribution to turtle sales in China, seemingly driving demand and thus potentially exacerbating the risk of release. We document the scale and spatial pattern of online sales of non-native turtles over 90 days on China's Taobao.com e-commerce site. The majority of sales were in the ecologically sensitive middle and lower Yangtze river basin (82.35% of > 840,000 slider turtles Trachemys scripta elegans, and 68.26% of > 100,000 snapping turtles, Chelydridae spp.). These species are native to the Americas. Concurrently, over 2008–2018, we found 104 mentions of feral turtle issues listed on Baidu News where, among the 53 prefectures mentioned, issues with invasive turtle populations also focused predominantly in the middle and lower Yangtze river basin. Although circumstantial, this association suggests that the substantial online sale of alien turtles could be having detrimental effects in China's Yangtze river basin. It is important to safeguard these wetland habitats, which are of global importance, by improving policies for detecting and regulating invasive alien turtle issues and by warning consumers about the ecological hazard of their purchases.
Studies have indicated that psychological stress impairs human fertility and that various stressors can induce apoptosis of testicular cells. However, the mechanisms by which psychological stress on males reduces semen quality and stressors induce apoptosis in testicular cells are largely unclear. Using a psychological (restraint) stress mouse model, we tested whether male psychological stress triggers apoptosis of spermatozoa and spermatogenic cells through activating tumour necrosis factor (TNF)-α signalling. Wild-type or TNF-α−/− male mice were restrained for 48 h before examination for apoptosis and expression of TNF-α and TNF receptor 1 (TNFR1) in spermatozoa, epididymis, seminiferous tubules and spermatogenic cells. The results showed that male restraint significantly decreased fertilization rate and mitochondrial membrane potential, while increasing levels of malondialdehyde, active caspase-3, TNF-α and TNFR1 in spermatozoa. Male restraint also increased apoptosis and expression of TNF-α and TNFR1 in caudae epididymides, seminiferous tubules and spermatogenic cells. Sperm quality was also significantly impaired when spermatozoa were recovered 35 days after male restraint. The restraint-induced damage to spermatozoa, epididymis and seminiferous tubules was significantly ameliorated in TNF-α−/− mice. Furthermore, incubation with soluble TNF-α significantly reduced sperm motility and fertilizing potential. Taken together, the results demonstrated that male psychological stress induces apoptosis in spermatozoa and spermatogenic cells through activating the TNF-α system and that the stress-induced apoptosis in spermatogenic cells can be translated into impaired quality in future spermatozoa.
Octapyrgites elongatus n. gen. n. sp., a relatively rare, tetraradial olivooid (Cnidaria, Medusozoa), is described from Bed 5 of the Yanjiahe Formation (Cambrian Stage 2) near Yichang, China. Although similar to Olivooides and Quadrapyrgites from the Fortunian Stage in consisting of a partially corrugated (longitudinal) periderm with a quadrate (transverse) apical portion and V-shaped apertural lobes, O. elongatus is substantially larger than other olivooids. The elongate apical region of O. elongatus is similar to four-sided Anaconularia anomala (Barrande, 1867), though with a flat tip that may have been an adaption for a sessile mode of life. As in other olivooids, embryonic development in O. elongatus may have been direct. Last, the paucity of olivooids and the absence of pentaradial cnidarians and carinachitids in Cambrian Stage 2 indicate a marked decline in the disparity of cnidarians near the Fortunian–Cambrian Age 2 boundary, when by contrast bilaterians underwent rapid diversification.
To evaluate the effects of gestational weight gain (GWG) in the first trimester (GWG-F) and the rate of gestational weight gain in the second trimester (RGWG-S) on gestational diabetes mellitus (GDM), exploring the optimal GWG ranges for the avoidance of GDM in Chinese women.
A population-based prospective study was conducted. Gestational weight was measured regularly in every antenatal visit and assessed by the Institute of Medicine (IOM) criteria (2009). GDM was assessed with the 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation. Multivariable logistic regression was performed to assess the effects of GWG-F and RGWG-S on GDM, stratified by pre-pregnancy BMI. In each BMI category, the GWG values corresponding to the lowest prevalence of GDM were defined as the optimal GWG range.
Pregnant women (n 1910) in 2017.
After adjusting for confounders, GWG-F above IOM recommendations increased the risk of GDM (OR; 95 % CI) among underweight (2·500; 1·106, 5·655), normal-weight (1·396; 1·023, 1·906) and overweight/obese women (3·017; 1·118, 8·138) compared with women within IOM recommendations. No significant difference was observed between RGWG-S and GDM (P > 0·05) after adjusting for GWG-F based on the previous model. The optimal GWG-F ranges for the avoidance of GDM were 0·8–1·2, 0·8–1·2 and 0·35–0·70 kg for underweight, normal-weight and overweight/obese women, respectively.
Excessive GWG in the first trimester, rather than the second trimester, is associated with increased risk of GDM regardless of pre-pregnancy BMI. Obstetricians should provide more pre-emptive guidance in achieving adequate GWG-F.
Affective temperaments have been considered antecedents of major depressive disorder (MDD). However, little is known about how the covariation between alterations in brain activity and distinct affective temperaments work collaboratively to contribute to MDD. Here, we focus on the insular cortex, a critical hub for the integration of subjective feelings, emotions, and motivations, to examine the neural correlates of affective temperaments and their relationship to depressive symptom dimensions.
Twenty-nine medication-free patients with MDD and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Patients also received assessments of the Hamilton Depression Rating Scale (HDRS). We used multivariate analyses of partial least squares regression and partial correlation analyses to explore the associations among the insular activity, affective temperaments, and depressive symptom dimensions.
A profile (linear combination) of increased fractional amplitude of low-frequency fluctuations (fALFF) of the anterior insular subregions (left dorsal agranular–dysgranular insula and right ventral agranuar insula) was positively associated with an affective-temperament (depressive, irritable, anxious, and less hyperthymic) profile. The covariation between the insula-fALFF profile and the affective-temperament profile was significantly correlated with the sleep disturbance dimension (especially the middle and late insomnia scores) in the medication-free MDD patients.
The resting-state spontaneous activity of the anterior insula and affective temperaments collaboratively contribute to sleep disturbances in medication-free MDD patients. The approach used in this study provides a practical way to explore the relationship of multivariate measures in investigating the etiology of mental disorders.
The collective hydrodynamics in fish schools and bird flocks, which includes self-organization of multiple dynamic bodies, is complex and lacks sufficient exploration. In this paper, we study the performance of multiple self-propelled foils in tandem formation, whose flapping motions are asynchronous with a phase difference. It is shown that a compact formation, in which all of the foils perform like a complete anguilliform swimmer, can be spontaneously formed by multiple foils via hydrodynamic interactions. Both velocity enhancement and energy saving can be achieved by multiple foils in anguilliform-like swimming. Furthermore, such anguilliform-like swimming behaviour can be observed over a wide range of parameters, including the number of foils, the phase difference, the initial distance, the heaving amplitude and the pitching amplitude. The results obtained here may provide some light on understanding the self-organization behaviour of biological collectives.
Relationship of genetic polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and interleukin-18 (IL-18) with susceptibility to viral hepatitis was already investigated by many association studies. The aim of this study was to more comprehensively analyse associations between genetic polymorphisms in CTLA-4/IL-18 and viral hepatitis by combing the results of all relevant association studies. We searched Pubmed, Embase, Web of Science and CNKI for eligible studies. We used Review Manager to combine the results of eligible studies. Thirty-seven studies were finally included in this meta-analysis. Combined results demonstrated that CTLA-4 rs231775 (recessive comparison: OR 1.31, 95% CI 1.11–1.55), IL-18 rs1946518 (dominant comparison: OR 0.82, 95% CI 0.75–0.90; recessive comparison: OR 1.29, 95% CI 1.11–1.50; allele comparison: OR 0.76, 95% CI 0.68–0.86) and IL-18 rs187238 (dominant comparison: OR 1.25, 95% CI 1.03–1.52; allele comparison: OR 1.20, 95% CI 1.05–1.37) polymorphisms were all significantly associated with viral hepatitis in the general population. Further subgroup analyses revealed that CTLA-4 rs231775, IL-18 rs1946518 and IL-18 rs187238 polymorphisms were significantly associated with susceptibility to hepatitis B virus (HBV), especially among East Asians. Moreover, CTLA-4 rs5742909, IL-18 rs1946518 and IL-18 rs187238 polymorphisms were also significantly associated with susceptibility to hepatitis C virus (HCV), especially among South Asians. So to conclude, this meta-analysis demonstrated that CTLA-4 rs231775, IL-18 rs1946518 and IL-18 rs187238 polymorphisms may confer susceptibility to HBV in East Asians, while CTLA-4 rs5742909, IL-18 rs1946518 and IL-18 rs187238 polymorphisms may confer susceptibility to HCV in South Asians.
To investigate the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of small for gestational age (SGA) and to examine the joint effect of folic acid supplementation and dietary folate intake on the risk of SGA.
Participants were interviewed by trained study interviewers using a standardized and structured questionnaire. Information on birth outcomes and maternal complications was abstracted from medical records and dietary information was collected via a semi-quantitative FFQ before conception and during pregnancy.
A birth cohort data analysis using the 2010–2012 Gansu Provincial Maternity and Child Care Hospital.
Women (n 8758) and their children enrolled in the study.
Folic acid supplementation was associated with a reduced risk of SGA (OR = 0·72, 95 % CI 0·60, 0·86), with the reduced risk seen mainly for SGA at ≥37 weeks of gestational age (OR = 0·70, 95 % CI 0·58, 0·85) and nulliparous SGA (OR = 0·67, 95 % CI 0·54, 0·84). There was no significant association between dietary folate intake and SGA risk.
Our study suggested that folic acid supplementation was associated with a reduced risk of SGA and the risk varied by preterm status and parity.
Viscous anti-parallel vortex reconnection is studied by means of direct numerical simulation for vortex Reynolds numbers
, circulation/viscosity) up to 40 000. To suppress the inherent symmetry breaking due to the Kelvin–Helmholtz (planar jet) instability, as prevalent in prior studies, and to better explore the progression of the mechanism details, the simulation is performed by imposing symmetry and using double-precision arithmetic. We show, for the first time, the evidence of vortex reconnection cascade scenario initially proposed by Melander and Hussain (CTR Report, 1988), who suggested that the remnant threads, following the first reconnection, undergo successive reconnections in a cascade. Secondary reconnection (the details distinctly captured and visualized at a lower
) leads to the successive generation of numerous small-scale structures, including vortex rings, hairpin-like vortex packets and vortex tangles. As
increases, the third and higher generations of reconnection form a turbulent cloud avalanche consisting of a tangle of fine vortices. The energy is rapidly transferred to finer scales during reconnection, and a distinct - 5/3 inertial range is observed for the kinetic energy spectrum, associated with numerous resulting fine-scale bridgelets and thread filaments. In addition, we also discover an inverse cascade at large scales through the accumulation of bridgelets. The separation distance
before the first reconnection is found to scale as
, which is different from the typical 1/2 scaling for classical and quantum vortex filament reconnections. Both peak enstrophy and its production rate grow with
faster than the power law suggested by Hussain and Duraisamy (Phys. Fluids, vol. 23, 2011, 021701). Our simulations not only reveal the detailed mechanisms of high-
reconnection, but also shed light on the physics of turbulence cascade and present the reconnection avalanche as a realistic physical model for turbulence cascade.