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This study aims to provide a systematic and complete knowledge map for researchers working in the field of research on the application of artificial intelligence in education. In addition, it is designed to help researchers quickly understand author collaboration characteristics, institutional collaboration characteristics, trending research topics, evolutionary trends, and research frontiers of scholars from a library informatics perspective. In this study, a bibliometric approach was used to quantitatively analyze the retrieved literature with the help of the bibliometric analysis software CiteSpace. The analysis results are presented in tables and visual images in this paper. The results of this study indicate that collaborative relationships among scholars need to be improved and collaborative research relationships among research institutions are more fragmented. This study also points out the shortcomings of this study: Chinese educational researchers and practitioners still have a relatively vague understanding of some fundamental issues in the process of integration and development of AI and education. Therefore, this paper uses quantitative research methods such as bibliometrics and visualization pictures to systematically and intuitively reveal the research progress and trends on the application of artificial intelligence in education based on the published literature and to provide a reference for further research on this topic in the future.

Mapping the proteomic landscape of mitochondria with spatiotemporal precision plays a pivotal role in elucidating the delicate biological functions and complex relationship with other organelles in a variety of dynamic physiological processes which necessitates efficient and controllable chemical tools. We herein report a photo-oxidation driven proximity labeling strategy to profile the mitochondrial proteome by light dependence in living cells with high spatiotemporal resolution. Taking advantage of organelle-localizable organic photoactivated probes generating reactive species and nucleophilic substrates for proximal protein oxidation and trapping, mitochondrial proteins were selectively labeled by spatially limited reactions in their native environment. Integration of photo-oxidation driven proximity labeling and quantitative proteomics facilitated the plotting of the mitochondrial proteome in which up to 310 mitochondrial proteins were identified with a specificity of 64% in HeLa cells. Furthermore, mitochondrial proteome dynamics was deciphered in drug resistant Huh7 and LPS stimulated HMC3 cells which were hard-to-transfect. A number of differential proteins were quantified which were intimately linked to critical processes and provided insights into the related molecular mechanisms of drug resistance and neuroinflammation in the perspective of mitochondria. The photo-oxidation driven proximity labeling strategy offers solid technical support to a highly precise proteomic platform in time and finer space for more knowledge of subcellular biology.

In-depth proteome quantitation is of great significance for understanding protein functions, advancing biological, medical, environmental and metabolic engineering research. Herein, benefiting from the high formation efficiencies and intensities of dimethyl-labeled a1 ions for accurate quantitation, we developed an in-depth a1 ion-based proteome quantitation method, named deep-APQ, by a sequential MS/MS acquisition of the high mass range for identification and the low mass range for a1 ion intensity extraction to increase quantitative protein number and sequence coverage. By the analysis of HeLa protein digests, our developed method showed deeper quantitative coverage than our previously reported a1 ion-based quantitation method without mass range segmentation and lower missing values than widely-used label-free quantitation method. It also exhibited excellent accuracy and precision within a 20-fold dynamic range. We further integrated a workflow combining the deep-APQ method with highly efficient sample preparation, high-pH and low-pH reversed-phase separation and high-field asymmetric waveform ion mobility spectrometry (FAIMS) to study E. coli proteome responses under the nutritional conditions of glucose and acetate. A total of 3447 proteins were quantified, representing 82% of protein-coding genes, with the average sequence coverage up to 40%, demonstrating the high coverage of quantitation results. We found that most of the quantified proteins related to chemotaxis were differentially expressed, including the low-abundance proteins such as trg, fliL, and cheA, indicating that chemotaxis would play an important role for E. coli cell to survive from acetate toxicity. The above results demonstrated that the deep-APQ method is of great promising to achieve the deep-coverage proteome quantitation with high confidence.GRAPHICAL ABSTRACT

Objective The data regarding the mutation landscape in Chinese patients with thyroid cancer are limited. The diagnostic performance of thyroid nodules by fine-needle aspiration (FNA) cytology needs optimization, especially in indeterminate nodules. Methods A total of 1039 FNA and surgical resection samples tested using the targeted multigene next-generation sequencing (NGS) panel were retrospectively collected. The features of gene alterations in different thyroid tumors were analyzed, and the diagnostic efficacy was evaluated. Results Among 1039 samples, there were 822 FNA and 217 surgical FFPE samples. Among 207 malignant thyroid resections, a total of 181 out of 193 papillary thyroid carcinomas (PTCs) were NGS-positive (93.8%), with a high prevalence of BRAF mutations (81.9%, 158/193) and a low prevalence of RAS (1.0%, 2/193) and TERT promoter mutations (3.6%, 7/193). Gene fusions, involving the RET and NTRK3 genes, were present in 20 PTCs (10.4%) and mutually exclusive with other driver mutations. Two of three follicular thyroid carcinomas harbored multiple mutations. RET gene point mutations were common in medullary thyroid carcinoma (8/11, 72.7%). The combination of cytology and DNA–RNA-based NGS analysis demonstrated superior diagnostic value (98.0%) in FNA samples. For indeterminate thyroid nodules, the diagnostic sensitivity and specificity of NGS testing were 79.2 (38/48) and 80.0% (8/10), respectively. Two mutation-positive benign cases harbored NRAS and TSHR mutations, respectively. Conclusions Our study revealed the distinct molecular profile of thyroid tumors in the Chinese population. The combination of NGS testing and FNA cytology could facilitate the accurate diagnosis of thyroid nodules, especially for indeterminate nodules.

The entrainment and detrainment rates are important quantities characterizing airmass exchange between clouds and the environment. One of the challenges in calculating the rates is the need to know the velocity vector of the cloud interface in relation to that of the cloud-free air; however, the interface is not well resolved in most cloud model simulations and so the precise value of the vector is not known. Here a new method is described to approximately calculate mass fluxes across the cloud surface in well-resolved simulations of cumulus convection. The method does away with the need to calculate a cloud interface velocity and instead uses gradients of a defined cloud scalar across the cloud interface. As a result, the entrainment and detrainment rates are expressed as an integration over a small region around the cloud interface. The integrand is composed of the total derivative of the cloud scalar. The new method is applied to large-eddy simulations (LES) of a shallow cumulus case and a deep convection case. Compared to a previous method, the approach described here gives 1.5–2 times smaller exchange rates and shows less noise. The smaller exchange rates are explained as the result of differences in how the two methods correct for the advective contribution to variations of cloud volume. Derived two-dimensional distributions of the exchange rates agree well for both methods. Spatial correlation coefficients are about 0.69–0.88 for entrainment and 0.55–0.78 for detrainment.

Isentropic stirring and mixing are important processes that determine the distribution of long-lived trace gases in the stratosphere. Stirring stretches tracer contours into filaments and mixing dissipates tracer variance. The combined effects on tracer transport by stirring and mixing are quantified by the effective diffusivity in the modified Lagrangian-mean (MLM) theory that diagnoses tracer transport in an areal coordinate. Here a method is developed to diagnose transport processes based on tracer contours in geographic coordinates. Compared to the MLM theory this method has resolving ability along tracer contours and quantifies stirring and mixing separately. Also, the influence of diabatic motion on the diagnosed stirring is reduced, which is useful for stratospheric analysis where diabatic motion is uncertain. The developed method is validated in a methane simulation experiment. The diagnosed stirring effects are consistent with established knowledge about stratospheric dynamics. Finally, stirring and mixing effects on trace gases in the polar vortex are diagnosed during a northern polar vortex period. According to the diagnosis stirring and mixing always increase the methane concentration in the polar vortex. However, their effects are reversed by vortex movement and deformation in most cases. Only in a few cases, planetary waves can penetrate into the vortex and stirring increases the methane concentration in the vortex. The developed method is readily applicable to diagnose stratospheric transport processes from satellite observed trace gas distributions.

Finding the critical factor and possible “Newton’s laws” in financial markets has been an important issue. However, with the development of information and communication technologies, financial models are becoming more realistic but complex, contradicting the objective law “Greatest truths are the simplest.” Therefore, this paper presents an evolutionary model independent of micro features and attempts to discover the most critical factor. In the model, information is the only critical factor, and stock price is the emergence of collective behavior. The statistical properties of the model are significantly similar to the real market. It also explains the correlations of stocks within an industry, which provides a new idea for studying critical factors and core structures in the financial markets.

This 2022 International Conference on Finance, Investment and Business Analysis (FIBA 2022) was successfully held virtually in Kuala Lumpur, Malaysia from June 25 to 26, 2022. Initially, it was planned to be held physically at University of Malaya, Malaysia. However, this conference was changed to a virtual format due to the current situation of covid-19 and travel restrictions in Malaysia and other countries. FIBA 2022 is a conference on international finance, global investment, business planning, economic management and business analysis. It provides a forum for researchers, practitioners and educators to introduce and discuss the latest innovations, trends, experiences and concerns in these fields. The main objective of this conference is to provide a forum for all attendees to share and exchange ideas and research findings in respective fields of research. The conference allows the exchange of knowledge between different research domestic and foreign centers representing various fields. The virtual format of FIBA 2022 was a success where all the participants gathered on the online platform regardless of the time zone and location and share experiences and research findings in their respective fields. As such, this conference will expand networks and foster potential collaborations between researchers in the same field of research. With best regards, Organizing Committees of FIBA Kuala Lumpur, Malaysia

Spiral artery remodeling is an important physiological process in the pregnant uterus which increases blood flow to the fetus. Impaired spiral artery remodeling contributes to preeclampsia, a major disease in pregnancy. Corin, a transmembrane serine protease, is up-regulated in the pregnant uterus to promote spiral artery remodeling. To date, the mechanism underlying uterine corin up-regulation remains unknown. Here we show that Kruppel-like factor (KLF) 17 is a key transcription factor for uterine corin expression in pregnancy. In cultured human uterine endometrial cells, KLF17 binds to the CORIN promoter and enhances the promoter activity. Disruption of the KLF17 gene in the endometrial cells abolishes CORIN expression. In mice, Klf17 is up-regulated in the pregnant uterus. Klf17 deficiency prevents uterine Corin expression in pregnancy. Moreover, Klf17-deficient mice have poorly remodeled uterine spiral arteries and develop gestational hypertension and proteinuria. Together, our results reveal an important function of KLF17 in regulating Corin expression and uterine physiology in pregnancy.

Type II transmembrane serine proteases (TTSPs) are a group of enzymes participating in diverse biological processes. Some members of the TTSP family are implicated in viral infection. TMPRSS11A is a TTSP expressed on the surface of airway epithelial cells, which has been shown to cleave and activate spike proteins of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome coronaviruses (CoVs). In this study, we examined the mechanism underlying the activation cleavage of TMPRSS11A that converts the one-chain zymogen to a two-chain enzyme. By expression in human embryonic kidney 293, esophageal EC9706, and lung epithelial A549 and 16HBE cells, Western blotting, and site-directed mutagenesis, we found that the activation cleavage of human TMPRSS11A was mediated by autocatalysis. Moreover, we found that TMPRSS11A activation cleavage occurred before the protein reached the cell surface, as indicated by studies with trypsin digestion to remove cell surface proteins, treatment with cell organelle-disturbing agents to block intracellular protein trafficking, and analysis of a soluble form of TMPRSS11A without the transmembrane domain. We also showed that TMPRSS11A was able to cleave the SARS-CoV-2 spike protein. These results reveal an intracellular autocleavage mechanism in TMPRSS11A zymogen activation, which differs from the extracellular zymogen activation reported in other TTSPs. These findings provide new insights into the diverse mechanisms in regulating TTSP activation.

International audience; Isentropic mixing properties in the stratosphere modeled by the forward calculation of an inverse model (TM5-4DVAR) are evaluated against Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) and Microwave Limb Sounder (MLS) observations. The isentropic mixing processes are separated into large-scale stirring described by the “equivalent length” and small-scale diffusion described by the diffusivity. Compared to the measurements, we find that the modeled stirring is not strong enough and that the small-scale diffusivity is too large. TM5-4DVAR produces excessive mixing-induced poleward flux for stratospheric CH4. The flux convergence presents negative biases in the tropics and positive biases in the polar regions. The biases cannot be reduced by improving the horizontal resolution only. Modeled isentropic mixing depends on the horizontal as well as the vertical resolution of the model. An increase in vertical resolution reduces numerical diffusion of the model in the vertical. The decreased vertical diffusion leads to reduction in the modeled isentropic diffusivity. Biases in modeled total column-averaged mixing ratios of CH4 are significant for both models with a coarse vertical resolution of 4° × 6° × 25 (and 2° × 3° × 25, 1° × 1° × 25) and an improved one of 1° × 1° × 40. They are estimated to be 7–14 and 3–7 ppb in the winter extratropics under the assumption that isentropic mixing is dominant over vertical transport on a time scale of 3 days. Correspondingly, resulted biases in inverted CH4 surface emissions are estimated to be 0.5–1 and 0.2–0.5 mg/m2/hr, respectively, in the extratropics.

Atmospheric carbon monoxide (CO) and methane ( CH4 ) mole fractions are measured by ground-based in situ cavity ring-down spectroscopy (CRDS) analyzers and Fourier transform infrared (FTIR) spectrometers at two sites (St Denis and Maido) on Reunion Island (21 ∘ S, 55 ∘ E) in the Indian Ocean. Currently, the FTIR Bruker IFS 125HR at St Denis records the direct solar spectra in the near-infrared range, contributing to the Total Carbon Column Observing Network (TCCON). The FTIR Bruker IFS 125HR at Maido records the direct solar spectra in the mid-infrared (MIR) range, contributing to the Network for the Detection of Atmospheric Composition Change (NDACC). In order to understand the atmospheric CO and CH4 variability on Reunion Island, the time series and seasonal cycles of CO and CH4 from in situ and FTIR (NDACC and TCCON) measurements are analyzed. Meanwhile, the difference between the in situ and FTIR measurements are discussed. The CO seasonal cycles observed from the in situ measurements at Maido and FTIR retrievals at both St Denis and Maido are in good agreement with a peak in September–November, primarily driven by the emissions from biomass burning in Africa and South America. The dry-air column averaged mole fraction of CO ( XCO ) derived from the FTIR MIR spectra (NDACC) is about 15.7 ppb larger than the CO mole fraction near the surface at Maido, because the air in the lower troposphere mainly comes from the Indian Ocean while the air in the middle and upper troposphere mainly comes from Africa and South America. The trend for CO on Reunion Island is unclear during the 2011–2017 period, and more data need to be collected to get a robust result. A very good agreement is observed in the tropospheric and stratospheric CH4 seasonal cycles between FTIR (NDACC and TCCON) measurements, and in situ and the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) satellite measurements, respectively. In the troposphere, the CH4 mole fraction is high in August–September and low in December–January, which is due to the OH seasonal variation. In the stratosphere, the CH4 mole fraction has its maximum in March–April and its minimum in August–October, which is dominated by vertical transport. In addition, the different CH4 mole fractions between the in situ, NDACC and TCCON CH4 measurements in the troposphere are discussed, and all measurements are in good agreement with the GEOS-Chem model simulation. The trend of X CH 4 is 7.6±0.4 ppb yr −1 from the TCCON measurements over the 2011 to 2017 time period, which is consistent with the CH4 trend of 7.4±0.5 ppb yr −1 from the in situ measurements for the same time period at St Denis.

The height of the atmospheric boundary layer (ABLH) or the mixing layer height (MLH) is a key parameter characterizing the planetary boundary layer, and the accurate estimation of that is critically important for boundary layer related studies, which include air quality forecasts and numerical weather prediction. Aerosol lidar is a powerful remote sensing instrument frequently used to retrieve the ABLH through detecting the vertical distributions of aerosol concentration. Presently available methods for ABLH determination from aerosol lidar are summarized in this review, including a lot of classical methodologies as well as some improved versions of them. Some new recently developed methods applying advanced techniques such as image edge detection, as well as some new methods based on multi-wavelength lidar systems, are also summarized. Although a lot of techniques have been proposed and have already given reasonable results in several studies, it is impossible to recommend a technique which is suitable in all atmospheric scenarios. More accurate instantaneous ABLH from robust techniques is required, which can be used to estimate or improve the boundary layer parameterization in the numerical model, or maybe possible to be assimilated into the weather and environment models to improve the simulation or forecast of weather and air quality in the future.

Indoles are essential heterocycles in medicinal chemistry, and therefore, novel and efficient approaches to their synthesis are in high demand. Among indoles, 2-aryl indoles have been described as privileged scaffolds. Advanced herein is a straightforward, practical, and transition-metal-free assembly of 2-aryl indoles. Simply combining readily available 2-fluorotoluenes, nitriles, LiN(SiMe3 )2 , and CsF enables the generation of a diverse array of indoles (38 examples, 48-92 % yield). A range of substituents can be introduced into each position of the indole backbone (C4 to C7, and aryl groups at C2), providing handles for further elaboration.

Accurate estimation of the atmospheric boundary layer height (ABLH) is critically important and it mainly relies on the detection of the vertical profiles of atmosphere variables (temperature, humidity,’ and horizontal wind speed) or aerosols. Aerosol Lidar is a powerful remote sensing instrument frequently used to retrieve ABLH through the detection of the vertical distribution of aerosol concentration. A challenge is that cloud, residual layer (RL), and local signal structure seriously interfere with the lidar measurement of ABLH. A new objective technique presenting as giving a top limiter altitude is introduced to reduce the interference of RL and cloud layer on ABLH determination. Cloud layers are identified by looking for the rapid increase and sharp attenuation of the signal combined with the relative increase in the signal. The cloud layers whether they overlay the ABL are classified or are decoupled from the ABL are classified by analyzing the continuity of the signal below the cloud base. For cloud layer capping of the ABL, the limiter is determined to be the altitude where a positive signal gradient first occurs above the cloud upper edge. For a cloud that is decoupled from the ABL, the cloud base is considered to be the altitude limiter. For RL in the morning, the altitude limiter is the greatest positive gradient altitude below the RL top. The ABLH will be determined below the top limiter altitude using Haar wavelet (HM) and the curve fitting method (CFM). Besides, the interference of local signal noise is eliminated through consideration of the temporal continuity. While comparing the lidar-determined ABLH by HM (or CFM) and nearby radiosonde measurements of the ABLH, a reasonable concordance is found with a correlation coefficient of 0.94 (or 0.96) and 0.79 (or 0.74), presenting a mean of the relative absolute differences with respect to radiosonde measurements of 10.5% (or 12.3%) and 22.3% (or 17.2%) for cloud-free and cloudy situations, respectively. The diurnal variations in the ABLH determined from HM and CFM on four selected cases show good agreement with a mean correlation coefficient higher than 0.99 and a mean absolute bias of 0.22 km. Also, the determined diurnal ABLH are consistent with surface turbulent kinetic energy (TKE) combined with the time-height distribution of the equivalent potential temperature.

Background: Canagliflozin (CANA) administration increases amputation risk of the lower limb in the clinic. The present study aimed to investigate whether and how CANA interferer with intracellular physiological processes of mesenchymal stem cells (MSCs), and its contribution to ischemic lower limb. Methods: The in vivo blood flow recovery of ischemic lower limb following CANA treatment was evaluated. The cellular function of MSCs after CANA treatment were also assessed in vitro. In silico docking analysis and mutant substitution assay were conducted to confirm the interaction of CANA and glutamate dehydrogenase 1 (GDH1). Findings: Following CANA treatment, attenuated angiogenesis and hampered recovery of blood flow were observed in ischemic region, and the proliferation inhibition, migration inhibition, and apoptosis of MSCs was evidenced. CANA was involved in MSC mitochondrial respiratory malfunction, ATP production inhibition, cytochrome c release and vessel endothelial growth factor A (VEGFA) secretion inhibition, which contribute to reduced tissue repair capacity of MSCs, resulting in compromised angiogenesis and blood reperfusion in ischemic region. The detrimental effects of CANA on MSCs result from the inhibition of GDH1 by CANA (evidenced by in silico docking analysis and H199A-GDH1/ N392A-GDH1 mutant substitution). Interpretation: Our work highlights that GDH1 activity inhibition by CANA interferes with metabolic activity of mitochondria, which deteriorates retention and VEGFA secretion of MSCs, hampering angiogenesis and the recovery of blood flow following lower limb ischemia. Funding Statement: This study was financially supported by National Natural Science Foundation of China (grant # 81800314 for J. N.), Natural Science Foundation of Zhejiang Province (grant # LQ18H090007 for Z. L.) and Wenzhou Science and Technology Bureau Foundation (grant # Y20190163 for Y. L.). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: All experimental protocols were approved by the Animal Care and Use Committee of Wenzhou Medical University.

Sweating is a basic skin function in body temperature control. In sweat glands, salt excretion and reabsorption are regulated to avoid electrolyte imbalance. To date, the mechanism underlying such regulation is not fully understood. Corin is a transmembrane protease that activates atrial natriuretic peptide (ANP), a cardiac hormone essential for normal blood volume and pressure. Here, we report an unexpected role of corin in sweat glands to promote sweat and salt excretion in regulating electrolyte homeostasis. In human and mouse eccrine sweat glands, corin and ANP are expressed in the luminal epithelial cells. In corin-deficient mice on normal- and high-salt diets, sweat and salt excretion is reduced. This phenotype is associated with enhanced epithelial sodium channel (ENaC) activity that mediates Na+ and water reabsorption. Treatment of amiloride, an ENaC inhibitor, normalizes sweat and salt excretion in corin-deficient mice. Moreover, treatment of aldosterone decreases sweat and salt excretion in wild-type (WT), but not corin-deficient, mice. These results reveal an important regulatory function of corin in eccrine sweat glands to promote sweat and salt excretion., Sweating is a basic skin function in body temperature control, and salt excretion and reabsorption in sweat glands are essential for salt-water balance. This study identifies corin, a transmembrane protease that activates atrial natriuretic peptide, as a key enzyme in regulating salt excretion in the skin.

Wicking, the absorption of liquid into narrow spaces without the assistance of external forces, has drawn much attention due to its potential applications in many engineering fields. Increasing surface roughness using micro/nanostructures can improve capillary action to enhance wicking. However, reducing the structure length scale can also result in significant viscous forces to impede wicking. In this work, we demonstrate enhanced wicking dynamics by using nanostructures with three-dimensional (3D) hierarchical features to increase the surface area while mitigating the obstruction of liquid flow. The proposed structures were engineered using a combination of interference lithography and hydrothermal synthesis of ZnO nanowires, where structures at two length scales were independently designed to control wicking behavior. The fabricated hierarchical 3D structures were tested for water and ethanol wicking properties, demonstrating improved wicking dynamics with intermediate nanowire lengths. The experimental data agree with the derived fluid model based on the balance of capillary and vicious forces. The hierarchical wicking structures can be potentially used in applications in water harvesting surfaces, microfluidics, and integrated heat exchangers.

Background: Canagliflozin (CANA) administration increases the risk of lower limb amputation in the clinic. The present study aimed to investigate whether and how CANA interferes with the intracellular physiological processes of bone marrow derived mesenchymal stem cells (BM-MSCs) and its contribution to ischaemic lower limb. Methods: The in vivo blood flow recovery in ischaemic lower limbs following CANA treatment was evaluated. The cellular function of BM-MSCs after CANA treatment were also assessed in vitro. In silico docking analysis and mutant substitution assay were conducted to confirm the interaction of CANA with glutamate dehydrogenase 1 (GDH1). Findings: Following CANA treatment, attenuated angiogenesis and hampered blood flow recovery in the ischaemic region were detected in diabetic and non-diabetic mice, and inhibition of the proliferation and migration of BM-MSCs were also observed. CANA was involved in mitochondrial respiratory malfunction in BM-MSCs and the inhibition of ATP production, cytochrome c release and vessel endothelial growth factor A (VEGFA) secretion, which may contribute to reductions in the tissue repair capacity of BM-MSCs. The detrimental effects of CANA on MSCs result from the inhibition of GDH1 by CANA (evidenced by in silico docking analysis and H199A-GDH1/N392A-GDH1 mutant substitution). Interpretation: Our work highlights that the inhibition of GDH1 activity by CANA interferes with the metabolic activity of the mitochondria, and this interference deteriorates the retention of and VEGFA secretion by MSCs. Funding: National Natural Science Foundation of China, Natural Science Foundation of Zhejiang Province and Wenzhou Science and Technology Bureau Foundation. Keywords: Canagliflozin, Mesenchymal Stem Cells, Mitochondria, Glutamate dehydrogenase, Ischaemia

Amines are fundamental motifs in bioactive natural products and pharmaceuticals. Using simple toluene derivatives, a one-pot aminobenzylation of aldehydes is introduced that provides rapid access to amines. Simply combining benzaldehydes, toluenes, NaN(SiMe3)2, and additive Cs(O2CCF3) (0.35 equiv.) generates a diverse array of 1,2-diarylethylamine derivatives (36 examples, 56–98% yield). Furthermore, suitably functionalized 1,2-diarylethylamines were transformed into 2-aryl-substituted indoline derivatives via Buchwald–Hartwig amination. It is proposed that the successful deprotonation of toluene by MN(SiMe3)2 is facilitated by cation–π interactions between the arene and the group(I) cation that acidify the benzylic C–Hs., Amines are common targets in synthetic chemistry as they often display biological activity. Here, the authors report a one-pot aminobenzylation of aldehydes with readily available toluenes in presence of a sodium amide derivative and a cesium salt additive generating an array of valuable 1,2-diarylethylamine compounds.

Atmospheric carbon monoxide (CO) and methane (CH4) concentrations are measured by ground-based in-situ Cavity Ring-Down Spectroscopy (CRDS) analyzers and Fourier transform infrared (FTIR) spectrometers at two sites (St Denis and Maïdo) on Reunion Island (21° S, 55° E) in the Indian Ocean. Currently, the FTIR Bruker IFS 125HR at St Denis records the direct solar spectra in the near-infrared range, contributing to the Total Carbon Column Observing Network (TCCON). The FTIR Bruker IFS 125HR at Maïdo records the direct solar spectra in the mid-infrared range, contributing to the Network for the Detection of Atmospheric Composition Change (NDACC). In order to understand the atmospheric CO and CH4 variability on Reunion Island, the time series and seasonal cycles of CO and CH4 from in-situ and FTIR (NDACC and TCCON) measurements are analysed. Meanwhile, the difference between the in-situ and FTIR measurements are discussed. The CO seasonal cycles observed from the in-situ measurements at Maïdo and FTIR retrievals both at St Denis and Maïdo are in good agreement with a peak in September–November, primarily driven by the emissions from biomass burning in Africa and South America. The dry-air column averaged mole fraction of CO (XCO) derived from the FTIR MIR spectra (NDACC) is about 15.7 ppb larger than the CO mole fraction near the surface at Maïdo, because the air in the lower troposphere mainly comes from the Indian Ocean while the air in the middle and upper troposphere mainly comes from Africa and South America. The trend for CO on Reunion Island is unclear during 2011–2017, and more data need to be collected to get a robust result. A very good agreement is observed in the tropospheric and stratospheric CH4 seasonal cycles between FTIR (NDACC and TCCON) measurements, and in-situ and the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) satellite measurements, respectively. In the troposphere, the CH4 mole fraction is high in August–September and low in December–January, which is due to the OH seasonal variation. In the stratosphere, CH4 concentration has its maximum in March–April and its minimum in August–October, which is dominated by the vertical transport. In addition, the different CH4 concentration between the in-situ, NDACC and TCCON CH4 measurements in the troposphere are discussed, and all measurements are in good agreement with the GEOS-Chem model simulation. The trend of XCH4 is 7.6 ± 0.4 ppb/year from the TCCON measurements over the 2011–2017 time period, which is consistent with the CH4 of 7.4 ± 0.5 ppb/year from the in-situ measurements for the same time period at St Denis.

Background/Aims: Primary hepatocellular carcinoma (HCC) is highly invasive, and often results in an early distal metastasis resulting in poor prognosis and therapeutic outcome. Cancer cells disseminating from the tumor and entering circulation are termed circulating tumor cells (CTCs). Although substantial progress has been made to identify those CTCs in HCC, no good marker (cocktail) has so far been identified. Methods: Since only tumorigenic CTCs form metastatic tumor in distal organs, we thus compared the HCC cells that form tumor spheres in culture to those that do not. We transduced HCC cells with a RFP reporter under MMP26 promoter and purified MMP26+CXCR4+ HCC cells. We examined tumor sphere formation in culture, presence of tumor cells in the circulation as well as capability of developing metastatic tumor after transplantation of MMP26+CXCR4+ HCC cells into nude mice, compared to other populations in HCC. Results: Sphere-forming HCC cells expressed high levels of MMP26 and CXCR4. MMP26+CXCR4+ HCC cells formed significantly more tumor spheres in culture, compared to MMP26-CXCR4-, MMP26-CXCR4+ or MMP26+CXCR4- HCC cells. Moreover, tumor cells were more frequently detected in the circulation when MMP26+CXCR4+ HCC cells were subcutaneously transplanted. Further, subcutaneous transplantation of MMP26+CXCR4+ HCC cells, but not transplantation of MMP26-CXCR4-, MMP26-CXCR4+ or MMP26+CXCR4-HCC cells significantly developed distal metastatic tumors. Conclusion: MMP26+CXCR4+ cells may be CTCs in HCC. Selective elimination of MMP26+CXCR4+ cells may substantially reduce HCC metastasis after primary tumor resection.

The equivalent length, a measure for mixing strength in the atmosphere, in meridional direction in the current application, is used here to investigate the causes of the atmospheric chemistry model (TM3, TM5-4DVAR and LMDz-PYVAR) biases in the stratosphere. Compared to measurements, we find that the modeled surf zone (a strongly stirred region caused by planetary wave breaking in mid-latitude stratosphere in the winter hemisphere), especially in the southern hemisphere, is not strong enough. We assume that this is due to an underestimation of the planetary wave breaking magnitude in the models. Consequently, the region with meridional uniform stratospheric CH4 concentrations has smaller latitudinal coverages in the models than the measurements, especially in the southern hemisphere between June and September. During the southern winter, a region with both vertically and horizontally well mixed CH4 concentrations occur between 450 and 850 K (~ 18 and 30 km) in surf zone latitudes. Such a region is absent in the models, and underestimations of CH4 concentrations within it are visible in comparisons with measured CH4 profiles. The modeled polar vortex breaks too fast and during the vortex period CH4 concentration differences across its barrier are underestimated compared to the measurements.

Inverse modelling is a useful tool for retrieving CH4 fluxes; however, evaluation of the applied chemical transport model is an important step before using the inverted emissions. For inversions using column data one concern is how well the model represents stratospheric and tropospheric CH4 when assimilating total column measurements. In this study atmospheric CH4 from three inverse models is compared to FTS (Fourier transform spectrometry), satellite and in situ measurements. Using the FTS measurements the model biases are separated into stratospheric and tropospheric contributions. When averaged over all FTS sites the model bias amplitudes (absolute model to FTS differences) are 7.4 +/- 5.1, 6.7 +/- 4.8, and 8.1 +/- 5.5 ppb in the tropospheric partial column (the column from the surface to the tropopause) for the models TM3, TM5-4DVAR, and LMDz-PYVAR, respectively, and 4.3 +/- 9.9, 4.7 +/- 9.9, and 6.2 +/- 11.2 ppb in the stratospheric partial column (the column from the tropopause to the top of the atmosphere). The model biases in the tropospheric partial column show a latitudinal gradient for all models; however there are no clear latitudinal dependencies for the model biases in the stratospheric partial column visible except with the LMDz-PYVAR model. Comparing modelled and FTS-measured tropospheric column-averaged mole fractions reveals a similar latitudinal gradient in the model biases but comparison with in situ measured mole fractions in the troposphere does not show a latitudinal gradient, which is attributed to the different longitudinal coverage of FTS and in situ measurements. Similarly, a latitudinal pattern exists in model biases in vertical CH4 gradients in the troposphere, which indicates that vertical transport of tropospheric CH4 is not represented correctly in the models.