Search

This review highlights recent advances in reaction mechanisms and catalyst design strategies for the electrochemical oxidation of ethanol over nickel-based catalysts.

Pervious concrete is a special type of concrete that is of high porosity and contains no or a small amount of fine aggregate, and it is an important basic material for sponge city construction. The presence of a large number of connected pores inside pervious concrete leads to a marked difference in durability failure mechanism compared with that of ordinary concrete.

Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, and have limited drug release control. Herein, we developed an ROS-responsive nanocarrier for targeted delivery of the neuroprotective agent rapamycin (RAPA) to mitigate ischemic brain damage. The nanocarrier consisted of a sulfated chitosan (SCS) polymer core modified with a ROS-responsive boronic ester enveloped by a red blood cell membrane shell incorporating a stroke homing peptide. When encountering high levels of intracellular ROS in ischemic brain tissues, the release of SCS combined with RAPA from nanoparticle disintegration facilitates effective microglia polarization and, in turn, maintains blood–brain barrier integrity, reduces cerebral infarction, and promotes cerebral neurovascular remodeling in a mouse stroke model involving transient middle cerebral artery occlusion (tMCAO). This work offers a promising strategy to treat ischemic stroke therapy.

The prime camera with a mosaic charge-coupled device (CCD) array is the imaging terminal of the wide field survey telescope (WFST), and the flatness of its focal plane array (FPA) is one of the critical indicators that determine the imaging quality of the telescope. The FPA works at $- 100~^{\circ }$ C in a vacuum Dewar to suppress the dark current of CCDs. A large-size FPA of high flatness is hard to realize due to the influence of multiple factors, such as geometric tolerance, force, and temperature deformation. To address this issue, a CCD mosaicking technique based on an error accumulation model is proposed. First, the error source of FPA is analyzed with high-precision measurement and finite element simulation. Second, an assembly deviation simulation calculation model is established based on the actual contact surface morphology characteristics, and the error transfer process is analyzed by combining the small displacement torsor (SDT) and homogeneous transformation matrix (HTM). Then, the effects of force and temperature deformation on each CCD are superimposed independently by HTM, and the feasibility is verified by finite element simulation. Finally, the mosaic FPA of the prime focus camera (PFC) is completed based on this model. Comparing the simulated and measured results, the flatness of the FPA at room temperature reaches a PV of $15.53~\mu $ m. The confidence interval for the flatness of the FPA is determined as [13.48, 17.60] $\mu $ m, with a confidence level of 95%. Also, upon comparing the distribution of CCDs between measurement and simulated assembly, it is evident that only a subset of CCDs shows a height deviation of $0.8~\mu $ m, thus affirming the effectiveness of the simulated assembly process. The FPA suffers a significant bow-shaped deformation at low temperatures, and 99.18% of the measured points are within $16.30~\mu $ m.

In vehicular cloud computing (VCC), cloud servers provide enormous storage and powerful computing capacity to Vehicular Ad-hoc Networks (VANETs). Resource-constrained vehicles outsource data to vehicular cloud platforms for timely traffic safety services, e.g., navigation, accident alarms, etc. Auditing the authenticity of data has become a critical issue in outsourcing data to untrusted servers. Existing data audit methods encode all data with error correction codes (ECC) techniques that retrieve corrupted data by downloading all data. The communication overhead of such methods is $O(n)$ ($n$ is the number of data blocks) which is unbearable for vehicles with limited resources. In addition, these schemes employ an inaccurate privacy-preserving model. This will lead to data leakage in the third-party audit process. Although they use randomness to confuse parts of the proof that is used to prove the data state, a small amount of information is still distinguishable. For such, in this paper, we propose a practical data audit scheme with retrievability and indistinguishable privacy-preserving to efficiently audit the state of outsourced data. We improve the Invertible Bloom Filter (IBF) to compress redundancy locally, which can retrieve corrupted data without prior context. Furthermore, we define an indistinguishable privacy-preserving model to capture the complete semantics of repeated audit attacks and achieve indistinguishability in the audit. We prove that our scheme is secure against adaptive chosen message attacks and is indistinguishable privacy-preserving against repeated audit attacks. The experiment results demonstrate that for 1.9 GB data when $\sqrt[]{n}$ blocks are corrupted, auditors complete a check in 3.31 seconds with 99% confidence, and vehicles retrieve corrupted data in 3.16 seconds with 16.67 MB communication overhead.

The comparative evaluation related to the promotion of Ru and Fe on Ni/ZrO2catalysts showed that Ru-modified Ni/ZrO2with Ni-Ru alloy formation and higher amount of oxygen vacancies enabled higher CO2methanation activity.

The loop impedance-based criterion (LIC) is a practical approach for studying the sub-synchronous oscillation (SSO) instability induced by converter-interfaced wind turbine generators (WTGs) via checking whether the resistance is positive or not. However, few existing works have discussed the background mathematical theory of such criterion. In this paper, a theoretical impedance solving method is raised based on a forced oscillation analysis method, which is efficient to obtain accurate impedance and can connects the state-space function, eigenvector and impedance inherently. Therefore, the applicability of LIC can be revealed in different stability regions from the viewpoint of the strict eigen-analysis based method (EBM). The general LIC stability criteria is then derived, and the conditions where LIC may cause misjudgment are discussed. Cases considering different operating scenarios are conducted to verify the proposed impedance calculation method and illustrate the connections and differences between LIC and EBM.

Self-organizing mechanical instabilities provide a promising route to programmatically micro/nanopatterning two-dimensional (2D) materials, which relies on deterministic control of instability-induced self-assemblies. However, due to ultra-low flexural rigidities, various non-deterministic multi-mode coupling mechanical instabilities are extremely prone to be triggered in 2D materials, which make it difficult to controllably self-assemble 2D nanocrystals into designed mode. Here, we report a deterministic mode of self-assembly in atomically thin 2D materials via mode-decoupled instabilities, which is the key to control self-assembled morphologies. Moreover, we capitalize on intermediate-multifunctional layers (IMLs) to construct 2D-materials/IML/substrate trilayer systems, which can implement three-order trans-scale directed and dynamic self-assemblies of 2D materials. Benefited from the unique properties induced by deterministic self-assemblies, we reported a concept for the fabrication of deterministically self-assembled micro/nano-electronics of 2D materials, such as ultra-fast gesture and anisotropic tactile sensors. The deterministic self-assemblies can considerably advance the development of post-programmable micro/nanopatterning technology and self-assembled electronics of 2D materials.

The advances and challenges of power-to-methane, especially the methanation process, including operation parameters, catalyst categories and roles, and reaction/deactivation mechanisms, are discussed in detail.

In vehicular edge computing (VEC), the execution of offloading task needs not only the task data uploaded by the requesting vehicle, but also the additional data to support the task to be executed successfully, and how to efficiently cache and access these supporting data becomes the key issue for task offloading in VEC. In this paper, we study the efficient caching mechanism to minimize the acquisition delay of the supporting data. Firstly, with the software defined network (SDN) based VEC framework, we analyze the acquisition ways of the supporting data and the caching collaboration between VEC servers. Then, according to the density of the requesting vehicles, we divide the VEC coverage into dense and ordinary areas. With the consideration of the similarity of the requested data and the distance between edge servers, the edge servers are clustered into multiple groups based on K-mean++ algorithm. Finally, each server's storage space is divided into three partitions, and the most beneficial data for itself, its group and the whole system are respectively stored in these partitions. Based on service area dividing, server grouping and storage space partitioning, we propose an efficient edge-cloud collaborative caching strategy, which can reduce the delay of data migration while task execution. Simulation results show that, compared with other schemes, the proposed caching strategy has better performance in terms of average data migration delay and application QoS.

In this research, a method employing micro-extrusion was designed to produce the micro-scaled barrel-shaped parts with complex geometrical features to study the feasibility of the proposed microforming method and its grain size effect on the formability of the complicated internal features in terms of deformation behavior, material evolution, accuracy of dimensions and final components quality. The results reveal that the deformation behavior is highly affected by grain size and becomes unpredictable with increased grain size. In addition, assembly parameters including feature dimension, tolerance and coaxiality also vary with grain size, and the variation of grain size needs to be accommodated by different assembly types, viz., clearance fit or transition fit. From the microstructural evolution aspect, it was identified there were two dead zones and four shear bands, and the formation of these deformation zones was barely affected by the variation in grain size. Though bulges, cracks, and fracture induced voids were observed on the surface of the final components, tailoring the microstructure of the working material with finer grains could significantly avoid these defects. This study advances the understanding of forming microparts by extrusion processes and provides guidance for microforming of similar microparts.

This paper investigates an unmanned aerial vehicle (UAV)-enabled maritime secure communication network, where the UAV aims to provide the communication service to a legitimate mobile vessel in the presence of multiple eavesdroppers. In this maritime communication networks (MCNs), it is challenging for the UAV to determine its trajectory on the ocean, since it cannot land or replenish energy on the sea surface, the trajectory should be pre-designed before the UAV takes off. Furthermore, the take-off location of the UAV and the sea lane of the vessel may be random, which leads to a highly dynamic environment. To address these issues, we propose two reinforcement learning schemes, Q-learning and deep deterministic policy gradient (DDPG) algorithms, to solve the discrete and continuous UAV trajectory design problem, respectively. Simulation results are provided to validate the effectiveness and superior performance of the proposed reinforcement learning schemes versus the existing schemes in the literature. Additionally, the proposed DDPG algorithm converges faster and achieves higher utilities for the UAV, compared to the Q-learning algorithm.

This paper describes control algorithm of minimum energy loss in the aeration process of wastewater treatment in the activated sludge system. The basic equations of the aeration process have been proposed in this paper with the dissolved oxygen concentration (DO) and the amount of sludge discharge (QW) being dual-parameter control variables and the organic matter concentration Sand the microbial concentration Xin the aeration tank being the state variables. Based on the present study on optimization control of wastewater treatment, the multivariable optimal control model with restriction factors have been presented in the paper. The model with modern control theory and system analysis are introduced into the field of activated sludge wastewater treatment. It takes the two most important control parameters (DO &QW), effluent quality as restriction factor. The minimum energy consumption in the aeration process is used as the objective function. This approach has been carried out and the results show that adopting optimal control strategy in the aeration process can effectively conserve energy with the assurance of effluent water quality.

Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, which is closely related to gut barrier dysfunction. Emerging evidence shows that interleukin-22 (IL-22) derived from group 3 innate lymphoid cells (ILC3s) confers benefits on intestinal barrier, and IL-22 expression is controlled by aryl hydrocarbon receptor (AhR). Previous studies show that baicalein protects the colon from inflammatory damage. In this study we elucidated the molecular mechanisms underlying the protective effect of baicalein on intestinal barrier function in colitis mice. Mice were administered baicalein (10, 20, 40 mg·kg−1·d−1, i.g.) for 10 days; the mice freely drank 3% dextran sulfate sodium (DSS) on D1–D7 to induce colitis. We showed that baicalein administration simultaneously ameliorated gut inflammation, decreased intestinal permeability, restored tight junctions of colons possibly via promoting AhR/IL-22 pathway. Co-administration of AhR antagonist CH223191 (10 mg/kg, i.p.) partially blocked the therapeutic effects of baicalein in colitis mice, whereas AhR agonist FICZ (1 μg, i.p.) ameliorated symptoms and gut barrier function in colitis mice. In a murine lymphocyte line MNK-3, baicalein (5–20 μM) dose-dependently increased the expression of AhR downstream target protein CYP1A1, and enhanced IL-22 production through facilitating AhR nuclear translocation, these effects were greatly diminished in shAhR-MNK3 cells, suggesting that baicalein induced IL-22 production in AhR-dependent manner. To further clarify that, we constructed an in vitro system consisting of MNK-3 and Caco-2 cells, in which MNK-3 cell supernatant treated with baicalein could decrease FITC-dextran permeability and promoted the expression of tight junction proteins ZO-1 and occluding in Caco-2 cells. In conclusion, this study demonstrates that baicalein ameliorates colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s, thus providing a potential therapy for UC.

Understanding the deactivation process is of great importance for tailored design of oxygen evolution electrocatalysts with increased stability.

Advanced glycation end products (AGEs), known promoters of diabetic complications, form abundantly in heated foods and are ingested in bioreactive forms. To test whether dietary AGEs play a role in the progression of insulin resistance, C57/BL/KsJ db/db mice were randomly placed for 20 weeks on a diet with either a low AGE content (LAD) or a 3.4-fold higher content of AGE (high AGE diet [HAD]), including [sup.ζ]N-carboxymethyllysine (CML) and methylglyoxal (MG). LAD-fed mice showed lower fasting plasma insulin levels throughout the study (P = 0.01). Body weight was reduced by ~13% compared with HAD-fed mice (P = 0.04) despite equal food intake. LAD-fed mice exhibited significantly improved responses to both glucose (at 40 min, P = 0.003) and insulin (at 60 min, P = 0.007) tolerance tests, which correlated with a twofold higher glucose uptake by adipose tissue (P = 0.02). Compared with the severe hypertrophy and morphological disorganization of islets from HAD-fed mice, LAD-fed mice presented a better-preserved structure of the islets. LAD-fed mice demonstrated significantly increased plasma HDL concentrations (P < 0.0001). Consistent with these observations, LAD-fed mice exhibited twofold lower serum CML and MG concentrations compared with HAD-fed mice (P = 0.02). These results demonstrate that reduced AGE intake leads to lower levels of circulating AGE and to improved insulin sensitivity in db/db mice., Diabetes is a major cause of morbidity and mortality in industrialized societies (1). Type 2 diabetes, the most prevalent form of diabetes, is characterized by resistance to the action of [...]

MicroRNAs (miRNA) have been shown to be associated with tumor diagnosis, prognosis, and therapeutic response. MiR-328-3p plays a significant role in breast cancer growth; however, its actual function and how it modulates specific biological functions is poorly understood. Here, miR-328-3p was significantly downregulated in breast cancer, especially in patients with metastasis. Mitochondrial carnitine palmitoyl transferase 1a (CPT1A) is a downstream target gene in the miR-328-3p-regulated pathway. Furthermore, the miR-328-3p/CPT1A/fatty acid β-oxidation/stemness axis was shown responsible for breast cancer metastasis. Collectively, this study revealed that miR-328-3p is a potential therapeutic target for the treatment of breast cancer patients with metastasis, and also a model for the miRNA-fatty acid β-oxidation-stemness axis, which may assist inunderstanding the cancer stem cell signaling functions of miRNA.

Background: Hepatocellular Carcinoma (HCC) is a primary liver cancer with high mortality. Paeoniflorin is a pinane monoterpene picroside with anti-tumor effect isolated from Chinese peony root and white peony root. Objective: The study was conducted to investigate the underlying mechanism of Paeoniflorin (PF) regulating Hepatocellular Carcinoma (HCC) progression via 5-hydroxytryptamine receptor 1D (5-HT1D). Methods: HepG2 and SMMC-7721 hepatoma cells were treated with different concentrations of PF (0, 5, 10, 20 μM). Cell proliferation, apoptosis, migration, and invasion were examined by CCK-8 and colony formation assays, flow cytometry, wound healing assay, and transwell assay, respectively. RTqPCR assay was used to detect the expression level of 5-HT1D, and Western blot assay was used to detect the expressions of 5-HT1D and Wnt/β-catenin pathway-related proteins. Results: With the increase in PF concentration, the mRNA levels of 5-HT1D in HepG2 and SMMC- 7721 hepatoma cells were decreased in a dose-dependent manner, and the proliferation, colony formation, migration and invasion ability of cells were gradually weakened, while the apoptosis rate was gradually increased. Overexpression of 5-HT1D significantly promoted the proliferation, colony formation, migration and invasion of HepG2 and SMMC-7721 cells, and increased the expression of Wnt/β-catenin pathway-related proteins, β -actenin, survivin, C-myc, and Cyclin D1. Furthermore, 5-HT1D overexpression could reverse the effect of PF on hepatoma cells and inhibit the expressions of Wnt/β-catenin pathway-related proteins. Conclusion: PF may inhibit the progression of HCC by blocking Wnt/β-catenin pathway expression through downregulating 5-HT1D.

Electrochemical water splitting is a process to store renewable energy in hydrogen, which is a green energy carrier producing only water when combusted. However, the overall electrochemical water splitting is limited by the low efficiency of the anodic oxygen evolution reaction (OER) leading to a high overpotential. In this study, finely dispersed cobalt particles supported on graphene are prepared as an anodic catalyst and coupled with phosphate activation to enhance and stabilize OER activity. The small particles enable a high exposure of the surface active sites. Also, the highly conductive graphene backbone accelerates electron transport. Activation by phosphate in the electrolyte leads to the formation of the active Co(iii) species with enriched oxygen vacancies meanwhile facilitating the kinetics. The finely dispersed cobalt particles supported on graphene together with phosphate activation lead to high electrochemical surface area and intrinsic activity, achieving a current density of 10 mA cm−2at an overpotential of 0.35 V and a low Tafel slope of 45 mV per decade, together with good stability. The cobalt mass based current density is 19–8000 times higher than current benchmarking catalysts.

Coronavirus disease 2019 (COVID-19) has rapidly evolved into a pandemic, causing a global public health crisis. Many frontline healthcare workers providing ear, nose and throat services have been reported to contract COVID-19 at work. Early during the COVID-19 outbreak, several medical professionals in Otolaryngology-Head and Neck Surgery were infected in Wuhan, China. A series of measures were then taken immediately, which successfully halted the spread of the disease. Here we would like to share the lessons we have learned, and our experience to protect our health care workers during the COVID-19 pandemic.

Oroxindin is a flavonoid isolated from the traditional Chinese medicine Huang-Qin, which has shown various pharmacological activities including anti-inflammatory, antitumor, antioxidant, etc. Thus far, the effect of oroxindin on colonic inflammation and the underlying mechanism remain unknown. In this study, we investigated the tissue distribution of oroxindin and its therapeutic effects on ulcerative colitis (UC) as well as the underlying mechanisms. UC model was established in mice by administrating dextran sulfate sodium (DSS) in drinking water for 7 d. We first showed that oroxindin was largely absorbed by the colon as an active ingredient after normal mice received Huang-Qin-Tang, a traditional Chinese medicine decoction. UC mice were then treated with oroxindin (12.5, 25, 50 mg ·kg−1·d−1, i.g.) for 10 d. We found that oroxindin treatment greatly suppressed massive macrophages infiltration and attenuated pathological changes in colonic tissue. Furthermore, oroxindin treatment significantly inhibited the generation of IL-1β and IL-18 in the colon via inhibiting the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome formation and activation. In cultured macrophages, LPS induced NLRP3 inflammasome formation and caspase-1 activation, which were suppressed by oroxindin (12.5–50 μM). In LPS-treated macrophages, oroxindin dose-dependently restored the expression of TXNIP protein, leading to suppressing TXNIP-dependent NF-κB activation. In conclusion, these results demonstrate that oroxindin could be absorbed by the colon and attenuate inflammatory responses via inhibiting NLRP3 inflammasome formation and activation, which is related to the inhibitory effect on TXNIP-dependent NF-κB-signaling pathway. Hence, oroxindin has the potential of becoming an effective drug for treating UC.

Background: Except conventional treatments, research on medical approach for radioiodine-refractory differentiated thyroid cancer (RR-DTC) was considered particularly challenging. Sorafenib, a novel biological agent, has been widely studied in the treatment of RR-DTC for years. We performed a systematic review and meta-analysis to explore the efficiency and safety of treating RR-DTC patients with sorafenib. Methods: An electronic search on PubMed/Medline and Embase was carried out to search associated articles. Fixed-effects or random-effects models were chose according to the heterogeneity. Results: A total of 15 eligible studies (636 patients) were included. As shown by the only randomised clinical trial-DECISION, sorafenib significantly improved progression-free survival (PFS) compared with placebo in patients with progressive RR-DTC. The pooled analysis indicated that there were 26% patients (95% CI: 0.19–0.34) achieved partial response (PR), and 44% patients (98% CI: 0.39–0.48) achieved stable disease (SD). The most frequent adverse effects (AEs) observed included hand-foot syndrome (HFS), diarrhoea, fatigue, alopecia, weight loss (WS) and rash, the incidence of all grades AEs for which were 71%, 60%, 59%, 55%, 51% and 50%, respectively. There were 68% patients (252/368), who had a dose reduction because of the drug toxicities and AEs. Conclusions: Sorafenib could improve PFS in patients with progressive RR-DTC, comparing with placebo. Due to the resistance to conventional treatments, sorafenib is considered as a promising treatment for RR-DTC by most physicians specialised in this field. However, the use of sorafenib should be cautious due to a high incidence of AEs caused by the agent. More effective agents with less toxicities are warranted.

Protoplast electrofusion between callus protoplasts of cultivar TMS60444 and mesophyll protoplasts of cultivar SC8 was performed as an approach for the genetic improvement of cassava. The fusion products were subsequently cultured in protoplast culture medium (TM2G) with gradual dilution for approximately 1–2 months. Then the protoplast-derived compact calli were transferred to suspension culture medium (SH) for suspension culture. The cultured products developed successively into embryos, mature embryos, and shoots on somatic embryo emerging medium (MSN), embryo maturation medium (CMM), and shoot elongation medium (CEM), respectively. And the shoots were then rooted on Murashige and Skoog (1962) medium (MS). Sixty-six cell lines were obtained and 12 of them developed into plantlets. Based on assessment of ploidy level and chromosome counting, four of these plantlets were tetraploid and the remaining eight were diploid. Based on assessment of ploidy level and simple sequence repeat (SSR) analysis, nine tetraploid cell lines, one diploid variant plant line and nine variant cell lines were obtained. The diploid variant plant line and the nine variant cell lines all showed partial loss of genetic material compared to that of the parent TMS60444, based on SSR patterns. These results showed that some new germplasm of cassava were created. In this study, a protocol for protoplast electrofusion was developed and validated. Another important conclusion from this work is the confirmation of a viable protocol for the regeneration of plants from cassava protoplasts. Going forward, we hope to provide technical guidance for cassava tissue culture, and also provide some useful inspiration and reference for further genetic improvement of cassava.

Exposure to phthalate acid esters (PAEs) has been found to have adverse effects on reproduction of human and animal. However, the effects on the semen quality are controversial. In this study, we have collected paired blood and sperm samples from patients (n = 103) at a medical clinic in Guangzhou, China, to determine the concentrations of eight phthalate metabolites (m-PAEs). The concentration ranges of ∑8m-PAEs were 2.7–55 and 0.99–17 ng/mL in blood and semen samples, respectively. MEHP (median, 3.6 ng/mL in blood and 0.55 ng/mL in semen) and MnOP (median, 3.4 ng/mL in blood and 0.69 ng/mL in semen) were the predominant analytes in both blood and semen samples. However, analytes were not correlated in paired blood and semen. Semen motility was significantly associated to the concentrations of ∑8m-PAEs in semen, but it did not associate to the concentrations of PAEs in blood. Multi-linear regression analysis, including concentrations of PAEs in both blood and semen, as well as BMI, occupation, living habits, suggested that exposure to PAEs at current environmental levels had very limited effects on semen quality of population in Guangzhou, China.

Metal cations can be adsorbed on the surface of PSMPs which change the surface properties of PSMPs and lead to the aggregation of PSMPs in aqueous solution. However, previous studies have only examined the processes of aggregation and adsorption independently, without investigating the correlation of adsorption and aggregation. In this study, the adsorption and aggregation experiment were carried out simultaneously and monitored simultaneously. The results of this study reveal that, prior to charge reversal of polystyrene microplastic (PSMPs), both adsorption and aggregation increased gradually with increasing metal cations concentration, and were mutually reinforcing. However, following charge reversal, adsorption increased while aggregation decreased, indicating that adsorption inhibited aggregation. The Zeta potentials of PSMPs increase consistently with increasing metal cations concentrations suggested that electrostatic force was one of the primary mechanisms for the adsorption of metal cations by PSMPs. The FTIR analysis reveal that the peak corresponding to CC stretching shifted from 1630 cm−1to 1628 cm−1, 1621 cm−1, and 1615 cm−1when Ag+, Cu2+or Cr3+metal cations were existed, and the results indicated that there might be interactions such as cations-π between PSMPs and metal cations. This information is crucial in determining the environmental fate and impact of PSMPs that have adsorbed metal cations pollutants.

This study investigates the interdecadal variability (IDV) of the interface between the Indian summer monsoon and the East Asian summer monsoon (IIE). Results suggest that the IDV of the IIE is characterized by a uniform zonal movement associated with seesaw variations between the Indian summer monsoon (ISM) and the East Asian summer monsoon (EASM). The IDV of the IIE is closely linked to two air–sea coupled modes: one resembles the Asian–Pacific Oscillation (APO) and the other resembles the North Atlantic tripole (NAT) pattern. Both the APO‐like and NAT‐like patterns facilitate an eastward shift of the IIE during their positive phase. The APO‐like mode strengthens the western North Pacific subtropical high (WNPSH), which further enhances the climatological southwesterly wind over East Asia and leads to an intensification of the EASM. The simultaneous anticyclonic anomaly over the India and Bay of Bengal (BOB) region weakens the ISM. The NAT‐like mode forces a wave train of alternating cyclonic and anticyclonic anomalies across Eurasia, causing southwesterly anomalies over East Asia that favors a stronger EASM. The atmospheric response is reversed during the negative phases of the APO‐like and NAT‐like patterns. Recent decades have seen a weakening influence of the APO‐like mode, but a growing impact of the NAT‐like mode on the IIE‐IDV. The interdecadal transition of the IIE–APO and IIE–NAT relationships has a smaller influence on the IIE than that of the phase change of the APO‐like and NAT‐like patterns. Modeling results confirm the influence of the APO‐like and NAT‐like patterns on the IIE‐IDV. We investigated the interdecadal variability (IDV) of the interface (IIE) between the Indian summer monsoon (ISM) and the East Asian summer monsoon (EASM). We found a significant IIE‐IDV characterized by a uniform zonal movement. The IIE‐IDV is closely linked to two air‐sea coupled modes: one resembles the Asia‐Pacific oscillation (APO) and the other resembles the North Atlantic tripole (NAT) mode. Both modes facilitate the eastward shift of the IIE during their positive phase. The APO‐like mode drives the IIE to shift eastward by strengthening the western North Pacific subtropical high (WNPSH), whereas the NAT‐like mode affects the IIE‐IDV by inducing a wave train of alternating cyclonic and anticyclonic anomaly across Eurasia. The effect of APO‐like mode has weakened in recent decades, but the NAT‐like mode have an increasing impact on the IIE‐IDV. The stronger the influence, the weaker the air‐sea coupled modes. The model results confirmed the main features of IIE‐IDV and the guiding role of APO‐like and NAT‐like modes. The interface between the Indian summer monsoon and the East Asian summer monsoon shows a uniform zonal movement at interdecadal timescaleThe Asian–Pacific Oscillation and the North Atlantic tripole modes have a major impact on the interface between the two monsoon systemsThere is an interdecadal transition in the relationship between the monsoon interface and exogenous modulators The interface between the Indian summer monsoon and the East Asian summer monsoon shows a uniform zonal movement at interdecadal timescale The Asian–Pacific Oscillation and the North Atlantic tripole modes have a major impact on the interface between the two monsoon systems There is an interdecadal transition in the relationship between the monsoon interface and exogenous modulators

FeCrAl alloy is regarded as the optimization material for coal-gasification purification with high temperature, due to its good mechanical property, oxidation resistance and sulfide resistance. This paper focuses on the effect of preoxidation on sulfidation resistance of porous FeCrAl alloy. The continuous and dense Al2O3 film, which was formed on the surface of porous FeCrAl alloy after preoxidation, can prevent the diffusions of atom S and metal ion and improve the sulfidation resistance.

The porous plate is the key part for distributing gas in the fluidized bed, which is subjected pressure, tension and shear from flowing gas and material during work. The porous plate is required to have good mechanical properties. The Monel porous plate was prepared by the powder metallurgy process in this paper. Meanwhile, in order to obtain the status of compressive resistance and shear, the compressive property and the shear property were studied. The results showed that the compressive resistance yield strength was 143MPa and elastic modulus was 18.1GPa at the edge of porous plate. In the central part, the compressive resistance yield strength was 67 MPa, elastic modulus was 8.2GPa and elastic strain range was 3 %.The minimum shear strength was 116 MPa in edge and 87 MPa in the central.

Malignant gliomas are the most common primary brain tumors and are associated with aggressive growth, high morbidity, and mortality. Aberrant mesenchymal-epithelial transition factor (MET) activation occurs in approximately 30% of glioma patients and correlates with poor prognosis, elevated invasion, and increased drug resistance. Therefore, MET has emerged as an attractive target for glioma therapy. In this study, we developed a novel nanoinhibitor by conjugating MET-targeting cMBP peptides on the G4 dendrimer. Compared to the binding affinity of the free peptide (KD= 3.96 × 10–7M), the binding affinity of the nanoinhibitor to MET increased 3 orders of magnitude to 1.32 × 10–10M. This nanoinhibitor efficiently reduced the proliferation and invasion of human glioblastoma U87MG cells in vitroby blocking MET signaling with remarkably attenuated levels of phosphorylated MET (pMET) and its downstream signaling proteins, such as pAKT and pERK1/2. Although no obvious therapeutic effect was observed after treatment with free cBMP peptide, in vivoT2-weighted magnetic resonance imaging (MRI) showed a significant delay in tumor growth after intravenous injection of the nanoinhibitor. The medium survival in mouse models was extended by 59%, which is similar to the effects of PF-04217903, a small molecule MET inhibitor currently in clinical trials. Immunoblotting studies of tumor homogenate verified that the nanoinhibitor restrained glioma growth by blocking MET downstream signaling. pMET and its downstream proteins pAKT and pERK1/2, which are involved in the survival and invasion of cancer cells, decreased in the nanoinhibitor-treated group by 44.2%, 62.2%, and 32.3%, respectively, compared with those in the control group. In summary, we developed a peptide-functionalized MET nanoinhibitor that showed extremely high binding affinity to MET and effectively inhibited glioma growth by blocking MET downstream signaling. To the best of our knowledge, this is the first report of therapeutic inhibition of glioma growth by blocking MET signaling with a novel nanoinhibitor. Compared to antibodies and chemical inhibitors in clinical trials, the nanoinhibitor blocks MET signaling and provides a new approach for the treatment of glioma with the advantages of high efficiency, affordability, and, most importantly, potentially reduced drug resistance.

In order to meet the requirements for the purpose of biological implant materials, analyzes the matching requirements of the compatibility and mechanical properties of titanium foam biological; by powder metallurgy method, using TiH2 powder as raw material, using ammonium bicarbonate as pore forming agent, preparation of titanium foam. The influences of pore forming agent content and particle size, sintering temperature and holding time on the pore structure, pore distribution, pore size and compressive properties of foam titanium were discussed in detail. The results show that with the increase of the sintering temperature and prolonging holding time, titanium foam compressive yield strength and modulus increased; with the increase of the content of pore forming agent, titanium foam compression yield strength and Young's modulus decreased. The preparation of a porosity of 48% ~ 77%, pore size between 300 ~ 500 m, foam pore structure and pore size in micron level through three-dimensional pore, pore size of bio materials meet the requirements. The compressive strength is 98~186MPa, and the young's modulus is 1.6 ~ 6.8 GPa, which matches the strength and the modulus of elasticity of biological implants.

Supplemental Digital Content is available in the text.HRAS, KRAS, and NRAS, highly homologous proteins, are often mutationally activated in cancer. Usually, mutations cluster in codons 12, 13, and 61 and are detected by molecular genetic testing of tumor DNA. Recently, immunohistochemistry with SP174 antibody has been introduced to detect NRAS Q61R-mutant protein. Studies on malignant melanomas showed that such an approach could be a viable alternative to molecular genetic testing. This investigation was undertaken to evaluate the value of SP174 immunohistochemistry for detection of NRAS Q61R-mutant isoform. Two hundred ninety-two malignant melanomas were evaluated using Leica Bond-Max automated immunostainer. Twenty-nine tumors (10%) showed positive immunoreactivity. NRAScodon 61 was polymerase chain reaction amplified and sequenced in 24 positive and 92 negative cases using Sanger sequencing, quantitative polymerase chain reaction, and next-generation sequencing approaches. A c.182A>G substitution leading to NRAS Q61R mutation was identified in 22 tumors. Two NRASwild-type tumors revealed c.182A>G substitutions in HRASand KRAScodon 61, respectively. Both mutations were detected by next-generation sequencing and independently confirmed by Sanger sequencing. None of 85 NRAScodon 61 wild-type tumors and 7 NRASmutants other than Q61R showed immunoreactivity with SP174 antibody. Thus, SP174 antibody was 100% sensitive in detecting NRAS Q61R-mutant isoform in malignant melanoma, but not fully specific as it cross-reacted with HRAS and KRAS Q61R-mutant proteins. Therefore, molecular testing is needed to determine which RASgene is mutated. The rarity of HRAS and KRAS Q61R mutants in malignant melanoma let previous investigations erroneously conclude that SP174 is specific for NRAS Q61R-mutant protein.

Molybdenum sulfide is a promising non-precious material for electrochemical hydrogen production from water. The number of active sites, the intrinsic activity and the electric conductivity of molybdenum sulfide have a significant influence on hydrogen evolution activity. Poor performance of any of these three factors may hamper the hydrogen evolution activity, so synergy between active sites and electric conductivity is of great importance. Here, we report a scalable wet chemistry method coupled with controllable calcination and the incorporation of carbon nanotubes. In this way, molybdenum sulfides showing optimum synergy between tailored and abundant active sites and high electric conductivity become accessible. Major factors governing the intrinsic catalytic activity could be identified. The optimized molybdenum sulfide based catalyst obtained by this method shows higher activity than sole molybdenum sulfide or molybdenum sulfide modified by either calcination or CNT addition. A low overpotential of 154 mV at a current density of 10 mA cm−2, a low Tafel slope of 31 mV per decade and very good stability were achieved. This versatile approach paves the way for the systematic optimization of various 2D materials utilizing the synergy between active site design and enhanced electric conductivity.

This study aimed to produce spherical TiNi powders suitable for additive manufacturing by plasma rotating electrode process (PREP). Scanning electron microscopy, X-ray diffractometry and differential scanning calorimetry were used to investigate the surface and inner micro-morphology, phase constituent and martensitic transformation temperature of the surface and inner of the atomized TiNi powders with different particle sizes. The results show that the powder surface becomes smoother and the grain becomes finer gradually with decreasing particle size. All the powders exhibit a main B2-TiNi phase, while large powders with the particle size ≥178 μm contain additional minor Ti2Ni and Ni3Ti secondary phases. These secondary phases are a result of the eutectoid decomposition during cooling. Particles with different particle sizes have experienced different cooling rates during atomization. Various cooling rates cause different martensitic transformation temperatures and routes of the TiNi powders; in particular, the transformation temperature decreases with decreasing particle size.

The study aims to explore how microRNA‐146a/b (miR‐146a/b) regulates the function of endothelial progenitor cells (EPCs) in acute ischemic stroke in mice. Eighty male SPF C57BL/6J mice were evenly divided into the model‐6 h, model‐12 h, model‐24 h (mice suffered from middle cerebral artery occlusion [MCAO] for 6 h, 12 h and model‐24 h) and normal groups. EPCs were transfected and assigned into the control, MCAO, MCAO‐miR‐146a, MCAO‐miR‐146b and MCAO‐miR‐146a/b groups. The qRT‐PCR was used to detect miR‐146a/b expression in EPCs. Expressions of tumor necrosis factor receptor‐associated factor 6 (TRAF6) and interleukin‐1 receptor‐associated kinase 1 (IRAK1) were detected using western blotting. Cell proliferation and migration of EPCs were testified using CCK‐8 assay and scratch test, respectively. Angiogenesis ability of EPCs was observed under microscope. MiR‐146a and miR‐146b expressions were lower in the model groups than the normal group. There were up‐regulated TRAF6 and IRAK1 expressions in the model‐6 h, model‐12 h and model‐24 h groups compared with the normal group. And there were down‐regulated TRAF6 and IRAK1 expressions in the MCAO‐miR‐146a, MCAO‐miR‐146b and MCAO‐miR‐146a/b groups than in the MCAO group. Compared with the control group, the proliferation, migration and angiogenesis ability of EPCs were significantly lower in the MCAO group, but higher in the MCAO‐miR‐146a, MCAO‐miR‐146b and MCAO‐miR‐146a/b groups. Besides, the miR‐146a/b group showed more enhancement than the MCAO‐miR‐146a and MCAO‐miR‐146b groups. MiR‐146a/b could down‐regulate the TRAF6 and IRAK1 expressions and promote proliferation, migration and angiogenesis ability of EPCs, which was important for recovery of patients with hyperacute ischemic stroke.

In the present study, the performances of the commonly used solid phase extraction (SPE) materials, i.e.alumina, Florisil and silica gel, for separating organophosphate esters (OPEs) from potential co-extracted interferents such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs), were evaluated. Silica gel/alumina (Si/Al) multilayer SPE for OPE sample preparation could effectively reduce matrix effects. A novel and selective method, based on sample preparation by microwave-assisted extraction (MAE) and Si/Al multilayer SPE cartridge cleanup, for the determination of OPEs in soil samples by gas chromatography-mass spectrometry (GC/MS), was developed. The method quantification limits for OPEs ranged from 0.09 to 2.39 ng g−1. A good linearity (r2> 0.991) between MQLs and 1000 × MQLs was achieved. The developed method was successfully applied to determine OPEs in soil samples collected from the campus of Sun Yat-sen University, China. Of the 11 OPEs analyzed, triethyl phosphate (TEP), tri-n-butyl phosphate (TnBP), tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCPP), tributoxyethyl phosphate (TBEP) and triphenylphosphate (TPhP) were present in all of the soil samples, and dominated by TBEP, TCEP, TnBP and TCPP. As compared to the results of other studies, the campus soils of Sun Yat-sen University, China, were moderately polluted by OPEs.

In a tampered blurred image generated by splicing, the spliced region and the original image may have different blur types. Splicing detection in this image is a challenging problem. In recent years, researchers have proposed various methods for detecting such splicing. In this paper, we propose a novel framework for image splicing detection based on partial blur type inconsistency. In this framework, after the cepstrum-based image transforming, a blur type classification parameter is extracted from the spectrum characteristics of spliced blurred image. The blurred image is restored based on the blur kernel which is constructed by estimating the blur parameters. Finally, a fine measure method is applied to segmentation inconsistent region in restored images that contain large amounts of ringing effect. Simulation results show the proposed method effectiveness in detecting forgery part in spliced images with different blur types. The proposed method has good robustness against lossy JPEG compression and noising, which outperforms the state-of-the-art methods for small spliced regions.

Numerous emerging applications require precise monitoring of humidity that is not only sensitive and miniaturized but also durable and portable. However, except for the existing sensing mechanisms, such as resistive, capacitive, impedance, and voltage-based devices, little attention has been paid to exploiting dual readout modes with novel properties that can meet the requirements of simplicity and convenience. In this work, an example of color/fluorescence dual-switching by using an aggregator building block of naphthalenediimide with a porous hygroscopic polymer matrix is proposed. With an increase in the water fraction, there are obvious variations in fluorescence, driven by H-aggregation of the aggregator, and in color, driven by intramolecular-charge transfer, which facilitate the monitoring of external humidity. More importantly, the prepared humidity-sensitive switch demonstrated excellent cycling stability and reversibility. This work may shed light on the precise fabrication of aggregation-activated materials for potential applications in humidity-sensitive systems and switching devices.

Synthesis of higher alcohols by CO2hydrogenation is a promising way to mitigate CO2emissions, meanwhile producing value-added fuels and chemicals. However, CO2hydrogenation to higher alcohols is kinetically hindered and due to the absence of highly efficient catalysts, its industrial implementation is still limited. Among the catalysts designed for this reaction, Co-based catalysts are widely investigated due to earth-abundance and economic, possessing also relatively high activity and selectivity for this reaction. Considering the nature of the active site, the hetero sites of Co-based catalysts such as Co0-CoO, Co0-Coδ+, and Co2C-NaCo2C are critical for higher alcohol synthesis by CO2hydrogenation. Thus, in this review, we first introduce the roles of Co0, CoO, Coδ+, and Co2C, as well as strategies to tailor their structure which influences the performance in CO2hydrogenation. Then, we discuss the strategies to create highly efficient hetero-site Co-based catalysts. Finally, emerging methodologies yet to be explored and future directions to achieve highly efficient hetero-site Co catalysts for CO2hydrogenation to higher alcohols are discussed.

Chemotherapy is one of the most important strategies for glioma treatment. However, the “impermeability” of the blood–brain barrier (BBB) impedes most chemotherapeutics from entering the brain, thereby rendering very few drugs suitable for glioma therapy, letting alone application of a combination of chemotherapeutics. Thereby, there is a pressing need to overcome the obstacles. A dual-targeting strategy was developed by a combination of magnetic guidance and transferrin receptor-binding peptide T7-mediated active targeting delivery. The T7-modified magnetic PLGA nanoparticle (NP) system was prepared with co-encapsulation of the hydrophobic magnetic nanoparticles and a combination of drugs (i.e., paclitaxel and curcumin) based on a “one-pot” process. The combined drugs yielded synergistic effects on inhibition of tumor growth via the mechanisms of apoptosis induction and cell cycle arrest, displaying significantly increased efficacy relative to the single use of each drug. Dual-targeting effects yielded a >10-fold increase in cellular uptake studies and a >5-fold enhancement in brain delivery compared to the nontargeting NPs. For the in vivo studies with an orthotopic glioma model, efficient brain accumulation was observed by using fluorescence imaging, synchrotron radiation X-ray imaging, and MRI. Furthermore, the antiglioma treatment efficacy of the delivery system was evaluated. With application of a magnetic field, this system exhibited enhanced treatment efficiency and reduced adverse effects. All mice bearing orthotopic glioma survived, compared to a 62.5% survival rate for the combination group receiving free drugs. This dual-targeting, co-delivery strategy provides a potential method for improving brain drug delivery and antiglioma treatment efficacy.

Stone wool external thermal insulation composite system is used more and more in China now. Former studies in China simply consider that water vapour permeability of render coating should be equal to the water vapour permeability of stone wool. Neither is there any necessary indicator for the liquid water (wind-driven rain) for the system. Therefore, an important issue to be solved currently is how to propose reasonable indicators for water vapour and liquid water transfer performance in stone wool system for different climate zones in China. This research studied on the simulation of hygrothermal distribution of stone wool system. Simulations of stone wool systems were done under different outdoor temperature, humidity, wind driving rain and other conditions to analyze the moisture content in each layer of the system. Meanwhile, simulations of different render coating performances were also done to analyze the moisture content in each layer. Based on these, indicators for water vapour and liquid water were proposed, which provides a foundation for the stone wool external thermal insulation composite system standards in China.

Two cancer testis antigens, the New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and the melanoma-antigen family A (MAGE-A), represent promising immunotherapy targets due to the low expression of these antigens in nonmalignant tissue. To assess overexpression patterns in various cancers, we performed a systematic immunohistochemical analysis for NY-ESO-1 and MAGE-A on tissue array samples of 3668 common epithelial carcinomas (CA) and germ cell tumors of high prevalence and mortality. Here, we find significantly higher expression of MAGE-A (>50% on tumor cells) compared with NY-ESO-1 in several CAs including cutaneous squamous cell carcinomas (SCC) (52.8%/2.8%), esophageal SCC (50%/0%), head and neck SCC (41.1%/<1%), bladder urothelial CA (40.4%/8.3%), cervical/anal SCC (37.5%/0%), lung SCC (34%/3.8%), lung adenocarcinomas (27.6%/3.9%), ovarian CA (26.4%/3.6%), endometrial CA (26.3%/1.3%), lung small cell CA (24.4%/2.4%), gastric adenocarcinomas (20%/4%), breast mucinous CA (19.3%/0%), hepatocellular CA (18.8%/1.2%), breast infiltrating ductal CA (16.4%/1.8%), colorectal adenocarcinomas (10.7%/<1%), cholangiocarcinomas (9.8%/0%), thymic CA (9%/4.5%), and mesotheliomas (7.9%/<1%). Furthermore, high expression of MAGE-A, but not NY-ESO-1, was seen in whole slide evaluations of an independent cohort of metastatic SCC (45.5%/3.6%) and metastatic CA (13.5%/0%) of various primaries with significantly higher expression of MAGE-A in metastatic SCC compared with other metastatic CA. MAGE-A is also more highly expressed in germ cell tumors, seminomas (69%/3.5%) and nonseminomas (40.1%/4.7%). In summary, MAGE-A is more highly expressed than NY-ESO-1 in a majority of human malignancies, and targeting MAGE-A may benefit a large number of patients.

Supplemental Digital Content is available in the text.Signet ring stromal cell tumor (SRSCT) of the ovary is a very rare benign ovarian neoplasm. To date, no underlying genetic mechanism has been identified. In this study, 50 oncogenes and tumor suppressor genes were evaluated for mutations in a typical SRSCT using the next-generation DNA sequencing approach. An in-frame deletion of 30 nucleotides in the glycogen serine kinase-3 beta phosphorylation region of the β-catenin gene (CTNNB1) was identified, and the finding was confirmed by Sanger sequencing. This deletion (c.68_97del) at the protein level would lead to a p.Ser23_Ser33delinsThr oncogenic-type mutation. Subsequent immunohistochemistry showed prominent nuclear accumulation of β-catenin and cyclin D1 in tumor cells. Thus, mutational activation of the Wnt/β-catenin pathway could be a crucial event in the molecular pathogenesis of SRSCT of the ovary. These findings may also assist in the diagnosis of this rare tumor.

Fusarium oxysporumf. sp. conglutinans(Foc) is the causal agent of Fusariumwilt disease of Brassica oleracea.A rapid, accurate, and reliable method to detect and identify plant pathogens is vitally important to integrated disease management. In this study, using a comparative genome analysis among Fusarium oxysporum(Fo), we developed a Foc-specific primer set (Focs-1/Focs-2) and established a multiplex-PCR assay. In the assay, the Focs-1/Focs-2 and universal primers for Fusariumspecies (W106R/F106S) could be used to detect Focisolates in a single PCR reaction. With the optimized PCR parameters, the multiplex-PCR assay showed a high specificity for detecting Focand was very sensitive to detect as little as 100 pg of pure Focgenomic DNA or 1 000 spores in 1 g of twice-autoclaved soil. We also demonstrated that Focisolates were easily detected from infected plant tissues, as well as from natural field soils, using the multiplex-PCR assay. To our knowledge, this is a first report on detection Foby comparative genomic method.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors usually driven by the mutational activation of receptor tyrosine kinases, KIT, or PDGFRA. Oncogenic activation of phosphatidylinositide-3-kinase (PI3K), a downstream effector in the KIT signaling pathway, has been identified in different types of cancer, with the PI3K 110α subunit encoded by PIK3CAbeing a common mutational target. In this study, the mutational hotspot in the PIK3CAkinase domain encoded by exon 20 was evaluated in 529 imatinib-naive GISTs using PCR amplification and Sanger sequencing. Eight mutations (two co-existing in one tumor) were identified. Subsequently, The cobas PIK3CA Mutation Test was employed to evaluate mutational hotspots in exons 1, 4, 7, and 9 in 119 PIK3CAexon 20-wild type tumors. In two cases, mutations in exons 1 and 9 were identified. In one GIST, previously undetected by Sanger sequencing, the exon 20 mutation was discovered. Altogether, eight primary and two metastatic GISTs carried PIK3CAmutations. The size of primary PIK3CA-mutant GISTs was ≥14 cm (mean size 17 cm), and mitotic activity varied from 0 to 72 per 50HPF (mean 5/50HPF). Follow-up data showed short survival in 6 of 7 studied cases. Detection of PIK3CAmutations in large or metastatic KIT-mutant GISTs may suggest that PIK3CA-mutant clones have a proliferative advantage during disease progression. Tyrosine kinase inhibitors have been successfully used in GIST treatment. However, resistance frequently develops due to secondary KITmutations or activation of downstream to KIT signaling pathways, such as the PI3K/AKT/mTOR pathway. PIK3CAmutations similar to the ones detected in GISTs have been shown to cause such activation. Therefore, genotyping of PIK3CAin GISTs might help to pinpoint primary and metastatic tumors with the potential to develop resistance to tyrosine kinase inhibitors and guide therapy with PI3K inhibitors.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors usually driven by the mutational activation of receptor tyrosine kinases, KIT, or PDGFRA. Oncogenic activation of phosphatidylinositide-3-kinase (PI3K), a downstream effector in the KIT signaling pathway, has been identified in different types of cancer, with the PI3K 110α subunit encoded by PIK3CA being a common mutational target. In this study, the mutational hotspot in the PIK3CA kinase domain encoded by exon 20 was evaluated in 529 imatinib-naive GISTs using PCR amplification and Sanger sequencing. Eight mutations (two co-existing in one tumor) were identified. Subsequently, The cobas PIK3CA Mutation Test was employed to evaluate mutational hotspots in exons 1, 4, 7, and 9 in 119 PIK3CA exon 20-wild type tumors. In two cases, mutations in exons 1 and 9 were identified. In one GIST, previously undetected by Sanger sequencing, the exon 20 mutation was discovered. Altogether, eight primary and two metastatic GISTs carried PIK3CA mutations. The size of primary PIK3CA-mutant GISTs was ≥14 cm (mean size 17 cm), and mitotic activity varied from 0 to 72 per 50HPF (mean 5/50HPF). Follow-up data showed short survival in 6 of 7 studied cases. Detection of PIK3CA mutations in large or metastatic KIT-mutant GISTs may suggest that PIK3CA-mutant clones have a proliferative advantage during disease progression. Tyrosine kinase inhibitors have been successfully used in GIST treatment. However, resistance frequently develops due to secondary KIT mutations or activation of downstream to KIT signaling pathways, such as the PI3K/AKT/mTOR pathway. PIK3CA mutations similar to the ones detected in GISTs have been shown to cause such activation. Therefore, genotyping of PIK3CA in GISTs might help to pinpoint primary and metastatic tumors with the potential to develop resistance to tyrosine kinase inhibitors and guide therapy with PI3K inhibitors.