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The cellular accumulation of drug delivery systems (DDSs) is a critical parameter to determine the final outcome of cancer chemotherapy. Herein, we designed a red blood cells membrane-based vehicle (RV) and employed it to load both doxorubicin (Dox) and IR 780 (RV/I-D). The photothermal-assisted chemotherapy efficacy of RV/I-D on the treatment of cancer was tested on a prostate cancer model. Excitingly, the results showed that RV/I-D was stable and safe nanoparticles with size at about 100 nm. Moreover, upon the increase of system temperature using photothermal effects of IR780, the drug release of the DDS was accelerated. Above all, the DDS also increased the accumulation of drugs into the Dox-resistant prostate cancer cells (PC-3/Dox) both in vitro and in vivo and showed enhanced anticancer performance.
We investigate the three-dimensional surface pattern and nonlinear dynamics of a condensing liquid layer suspended from a cooled substrate and in contact with a mixture of its vapour and an inert gas below. A vapour boundary layer (VBL) is introduced, to which the changes in gaseous composition and temperature are assumed to be confined. An interfacial transport equation is derived, which incorporates the physical effects of convection and diffusion of vapour within the VBL, coupled with a long-wave evolution equation for the location of the free surface. This work extends the study of Kanatani (J. Fluid Mech., vol. 732, 2013, pp. 128–149) on a sessile evaporating film to the Rayleigh–Taylor unstable condensing/evaporating case with nonlinear analyses which also accounts for the effect of vapour recoil due to mass transfer on interfacial evolution and that of gravity combined with buoyancy on the internal convection of pendent drops in a condensate layer. The coupled nonlinear evolutionary system is referred to as a
-sided model. It can be reduced to the conventional one-sided model when phase change is limited by processes in the liquid. An extended basic state is obtained, whose stability is investigated with pseudo-steady linear theory and time-dependent nonlinear simulations. With the one-sided model, the influences of vapour recoil and Marangoni effects are illustrated with three representative cases. In the one-sided simulations with a random perturbation, the interface is prone to finite-time rupture and the surface patterns feature isolated droplets when vapour recoil is significant, while it becomes more regular and even without rupture as vapour recoil is weakened relative to the Marangoni effect. This suggests that, in the absence of the convection and diffusion of vapour, the destabilizations of vapour recoil and negative gravity could prevail over the stabilizations of thermocapillarity, capillarity, viscous dissipation and mass gain. With an unsaturated initial interface concentration,
-sided model indicates that the liquid layer can be stabilized to a quasi-hexagon pattern and the Rayleigh–Taylor-driven rupture can be suppressed with the effects of vapour convection and diffusion near the interface. However, the initial dynamics is in contrast to the case with a saturated
, where transition from weak evaporation to a condensation-dominated regime is seen in the later stage. The viewpoint of stability competition offers vital evidence for an induced Marangoni stabilization, which is a quintessential characteristic of the
-sided model. Comparisons of the theory and simulations with available experiments are included throughout.
Rare earth elements (REE) in marine minerals have been widely used as proxies for the redox status of depositional and/or diagenetic environments. Phosphate nodules, which are thought to grow within decimetres below the sediment–water interface and to be able to scavenge REE from the ambient pore water, are potential archives of subtle changes in REE compositions. Whether their REE signals represent specific redox conditions or they can be used to track the overlying water chemistry is worth exploring. Through in situ laser ablation – inductively coupled plasma – mass spectrometry (LA-ICP-MS), we investigate the REE compositions of a drill-core-preserved phosphate nodule from the lower Cambrian Niutitang Formation in the Daotuo area, northeastern Guizhou Province, South China. REE distributions of the nodule show concentric layers with systematic decreases in Ce anomalies (Ce/Ce*) from the core to the rim. The lowest Ce/Ce* appears in the outer rim where REE concentrations are relatively high. These results are interpreted to reflect REE exchange with pore water at a very early stage or bathymetric variation during apatite precipitation. The origin of the shale-normalized middle REE (MREE) enrichment in our sample is less constrained. Possible driving factors include preferential MREE substitution for Ca in the apatite lattice, degradation of organic matter and deposition beneath a ferruginous zone. Although speculative, the last possibility is consistent with the chemically stratified model for early Cambrian oceans, in which dynamic fluctuations of the chemocline provided an ideal depositional context for phosphogenesis.
We aimed to describe the clinical features in coronavirus disease 2019 (COVID-19) cases. We studied 134 critically ill COVID-19 cases from 30 December 2019 to 20 February 2020 in an intensive care unit (ICU) at Wuhan Jinyintan Hospital. Demographics, underlying diseases, therapy strategies and test results were collected and analysed from patients on admission, admission to the ICU and 48 h before death. The non-survivors were older (65.46 (s.d. 9.74) vs. 46.45 (s.d. 11.09)) and were more likely to have underlying diseases. The blood group distribution of the COVID-19 cases differed from that of the Han population in Wuhan, with type A being 43.85%; type B, 26.92%; type AB, 10% and type O, 19.23%. Non-survivors tend to develop more severe lymphopaenia, with higher C-reactive protein, interleukin-6, procalcitonin, D-dimer levels and gradually increased with time. The clinical manifestations were non-specific. Compared with survivors, non-survivors more likely to have organ function injury, and to receive mechanical ventilation, either invasively or noninvasively. Multiple organ failure and secondary bacterial infection in the later period is worthy of attention.
Accurate torque control is a critical issue in the compliant human–robot interaction scenario, which is, however, challenging due to the ever-changing human intentions, input delay, and various disturbances. Even worse, the performances of existing control strategies are limited on account of the compromise between precision and stability. To this end, this paper presents a novel high-performance torque control scheme without compromise. In this scheme, a new nonlinear disturbance observer incorporated with equivalent control concept is proposed, where the faster convergence and stronger anti-noise capability can be obtained simultaneously. Meanwhile, a continuous fractional power control law is designed with an iteration method to address the matched/unmatched disturbance rejection and global finite-time convergence. Moreover, the finite-time stability proof and prescribed control performance are guaranteed using constructed Lyapunov function with adding power integrator technique. Both the simulation and experiments demonstrate enhanced control accuracy, faster convergence rate, perfect disturbance rejection capability, and stronger robustness of the proposed control scheme. Furthermore, the evaluated assistance effects present improved gait patterns and reduced muscle efforts during walking and upstair activity.
The aim of the study was to investigate the continuous changing pattern of H4K12 acetylation, and the expression levels of histone acetyltransferases (HATs) and histone deacetyltransferases (HDACs) in mouse oocytes during meiosis and after parthenogenetic activation (PA). The immunofluorescence results showed hyperacetylation of lysine-12 on histone H4 (H4K12) in the germinal vesicle (GV) oocytes that then decreased during germinal vesicle breakdown (GVBD), and disappeared in metaphase II (MII). However, it reappeared in the early 1-cell embryos derived after 4 h of PA. The expression levels of some selected HATs and HDACs also validated the changing pattern of H4K12 acetylation during meiosis and PA. In conclusion, H4K12 is deacetylated in GVBD and MII, and re-hyperacetylated after PA.
Data on average iodine requirements for the Chinese population are limited following implementation of long-term universal salt iodisation. We explored the minimum iodine requirements of young adults in China using a balance experiment and the ‘iodine overflow’ hypothesis proposed by our team. Sixty healthy young adults were enrolled to consume a sequential experimental diet containing low, medium and high levels of iodine (about 20, 40 and 60 μg/d, respectively). Each dose was consumed for 4 d, and daily iodine intake, excretion and retention were assessed. All participants were in negative iodine balance throughout the study. Iodine intake, excretion and retention differed among the three iodine levels (P < 0·01 for all groups). The zero-iodine balance derived from a random effect model indicated a mean iodine intake of 102 μg/d, but poor correlation coefficients between observed and predicted iodine excretion (r 0·538 for μg/d data) and retention (r 0·304 for μg/d data). As iodine intake increased from medium to high, all of the increased iodine was excreted (‘overflow’) through urine and faeces by males, and 89·5 % was excreted by females. Although the high iodine level (63·4 μg/d) might be adequate in males, the corresponding level of 61·6 μg/d in females did not meet optimal requirements. Our findings indicate that a daily iodine intake of approximately half the current recommended nutrient intake (120 μg/d) may satisfy the minimum iodine requirements of young male adults in China, while a similar level is insufficient for females based on the ‘iodine overflow’ hypothesis.
The lane-level map, which contains the lane-level information severely lacking in widely used commercial navigation maps, has become an essential data source for autonomous driving systems. The linking relations between lane-level map and commercial navigation map can facilitate an autonomous driving system mapping information between different applications using different maps. In this paper, an approach is proposed to build the linking relations automatically. The different topology networks are first reconstructed into similar structures. Then, to build the linking relations automatically, the adaptive multi-filter algorithm and forward path exploring algorithm are proposed to detect corresponding junctions and paths, respectively. The approach is validated by two real data sets of more than 150 km of roads, mainly highway. The linking relations for nearly 94% of the total road length have been built successfully.
The Arsenic (+3 oxidation state) methyltransferase (AS3MT) gene has been identified as a top risk gene for schizophrenia in several large-scale genome-wide association studies. A variable number tandem repeat (VNTR) of this gene is the most significant expression quantitative trait locus, but its role in brain activity in vivo is still unknown.
We first performed a functional magnetic resonance imaging (fMRI) scan of 101 healthy subjects during a memory span task, trained all subjects on an adaptive memory span task for 1 month, and finally performed another fMRI scan after the training. After excluding subjects with excessive head movements for one or more scanning sessions, data from 93 subjects were included in the final analyses.
The VNTR was significantly associated with both baseline brain activation and training-induced changes in multiple regions including the prefrontal cortex and the anterior and posterior cingulate cortex. Additionally, it was associated with baseline brain activation in the striatum and the parietal cortex. All these results were corrected based on the family-wise error rate method across the whole brain at the peak level.
This study sheds light on the role of AS3MT gene variants in neural plasticity related to memory span training.
Previous studies have shown conflicting findings regarding the relationship between maternal vitamin D deficiency (VDD) and fetal growth restriction (FGR). We hypothesised that parathyroid hormone (PTH) may be an underlying factor relevant to this potential association. In a prospective birth cohort study, descriptive statistics were evaluated for the demographic characteristics of 3407 pregnancies in the second trimester from three antenatal clinics in Hefei, China. The association of the combined status of vitamin D and PTH with birth weight and the risk of small for gestational age (SGA) was assessed by a multivariate linear and binary logistic regression. We found that declined status of 25-hydroxyvitamin D is associated with lower birth weight (for moderate VDD: adjusted β = −49·4 g, 95 % CI −91·1, −7·8, P < 0·05; for severe VDD: adjusted β = −79·8 g, 95 % CI −127·2, −32·5, P < 0·01), as well as ascended levels of PTH (for elevated PTH: adjusted β = −44·5 g, 95 % CI −82·6, −6·4, P < 0·05). Compared with the non-VDD group with non-elevated PTH, pregnancies with severe VDD and elevated PTH had the lowest neonatal birth weight (adjusted β = −124·7 g, 95 % CI −194·6, −54·8, P < 0·001) and the highest risk of SGA (adjusted risk ratio (RR) = 3·36, 95 % CI 1·41, 8·03, P < 0·01). Notably, the highest risk of less Ca supplementation was founded in severe VDD group with elevated PTH (adjusted RR = 4·67, 95 % CI 2·78, 7·85, P < 0·001). In conclusion, elevated PTH induced by less Ca supplementation would further aggravate the risk of FGR in pregnancies with severe VDD through impaired maternal Ca metabolism homoeostasis.
The head-on collision between two dust-acoustic solitary waves in a non-magnetized, collisionless and strongly coupled dust plasma has been studied. The application scope of the analytical solution of the head-on collision is given in the present paper by using the particle-in-cell simulation method. It is noted that the analytical results are valid if the amplitudes of both of the solitary waves are small enough. The effects of the coupling parameters on both the head-on collision and the waveform are also studied in the present paper.
Natural disasters are increasing in frequency and impact; they cause widespread disruption and adversity throughout the world. The Canterbury earthquakes of 2010–2011 were devastating for the people of Christchurch, New Zealand. It is important to understand the impact of this disaster on the mental health of children and adolescents.
To report psychiatric medication use for children and adolescents following the Canterbury earthquakes.
Dispensing data from community pharmacies for the medication classes antidepressants, antipsychotics, anxiolytics, sedatives/hypnotics and methylphenidate are routinely recorded in a national database. Longitudinal data are available for residents of the Canterbury District Health Board (DHB) and nationally. We compared dispensing data for children and adolescents residing in Canterbury DHB with national dispensing data to assess the impact of the Canterbury earthquakes on psychotropic prescribing for children and adolescents.
After longer-term trends and population adjustments are considered, a subtle adverse effect of the Canterbury earthquakes on dispensing of antidepressants was detected. However, the Canterbury earthquakes were not associated with higher dispensing rates for antipsychotics, anxiolytics, sedatives/hypnotics or methylphenidate.
Mental disorders or psychological distress of a sufficient severity to result in treatment of children and adolescents with psychiatric medication were not substantially affected by the Canterbury earthquakes.
Vision and language are two fundamental capabilities of human intelligence. Humans routinely perform tasks through the interactions between vision and language, supporting the uniquely human capacity to talk about what they see or hallucinate a picture on a natural-language description. The valid question of how language interacts with vision motivates us researchers to expand the horizons of computer vision area. In particular, “vision to language” is probably one of the most popular topics in the past 5 years, with a significant growth in both volume of publications and extensive applications, e.g. captioning, visual question answering, visual dialog, language navigation, etc. Such tasks boost visual perception with more comprehensive understanding and diverse linguistic representations. Going beyond the progresses made in “vision to language,” language can also contribute to vision understanding and offer new possibilities of visual content creation, i.e. “language to vision.” The process performs as a prism through which to create visual content conditioning on the language inputs. This paper reviews the recent advances along these two dimensions: “vision to language” and “language to vision.” More concretely, the former mainly focuses on the development of image/video captioning, as well as typical encoder–decoder structures and benchmarks, while the latter summarizes the technologies of visual content creation. The real-world deployment or services of vision and language are elaborated as well.
The fatigue behavior of a low-cost Zr52.1Ti5Cu17.9Ni14.6Al10Y0.4 (at%) (ZrCuNi-based) bulk-metallic glass (BMG) prepared by industrial-grade material was investigated under three-point bending loading modes. In order to obtain the fatigue stress-life (S-N) data, stress-controlled experiments were conducted using a computer-controlled material test system electrohydraulic testing machine at 60 Hz with a 0.1 R ratio in the air at room temperature. The fatigue limit (~174 MPa) in stress amplitude and fatigue ratio (~0.14) of this BMG is comparative to the similar BMG (Vit-105) prepared by high pure raw materials. The crack initiated from inclusions near the rectangular corners at the outer surface of the rectangular beam due to stress concentration. The striations and vein-like patterns were observed in the crack propagation region and fast fracture region, respectively.
The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.
We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.
The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.
The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.
Episodic memory starts to decline very early in the development of Alzheimer’s disease (AD). Subtle impairments in memory binding may be detected in mild cognitive impairment (MCI). This study aims to examine the psychometric properties of the Chinese version of the memory binding test (MBT).
One hundred and sixty-four subjects (26 individuals with AD, 67 individuals with amnestic MCI (aMCI), 30 individuals with subjective cognitive impairment (SCI), and 41 cognitively normal elderly individuals (NC)) participated in the study. Twenty-two subjects repeated the assessment of the MBT within 6 weeks (± 2 weeks). Pearson correlation was used to calculate the convergent validity. The test––retest reliability was determined by the calculation of the intraclass correlation coefficient (ICC). Discriminative validity was calculated to evaluate the receiver–operating characteristic curves. The optimal index was chosen by comparing the area under the curve for specificity and sensitivity ≥ 0.80. The optimal cutoff score of the index was chosen to maximize the sum of sensitivity and specificity.
The absolute value of the convergent validity of the direct indexes of MBT ranged from 0.443 to 0.684. The ICC for each of direct indexes was 0.887–0.958. Total delayed paired recall (TDPR) was the optimal index for discriminating aMCI from NC. The cutoff score for TDPR was ≤25 to distinguish aMCI from NC (sensitivity = 0.896, specificity = 0.707).
The Chinese version of MBT is a valid and reliable instrument to detect MCI.