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Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown and to date no genetic mechanisms for AKI have been established. Clonal hematopoiesis of indeterminate potential (CHIP) is a recently recognized biological mechanism conferring risk of several chronic aging diseases including cardiovascular disease, pulmonary disease and liver disease. In CHIP, blood stem cells acquire mutations in myeloid cancer driver genes such asDNMT3A, TET2, ASXL1andJAK2and the myeloid progeny of these mutated cells contribute to end-organ damage through inflammatory dysregulation. We sought to establish whether CHIP causes acute kidney injury (AKI). To address this question, we first evaluated associations with incident AKI events in three population-based epidemiology cohorts (N = 442,153). We found that CHIP was associated with a greater risk of AKI (adjusted HR 1.26, 95% CI: 1.19–1.34, pDNMT3A(HR: 1.49, 95% CI: 1.37–1.61, pDNMT3ACHIP was more common among those with a non-resolving pattern of injury (HR 2.3, 95% CI: 1.14–4.64, p = 0.03). To gain mechanistic insight, we evaluated the role ofTet2-CHIP to AKI in ischemia-reperfusion injury (IRI) and unilateral ureteral obstruction (UUO) mouse models. In both models, we observed more severe AKI and greater post-AKI kidney fibrosis inTet2-CHIP mice. Kidney macrophage infiltration was markedly increased inTet2-CHIP mice andTet2-CHIP mutant renal macrophages displayed greater pro-inflammatory responses. In summary, this work establishes CHIP as a genetic mechanism conferring risk of AKI and impaired kidney function recovery following AKI via an aberrant inflammatory response in CHIP derived renal macrophages.

“With copper as a mirror, you can wear a crown; with history as a mirror, you can know the rise and fall.” This paper takes the 70-year development process of Southwest Minzu University as the carrier, the casting of the Chinese national community as the main line while tracing back to the source, adopts the recording method of “oral history of the school,” interviews witnesses to the development of Southwest Minzu University, including school leaders, teachers, alumni, and other representative figures, records the memories of these parties on the practices of Southwest Minzu University in different periods to cast the awareness of the Chinese national community, and collates them into a text. From the perspective of students, it is important to understand the history of the Chinese national community in the past 70 years since the establishment of Southwest Minzu University, collect and sort out the historical memories of Southwest Minzu University for the education of the Chinese national community, supplement and confirm the school’s historical documents, preserve the history, make up for the gap in the history of the school, and at the same time provide a realistic basis for Southwest Minzu University to formulate future development strategies.

Purpose Talents are the critical resource of sustainable development for countries, and attracting talents all over the world is the important way for increasing the country's talent reverse. Therefore, the purpose of this paper is to make the governments understand the evolving pattern of international talent mobility. Design/methodology/approach This paper constructs the networked model of talent mobility among 15 major countries during the years 1990–2012 under the database of the Patent Cooperation Treaty and analyzes the global characteristics and the evolvement of international mobility of talents under complex network perspective. Findings It is found that the mobility network is scale-free, which means that a few developed countries, such as the USA, England and France, have enjoyed considerable migratory flows of talents, but most of the other countries only have moderate levels of brain circulation. Besides a very few exceptions, a dynamic equilibrium is reached for most countries, with numbers of talents evening out between emigration and immigration. As time passes by, the volume of talent flows is gradually stabilized, with the numerical gap existing between developed countries and developing ones. Nowadays, the scale of international mobility of talents is growing at an unprecedented speed, facilitated by technological progress and more flexible migratory policies. Originality/value This paper sheds light on the evolving pattern of the international talent mobility using complex network analysis. The cogent quantitative analysis highlights the huge challenges faced by national governments and provides the basis for deliberative policy-making aimed at winning the brain war internationally.

Purpose This paper aims to explore international talent mobility and identify its negative/positive factors. Design/methodology/approach Bibliometric data from Scopus are explicated to model the mobility network and providing a more comprehensive posture. In addition, by using indicators of complex network, significant features of international talent mobility are described quantitatively. After that, by introducing a kind of improved gravity model with multiple linear regression, the authors identify factors to explain international talent mobility flows. Findings With the analysis of international talent mobility in complex network, the overall network is not balanced. A small part of developed countries and developing countries with good emergency attract and drain a lot of talents and talents usually moving between these countries, the amount of talents leaving or entering into other countries is very limited. Furthermore, according to multiple linear regression, it is found that the share of migrants in population is the major negative factor for international talent mobility, and the factors of destination countries is more significant than original countries. Originality/value The result of this paper may support further research studies and political suggestions for cultivating, attracting and retaining scientific and technological talents in the world.

Following acute injury to the kidney, macrophages play an important role in recovery of functional and structural integrity, but organ fibrosis and progressive functional decline occur with incomplete recovery. Pro-resolving macrophages are characterized by increased cyclooxygenase 2 (COX-2) expression and this expression was selectively increased in kidney macrophages following injury and myeloid-specific COX-2 deletion inhibited recovery. Deletion of the myeloid prostaglandin E2 (PGE2) receptor, E-type prostanoid receptor 4 (EP4), mimicked effects seen with myeloid COX-2−/− deletion. PGE2-mediated EP4 activation induced expression of the transcription factor MafB in kidney macrophages, which upregulated anti-inflammatory genes and suppressed pro-inflammatory genes. Myeloid Mafb deletion recapitulated the effects seen with either myeloid COX-2 or EP4 deletion following acute kidney injury, with delayed recovery, persistent presence of pro-inflammatory kidney macrophages, and increased kidney fibrosis. Thus, our studies identified a previously unknown mechanism by which prostaglandins modulate macrophage phenotype following acute organ injury and provide new insight into mechanisms underlying detrimental kidney effects of non-steroidal anti-inflammatory drugs that inhibit cyclooxygenase activity.

Podocyte injury is important in development of diabetic nephropathy (DN). Although several studies have reported single cell-based RNA-seq of podocytes in type 1 DN (T1DN), the podocyte translating mRNA profile in type 2 DN (T2DN) has not been previously compared to that of T1DN. We analyzed the podocyte translatome in T2DN in podocin-Cre; Rosa26fsTRAP; eNOS-/-; db/db mice and compared it to streptozotocin-induced T1DN in podocin-Cre; Rosa26fsTRAP; eNOS-/- mice utilizing Translating Ribosome Affinity Purification (TRAP) and RNA-seq. Over 125 genes were highly enriched in the podocyte ribosome. More podocyte TRAP genes were differentially expressed in T2DN compared to T1DN. TGF-β signaling pathway genes were upregulated while MAPK pathway genes were downregulated only in T2DN while ATP binding and cAMP-mediated signaling genes were downregulated only in T1DN. Genes regulating actin filament organization and apoptosis increased while genes regulating VEGFR signaling and glomerular basement membrane components decreased in both type 1 and type 2 diabetic podocytes. A number diabetes-induced genes not previously been linked to podocyte injury were confirmed in both mouse and human DN. Differences and similarities in the podocyte translatome in T2DN and T1DN can identify factors underlying the pathophysiology of DN and novel therapeutic targets to treat diabetes-induced podocyte injury.

COX (cyclooxygenase)-derived prostaglandins regulate renal hemodynamics and salt and water homeostasis. Inhibition of COX activity causes blood pressure elevation. In addition, chronic analgesic abuse can induce renal injury, including papillary necrosis. COX-2 is highly expressed in the kidney papilla in renal medullary interstitial cells (RMICs). However, its role in blood pressure and papillary integrity in vivo has not been definitively studied. In mice with selective, inducible RMIC COX-2 deletion, a high-salt diet led to an increase in blood pressure that peaked at 4 to 5 weeks and was associated with increased papillary expression of AQP2 (aquaporin 2) and ENac (epithelial sodium channel) and decreased expression of cystic fibrosis transmembrane conductance regulator. With continued high-salt feeding, the mice with RMIC COX-2 deletion had progressive decreases in blood pressure from its peak. After return to a normal-salt diet for 3 weeks, blood pressure remained low and was associated with a persistent urinary concentrating defect. Within 2 weeks of institution of a high-salt diet, increased apoptotic RMICs and collecting duct cells could be detected in papillae with RMIC deletion of COX-2, and by 9 weeks of high salt, there was a striking loss of the papillae. Therefore, RMIC COX-2 expression plays a crucial role in renal handling water and sodium homeostasis, preventing salt-sensitive hypertension and maintaining structural integrity of papilla.

ErbB4, a member of the EGF receptor family, plays a variety of roles in physiological and pathological states. Genetic studies have indicated a link between ErbB4 and type 2 diabetes and obesity, but its role in metabolic syndrome (MetS) has not been reported. In the current study we found that mice with ErbB4 deletion developed MetS after 24 wk on a medium-fat diet (MFD), as indicated by development of obesity, dyslipidemia, hepatic steatosis, hyperglycemia, hyperinsulinemia, and insulin resistance, compared with wild-type mice. ErbB4 deletion mice also exhibited increased amounts of subcutaneous and visceral fat, with increased serum leptin levels, compared with wild-type mice, whereas levels of adiponectin were not significantly different. Histologically, severe inflammation, indicated by F4/80 immunostaining and M1 macrophage polarization, was detected in inguinal and epididymal white adipose tissue in ErbB4 deletion mice. ErbB4 expression decreased during 3T3-L1 preadipocyte differentiation. Administration of neuroregulin 4, a specific ligand for ErbB4, to 3T3-L1 adipocytes had no effect on adipogenesis and lipolysis but significantly inhibited lipogenesis, promoted browning, induced GLUT4 redistribution to the cell membrane, and increased glucose uptake. Neuroregulin 4 also significantly increased glucose uptake in adipocytes isolated from wild-type mice, while these effects were significantly decreased in adipocytes isolated from ErbB4 deletion mice. In conclusion, our results indicate that ErbB4 may play an important role in glucose homeostasis and lipogenesis. ErbB4 deficiency-related obesity and adipose tissue inflammation may contribute to the development of MetS.

Renal epidermal growth factor receptor (EGFR) signaling is activated in models of diabetic nephropathy (DN), and inhibition of EGFR signaling pathway protects against the development of DN. We have now determined that in cultured podocytes, high glucose led to increases in activation of EGFR signaling but decreases in autophagy activity as indicated by decreased beclin-1 and inhibition of LC3B autophagosome formation as well as increased rubicon (an autophagy inhibitor) and SQSTM1 (autophagy substrate). Either genetic (siEGFR) or pharmacologic (AG1478) inhibition of EGFR signaling attenuated the decreased autophagy activity. In addition, rubicon siRNA knockdown prevented high glucose-induced inhibition of autophagy in podocytes. We further examined whether selective EGFR deletion in podocytes affected the progression of DN in type II diabetes. Selective podocyte EGFR deletion had no effect on body weight or fasting blood sugars in either db/db mice or nos3-/-; db/db mice, a model of accelerated type II DN. However selective podocyte EGFR deletion led to relative podocyte preservation and marked reduction in albuminuria and glomerulosclerosis, renal proinflammatory cytokine/chemokine expression and decreased pro-fibrotic and fibrotic components in nos3-/-; db/db mice. Podocyte EGFR deletion led to decreased podocyte expression of rubicon, in association with increased podocyte autophagy activity. Therefore, activation of EGFR signaling in podocytes contributes to progression of DN at least in part by increasing rubicon expression, leading to subsequent autophagy inhibition and podocyte injury.

BACKGROUND: AKI is characterized by abrupt and reversible kidney dysfunction, and incomplete recovery leads to chronic kidney injury. Previous studies by us and others have indicated that macrophage infiltration and polarization play key roles in recovery from AKI. The role in AKI recovery played by IFN regulatory factor 4 (IRF4), a mediator of polarization of macrophages to the M2 phenotype, is unclear. METHODS: We used mice with myeloid or macrophage cell–specific deletion of Irf4 (MΦ Irf4 (−/−)) to evaluate Irf4’s role in renal macrophage polarization and development of fibrosis after severe AKI. RESULTS: Surprisingly, although macrophage Irf4 deletion had a minimal effect on early renal functional recovery from AKI, it resulted in decreased renal fibrosis 4 weeks after severe AKI, in association with less-activated macrophages. Macrophage Irf4 deletion also protected against renal fibrosis in unilateral ureteral obstruction. Bone marrow–derived monocytes (BMDMs) from MΦ Irf4 (−/−) mice had diminished chemotactic responses to macrophage chemoattractants, with decreased activation of AKT and PI3 kinase and increased PTEN expression. PI3K and AKT inhibitors markedly decreased chemotaxis in wild-type BMDMs, and in a cultured macrophage cell line. There was significant inhibition of homing of labeled Irf4 (−/−) BMDMs to postischemic kidneys. Renal macrophage infiltration in response to AKI was markedly decreased in MΦ Irf4 (−/−) mice or in wild-type mice with inhibition of AKT activity. CONCLUSIONS: Deletion of Irf4 from myeloid cells protected against development of tubulointerstitial fibrosis after severe ischemic renal injury in mice, due primarily to inhibition of AKT-mediated monocyte recruitment to the injured kidney and reduced activation and subsequent polarization into a profibrotic M2 phenotype.

Renal epidermal growth factor receptor (EGFR) signaling is activated in models of diabetic nephropathy (DN), and inhibition of the EGFR signaling pathway protects against the development of DN. We have now determined that in cultured podocytes, high glucose led to increases in activation of EGFR signaling but decreases in autophagy activity as indicated by decreased beclin-1 and inhibition of LC3B autophagosome formation as well as increased rubicon (an autophagy inhibitor) and SQSTM1 (autophagy substrate). Either genetic (small interfering [si]EGFR) or pharmacologic (AG1478) inhibition of EGFR signaling attenuated the decreased autophagy activity. In addition, rubicon siRNA knockdown prevented high glucose–induced inhibition of autophagy in podocytes. We further examined whether selective EGFR deletion in podocytes affected the progression of DN in type 2 diabetes. Selective podocyte EGFR deletion had no effect on body weight or fasting blood sugars in either db/db mice or nos3−/−; db/db mice, a model of accelerated type 2 DN. However selective podocyte EGFR deletion led to relative podocyte preservation and marked reduction in albuminuria and glomerulosclerosis, renal proinflammatory cytokine/chemokine expression, and decreased profibrotic and fibrotic components in nos3−/−; db/db mice. Podocyte EGFR deletion led to decreased podocyte expression of rubicon, in association with increased podocyte autophagy activity. Therefore, activation of EGFR signaling in podocytes contributes to progression of DN at least in part by increasing rubicon expression, leading to subsequent autophagy inhibition and podocyte injury.

Scientific talents can make great contributions, including scientific breakthrough innovations and discoveries, and coordinate and guide the actions of many others, propelling the scientific knowledge frontier. We investigate international scientific talent migration from 2001 to 2013 with the quantitative method. The relationship between complex network and international talent migration is introduced. Considering most of talents migrate between some countries with good economy and innovation, the migration network including 37 countries is analysed. The countries are noted by nodes of the migration network, and the migratory flow of talents from one country to another country is viewed as the directed weight edge between the corresponding nodes. The discrete dynamics of talent migration under complex network is proposed. The unknown parameters of the proposed model are identified. The overall situation and time evolution of international talent migration from 2001 to 2013 are given from the discussion on the indicators of complex network. Furthermore, we study the talent migration flows in the view of obstacle factors. It is found that the great majority of talents migrate between developed countries and emerging economies from 2001 to 2013, and this phenomenon becomes more significant. The USA has attracted a great number of talents all over the world, and the country is also the ideal destination for talents who want to live or work in another country for more job opportunities, attractive payment, and better innovation environment. China and India begin to attract talents. Talents emigrate from more and more original countries. It becomes more convenient for talents to immigrate to other countries. The effectiveness of obstructs to migration has become weakening. For immigrating to a certain country, the obstacles have a relationship with the country’s innovation.

Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of diabetic nephropathy and renal fibrosis; however, the causative role of sustained EGFR activation is unclear. Here, we generated a novel kidney fibrotic mouse model of persistent EGFR activation by selectively expressing the EGFR ligand, human heparin-binding EGF-like growth factor (hHB-EGF), in renal proximal tubule epithelium. hHB-EGF expression increased tyrosine kinase phosphorylation of EGFR and the subsequent activation of downstream signaling pathways, including ERK and AKT, as well as the profibrotic TGF-β1/SMAD pathway. Epithelial-specific activation of EGFR was sufficient to promote spontaneous and progressive renal tubulointerstitial fibrosis, as characterized by increased collagen deposition, immune cell infiltration, and α-smooth muscle actin (α-SMA)–positive myofibroblasts. Tubule-specific EGFR activation promoted epithelial dedifferentiation and cell-cycle arrest. Furthermore, EGFR activation in epithelial cells promoted the proliferation of α-SMA+ myofibroblasts in a paracrine manner. Genetic or pharmacologic inhibition of EGFR tyrosine kinase activity or downstream MEK activity attenuated the fibrotic phenotype. This study provides definitive evidence that sustained activation of EGFR in proximal epithelia is sufficient to cause spontaneous, progressive renal tubulointerstitial fibrosis, evident by epithelial dedifferentiation, increased myofibroblasts, immune cell infiltration, and increased matrix deposition.—Overstreet, J. M., Wang, Y., Wang, X., Niu, A., Gewin, L. S., Yao, B., Harris, R. C., Zhang, M.-Z. Selective activation of epidermal growth factor receptor in renal proximal tubule induces tubulointerstitial fibrosis.

Summary This paper provides unified solutions for distributed attitude and translation consensus problems for networked fully actuated rigid bodies under the fixed and undirected communication topology with the tool of unit dual quaternion. We investigate two kinds of consensus, that is, leaderless consensus and leader-following consensus with a static leader. Firstly, the dynamics of rigid bodies are presented by unit dual quaternion. The control inputs of rigid bodies are also obtained from unit dual quaternion. Secondly, we propose a distributed consensus law in the form of dual quaternion to guarantee that the attitudes and translations of all rigid bodies reach consensus, respectively, without a leader. Thirdly, the leader-following consensus problem with a static leader is studied. With the proposed leader-following consensus law, the states of all rigid bodies converge to the corresponding states of the static leader, including the attitude and the translation. Finally, numerical examples are provided to validate the effectiveness of the theoretical results. Copyright © 2017 John Wiley & Sons, Ltd.

Cytokines IL-4 and IL-13 play important roles in polarization of macrophages/dendritic cells to an M2 phenotype, which is important for recovery from acute kidney injury. Both IL-4 and IL-13 activate JAK3/STAT6 signaling. In mice with diphtheria toxin receptor expression in proximal tubules (selective injury model), a relatively selective JAK3 inhibitor, tofacitinib, led to more severe kidney injury, delayed recovery from acute kidney injury, increased inflammatory M1 phenotype markers and decreased reparative M2 phenotype markers of macrophages/dendritic cells, and development of more severe renal fibrosis after diphtheria toxin administration. Similarly, there was delayed recovery and increased tubulointerstitial fibrosis in these diphtheria toxin-treated mice following tamoxifen-induced deletion of both IL-4 and IL-13, with increased levels of M1 and decreased levels of M2 markers in the macrophages/dendritic cells. Furthermore, deletion of IL-4 and IL-13 led to a decrease of tissue reparative M2a phenotype markers but had no effect on anti-inflammatory M2c phenotype markers. Deletion of IL-4 and IL-13 also inhibited recovery from ischemia-reperfusion injury in association with increased M1 and decreased M2 markers and promoted subsequent tubulointerstitial fibrosis. Thus, IL-4 and IL-13 are required to effectively polarize macrophages/dendritic cells to an M2a phenotype and to promote recovery from acute kidney injury.

Diabetic nephropathy (DN) is characterized by increased macrophage infiltration, and proinflammatory M1 macrophages contribute to development of DN. Previous studies by us and others have reported that macrophage cyclooxygenase-2 (COX-2) plays a role in polarization and maintenance of a macrophage tissue-reparative M2 phenotype. We examined the effects of macrophage COX-2 on development of DN in type 1 diabetes. Cultured macrophages with COX-2 deletion exhibited an M1 phenotype, as demonstrated by higher inducible nitric oxide synthase and nuclear factor-κB levels but lower interleukin-4 receptor-α levels. Compared with corresponding wild-type diabetic mice, mice with COX-2 deletion in hematopoietic cells (COX-2 knockout bone marrow transplantation) or macrophages (CD11b-Cre COX2f/f) developed severe DN, as indicated by increased albuminuria, fibrosis, and renal infiltration of T cells, neutrophils, and macrophages. Although diabetic kidneys with macrophage COX-2 deletion had more macrophage infiltration, they had fewer renal M2 macrophages. Diabetic kidneys with macrophage COX-2 deletion also had increased endoplasmic reticulum stress and decreased number of podocytes. Similar results were found in diabetic mice with macrophage PGE2 receptor subtype 4 deletion. In summary, these studies have demonstrated an important but unexpected role for macrophage COX-2/prostaglandin E2/PGE2 receptor subtype 4 signaling to lessen progression of diabetic kidney disease, unlike the pathogenic effects of increased COX-2 expression in intrinsic renal cells.

Background Sex differences mediating predisposition to kidney injury are well known, with evidence indicating lower CKD incidence rates and slower decline in renal function in nondiabetic CKD for premenopausal women compared with men. However, signaling pathways involved have not been elucidated to date. The EGF receptor (EGFR) is widely expressed in the kidney in glomeruli and tubules, and persistent and dysregulated EGFR activation mediates progressive renal injury. Methods To investigate the sex differences in response to renal injury, we examined EGFR expression in mice, in human kidney tissue, and in cultured cell lines. Results In wild type mice, renal mRNA and protein EGFR levels were comparable in males and females at postnatal day 7 but were significantly lower in age-matched adult females than in adult males. Similar gender differences in renal EGFR expression were detected in normal adult human kidneys. In Dsk5 mutant mice with a gain-of-function allele that increases basal EGFR kinase activity, males had progressive glomerulopathy, albuminuria, loss of podocytes, and tubulointerstitial fibrosis, but female Dsk5 mice had minimal kidney injury. Oophorectomy had no effect on renal EGFR levels in female Dsk5 mice, while castration protected against the kidney injury in male Dsk5 mice, in association with a reduction in EGFR expression to levels seen in females. Conversely, testosterone increased EGFR expression and renal injury in female Dsk5 mice. Testosterone directly stimulated EGFR expression in cultured kidney cells. Conclusions These studies indicate that differential renal EGFR expression plays a role in the sex differences in susceptibility to progressive kidney injury that may be mediated at least in part by testosterone.

TGF-β signals through a receptor complex composed of 2 type I and 2 type II (TGF-βRII) subunits. We investigated the role of macrophage TGF-β signaling in fibrosis after AKI in mice with selective monocyte/macrophage TGF-βRII deletion (macrophage TGF-βRII-/- mice). Four weeks after injury, renal TGF-β1 expression and fibrosis were higher in WT mice than macrophage TGF-βRII-/- mice, which had decreased renal macrophages. The in vitro chemotactic response to f-Met-Leu-Phe was comparable between bone marrow-derived monocytes (BMMs) from WT and macrophage TGF-βRII-/- mice, but TGF-βRII-/- BMMs did not respond to TGF-β. We then implanted Matrigel plugs suffused with either f-Met-Leu-Phe or TGF-β1 into WT or macrophage TGF-βRII-/- mice. After 6 days, f-Met-Leu-Phe induced similar macrophage infiltration into the Matrigel plugs of WT and macrophage TGF-βRII-/- mice, but TGF-β induced infiltration only in WT mice. We further determined the number of labeled WT or TGF-βRII-/- BMMs infiltrating into WT kidneys 20 days after ischemic injury. There were more labeled WT BMMs than TGF-βRII-/- BMMs. Therefore, macrophage TGF-βRII deletion protects against the development of tubulointerstitial fibrosis following severe ischemic renal injury. Chemoattraction of macrophages to the injured kidney through a TGF-β/TGF-βRII axis is a heretofore undescribed mechanism by which TGF-β can mediate renal fibrosis during progressive renal injury.

This paper concentrates on the quaternion-based attitude synchronisation problems of networked rigid bodies under fixed and undirected communication topology without relative angular measurements in the presence of actuator saturation. We first consider the leaderless attitude synchronisation problem with zero final angular velocity. In this case, we not only discuss the performance under the acyclic communication topology with the proposed bounded control algorithm, but also analyse that if there exist cycles in the topology, the proposed bounded algorithm guarantees that all equilibrium points are unstable except that the attitudes of networked rigid bodies achieve synchronisation. We also expand the result to the case of attitude tracking synchronisation with a static leader in the presence of actuator saturation. Next, the tracking synchronisation problem with the desired time-varying attitude is addressed in the presence of actuator saturation. Numerical examples are provided to validate the effectiveness of the proposed bounded schemes and illustrate the performances of multiple rigid bodies.

Infiltrating cells play an important role in both the development of and recovery from acute kidney injury (AKI). Macrophages and renal dendritic cells are of particular interest because they can exhibit distinctly different functional phenotypes, broadly characterized as proinflammatory (M1) or tissue reparative (M2). Resident renal macrophages and dendritic cells participate in recovery from AKI in response to either ischemia/reperfusion or a model of selective proximal tubule injury induced by diphtheria-toxin-induced apoptosis in transgenic mice expressing the human diphtheria toxin receptor on proximal tubule cells. Colony-stimulating factor-1 (CSF-1) is an important factor mediating the recovery from AKI, and CSF-1 can stimulate macrophage and dendritic cell proliferation and polarization during the recovery phase of AKI. The kidney, and specifically the proximal tubule, is a major source of intrarenal CSF-1 production in response to AKI. We induced selective deletion of proximal tubule CSF-1 to determine its role in expansion and proliferation of renal macrophages and dendritic cells and in recovery from AKI. In both models of AKI, there was decreased M2 polarization, delayed functional and structural recovery, and increased tubulointerstitial fibrosis. Thus, intrarenal CSF-1 is an important mediator of macrophage/dendritic cell polarization and recovery from AKI.

Event-triggered control approaches of networked control systems are motivated by applications of embedded microprocessors with limited computation and storage resources . This paper investigates an event-triggered consensus control scheme with random switching directed topologies and time-varying transmission delay in a general class of networked control systems. A distributed sampling scheme triggering at node's independent time instants is designed for updates of control inputs. The desired properties of the resulted error dynamical system, such as stability and convergence can be preserved. It is not only proven that the event-triggered consensus is reachable, but also given an estimation of the convergence rate. It is shown that before the consensus is achieved, the inner-event interval is lower bounded by a positive constant, which excludes the Zeno behavior. The results are also applied to other special cases including time-delay free, fixed topology and leader-following consensus cases. Numerical simulation examples are presented to demonstrate the correctness of the theoretical results.

A simple colorimetric aptasensor system has been developed to detect Vibrio parahemolyticus. Magnetic nanoparticles (MNPs) are synthesized and conjugated with specific aptamers against target and used as capture probes. In addition, this method employs gold nanoparticles (AuNPs) as carriers of horseradish peroxidase (HRP) and aptamers, which served as signal probes. In the presence of target, a "sandwich-type" complex of AuNPs-HRP-aptamer-target-aptamer-MNPs is formed through specific recognition of aptamers and corresponding target. As a result, HRP molecules confined at the surface of the "sandwich" complexes catalyze the enzyme substrate, 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 and generate an optical signal. Under optimal conditions, the signals are linearly dependent on V. parahemolyticus concentrations from 10 to 10(6) colony-forming units (cfu)/mL in a logarithmic plot, with a limit of detection of 10 cfu/mL. Owing to AuNPs, a large amount of HRP could be loaded, resulting in an amplified signal, and the sensitivity would be improved. This strategy has the potential of being extended to the construction of simple monitor systems for a variety of biomolecules related to food safety.

A disintegrin and metalloproteinase domain 10 (Adam10), a member of the ADAM family of cell membrane-anchored proteins, has been linked to the regulation of the Notch, EGF, E-cadherin, and other signaling pathways. However, it is unclear what role Adam10 has in the kidney in vivo. In this study, we showed that Adam10 deficiency in ureteric bud (UB) derivatives leads to a decrease in urinary concentrating ability, polyuria, and hydronephrosis in mice. Furthermore, Adam10 deficiency led to a reduction in the percentage of aquaporin 2 (Aqp2)(+) principal cells (PCs) in the collecting ducts that was accompanied by a proportional increase in the percentage of intercalated cells (ICs). This increase was more prominent in type A ICs than in type B ICs. Foxi1, a transcription factor important for the differentiation of ICs, was upregulated in the Adam10 mutants. The observed reduction of Notch activity in Adam10 mutant collecting duct epithelium and the similar reduction of PC/IC ratios in the collecting ducts in mice deficient for mindbomb E3 ubiquitin protein ligase 1, a key regulator of the Notch and Wnt/receptor-like tyrosine kinase signaling pathways, suggest that Adam10 regulates cell fate determination through the activation of Notch signaling, probably through the regulation of Foxi1 expression. However, phenotypic differences between the Adam10 mutants, the Mib1 mutants, and the Foxi1 mutants suggest that the functions of Adam10 in determining the fate of collecting duct cells are more complex than those of a simple upstream factor in a linear pathway involving Notch and Foxi1.

This paper addresses the distributed consensus problem for multiple rigid-bodies under directed communication topology having a spanning tree with the tool of unit dual quaternion. The dynamics of rigid-bodies in 3-D are represented by unit dual quaternion with notion concision and nonsingularity. A distritbuted consensus algorithm is proposed to control attitudes and positions of all rigidbodies to the same values. We also expand the leaderless distributed algorithm to tracking consensus case with a static leader. Finally, the proposed control algorithms are simulated to illustrate the theoretical results.

Colorectal cancer (CRC) continues to be a major cause of morbidity and mortality. The arachidonic acid (AA) pathway and linoleic acid (LA) pathway have been implicated as important contributors to CRC development and growth. Human 15-lipoxygenase 1 (15-LOX-1) converts LA to anti-tumor 13-S-hydroxyoctadecadienoic acid (13-HODE)and 15-LOX-2 converts AA to 15-hydroxyeicosatetraenoic acid (15-HETE). In addition, human 12-LOX metabolizes AA to pro-tumor 12-HETE. In rodents, the function of 12-LOX and 15-LOX-1 and 15-LOX-2 is carried out by a single enzyme, 12/15-LOX. As a result, conflicting conclusions concerning the role of 12-LOX and 15-LOX have been obtained in animal studies. In the present studies, we determined that PD146176, a selective 15-LOX-1 inhibitor, markedly suppressed 13-HODE generation in human colon cancer HCA-7 cells and HCA-7 tumors, in association with increased tumor growth. In contrast, PD146176 treatment led to decreases in 12-HETE generation in mouse colon cancer MC38 cells and MC38 tumors, in association with tumor inhibition. Surprisingly, deletion of host 12/15-LOX alone led to increased MC38 tumor growth, in association with decreased tumor 13-HODE levels, possibly due to inhibition of 12/15-LOX activity in stroma. Therefore, the effect of 12/15-LOX on colorectal tumorigenesis in mouse models could be affected by tumor cell type (human or mouse), relative 12/15 LOX activity in tumor cells and stroma as well as the relative tumor 13-HODE and 12-HETE levels.

Big data and cloud computing, which can help China to implement innovation-driven development strategy and promote industrial transformation and upgrading, is a new and emerging industrial field in China. Educated, productive and healthy workforces are necessary factor to develop big data and cloud computing industry, especially top talents are essential. Therefore, a three-step method named 3-F has been introduced to help describing the distribution of top talents globally and making decision whether they are needed in China. The 3-F method relies on calculating the brain gain index to analysis the top talent introduction demand of a country. Firstly, Focus on the high-frequency keywords of a specific field by retrieving the highly cited papers. Secondly, using those keywords to Find out the top talents of this specific field in the Web of Science. Finally, Figure out the brain gain index to estimate whether a country need to introduce top talents of a specific field abroad. The result showed that the brain gain index value of China's big data and cloud computing field was 2.61, which means China need to introduce top talents abroad. Besides P. R. China, those top talents mainly distributed in the United States, the United Kingdom, Germany, Netherlands and France.

The mobility of researchers helps knowledge transmission and collaboration in the process of globalization, and is becoming a major policy objective in recent years. Research system and the individual researcher can benefit from mobility. As a developing country, China is trying to do more to learn from developed countries, including academic exchange. The US is the world's largest talent magnet. It is meaningful to study the researcher mobility between China and the US. Based on Scopus author data, the researchers are divided into 3 groups on the perspective of China, which are outflow group, transitory group and inflow group. According to a set of 728421 active researchers in this study, China has a net total inflow of researchers from the US in the period of 1996 to 2015. Different classes of researchers performances differently in production quantity and quality. The Brain Inflow produced most paper among all the researchers; the Transitory Brain Mobility has highest quality production among the 3 groups. The production quality of Brain Outflow is much better than the Brain Inflow. The characteristic of researcher movement between the two countries and its impacts should be better understood to help talent development.

In this paper, we propose a control algorithm to achieve consensus of multi-agent systems with time delay and heterogeneous topologies. The proposed control scheme is capable of dealing with both velocity and position time delay. The stability analysis is conducted based on Lyapunov method and graph theory and provides the proof that consensus of multi-agent systems can be achieve if the time delay is sufficiently small. Simulation results confirm our claims that positions and velocities of all agents can achieve consensus under the proposed control laws.

In this paper, we investigate the distributed synchronization problem for multiple fully actuated rigid bodies without a leader. A new mathematical tool-dual quaternion is employed to design the distributed control law. The definition and some properties about dual quaternion are introduced. A distributed control law is proposed to control the attitude and translation of these rigid bodies simultaneously with notion concision and non-singularity. And the analysis based on dual quaternion is a unified solution for the attitude and translation. Finally, the proposed control algorithm is simulated to illustrate the theoretical results.

In this paper, we propose dual quaternion based dynamic output feedbacks for the translational and rotational stability problem of a rigid body without linear velocity and angular velocity measurements. Dual quaternion is a new kind of tools to express the motion of rigid bodies in 3D space, including translation and rotation. Our approach consists of an output feedback controller and introducing an auxiliary system whose input is the relative error between the states of the rigid body and the states of the auxiliary system. The resulting linear and angular velocity free control algorithm guarantees the asymptotical stability of the rigid body. Next, a stability algorithm based on unit dual quaternion is also proposed for the rigid body under its general dynamics. One simulation is provided to show the effectiveness of the proposed control algorithm.

This paper focuses on the consensus of multi-agent systems with unknown nonlinear dynamics under heterogenous topologies. The stability analysis is based on Lyapunov method and graph theory. Sufficient conditions in terms of linear matrix inequality (LMI) are given to guarantee the consensus of the multi-agent systems. The algorithms of none-zero velocity consensus and the zero velocity consensus are provided in this paper. We give two simulations at the end of this paper, showing the states of positions and velocities of all agents can reach consensus, under the proposed control laws.

Simulation of unmanned aerial vehicle (UAV) flight environment is one of the key technologies in three-dimensional path planning. We adopt efficient intelligent algorithm for path planning in the simulation environment. Basic ant colony algorithm is easy to reach local optimum prematurely with slow convergence speed and long computing time. In this paper, information of the shortest distance is sent to the system for controlling, and optimize the node selection method by improving the calculation of state transition probability. In addition, the local updating rules are improved in order to improve the efficiency of the algorithm. The simulation results show that the improved ant colony algorithm is used to meet the requirements of the unmanned aerial vehicle flight track.

This paper presents a general algorithm to track the line on the ground based on computer vision, which utilizes Raspberry Pi 2 to complete the image processing. The algorithm accomplishes image processing firstly, then recognizes the line by edge detection and scanning model. The proposed algorithm can be used in a variety of platforms including intelligent car system, robot platform, UAV platform and other mobile platforms. In this paper, the algorithm is verified by quadrotor platform and achieves great line-tracking effect by tuning parameters. Series of experiments show that the algorithm has great validity, robustness, and generality.

© 2016 IEEE. In this paper, the tracking problem for a rigid spacecraft with input saturation is investigated. Due to the complexity of the dynamic of a rigid spacecraft, a hierarchical control scheme, dividing the model of a rigid spacecraft into translational level and attitude level, is designed. The controllers for translational dynamic and attitude dynamic of the six-freedom-degrees spacecraft are successively proposed respectively. The input saturation is also considered in designing the two controllers. For translational level, a kind of special saturation function is employed to get the controller whose amplitude is constrained. For the attitude dynamic, a new adaptive quaternion-based control scheme is proposed to withstand the effect of bounded uncertain items and input saturation. Finally, simulation results are provided to show the effectiveness of the proposed scheme.

This paper proposes a scheme using open source autopilot controller and on-board computer (i.e. Raspberry Pi 2) to realize vision tracking flight mission based on computer vision. System structure design, image processing and controller are introduced respectively. The proposed image processing algorithm can reduce computational work and also the well designed controller can realize line tracking. Experiment result based on DJI F450 quadrotor is provided to demonstrate the effectiveness of the proposed scheme.

The cytochrome P450 epoxygenase-dependent arachidonic acid metabolites, epoxyeicosatrienoic acids (EETs), are potent survival factors and mitogens for renal epithelial cells, but the molecular identity in the cells that initiates the mitogenic signaling of EETs has remained elusive. We screened kidney cell lines for the expression of G-protein-coupled receptor 40 (GPR40) and found that the porcine renal tubular epithelial cell line LLCPKcl4, which has been previously demonstrated to be sensitive to the mitogenic effect of EETs, expresses higher levels of GPR40 mRNA and protein than the human embryonic kidney cell line HEK293. EETs induced only a weak mitogenic EGFR signaling and mild cell proliferation in HEK293 cells. To determine whether GPR40 expression level is what mediates the mitogenic sensitivity of cells to EETs, we created a human GPR40 (hGPR40) cDNA construct and transfected it into HEK293 cells and picked up a number of stable transfectants. We found that GPR40 overexpression in HEK293 cells indeed significantly enhanced EET-induced cell proliferation and markedly augmented EGFR phosphorylation ERK activation, which were inhibited by the EGFR tyrosine kinase inhibitor, AG1478, or the HB-EGF inhibitor, CRM197. EETs significantly enhanced release of soluble HB-EGF, a natural ligand of EGFR, into the culture medium of hGPR40-transfected HEK293 cells, compared to empty vector-transfected cells. In mouse kidneys, markedly higher level of GPR40 protein was found in the cortex and outer stripe of outer medulla compared to the inner stripe of outer medulla and inner medulla. In situ hybridization confirmed that GPR40 mRNA was localized to a subset of renal tubules in the kidney, including the cortical collecting duct. Thus, this study provides the first demonstration that upregulation of GPR40 expression enhances the mitogenic response to EETs and a relatively high expression level of GPR40 is detected in a subset of tubules including cortical collecting ducts in the mammalian kidney.