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The recent remarkable increase in induced seismicity in Western Canada has been largely attributed to hydraulic fracturing in unconventional reservoirs. The nucleation of large magnitude events has been demonstrated to be closely linked to site-specific geological and operational factors. A mitigation strategy of fracturing-induced seismicity concerning both factors has not been well investigated. In this paper, a comprehensive investigation of risk mitigations from induced seismicity is conducted based on the formation overpressure, distance to Precambrian basement, proximity to faults, fracturing job size and safe hydraulic fracture-fault distance. It is found that the middle-south region near Crooked Lake is an optimal region for fracturing operations with low formation pressure, a great distance to the basement and relatively fewer pre-existing faults. A field case study suggests that fracturing operations of three new horizontal wells are successful with low magnitude induced events and with high production performance, demonstrating the applicability of a comprehensive approach of seismicity risk mitigations. Such an approach can be applied to other field cases to mitigate the potential fracturing-induced seismicity in unconventional reservoirs., (© 2022. The Author(s).)

Objective: To explore the effects of cardiopulmonary exercise testing (CPET) on the cardiopulmonary function, the exercise endurance, and the NT-proBNP and hscTnT levels in chronic heart failure (CHF) patients., Methods: Altogether 98 patients with CHF were randomly divided into a control group and a CPET group, with 49 cases in each group. The control group was administered routine treatment, and the CPET group was administered CPET cardiac rehabilitation training in addition to the routine treatment. Heart and lung function, exercise endurance, and the peripheral blood NTproBNP, hscTnT, and CRP levels were observed. The patients' quality of life, anxiety, and depression were observed using the scale., Results: After the treatment, the left ventricular end systolic diameters (LVESD) and the left ventricular end diastolic diameters (LVEDD) were significantly decreased, the left ventricular ejection fractions (LVEF), the stroke volumes (SV), and the CI levels were significantly increased, and there were significant differences in these indexes between the CPET group and the control group (all P<0.05). After the treatment, the carbon dioxide ventilation equivalent slope (VE/VCO 2 slop) decreased significantly, the peak oxygen consumption (peakVO 2 ) and anaerobic threshold oxygen consumption (VO 2 AT) levels increased significantly, and there were significant differences in these indicators between the CPET group and the control group (all P<0.05). Compared with the control group, the exercise endurance, the maximum oxygen uptake capacity (VO 2 max), the maximum power, the exhaustion times, and the six-minute walking test (6MWT) levels in the CPET group increased significantly (all P<0.05). After the treatment, the N-terminal precursor brain natriuretic peptide (NTproBNP), the high sensitivity cardiac troponin (hscTnT), and the C-reactive protein (CRP) levels in the two groups were decreased compared with their pre-treatment levels, and there were significant differences in these indexes between the CPET group and the control group (all P<0.05). After the treatment, the Minnesota living with heart failure questionnaire (MLHFQ), the self-rating anxiety scale (SAS), and the self-rating depression scale (SDS) scores in the two groups were significantly lower than they were before the treatment, and there were significant differences in the two scores between the CPET group and the control group (all P<0.05)., Conclusion: CPET for patients with CHF helps increase heart and lung function, improves exercise endurance, reduces the NT-proBNP and hscTnT levels, and improves patients' quality of life., Competing Interests: None., (AJTR Copyright © 2021.)

N-Heterocyclic carbene-catalyzed asymmetric construction of cyclopentenones using enals and α-diketones is achieved, furnishing a series of highly functionalized cyclopentenones in a highly diastereo- and enantioselective manner. The protocol tolerates substrates with both aromatic and aliphatic groups, and further transformations of the products delivered a range of value-added molecules.

A unique deoxygenative cyclodimerization of alkynyl 1,2-diketones facilitated by Ti(O i Pr) 4 is achieved, affording a series of highly functionalized furan products. An unusual C-C bond and C═O bond cleavage of the substrates is observed, and Ti(O i Pr) 4 plays triplicate roles in the reaction. Furthermore, the products show uncommon fluorescent emission in the solid state, indicating the potential practical applications of this work.

Lung cancer is a life-threatening disease and its diagnosis is of great significance. Data scarcity and unavailability of datasets is a major bottleneck in lung cancer research. In this paper, we introduce a dataset of pulmonary lesions for designing the computer-aided diagnosis (CAD) systems. The dataset has fine contour annotations and nine attribute annotations. We define the structure of the dataset in detail, and then discuss the relationship of the attributes and pathology, and the correlation between the nine attributes with the chi-square test. To demonstrate the contribution of our dataset to computer-aided system design, we define four tasks that can be developed using our dataset. Then, we use our dataset to model multi-attribute classification tasks. We discuss the performance in 2D, 2.5D, and 3D input modes of the classification model. To improve performance, we introduce two attention mechanisms and verify the principles of the attention mechanisms through visualization. Experimental results show the relationship between different models and different levels of attributes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Kong, Li, Zhu, Lu, Shen, Shah, Bennamoun and Hua.)

Based on intracellular second messenger cAMP, the cyclic AMP-protein kinase A (cAMP-PKA) pathway transforms extracellular stimuli to activate effectors and downstream signaling components, mediating physiological processes in filamentous fungi. The concentration of intracellular cAMP was regulated by adenylate cyclase biosynthesis and cAMP phosphodiesterase (PDEs) hydrolysis, which mediate signal transduction and termination. In this study, we used a gene deletion and complementary strategy to characterize the functions of AaPdel and AaPdeh genes, which encoded low-affinity PDEs (Pdel) and high-affinity PDEs (Pdeh), respectively, in Alternaria alternata. AaPdel , but not AaPdeh , was found to be a key regulator in conidiation and pathogenesis in A. alternata . Δ AaPdel showed defects in conidiation, producing approximately 65% reduced conidiation and forming lowly pigmented aberrant structures. In response to osmotic stress, Δ AaPdel was more sensitive to non-ionic osmotic stress than ionic osmotic stress. Moreover, AaPdel deletion mutants had defects in vegetative growth and hyphal growth. Further analyses showed that the high chitin content of Δ AaPdel might account for the sensitivity to Congo red. Based on the attenuated pathogenicity and lowly pigmented aberrant structures, the laccase activity analysis found that both AaPdel and AaPdeh were involved in laccase activity regulation. Our data further support the PKA-mediated cAMP signaling pathway, as we have found that AaPdel was involved in intracellular cAMP levels in A. alternata., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Lv, Kong, Zhou and Tang.)

Objective: This research aims to analyze the application regularity of Chinese patent medicine during the COVID-19 epidemic by collecting the names of the top three Chinese patent medicines used by 24 hospitals in 14 provinces of China in four time periods (January 20-22, February 16-18, March 01-03, April 01-03, 2020), and explore its contribution to combating the disease. Methods: 1) We built a database of the top three Chinese patent medicines used by 24 hospitals. 2) The frequency and efficacy distribution of Chinese patent medicine were analyzed with risk areas, regions, and hospitals of different properties as three factors. 3) Finally, we analyzed the differences in the use of heat-clearing and non-heat-clearing medicines among the three factors (χ 2 test) and the correlation between the Chinese patent medicine and COVID-19 epidemic (correlation analysis) with SPSS 23.0 statistical software. Results: 1) The heat-clearing medicine was the main use category nationwide during January 20-22, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas ( p < 0.01). 2) The variety of Chinese patent medicine was increased nationwide during February 16-18, 2020, mainly including tonics, blood-activating and resolving-stasis, and heat-clearing medicines. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in the southern and northern regions ( p < 0.05). 3) Tonics, and blood-activating and resolving-stasis medicines became the primary use categories nationwide during March 01-03, 2020. 4) The tonics class, and blood-activating and resolving-stasis medicine were still the primary categories nationwide during April 01-03, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas ( p < 0.01). Conclusion: Chinese patent medicine has a certain degree of participation in fighting against the COVID-19. The efficacy distribution is related to the risk area, region, and hospital of different properties, among which the risk area is the main influencing factor. It is hoped that future research can further collect the application amount of Chinese patent medicine used in hospitals all over the country, so as to perfectly reflect the relationship between Chinese patent medicine and the epidemic situation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Zhang, Shi, Li, Liu, Han, Liu, Zhang, Kong, Zhang, Yuan, Liu, Deng, Zheng, Zhang, Li, Wang, Wu, Lin, Nian, Wu, Wang, Liu, Wang, Wang, Liu, Liu, Zeng, Yang, Wang, Zhai and Wang.)

We report the highly regio- and enantioselective alkynylation of alkynyl 1,2-diketones under Lewis acid catalysis, leading to the formation of a series of biologically important 3(2 H )-furanones with high to excellent ee values. Moreover, a slight change of the reaction conditions produces a range of highly functionalized α-hydroxy ketones with a high level of enantioselectivity. A variety of further transformations can be easily achieved, demonstrating the synthetic potential of this protocol.

Inverse-electron-demand Diels-Alder reactions have attracted intense research focus. However, enolate and enamine are the most employed intermediates to realize such transformation, and the use of dienolate intermediate remains elusive. Reported herein is the asymmetric inverse-electron-demand oxa-Diels-Alder reaction between allyl ketones and alkenyl 1,2-diketones using a bifunctional thiourea catalyst. The reaction afforded various highly functionalized dihydropyrans with good to excellent enantioselectivities under mild conditions, and further novel transformations on the products have also been realized.

Racemic mixtures of four stereoisomers are easily formed via many fundamental organic transformations, but the direct utilities of these mixtures have been less studied and remain large challenges to date. In this work, we introduce a new method, i.e., divergent dynamic kinetic resolution, to achieve the separation of racemic mixtures of four stereoisomers. The hypothesis was proved by using a N-heterocyclic carbene-catalyzed benzoin reaction, which afforded two separable diastereomeric products bearing three consecutive stereocenters with good to excellent enantioselectivties. We believe that this resolution protocol will find applications in more transformations., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report that α-acyloxy-β,γ-unsaturated cyclopentenones were used as starting substrates to make various trisubstituted cyclopentadienones. The substrates are easily available in one step from our previously developed protocol, and the potential of this cyclopentadienone formation method was demonstrated in a series of Diels-Alder reactions, forming dimerization products, dimethyl phthalate derivatives, and polyaryl benzene compounds.

The discovery of new reaction modes mediated by easily available substrates is an important research topic in organic synthesis. Allyl ketones and related compounds have been demonstrated to undergo γ- or α-selective additions to different electrophiles. We disclose here the Brønsted base-catalyzed reaction of allyl ketones and alkynyl 1,2-diketones, which undergo a unique α-selective addition/intramolecular aldol-type annulation/C-C bond cleavage process, and a series of 2-acyloxycyclopent-3-enones can be obtained under very mild conditions.