Lateral shearing interferometry method based on double-checkerboard grating by suppressing aliasing effect.

Ronchi lateral shearing interferometry is a promising wavefront sensing technology with the advantages of simple structure and no reference light, which can realize a high-precision wavefront aberration measurement. To obtain shear information in both directions, the conventional double-Ronchi interferometer sequentially applies two orthogonal one-dimensional Ronchi gratings as the object-plane splitting element of the optics under test. Simultaneously, another Ronchi grating is positioned on the image plane in the same orientation to capture two sets of interferograms, thereby enabling two-dimensional wavefront reconstruction. Mechanical errors will inevitably be introduced during grating conversion, affecting reconstruction accuracy. Based on this, we propose a lateral shearing interferometry applying double-checkerboard grating. Only unidirectional phase shift is needed to obtain shear information in two directions while evading the grating conversion step, aiming to streamline operational processes and mitigate the potential for avoidable errors. We employ scalar diffraction theory to analyze the full optical path propagation process of the double-checkerboard shearing interferometry and introduce a new reconstruction algorithm to effectively extract the two-dimensional shear phase by changing the grating morphology, suppressing the aliasing effect of irrelevant diffraction orders. We reduce the fitting error through iterative optimization to realize high-precision wavefront reconstruction. Compared with conventional Ronchi lateral shearing interferometry, the proposed method exhibits better robustness and stability in noisy environments.

Study of the effect of keap1 on oxidative stress in human umbilical cord mesenchymal stem cells.

BACKGROUND: HucMSCs had shown promising efficacy in treating childhood diseases, but oxidative stress induced by the poor microenvironment at the site of damage resulted in low cell survival after transplantation, thus preventing the cells from maximizing therapeutic efficacy. Therefore, this study aimed to investigate the role and mechanism of keap1 in oxidative stress injury of human umbilical cord mesenchymal stem cells (hucMSCs), and to provide theoretical support for improving the efficacy of stem cell therapy. METHODS: The hucMSCs were treated with hypoxic low-sugar-free serum (GSDH) to mimic the damaged site microenvironment after implantation. Adenoviral overexpression of keap1 gene of hucMSCs was performed in vitro, and cell proliferation ability was detected by CCK8 assay, crystal violet staining assay, and cell cycle assay. Cellular redox level was assessed by Amplex Red, MDA, and GSH/GSSG kit. Mitochondrial morphology was evaluated by mitotracker Red staining. ATP production was estimated by ATP detection kit. The mRNA and protein expression levels were tested by western blotting and RT-qPCR. RESULTS: GSDH treatment substantially upregulated keap1 expression. Subsequently, we found that overexpression of keap1 notably inhibited cell proliferation and caused cells to stagnate in G1 phase. At the same time, overexpression of keap1 induced the production of large amounts of H2O2 and the accumulation of MDA, but suppressed the GSH/GSSG ratio and the expression of antioxidant proteins NQO1 and SOD1, which caused oxidative stress damage. Overexpression of keap1 induced cells to produce a large number of dysfunctional mitochondria resulting in reduced ATP production. Moreover, Overexpression of keap1 significantly decreased the IKKß protein level, while upregulating IkB mRNA levels and downregulating P50 mRNA levels. CONCLUSIONS: Overexpression of keap1 may induce oxidative stress injury in hucMSCs by down-regulating IKKß expression and inhibiting NF-κB pathway activation. This implies the importance of keap1 in hucMSCs and it may be a potential gene for genetic modification of hucMSCs.

Quantitative proteomic and phosphoproteomic analysis reveal the relationship between mitochondrial dysfunction and cytoskeletal remodeling in hiPSC-CMs deficient in PINK1.

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are seed cells that can be used for alternative treatment of myocardial damage. However, their immaturity limits their clinical application. Mitochondrial development accompanies cardiomyocyte maturation, and PINK1 plays an important role in the regulation of mitochondrial quality. However, the role and mechanism of PINK1 in cardiomyocyte development remain unclear. METHODS: We used proteomic and phosphoproteomic to identify protein and phosphosite changes in hiPSC-CMs deficient in PINK1. Bioinformatics analysis was performed to identify the potential biological functions and regulatory mechanisms of these differentially expressed proteins and validate potential downstream mechanisms. RESULTS: Deletion of PINK1 resulted in mitochondrial structural breakdown and dysfunction, accompanied by disordered myofibrils arrangement. hiPSC-CMs deficient in PINK1 exhibited significantly decreased expression of mitochondrial ATP synthesis proteins and inhibition of the oxidative phosphorylation pathway. In contrast, the expression of proteins related to cardiac pathology was increased, and the phosphoproteins involved in cytoskeleton construction were significantly altered. Mechanistically, PINK1 deletion damaged the mitochondrial cristae of hiPSC-CMs and reduced the efficiency of mitochondrial respiratory chain assembly. CONCLUSION: The significantly differentially expressed proteins identified in this study highlight the important role of PINK1 in regulating mitochondrial quality in hiPSC-CMs. PINK1-mediated mitochondrial respiratory chain assembly is the basis for mitochondrial function. Whereas the cytoskeleton may be adaptively altered in response to mitochondrial dysfunction caused by PINK1 deletion, inadequate energy supply hinders myocardial development. These findings facilitate the exploration of the mechanism of PINK1 in cardiomyocyte development and guide efforts to promote the maturation of hiPSC-CMs.

Fast wavefront sensing method based on diffraction basis vectors for tightly focused optical systems.

Recently, phase retrieval techniques have garnered significant attention with their exceptional flexibility. However, their application is limited in optical systems with high numerical aperture due to the disregarded polarization properties of the beam. In this paper, a fast wavefront sensing method for tightly focused systems is proposed. Firstly, a vector diffraction model based on the chirp-Z transform is established to analytically describe the focal spot using the modal coefficients of polynomials and diffraction basis vectors, which accommodating any pixel size and resolution, thereby enabling to break through sampling constraints and remove lateral errors. Additionally, a modified Newton-gradient second-order algorithm is introduced to simultaneously optimize wavefront in multiple polarization directions, without the need for diffraction operators during iterations. Both numerical simulations and error analysis confirm the efficacy and precision of the proposed wavefront sensing method.

Room Temperature Hydroxyl Group-Assisted Preparation of Hydrophobicity-Adjustable Metal-Organic Framework UiO-66 Composites: Towards Continuous Oil Collection and Emulsion Separation.

Developing a straightforward and effective hydrophobic modification for metal-organic frameworks (MOFs) under mild conditions is meaningful for MOF applications. Here, a post-synthetic modification approach assisted with metal hydroxyl groups at room temperature is reported to induce hydrophobicity in the hydrophilic UiO-66. The bonding between Zr-OH in UiO-66 and n-tetradecylphosphonic acid (TDPA) is the vital force for the modifier TDPA. Superhydrophobic and superoleophilic composites were constructed for efficient oil-water separation by coating TDPA-modified UiO-66 (P-UiO-66) on commercial melamine sponges (MS) and filter papers (FP) with water contact angles of 153.2° and 155.6°, respectively. The P-UiO-66/MS composite could quickly and selectively absorb oily liquids up to 43 times its weight from water. The P-UiO-66/MS achieved continuous oil collection with high separation efficiencies (≥99.4 %). In addition, P-UiO-66/FP and P-UiO-66/MS showed high separation efficiencies for water-in-oil emulsions (≥98.5 %) and oil-in-water emulsions, respectively, with high resistance to low/high temperatures and acid/base conditions. The metal hydroxyl group-assisted post-synthetic modification strategy offers a facile and broad way to prepare hydrophobic MOFs for promising applications in environmental fields.

Ferrostatin-1 improves BMSC survival by inhibiting ferroptosis.

OBJECTIVE: To investigate the effect of ferroptosis in BMSCs and explore the protective metabolism of ferrostatin-1 under GSDH treatment. METHODS: BMSCs were treated with GSDH to simulate the damaged microenvironment in vivo to establish a cell injury model. Propidium iodide and CCK8 were utilized to detect the ratio of dead cells and cell viability. DCFH-DA and Amplex Red, FerroOrange, and BPDIPY were used to visualize the cellular fluorescent images of ROS, Fe2+, and lipid droplets, respectively. The quantified detection of MDA was conducted by a Lipid Peroxidation MDA Assay Kit. JC-1 staining, Mito-Tracker staining, and TEM were implemented to detect the membrane potential, morphology, and ultrastructure of mitochondria, respectively. The expression levels of ferroptosis-related proteins such as GPX4 and FTH1 were measured by Western blotting. RESULTS: GSDH treatment induced ferroptosis in BMSCs based on an increased ratio of cell death, Fe2+, ROS, lipid droplets, and MDA in cells plus decreased protein levels of antioxidant systems, such as GPX4, and increased protein levels related to fatty acid synthesis. Compared to the blank group, mitochondria in the GSDH group underwent lower membrane potential, damaged morphology, and shrunken ultrastructure; Ferr-1 rescued the injured BMSCs to a certain extent as the declined ratio of cell death, Fe2+, ROS, lipid droplets, MDA, and the increased level antioxidant protein. AMPK was phosphorylated and activated after Ferr-1 treatment, and its downstream lipid peroxidation and antioxidation proteins changed accordingly. Inhibition of AMPK hindered the curative effect of Ferr-1. CONCLUSION: Ferr-1 rescued ferroptosis-induced injury to BMSCs under GSDH conditions, and AMPK might have a relationship with the mitigative effect of Ferr-1.

Andrographolide-treated bone marrow mesenchymal stem cells-derived conditioned medium protects cardiomyocytes from injury by metabolic remodeling.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) transplantation therapy providing a great hope for the recovery of myocardial ischemic hypoxic injury. However, the microenvironment after myocardial injury is not conducive to the survival of BMSCs, which limits the therapeutic application of BMSCs. Our previous study has confirmed that the survival of BMSCs cells in the glucose and serum deprivation under hypoxia (GSDH) is increased after Andrographolide (AG) pretreatment, but whether this treatment could improve the effect of BMSCs in repairing of myocardial injury has not been verified. METHODS AND RESULT: We first treated H9C2 with GSDH to simulate the microenvironment of myocardial injury in vitro, then we pretreated rat primary BMSCs with AG, and collected conditioned medium derived from BMSCs (BMSCs-CM) and conditioned medium derived from AG-pretreated BMSCs (AG-BMSCs-CM) after GSDH treatment. And they were used to treat H9C2 cells under GSDH to further detect oxidative stress and metabolic changes. The results showed that AG-BMSCs-CM could be more advantageous for cardiomyocyte injury repair than BMSCs-CM, as indicated by the decrease of apoptosis rate and oxidative stress. The changes of mitochondria and lipid droplets results suggested that AG-BMSCs-CM can regulate metabolic remodeling of H9C2 cells to repair cell injury, and that AMPK was activated during this process. CONCLUSIONS: This study demonstrates, for the first time, the protective effect of AG-BMSCs-CM on GSDH-induced myocardial cell injury, providing a potential therapeutic strategy for clinical application.

Siderophore-synthesizing NRPS reprogram lipid metabolic profiles for phenotype and function changes of Arthrobotrys oligospora.

The objective of this paper is to explore the function of the AOL-s00215g415 (Aog415) gene, which encodes for the synthesis of siderophore in the nematode trapping fungal model strain A. oligospora, in order to understand the relationship between siderophore biosynthesis and nematode trapping activity. After a through sequence analysis, it was determined that Aog415 is a siderophore-synthesizing NRPS. The product of this gene was then identified to be the hydroxamate siderophore desferriferrichrome, using mass spectrometry analysis. When compared to the WT strains, the Aog415 knockout strain exhibited a 60% decrease in siderophore content in fermentation broth. Additionally, the number of predatory rings of decreased by 23.21%, while the spore yield increased by 37.34%. The deletion of Aog415 did not affect the growth of A. oligospora in diverse nutrient medium. Lipid metabolism-related pathways were the primary targets of Aog415 disruption as revealed by the metabolomic analysis. In comparison to the WT, a significant reduction in the levels of glycerophospholipids, and glycolipids was observed in the mutation. The metabolic alteration in fatty acyls and amino acid-like molecules were significantly disrupted. The knockout of Aog415 impaired the biosynthesis of the hydroxamate siderophore desferriferrichrome, remodeled the flow of fatty acid in A. oligospora, and mainly reprogrammed the membrane lipid metabolism in cells. Desferriferrichrome, a hydroxamate siderophore affects the growth, metabolism and nematode trapping ability of A. oligospora by regulating iron intake and cell membrane homeostasis. Our study uncovered the significant contribution of siderophores to the growth and nematode trapping ability and constructed the relationship among siderophores biosynthesis, lipid metabolism and nematode trapping activity of A. oligospora, which provides a new insight for the development of nematode biocontrol agents based on nematode trapping fungi.

Highly Efficient Aggregation-Induced Enhanced Electrochemiluminescence of Cyanophenyl-Functionalized Tetraphenylethene and Its Application in Biothiols Analysis.

Exploring new electrochemiluminescence (ECL) luminophores with high ECL efficiency and good stability in aqueous solution is in great demand for biological sensing. In this work, highly efficient aggregation-induced enhanced ECL of cyanophenyl-functionalized tetraphenylethene (tetra[4-(4-cyanophenyl)phenyl]ethene, TCPPE) and its application in biothiols analysis were reported. TCPPE contains four 4-cyanophenyl groups covalently attached to the tetraphenylethene (TPE) core, generating a nonplanar three-dimensional twisted conformation structure. TCPPE nanoparticles (NPs) with an average size of 15.84 nm were prepared by a precipitation method. High ECL efficiency (593%, CdS as standard) and stable ECL emission (over one month) were obtained for TCPPE NPs in aqueous solution. The unique properties of TCPPE NPs could be ascribed to the efficient suppression of nonradiative transition, the decrease of the energy gap, and the increase of anionic radical stability, which were proved by theoretical calculation and electrochemical and fluorescence methods. Contrasting aggregation-induced ECL chromic emission was first observed for TCPPE NPs. As a proof-of-methodology, an ECL method was developed for three biothiol assays with detection limits of 6, 7, and 300 nM for cysteine, homocysteine, and glutathione, respectively. This work demonstrates that TCPPE NPs are promising ECL luminophores, and the incorporation of appropriate substituents into luminophores can improve ECL efficiency and radical stability.

Airway Epithelial cGAS Is Critical for Induction of Experimental Allergic Airway Inflammation.

DNA damage could lead to the accumulation of cytosolic DNA, and the cytosolic DNA-sensing pathway has been implicated in multiple inflammatory diseases. However, the role of cytosolic DNA-sensing pathway in asthma pathogenesis is still unclear. This article explored the role of airway epithelial cyclic GMP-AMP synthase (cGAS), the major sensor of cytosolic dsDNA, in asthma pathogenesis. Cytosolic dsDNA accumulation in airway epithelial cells (ECs) was detected in the setting of allergic inflammation both in vitro and in vivo. Mice with cGAS deletion in airway ECs were used for OVA- or house dust mite (HDM)-induced allergic airway inflammation. Additionally, the effects of cGAS knockdown on IL-33-induced GM-CSF production and the mechanisms by which IL-33 induced cytosolic dsDNA accumulation in human bronchial epithelial (HBE) cells were explored. Increased accumulation of cytosolic dsDNA was observed in airway epithelium of OVA- or HDM-challenged mice and in HBE cells treated with IL-33. Deletion of cGAS in the airway ECs of mice significantly attenuated the allergic airway inflammation induced by OVA or HDM. Mechanistically, cGAS participates in promoting TH2 immunity likely via regulating the production of airway epithelial GM-CSF. Furthermore, Mito-TEMPO could reduce IL-33-induced cytoplasmic dsDNA accumulation in HBE cells possibly through suppressing the release of mitochondrial DNA into the cytosol. In conclusion, airway epithelial cGAS plays an important role via sensing the cytosolic dsDNA in asthma pathogenesis and could serve as a promising therapeutic target against allergic airway inflammation.

Examining industrial air pollution embodied in trade: implications of a hypothetical China-UK FTA.

Very few developed economies have a full free trade agreement (FTA) with China. This study employs one GTAP model and builds an extended environmental multi-region input-output model to investigate a hypothetical China-UK FTA, concerning embodied industrial emissions of SO2, PM2.5, NOX, and NH3. The economic sectors are also classified based on their embodied pollution intensity and trade advantage index under various FTA scenarios. Results show that the UK's GDP and welfare and China's welfare will increase, along with changes in their trade structures. Overall, this FTA brings about larger net impacts on embodied emissions of SO2 than on PM2.5, NOX and NH3, and both countries are net importers of the latter three pollutants. Key sectors such as non-metallic mineral products, chemical products, and agriculture are inclined to become less competitive and less polluting under the FTA. The inclusion of agri-food sectors exhibits slight counteracting effects in general. The findings are of policy importance as they provide insights into how best to target key sectors, seeking a balance between trade development and environmental protection. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-022-02612-z.

4-Acetylantroquinonol B induced DNA damage response signaling and apoptosis via suppressing CDK2/CDK4 expression in triple negative breast cancer cells.

BACKGROUND: Triple-negative breast cancer (TNBC) has a more aggressive phenotype and poorer prognosis than hormone receptor (HR+) and human epidermal growth factor receptor (HER2 -) subtypes. Inhibition of cyclin-dependent kinase (CDK)4 and CDK6 was successful in patients with advanced metastatic HR+/HER2- breast cancer, but those with TNBC exhibited low or no response to this therapeutic approach. This study investigated the dual therapeutic targeting of CDK2 and CDK4 by using 4-acetyl-antroquinonol B (4-AAQB) against TNBC cells. METHODS: We examined the effects of CDK2, CDK4, and CDK6 inhibition through 4-AAQB treatment on TNBC cell lines and established an orthotropic xenograft mouse model to confirm the in vitro results of inhibiting CDK2, CDK4, and CDK6 by 4-AAQB treatment. RESULTS: High expression and alteration of CDK2 and CDK4 but not CDK6 significantly correlated with poor overall survival of patients with breast cancer. CDK2 and CDK4 were positively correlated with damage in DNA replication and repair pathways. Docking results indicated that 4-AAQB was bound to CDK2 and CDK4 with high affinity. Treatment of TNBC cells with 4-AAQB suppressed the expression of CDK2 and CDK4 in vitro. Additionally, 4-AAQB induced cell cycle arrest, DNA damage, and apoptosis in TNBC cells. In vivo study results confirmed that the anticancer activity of 4-AAQB suppressed tumor growth through the inhibition of CDK2 and CDK4. CONCLUSION: The expression level of CDK2 and CDK4 and DNA damage response (DDR) signaling are prominent in TNBC cell cycle regulation. Thus, 4-AAQB is a potential agent for targeting CDK2/4 and DDR in TNBC cells.

Achieving full-color emission of Cu nanocluster self-assembly nanosheets by the virtue of halogen effects.

Fluorescent Cu nanoclusters (NCs) have shown potential in lighting and display, because Cu is cheap and easily available. Despite recent successes in improving the emission intensity of Cu NCs on the basis of aggregation-induced emission enhancement and self-assembly-induced emission enhancement, the difficulty in tuning the emission color sheds the doubt for achieving high-performance white light-emitting diodes (WLEDs). In this work, halogen effects are utilized to tune the emission color of Cu nanocluster self-assembly nanosheets (NSASs). By altering the adsorbed halogens from Cl, Br to I, the emission peak of Cu NSASs is tunable from 495 to 674 nm. In this context, halogen atoms are capable of improving the charge transfer and molecular spin coupling of Cu NCs, and thereby narrow the S0T1 gap and facilitate the intersystem crossing of excitons from a singlet to triplet state. As a result, emission spectra redshift and the population of the exiton recombination via the triplet state pathway is increased, which leads to the improvement of the photoluminescence quantum yield (PLQY). By simply introducing and/or mixing different types of cuprous halides, Cu nanocluster co-assembly nanosheets (NCASs) with full-color emission are obtained. The as-prepared Cu NSASs and NCASs are further employed to fabricate monochrome and white LEDs.

Pharmacological bypass of NAD+ salvage pathway protects neurons from chemotherapy-induced degeneration.

Axon degeneration, a hallmark of chemotherapy-induced peripheral neuropathy (CIPN), is thought to be caused by a loss of the essential metabolite nicotinamide adenine dinucleotide (NAD+) via the prodegenerative protein SARM1. Some studies challenge this notion, however, and suggest that an aberrant increase in a direct precursor of NAD+, nicotinamide mononucleotide (NMN), rather than loss of NAD+, is responsible. In support of this idea, blocking NMN accumulation in neurons by expressing a bacterial NMN deamidase protected axons from degeneration. We hypothesized that protection could similarly be achieved by reducing NMN production pharmacologically. To achieve this, we took advantage of an alternative pathway for NAD+ generation that goes through the intermediate nicotinic acid mononucleotide (NAMN), rather than NMN. We discovered that nicotinic acid riboside (NAR), a precursor of NAMN, administered in combination with FK866, an inhibitor of the enzyme nicotinamide phosphoribosyltransferase that produces NMN, protected dorsal root ganglion (DRG) axons against vincristine-induced degeneration as well as NMN deamidase. Introducing a different bacterial enzyme that converts NAMN to NMN reversed this protection. Collectively, our data indicate that maintaining NAD+ is not sufficient to protect DRG neurons from vincristine-induced axon degeneration, and elevating NMN, by itself, is not sufficient to cause degeneration. Nonetheless, the combination of FK866 and NAR, which bypasses NMN formation, may provide a therapeutic strategy for neuroprotection.

In Situ Magnetic Control of Macroscale Nanoligand Density Regulates the Adhesion and Differentiation of Stem Cells.

Developing materials with remote controllability of macroscale ligand presentation can mimic extracellular matrix (ECM) remodeling to regulate cellular adhesion in vivo. Herein, we designed charged mobile nanoligands with superparamagnetic nanomaterials amine-functionalized and conjugated with polyethylene glycol linker and negatively charged RGD ligand. We coupled negatively a charged nanoligand to a positively charged substrate by optimizing electrostatic interactions to allow reversible planar movement. We demonstrate the imaging of both macroscale and in situ nanoscale nanoligand movement by magnetically attracting charged nanoligand to manipulate macroscale ligand density. We show that in situ magnetic control of attracting charged nanoligand facilitates stem cell adhesion, both in vitro and in vivo, with reversible control. Furthermore, we unravel that in situ magnetic attraction of charged nanoligand stimulates mechanosensing-mediated differentiation of stem cells. This remote controllability of ECM-mimicking reversible ligand variations is promising for regulating diverse reparative cellular processes in vivo.

MTOR suppresses autophagy-mediated production of IL25 in allergic airway inflammation.

INTRODUCTION: Airway epithelial cells are recognised as an essential controller for the initiation and perpetuation of asthmatic inflammation, yet the detailed mechanisms remain largely unknown. This study aims to investigate the roles and mechanisms of the mechanistic target of rapamycin (MTOR)-autophagy axis in airway epithelial injury in asthma. METHODS: We examined the MTOR-autophagy signalling in airway epithelium from asthmatic patients or allergic mice induced by ovalbumin or house dust mites, or in human bronchial epithelial (HBE) cells. Furthermore, mice with specific MTOR knockdown in airway epithelium and autophagy-related lc3b-/- mice were used for allergic models. RESULTS: MTOR activity was decreased, while autophagy was elevated, in airway epithelium from asthmatic patients or allergic mice, or in HBE cells treated with IL33 or IL13. These changes were associated with upstream tuberous sclerosis protein 2 signalling. Specific MTOR knockdown in mouse bronchial epithelium augmented, while LC3B deletion diminished allergen-induced airway inflammation and mucus hyperproduction. The worsened inflammation caused by MTOR deficiency was also ameliorated in lc3b-/- mice. Mechanistically, autophagy was induced later than the emergence of allergen-initiated inflammation, particularly IL33 expression. MTOR deficiency increased, while knocking out of LC3B abolished the production of IL25 and the eventual airway inflammation on allergen challenge. Blocking IL25 markedly attenuated the exacerbated airway inflammation in MTOR-deficiency mice. CONCLUSION: Collectively, these results demonstrate that allergen-initiated inflammation suppresses MTOR and induces autophagy in airway epithelial cells, which results in the production of certain proallergic cytokines such as IL25, further promoting the type 2 response and eventually perpetuating airway inflammation in asthma.

Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside-Wuhan patients, China.

Cases of coronavirus disease 2019 (COVID-19) emigrating from Wuhan escalated the risk of spreading the disease in other cities. This report focused on outside-Wuhan patients to assess the transmission and clinical characteristics of this illness. Contact investigation was conducted on each patient who was admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from 22 January to 23 February 2020. Cases were confirmed by the polymerase chain reaction test. Demographic, clinical, and outcomes were collected and analyzed. Of the 104 patients, 48 (46.15%) were cases who immigrated from Wuhan; 93 (89.42%) had a definite contact history with infection. Family clusters were the major body of patients. Transmission along the chain of three "generations" was observed. Five asymptomatic infected cases were found and two of them infected their relatives. Mean age was 43 (range, 8-84) years, and 49 (47.12%) were male. The median incubation period was 6 (range, 1-32) days, which of 8 patients ranged from 18 to 32 days, 96 (92.31%) were discharged, and 1 (0.96%) died. The average hospital stay was 10 (range, 8-14) days. Family but not community transmission became the main body of infections in the two centers, suggesting the timely control measures after the Wuhan shutdown worked well. Asymptomatic transmission demonstrated here warned us that it may lead to the widespread of COVID-19. A 14-day quarantine may need to be prolonged.

MTOR Suppresses Environmental Particle-Induced Inflammatory Response in Macrophages.

Increasing toxicological and epidemiological studies have demonstrated that ambient particulate matter (PM) could cause adverse health effects including inflammation in the lung. Alveolar macrophages represent a major type of innate immune responses to foreign substances. However, the detailed mechanisms of inflammatory responses induced by PM exposure in macrophages are still unclear. We observed that coarse PM treatment rapidly activated mechanistic target of rapamycin (MTOR) in mouse alveolar macrophages in vivo, and in cultured mouse bone marrow-derived macrophages, mouse peritoneal macrophages, and RAW264.7 cells. Pharmacological inhibition or genetic knockdown of MTOR in bone marrow-derived macrophages leads to an amplified cytokine production upon PM exposure, and mice with specific knockdown of MTOR or ras homolog enriched in brain in myeloid cells exhibit significantly aggregated airway inflammation. Mechanistically, PM activated MTOR through modulation of ERK, AKT serine/threonine kinase 1, and tuberous sclerosis complex signals, whereas MTOR deficiency further enhanced the PM-induced necroptosis and activation of subsequent NF κ light-chain-enhancer of activated B cells (NFKB) signaling. Inhibition of necroptosis or NFKB pathways significantly ameliorated PM-induced inflammatory response in MTOR-deficient macrophages. The present study thus demonstrates that MTOR serves as an early adaptive signal that suppresses the PM-induced necroptosis, NFKB activation, and inflammatory response in lung macrophages, and suggests that activation of MTOR or inhibition of necroptosis in macrophages may represent novel therapeutic strategies for PM-related airway disorders.

Re-examining the embodied air pollutants in Chinese exports.

China is the world's largest exporter and may release lots of air pollutants to produce exported commodities due to taking coal as its main source of energy. Processing exports play a significant role in Chinese exports, yet previous studies of embodied air pollutants in Chinese exports failed to distinguish processing exports from normal exports. This paper investigates the effect of trade heterogeneity on the estimation of embodied emissions by re-examining the embodied air pollutants in Chinese exports based on an extended non-competitive input-output table that distinguishes processing from normal exports. The results show that processing exports generate 22.81% of the value added embodied in gross exports and 16.48% of the emissions embodied in gross exports. The embodied air pollutants in Chinese exports would be overestimated by 12%-22% without accounting for trade heterogeneity. Unequal distributions of export-related air pollutants and value added exist among different sectors. In particular, Manufacturing of Electronics and Communication Equipment sector induces 39.56% of embodied emissions in processing exports, and 41.78% of which are generated by Production and Supply of Electric Power and Steam Hot Water sector. China's restrictions on processing exports should focus not only on the direct emissions generated by each sector but also on the emissions embodied in domestic supply chains.

Split aptamer-based detection of adenosine triphosphate using surface enhanced Raman spectroscopy and two kinds of gold nanoparticles.

An ultrasensitive and highly selective method is described for the determination of adenosine triphosphate (ATP) via surface-enhanced Raman scattering (SERS). Two split aptamers are used for specific recognition of ATP. They were attached to two SERS substrates. The first was placed on a nanolayer of gold nanoparticle-decorated graphene oxide (GO/Au3), and the other on gold nanoparticles (Au2). When ATP is introduced, it will interact with the split aptamers on the gold nanostructures to form a sandwich structure that brings the GO/Au3 nanolayer and the Au2 nanoparticle in close proximity. Consequently, the SERS signal, best measured at 1072 cm-1, is strongly enhanced. The sandwich structure also displays good water solubility and stability. Under optimized conditions, the SERS signal increases in the 10 pM - 10 nM ATP concentration range, and the limit of detection (LOD) is 0.85 pM. The method was applied to the determination of ATP in spiked human serum, and the LODs in serum and buffer are comparable. In our perception, the method has a wide scope in that numerous other aptamers may be used. This may result in a variety of other highly sensitive aptasensors for use in in-vitro diagnostics. Graphical abstract Schematic presentation of a self-assembly sandwich nanostructure as unique SERS assay platform for the sensitive detection of ATP.