Four metallic metamaterials with tailorable mechanical properties are designed using bi-material star-shaped re-entrant planar lattice structures, which do not involve pins, adhesive, welding or ...pressure-fit joints and can be fabricated through laser-based additive manufacturing. Three length parameters, one angle parameter and three material combinations are used as adjustable design parameters to explore structure-property relations. For each of the four designed metamaterials, the effects of the design parameters on the Poisson’s ratio (PR), coefficient of thermal expansion (CTE), Young’s modulus and relative density are systematically investigated using unit cell-based finite element simulations that incorporate periodic boundary conditions. It is found that the bi-material lattice structures can be tailored to obtain 3-D printable metallic metamaterials with positive, near-zero or negative PR and CTE together with an uncompromised Young’s modulus. In particular, it is shown that metamaterial # 1 can exhibit both a negative PR and a non-positive CTE simultaneously. These metallic metamaterials can find applications in structures or devices such as antennas and precision instruments to reduce thermomechanical stresses and extend service lives.
Aberrant DNA hypermethylation contributes to myelomagenesis by silencing tumor-suppressor genes. Recently, a few reports have suggested that a novel class of small non-coding RNAs, called ...Piwi-interacting RNAs (piRNAs), may be involved in the epigenetic regulation of cancer. In this study, for the first time we provided evidence that the expression of piRNA-823 was upregulated in multiple myeloma (MM) patients and cell lines, and positively correlated with clinical stage. Silencing piRNA-823 in MM cells induced deregulation of cell cycle regulators and apoptosis-related proteins expression, accompanied by inhibition of tumorigenicity in vitro and in vivo. Moreover, piRNA-823 was directly relevant to de novo DNA methyltransferases, DNMT3A and 3B, in primary CD138(+) MM cells. The inhibited expression of piRNA-823 in MM cells resulted in marked reduction of DNMT3A and 3B at both mRNA and protein levels, which in turn led to decrease in global DNA methylation and reexpression of methylation-silenced tumor suppressor, p16(INK4A). In addition, piRNA-823 abrogation in MM cells induced reduction of vascular endothelial growth factor secretion, with consequent decreased proangiogenic activity. Altogether, these data support an oncogenic role of piRNA-823 in the biology of MM, providing a rational for the development of piRNA-targeted therapeutic strategies in MM.
Commensal bacteria shape the colonic regulatory T (Treg) cell population required for intestinal tolerance. However, little is known about this process. Here, we use the transfer of naive ...commensal-reactive transgenic T cells expressing colonic Treg T cell receptors (TCRs) to study peripheral Treg (pTreg) cell development in normal hosts. We found that T cells were activated primarily in the distal mesenteric lymph node. Treg cell induction was rapid, generating >40% Foxp3+ cells 1 week after transfer. Contrary to prior reports, Foxp3+ cells underwent the most cell divisions, demonstrating that pTreg cell generation can be the dominant outcome from naive T cell activation. Moreover, Notch2-dependent, but not Batf3-dependent, dendritic cells were involved in Treg cell selection. Finally, neither deletion of the conserved nucleotide sequence 1 (CNS1) region in Foxp3 nor blockade of TGF-β (transforming growth factor-β)-receptor signaling completely abrogated Foxp3 induction. Thus, these data show that pTreg cell selection to commensal bacteria is rapid, is robust, and may be specified by TGF-β-independent signals.
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•Rapid Treg cell selection to commensals occurs in the distal mesenteric lymph node•TGF-β receptor signaling is not a “master” specifier of Treg versus effector selection•CNS1 deficiency in Foxp3 delays, but does not abrogate, Treg cell selection•Notch2-dependent dendritic cells are involved in Treg cell selection
The manner in which T cells interact with gut commensal bacteria and become regulatory T cells important for tolerance to these microbes remains incompletely understood. Nutsch et al. use naive transgenic cells specific for commensal antigens to study the kinetics, efficiency, location, and molecular and cellular requirements of peripheral regulatory T cell conversion in the gut.
•We studied the water contamination response to various landscape characteristics.•The practical PLSR approach is applicable for analyzing co-dependent data.•Land use and physiography have major ...impact on the water contamination.
Landscape characteristics are widely accepted as strongly influencing stream water quality in heterogeneous watersheds. Understanding the relationships between landscape and specific water contaminant can greatly improve the predictability of potential contamination and the assessment of contaminant export. In this work, we examined the combined effects of watershed complexity, in terms of land use and physiography, on specific water contaminant across watersheds close to the Danjiangkou Reservoir. The land use composition, land use pattern, morphometric variables and soil properties were calculated at the watershed scale and considered potential factors of influence. Due to high co-dependence of these watershed characteristics, partial least squares regression was used to elucidate the linkages between some specific water contaminants and the 16 selected watershed characteristic variables. Water contaminant maps revealed spatial and seasonal heterogeneity. The dissolved oxygen values in the dry season were higher than those in the wet season, whereas the other contaminant concentrations displayed the opposite trend. The studied watersheds which are influenced strongly by urbanization, showed higher levels of ammonia nitrogen, total phosphorus, potassium permanganate index and petroleum, and lower levels of dissolved oxygen. The urban land use, largest patch index and the hypsometric integral were the dominant factors affecting specific water contaminant.
Objectives:
Nonalcoholic fatty liver disease (NAFLD) is increasingly an indication for liver transplantation in adults. While severe obesity (SO, BMI ≥40 kg m−2) in adults is long standing, it is ...recent in duration in adolescents. With adolescent obesity on the rise, NAFLD is becoming the most frequent liver disease in adolescents. The hypothesis that SO adolescents and adults have different severity of NAFLD because of longer duration of obesity in SO adults was tested.
Design and Methods:
Preoperative clinical data, NAFLD activity and NASH (Nonalcoholic steatohepatitis) scores from intraoperative liver biopsies were extracted from a prospective database of consecutively operated SO adolescents and adults (n = 24 each). Fasting preoperative serum inflammatory mediators were evaluated by ELISA.
Results:
Other than age, baseline BMI, ethnicity and gender distribution, the incidence and extent of dyslipidemia, hypertension, and metabolic syndrome were comparable between groups. Histologic scores for steatosis and inflammation were similar. Adolescents have significantly higher NASH incidence, hepatocyte injury scores and fibrosis. This was associated with higher serum C‐reactive protein and sCD14 levels.
Conclusion:
For comparable BMI and metabolic profile, SO adolescents have more advanced liver damage, more severe systemic inflammation, suggesting differences in NAFLD etiologies and more aggressive disease progression in the young obese population.
Patients with stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) develop systemic inflammation characterized by vasculopathy, interstitial lung disease, ...ulcerative skin lesions, and premature death. Autosomal dominant mutations in STING are thought to trigger activation of IRF3 and subsequent up-regulation of interferon (IFN)-stimulated genes (ISGs) in patients with SAVI. We generated heterozygous STING N153S knock-in mice as a model of SAVI. These mice spontaneously developed inflammation within the lung, hypercytokinemia, T cell cytopenia, skin ulcerations, and premature death. Cytometry by time-of-flight (CyTOF) analysis revealed that the STING N153S mutation caused myeloid cell expansion, T cell cytopenia, and dysregulation of immune cell signaling. Unexpectedly, we observed only mild up-regulation of ISGs in STING N153S fibroblasts and splenocytes and STING N154S SAVI patient fibroblasts. STING N153S mice lacking IRF3 also developed lung disease, myeloid cell expansion, and T cell cytopenia. Thus, the SAVI-associated STING N153S mutation triggers IRF3-independent immune cell dysregulation and lung disease in mice.
The wild resources of
Psammosilene tunicoides
have decreased sharply because of the long-term mining and excavation, which has led to the increased demand for its artificial cultivation. However, ...root rot represents a significant obstacle leading to a poor quality and product of
P. tunicoides
. Previous reports have not focused on root rot in
P. tunicoides.
Therefore, this study explores the rhizospheric and root endophytic microbial community structure and composition of healthy and root rot
P. tunicoides
to understand the mechanism underlying root rot
.
The properties of the rhizosphere soil were assessed using physiochemical methods, and the bacterial and fungal populations were studied through amplicon sequencing of the 16S rRNA genes and ITS regions in the root and soil. Compared to healthy samples, the pH, hydrolysis N, available P, and available K were significantly decreased in the diseased samples while the organic matter and total organic carbon were significantly increased in the diseased samples. Redundancy analysis (RDA) showed that soil environmental factors are related to changes in the root and rhizosphere soil microbial community of
P. tunicoides
indicating that the physiochemical properties of soil affect plant health. Alpha diversity analysis showed that the microbial communities of healthy and diseased samples were similar. Some bacterial and fungal genera were significantly increased or decreased (
P
< 0.05) in diseased
P. tunicoides
, and certain microbial factors that antagonized root rot were further explored. This study provides an abundant microbial resource for future studies and contributes to improving soil quality and
P. tunicoides
agricultural production.
A mathematical model is developed for the coupled analysis of the transport of macromolecules, such as low-density lipoproteins (LDL), in the blood stream and in the arterial walls. The ...advection–diffusion equations in porous media are used to model the species field in the arterial wall layers. The physical parameters needed are computed based on the available data from in vivo and in vitro measurements. The computed parameters are compared to those provided by other models and the differences are discussed. The advantage of the current model is that its set up is based on in vivo/vitro measurements and the calculated exact solutions of concentration field, leading to more reliable results. The model is used to simulate the LDL transport in a stenosed artery with various area reductions and stenosis numbers. The effects of hypertension and geometrical variation on the LDL accumulation within the wall are studied and discussed. This work provides essential information for studying atherogenesis.
Sediment and turbidity are primary causes of impaired river ecosystems; remedial action for these impairments requires the identification of their sources and controlling factors. This paper examines ...the combined effects of watershed complexity in terms of land use and physiography on the specific sediment yield of the upper Du River watershed (8973km2) in China. The land use composition, land use pattern, morphometric variables, and soil properties of the watershed were calculated at the subwatershed scale and considered to be potentially influential factors. Because these watershed characteristics are highly codependent, a partial least-squares regression (PLSR) was used to elucidate the linkages between the specific sediment yield and metrics composed of 19 selected watershed characteristics. The first-order factors were identified by calculating the variable importance for the projection (VIP). The results revealed that the land use composition and land use pattern exerted the largest effects on the specific sediment yield and explained 65.2% of the variation in the specific sediment yield. A set of physiographic indices was also found to have a large effect on the specific sediment yield and explained 17.7% of the observed variation in the specific sediment yield. The following are the dominant first-order factors of the specific sediment yield at the subwatershed scale: the areal percentages of agriculture and forest, patch density, value of the Shannon's diversity index, contagion, value of the hypsometric integral, and saturated soil hydraulic conductivity. The watershed size exerted a substantial effect on the sediment delivery ratio (SDR). The VIP values also suggested that the Shannon's diversity index, contagion, and hypsometric integral are important factors in the SDR. With a readily available digital spatial database and rapid developments in geographic information system (GIS) technology, this practical and simple PLSR approach could be applied to a variety of watersheds.
•We studied the sediment yield response to various watershed characteristics.•The PLSR approach is a useful tool for analyzing correlated data.•Land-use type and patterns have the largest effect on the specific sediment yield.•An SDR model as a function of watershed characteristics was developed.
Hepcidin, the body's main regulator of systemic iron homeostasis, is upregulated in response to inflammation and is thought to play a role in the manifestation of iron deficiency (ID) observed in ...obese populations. We determined systemic hepcidin levels and its association with body mass, inflammation, erythropoiesis, and iron status in premenopausal obese and nonobese women (n = 20/group) matched for hemoglobin (Hb). The obese participants also had liver and abdominal visceral and subcutaneous adipose tissue assessed for tissue iron accumulation and hepcidin mRNA expression. Despite similar Hb levels, the obese women had significantly higher serum hepcidin (88.02 vs. 9.70 ng/ml; P < 0.0001) and serum transferrin receptor (sTfR) (P = 0.001) compared to nonobese. In the obese women hepcidin was not correlated with serum iron (r = −0.02), transferrin saturation (Tsat) (r = 0.17) or sTfR (r = −0.12); in the nonobese it was significantly positively correlated with Tsat (r = 0.70) and serum iron (r = 0.58), and inversely with sTfR (r = −0.63). Detectable iron accumulation in the liver and abdominal adipose tissue of the obese women was minimal. Liver hepcidin mRNA expression was ∼700 times greater than adipose tissue production and highly correlated with circulating hepcidin levels (r = 0.61). Serum hepcidin is elevated in obese women despite iron depletion, suggesting that it is responding to inflammation rather than iron status. The source of excess hepcidin appears to be the liver and not adipose tissue. The ID of obesity is predominantly a condition of a true body iron deficit rather than maldistribution of iron due to inflammation. However, these findings suggest inflammation may perpetuate this condition by hepcidin‐mediated inhibition of dietary iron absorption.
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