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As a folate antagonist, methotrexate (MTX) has been widely used in clinics with good effects on various tumors and inflammatory diseases. While the optimum dosage and total body clearance of MTX usually varies between individuals and even low-dose MTX has side effects, high-dose MTX may cause life-threatening side effects. Therefore, a convenient and simple method toward MTX sensing is highly demanded. Herein, we report a highly sensitive and selective method for therapeutic drug monitoring (TMD) of MTX by integrating a highly specific MTX-dependent structure-switching aptamer with a primer exchange reaction-based signal amplification technique. The detection limit is down to 1.7 nM with a linear range from 0.01 to 1 μM in buffer. More importantly, the sensing strategy can effectively detect MTX in a complex bio-environment with a linear response range from 0.05 to 2 μM and a LOD of 12.4 nM in 10% FBS and a range of 0.2 to 5 μM with a LOD of 63.73 nM in 10% whole blood. Considering the high sensitivity and selectivity and good performance in blood, the method reported herein paves a new avenue for the effective determination of MTX in clinics. [ABSTRACT FROM AUTHOR]

Herein, we report a portable point-of-care testing (POCT) device based on an aptamer-engineered extended-gate field-effect transistor (EG-FET) for therapeutic monitoring of the drug methotrexate. This method was shown to be highly sensitive, efficient, and convenient to use, features contributing to its realizing a clinical detection of drugs in blood. [ABSTRACT FROM AUTHOR]

The landscapes on Earth are shaped by the interaction of tectonics and erosion processes and thus is a recorder for past tectonic and climatic histories. A recently proposed geomorphologic index for fluvial landscape, χ, can indicate the drainage divide migration from the smaller‐χ‐value side to the other and provide a quick estimation of the dynamic state of drainage systems. Since then, this index has been frequently used to determine divide mobility and hence landscape evolution. Some factors, however, have substantial impacts on the interpretation of the χ value, including tectonic activities, rock erodibility, and precipitation differences. Here we set a series of numerical simulations implemented on the landscape evolution model of DAC (Divide and Capture). Each simulation includes a spatial variation of a particular factor to examine the relationship between divide migration and χ values. Our numerical modelling results indicate that the migration direction is related to cross‐divide contrast in erosion rate rather than χ. We take the Wula Shan horst as a natural example to demonstrate a static drainage divide but with discrepancies of cross‐divide χ values in a setting of spatially asymmetric uplift. Our results suggest that a straightforward relationship between cross‐divide contrasts in χ values and the drainage divide motion may not exist when spatial and temporal variations exist in the rock uplift rate, lithology, and precipitation. We emphasize that researchers should take notice of the requisite assumptions and scope of the application when using this index in landscape analysis. [ABSTRACT FROM AUTHOR]

This paper first reestimates the public capital stock of each China province from 1994 to 2019 by improving the computing method of the components of the perpetual inventory method (PIM). Then, it brings the public investment and public capital into the extended Cobb-Douglas production function and explores the mechanism of public investment affecting economic growth from the regional perspective. Furthermore, through the analysis of the Local Government Financing Vehicles (LGFVs) as the major investor of local public investment during the last two decades, This paper confirms the importance of complementary factors such as institutional innovation and effective management of the public infrastructure in making public investment an "effective catalyst for growth" (Kessides, 1993). [ABSTRACT FROM AUTHOR]

In this work, perfluoroalkylmethacrylate ester (PFAMAE)-grafted-linear low-density polyethylene (LLDPE) was synthesized by UV-induced surface graft polymerization. The effect of PFAMAE-grafted-LLDPE on the tribological behavior of LLDPE-filled polyoxymethylene (POM) composite was investigated using a friction and abrasion testing machine. The results showed that LLDPE-g-PFAMAE was a more effective modifier in improving tribological property of LLDPE-filled POM composite than conventional maleic anhydride-grafted-polyethylene (PE-g-MAH). POM/LLDPE composite possessed much lower friction coefficient but higher wear rate than pristine POM. The incorporation of LLDPE-g-PFAMAE into POM/LLDPE further decreased the friction coefficient, which was 45% lower than that of POM. The wear rate of POM/LLDPE/LLDPE-g-PFAMAE composite was also reduced and was lower than that of pristine POM. The primary wear mechanisms of POM/ LLDPE composite with and without LLDPE-g-PFAMAE were adhesive and abrasive wear. POLYM. ENG. SCI., 51:925-930, 2011. [C]2011 Society of Plastics Engineers, INTRODUCTION As an engineering plastic, polyoxymethylene (POM) exhibits low friction coefficient, excellent wear resistance, good fatigue resistance, creep resistance, and high impact strength with a unique balance of mechanical, thermal, [...]

The polyoxymethylene (POM) composites with different copper contents were prepared by extrusion. The thermal conductivity and tribological behavior of POM-Cu composites with various contents of copper particles were investigated by a hot disk thermal analyzer and an M-2000 friction and abrasion testing machine, respectively. The effect of copper particles on the thermal conductivity of POM composites was negligible when copper content was below 10 wt %. As the copper content increased, the thermal conductivity of composites increased and reached 0.477 W [m.sup.-1] [K.sup.-1] for POM-25 wt % Cu composite, which increased by 35.9% compared with that of unfilled POM. The incorporation of copper particles into POM reduced the friction coefficient of POM composites. The wear mechanisms of POM-Cu composites were adhesive and abrasive wear. POLYM. ENG. SCI., 50:2153-2159, 2010. [C] 2010 Society of Plastics Engineers, INTRODUCTION Polyoxymethylene (POM) as a good wear resistant material with excellent friction and wear properties, high strength, and good chemical stability is widely employed to replace the traditional metals and [...]

A novel self-modulated superjunction lateral double-diffused MOSFET (SM-SJ LDMOS) is proposed and experimentally realized in this letter. When a SJ is introduced into a lightly doped N-drift region, the 3-D depletion regions appear surrounding the P-pillars. This 3-D junction field effect transistor (JFET) effect decreases the current paths in both N-pillars and N-drift, causing a largely increased specific on-resistance ${R} _{\text {on,sp}}$ especially for the SJ with a narrow cell pitch. To suppress the inherent 3-D JFET effect, the SM-SJ structure is proposed by replacing the P-pillars with a series of P-islands. These P-islands with linearly reduced lengths modulate the surface electric field to increase the breakdown voltage ${V} _{{\text {B}}}$ while the N-drift areas between P-islands weaken the 3-D JFET effect to reduce ${R} _{\text {on,sp}}$. Compared with the conventional SJ device, the measured ${V} _{\text {B}}$ of the SM-SJ LDMOS is increased by 53.1% from 260 V to 398 V with ${R} _{on,sp}$ reduced by 22.3% from 35.4 $\text{m}\Omega ~\cdot $ cm2 to 27.5 $\text{m}\Omega ~\cdot $ cm2. [ABSTRACT FROM AUTHOR]

The plant cuticle is a complex structure composed primarily of wax and cutin, but also contains cutan, glycerolipids, phenolics, polysaccharides and proteins. The cuticle plays an important protective role as barrier between plants and their environment. In this paper, 4‐week‐old leaves produced either on the rosette or on the inflorescence stem of the model extremophyte Thellungiella salsuginea were examined using scanning electron microscopy, cuticle permeability assays and chemical composition analysis. Results showed that stem leaves (SL) had more abundant cuticle lipids and lower cuticle permeability than rosette leaves (RL). SL were dominated by alkanes, especially the C29 and C31 homologs, whereas in RL the most abundant wax class was free very long‐chain acids. The major cutin monomers for both leaf types were C18:2 dioic acids and 18‐OH C18:2 acids. We performed Illumina high‐throughput sequencing for SL and RL, and 3577 differentially expressed genes were identified. Sixty‐five genes possibly involved in cuticular lipid biosynthesis, transport, or regulation was selected for further analysis. Many cuticle‐associated genes exhibited differential expression levels that could be associated with compositional differences between these two leaf types. Furthermore, transcription factors and other regulatory proteins previously associated with cuticle production were expressed at higher levels in SL than in RL. The associations between gene expression and characteristics of this extremophile's leaf cuticles sheds new light on cuticle as an adaptive trait in extreme environments, and contributes new information that may guide efforts to modify crop cuticles for improved stress tolerance. [ABSTRACT FROM AUTHOR]

The article presents a study which investigated the crystallization behavior and ultraviolet (UV)-protection property of polyethylene terephthalate (PET)-ZnO nanocomposites. PET-ZnO nanocomposites were prepared by in situ polymerization. It was shown that the silane coupling agent was anchored onto the surface of ZnO.

Precise doses of antibiotics are necessary to prevent bacterial drug resistance. Although fluorescent sensors are promising for quantitative analyses of antibiotics, improvements in feasibility, selectivity, and sensitivity are needed. In this study, a dual-emission fluorescence biosensor platform was developed for simple, selective, and sensitive determination of vancomycin (Van) based on a peptide conjugated with blue-emitting aggregation-induced emission luminogens (AIEgen) and aptamer-modified red-emitting gold nanoclusters (AuNCs-apt). The peptide and aptamer together recognized Van with high affinity, thus changing the fluorescence intensity at 470 nm and 650 nm, respectively. This platform displayed excellent linear correlation between the fluorescence response and a Van concentration ranging 0.01–100 μg mL−1, and the limit of detection (LOD) was 2.79 ng mL−1. In addition to the ability to accurately distinguish Van from glycopeptide antibiotics, the newly developed biosensor allowed for naked-eye detection of 1 μg mL−1 Van. These results and those of serum samples and microdialysate samples support the application of this newly developed method for Van monitoring and clinical diagnosis. Image 1 • An AIEgen-Peptide/AuNCs-apt fluorescent sensor was developed for Van detection. • The system showed good sensitivity and selectivity in the range of 0.01–100 μg mL−1. • Dual-emitting ratiometric fluorescent sensing of Van was demonstrated. • The sensor effectively distinguishes Van from glycopeptide antibiotics. [ABSTRACT FROM AUTHOR]

Plant cuticle lipids form outer protective layers to resist environmental stresses; however, the relationship between cuticle properties and cold tolerance is unclear. Here, the extremophyte Thellungiella salsuginea was stressed under cold conditions (4 °C) and the cuticle of rosette leaves was examined in terms of epicuticular wax crystal morphology, chemical composition, and cuticle-associated gene expression. The results show that cold induced formation of distinct lamellas within the cuticle ultrastructure. Cold stress caused 14.58% and 12.04% increases in the amount of total waxes and cutin monomer per unit of leaf area, respectively, probably associated with the increase in total fatty acids. The transcriptomic analysis was performed on rosette leaves of Thellungiella exposed to cold for 24 h. We analyzed the expression of 72 genes putatively involved in cuticle lipid metabolism, some of which were validated by qRT-PCR (quantitative reverse transcription PCR) after both 24 h and one week of cold exposure. Most cuticle-associated genes exhibited higher expression levels under cold conditions, and some key genes increased more dramatically over the one week than after just 24 h, which could be associated with increased amounts of some cuticle components. These results demonstrate that the cuticle provides some aspects of cold adaptation in T. salsuginea. [ABSTRACT FROM AUTHOR]

• T. mongolica and Z. xanthoxylum are close relatives with different cuticle characters. • Chemical composition of their cuticle is significantly different. • Their cuticle-associated genes expression was compared through transcriptome sequencing. • Their different leaf cuticle is associated with different drought tolerance. Tetraena mongolica Maxim, a relic shrub of the paleo-Mediterranean flora, is normally accompanied in the Western Ordos desert by another plant species in the same taxonomic family, Zygophyllum xanthoxylum (Bunge) Maxim, and together they play a vital role in the ecology of the local environment. Z. xanthoxylum has been identified as having stronger drought tolerance than T. mongolica. As an important water barrier, cuticles were compared between these two relatives to better reveal the mechanism of their different drought tolerance. Z. xanthoxylum possesses more flattened wax crystals, lower epidermal permeability and higher water use efficiency (WUE) than T. mongolica. The composition of cuticular lipids were analyzed, and the results showed that Z. xanthoxylum had significantly higher total amounts of both cuticular wax and cutin monomers than T. mongolica , with all wax class (especially alkanes) and cutin monomer amounts being much higher in Z. xanthoxylum. Cuticle-associated genes were analyzed by transcriptome sequencing, and the results showed that more alkane synthesis genes were up-regulated in Z. xanthoxylum. These findings provide different cuticles on these two succulent xerophytes and reveal the relationships with their different drought tolerance. This study is helpful to reveal the function of plant cuticle in adaptability to extreme environments. [ABSTRACT FROM AUTHOR]

• Cuticle morphology was viewed by SEM of five organs of Thellungiella. • Cuticular lipids (wax and cutin) composition was determined in Thellungiella. • Cuticle-associated genes expression was performed by transcriptome sequencing. • Relationship between cuticle and adaptation to extreme environments was discussed. The cuticle plays a critical role as barrier between plant and environment. Here, cuticular wax morphology, cuticular wax and cutin monomer composition, and expression of associated genes in five above ground organs were examined in model extremophyte Thellungiella salsugineum. Alkanes, ketones, and 2-alcohols were the predominant wax constitutes in rosette leaves, inflorescence stem leaves, stems, and siliques, whereas alkanes and acids were the predominant cuticular lipids in whole flowers. Unsubstituted acids were the most abundant cutin monomers in vegetative organs, especially C18:2 dioic acids, which reached the highest levels in stems. Hydroxy fatty acids were the predominant cutin monomers in flowers, especially 16−OH C16:0 and diOH C16:0. High-throughput RNA-Seq analysis using the Hiseq4000 platform was performed on these five above organs of T. salsugineum , and the differentially expressed lipid-associated genes and their associated metabolic pathways were identified. Expression of genes associated in previous reports to cuticle production, including those having roles in cuticle lipid biosynthesis, transport, and regulation were examined. The association of cuticle lipid composition and gene expression within different organs of T. salsugineum , and potential relationships between T. salsugineum 's extreme cuticle and its adaptation to extreme environments is discussed. [ABSTRACT FROM AUTHOR]

This study comprehensively examines and characterizes global membrane bioreactor (MBR) practices for hospital wastewater treatment, focusing on development trends, technical performance (pollutant removal and carbon emissions), and economic costs, including both capital expenditures (CAPEX) for civil engineering and equipment procurement, and operational expenditures (OPEX) for electricity, membrane replacement, labor, and chemical costs, as well as system footprint. The results show that MBR has been widely used for hospital wastewater treatment for over two decades, with global applications and scales significantly increasing, especially after the COVID-19 pandemic. A notable shift in membrane types has occurred, with hollow fiber membranes dominating before 2010 and flat inorganic membranes gaining prominence after 2020. MBR not only effectively removes conventional pollutants but also greatly reduces pathogens, ARBs and ARGs before disinfection, thus alleviating the subsequent disinfection burden. In addition, MBR is a crucial step in the process of completely removing emerging contaminants (ECs) that pose significant environmental and health risks. The CAPEX of MBR has decreased at the technical level in recent years. MBR requires only 62 % and 21 % of footprint for conventional activated sludge (CAS) and biofilm-based processes, respectively. MBR's land-saving advantage offsets the CAPEX gap with CAS in high land-cost areas. From before 2010 to after 2020, membrane costs saw the largest reduction in OPEX, dropping by 71 %, while electricity consumption saw a 10.71 % reduction, now comparable to biofilm-based processes. Currently, MBR's OPEX (0.158 USD/m 3 ) is only slightly higher than that of biological contact oxidation (0.138 USD/m 3 ). MBR also minimizes sludge production, reducing both treatment costs and associated disposal risks. MBR exhibit minimal concerns of excessive carbon emissions, with a carbon emission intensity (1.11 kg CO 2 eq·m -3 ), only slightly higher than biofilm-based processes (0.92 kg CO 2 eq·m -3 ). This study demonstrates that MBR is the valuable and practical solution for hospital wastewater treatment, as well as a preferred choice for upgrading existing facilities., (Copyright © 2024. Published by Elsevier B.V.)

Probiotics hold great potential for treating metabolic diseases such as obesity. Given the complex and multifactorial nature of these diseases, research on probiotic combination with multiple targets has become popular. Here, we choose four obesity-related targets to perform high-throughput screening, including pancreatic lipase activity, bile salt hydrolase activity, glucagon-like peptide-1 secretion and adipocyte differentiation. Then, we obtained 649 multi-strain combinations with the requirement that each must cover all these targets in principle. After in vitro co-culture and in vivo co-colonization experiments, only four (<0.7%) combinations were selected as symbiotic probiotic communities (SPCs). Next, genome-scale metabolic model analysis revealed that these SPCs showed lower metabolic resource overlap and higher metabolic interaction potential involving amino acid metabolism (Ammonium, L-Lysine, etc.) and energy metabolism (Phosphate, etc.). Further animal experiments demonstrated that all SPCs exhibited a good safety profile and excellent effects in improving obesity and associated glucose metabolism disruptions and depression-like behaviors in high-fat-diet-fed mice. This anti-obesity improvement was achieved through reduced cholesterol level, fat accumulation and inhibited adipocyte differentiation. Taken together, our study provides a new perspective for designing multi-strain combinations, which may facilitate greater therapeutic effect on obesity and other complex diseases in the future.

Cuticular lipids, including wax and cutin, protect plants against external environmental stress. The relationship between the cuticle properties and salt tolerance is not clear. In this article, photosynthetic and physiological characteristics related to water use and cuticle permeability were assessed in the leaves of Thellungiella salsuginea under NaCl stress. The chemical composition of wax and cutin monomers, and the expression of cuticle-associated genes were also analyzed. The results showed that the net photosynthetic rate and stomatal conductance in the leaves of T. salsuginea decreased, and the water use efficiency increased with increasing NaCl concentration. Salt stress caused a significant increase in total wax, but total cutin monomers only increased under high salt. Transcriptome sequencing and lipid metabolism pathway analysis were performed on rosette leaves of T. salsuginea after 24 h of NaCl treatment. We analyzed the expression of 42 genes involved in cuticle lipid metabolism, and found that most of them exhibited higher expression levels at 0.15 mol L -1 NaCl, but lower expression levels at 0.3 mol L -1 NaCl. The expression of 12 of these genes was further detected by qRT-PCR after 1 week of NaCl treatment: most of them were upregulated both under low and high NaCl stress. Hence, we speculate that the cuticle acts as an adaptive trait in T. salsuginea in salty environments., (© 2022 Scandinavian Plant Physiology Society.)

Methotrexate (MTX), a folate antagonist drug, has been widely used for treating various cancers. Since high-dose MTX treatment can cause unwanted serious side effects, tracking the blood concentration of MTX is essential for safe medication. However, available methods are often complex, time-consuming, and expensive. In this study, a highly selective DNA aptamer was selected for recognizing MTX based on a capture-systematic evolution of ligands by an exponential enrichment (C-SELEX) approach. Taking advantage of our selected MTX aptamer, we further unveil a novel structure-switching fluorescent sensor for the specific and rapid monitoring of MTX with good analytical performances (i.e., a linear detection range of 0.1-2 μM with a low detection limit (LOD) of 0.03 μM in buffer and a linear detection range of 0.5-10 μM with an LOD of 0.18 μM in 50% serum). Compared with conventional methods, this assay has great potential for detecting the blood concentration of MTX in clinical use. By coupling with other sensory techniques, our presented aptamer will potentially inspire the development of various sensors toward the monitoring of MTX.

The G-quadruplex (G4) structures of nucleic acids are considered to play an intrinsic role in gene expression. To this end, the development of new G4 ligands has attracted extensive research interests towards potential applications as G4-targeted drugs and molecular probes. To date, the majority of G4 ligands have been composed of an extended planar aromatic scaffold that interacts with the terminal G-tetrad plane via π-π interactions, and various side chains that interact with the sugar-phosphate backbone, loops or grooves of the G4 structures. The side chains act to modulate the affinity and selectivity of the G4 ligands, alongside influencing their biodistribution. Here, we present a click chemistry methodology to generate a series of squaraine-based G4 ligand derivatives based on our previously reported G4 probe (named CSTS) but with varing side chains. We find that importantly these new G4 ligand derivatives retain the G4 selectivity, optical properties and low cytotoxicity of CSTS, but exhibit different binding behaviors to G4 structures, and distinct cellular uptake efficiencies. Indeed, of these new complexes, several exhibit much higher affinity and cellular uptake than CSTS. Overall, this novel, facile and highly effective strategy has significant future potential for the high-throughput screening of G4 ligands or probes targeted towards in vivo applications.

Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells, but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the nonoxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBP) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients., (©2014 American Association for Cancer Research.)

We determined whether lyophilized High Five (H5) insect cells engineered to produce IFN-beta (H5BVIFN-beta) could induce systemic immunity against occult brain metastases. C3H/HeN mice were injected s.c. with syngeneic UV-2237M fibrosarcoma or K-1735M2 melanoma cells. Intralesional injection of 2 x 10(6) lyophilized H5BVIFN-beta cells produced complete regression of the s.c. tumors. Six weeks later, UV-2237M fibrosarcoma cells or K-1735M2 melanoma cells were injected into the internal carotid artery of naive or treated mice. UV-2237M brain metastases developed in naive mice or mice cured of K-1735M2 tumors but not in mice cured of UV-2237M tumors. Similarly, K-1735M2 brain metastases developed in naive mice or mice cured of UV-2237M fibrosarcomas but not in mice cured of K-1735M2 melanoma. In the next set of studies, mice were injected s.c. with UV-2237M fibrosarcoma cells. On day 7, UV-2237M fibrosarcoma cells or K-1735M2 cells were implanted into the internal carotid artery, and on day 10, the s.c. tumors were injected with lyophilized H5BVIFN-beta. Both the s.c. tumors and the occult brain metastases produced from carotid injections were eradicated in a tumor-specific manner. The regression of the brain metastases was abrogated by depletion of CD4(+) or CD8(+) cells from immunized mice. These results demonstrate that specific systemic immunity can be induced by lyophilized H5BVIFN-beta and that the resultant immune response can eliminate established brain metastasis.