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Premium-tasty japonica rice, distinguished by its unique flavor and enriched nutritional value, has attracted significant attention across Asia. Nitrogen metabolism plays a crucial role in determining the growth, development, and quality of rice grains. This study investigates the effects of nitrogen application rates on the enzymatic activities related to nitrogen metabolism, nitrogen metabolites, and grain protein content in the premium-tasty japonica rice variety, Suxiangjing 100. Using a range of nitrogen application rates (0, 80, 160, 240, 320, and 400 kg per hectare), comprehensive analyses were conducted across various developmental stages. Results indicate that as nitrogen application increased, there were distinct patterns in the enzyme activities and metabolite concentrations related to nitrogen metabolism in the leaves of premium-tasty japonica rice. The activities of nitrate reductase (NR), glutamine synthetase (GS), and glutamate synthase (GOGAT) peaked at moderate nitrogen applications, while excessive nitrogen led to a decrease in their activities. The activity of Glutamate Dehydrogenase (GDH) generally increased, but showed a decline after the filling stage. With increasing nitrogen application, the concentrations of nitrate nitrogen (NO3–N), ammonium nitrogen (NH4–N), free amino acids (FAA), and soluble proteins (SP) initially rose but declined at excessive application rates. The grain protein content increased, with levels of prolamin, glutelin, and globulin peaking at nitrogen applications of 240 kg/ha and 320 kg/ha, while changes in albumin levels were minimal. This study not only provides novel insights into the role of nitrogen in shaping the growth and quality of premium-tasty japonica rice, but also suggests refined nitrogen management strategies for sustainable agricultural practices.

High-quality japonica rice, distinguished by its unique flavor and enriched nutritional value, has attracted significant attention across Asia. The over-application of nitrogen (N) fertilizers, however, is a growing concern, threatening both the rice quality and the environmental sustainability of its production. This situation calls for a reevaluation and modification of traditional agricultural practices. Our study investigates the effects of reduced N fertilizer use, complemented by foliar fertilizer application, on the physiological attributes and yield of high-quality japonica rice. The aim is to achieve efficient N use and enhanced crop productivity. The experiment employed ‘Sujing 1180’, a high-quality japonica rice cultivar, utilizing urea as the N source and a comprehensive macronutrient-rich water-soluble fertilizer for foliar application. Five treatments were established: conventional N application (270 kg ha− 1, N100), 10% N reduction (N90), 10% N reduction with foliar application (N90+ FF), 20% N reduction (N80), and 20% N reduction with foliar application (N80+ FF). These treatments were meticulously examined throughout various growth stages. Photosynthetic parameter analysis indicated that N90+ FF significantly boosted the net photosynthetic rate during the heading stage. N80+ FF maintained higher stomatal conductance at the maturity stage, suggesting that foliar fertilizer is effective in enhancing photosynthetic efficiency and stomatal conductance. In terms of N metabolism, N90+ FF notably increased the accumulation of nitrate N during the jointing stage, surpassing other treatments. While N90and N80showed reductions in both nitrate and ammonium N levels compared to N100, N90+ FF was particularly effective in elevating nitrate and ammonium N as well as free amino acid concentrations. Regarding N fertilizer efficiency, N90+ FF surpassed N100across several critical parameters, specifically total N absorption, N recovery efficiency, N agronomic efficiency, and N physiological efficiency. Significantly, N90+ FF showed marked improvements in both N agronomic efficiency and N partial factor productivity. In examining yield and its components, the N90+ FF treatment achieved a higher yield of 9872.48 kg ha− 1, surpassing the 9383.75 kg ha− 1of N100. N90+ FF had better results in seed-setting rate and average grain number per panicle, with its 1000-grain weight similar to that of N100. The N90and N80treatments, however, were less effective in terms of yield and its components. The integrated study findings demonstrate that a strategy incorporating moderate N reduction and foliar fertilizer application markedly optimizes rice photosynthesis, augments N metabolism, and enhances utilization efficiency, leading to increased yields. These insights are valuable for advancing precision agriculture, enhancing japonica rice production efficiency, and promoting sustainable farming.

Tantalum disilicide (TaSi2) has been widely studied for its excellent physical properties such as high hardness, high temperature oxidation resistance and low resistivity. Here, we aim to investigate the effects of different sintering temperatures and pressures on the microstructure and physical properties of TaSi2ceramics. We successfully prepared dense TaSi2ceramics using high-pressure and high-temperature (HPHT) sintering techniques. Characterization results show that TaSi2ceramic properties are strongly influenced by the sintering temperature. The density, Vickers hardness and fracture toughness of TaSi2sintered samples reaches a maximum value of 9.182 g/cm3, 11.34 GPa and 11.97 MPa m1/2, respectively. The fracture toughness of TaSi2sintered samples was significantly improved and also exhibited excellent high-temperature oxidation resistance. Meanwhile, we also investigated the microstructure and grain size variation of TaSi2sintered samples with sintering conditions using scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD). The results show that HPHT sintering can effectively refine the grains of TaSi2ceramics. It provides effective data and ideas for more efficient utilization of TaSi2and preparation of other high-performance ceramics.

The object detection of the substation is the key to ensuring the safety and reliable operation of the substation. The traditional image detection algorithms use the corresponding texture features of single-class objects and would not handle other different class objects easily. The object detection algorithm based on deep networks has generalization, and its sizeable complex backbone limits the application in the substation monitoring terminals with weak computing power. This article proposes a multitargets joint training lightweight model. The proposed model uses the feature maps of the complex model and the labels of objects in images as training multitargets. The feature maps have deeper feature information, and the feature maps of complex networks have higher information entropy than lightweight networks have. This article proposes the heat pixels method to improve the adequate object information because of the imbalance of the proportion between the foreground and the background. The heat pixels method is designed as a kind of reverse network calculation and reflects the object’s position to the pixels of the feature maps. The temperature of the pixels indicates the probability of the existence of the objects in the locations. Three different lightweight networks use the complex model feature maps and the traditional tags as the training multitargets. The public dataset VOC and the substation equipment dataset are adopted in the experiments. The experimental results demonstrate that the proposed model can effectively improve object detection accuracy and reduce the time-consuming and calculation amount.

The results obtained through GRACE/GRACE Follow-On spherical harmonic coefficient model exhibit noticeable north–south strip noise. While applying low-pass filtering along the latitude circle direction can effectively eliminate the north–south strip error, it unavoidably introduces east–west strip noise. This paper introduces a method that utilizes the cosine function to determine the cutoff frequency for the low-pass filtering in the latitude direction. Additionally, a low-pass filtering step is added in the meridian circle direction. This combined approach successfully mitigates the north–south strip error and simultaneously suppresses the east–west strip noise. The analysis results highlight the improvement in signal to noise ratio of global surface quality anomaly estimation achieved by utilizing the cosine function to determine the cutoff frequency. The use of data from five institutions reveals that the dual low-pass filtering (DLP) improves the signal to noise ratio by more than 2% compared to the traditional efficient low-pass-filtering (ELP). When analyzing the uncertainty in the Yangtze River Basin using the three-cornered hat method, it is observed that the uncertainties of the DLP solution, traditional ELP solution, and mascon solution are comparable. Furthermore, the DLP solution exhibits the smallest uncertainty, measured at 4.89 cm. In terms of root mean square error, the DLP almost consistently yields the lowest values across various regions, with the difference from the smallest root mean square error value remaining within 2 mm in certain regions.

Side chains of natural occurring amino acids vary greatly in terms of charge state, polarity, size and hydrophobicity. Using a linear synthetic route, two amino acids were sequentially coupled to a potent glucocorticoid receptor modulator (GRM) to afford a library of dipeptide-GRM linker payloads with a range of in silicoproperties. The linker payloads were conjugated to a mouse anti-TNF antibody through interchain disulfide Cys. Impact of various dipeptide linkers on ADC physical properties, including solubility, hydrophobicity, and aggregation were evaluated and the in silicoproperties pI, Log Pand tPSA of the linker drugs used to correlate with these properties. ADCs were screened in a GRE luciferase reporter assay to compare their in vitroefficacy. Data identified Ala–Ala as a superior dipeptide linker that allowed a maximum drug load of 10 while affording ADCs with low aggregation.

Maleimide chemistry is widely used in antibody–drug conjugate (ADC) generation to connect drugs to antibodies through a succinimide linker. The resulting ADC is prone to payload loss viaa reverse Michael reaction, leading to premature drug release in vivo. Complete succinimide hydrolysis is an effective strategy to overcome the instability of ADC. However, we discovered through previous work that hydrolysed succinimide rings can close again in a liquid formulation during storage and under thermal stress conditions. In this work, a set of maleimide linkers with hydrolysis–prone groups were designed. The corresponding ADCs were prepared and subjected to thermal stress conditions. The extent of succinimide hydrolysis and drug release was measured, and ADC properties such as SEC, DAR, pI and clog Pof linkers were calculated. Our results demonstrated that even though all these groups increased the hydrolysis rate, they have different impacts on maintaining the hydrolysed succinimide ring in an open conformation and ADC stability in a liquid formulation.

Coriander (Coriandrum sativumL.) is recognized for its antioxidant property, as a kind of natural phenolic-rich ingredient. Polycyclic aromatic hydrocarbons (PAHs) present a class of heat-driven hazards in foods, especially the processed meat. In this study, the effect of coriander root and leaf extract on the formation and inhibition of PAH8 in roasted duck wings was firstly investigated. Coriander root extract (CRE) and coriander leaf extract (CLE) with five concentration groups (200, 400, 600, 800, 1000 mg/L) were prepared respectively to marinate the duck wings. CRE marinade exhibited greater inhibitory effect on PAH8 formation in roasted duck wings that ranged from 65.0 %–87.4 %. The electron spin resonance study indicated a significantly positive correlation between PAH8 and free radical level, suggesting the participation of radicals in PAHs formation. Also, it was speculated that the inhibitory effect on PAH8 was related to the phenolic compounds identified in coriander marinades. CRE made greater inhibitory effect on the formation of PAH8 and could be considered as a kind of natural source to mitigate PAHs in heat-processed meat products.

Using a convergent synthetic route to enable multiple points of diversity, a series of glucocorticoid receptor modulators (GRM) were profiled for potency, selectivity, and drug-like properties in vitro. Despite covering a large range of diversity, profiling the nonconjugated small molecule was suboptimal and they were conjugated to a mouse antitumor necrosis factor (TNF) antibody using the MP-Ala-Ala linker. Screening of the resulting antibody drug conjugates (ADCs) provided a better assessment of efficacy and physical properties, reinforcing the need to conduct structure–activity relationship studies on the complete ADC. DAR4 ADCs were screened in an acute mouse contact hypersensitivity model measuring biomarkers to ensure a sufficient therapeutic window. In a chronic mouse arthritis model, mouse anti-TNF GRM ADCs were efficacious after a single dose of 10 mg/kg i.p. for over 30 days. Data on the unconjugated payloads and mouse surrogate anti-TNF ADCs identified payload 17which was conjugated to a human anti-TNF antibody and advanced to the clinic as ABBV-3373.

To evaluate the clinical and retinal imaging features of Chinese patients with acute macular neuroretinopathy (AMN) associated with COVID-19.

Glucocorticoid receptor modulators (GRM) are the first-line treatment for many immune diseases, but unwanted side effects restrict chronic dosing. However, targeted delivery of a GRM payload via an immunology antibody–drug conjugate (iADC) may deliver significant efficacy at doses that do not lead to unwanted side effects. We initiated our α-TNF-GRM ADC project focusing on identifying the optimal payload and a linker that afforded stable attachment to both the payload and antibody, resulting in the identification of the synthetically accessible maleimide-Gly-Ala-Ala linker. DAR 4 purified ADCs were shown to be more efficacious in a mouse contact hypersensitivity model than the parent α-TNF antibody. Analysis of P1NP and corticosterone biomarkers showed there was a sufficient therapeutic window between efficacy and unwanted effects. In a chronic mouse arthritis model, α-TNF-GRM ADCs were more efficacious than both the parent α-TNF mAb and an isotype control bearing the same GRM payload.

The study aimed to investigate and compare the contents of carboxymethyllysine (CML) in two kinds of broilers during postmortem ageing and storage. The contents of CML in raw and boiled (100°C, 30min) broiler briskets and legs which were from white feather broilers (n=8) and yellow feather broilers (n=8) with ageing and storage at 4°C for 0–168h were determined. Postmortem ageing and storage had a significant (P<0.05) effect on the color and A420nmin both boiled broilers meat. In addition, with the ageing and storage time increasing, CML content in raw white feather broiler brisket meat had no significant (P>0.05) change, while that in boiled brisket meat significantly (P<0.05) increased during 0–6h, then decreased during 6–24h, finally increased again. CML content in leg meat increased significantly (P<0.05) with the ageing and storage time prolonging. But postmortem ageing and storage had no significant (P>0.05) effect on the CML contents in raw/boiled yellow feather broilers. Meanwhile, CML contents in white feather broilers were much higher than that in yellow feather broilers. Thus, white feather broilers can be selected as the research object to study the mechanism of ageing and storage on CML content in the postmortem broiler in the future.

ABSTRACTThe function of long non-coding RNA LHFPL3 antisense RNA 1 (LHFPL3-AS1) in cancer progression has been studied, while its role in nasopharyngeal carcinoma (NPC) remains unclear. This study aims to unravel the effects of LHFPL3-AS1 on NPC progression via microRNA (miR)-143-5p/homeobox A6 (HOXA6) axis. NPC tissues were collected and NPC cells were cultured. NPC cells were subjected to radiation therapy to construct the radiation therapy resistance NPC cell line. The levels of LHFPL3-AS1, miR-143-5p and HOXA6 in NPC cells and tissues were examined. LHFPL3-AS1, miR-143-5p or HOXA6 expression was changed and then transfected into radiation-resistant NPC cells to detect cell proliferation, colony formation, migration, invasion and cell apoptosis in vitro. The tumorigenesis in nude mice in vivowas conducted to detect tumor growth. The targeting relations among LHFPL3-AS1, miR-143-5p and HOXA6 were validated. It was discovered that LHFPL3-AS1 and HOXA6 expression was elevated while the miR-143-5p level was depleted in radiation-resistant NPC cells and NPC tissues. The silenced LHFPL3-AS1 or augmented miR-143-5p repressed the proliferation, colony formation, migration and invasion of radiation-resistant NPC cells, while accelerated cell apoptosis in vitro. Silenced LHFPL3-AS1 hindered tumor growth in vivo. MiR-143-5p deletion reversed the effects of reduced LHFPL3-AS1; while HOXA6 upregulation reversed the effects of enriched miR-143-5p. LHFPL3-AS1 sponged miR-143-5p that targeted HOXA6. It is concluded that the down-regulated LHFPL3-AS1 retards the development of radiation-resistant NPC cells via sponging miR-143-5p to modulate HOXA6. This study reveals novel therapeutic targets for NPC treatment.

ABSTRACTThe prognostic significance of miR-24 in tumors has not been determined. Therefore, we conducted a meta-analysis to systematically assess the correlation between miR-24 and its prognostic value in cancers PubMed, EMBASE, and Web of Science databases were used to search relevant articles (up to 1 October 2020). Studies that evaluated the prognostic value of miR-24 in tumors were included. The hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were used to evaluate survival outcomes and clinical characteristics. All data analyses were implemented using STATA 12.0 software. A total of 17 studies from 15 articles involving 1705 patients were collected for the meta-analysis. The pooled analysis revealed that elevated miR-24 expression was obviously associated with poor overall survival (OS) (HR = 1.66, 95% CI: 1.20–2.31). Furthermore, we also found that elevated miR-24 expression was positively correlated with tumor size (large or small) and tumor stage (III–IV vs I–II). Elevated miR-24 expression indicates poor prognosis and may be a promising prognostic marker in different cancers. Our findings needed to be verified through further investigations.

The cocombustion of coal with biomass for energy generation has emerged as a method with tremendous potential in the protection of the environment and the upgrade of the energy structure. The transformation behavior of toxic elements (TEs) during the combustion of coal with biomass does not follow a simple additivity rule. The laboratory-scale fluidized bed reactor is utilized to elucidate the effect of biomass types (corn stalk and sawdust) on the transformation behavior of the TEs during cocombustion. The sequential chemical extraction and thermodynamic equilibrium calculation are applied to investigate the transformation mechanism of the TEs. Results show that the redistribution characteristics of the TEs are feedstock dependent. The gaseous emissions of most TEs are reduced obviously during the cocombustion of coal with biomass, which is attributed to the interactions of the TEs with alkali (earth) metals. As, Cd, Sb, and Se are favored to react with Ca and Fe, while Pb, Cu, and Zn have positive proportions to alkali metals (Na and K). The association of the TEs, thermal stability of the host matrix, and interaction with ash composition play significant roles in the transformation behavior of the TEs during thermal treatment. The cocombustion residues are thought to be a medium risk to the ecological environment due to the elevated liberation of the TEs. Stringent management and countermeasures should be executed during the utilization of these cocombustion residues.

The speciation characterizations of toxic elements (TEs) under air and oxy-fuel combustion of bituminous coal/biomass blends were determined via laboratory simulation experiments. The experiments were performed in a fluidized bed reactor with different combustion temperatures (800, 900, and 1000 °C) and combustion atmospheres (21% O2+ 79% N2, 21% O2+ 79% CO2, 30% O2+ 70% CO2, and 35% O2+ 65% CO2). The concentrations of the selected TEs (As, Cr, Cu, Pb, V, Sb, Se, and Zn) in feedstock, bottom ash, and fly ash were determined using inductively coupled plasma mass spectrometry. The results showed that the redistribution characterizations of the selected TEs were greatly proportional to the reactivity of TE, association of TE, and combustion temperature and atmosphere. The selected gaseous TEs could be captured effectively by adding biomass for the chemical reactions with alkali and alkaline earth metals (Ca, Mg, Fe, K, and Na). The volatile TEs (As, Cu, Pb, Sb, Se, and Zn) were favored to enrich in gaseous and fine particles with the increase of the combustion temperature and oxygen concentration. The non-volatile TEs (Cr and V) were mainly associated with bottom ash and fly ash. More critical measures should be adopted to clean up fly ash and atmospheric pollutants during oxy-fuel combustion.

The monitoring of flue gas of the thermal power plants is of great significance in energy conservation and environmental protection. Spectral technique has been widely used in the gas monitoring system for predicting the concentrations of specific gas components. This paper proposes flue gas monitoring system with empirically-trained dictionary &#x0028 ETD &#x0029 to deal with the complexity and biases brought by the uninformative spectral data. Firstly, ETD is extracted from the raw spectral data by an alternative optimization between the sparse coding stage and the dictionary update stage to minimize the error of sparse representation. D1, D2 and D3 are three types of ETD obtained by different methods. Then, the predictive model of component concentration is constructed on the ETD. In the experiments, two real flue gas spectral datasets are collected and the proposed method combined with the partial least squares, the background propagation neural network and the support vector machines are performed. Moreover, the optimal parameters are chosen according to the 10-fold root-mean-square error of cross validation. The experimental results demonstrate that the proposed method can be used for quantitative analysis effectively and ETD can be applied to the gas monitoring systems.

Thiophene-based monohelicene (TS[7]H), triple helicenes (TT[7]H), and hexapole helicenes (TH[7]H) were synthesized via oxidative photocyclization and cascade Suzuki/intramolecular cyclization as the crucial steps. The enantiomers of TS[7]H, TT[7]H-2, and TH[7]Hexhibited circularly polarized luminescence (CPL), and the luminescence dissymmetry factors (glum) gradually increased from −5.1 × 10–4to −2.0 × 10–3with an increase in multiplicity from TS[7]Hto TH[7]H. In addition, TS[7]H, TT[7]H, and TH[7]Hdisplayed a second-level long afterglow at 77 K.

Genomic amplification of the oncogene MYCNis a major driver in the development of high-risk neuroblastoma, a pediatric cancer with poor prognosis. Given the challenge in targeting MYCN directly for therapy, we sought to identify MYCN-dependent metabolic vulnerabilities that can be targeted therapeutically. Here, we report that the gene encoding glycine decarboxylase (GLDC), which catalyzes the first and rate-limiting step in glycine breakdown with the production of the one-carbon unit 5,10-methylene-tetrahydrofolate, is a direct transcriptional target of MYCN. As a result, GLDC expression is markedly elevated in MYCN-amplified neuroblastoma tumors and cell lines. This transcriptional upregulation of GLDC expression is of functional significance, as GLDC depletion by RNA interference inhibits the proliferation and tumorigenicity of MYCN-amplified neuroblastoma cell lines by inducing G1 arrest. Metabolomic profiling reveals that GLDC knockdown disrupts purine and central carbon metabolism and reduces citrate production, leading to a decrease in the steady-state levels of cholesterol and fatty acids. Moreover, blocking purine or cholesterol synthesis recapitulates the growth-inhibitory effect of GLDC knockdown. These findings reveal a critical role of GLDC in sustaining the proliferation of neuroblastoma cells with high-level GLDC expression and suggest that MYCNamplification is a biomarker for GLDC-based therapeutic strategies against high-risk neuroblastoma.

BACKGROUND AND OBJECTIVE:Classic vitreous biopsy, which targets the vitreous with an undiluted sample of 1 mL to 2 mL, has been used as a diagnostic analysis. Vitrectomy under air infusions have been reported to be able to extract more vitreous sample. In this study, the authors introduce a way of obtaining vitreous sample under air irrigation using 23-gauge vitrectomy and discuss the benefits and potential risks of this procedure.PATIENTS AND METHODS:In this retrospective case series study, a total of 65 eyes of 65 patients with macular epiretinal membrane (ERM) or macular hole (MH) were enrolled. A vitreous biopsy was carried out with air infusion. Vitrectomy with fluid infusion was then carried out to remove the residual vitreous. Medical records of patients with macular ERM or MH were reviewed and analyzed. Clinical data, including age, sex, best-corrected visual acuity (BCVA), optical coherence tomography (OCT), axial length, presence of posterior vitreous detachment (PVD), presence of liquefication of vitreous, and refraction, were recorded and investigated. The volume of vitreous sample, visual outcome, and complications related to vitreous biopsy at 1-month follow-up were recorded and analyzed.RESULTS:The mean of undiluted vitreous sample volume was 2.1 mL ± 0.2 mL. There were seven patients whose vitreous samples were less than 2 mL during the vitreous biopsy. The mean age of patients was 62.9 years ± 8.4 years (range: 35 years to 85 years) at diagnosis. There were 18 male and 47 female patients. At 1-month follow-up, no patient had decreased visual acuity. There was one patient who had a peripheral retinal break and was treated with photocoagulation during the operation (1.5%). The insufficient vitreous sample that may occur during the vitreous biopsy under air infusion was related to liquefication of vitreous (28.8%).CONCLUSION:In summary, vitreous biopsy with air infusion is a safe and effective maneuver to harvest undiluted vitreous in patients without significant vitreous inflammation.[[Ophthalmic Surg Lasers Imaging Retina. 2019;50:365–370.]

AMP-activated protein kinase (AMPK) is an evolutionary conserved energy-sensing enzyme that regulates cell metabolism. Emerging evidence indicates that AMPK also plays an important role in modulating endothelial cell function. In the present study, we investigated whether AMPK modulates endothelial cell growth. Treatment of cultured human umbilical vein endothelial cells with the AMPK activators 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), 6,7-dihydro-4-hydroxy-3-(2'-hydroxy[1,1'-biphenyl]-4-yl)-6-oxo-thieno[2,3-b]pyridine-5-carbonitrile (A-769662), or metformin inhibited cell proliferation and DNA synthesis. The antiproliferative action of AICAR was largely prevented by the adenosine kinase inhibitor 5'-iodotubercidin and mimicked by infecting endothelial cells with an adenovirus expressing constitutively active AMPK. In contrast, pharmacological blockade of endothelial nitric oxide synthase or heme oxygenase-1 activity failed to reverse the inhibition of endothelial cell growth by AICAR. Flow cytometry experiments revealed that pharmacological activation of AMPK arrested endothelial cells in the G₀/G₁ phase of the cell cycle, and this was associated with increases in p53 phosphorylation and p53, p21, and p27 protein expression and decreases in cyclin A protein expression and retinoblastoma protein phosphorylation. In addition, silencing p21 and p27 expression partially restored the mitogenic response of AMPK-activated cells. Finally, activation of AMPK by AICAR blocked the migration of endothelial cells after scrape injury and stimulated tube formation by endothelial cells plated onto Matrigel-coated plates. In conclusion, these studies demonstrate that AMPK activation inhibits endothelial cell proliferation by elevating p21 and p27 expression. In addition, they show that AMPK regulates endothelial cell migration and differentiation and identify AMPK as an attractive therapeutic target in treating diseases associated with aberrant endothelial cell growth.

6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-a] pyrimidine (compound C) is a cell-permeable pyrrazolopyrimidine derivative that acts as a potent inhibitor of AMP-activated protein kinase (AMPK). Although compound C is often used to determine the role of AMPK in various physiological processes, it also evokes AMPK-independent actions. In the present study, we investigated whether compound C influences vascular smooth muscle cell (SMC) function through the AMPK pathway. Treatment of rat aortic SMCs with compound C (0.02-10 μM) inhibited vascular SMC proliferation and migration in a concentration-dependent fashion. These actions of compound C were not mimicked or affected by silencing AMPKα expression or infecting SMCs with an adenovirus expressing a dominant-negative mutant of AMPK. In contrast, the pharmacological activator of AMPK 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside inhibited the proliferation and migration of SMCs in a manner that was strictly dependent on AMPK activity. Flow cytometry experiments revealed that compound C arrested SMCs in the G(0)/G(1) phase of the cell cycle, and this was associated with a decrease in cyclin D1 and cyclin A protein expression and retinoblastoma protein phosphorylation and an increase in p21 protein expression. Finally, local perivascular delivery of compound C immediately after balloon injury of rat carotid arteries markedly attenuated neointima formation. These studies identify compound C as a novel AMPK-independent regulator of vascular SMC function that exerts inhibitory effects on SMC proliferation and migration and neointima formation after arterial injury. Compound C represents a potentially new therapeutic agent in treating and preventing occlusive vascular disease.

Spectroscopy is an efficient and widely used quantitative analysis method. In this paper, a spectral quantitative analysis model with combining wavelength selection and topology structure optimization is proposed. For the proposed method, backpropagation neural network is adopted for building the component prediction model, and the simultaneousness optimization of the wavelength selection and the topology structure of neural network is realized by nonlinear adaptive evolutionary programming (NAEP). The hybrid chromosome in binary scheme of NAEP has three parts. The first part represents the topology structure of neural network, the second part represents the selection of wavelengths in the spectral data, and the third part represents the parameters of mutation of NAEP. Two real flue gas datasets are used in the experiments. In order to present the effectiveness of the methods, the partial least squares with full spectrum, the partial least squares combined with genetic algorithm, the uninformative variable elimination method, the backpropagation neural network with full spectrum, the backpropagation neural network combined with genetic algorithm, and the proposed method are performed for building the component prediction model. Experimental results verify that the proposed method has the ability to predict more accurately and robustly as a practical spectral analysis tool.