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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.
Iridium (Ir) has an extremely high melting point (2443 °C), high chemical stability and is one of the most promising high-temperature materials. However, Ir is more difficult to process compared with other face-centered cubic metals, such as Ni and Al, which limits its applications. To solve this problem, we study the effect of 32 alloying elements (X) on stacking fault energy of dilute Ir-based alloys generated by shear deformation using the first-principles calculations. The investigation reveals that there are many alloying elements studied herein decrease the stacking fault energy of face-centered cubic (fcc) Ir, and the most effective element in reducing stacking fault energy of fcc Ir is Zn. The microscopic mechanism is caused by electron redistribution in the local stacking fault area. These results are expected to provide valuable guidance for the further design and application of Ir-based alloys.
Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by anxious avoidance.
The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252).
Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes.
The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat avoidance, thus promoting early adaptation to an adverse environment.
In the current research, a 60-day experiment was conducted with the purpose of exploring the impacts of methionine on growth performance, muscle nutritive deposition, muscle fibre growth and type I collagen synthesis as well as related signaling pathway. Six diets (iso-nitrogenous) differing in methionine concentrations (2.54, 4.85, 7.43, 10.12, 12.40 and 15.11 g kg-1 diets) were fed to 540 grass carp (178.47 ± 0.36 g). Results showed (P < 0.05) that, compared with methionine deficiency, optimal level of dietary methionine (1) increased feed intake (FI), feed efficiency (FE), specific growth rate (SGR) and percentage weight gain (PWG); (2) increased fish muscle protein, lipid and free amino acid contents, and improved fish muscle fatty acid profile as well as increased protein content in part associated with TORC1/S6K1 signaling pathway; (3) increased the frequency distribution of muscle fibre with >50 µm of diameter; (4) increased type I collagen synthesis partly related to TGF-β1/Smads and CK2/TORC1 signaling pathways. In conclusion, dietary methionine improved muscle growth, which might be due to the regulation of muscle nutritive deposition, and muscle fibre growth and type I collagen synthesis related signal molecules. Finally, according to PWG and muscle collagen content, the methionine requirements for on-growing grass carp (178-626 g) were estimated to be 9.56 g kg-1 diet (33.26 g kg-1 protein of diet) and 9.28 g kg-1 diet (32.29 g kg-1 of dietary protein), respectively.
HfO2–Sm3TaO7 ceramics are prepared through a solid-state reaction method. The X-ray diffraction and structural refinement show that the phase structures of HfO2–Sm3TaO7 ceramics are an ordered orthorhombic phase and the space groups are belonging to Ccmm. The degree of the structural disorder increases with increasing HfO2 content. The solid solution mechanism reveals that Hf4+ exists in the form of interstitial ions that cause crystal expansion when the doping content is less than 4 mol%. When the doping concentration of HfO2 ≥ 4 mol%, the Hf4+ ions can substitute an equal number of Sm3+ and Ta5+ ions. The phase transition of Sm3TaO7 ceramics is removed with increasing HfO2 content, and the 8 mol% HfO2–Sm3TaO7 ceramics have a high thermal expansion coefficient of 10.2 × 10−6 K−1 at 1200 °C. The 2 mol% HfO2–Sm3TaO7 ceramics have the lowest thermal conductivity (1.03 W/m K at 900 °C), which is lower than previous research of the 7–8 YSZ. The outstanding thermophysical properties of HfO2–Sm3TaO7 ceramics indicate that they are potential thermal-barrier coating materials.
In this research communication, a cell model with elevated β-CASEIN synthesis was established by stimulating bovine mammary epithelial cells with 0.6 mM methionine, and the genome-wide gene expression profiles of methionine-stimulated cells and untreated cells were investigated by RNA sequencing. A total of 458 differentially expressed genes (DEGs; 219 upregulated and 239 downregulated) were identified between the two groups. Gene Ontology (GO) analysis showed that the two highest-ranked GO terms in ‘molecular function’ category were ‘binding’ and ‘catalytic activity’, suggesting that milk protein synthesis in methionine-stimulated cells requires induction of gene expression to increase metabolic activity. Kyoto Encyclopedia of Genes and Genomes analysis revealed that within the ‘environmental information processing’ category, the subcategory that is most highly enriched for DEGs was ‘signal transduction’. cGMP-PKG, Rap1, calcium, cAMP, PI3K-AKT, MAPK, and JAK-STAT are the pathways with the highest number of DEGs, suggesting that these signaling pathways have potential roles in mediating methionine-induced milk protein synthesis in bovine mammary epithelial cells. This study provides valuable insights into the physiological and metabolic adaptations in cells stimulated with methionine. Understanding the regulation of this transition is essential for effective intervention in the lactation process.
To explore the association between dietary Na intake and non-alcoholic fatty liver disease (NAFLD) in a nationally representative sample of the US population.
In this cross-sectional study, the associations between Na intake and NAFLD, defined by the hepatic steatosis index (HSI) and the fatty liver index (FLI), were assessed through multivariable logistic regression models.
Communities in the USA from 2007 to 2014.
Men and women aged 20 years and older.
A total of 11 022 participants were included in the HSI-defined NAFLD analysis, and a subsample of 5320 participants was included in the FLI-defined NAFLD analysis. Compared with the lowest quartile of Na intake, the highest quartile had a multivariate-adjusted OR and 95 % CI of 1·46 (1·29, 1·65) for NAFLD as defined by HSI, and 1·41 (1·18, 1·69) for NAFLD as defined by FLI. This association was, to some degree, attenuated but remained significant after adjusting for several related metabolic parameters, including BMI, hypertension, hypercholesterolaemia, and diabetes.
Findings from the current study indicate that dietary Na intake is positively associated with NAFLD in US adults.
Since the first report of the 2019 novel coronavirus disease (COVID-19) in December 2019 in Wuhan, China, the outbreak of the disease has been continuously evolving. Until March 17, 2020, 185, 178 cases had been confirmed, including 81,134 cases in China and 104,044 cases outside of China. In this comment, we report the unexpected beneficial effect of a deployable rapid-assembly shelter hospital on the prevention and treatment of COVID-19. We describe the shelter hospital maintenance, treatment mode and primary treatment methods, which will provide a valuable experience in dealing with public health emergencies, such as COVID-19, for other countries and areas.
Varicella is an acute respiratory infectious diseases, with high transmissibility and quick dissemination. In this study, an SEIR (susceptible-exposed-infected-recovered) dynamic model was established to explore the optimal prevention and control measures according to the epidemiological characteristics about varicella outbreak in a school in a central city of China. Berkeley Madonna 8.3.18 and Microsoft Office Excel 2010 software were employed for the model simulation and data management, respectively. The result showed that the simulated result of SEIR model agreed well with the reported data when β (infected rate) equal to 0.067. Models showed that the cumulative number of cases was only 13 when isolation adopted when the infected individuals were identified (assuming isolation rate was up to 100%); the cumulative number of cases was only two and the TAR (total attack rate) was 0.56% when the vaccination coefficient reached 50%. The cumulative number of cases did not change significantly with the change of efficiency of ventilation and disinfection, but the peak time was delayed; when δ (vaccination coefficient) = 0.1, m (ventilation efficiency) = 0.7 or δ = 0.2, m = 0.5 or δ = 0.3, m = 0.1 or δ = 0.4 and above, the cumulative number of cases would reduce to one case and TAR would reduce to 0.28% with combined interventions. Varicella outbreak in school could be controlled through strict isolation or vaccination singly; combined interventions have been adopted when the vaccination coefficient was low.
SmTaO4 ceramics have excellent high-temperature phase stabilities and mechanical properties and show great potential for use as next-generation thermal barrier coating (TBC) materials. CeO2–SmTaO4 ceramics are prepared via high-temperature solid–state reaction. It retains a single monoclinic phase structure. Ce4+ was reduced to Ce3+ by high-temperature deoxidation, and the Ce3+ ions substitute for an equal number of Sm3+ ions. The CeO2–SmTaO4 ceramics had lower thermal conductivities [1.09–2.75 W/(m K)] than yttria-stabilized zirconia (YSZ) [2.1–2.7 W/(m K)] at 100–800 °C, which decreased dramatically with increasing temperature. SmTaO4 doped with 2% CeO2 had lower thermal conductivity [1.09 W/(m K), 800 °C] than SmTaO4 [1.42 W/(m K), 800 °C] and 2% ZrO2-doped SmTaO4 ceramics [1.22 W/(m K), 800 °C]. The low thermal conductivity is attributed to Ce3+ substitution for an equal number of Sm3+ ions, and because Ce3+ ions are the strongest phonon scattering centers, they can decrease the phonon mean free path effectively. The thermal expansion coefficient of 8% CeO2–SmTaO4 ceramics is approximately 10.3 × 10−6 K−1 at 1200 °C, which is slightly higher than that of both YSZ (10.0 × 10−6 K−1) and SmTaO4 (9.58 × 10−6 K−1). The outstanding thermophysical properties indicate that CeO2–SmTaO4 ceramics are potential TBC materials.
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.
This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment.
This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization.
A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects.
After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.
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.
The experiment was conducted to investigate the effects of dietary threonine (Thr) on growth performance and muscle growth, protein synthesis and antioxidant-related signalling pathways of hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. A total of 1200 fish (14·19 (se 0·13) g) were randomly distributed into six groups with four replicates each, fed six diets with graded level of Thr (9·5, 11·5, 13·5, 15·4, 17·4 and 19·3 g/kg diets) for 56 d. Results showed (P < 0·05) that dietary Thr (1) increased percentage weight gain, specific growth rate, feed efficiency and protein efficiency ratio; (2) up-regulated growth hormone (GH), insulin-like growth factor 1 (IGF-1), proliferating cell nuclear antigen, myogenic regulation factors (MyoD, Myf5, MyoG and Mrf4) and myosin heavy chain (MyHC) mRNA levels; (3) increased muscle protein content via regulating the protein kinase B/target of rapamycin signalling pathway and (4) decreased malondialdehyde and protein carbonyl contents, increased catalase, glutathione-S-transferase, glutathione reductase and GSH activities, up-regulated mRNA levels of antioxidant enzymes related to NFE2-related factor 2 and γ-glutamylcysteine ligase catalytic subunit. These results suggest that Thr has a potential role to improve muscle growth and protein synthesis, which might be due to the regulation of GH-IGF system, muscle growth-related gene, antioxidative capacity and protein synthesis-related signalling pathways. Based on the quadratic regression analysis of specific growth rate, the Thr requirement of hybrid catfish (14·19–25·77 g) was estimated to be 13·77 g/kg of the diet (33·40 g/kg of dietary protein).
The present study investigated the effects of condensed tannins (CT) on intestinal immune function in on-growing grass carp (Ctenopharyngodon idella). A total of 540 healthy grass carp were fed six diets containing different levels of CT (0, 10·00, 20·00, 30·00, 40·00 and 50·00 g/kg diet) for 70 d and then challenged with Aeromonas hydrophila for 14 d. The results showed that, compared with the control group, dietary CT (1) induced intestinal histopathological lesions and aggravated enteritis; (2) decreased lysozyme and acid phosphatase activities, complement 3 (C3), C4 and IgM contents and down-regulated the Hepcidin, liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, Mucin2 and β-defensin-1 mRNA levels in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) (P < 0·05); (3) down-regulated the mRNA levels of anti-inflammatory cytokines transforming growth factor (TGF)-β1, TGF-β2 (not in MI and DI), IL-4/13A (not IL-4/13B), IL-10 and IL-11 partly correlated with target of rapamycin (TOR) signalling; and (4) up-regulated the mRNA levels of pro-inflammatory cytokines interferon-γ2, IL-1β, IL-6, IL-8 (not in PI), IL-12p35, IL-12p40, IL-15 and IL-17D partly related to NF-κB signalling in the intestine of on-growing grass carp. Overall, the results indicated that CT could impair the intestinal immune function, and its potential regulation mechanisms were partly associated with the TOR and NF-κB signalling pathways. Finally, based on the percentage weight gain and enteritis morbidity, the maximum allowable levels of CT for on-growing grass carp (232·22–890·11 g) were estimated to be 18·6 and 17·4 g/kg diet, respectively.
Autonomous ships are gaining in importance and are expected to shape the future of the global shipping industry. This evolutionary shift raises serious issues about compliance with the International Regulations for Preventing Collisions at Sea 1972 (COLREGs). This paper reviews the literature on autonomous ships from the perspective of the obligations of good seamanship imposed by COLREGs. The authors conclude that to facilitate the introduction of autonomous ships, the application barriers presented by COLREGs need to be analysed. With this goal, this paper presents a perspective from navigational practice. Four nautical scientists and two deck officers were invited to give their opinions. The analysis indicates that COLREGs require further elaboration and amendments to eliminate uncertainty of interpretation. In particular, the paper highlights the need to amend the ‘look-out’ rule (COLREGs Rule 5) to permit look-out by ‘computer vision’ alone while, at the same time, preserving the distinction between vessels navigating in restricted visibility and in sight of one another.
This study seeks to identify healthcare utilization patterns following symptomatic respiratory tract infections (RTIs) and the variables that may influence these patterns.
RTIs are responsible for the bulk of the primary healthcare burden worldwide. Yet, the use of health services for RTIs displays great discrepancies between populations. This research examines the influence of social demographics, economic factors, and accessibility on healthcare utilization following RTIs.
Structured interviews were administered by trained physicians at the households of informants selected by cluster randomization. Descriptive and multivariate binary logistic regression analysis was performed to assess healthcare utilization and associated independent variables.
A total of 60 678 informants completed the interviews. Of the 2.9% informants exhibiting upper RTIs, 69.5–73.9% sought clinical care. Healthcare utilization rates for common cold, influenza, nine acute upper RTIs, and overall RTIs demonstrate statistically significant associations with the variables of age, type of residence, employment, medical insurance, annual food expenditure, distance to medical facilities, and others. The odds ratios for healthcare utilization rates varied substantially, ranging from 0.026 to 9.364. More than 69% of informants with RTIs sought clinical interventions. These findings signify a marked issue with the large amount of healthcare for self-limited RTIs.
Minor and major zygotic genome activation (ZGA) are crucial for preimplantation development. During this process, histone variants and methylation influence chromatin accessibility and consequently regulated the expression of zygotic genes. However, the detailed exchanges of these modifications during ZGA remain to be determined. In the present study, the epigenetic modifications of histone 3 on lysine 9 (H3K9), 27 (H3K27) and 36 (H3K36), as well as four histone variants were determined during minor and major ZGA and in post-ZGA stages of mouse embryos. Firstly, microH2A1, H3K27me3 and H3K36me3 were asymmetrically stained in the female pronucleus during minor ZGA but lost staining in major ZGA. Secondly, H3K9me2 and H3K9me3 were strongly stained in the female pronucleus, but weakly stained in the male pronucleus and disappeared after ZGA. Thirdly, H2A.Z and H3.3 were symmetrically stained in male and female pronuclei during minor ZGA. Moreover, H3K27me2 was not statistically changed during mouse early development, while H3K36me2 was only detected in 2- and 4-cell embryos. In conclusion, our data revealed dynamics of histone methylation and variants during mice ZGA and provided details of their exchange in mice embryogenesis. Moreover, we further inferred that macroH2A1, H2A.Z, H3K9me2/3 and H3K27me2/3 may play crucial roles during mouse ZGA.