RESUMEN
Renewable electricity-driven seawater splitting presents a green, effective, and promising strategy for building hydrogen (H2)-based energy systems (e.g., storing wind power as H2), especially in many coastal cities. The abundance of Cl- in seawater, however, will cause severe corrosion of anode catalyst during the seawater electrolysis, and thus affect the long-term stability of the catalyst. Herein, seawater oxidation performances of NiFe layered double hydroxides (LDH), a classic oxygen (O2) evolution material, can be boosted by employing tungstate (WO4 2-) as the intercalated guest. Notably, insertion of WO4 2- to LDH layers upgrades the reaction kinetics and selectivity, attaining higher current densities with ≈100% O2 generation efficiency in alkaline seawater. Moreover, after a 350 h test at 1000 mA cm-2, only trace active chlorine can be detected in the electrolyte. Additionally, O2 evolution follows lattice oxygen mechanism on NiFe LDH with intercalated WO4 2-.
RESUMEN
The solid electrolyte interphase (SEI) membrane on the Li metal anode tends to breakdown and undergo reconstruction during operation, causing Li metal batteries to experience accelerated decay. Notably, an SEI membrane with self-healing characteristics can help considerably in stabilizing the Li-electrolyte interface; however, uniformly fixing the repairing agent onto the anode remains a challenging task. By leveraging the noteworthy film-forming attributes of bis(fluorosulfonyl)imide (FSI-) anions and the photopolymerization property of the vinyl group, the ionic liquid 1-vinyl-3-methylimidazolium bis(fluorosulfonyl)imide (VMI-FSI) was crosslinked with polyethylene oxide (PEO) in this study to form a self-healing film fixing FSI- groups as the repairing agent. When they encounter lithium metal, the FSI- groups are chemically decomposed into LiF & Li3N, which assist forming SEI membrane on lithium sheet and repairing SEI membrane in the cracks lacerated by lithium dendrite. Furthermore, the FSI- anions exchanged from film are electrochemically decomposed to generate inorganic salts to strengthen the SEI membrane. Benefiting from the self-healing behavior of the film, Li/LiCoO2 cells with the loading of 16.3â mg cm-2 exhibit the initial discharge capacities of 183.0â mAh â g-1 and are stably operated for 500â cycles with the retention rates of 81.4 % and the average coulombic efficiency of 99.97 %, operated between 3.0-4.5â V vs. Li+/Li. This study presents a new design approach for self-healing Li metal anodes and durable lithium metal battery.
RESUMEN
With the development of deep learning, the use of convolutional neural networks (CNN) to improve the land cover classification accuracy of hyperspectral remote sensing images (HSRSI) has become a research hotspot. In HSRSI semantics segmentation, the traditional dataset partition method may cause information leakage, which poses challenges for a fair comparison between models. The performance of the model based on "convolutional-pooling-fully connected" structure is limited by small sample sizes and high dimensions of HSRSI. Moreover, most current studies did not involve how to choose the number of principal components with the application of the principal component analysis (PCA) to reduce dimensionality. To overcome the above challenges, firstly, the non-overlapping sliding window strategy combined with the judgment mechanism is introduced, used to split the hyperspectral dataset. Then, a PSE-UNet model for HSRSI semantic segmentation is designed by combining PCA, the attention mechanism, and UNet, and the factors affecting the performance of PSE-UNet are analyzed. Finally, the cumulative variance contribution rate (CVCR) is introduced as a dimensionality reduction metric of PCA to study the Hughes phenomenon. The experimental results with the Salinas dataset show that the PSE-UNet is superior to other semantic segmentation algorithms and the results can provide a reference for HSRSI semantic segmentation.
Asunto(s)
Artrópodos , Imágenes Hiperespectrales , Animales , Semántica , Algoritmos , Juicio , Procesamiento de Imagen Asistido por ComputadorRESUMEN
Solving the eigenproblems of Hermitian matrices is a significant problem in many fields. The quantum resonant transition (QRT) algorithm has been proposed and demonstrated to solve this problem using quantum devices. To better realize the capabilities of the QRT with recent quantum devices, we improve this algorithm and develop a new procedure to reduce the time complexity. Compared with the original algorithm, it saves one qubit and reduces the complexity with error ϵ from O(1/ϵ2) to O(1/ϵ). Thanks to these optimizations, we can obtain the energy spectrum and ground state of the effective Hamiltonian of the water molecule more accurately and in only 20 percent of the time in a four-qubit processor compared to previous work. More generally, for non-Hermitian matrices, a singular-value decomposition has essential applications in more areas, such as recommendation systems and principal component analysis. The QRT has also been used to prepare singular vectors corresponding to the largest singular values, demonstrating its potential for applications in quantum machine learning.
RESUMEN
Studies have reported that miR-195-5p plays a role in the Hirschsprung disease (HSCR). Our previous work found GDNF family receptor alpha 4 (GFRA4) is also associated with HSCR. In this study, we focused on whether miR-195-5p induces the absence of enteric neurons and enteric neural crest in HSCR by regulating GFRA4. The expression levels of GFRA4 and miR-195-5p in colon tissues were evaluated by real-time PCR (RT-PCR) assay. We overexpressed GFRA4 or miR-195-5p in SH-SY5Y cells, the cell proliferation, cell cycle, apoptosis and invasion were subsequently investigated by CCK-8 assay, EdU staining, Flow cytometry analysis and Transwell assay, respectively. We also established the xenograft model to detect the effect of miR-195-5p on tumor growth and GFRA4 and p-RET expressions. GFRA4 expression was significantly downregulated in the HSCR colon tissues when compared with that in the control tissues. Overexpression of GFRA4 significantly promoted proliferation, invasion and cell cycle arrest, and inhibited apoptosis of SH-SY5Y cells. We also proved that GFRA4 is a direct target of miR-195-5p, and miR-195-5p inhibited proliferation, invasion, cell cycle arrest and differentiation, and accelerated apoptosis in SH-SY5Y cells which can be reversed by GFRA4 overexpression. Furthermore, we demonstrated that miR-195-5p suppressed tumor growth, and observably decreased GFRA4 and p-RET expressions. Our findings suggest that miR-195-5p plays an important role in the pathogenesis of HSCR. MiR-195-5p inhibited proliferation, invasion and cell cycle arrest, and accelerated apoptosis of nerve cells by targeting GFRA4.
Asunto(s)
Proliferación Celular , Sistema Nervioso Entérico/metabolismo , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Enfermedad de Hirschsprung/metabolismo , MicroARNs/metabolismo , Neuronas/metabolismo , Animales , Línea Celular Tumoral , Sistema Nervioso Entérico/patología , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/patología , Humanos , Ratones , MicroARNs/genética , Neuronas/patologíaRESUMEN
ABSTRACT: Chinese people have used the root of Salvia miltiorrhiza Bunge (called "Danshen" in Chinese) for centuries as an anticancer agent, anti-inflammatory agent, antioxidant, and cardiovascular disease drug. In addition, Danshen is considered to be a drug that can improve ischemia/reperfusion (I/R)-induced myocardium injury in traditional Chinese medicine. However, Danshen is a mixture that includes various bioactive substances. In this study, we aimed to identify the protective component and mechanism of Danshen on myocardium through network pharmacology and molecular simulation methods. First, cryptotanshinone (CTS) was identified as a potential active compound from Danshen that was associated with apoptosis by a network pharmacology approach. Subsequently, biological experiments validated that CTS inhibited ischemia/reperfusion-induced cardiomyocyte apoptosis in vivo and in vitro. Molecular docking techniques were used to screen key target information. Based on the simulative results, MAPKs were verified as well-connected molecules of CTS. Western blotting assays also demonstrated that CTS could enhance MAPK expression. Furthermore, we demonstrated that inhibition of the MAPK pathway reversed the CTS-mediated effect on cardiomyocyte apoptosis. Altogether, our work screened out CTS from Danshen and demonstrated that it protected cardiomyocytes from apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Fenantrenos/farmacología , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos C57BL , Proteína Quinasa 3 Activada por Mitógenos/genética , Simulación del Acoplamiento Molecular , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Farmacología en Red , Salvia miltiorrhiza , Transducción de SeñalRESUMEN
It is difficult to calculate the energy levels and eigenstates of a large physical system on a classical computer because of the exponentially growing size of the Hilbert space. In this work, we experimentally demonstrate a quantum algorithm which could solve this problem via simulated resonant transitions. Using a four-qubit quantum simulator in which two qubits are used as ancillas for control and measurement, we obtain the energy spectrum of a 2-qubit low-energy effective Hamiltonian of the water molecule. The simulated transitions allow the state of the quantum simulator to transform and access large regions of the Hilbert space, including states that have no overlap with the initial state. Furthermore, we make use of this algorithm to efficiently prepare specific eigenstates on the simulator according to the measured eigenenergies.
RESUMEN
PURPOSE: The purpose of this study was to investigate the comparison of AR and AUS in predicting prognosis in infants with necrotizing enterocolitis. METHODS: All patients were diagnosed as NEC at the department of general surgery and neonatal surgery, Qilu children's hospital between 1st, Jun, 2010 and 30th, Dec, 2016. The logistic regression analysis and the area under ROC curve (AUC)s were also used to compare the prognostic values of radiograph and sonograph for NEC. RESULTS: Throughout the study period, 86 preterm neonates were hospitalized with diagnosis of definite NEC. Among these patients, 39 infants (45.3%) required surgical treatment. After adjusting for competing sonographic factors, we identified that thick bowel wall (more than 2.5 mm) (p = 0.001, HR: 1.849), intramural gas (pneumatosis intestinalis) (p = 0.017, HR: 1.265), portal venous gas (p = 0.002, HR: 1.824), and reduced peristalsis (p = 0.021, HR: 1.544) were independent prognostic factors associated with NEC. After adjusting for competing radiographic factors, we identified that free peritoneal gas (p = 0.007, HR: 1.472), portal venous gas (p = 0.012, HR: 1.649), and dilatation and elongation (p = 0.025, HR: 1.327). Moreover, we found that the AUROC for AR logistic model was 0.745 (95% CI 0.629-0.812), which was significant lower than the AUS logistic model (AUROC: 0.857, 95% CI 0.802-0.946) for predicting prognosis of NEC. CONCLUSIONS: In conclusion, we found that several radiographic and sonographic parameters were associated with the prognosis of patients with NEC. The AUS model based on the logistic regression analysis was significant superior to the AR model in the prognostic prediction of NEC.
Asunto(s)
Enterocolitis Necrotizante/diagnóstico , Recien Nacido Prematuro , Intestinos/diagnóstico por imagen , Radiografía Abdominal/métodos , Ultrasonografía/métodos , Adulto , China/epidemiología , Enterocolitis Necrotizante/mortalidad , Femenino , Humanos , Recién Nacido , Masculino , Curva ROC , Tasa de Supervivencia/tendenciasRESUMEN
OBJECTIVE: To review the application of thoracoscopic repair for treatment of congenital diaphragmatic hernia in neonates, so as to improve the cure rate. METHODS: Clinical data of 47 neonates with congenital diaphragmatic hernia receiving thoracoscopic repair from June 2012 to June 2017 were reviewed. The admission age, gestational age, birth weight, timing of diagnosis, hernia location, clinical manifestation, surgical timing, surgical method, operation time, postoperative mechanical ventilation time of patients were analyzed. RESULTS: There were 42 cases of left diaphragmatic hernia and 5 cases of right diaphragmatic hernia. Thirteen cases were diagnosed prenatally. Primary diaphragmatic repair was successfully accomplished under thoracoscope in 45 neonates without perioperative complications, while 2 patients were converted to open surgery. The average operation time was (63±13) min (42-150 min), the average blood loss was (3.0±1.7) mL (1.0-9.0 mL), and the average postoperative mechanical ventilation time was (3.9±1.4) d (2.0-11.0 d). Two patients died and the treatment was withdrawn in 3 patients with an overall cure rate of 89.4% (42/47). CONCLUSIONS: Thoracoscopic repair is effective and can be used as first-choice treatment of diaphragmatic hernia in neonates.
Asunto(s)
Hernias Diafragmáticas Congénitas , Toracoscopía , Hernias Diafragmáticas Congénitas/cirugía , Humanos , Recién Nacido , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We present a quantum algorithm that provides a general approach for obtaining the energy spectrum of a physical system without making a guess on its eigenstates. In this algorithm, a probe qubit is coupled to a quantum register R which consists of one ancilla qubit and an n-qubit register that represents the system. R is prepared in a general reference state, and a general excitation operator that acts on R is constructed. The probe exhibits a dynamical response only when it is resonant with a transition from the reference state to an excited state of R which contains the eigenstates of the system. By varying the probe's frequency, the energy spectrum and the eigenstates of the system can be obtained.
RESUMEN
A functionalized nitrogen-containing ordered mesoporous carbon (N-OMC), which shows good electrical properties, was synthesized by the carbonization of polyaniline inside a SBA-15 mesoporous silica template. Based on this, through entrapping laccase onto the N-OMC/polyvinyl alcohol (PVA) film a facilely fabricated amperometric biosensor was developed. Laccase from Trametes versicolor was assembled on a composite film of a N-OMC/PVA modified Au electrode and the electrochemical behavior was investigated. The results indicated that the N-OMC modified electrode exhibits electrical properties towards catechol. The optimum experimental conditions of a biosensor for the detection of catechol were studied in detail. Under the optimal conditions, the sensitivity of the biosensor was 0.29 A*M-1 with a detection limit of 0.31 µM and a linear detection range from 0.39 µM to 8.98 µM for catechol. The calibration curve followed the Michaelis-Menten kinetics and the apparent Michaelis-Menten [Formula: see text] was 6.28 µM. This work demonstrated that the N-OMC/PVA composite provides a suitable support for laccase immobilization and the construction of a biosensor.
RESUMEN
Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from ⼠57.31 kPa to ⼠98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of ⼠94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.
Asunto(s)
Dendrímeros , Hidrogeles , Meloxicam , Nylons , Ácido Poliglutámico , Hidrogeles/química , Hidrogeles/farmacología , Animales , Ácido Poliglutámico/química , Ácido Poliglutámico/farmacología , Ácido Poliglutámico/análogos & derivados , Nylons/química , Adherencias Tisulares/prevención & control , Dendrímeros/química , Dendrímeros/farmacología , Meloxicam/química , Meloxicam/farmacología , Meloxicam/administración & dosificación , Ratones , Inflamación/prevención & control , Inflamación/tratamiento farmacológico , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Fibrinólisis/efectos de los fármacos , Complicaciones Posoperatorias/prevención & control , Tamaño de la Partícula , Inyecciones , Portadores de Fármacos/químicaRESUMEN
Seawater electrolysis is gaining recognition as a promising method for hydrogen production. However, severe anode corrosion caused by the high concentration of chloride ions (Cl-) poses a challenge for the long-term oxygen evolution reaction. Herein, an anti-corrosion strategy of oxalate anions intercalation in NiFe layered double hydroxide on nickel foam (NiFe-C2O42- LDH/NF) is proposed. The intercalation of these highly negatively charged C2O42- serves to establish electrostatic repulsion and impede Cl- adsorption. In alkaline seawater, NiFe-C2O42- LDH/NF requires an overpotential of 337 mV to gain the large current density of 1000 mA cm-2 and operates continuously for 500 h. The intercalation of C2O42- is demonstrated to significantly boost the activity and stability of NiFe LDH-based materials during alkaline seawater oxidation.
RESUMEN
Seawater electrolysis taking advantage of coastal/offshore areas is acknowledged as a potential way of large-scale producing H2 to substitute traditional technology. However, anodic catalysts with high overpotentials and limited lifespans (caused by chloride-induced competitive chemical reactions) hinder the system of seawater electrolysis for H2 production. Herein, we present a citrate anion (CA) modified NiFe layered double hydroxide nanosheet array on nickel foam (NiFe LDH@NiFe-CA/NF), which serves as an efficient and stable electrocatalyst towards long-term alkaline seawater oxidation. It requires only a low overpotential of 387 mV to achieve a current density of 1000 mA cm-2, outperforming NiFe LDH/NF (414 mV). Moreover, NiFe LDH@NiFe-CA/NF exhibits continuous oxygen evolution testing for 300 h at 1000 mA cm-2 due to its anti-corrosion characterization. Additionally, the fabricated cell can stably operate at 300 mA cm-2 (60 °C, 6 M KOH + seawater) and only require 1.69 V, achieving low energy consumption of seawater splitting.
RESUMEN
This study assessed the effects of a simulated high-altitude environment on the reproductive system of prepubertal male rats and the reversibility of these effects upon return to a normal environment. Three-week-old male Wistar rats were randomly allocated to 4 groups that were exposed to different conditions: a normal environment for 6 weeks and 12 weeks, respectively, hypobaric hypoxia for 6 weeks, and hypobaric hypoxia for 6 weeks followed by a normal environment for 6 weeks. Multiple pathophysiological parameters were evaluated at the histological, endocrine, and molecular levels. Hypobaric hypoxia exposure for 6 weeks during the prepubertal phase significantly altered physiological parameters, body functions, blood indices, and reproductive potential. Six weeks after returning to a normal environment, the damaged reproductive functions partially recovered due to compensatory mechanisms. However, several changes were not reversed after returning to a normal environment for 6 weeks, including disorders of body development and metabolism, increased red blood cells, increased fasting blood glucose, abnormal blood lipid metabolism, decreased testicular and epididymis weights, abnormal reproductive hormone levels, excessive apoptosis of reproductive cells, and decreased sperm concentration. In summary, a hypobaric hypoxic environment significantly impaired the reproductive function of prepubertal male rats, and a return to normal conditions during the postpubertal phase did not fully recover these impairments.
Asunto(s)
Altitud , Semen , Ratas , Masculino , Animales , Ratas Wistar , Semen/metabolismo , Hipoxia/metabolismo , Hipoxia/patología , Genitales MasculinosRESUMEN
The comprehensive performance of the state-of-the-art solid-state electrolytes (SSEs) cannot match the requirements of commercial applications, and constructing an organic-inorganic composite electrolyte in situ on a porous electrode is an effective coping strategy. However, there are few studies focused on the influence of inorganic ceramics on the polymerization of multi-organic components. In this study, it was found that the addition of Li6.4La3Zr1.4Ta0.6O12 (LLZO) weakens the interaction between different polymers and makes organic and inorganic components contact directly in the solid electrolyte. These suppress the segregation of components in the in situ polymerized composite SSE, leading to a decrease in the polymer crystallization and improvement of electrolyte properties such as electrochemical stability window and mechanical properties. The composite solid-state electrolyte can be in situ constructed on different porous electrodes, which can establish close contact with active material particles, showing an ionic conductivity 4.4 × 10-5 S cm-1 at 25 °C, and afford the ternary cathode stability for 100 cycles.
RESUMEN
It is of great practical significance to understand the current situation of urban land carrying capacity, explore its potential space, and continuously improve the economic adaptability and resilience and population carrying capacity of megacities. Based on the guiding principle of territorial spatial division and the concept of moderate-scale resilient cities, combined with GIS technology, this study aims to divide land spaces into three types and construct different index systems to evaluate the land carrying capacity of Shanghai in different spaces. Furthermore, we propose different schemes of estimating subspace land population carrying capacity, and the carrying potential of land population is analysed as well. The acquired results demonstrate three key points. Firstly, the total land population capacity of Shanghai is estimated at 25,476.61-32,047.27 people, with urban land space being the most dominant for the city's population carrying capacity. Furthermore, the inner suburbs carry the largest population, and the urban centre carries a larger population density than other areas. Secondly, there are significant spatial differences in land population carrying potential. Compared with the demographic data from 2017, Shanghai still has a population carrying potential of 1293.30-7863.97 people and a suitable population carrying potential of 4578.64 people. The population of the urban centre is near the upper limit of the estimated population carrying capacity, and the suburbs, especially the outer suburbs, have large population carrying potential. Thirdly, the estimation method adopted in this study can effectively reveal the spatial differences in population carrying capacity and the potential of different land spaces and different regions in Shanghai, with the estimation results being highly credible. The results will provide references for the improvement of the multi-scenario population planning strategy in Shanghai, as well as enrich the research span and methods currently employed in land carrying capacity.
Asunto(s)
Conservación de los Recursos Naturales , China , Ciudades , HumanosRESUMEN
ß-Lactams have been a clinical focus since their emergence and indeed act as a powerful tool to combat severe bacterial infections, but their effectiveness is threatened by drug resistance in bacteria, primarily by the production of serine- and metallo-ß-lactamases. Although once of less clinical relevance, metallo-ß-lactamases are now increasingly threatening. The rapid dissemination of resistance mediated by metallo-ß-lactamases poses an increasing challenge to public health worldwide and comprises most existing antibacterial chemotherapies. Regrettably, there have been no clinically available inhibitors of metallo-ß-lactamases until now. To cope with this unique challenge, researchers are exploring multidimensional strategies to combat metallo-ß-lactamases. Several studies have been conducted to develop new drug candidates or calibrate already available drugs against metallo-ß-lactamases. To provide an overview of this field and inspire more researchers to explore it further, we outline some promising candidates targeting metallo-ß-lactamase producers, with a focus on Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Promising candidates in this review are composed of new antibacterial drugs, non-antibacterial drugs, antimicrobial peptides, natural products, and zinc chelators, as well as their combinations with existing antibiotics. This review may provide ideas and insight for others to explore candidate metallo-ß-lactamases as well as promote the improvement of existing data to obtain further convincing evidence.
RESUMEN
Humankind has been interested in reproduction for millennia. Infertility, in which male factors contribute to approximately 50%, is estimated to concern over 72 million people worldwide. Despite advances in the diagnosis, medical treatment, and psychosocial management of male infertility over the past few decades, approximately 30% of male infertility is still thought to be idiopathic. Despite emerging advances in the microbiome associated with male infertility have indicated that the microbiome may be a key factor to the management of male infertility, roles, and mechanisms of the microbiome remain ambiguous. Here, we mainly discussed the association between microbial infection in the genital tract and male infertility, effect of antimicrobial therapy on male reproduction, association between microbial dysbiosis and male infertility, and effect of probiotic intervention on male reproduction. This review made progress toward establishing a relationship between the microbiome and male infertility, and explored the role of the microbiome in male infertility. We call for more high-quality studies to focus on the relationship between microbes and male infertility, and strongly suggest increasing awareness among sterile males with microbial infection and/or microbial dysbiosis when they seek fertility help.
RESUMEN
Activation of integrins is crucial for recruitment of flowing leukocytes to inflammatory or injured vascular sites, but their spatiotemporal characteristics are incompletely understood. We discovered that ß2-integrin activation over the entire surface of neutrophils on immobilized P-selectin occurred via mitogen-activated protein kinase (MAPK) or non-MAPK signaling with a minute-level timescale in a force-dependent manner. In flow, MAPK signaling required intracellular Ca2+ release to activate integrin within 2 min. Integrin activation via non-MAPK signaling occurred first locally in the vicinity of ligated P-selectin glycoprotein ligand-1 (PSGL-1) within sub-seconds, and then over the entire cell surface within 1 min in an extracellular Ca2+ influx-dependent manner. The transition from a local (but rapid) to global (but slow) activation mode was triggered by ligating the freshly activated integrin. Lipid rafts, moesin, actin, and talin were involved in non-MAPK signaling. Fluid loads had a slight effect on local integrin activation with a second-level timescale, but served as enhancers of global integrin activation.