Significantly Enhanced Energy Density of Polyvinylidene Fluoride/Polyimide-Based Nanocomposites by Core-Shell BaTiO3@SiO2.

Improving the limited energy storage capacity of dielectric materials has long been an attractive challenge. In this work, a four-phase hybridized nanocomposite was designed. The linear polymer polyimide (PI) was added to the ferroelectric polymer polyvinylidene fluoride (PVDF) and compounded with a nanoceramic BT@SiO2 with a core-shell structure. The results show that PVDF-PI/BT@SiO2 nanocomposites prepared by a straightforward spin-coating method have a significantly increased discharge energy density. The polymer blends obtain a tightly extended conformation in the amorphous region. Also, this provides an excellent matrix environment for the homogeneous dispersion of fillers. The core-shell structure, as a physical barrier, not only hinders the expansion of the breakdown path but also extends multiple polarization surfaces with gradient variations at the microscopic level. Therefore, the synergistic effect generated by polymer blending and core-shell structure effectively enhances the dielectric and stored energy characteristics of nanocomposites. The dielectric constant is stable at 11.39-18.7, and the dielectric loss is always lower than 0.136. The discharge energy density is 2.5 J/cm3, almost 110% higher than that of the BOPP films (about 1.2 J/cm3). These experimental results suggest that the composite system using core-shell structure and polymer blending is a new way to improve the energy density of dielectric materials.

The global, regional, and national burden of foreign bodies from 1990 to 2019: a systematic analysis of the global burden of disease study 2019.

BACKGROUND: Foreign bodies (FBs) are a common emergency in medical institutions, that can occur in any area and among people of any age, which are common public health problems. Understanding the epidemiological characteristics of FBs is crucial for their prevention and control. The purpose of this study was to analyze the epidemiological characteristics of FBs worldwide through the data from the Global Burden of Disease Study 2019 (GBD 2019). METHODS: We obtained data from the GBD 2019, which is an important public database to understand the disease burden of FBs. Joinpoint was used to analyze temporal trends in the incidence and death trends of FBs, which is widely used to study the long-term temporal trend of the burden of diseases. SaTScan was used to detect spatial-temporal clusters of pulmonary aspiration and foreign body in the airway (PAFBA), which is based on a Poisson model, scanning the number of people and diseases in the study area to obtain the spatial-temporal clusters of diseases. RESULTS: Globally, the age-standardized incidence rate (ASIR) and the age-standardized death rate (ASDR) of FBs in 2019 were 869.23/100,000 (679.92/100,000-1120.69/100,000) and 1.55/100,000 (1.41/100,000-1.67/100,000), respectively. The ASIR and ASDR showed downtrends with average annual percent changes (AAPCs) of -0.31% and - 1.47% from 1990 to 2019. Of note, the ASIR showed an uptrend during 2010-2019, especially in high, high-middle, and middle SDI regions. Stratified analysis by age group showed that ASIR increased in each age group in recent years. From 1990 to 2019, the ASDR in the over-70 age group showed an uptrend worldwide, especially in high and high-middle SDI regions. In different types of FBs, the ASDR of PAFBA was the highest. The death burden of PAFBA was mainly clustered in 82 countries during 1993-2007, such as Canada, Cuba, and Mexico. CONCLUSION: The most important goal is to improve public awareness and emergency knowledge of FBs through publicity methods, such as the internet or offline activities, and to improve laws and regulations. Additionally, different age groups need different targeted measures, such as strengthening the care of children, caring for elderly individuals, improving necessary monitoring programs and reporting systems, conducting effective hazard assessments, and publicity and education activities.

Mechanically Induced Nuclear Shuttling of ß-Catenin Requires Co-transfer of Actin.

Mesenchymal stem cells (MSCs) respond to environmental forces with both cytoskeletal re-structuring and activation of protein chaperones of mechanical information, ß-catenin, and yes-associated protein 1 (YAP1). To function, MSCs must differentiate between dynamic forces such as cyclic strains of extracellular matrix due to physical activity and static strains due to ECM stiffening. To delineate how MSCs recognize and respond differently to both force types, we compared effects of dynamic (200 cycles × 2%) and static (1 × 2% hold) strain on nuclear translocation of ß-catenin and YAP1 at 3 hours after force application. Dynamic strain induced nuclear accumulation of ß-catenin, and increased cytoskeletal actin structure and cell stiffness, but had no effect on nuclear YAP1 levels. Critically, both nuclear actin and nuclear stiffness increased along with dynamic strain-induced ß-catenin transport. Augmentation of cytoskeletal structure using either static strain or lysophosphatidic acid did not increase nuclear content of ß-catenin or actin, but induced robust nuclear increase in YAP1. As actin binds ß-catenin, we considered whether ß-catenin, which lacks a nuclear localization signal, was dependent on actin to gain entry to the nucleus. Knockdown of cofilin-1 (Cfl1) or importin-9 (Ipo9), which co-mediate nuclear transfer of G-actin, prevented dynamic strain-mediated nuclear transfer of both ß-catenin and actin. In sum, dynamic strain induction of actin re-structuring promotes nuclear transport of G-actin, concurrently supporting nuclear access of ß-catenin via mechanisms used for actin transport. Thus, dynamic and static strain activate alternative mechanoresponses reflected by differences in the cellular distributions of actin, ß-catenin, and YAP1.

Effect of iron ion configurations on Ni2+ removal in electrocoagulation.

Electrocoagulation (EC) has been widely used to treat the heavy metal wastewater in industry. A novel process of sinusoidal alternating current electrocoagulation (SACC) is adopted to remove Ni2+ in wastewater in this study. The morphology of precipitates and the distribution of the main functional iron configurations were investigated. Ferron timed complex spectroscopy can identify the monomeric iron configurations [Fe(a)], oligomeric iron configurations [Fe(b)] and polymeric iron configurations [Fe(c)]. The optimal operating conditions of SACC process were determined through single-factor experiments. The maximum Ni2+ removal efficiency [Re(Ni2+)] was achieved under the conditions of pH0=7, current density (j) = 7 A/m2, electrolysis time (t) = 25 min, c0(Ni2+) = 100 mg/L. At pH=7, the proportion of Fe(b) and Fe(c) in the system was 50.4 at.% and 23.1 at.%, respectively. In the SACC process, Fe(b) and Fe(c) are the main iron configurations in solution, while Fe(c) are the vast majority of the iron configurations in the direct current electrocoagulation (DCC) process. Re(Ni2+) is 99.56% for SACC and 98.75% for DCC under the same optimum conditions, respectively. The precipitates produced by SACC have a high proportion of Fe(b) configurations with spherical α-FeOOH and γ-FeOOH structures which contain abundant hydroxyl groups. Moreover, it is demonstrated that Fe(b) has better adsorption capacity than Fe(c) through adsorption experiments of methyl orange (MO) dye. Fe(a) configurations in the homogeneous solution had no effect on the removal of nickel.

Markers of endothelial glycocalyx dysfunction in Clarkson disease.

BACKGROUND: Clarkson disease (monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome, ISCLS) is a rare idiopathic condition marked by transient, relapsing-remitting episodes of systemic microvascular hyper-permeability, which liberates plasma fluid and macromolecules into the peripheral tissues. This pathology manifests clinically as the abrupt onset of hypotensive shock, hemoconcentration, and hypoalbuminemia. METHODS: We analysed endothelial glycocalyx (eGCX)-related markers in plasma from patients with ISCLS during acute disease flares and convalescence by ELISA and comprehensive proteomic profiling. We evaluated eGCX-related components and gene expression in cultured endothelial cells using RNA-sequencing, real-time PCR, and fluorescence staining. RESULTS: Serum levels of eGCX-related core components including hyaluronic acid (HA) and the core proteoglycan soluble syndecan-1 (sCD138) were elevated at baseline and during acute ISCLS flares. Serial measurements demonstrated that sCD138 levels peaked during the recovery (post-leak) phase of the illness. Proteomic analysis of matched acute and convalescent ISCLS plasma revealed increased abundance of eGCX-related proteins, including glypicans, thrombospondin-1 (TSP-1), and eGCX-degrading enzymes in acute compared to remission plasma. Abundance of endothelial cell damage markers did not differ in acute and baseline plasma. Expression of several eGCX-related genes and surface carbohydrate content in endothelial cells from patients with ISCLS did not differ significantly from that observed in healthy control cells. CONCLUSIONS: eGCX dysfunction, but not endothelial injury, may contribute to clinical symptoms of acute ISCLS. Serum levels of of eGCX components including sCD138 may be measured during acute episodes of ISCLS to monitor clinical status and therapeutic responses.

Corrosion Resistance of the GO/ZIF-8 Hybrid Loading Benzotriazole as a Multifunctional Composite Filler-Modified MgAlY Layered Double Hydroxide Coating.

A composite coating with good load-carrying and controlled release capabilities for the corrosion inhibitor benzotriazole (BTA) was prepared while providing active and passive corrosion protection for magnesium alloy systems. In this paper, the organic corrosion inhibitor BTA was loaded into the ZIF-8/GO hybrid (GZB), and then, the GZB composite was coated with hexadecyltrimethoxysilane (HDTMS). Then, the GZB composites carried by HDTMS were made to adhere a ternary MgAlY layered double hydroxide (LDH) coating based on microarc oxidation (MAO) coating by electrophoresis (Si-MgAlY LDH coating). The successful loading of BTA by GZB composites was verified by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Meanwhile, the Si-MgAlY LDH coating was characterized by X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. The potentiodynamic polarization curves show that the corrosion current density of the Si-MgAlY LDH coating reaches (2.08 ± 0.49) × 10-9 A/cm2, which means that the Si-MgAlY LDH coating greatly improves the corrosion resistance of magnesium alloy AZ31. The Si-MgAlY LDH coating can also achieve self-healing function in harsh environments, which is attributed to the synergistic effect of passive and active protection. The composite coating is of great significance to expand the potential applications of magnesium alloys.

Effects of Molecular Structure on Organic Contaminants' Degradation Efficiency and Dominant ROS in the Advanced Oxidation Process with Multiple ROS.

In this study, the previously overlooked effects of contaminants' molecular structure on their degradation efficiencies and dominant reactive oxygen species (ROS) in advanced oxidation processes (AOPs) are investigated with a peroxymonosulfate (PMS) activation system selected as the typical AOP system. Averagely, degradation efficiencies of 19 contaminants are discrepant in the CoCaAl-LDO/PMS system with production of SO4•-, •OH, and 1O2. Density functional theory calculations indicated that compounds with high EHOMO, low-energy gap (ΔE = ELUMO - EHOMO), and low vertical ionization potential are more vulnerable to be attacked. Further analysis disclosed that the dominant ROS was the same one when treating similar types of contaminants, namely SO4•-, 1O2, 1O2, and •OH for the degradation of CBZ-like compounds, SAs, bisphenol, and triazine compounds, respectively. This phenomenon may be caused by the contaminants' structures especially the commonly shared or basic parent structures which can affect their effective reaction time and second-order rate constants with ROS, thus influencing the contribution of each ROS during its degradation. Overall, the new insights gained in this study provide a basis for designing more effective AOPs to improve their practical application in wastewater treatment.

Abnormal ADAMTS2 and VSIG4 in Serum of HF Patients and their Relationship with CRP, UA, and HCY.

BACKGROUND: Abnormal A Disintegrin and Metalloproteinase with Thrombospondin Motifs 2 (ADAMTS2) and V-set and immunoglobulin domain-containing 4 (VSIG4) were explored in serum of heart failure (HF) patients and its association with C-reactive protein (CRP), uric acid (UA), and homocysteine (HCY) indexes was manifested. METHODS: ADAMTS2 and VSIG4 expression in serum of HF patients was analyzed. Pearson's correlation coefficient analysis was employed to evaluate the correlation between the indexes. Receiver operating characteristic (ROC) curves to assess the recognition ability of ADAMTS2, VSIG4, and brain natriuretic peptide (BNP) for HF. Kaplan-Meier survival curve and multivariate Cox regression were applied to analyze the prognostic value of ADAMTS2 and VSIG4. RESULTS: ADAMTS2 and VSIG4 were upregulated in serum of HF patients. ROC curve affirmed that ADAMTS2 and VSIG4 in serum manifested diagnostic value for HF, and the combined diagnosis accuracy of ADAMTS2, VSIG4, and BNP was greatly improved. Kaplan-Meier and multivariate Cox regression analysis suggested that reduced ADAMTS2 and VSIG4 could forecast the overall survival of HF patients. CONCLUSIONS: This study assures that ADAMTS2 and VSIG4 are strengthening in HF patients, which makes them new non-invasive biomarkers for the diagnosis and prognosis of HF.

Constructal Optimizations of Line-to-Line Vascular Channels with Turbulent Convection Heat Transfer.

The multi-scale line-to-line vascular channels (LVCs) widely exist in nature because of their excellent transmission characteristics. In this paper, models of LVCs with turbulent convection heat transfer are established. Based on constructal theory and the entropy generation minimization principle, the constructal optimizations of LVCs with any order are conducted by taking the angles at bifurcations as the optimization variables. The heat flux on the channel wall per unit length is fixed and uniform. The areas occupied by vasculature and the total volumes of channels are fixed. The analytical expressions of the optimal angles, dimensionless total entropy generation rate and entropy generation number (EGN) of LVCs with any order versus dimensionless mass flow rate are obtained, respectively. The results indicate that the dimensionless total entropy generation rate of LVCs with any order can be significantly decreased by optimizing the angles of LVCs, which is significantly more when the order of LVCs is higher. As the dimensionless mass flow rate increases, the optimal angles of LVCs with any order remain unchanged first, then the optimal angles at the entrance (root) increase, and the other optimal angles decrease continuously and finally tend to the respective stable values. The optimal angles of LVCs continue to increase from the entrance to the outlet (crown), i.e., the LVCs with a certain order gradually spread out from the root to the crown. The dimensionless total entropy generation rate and EGN of LVCs first decrease and then increase with the growth of the dimensionless mass flow rate. There is optimal dimensionless mass flow rate, making the dimensionless total entropy generation rate and the EGN reach their respective minimums. The results obtained herein can provide some new theoretical guidelines of thermal design and management for the practical applications of LVCs.

Knockdown of formin mDia2 alters lamin B1 levels and increases osteogenesis in stem cells.

Nuclear actin plays a critical role in mediating mesenchymal stem cell (MSC) fate commitment. In marrow-derived MSCs, the principal diaphanous-related formin Diaph3 (mDia2) is present in the nucleus and regulates intranuclear actin polymerization, whereas Diaph1 (mDia1) is localized to the cytoplasm and controls cytoplasmic actin polymerization. We here show that mDia2 can be used as a tool to query actin-lamin nucleoskeletal structure. Silencing mDia2 affected the nucleoskeletal lamin scaffold, altering nuclear morphology without affecting cytoplasmic actin cytoskeleton, and promoted MSC differentiation. Attempting to target intranuclear actin polymerization by silencing mDia2 led to a profound loss in lamin B1 nuclear envelope structure and integrity, increased nuclear height, and reduced nuclear stiffness without compensatory changes in other actin nucleation factors. Loss of mDia2 with the associated loss in lamin B1 promoted Runx2 transcription and robust osteogenic differentiation and suppressed adipogenic differentiation. Hence, mDia2 is a potent tool to query intranuclear actin-lamin nucleoskeletal structure, and its presence serves to retain multipotent stromal cells in an undifferentiated state.

Constructal Optimization of Rectangular Microchannel Heat Sink with Porous Medium for Entropy Generation Minimization.

A model of rectangular microchannel heat sink (MCHS) with porous medium (PM) is developed. Aspect ratio of heat sink (HS) cell and length-width ratio of HS are optimized by numerical simulation method for entropy generation minimization (EGM) according to constructal theory. The effects of inlet Reynolds number (Re) of coolant, heat flux on bottom, porosity and volume proportion of PM on dimensionless entropy generation rate (DEGR) are analyzed. From the results, there are optimal aspect ratios to minimize DEGR. Given the initial condition, DEGR is 33.10% lower than its initial value after the aspect ratio is optimized. With the increase of Re, the optimal aspect ratio declines, and the minimum DEGR drops as well. DEGR gets larger and the optimal aspect ratio remains constant with the increasing of heat flux on bottom. For the different volume proportion of PM, the optimal aspect ratios are diverse, but the minimum DEGR almost stays unchanged. The twice minimized DEGR, which results from aspect ratio and length-width ratio optimized simultaneously, is 10.70% lower than the once minimized DEGR. For a rectangular bottom, a lower DEGR can be reached by choosing the proper direction of fluid flow.

PTP1B up-regulates EGFR expression by dephosphorylating MYH9 at Y1408 to promote cell migration and invasion in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. Protein tyrosine phosphatase 1B (PTP1B) is a member of protein tyrosine phosphatases (PTPs) family. In our previous work, PTP1B was found to be overexpressed in ESCC tissues and made contributions to the the cell migration and invasion as well as lung metastasis of ESCC. In this study, we explored the underlying molecular mechanisms. PTP1B enhanced cell migration and invasion by promoting epidermal growth factor receptor (EGFR) expression in ESCC, which was relied on phosphatase activity of PTP1B. Using GST-pulldown combined with LC/MS/MS, we found that nonmuscle myosin IIA (MYH9) was a novel substrate of PTP1B in ESCC cells. PTP1B dephosphorylated MYH9 at Y1408, by which PTP1B up-regulated EGFR expression and enhanced cell migration and invasion in ESCC. In conclusion, our study first reported that PTP1B was the positive regulator of EGFR by dephosphorylating MYH9 at Y1408 to promote cell migration and invasion, which revealed the regulatory mechanism of PTP1B-MYH9-EGFR axis in ESCC.

Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13.

Mast cells elicit allergic responses through degranulation and release of proinflammatory mediators after antigen crosslinking of the immunoglobulin E receptor FcepsilonRI. Proteins of the 'regulator of G protein signaling' (RGS) family negatively control signaling mediated by G protein-coupled receptors through GTPase-accelerating protein activity. Here we show that RGS13 inhibited allergic responses by physically interacting with the regulatory p85alpha subunit of phosphatidylinositol-3-OH kinase in mast cells and disrupting its association with an FcepsilonRI-activated scaffolding complex. Rgs13-/- mice had enhanced immunoglobulin E-mediated mast cell degranulation and anaphylaxis. Thus, RGS13 inhibits the assembly of immune receptor-induced signalosomes in mast cells. Abnormal RGS13 expression or function may contribute to disorders of amplified mast cell activity, such as idiopathic anaphylaxis.

Constructal Design of an Arrow-Shaped High Thermal Conductivity Channel in a Square Heat Generation Body.

A heat conduction model with an arrow-shaped high thermal conductivity channel (ASHTCC) in a square heat generation body (SHGB) is established in this paper. By taking the minimum maximum temperature difference (MMTD) as the optimization goal, constructal designs of the ASHTCC are conducted based on single, two, and three degrees of freedom optimizations under the condition of fixed ASHTCC material. The outcomes illustrate that the heat conduction performance (HCP) of the SHGB is better when the structure of the ASHTCC tends to be flat. Increasing the thermal conductivity ratio and area fraction of the ASHTCC material can improve the HCP of the SHGB. In the discussed numerical examples, the MMTD obtained by three degrees of freedom optimization are reduced by 8.42% and 4.40%, respectively, compared with those obtained by single and two degrees of freedom optimizations. Therefore, three degrees of freedom optimization can further improve the HCP of the SHGB. Compared the HCPs of the SHGBs with ASHTCC and the T-shaped one, the MMTD of the former is reduced by 13.0%. Thus, the structure of the ASHTCC is proven to be superior to that of the T-shaped one. The optimization results gained in this paper have reference values for the optimal structure designs for the heat dissipations of various electronic devices.

Constructal Design of Elliptical Cylinders with Heat Generating for Entropy Generation Minimization.

A heat dissipation model of discrete elliptical cylinders with heat generation on a thermal conduction pedestal cooled by forced convection is established. Constructal design is conducted numerically by taking the distributions of thermal conductivity and heat generating intensity as design variables, the dimensionless entropy generation rate (DEGR) as performance indicator. The optimal designs for discrete elliptical cylinders with heat generating are obtained respectively, i.e., there are optimal distributions of heat generating intensity with its fixed total amount of heat sources, and there are optimal distributions of thermal conductivity with its fixed total amount of heat sources. These optimums for minimum DEGRs are different at different Reynolds numbers of airflow. The heat generating intensity can be decreased one by one appropriately in the fluid flow direction to achieve the best effect. When the Reynolds number of airflow is smaller, the thermal conductivity of heat source can be increased one by one appropriately in the fluid flow direction to achieve the best effect; when the Reynolds number of airflow is larger, the thermal conductivity of each heat source should be equalized to achieve the best effect. The results can give thermal design guidelines for the practical heat generating devices with different materials and heat generating intensities.

Neutrophil activation in systemic capillary leak syndrome (Clarkson disease).

Systemic capillary leak syndrome (SCLS; Clarkson disease) is a rare orphan disorder characterized by transient yet recurrent episodes of hypotension and peripheral oedema due to diffuse vascular leakage of fluids and proteins into soft tissues. Humoral mediators, cellular responses and genetic features accounting for the clinical phenotype of SCLS are virtually unknown. Here, we searched for factors altered in acute SCLS plasma relative to matched convalescent samples using multiplexed aptamer-based proteomic screening. Relative amounts of 612 proteins were changed greater than twofold and 81 proteins were changed at least threefold. Among the most enriched proteins in acute SCLS plasma were neutrophil granule components including bactericidal permeability inducing protein, myeloperoxidase and matrix metalloproteinase 8. Neutrophils isolated from blood of subjects with SCLS or healthy controls responded similarly to routine pro-inflammatory mediators. However, acute SCLS sera activated neutrophils relative to remission sera. Activated neutrophil supernatants increased permeability of endothelial cells from both controls and SCLS subjects equivalently. Our results suggest systemic neutrophil degranulation during SCLS acute flares, which may contribute to the clinical manifestations of acute vascular leak.

Regulator of G protein signaling 5 restricts neutrophil chemotaxis and trafficking.

Neutrophils are white blood cells that are mobilized to damaged tissues and to sites of pathogen invasion, providing the first line of host defense. Chemokines displayed on the surface of blood vessels promote migration of neutrophils to these sites, and tissue- and pathogen-derived chemoattractant signals, including N-formylmethionylleucylphenylalanine (fMLP), elicit further migration to sites of infection. Although nearly all chemoattractant receptors use heterotrimeric G proteins to transmit signals, many of the mechanisms lying downstream of chemoattractant receptors that either promote or limit neutrophil motility are incompletely defined. Here, we show that regulator of G protein signaling 5 (RGS5), a protein that modulates G protein activity, is expressed in both human and murine neutrophils. We detected significantly more neutrophils in the airways of Rgs5-/- mice than WT counterparts following acute respiratory virus infection and in the peritoneum in response to injection of thioglycollate, a biochemical proinflammatory stimulus. RGS5-deficient neutrophils responded with increased chemotaxis elicited by the chemokines CXC motif chemokine ligand 1 (CXCL1), CXCL2, and CXCL12 but not fMLP. Moreover, adhesion of these cells was increased in the presence of both CXCL2 and fMLP. In summary, our results indicate that RGS5 deficiency increases chemotaxis and adhesion, leading to more efficient neutrophil mobilization to inflamed tissues in mice. These findings suggest that RGS5 expression and activity in neutrophils determine their migrational patterns in the complex microenvironments characteristic of inflamed tissues.

Intranuclear Actin Structure Modulates Mesenchymal Stem Cell Differentiation.

Actin structure contributes to physiologic events within the nucleus to control mesenchymal stromal cell (MSC) differentiation. Continuous cytochalasin D (Cyto D) disruption of the MSC actin cytoskeleton leads to osteogenic or adipogenic differentiation, both requiring mass transfer of actin into the nucleus. Cyto D remains extranuclear, thus intranuclear actin polymerization is potentiated by actin transfer: we asked whether actin structure affects differentiation. We show that secondary actin filament branching via the Arp2/3 complex is required for osteogenesis and that preventing actin branching stimulates adipogenesis, as shown by expression profiling of osteogenic and adipogenic biomarkers and unbiased RNA-seq analysis. Mechanistically, Cyto D activates osteoblast master regulators (e.g., Runx2, Sp7, Dlx5) and novel coregulated genes (e.g., Atoh8, Nr4a3, Slfn5). Formin-induced primary actin filament formation is critical for Arp2/3 complex recruitment: osteogenesis is prevented by silencing of the formin mDia1, but not its paralog mDia2. Furthermore, while inhibition of actin, branching is a potent adipogenic stimulus, silencing of either mDia1 or mDia2 blocks adipogenic gene expression. We propose that mDia1, which localizes in the cytoplasm of multipotential MSCs and traffics into the nucleus after cytoskeletal disruption, joins intranuclear mDia2 to facilitate primary filament formation before mediating subsequent branching via Arp2/3 complex recruitment. The resulting intranuclear branched actin network specifies osteogenic differentiation, while actin polymerization in the absence of Arp2/3 complex-mediated secondary branching causes adipogenic differentiation. Stem Cells 2017;35:1624-1635.

Constructal Optimization for Cooling a Non-Uniform Heat Generating Radial-Pattern Disc by Conduction.

A heat conduction model in a radial-pattern disc by considering non-uniform heat generation (NUHG) is established in this paper. A series of high conductivity channels (HCCs) are attached on the rim of the disc and extended to its center. Constructal optimizations of the discs with constant and variable cross-sectional HCCs are carried out, respectively, and their maximum temperature differences (MTDs) are minimized based on analytical method and finite element method. Besides, the influences of the NUHG coefficient, HCC number and width coefficient on the optimal results are studied. The results indicate that the deviation of the optimal constructs obtained from the analytical method and finite element method are comparatively slight. When the NUHG coefficient is equal to 10, the minimum MTD of the disc with 25 constant cross-sectional HCCs is specifically reduced by 48.8% compared to that with 10 HCCs. As a result, the heat conduction performance (HCP) of the disc can be efficiently improved by properly increasing the number of HCCs. The minimum MTD of the disc with variable cross-sectional HCC is decreased by 15.0% when the width coefficient is changed from 1 to 4. Therefore, the geometry of variable cross-sectional HCC can be applied in the constructal design of the disc to a better heat transfer performance. The constructal results obtained by investigating the non-uniform heat generating case in this paper can contribute to the design of practical electronic device to a better heat transfer performance.

Prognostic relevance of lactate dehydrogenase in advanced pancreatic ductal adenocarcinoma patients.

BACKGROUND: The prognostic role of pretreatment serum lactate dehydronegase (LDH) has been well established in many malignant tumors, albeit it remains under-discussed in pancreatic cancer. In the present study, we aimed to assess the association between baseline LDH levels and overall survival (OS) in advanced pancreatic ductal adenocarcinoma (PDAC) patients who did and did not receive subsequent chemotherapy. METHODS: In total, 135 retrospectively determined patients with locally advanced or metastatic PDAC, who were diagnosed between 2012 and 2013, were analyzed. Baseline LDH levels were detected within 20 days after histopathological confirmation of the diagnosis. Multivariate Cox proportional hazards regression model was applied to estimate the adjusted hazards ratio (HR) for LDH levels and OS of PDAC. We used restricted cubic spline (RCS) to further investigate dose-effect relationship in the association. RESULTS: Having adjusted for possible confounders, we found that in advanced PDAC patients who went through subsequent chemotherapy, an elevated pretreatment LDH level (≥250 U/L) had an adjusted HR of 2.47 (95% CI = 1.28-4.77) for death, but patients, who did not receive chemotherapy, had no significant HR (adjusted HR = 1.57; 95% CI = 0.83-2.96). RCS fitting results revealed a steep increase in HR for PDAC patients received chemotherapy with a baseline LDH > 500 U/L. CONCLUSIONS: Pretreatment LDH levels had noticeable prognostic value in PDAC patients who received subsequent chemotherapy. Tackling elevated LDH levels before the initiation of chemotherapy might be a promising measure for improving OS of patients after treatment for their advanced PDAC. Studies with a large sample size and a prospective design are warranted to substantiate our findings.