•There were season variations of influence factors on land surface temperature (LST) and aerosol optical depth (AOD)•A part of landscape metrics only effect simultaneously to relieve LST and ...AOD.•Interactive effects of factor layers on LST and AOD were explored.•The direct impact of landscape metrics on LST and AOD was greater than the indirect.
Urban heat island (UHI) and air pollution are common environmental problems in urban areas. However, there is no comprehensive analysis of influencing factors and their interactions on land surface temperature (LST) and aerosol optical depth (AOD). To propose strategies to comprehensively mitigate LST and AOD by optimizing the landscape pattern, we used a series of statistical analysis methods to quantify the correlation, interactive contribution, and influence mechanism that how landscape metrics influenced LST and AOD directly or indirectly. In warmer seasons and year, the percentage of landscape (PLAND), largest patch index (LPI), aggregation index (AI) in forest land (FL), and mean shape index distribution (SHAPE_MN) in wetlands (WL) were negatively correlated with LST and AOD consistently. In contrast, landscape shape index (LSI) in FL, patch density (PD) and LSI in WL, edge density (ED), PD, LPI, SHAPE_MN, and LSI in artificial surfaces were positively correlated. Landscape metrics were weakly correlated with LST and AOD in winter. The climate condition layer was dominant overall. The dominant factor layer of landscape composition, landscape configuration and green quantity on LST and AOD differed in different land types and seasons. Landscape metrics and green quantity could directly or indirectly affect LST and AOD, with the direct effects of landscape metrics and green quantity being the primary. Increasing the percentage of FL, configuring large, aggregated and simple FL, regular, simple and better connected wetlands, and increasing patterns in artificial surfaces with simple, regular, small and better connectivity characteristics are effective mitigation measures. These findings can be helpful in developing UHI and air pollution adaptation strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cyber attacks and malfunctions challenge the wide applications of Internet of Things (IoT). Since they are generally designed as embedded systems, typical auto-sustainable IoT devices usually have a ...limited capacity and a low processing power. Because of the limited computation resources, it is difficult to apply the traditional techniques designed for personal computers or super computers, like traffic analyzers and antivirus software. In this paper, we propose to leverage statistical learning methods to characterize the device behavior and flag deviations as anomalies. Because the system statistics, such as CPU usage cycles, disk usage, etc., can be obtained by IoT application program interfaces, the proposed framework is platform and deviceindependent. Considering IoT applications, we train multiple machine learning models to evaluate their feasibility and suitability. For the target auto-sustainable IoT devices, which operate well-planned processes, the normal system performances can be modeled accurately. Based on time series analysis methods, such as local outlier factor, cumulative sum, and the proposed adaptive online thresholding, the anomalous behaviors can be effectively detected. Comparing their performances on detecting anomalies as well as the computation sources required, we conclude that relatively simple machine learning models are more suitable for IoT security, and a data-driven anomaly detection method is preferred.
Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting ...stress response to surgery. This trial therefore tested the hypothesis that combined epidural-general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery.
Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days.
Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural-general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural-general anesthesia group (15 1.8% of 857 patients) than in the general anesthesia group (43 5.0% of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 49% vs. 288 33%; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 58% vs. 387 45%; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001).
Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension.
Early diagnosis is critical to improve outcomes in rheumatoid arthritis (RA), but current diagnostic tools have limited sensitivity. Here we report a large-scale multicenter study involving training ...and validation cohorts of 3,262 participants. We show that serum levels of soluble scavenger receptor-A (sSR-A) are increased in patients with RA and correlate positively with clinical and immunological features of the disease. This discriminatory capacity of sSR-A is clinically valuable and complements the diagnosis for early stage and seronegative RA. sSR-A also has 15.97% prevalence in undifferentiated arthritis patients. Furthermore, administration of SR-A accelerates the onset of experimental arthritis in mice, whereas inhibition of SR-A ameliorates the disease pathogenesis. Together, these data identify sSR-A as a potential biomarker in diagnosis of RA, and targeting SR-A might be a therapeutic strategy.
The Internet and big data have deeply penetrated into various fields, which has greatly affected and changed our music education. The purpose of this article is to explore the cultivation of ...personalized music teaching talents in universities based on big data, with a view to promoting the cultivation of personalized music talents in universities under big data. This article conducted a questionnaire survey on some students majoring in music in our sophomore and junior colleges. Through analysis, it can be concluded that 85.29% of the students believe that the school's music teaching method is relatively traditional and the talent training model is backward; 74.51% of the students think that the school has neglected personalized training and still adopts the traditional "one size fits all" teaching model. Based on this, the recommendations for the cultivation of personalized music teaching talents in colleges and universities are put forward, which is expected to meet the personalized and diverse music learning needs of students and promote the cultivation of personalized music talents in my country.
Post-translational modifications (PTMs) of histone by histone demethylases (KDMs) play an important role in the regulation of gene expression, which implicates the development of various human ...cancers and other diseases. Discovering and developing inhibitors targeting KDMs have become an active and fast-growing research area over the past decades. In this review, the latest emerging small-molecule inhibitors of KDMs were surveyed with the emphasis on the literature since 2018, including lysine specific demethylases (LSD or KDM1) inhibitors and JmjC family N-methyl lysine demethylases (JmjC KDMs, i.e. KDM2-7) inhibitors. The drug design strategy, the structure-activity relationships (SARs), the analysis and insight of co-crystal structures, and the mechanisms of action (MOA) were also discussed.
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•Discovering and developing inhibitors targeting KDMs have become an active and fast-growing research area over the past decades.•This review provides the medicinal chemistry community with up-to-date information of novel KDMs inhibitors since 2018, including lysine specific demethylases inhibitors and JmjC family N-methyl lysine demethylases inhibitors.•Co-crystal structures of representative KDMs/inhibitors were highlighted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
As one of the key phosphatidylinositol 3-kinase-related kinases (PIKKs) family members, ataxia telangiectasia and RAD3-related protein kinase (ATR) is crucial in maintaining mammalian cell genomic ...integrity in DNA damage response (DDR) and repair pathways. Dysregulation of ATR has been found across different cancer types. In recent years, the inhibition of ATR has been proven to be effective in cancer therapy in preclinical and clinical studies. Importantly, tumor-specific alterations such as ATM loss and Cyclin E1 (CCNE1) amplification are more sensitive to ATR inhibition and are being exploited in synthetic lethality (SL) strategy. Besides SL, synergistic anticancer effects involving ATRi have been reported in an increasing number in recent years. This review focuses on the recent advances in different forms of synergistic antitumor effects, summarizes the pharmacological benefits and ongoing clinical trials behind the biological mechanism, and provides perspectives for future challenges and opportunities. The hope is to draw awareness to the community that targeting ATR should have great potential in developing effective anticancer medicines.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction: Tyrosine kinase 2 (Tyk2) is a non-receptor tyrosine-protein kinase, an enzyme that in humans is encoded by the TYK2 gene. Tyk2, together with three other family subtypes, namely, Jak1, ...Jak2, and Jak3, belong to the JAK family. Before 2014, far more publications and patents appeared in public domain attributing to the development of selective Jak2 and Jak3 inhibitors than those for selective Tyk2 and Jak1 inhibitors.
Areas covered: This review sought to give an overview of patents related to small molecule selective Tyk2 inhibitors published from 2015 to 2018. The article also covers clinical activities of small molecule selective Tyk2 inhibitors in recent years.
Expert opinion: As a key component of the JAK-STAT signaling pathway, Tyk2 regulates INFα, IL12, and IL23. Selective inhibition of Tyk2 can provide pharmacological benefits in the treatment of many diseases such as psoriasis, systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), cancer, and diabetes. The selectivity against other Jak family subtypes (such as Jak2) is crucial in order to minimize the potential side effects and to maximize the desired pharmacological effects. In this context, this review of recent selective Tyk2 inhibitor patents may prove valid, interesting, and promising within the therapeutic paradigm.
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Herein we present the plain manufacture of sterically hindered tertiary alkyl thioethers via the Cu-catalyzed coupling of unactivated tertiary alkyl alcohols with ...thio-alcohols/phenols. The present strategy with easy-to-operate reaction conditions represents one of the most effective unactivated tertiary C(sp3)–S bond-forming methods via readily accessible Lewis acid catalysis. Moreover, this protocol has high functional group compatibility and wide substrate adaptability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Catalytic PMA greatly accelerates microwave-mediated Claisen rearrangement reaction.•Substrates bearing Br and NO2 groups require specially tailored conditions.•The method is useful ...to access intermediates previously required precious metal catalysts.•Twenty seven examples were prepared in 20–96% yields.
The microwave-accelerated Claisen rearrangement of allyl aryl ethers was investigated, in order to gain insight into the scope of the catalysts, solvents, temperatures, and substrates. Among the catalysts examined, phosphomolybdic acid (PMA) was found to greatly accelerate the reaction in NMP, at temperatures ranging from 220 to 300 °C. This method was found to be useful for preparing several intermediates previously reported in the literature using precious metal catalysts such as Au(I), Ag(I), and Pt(II). Additionally, substrates bearing bromo and nitro groups on the aryl portion required careful tailoring of the reaction conditions to avoid complex product profiles.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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