Dynamic Kinetic Reductive Conjugate Addition for Construction of Axial Chirality Enabled by Synergistic Photoredox/Cobalt Catalysis.

Conjugate addition is among the most important synthetic protocols for constructing carbon skeletons and is widely used to synthesize natural products and drugs. However, asymmetric catalysis studies have mainly focused on constructing stereogenic centers arising from conjugate alkenes. Here, we report the first photoinduced cobalt-catalyzed dynamic kinetic reductive conjugate addition reaction that enables the formation of heterobiaryls with axial chirality (45 examples, up to 91% yield and 97% ee). This method features mild reaction conditions, good functional-group tolerance, and excellent enantiomeric control. Significantly, large amounts of metal waste and precious metal catalysts can be avoided under these conditions. Migration of the chiral arylcobalt species into the alkene might be the rate-determining step based on kinetic studies.

Iodine-Promoted Oxidative Cyclization of Methyl Azaarenes and α-Amino Ketones for One-Pot Synthesis of 2-Azaaryl-5-aryl Oxazoles.

A high efficiency protocol was developed for the synthesis of 2,5-disubstituted oxazoles via iodine-promoted oxidative domino cyclization. These reactions were performed with readily available methyl azaarenes and α-amino ketones under metal-free conditions. This protocol is a simple method with high functional group compatibility, a wide range of substrates, and excellent yield, providing a new way to synthesize azaarene-attached oxazoles.

Northern Hemisphere Urban Heat Stress and Associated Labor Hour Hazard from ERA5 Reanalysis.

Increasing surface air temperature is a fundamental characteristic of a warming world. Rising temperatures have potential impacts on human health through heat stress. One heat stress metric is the wet-bulb globe temperature, which takes into consideration the effects of radiation, humidity, and wind speed. It also has broad health and environmental implications. This study presents wet-bulb globe temperatures calculated from the fifth-generation European Centre for Medium-Range Weather Forecasts atmospheric reanalysis and combines it with health guidelines to assess heat stress variability and the potential for reduction in labor hours over the past decade on both the continental and urban scale. Compared to 2010-2014, there was a general increase in heat stress during the period from 2015 to 2019 throughout the northern hemisphere, with the largest warming found in tropical regions, especially in the northern part of the Indian Peninsula. On the urban scale, our results suggest that heat stress might have led to a reduction in labor hours by up to ~20% in some Asian cities subject to work-rest regulations. Extremes in heat stress can be explained by changes in radiation and circulation. The resultant threat is highest in developing countries in tropical areas where workers often have limited legal protection and healthcare. The effect of heat stress exposure is therefore a collective challenge with environmental, economic, and social implications.

Research Priorities of Applying Low-Cost PM2.5 Sensors in Southeast Asian Countries.

The low-cost and easy-to-use nature of rapidly developed PM2.5 sensors provide an opportunity to bring breakthroughs in PM2.5 research to resource-limited countries in Southeast Asia (SEA). This review provides an evaluation of the currently available literature and identifies research priorities in applying low-cost sensors (LCS) in PM2.5 environmental and health research in SEA. The research priority is an outcome of a series of participatory workshops under the umbrella of the International Global Atmospheric Chemistry Project-Monsoon Asia and Oceania Networking Group (IGAC-MANGO). A literature review and research prioritization are conducted with a transdisciplinary perspective of providing useful scientific evidence in assisting authorities in formulating targeted strategies to reduce severe PM2.5 pollution and health risks in this region. The PM2.5 research gaps that could be filled by LCS application are identified in five categories: source evaluation, especially for the distinctive sources in the SEA countries; hot spot investigation; peak exposure assessment; exposure-health evaluation on acute health impacts; and short-term standards. The affordability of LCS, methodology transferability, international collaboration, and stakeholder engagement are keys to success in such transdisciplinary PM2.5 research. Unique contributions to the international science community and challenges with LCS application in PM2.5 research in SEA are also discussed.

Assessing the Knowledge, Attitudes and Practices of COVID-19 among Quarantine Hotel Workers in China.

During the pandemic, quarantine hotel workers face a higher risk of infection while they host quarantine guests from overseas. This study's aim is to gain an understanding of the knowledge, attitudes, and practices (KAP) of quarantine hotel workers in China. A total of 170 participants took part in a cross-sectional survey to assess the KAP of quarantine hotel workers in China, during the COVID-19 pandemic. The chi-square test, independent t-test, one-way analysis of variance (ANOVA), descriptive analysis, and binary logistic regression were used to examine the sociodemographic factors associated with KAP levels during the COVID-19 pandemic. The results show that 62.41% have good knowledge, 94.7% have a positive attitude towards COVID-19, but only 78.2% have good practices. Most quarantine hotel workers (95.3%) are confident that COVID-19 will be successfully controlled and that China is handling the COVID-19 crisis well (98.8%). Most quarantine hotel workers are also taking personal precautions, such as avoiding crowds (80.6%) and wearing facemasks (97.6%). The results evidence that quarantine hotel workers in China have acquired the necessary knowledge, positive attitudes and proactive practices in response to the COVID-19 pandemic. The results of this study can provide a reference for quarantine hotel workers and their targeted education and intervention.

Concurrent assessment of personal, indoor, and outdoor PM2.5 and PM1 levels and source contributions using novel low-cost sensing devices.

The intensity, frequency, duration, and contribution of distinct PM2.5 sources in Asian households have seldom been assessed; these are evaluated in this work with concurrent personal, indoor, and outdoor PM2.5 and PM1 monitoring using novel low-cost sensing (LCS) devices, AS-LUNG. GRIMM-comparable observations were acquired by the corrected AS-LUNG readings, with R2 up to 0.998. Twenty-six non-smoking healthy adults were recruited in Taiwan in 2018 for 7-day personal, home indoor, and home outdoor PM monitoring. The results showed 5-min PM2.5 and PM1 exposures of 11.2 ± 10.9 and 10.5 ± 9.8 µg/m3 , respectively. Cooking occurred most frequently; cooking with and without solid fuel contributed to high PM2.5 increments of 76.5 and 183.8 µg/m3 (1 min), respectively. Incense burning had the highest mean PM2.5 indoor/outdoor (1.44 ± 1.44) ratios at home and on average the highest 5-min PM2.5 increments (15.0 µg/m3 ) to indoor levels, among all single sources. Certain events accounted for 14.0%-39.6% of subjects' daily exposures. With the high resolution of AS-LUNG data and detailed time-activity diaries, the impacts of sources and ventilations were assessed in detail.

Application of Machine Learning for the in-Field Correction of a PM2.5 Low-Cost Sensor Network.

Many low-cost sensors (LCSs) are distributed for air monitoring without any rigorous calibrations. This work applies machine learning with PM2.5 from Taiwan monitoring stations to conduct in-field corrections on a network of 39 PM2.5 LCSs from July 2017 to December 2018. Three candidate models were evaluated: Multiple linear regression (MLR), support vector regression (SVR), and random forest regression (RFR). The model-corrected PM2.5 levels were compared with those of GRIMM-calibrated PM2.5. RFR was superior to MLR and SVR in its correction accuracy and computing efficiency. Compared to SVR, the root mean square errors (RMSEs) of RFR were 35% and 85% lower for the training and validation sets, respectively, and the computational speed was 35 times faster. An RFR with 300 decision trees was chosen as the optimal setting considering both the correction performance and the modeling time. An RFR with a nighttime pattern was established as the optimal correction model, and the RMSEs were 5.9 ± 2.0 µg/m3, reduced from 18.4 ± 6.5 µg/m3 before correction. This is the first work to correct LCSs at locations without monitoring stations, validated using laboratory-calibrated data. Similar models could be established in other countries to greatly enhance the usefulness of their PM2.5 sensor networks.

Correction: Panel study using novel sensing devices to assess associations of PM2.5 with heart rate variability and exposure sources.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Fusion of Environmental Sensing on PM2.5 and Deep Learning on Vehicle Detecting for Acquiring Roadside PM2.5 Concentration Increments.

Traffic emission is one of the major contributors to urban PM2.5, an important environmental health hazard. Estimating roadside PM2.5 concentration increments (above background levels) due to vehicles would assist in understanding pedestrians' actual exposures. This work combines PM2.5 sensing and vehicle detecting to acquire roadside PM2.5 concentration increments due to vehicles. An automatic traffic analysis system (YOLOv3-tiny-3l) was applied to simultaneously detect and track vehicles with deep learning and traditional optical flow techniques, respectively, from governmental cameras that have low resolutions of only 352 × 240 pixels. Evaluation with 20% of the 2439 manually labeled images from 23 cameras showed that this system has 87% and 84% of the precision and recall rates, respectively, for five types of vehicles, namely, sedan, motorcycle, bus, truck, and trailer. By fusing the research-grade observations from PM2.5 sensors installed at two roadside locations with vehicle counts from the nearby governmental cameras analyzed by YOLOv3-tiny-3l, roadside PM2.5 concentration increments due to on-road sedans were estimated to be 0.0027-0.0050 µg/m3. This practical and low-cost method can be further applied in other countries to assess the impacts of vehicles on roadside PM2.5 concentrations.

Panel study using novel sensing devices to assess associations of PM2.5 with heart rate variability and exposure sources.

BACKGROUND/OBJECTIVE: This work applied a newly developed low-cost sensing (LCS) device (AS-LUNG-P) and a certified medical LCS device (Rooti RX) to assessing PM2.5 impacts on heart rate variability (HRV) and determining important exposure sources, with less inconvenience to subjects. METHODS: Observations using AS-LUNG-P were corrected by side-by-side comparison with GRIMM instruments. Thirty-six nonsmoking healthy subjects aged 20-65 years were wearing AS-LUNG-P and Rooti RX for 2-4 days in both Summer and Winter in Taiwan. RESULTS: PM2.5 exposures were 12.6 ± 8.9 µg/m3. After adjusting for confounding factors using the general additive mixed model, the standard deviations of all normal to normal intervals reduced by 3.68% (95% confidence level (CI) = 3.06-4.29%) and the ratios of low-frequency power to high-frequency power increased by 3.86% (CI = 2.74-4.99%) for an IQR of 10.7 µg/m3 PM2.5, with impacts lasting for 4.5-5 h. The top three exposure sources were environmental tobacco smoke, incense burning, and cooking, contributing PM2.5 increase of 8.53, 5.85, and 3.52 µg/m3, respectively, during 30-min intervals. SIGNIFICANCE: This is a pioneer in demonstrating application of novel LCS devices to assessing close-to-reality PM2.5 exposure and exposure-health relationships. Significant HRV changes were observed in healthy adults even at low PM2.5 levels.

Laboratory Evaluations of Correction Equations with Multiple Choices for Seed Low-Cost Particle Sensing Devices in Sensor Networks.

To tackle the challenge of the data accuracy issues of low-cost sensors (LCSs), the objective of this work was to obtain robust correction equations to convert LCS signals into data comparable to that of research-grade instruments using side-by-side comparisons. Limited sets of seed LCS devices, after laboratory evaluations, can be installed strategically in areas of interest without official monitoring stations to enable reading adjustments of other uncalibrated LCS devices to enhance the data quality of sensor networks. The robustness of these equations for LCS devices (AS-LUNG with PMS3003 sensor) under a hood and a chamber with two different burnt materials and before and after 1.5 years of field campaigns were evaluated. Correction equations with incense or mosquito coils burning inside a chamber with segmented regressions had a high R2 of 0.999, less than 6.0% variability in the slopes, and a mean RMSE of 1.18 µg/m3 for 0.1-200 µg/m3 of PM2.5, with a slightly higher RMSE for 0.1-400 µg/m3 compared to EDM-180. Similar results were obtained for PM1, with an upper limit of 200 µg/m3. Sensor signals drifted 19-24% after 1.5 years in the field. Practical recommendations are given to obtain equations for Federal-Equivalent-Method-comparable measurements considering variability and cost.

A versatile low-cost sensing device for assessing PM2.5 spatiotemporal variation and quantifying source contribution.

This study evaluated a newly developed sensing device, AS-LUNG-O, against a research-grade GRIMM in laboratory and ambient conditions and used AS-LUNG-O to assess PM2.5 spatiotemporal variations at street levels of an Asian mountain community, which represented residents' exposure (at the interface of atmosphere and human bodies leading to potential health impacts). In laboratory, R2 of 1-min AS-LUNG-O and GRIMM was 0.95 ± 0.04 (n = 64,179 for 40 sets). After conversion with individual correction equations, their correlation in ambient tests was 0.93 ± 0.05, with absolute % difference of only 10 ± 9%. Ten AS-LUNG-O sets were installed at street sites with another one at 10 m above ground on July 1-28 and December 2-31, 2017 in Nantou, Taiwan. Important source contributions to PM2.5 were quantified with regression analysis. Temporal variation expressed as the daily max/mean of 5-min PM2.5 reached 13.7 in July and 12.2 in December. Spatial variation expressed as the percent coefficients of variance (%CV) across ten community locations was 22% ± 20% (max: 199%) in July and 19 ± 18% (max: 206%) in December. Incremental contribution from the stop-and-go traffic, market, temple, and fried-chicken vendor to PM2.5 at 3-5 m away were 4.38, 3.90, 2.72, and 1.80 µg/m3, respectively. Significant spatiotemporal variations and community source contributions revealed the importance of assessing neighborhood air quality for public health protection. For long-term air quality monitoring, the percentage of available power and signals of G-sensor provided indicative information of maintenance required. Advantages of low cost (USD 650), small size, light weight, solar power supply, backup data storage, waterproof housing, multiple-sensor flexibility, and high precision and accuracy (after correction) enable AS-LUNG-O to be widely applied in environmental studies.

Aurora B functions at the apical surface after specialized cytokinesis during morphogenesis in C. elegans.

Although cytokinesis has been intensely studied, the way it is executed during development is not well understood, despite a long-standing appreciation that various aspects of cytokinesis vary across cell and tissue types. To address this, we investigated cytokinesis during the invariant Caenorhabditis elegans embryonic divisions and found several parameters that are altered at different stages in a reproducible manner. During early divisions, furrow ingression asymmetry and midbody inheritance is consistent, suggesting specific regulation of these events. During morphogenesis, we found several unexpected alterations to cytokinesis, including apical midbody migration in polarizing epithelial cells of the gut, pharynx and sensory neurons. Aurora B kinase, which is essential for several aspects of cytokinesis, remains apically localized in each of these tissues after internalization of midbody ring components. Aurora B inactivation disrupts cytokinesis and causes defects in apical structures, even if inactivated post-mitotically. Therefore, we demonstrate that cytokinesis is implemented in a specialized way during epithelial polarization and that Aurora B has a role in the formation of the apical surface.

Rapid single-wavelength lightsheet localization microscopy for clarified tissue.

Optical super-resolution microscopy allows nanoscale imaging of protein molecules in intact biological tissues. However, it is still challenging to perform large volume super-resolution imaging for entire animal organs. Here we develop a single-wavelength Bessel lightsheet method, optimized for refractive-index matching with clarified specimens to overcome the aberrations encountered in imaging thick tissues. Using spontaneous blinking fluorophores to label proteins of interest, we resolve the morphology of most, if not all, dopaminergic neurons in the whole adult brain (3.64 × 107 µm3) of Drosophila melanogaster at the nanometer scale with high imaging speed (436 µm3 per second) for localization. Quantitative single-molecule localization reveals the subcellular distribution of a monoamine transporter protein in the axons of a single, identified serotonergic Dorsal Paired Medial (DPM) neuron. Large datasets are obtained from imaging one brain per day to provide a robust statistical analysis of these imaging data.

Isoflurane produces antidepressant effects inducing BDNF-TrkB signaling in CUMS mice.

RATIONALE: The volatile anesthetic isoflurane is suggested to produce a rapid and robust antidepressive effect in preliminary clinical trials. Recently, isoflurane was found to activate the tropomyosin receptor kinase B (TrkB) signaling which is the underlying mechanism of the rapid antidepressant ketamine. OBJECTIVE: Our study investigated the effect of isoflurane anesthesia on chronic unpredictable mild stressed (CUMS) model in mice and verified the role of brain-derived neurotrophic factor (BDNF)/TrkB/ the mammalian target of rapamycin (mTOR) signaling in the antidepressant effect of isoflurane. METHODS: We employed the CUMS model of depression to assess the rapid antidepressant effect of isoflurane by the forced swimming test (FST), the sucrose preference test (SPT), and the novelty suppressed feeding test (NSFT). The protein expression of BDNF and TrkB/protein kinase B (PKB or Akt)/mTOR was determined through Western blot. The dendritic spine density in the hippocampus and medial prefrontal cortex (PFC) was measured by the Golgi staining. RESULTS: A brief burst-suppressing isoflurane anesthesia rapidly reversed the behavioral deficits caused by CUMS procedure, normalized the expression of BDNF and further activated the TrkB signaling pathway in CUMS-induced stressed mice in both prefrontal cortex (PFC) and hippocampus (HC). All of those behavioral and proteomic effects were blocked by K252a, a selective receptor inhibitor of TrkB. Isoflurane significantly promoted the formation of dendritic spines in both medial prefrontal cortex (mPFC), CA1, CA3, and DG of the hippocampus. CONCLUSION: Our study indicates that isoflurane exerts a rapid antidepressant-like effect in CUMS depression animal model, and the activation of BDNF/TrkB signaling pathway plays an indispensable role in the biological and behavioral antidepressant effects of isoflurane. A single exposure to isoflurane could repair synaptic damage caused by chronic stimulation.

Industrial PM2.5 cause pulmonary adverse effect through RhoA/ROCK pathway.

According to the Chinese Ministry of Health, industrial pollution-induced health impacts have been the leading cause of death in China. While industrial fine particulate matter (PM2.5) is associated with adverse health effects, the major action mechanisms of different compositions of PM2.5 are currently unclear. In this study, we treated normal human lung epithelial BEAS-2B cells with industrial organic and water-soluble PM2.5 extracts under daily alveolar deposition dose to elucidate the molecular mechanisms underlying adverse pulmonary effects induced by PM2.5, including oxidative damage, inflammatory response, lung epithelial barrier dysfunction, and the recruitment of macrophages. We found that water-soluble PM2.5 extracts caused more severe cytotoxic effects on BEAS-2B cells compared with that of organic extracts. Both organic and water-soluble PM2.5 extracts induced activation of the RhoA/ROCK pathway. Inflammatory response, epithelial barrier dysfunction, and the activation of NF-кB caused by both PM2.5 extracts were attenuated by ROCK inhibitor Y-27632. This indicated that both PM2.5 extracts could cause damage to epithelial cells through RhoA/ROCK-dependent NF-кB activation. Furthermore, the upregulation of macrophage adhesion induced by both PM2.5 extracts was also attenuated by Y-27632 in a co-culture model of macrophages and the epithelial cells. Therefore, our results support that industrial PM2.5 extracts-induced activation of the RhoA/ROCK-dependent NF-кB pathway induces pulmonary adverse effect. Thus, pharmacological inhibition of ROCK activation might have therapeutic potential in preventing lung disease associated with PM2.5.

Carbon black aggregates cause endothelial dysfunction by activating ROCK.

Carbon black nanoparticles (CBNs) have been associated with the progression of atherosclerosis. CBNs normally enter the bloodstream and crosslink together to form agglomerates. However, most studies have used nano-sized CB particles to clarify the involvement of CBN exposure in CBN-induced endothelial dysfunction. Herein, we studied endothelial toxicity of CBN aggregates (CBA) to human EA.hy926 vascular cells. Cell viability, lactate dehydrogenase leakage, and oxidative stress were affected by the highest concentration of CBA. Moreover, transmission electron microscopic results showed that CBA entered cells through membrane enclosed vesicles. Rho-associated kinase (ROCK) is involved in regulating vascular diseases. Thus, we co-treated with the of ROCK inhibitor Y-27632 to study whether other adverse effects caused by CBA are related to activating ROCK. As expected, co-treatment with Y-27632 attenuated CBA-induced cytoskeletal damage, dysfunction of the endothelial barrier, and expression of inflammatory factors. Taken together, these results demonstrate that aggregated CBNs can cause endothelial dysfunction possibly by activating ROCK.

Consecutive evaluation of graphene oxide and reduced graphene oxide nanoplatelets immunotoxicity on monocytes.

The biocompatibilities of graphene-family nanomaterials (GFNs) should be thoroughly evaluated before their application in drug delivery and anticancer therapy. The present study aimed to consecutively assess the immunotoxicity of graphene oxide nanoplatelets (GONPs) and reduced GONPs (rGONPs) on THP-1 cells, a human acute monocytic leukemia cell line. GONPs induced the expression of antioxidative enzymes and inflammatory factors, whereas rGONPs had substantially higher cellular uptake rate, higher levels of NF-κB expression. These distinct toxic mechanisms were observed because the two nanomaterials differ in their oxidation state, which imparts different affinities for the cell membrane. Because GONPs have a higher cell membrane affinity and higher impact on membrane proteins compared with rGONPs, macrophages (THP-1a) derived from GONPs treated THP-1cells showed a severer effect on phagocytosis. By consecutive evaluation the effects of GONPs and rGONPs on THP-1 and THP-1a, we demonstrated that their surface oxidation states may cause GFNs to behave differently and cause different immunotoxic effects.

Polycyclic aromatic hydrocarbons are associated with increased risk of chronic obstructive pulmonary disease during haze events in China.

Although exposure to particulate matter with a diameter of <2.5µm (PM2.5) is associated with chronic obstructive pulmonary disease (COPD), the major components of PM2.5 in COPD pathogenesis are controversial. Here we employed the human lung epithelial cell line BEAS-2B to elucidate the association between COPD and the organic and water-soluble components of PM2.5. We found that the PM2.5 organic extract was a potential major risk factor for pulmonary epithelial barrier dysfunction through the depletion of proteins from the zonula occludens. This extract induced severe oxidative stress that increased DNA damage and the production of proinflammatory cytokines by BEAS-2B cells as well as decreased α1-antitrypsin expression, suggesting a mechanism that increases the risk of COPD. These effects were mainly mediated by polycyclic aromatic hydrocarbons (PAHs) through the aryl hydrocarbon receptor pathway. PAHs with high benzo(a)pyrene (BaP)-equivalent concentrations, but not major PAH components, have an increased risk of causing COPD, suggesting that BaP-equivalent concentrations represent a PM2.5-induced COPD risk metric, which may contribute to provide a rationale for the remediation of air pollution.

Improved Anticancer Photothermal Therapy Using the Bystander Effect Enhanced by Antiarrhythmic Peptide Conjugated Dopamine-Modified Reduced Graphene Oxide Nanocomposite.

Despite tremendous efforts toward developing novel near-infrared (NIR)-absorbing nanomaterials, improvement in therapeutic efficiency remains a formidable challenge in photothermal cancer therapy. This study aims to synthesize a specific peptide conjugated polydopamine-modified reduced graphene oxide (pDA/rGO) nanocomposite that promotes the bystander effect to facilitate cancer treatment using NIR-activated photothermal therapy. To prepare a nanoplatform capable of promoting the bystander effect in cancer cells, we immobilized antiarrhythmic peptide 10 (AAP10) on the surface of dopamine-modified rGO (AAP10-pDA/rGO). Our AAP10-pDA/rGO could promote the bystander effect by increasing the expression of connexin 43 protein in MCF-7 breast-cancer cells. Because of its tremendous ability to absorb NIR absorption, AAP10-pDA/rGO offers a high photothermal effect under NIR irradiation. This leads to a massive death of MCF-7 cells via the bystander effect. Using tumor-bearing mice as the model, it is found that NIR radiation effectively ablates breast tumor in the presence of AAP10-pDA/rGO and inhibits tumor growth by ≈100%. Therefore, this research integrates the bystander and photothermal effects into a single nanoplatform in order to facilitate an efficient photothermal therapy. Furthermore, our AAP10-pDA/rGO, which exhibits both hyperthermia and the bystander effect, can prevent breast-cancer recurrence and, therefore, has great potential for future clinical and research applications.