Image1_Impaired FGF10 Signaling and Epithelial Development in Experimental Lung Hypoplasia With Esophageal Atresia.tiff

<p>Patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) often experience persistent respiratory tract disease. In experimental models, doxorubicin-induced developmental lung abnormalities may result from downregulation of branching morphogenesis factor fibroblast growth factor (Fgf10). This study investigated the temporospatial expression of Fgf10 pathway components and lung epithelial factors in an doxorubicin-induced EA-TEF model by quantitative polymerase chain reaction, immunohistochemistry, and immunoblotting. Epigenetic regulation of gene expression by histone deacetylation was also investigated. Bone morphogenetic protein (Bmp) 4 and Cathepsin H (Ctsh), downstream targets of Fgf10, were significantly downregulated in the EA-TEF model during the saccular stage, consistent with Fgf10 expression. The developmental expression pattern of P2x7 receptor (ATI-cell marker), Sftpa, and Sftpb in lung epithelial cells was not affected. Sftpc (ATII-cell Marker) and Scgb1a1 (Clara cell marker) were significantly downregulated at the canalicular stage. Meanwhile, histone deacetylase (Hdac) 1 was upregulated and subsequently decreased acetylation of histone H3 Lys56 in the EA-TEF model, which returned to a normal level at the saccular stage. In conclusion, disturbed molecular signaling involving Fgf10/Ctsh was associated with impaired airway branching and epithelial cell development in lung morphogenesis, as evidenced by downregulated Sftpc and Scgb1a1 protein expression. The influence of Hdac1 activity on gene and protein expression in lung epithelial cells deserves further study.</p

Event-triggered coordination for formation tracking control in constrained space with limited communication

In this paper, the formation tracking control is studied for a multi-agent system (MAS) with communication limitations. The objective is to control a group of agents to track a desired trajectory while maintaining a given formation in non omniscient constrained space. The role switching triggered by the detection of unexpected spatial constraints facilitates efficiency of event-triggered control in communication bandwidth, energy consumption and processor usage. A coordination mechanism is proposed based on a novel role ‘coordinator’ to indirectly spread environmental information among the whole communication network and form a feedback link from followers to the leader to guarantee the formation keeping. A formation scaling factor is introduced to scale up or scale down the given formation size in the case that the region is impassable for MAS with the original formation size. Controllers for the leader and followers are designed and the adaptation law is developed for the formation scaling factor. The conditions for asymptotic stability of MAS are discussed based on the Lyapunov theory. Simulation results are presented to illustrate the performance of proposed approaches

Table_1_Maternal Protein Restriction Induces Alterations in Hepatic Unfolded Protein Response-Related Molecules in Adult Rat Offspring.DOCX

Intrauterine growth restriction (IUGR) leads to the development of metabolic syndrome in adulthood. To explore the potential mechanisms of metabolic imprinting, we investigated the effect of malnutrition in utero on hepatic unfolded protein response (UPR)-related genes in IUGR offspring. An IUGR rat model was developed by feeding a low-protein diet to pregnant rats. The expression levels and activity of hepatic UPR genes were analysed by quantitative PCR (qPCR) arrays and western blotting. The hepatic UPR molecules heat-shock 70-kDa protein 4l (Hspa4l), mitogen-activated protein kinase 10 (Mapk10), and endoplasmic reticulum to nucleus signalling 2 (Ern2) were markedly downregulated in IUGR foetuses, but the expression of Mapk10 and Ern2 returned to normal levels at 3 weeks postnatal. In contrast, cAMP responsive element binding protein 3-like 3 (Creb3l3) was upregulated in hepatic tissues at embryo 20(E20), then restored to normal in adulthood (12 weeks). The protein levels of activating transcription factor 2 (Atf2) and Atf6, two key factors of the UPR pathway, were upregulated in the livers of IUGR foetuses, and the latter remained upregulated until 12 weeks. Combined with our previous findings showing an increase in hepatic gluconeogenesis enzymes in IUGR offspring, we speculated that aberrant intrauterine milieu impaired UPR signalling in hepatic tissues; these alterations early in life might contribute to the predisposition of IUGR foetuses to adult metabolic disorders.</p

Image_1_Impact of IgG Isotype on the Induction of Antibody-Dependent Cellular Phagocytosis of HIV by Human Milk Leukocytes.tif

Approximately 100,000 mother-to-child transmission (MTCT) events of HIV via human milk feeding occur each year. However, only about 15% of infants milk-fed by untreated HIV+ mothers become infected, suggesting a protective effect of the milk itself. Infants ingest 105-108 maternal leukocytes daily via milk, which remain functional beyond ingestion. Such function may be elicited by maternal milk antibody (Ab). Though IgA is dominant in milk, most HIV-specific milk Abs are of the IgG subclass, highlighting the importance of investigating the function of each IgG isotype in the milk context. Though Ab effector function mediated by the constant (Fc) domain via interaction with Fc Receptors (FcRs), such as Ab-dependent cellular phagocytosis (ADCP), are critical in protecting against HIV infection, ADCP is largely unexplored as it relates to mitigation of MTCT. Presently we report the ADCP activity of milk leukocytes against HIV particles and immune complexes (ICs), using 57 unique samples from 34 women, elicited by IgG1/2/3/4 of monoclonal (m)Ab 246-D. Granulocyte ADCP of HIV was most potent compared to other phagocytes when elicited by IgG1/3/4. IgG1/3 activated granulocytes similarly, exhibiting 1.6x-4.4x greater activity compared to IgG2/4, and a preference for virus compared to ICs. Notably, CD16- monocyte ADCP of a given target were unaffected by isotype, and CD16+ monocytes were poorly stimulated by IgG1. IgG2/4 elicited potent IC ADCP, and in terms of total leukocyte IC ADCP, IgG4 and IgG3 exhibited similar function, with IgG4 eliciting 1.6x-2.1x greater activity compared to IgG1/IgG2, and CD16+ monocytes most stimulated by IgG2. These data contribute to a more comprehensive understanding of Fc-mediated functionality of milk leukocytes, which is critical in order to develop therapeutic approaches to eliminating this route of MTCT, including mucosal administration of mAbs and/or a maternal vaccination aimed to elicit a potent milk Ab response.</p

Highly Selective and Reversible Chemosensor for Pd²⁺ Detected by Fluorescence, Colorimetry, and Test Paper

A “turn-on” fluorescent and colorimetric chemosensor (<b>RBS</b>) for Pd²⁺ has been designed and synthesized through introduction of sulfur as a ligand atom to Rhodamine B. <b>RBS</b> exhibits high selectivity (freedom from the interference of Hg²⁺in particular) and sensitivity toward Pd²⁺ with a detection limit as low as 2.4 nM. <b>RBS</b> is also a reversible sensor, and it can be made into test paper to detect Pd²⁺ in pure water. Compared to the chemosensors that introduced phosphorus to Rhodamine to detect Pd²⁺, <b>RBS</b> can be synthesized more simply and economically

Video_1_Robust quasi-uniform surface meshing of neuronal morphology using line skeleton-based progressive convolution approximation.MP4

Creating high-quality polygonal meshes which represent the membrane surface of neurons for both visualization and numerical simulation purposes is an important yet nontrivial task, due to their irregular and complicated structures. In this paper, we develop a novel approach of constructing a watertight 3D mesh from the abstract point-and-diameter representation of the given neuronal morphology. The membrane shape of the neuron is reconstructed by progressively deforming an initial sphere with the guidance of the neuronal skeleton, which can be regarded as a digital sculpting process. To efficiently deform the surface, a local mapping is adopted to simulate the animation skinning. As a result, only the vertices within the region of influence (ROI) of the current skeletal position need to be updated. The ROI is determined based on the finite-support convolution kernel, which is convolved along the line skeleton of the neuron to generate a potential field that further smooths the overall surface at both unidirectional and bifurcating regions. Meanwhile, the mesh quality during the entire evolution is always guaranteed by a set of quasi-uniform rules, which split excessively long edges, collapse undersized ones, and adjust vertices within the tangent plane to produce regular triangles. Additionally, the local vertices density on the result mesh is decided by the radius and curvature of neurites to achieve adaptiveness.</p

Expression profiles of <i>FvNAC</i> genes in leaves under salt stress.

The salt stress treatment was simulated by irrigating potted woodland strawberry plants with 100 mM NaCl. Log2 based values from cold stress of qRT-PCR data were used to create the heat map.</p

Image_1_Effectiveness and Safety of Toripalimab Combination Therapies for Patients With Chemo-Resistant Choriocarcinoma.tif

Toripalimab as a novel PD-1 inhibitor has presented its promising efficacy in patients who developed chemo-refractory carcinomas, whereas no study has ever investigated the effectiveness of toripalimab in chemo-resistant choriocarcinoma. Here we reported the effectiveness and safety data of 4 patients with chemo-resistant choriocarcinoma who underwent PD-1 antibody therapy by toripalimab and individualized chemotherapies. From January 2019 to August 2020, 4 patients with choriocarcinoma were admitted in Shengjing Hospital of China Medical University. The patients’ age ranged from 29 to 52 years with a median of 36 years. All the patients achieved CR after the combined therapy of toripalimab with individualized chemotherapies according to the decreased serum β-hcg level. Two of the four patients were observed with treatment-related adverse events (AEs), including one grade I skin rash and one grade I pruritus. Our cases showed that toripalimab combined with chemotherapy presented a tolerable safety profile and promising effectiveness in patients with chemo-resistant choriocarcinoma, indicating its potential as salvage therapy for this subset of patients.</p

Genome-wide identification and expression profile analysis of the NAC transcription factor family during abiotic and biotic stress in woodland strawberry

<div><p>The NAC transcription factors involved plant development and response to various stress stimuli. However, little information is available concerning the NAC family in the woodland strawberry. Herein, 37 <i>NAC</i> genes were identified from the woodland strawberry genome and were classified into 13 groups based on phylogenetic analysis. And further analyses of gene structure and conserved motifs showed closer relationship of them in every subgroup. Quantitative real-time PCR evaluation different tissues revealed distinct spatial expression profiles of the <i>FvNAC</i> genes. The comprehensive expression of <i>FvNAC</i> genes revealed under abiotic stress (cold, heat, drought, salt), signal molecule treatments (H₂O₂, ABA, melatonin, rapamycin), biotic stress (<i>Colletotrichum gloeosporioides</i> and <i>Ralstonia solanacearum</i>). Expression profiles derived from quantitative real-time PCR suggested that 5 <i>FvNAC</i> genes responded dramatically to the various abiotic and biotic stresses, indicating their contribution to abiotic and biotic stresses resistance in woodland strawberry. Interestingly, <i>FvNAC</i> genes showed greater extent responded to the cold treatment than other abiotic stress, and H₂O₂ exhibited a greater response than ABA, melatonin, and rapamycin. For biotic stresses, 3 <i>FvNAC</i> genes were up-regulated during infection with <i>C</i>. <i>gloeosporioides</i>, while 6 <i>FvNAC</i> genes were down-regulated during infection with <i>R</i>. <i>solanacearum</i>. In conclusion, this study identified candidate <i>FvNAC</i> genes to be used for the genetic improvement of abiotic and biotic stress tolerance in woodland strawberry.</p></div

MOESM1 of Psoralen inhibits malignant proliferation and induces apoptosis through triggering endoplasmic reticulum stress in human SMMC7721 hepatoma cells

Additional file 1: Figure S1. Effects of psoralen on gene expression of ER-stress in HepG2. The mRNA levels of key gene in ER-stress in the dose of 40 μM psoralen or 0.1 μM thapsigargin for 24 h. Values are means ± SD (n = 3) and * is means compared to the Con group, **, p < 0.01; ***, p < 0.001