Synthesis of gem-Difluorinated 2,3-Dihydrobenzofurans Using Freon-22 via [4 + 1] Annulation of Difluorocarbene and Antitumor Activity Evaluation.

As an inexpensive industrial chemical, chlorodifluoromethane (Freon-22), despite its relatively low reactivity, can serve as a practical CF2 source for the construction of gem-difluorinated ring structures. Here, we develop a protocol for the efficient assembly of valuable fluorinated 2,3-dihydrobenzofurans from the [4 + 1] annulation in good yields under basic conditions. The reliable practicability and scalability of the process have also been demonstrated by preparation at the multigram scale, late-stage modifications of pharmaceutical molecules, and potential antitumor potency.

How digitalization and financial development impact eco-efficiency? Evidence from China.

The rapid growth of industrial digitalization and financial support are the main driving forces for the green transformation of China's economy. Aiming to explore how digitalization and financial development impact ecological efficiency (eco-efficiency), this study proposes a unified research framework by integrating multiple technologies using the panel data that covered 30 China's provinces from 2006 to 2018. First, China's provincial digital development index is constructed to measure the level of digitalization, and regional eco-efficiency is estimated by a non-radial data envelope analysis (DEA) model. Based on that, the panel data regression model and panel vector autoregression (PVAR) model are used to explore the direct effects and dynamic effect of digitalization and financial development on eco-efficiency, respectively. Then, the threshold regression model is employed to check the threshold effect of the two variables on eco-efficiency. The following conclusions are drawn: (1) Both digitalization and financial development have a significantly positive correlation with regional eco-efficiency, indicating that China's digitalization and financial development in recent years have both improved regional eco-efficiency. (2) Eco-efficiency has positive and longer responses to the impulse coming from digitalization and financial development, and the response of ecological efficiency to financial development is greater than its response to digitalization. (3) Threshold effects exist in the impact mechanism of digitalization on regional eco-efficiency. This indicates that the level of financial support is too low to promote the improvement in ecological efficiency. Eco-efficiency can be improved only to a certain extent. The research conclusions provide a policy reference for improving eco-efficiency and promoting China's green development.

In situ self-assembly of three-dimensional porous graphene film on zinc fiber for solid-phase microextraction of polychlorinated biphenyls.

Three-dimensional porous graphene film (3DPGF) was fabricated on Zn fiber for solid-phase microextraction (SPME) through in-situ self-assembly strategy at room temperature. Fast electron transfer due to ionization of zinc induces reduction of graphene oxide and thus leads to the layer-by-layer interfacial deposition of graphene sheets, forming three-dimensional porous network morphology. The 3D interpenetrating porous structure could provide more available adsorption site for the target molecules and also enhance mass transfer efficiency in the extraction process. Therefore, the obtained 3DPGF fiber exhibited excellent performance when applied in the SPME of preconcentration and quantification of polychlorinated biphenyls (PCBs) in environment waters. The developed method showed a linear range from 1.0 ng L-1 and 200 ng L-1 with an acceptable correlation (R2=0.990). The limit of detection (LOD) and limit of quantification (LOQ) were found 0.03-0.2 ng L-1 and 0.1-0.8 ng L-1, respectively. The proposed method was applied in real water samples analysis with the recoveries ranging from 63.1 to 111.3%. The present study expanded the application of three-dimensional porous graphene materials in sample preparation and revealed its potential in SPME application.

A Field Study on Safety Performance of Apron Controllers at a Large-Scale Airport Based on Digital Tower.

The innovative concept of digital tower provides a new solution for reducing the construction and operation costs of airports with adverse natural environments, poor intervisibility conditions, or sparse traffic. However, it leads to changes in the situational awareness of air traffic controllers and to challenges in safety performance. To research the safety performance of apron controllers at a large-scale airport applying a digital tower, a field study was conducted at Baiyun International Airport in Guangzhou, China. In this study, we established a comprehensive index system from the perspective of situational awareness, which provided measurements on the areas of interests, gaze and physiological features, and vigilance of controllers. Three modules were compared: a physical tower module, a digital tower module with a large panoramic screen, and a digital tower module with a small panoramic screen. The differences in the safety performances of apron controllers are discussed in two aspects: adaptability and reliability. The results indicated that the apron controllers at the three modules performed different cognition patterns, but similar cognition effort was paid toward maintaining performance. Furthermore, the significant vigilance decrement of controllers exists between after-duty and before-duty, but with no significant difference among the three modules. In conclusion, apron controllers at a large-scale airport could obtain effective safety performances based on a digital tower that were no less than those from a physical tower.

Policy shock effect of SDP on environmental total factors productivity: 53 coal cities versus 165 non-resource-based cities.

The trend of economic decline for coal cities is a serious threat to the high-quality development of China's economy, and how to improve the environmental total factor productivity (ETFP) has become an urgent issue. Based on the framework of data envelopment analysis (DEA), this paper estimates ETFP using the global Malmquist-Luenberger productivity index (GMLPI). We decompose GMLPI into environmental technical efficiency change (ETEC) and the best practice gap change (BPGC). Then, the difference-in-difference (DID) model combining propensity score matching (PSM) method is used to investigate the effect of the Sustainable Development Plan of National Resource-based Cities (2013-2020) (SDP) aiming to improve ETFP. The results indicate that (1) On average, the GMLPI and BPGC are rising, while the ETEC is decreasing in the observed sample period; the western regions have the biggest BPGC, while the eastern regions have the biggest ETEC; (2) The SDP significantly improves the GMLPI and BPGC but has little effect on the ETEC; Coal cities located in eastern and central regions have policy effect, while the western regions do not have. (3) The SDP affects ETFP through slowing down the economic growth rate and reducing population agglomeration, but promoting the optimization of industrial structure. Those findings have policy implications for improving ETFP and promoting the industrial upgrade of coal cities.

A Field Study of Work Type Influence on Air Traffic Controllers' Fatigue Based on Data-Driven PERCLOS Detection.

The fatigue of air traffic controllers (ATCOs) on duty seriously threatens air traffic safety and needs to be managed. ATCOs perform several different types of work, with each type of work having different characteristics. Nonetheless, the influence of work type on an ATCO's fatigue has yet to be demonstrated. Here, we present a field study in which the fatigue of ATCOs working in two types of work was compared based on an optimized data-driven method that was employed to detect the percentage of eyelid closure over the pupil over time (PERCLOS). Sixty-seven ATCOs working within two typical jobs (i.e., from the terminal control unit (TCU) and area control unit (ACU)) were recruited, and their fatigue was detected immediately before and after shift work using PERCLOS. Using a Spearman correlation test analysis, the results showed that the influence of work type on an ATCO's fatigue had interesting trends. Specifically, the ATCOs at the TCU who handle departures and arrivals, which include converging with and maneuvering around conflicts, retain normal circadian rhythms. Their fatigue was significantly influenced by the various demands from tasks focusing on sequencing and conflict resolution and by the time phase of a normal circadian rhythm. At the ACU, ATCOs manage flights that are mainly on route, causing monotonous monitoring and routine reporting tasks, and the ATCOs generally have frequent night shifts to handle overflights. Their fatigue was significantly influenced by the demand characteristics from tasks, but changes in fatigue rule were not consistent with a normal circadian rhythm, revealing that the ATCOs' circadian rhythms may have already been slightly disturbed. Furthermore, the interactions between task demand and circadian rhythm with an ATCO's fatigue were significantly observed in ATCOs working in the TCU but not in those in the ACU. This study provides first evidence that an ATCO's work type influences his or her fatigue. This discovery may incite stakeholders to consider work type in the management of employee fatigue, not only in the civil aviation industry but also in other transport industries.

Modelling the symmetrical and asymmetrical effects of global oil prices on local food prices: A MENA region application.

This paper explores the complex nexus between the global oil prices and the food prices of the Middle East and North Africa (MENA) region during the period 2000-2020. Both linear and nonlinear models of the autoregressive distributed lag (ARDL) approach are adapted into panel data form to investigate the symmetrical and asymmetrical influence of oil prices on food prices. The key results are summarized: (i) the long-term effect of oil prices on food prices is significantly positive including both oil-exporting and oil-importing nations. The positive impact on oil exporters-due to higher oil revenues-is greater than importing nations, leading to an increased demand for food. Additionally, the effect on oil exporters is negative and significant in the short term but not significant for importers. (ii) The nonlinear ARDL panel analysis for the whole MENA sample confirms the presence of negative short-term asymmetric behaviour due to the heterogeneous response within the oil-importing and oil-exporting samples, while in the long term, the asymmetric effect is positive, indicating that food prices increase regardless of fluctuations in oil prices. (iii) The nonlinear ARDL results using time series affirm the absence of an asymmetric nexus among oil and food prices for some oil-exporting nations (including Kuwait, Saudi Arabia, United Arab Emirates) and Tunisia within the oil-importing group. However, the food prices of other countries are asymmetric to the oil price. This study provides recommendations that are useful to MENA countries to establish a stable mechanism for oil and food prices to ensure food security in the region.

Application of LC-MS-Based Global Metabolomic Profiling Methods to Human Mental Fatigue.

Mental fatigue is characterized by a reduced capacity for work and a loss of capacity to respond to stimulation and is usually accompanied by a feeling of tiredness and drowsiness. Mental fatigue at work is a serious problem and can raise safety concerns especially in the transportation system. It is believed that mental fatigue is a direct or contributing cause of road and air related accidents and incidents. Psychological studies indicate that fatigue results in reduced work efficiency, alertness, and impaired mental performance. However, its underlying biochemical mechanisms are poorly understood. We hypothesized that the human body is an integrated system, and mental fatigue results in changes not only in psychology but also in biochemistry of the human body. These biochemical changes are detectable in metabolites. We employed global metabolomic profiling methods to screen biochemical changes that occur with mental fatigue in air traffic controllers (ATCs) in civil aviation. A total of 45, all male, ATCs (two batches) were recruited as two mental fatigue groups and 23 executive staff acted as a control group for this study. The volunteers' urine samples were collected before and after their work. The samples were analyzed with liquid chromatography/mass spectrometry equipped with a polar, a weak polar, and a nonpolar column, respectively. Three candidate biomarkers were selected on the basis of statistical significance, coefficient of variance, and compared with data of the three groups. The results suggest that urine metabolites may provide a complete new clue from biochemistry to understand, monitor, and manage human mental fatigue.

Application of quantum weak measurement for glucose concentration detection.

A quantum weak measurement scheme based on a Mach-Zehnder interferometer is proposed to detect the concentration of glucose, bringing this mechanism into the field of biomedical sensing for the first time, to the best of our knowledge. With a Mach-Zehnder interferometer system, we can analyze tiny phase differences between the two paths by measuring spectrum shift. We measured the concentration of glucose with weak measurement to achieve a concentration resolution of 8.98×10⁻5 g/L corresponding to a volume refractive index of 1.39×10⁻8 RIU, which was more than five times higher than the resolution achieved by conventional interference, 4.99×10⁻4 g/L. In the detection of glucose concentration in the blood serum of mice, a resolution of 1.0136×10⁻7 g/L for weak measurement was obtained.

Resolution enhancement of surface plasmon resonance sensors with spectral interrogation: resonant wavelength considerations.

Surface plasmon resonance (SPR) has been used extensively in biosensing implementation as a high-sensitivity and label-free sensing technique. For SPR sensors based on spectral interrogation, their performance in terms of refractive index (RI) resolution differs substantially when operating at different resonant wavelengths. This paper presents a feasible scheme of enhancing the sensor resolution by simulating measured SPR curves using an experiment-assisted simulation model to effectively explore the optimal resonant wavelength for the sensing system. It shows that the variation of experimentally obtained RI resolution with the resonant wavelength is in good accordance with the simulation results. In addition, the RI resolution at the derived optimal resonant wavelength is at least 2 times better than that at the commonly used resonant wavelength region both experimentally and theoretically. The methods of the proposed scheme potentially facilitate optimization of various sensor instrumentation for high-resolution SPR sensing.

Efficient enantioselective synthesis of dihydropyrans using a chiral N,N'-dioxide as organocatalyst.

The bifunctional organocatalyst C3 N,N'-dioxide has been successfully applied to the asymmetric cascade Michael/hemiacetalization reaction of α-substituted cyano ketones and ß,γ-unsaturated α-ketoesters for the synthesis of multifunctionalized chiral dihydropyrans. The corresponding products were obtained in excellent yields (up to 99%) with high to excellent enantioselectivities (up to 99% ee).

Asymmetric synthesis of trans-ß-lactams by a Kinugasa reaction on water.

The asymmetric Kinugasa reaction was performed on pure water for the first time without the need for any organic co-solvents. In contrast to most asymmetric Kinugasa reactions, trans-ß-lactams were obtained as the major products in good yields, enantioselectivities, and diastereoselectivities (up to 90 % yield, 98 % ee, and >99:1 d.r.). This reaction is atom-economical, environmentally friendly, and affords synthetically useful but challenging products.

Co-cultured endometrial stromal cells and peritoneal mesothelial cells for an in vitro model of endometriosis.

This paper demonstrates an in vitro model to simulate the microenvironment of endometriosis. We used microfluidic channels with cover slips to pattern and release endometrial stromal cells (ESCs) and human peritoneal mesothelial cells (HPMCs) in a way that mimicked the pathophysiology of peritoneal endometriosis. This approach enabled observation in real time interactions between ESCs and HPMCs both in their normal and pathological states. HPMCs from control individuals were able to resist the invasion of ESCs from both control and endometriotic individuals. By contrast, HPMCs from endometriotic individuals were unable to resist the invasion of ESCs from both normal and endometriotic individuals. We further analyzed the dynamics between HPMCs and ESCs from endometriotic individuals. HPMCs from endometriotic individuals relaxed their adhesion to each other at the beginning of invasion of ESCs, lose their adhesion to the substrate and apoptosed when surrounded by ESCs. These data implicate that the peritoneal physiology may play an important role in endometriosis.

Continuous electrochemical monitoring of extracellular lactate production from neonatal rat cardiomyocytes following myocardial hypoxia.

Continuous monitoring of lactate production from cardiomyocytes is of great physiological and pathological importance since the level of lactate in extracellular fluid is closely associated with myocardial energy metabolism with implication in the diagnosis and therapeutics of myocardial hypoxia and ischemia. This study demonstrates an electrochemical approach to continuous monitoring of lactate production from neonatal rat cardiomyocytes following myocardial hypoxia with a dehydrogenase-based electrochemical biosensor and a negative pressure driven culture sampling. To eliminate the effect of pH variation occurring following the cardiomyocyte hypoxia on the biosensor response and to supply nicotinamide adenine dinucleotide (NAD(+)) cofactor necessary for the enzymatic reaction of lactate dehydrogenase (LDH), artificial cerebrospinal fluid (aCSF) containing NAD(+) cofactor is externally perfused and mixed online with cell culture before the culture goes to the detector. The method exhibits a high selectivity against the electrochemically active species endogenously existing in the extracellular culture of cardiomyocytes and a high tolerance against the variation of pH following cardiomyocyte hypoxia. The dynamic linear range for lactate detection is from 0.20 to 10 mM (I (nA) = 25.6 C(Lactate) (mM) + 20.1, γ = 0.996) with a detection limit of 0.16 mM (S/N = 3). The physiological level of the extracellular lactate of neonatal rat cardiomyocytes is determined to be 1.1 ± 0.1 mM (n = 3) with the cell density of about 0.5 × 10(3) cells/mm(2). When the cardiomyocytes are subject to hypoxia induced with anoxic reagents, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), the extracellular lactate increases to 255 ± 30.3% (n = 3), relative to the physiological level, following 20 min of the hypoxia. This study essentially offers a new and effective electrochemical platform for investigating energy metabolism during cardiac physiological and pathological processes.

Evaluating cell migration in vitro by the method based on cell patterning within microfluidic channels.

Cell migration is an early-stage and critical step for cancer metastasis. The most common approach to monitor this process is wound-healing assay. However, this traditional method has some unavoidable limitations. We observed that simply scratching the monolayer of cultured cells might cause local cell damage around the injury line. The cells along the scratched border seemed to be irritated and exhibited abnormal distribution of cytoskeleton reassembly with protruding "cell islands" and "pseudopodia" during wound healing, which might potentially affect the assessment of cell migration behavior. Herein, we applied a microfluidic device that mechanically constrained cells seeded in a designed pattern inside microchannels, and monitored cell movement in a way of mimicking the natural microenvironment of cancerous tissues. We illustrated the capacity of this simple method to probe cellular migration behaviors and to screen some biological active agents that reflected in their influence on cellular motility.

Highly Z-selective asymmetric conjugate addition of alkynones with pyrazol-5-ones promoted by N,N'-dioxide-metal complexes.

Highly selective: the title reaction is achieved with high enantiomeric and geometric control and thermodynamically unstable (Z)-enone derivatives are obtained as the major products. The procedure tolerates a wide range of substrates to generate optically active pyrazolones with vinyl-substituted quaternary stereocenters.

A naked-eye visible and fluorescence "turn-on" probe for acetyl-cholinesterase assay and thiols as well as imaging of living cells.

A resorufin derivative with a DBS group (probe 1) was designed and investigated for the detection of acetylcholinesterase (AChE) and inhibitor screening. The new assay is based on cascade enzymatic and chemical reactions of ATC, AChE and probe 1, and it can be carried out in a dual-signal detection mode. Moreover, the results show that probe 1 can be used for cell fluorescence staining.

In vitro model on glass surfaces for complex interactions between different types of cells.

This report establishes an in vitro model on glass surfaces for patterning multiple types of cells to simulate cell-cell interactions in vivo. The model employs a microfluidic system and poly(ethylene glycol)-terminated oxysilane (PEG-oxysilane) to modify glass surfaces in order to resist cell adhesion. The system allows the selective confinement of different types of cells to realize complete confinement, partial confinement, and no confinement of three types of cells on glass surfaces. The model was applied to study intercellular interactions among human umbilical vein endothelial cells (HUVEC), PLA 801 C and PLA801 D cells.