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Cortisol secreted by the adrenal gland can lead to a significant increase in volume, vascular dilation, and hyperperfusion of the choroid. The retinal thickness increased after the cortisol level turned normal.

Humans are the primary sources of CO2and NH3indoors. Their emission rates may be influenced by human physiological and psychological status. This study investigated the impact of physiological and psychological engagements on the human emissions of CO2and NH3. In a climate chamber, we measured CO2and NH3emissions from participants performing physical activities (walking and running at metabolic rates of 2.5 and 5 met, respectively) and psychological stimuli (meditation and cognitive tasks). Participants’ physiological responses were recorded, including the skin temperature, electrodermal activity (EDA), and heart rate, and then analyzed for their relationship with CO2and NH3emissions. The results showed that physiological engagement considerably elevated per-person CO2emission rates from 19.6 (seated) to 46.9 (2.5 met) and 115.4 L/h (5 met) and NH3emission rates from 2.7 to 5.1 and 8.3 mg/h, respectively. CO2emissions reduced when participants stopped running, whereas NH3emissions continued to increase owing to their distinct emission mechanisms. Psychological engagement did not significantly alter participants’ emissions of CO2and NH3. Regression analysis revealed that CO2emissions were predominantly correlated with heart rate, whereas NH3emissions were mainly associated with skin temperature and EDA. These findings contribute to a deeper understanding of human metabolic emissions of CO2and NH3.

Focusing on the photoinduced electron transfer properties of the D-D-A molecule ((TPA-TT)-BODIPY-C60) in an external electric field (Fext), the excited-state properties in which the double-donor molecule is excited to form three charge-separated states were simulated. The charge-transfer processes of these three charge-separated states were investigated by considering the two donors as a whole ((TPA-TT-BODIPY)·+-C60·–) as a comparison object. The electronic coupling (VDA), reorganization energy (λ), and free energy (ΔG) of the different charge-separated states in Fextwere calculated and simulated. The calculated results show that the λ of (TPA-TT-BODIPY)·+-C60·–ranges from 0.576 to 0.51 eV, and the calculated ΔGof exciton dissociation ranges from −1.402 to −1.143 eV, indicating that exciton dissociation occurs in the Marcus inverted region. In the range of Fext= −10 × 10–5to 10 × 10–5au, the trend of the charge-transfer rate is gradually increasing, and the rate increase is mainly from the VDAand ΔGchanges. Moreover, the rapid formation of the (TPA-TT)-BODIPY·+-C60·–charge-separated state and the formation of the long-lived (TPA-TT)·+-BODIPY-C60·–are indicated by the exciton dissociation rate. By studying the charge-transfer parameters under different electric field directions, it is found that the regulation of electric field strength on the charge-transfer rate is consistent. These results provide a feasible method for the rational design of a new type of electron transfer process with high efficiency of the D-D-A system.

Purpose: To report three cases of Parry-Romberg syndrome (PRS) with progressive hemifacial atrophy and similar fundus changes.Methods: Retrospective case series of three patients who presented to the ophthalmology department with blurred vision in one eye. All of them underwent three-dimensional reconstruction of head computed tomography (CT), related physical examinations, and also monthly ocular examinations of both eyes, including the slit-lamp microscope, fundus autofluorescence, optical coherence tomography (OCT), and fundus fluorescein angiography (FFA). We also reviewed the current literature about the fundus change in PRS from inception to March 2020 via PubMed.Results: Coats-like fundus and exudative retinal detachment were found in all three eyes of three patients during the follow-up. No systematic changes were found except for hemifacial atrophy. The final diagnoses of these three patients were PRS.Conclusion: Only a subset of PRS patients have concomitant ocular changes, but it still should be noticed that the diagnosis of PRS should be considered if adults presented with Coats-like retinopathy and hemifacial atrophy.

Purpose: To present retinal pigment epithelium (RPE) aperture related to an avascular pigment epithelium detachment (PED) secondary to acute central serous chorioretinopathy (CSC).Methods: Case report.Results: A 47-year-old man diagnosed as acute CSC presented with RPE aperture in the superonasal area of the macula in his left eye during follow-up. At 2-week follow-up, his decimal best-corrected visual acuity (BCVA) was improved from 0.08 to 0.6 and subretinal fluid was partially absorbed. However, the near-infrared reflectance demonstrated a round mild hyperreflective lesion on the superonasal area of the macula. On spectral-domain optical coherence tomography (SD-OCT), RPE band of the round lesion discontinued but RPE fractured edges without shrinkage and curling. Fundus autofluorescence (FAF) showed RPE aperture appeared as round hypoautofluorescence and hyperautofluorescence outlined its borderline. OCT angiography demonstrated that no evidence of neovascularization within the sub-RPE space. En Face OCT confirmed that the RPE aperture developed at the edge of the PED lesion. At 8-month follow-up, his decimal BCVA was improved to 1.0 and SD-OCT demonstrated spontaneous resolution of subretinal fluid and restoration of RPE structure, with complete flattening of PED. However, FAF revealed hypoautofluorescence mingled with slight hyperautofluorescence within the lesion.Conclusions: To the best of our knowledge, this is the first report of an RPE aperture secondary to acute CSC. Our case indicated another novel possible pathological mechanism that in the relatively healthy RPE, increased hydrostatic pressure simply itself could contribute to RPE aperture.

This article theoretically studies the photoinduced charge transfer (CT) of rigid D-B-A molecules in two-photon absorption (TPA) adjusted by the external electric fields. Using a visualization method, the dynamic changes of light-induced CT in different channels of TPA are presented through a two-dimensional (2D) transition density matrix and a three-dimensional (3D) charge different density. Here, we prove the controllability of TPA on CT under the induction of a strong electric field. Adjusting the field direction and intensity significantly affects the position of the strong absorption peak in the TPA spectra, thereby further changing the electron–hole coherence length and the degree of dispersion. Our results can promote the recognition of the optical properties of the D-B-A system in synthetic molecules and provide an idea for increasing the proportion of excited states for CT in the molecule.

Anterior segment eye diseases account for a significant proportion of presentations to eye clinics worldwide, including diseases associated with corneal pathologies, anterior chamber abnormalities (e.g. blood or inflammation), and lens diseases. The construction of an automatic tool for segmentation of anterior segment eye lesions would greatly improve the efficiency of clinical care. With research on artificial intelligence progressing in recent years, deep learning models have shown their superiority in image classification and segmentation. The training and evaluation of deep learning models should be based on a large amount of data annotated with expertise; however, such data are relatively scarce in the domain of medicine. Herein, the authors developed a new medical image annotation system, called EyeHealer. It is a large-scale anterior eye segment dataset with both eye structures and lesions annotated at the pixel level. Comprehensive experiments were conducted to verify its performance in disease classification and eye lesion segmentation. The results showed that semantic segmentation models outperformed medical segmentation models. This paper describes the establishment of the system for automated classification and segmentation tasks. The dataset will be made publicly available to encourage future research in this area.

Squalene can react with indoor ozone to generate a series of volatile and semi-volatile organic compounds, some of which may be skin or respiratory irritants, causing adverse health effects. Better understanding of the ozone/squalene reaction and product transport characteristics is thus important. In this study, we developed a physical–chemical coupling model to describe the behavior of ozone/squalene reaction products, that is, 6-methyl-5-hepten-2-one (6-MHO) and 4-oxopentanal (4-OPA) in the gas phase and skin, by considering the chemical reaction and physical transport processes (external convection, internal diffusion, and surface uptake). Experiments without intervention were performed in a single-family house in California utilizing time- and space-resolved measurements. The key parameters in the model were extracted from 5 day data and then used to predict the behaviors in some other days. Predictions from the present model can reproduce the concentration profiles of the three compounds (ozone, 6-MHO, and 4-OPA) well (R2= 0.82–0.89), indicating high accuracy of the model. Exposure analysis shows that the total amount of 6-MHO and 4-OPA entering the blood capillaries in 4 days can reach 14.6 and 30.1 μg, respectively. The contribution of different sinks to ozone removal in the tested realistic indoor environment was also analyzed.

Objectives: We performed a systematic review and meta-analysis to assess the efficacy and safety of the mineralocorticoid receptor antagonist (MRA) treatment for central serous chorioretinopathy (CSC). Methods: We searched the PubMed, Embase, and the Cochrane Library to identify relevant clinical studies published prior to March 2020. The primary outcome was change in best-corrected visual acuity (BCVA), and the secondary outcomes included the subretinal fluid (SRF), subfoveal choroidal thickness (SFCT), and central macular thickness (CMT). Results: Five randomized controlled trials (RCT) and four cohort studies met the inclusion criteria with a total of 352 eyes. The MRA treatment was not superior to placebo in BCVA at 1 month (WMD = −0.06, 95% CI −0.15–0.02, P= 0.15, I2= 86%), 3 months (WMD = −0.04, 95% CI −0.14–0.06, P= 0.44, I2= 77%) and 6 months (WMD = −0, 95% CI −0.05–0.05, P= 0.92, I2= 0%). The MRA treatment resulted in significant reduction than the placebo in the SRF (WMD = −60.64, 95% CI −97.91 to −23.37, P= 0.001, I2= 49%), SFCT (WMD = −39.15, 95% CI −52.58 to −25.72, P< 0.001, I2= 0%), and CMT (WMD = −60.75, 95% CI −97.85 to −23.65, P= 0.01, I2= 53%). Conclusions: Our meta-analysis shows that the MRA treatment can improve anatomical structure in CSC patients, but it is not effective for achieving BCVA gain. The applicant of the MRA is safe and have no severe effect.

ABSTRACTDiabetic retinopathy (DR) represents the most typical complication of type 2 diabetes mellitus and one of the most primary oculopathy causing blindness. However, the mechanism of DR remains unknown. RIPK1/RIPK3, as homologous serine/threonine kinases, are key elements in mediating necroptosis and may have functions in DR development. To clarify the relationship between DR and RIPK1/RIPK3, this study established a model of apoptosis using high-glucose induced RGCs, which were treated with 7.5, 19.5, and 35 mM D-glucose for 12, 24, and 48 h, respectively. Subsequently, the expression of RIPK1/RIPK3 was determined and the protective effect of necrostatin-1 on RGCs injury induced by high glucose was explored. The results demonstrated that the expression of RIPK1 and RIPK3 in the cells was increased markedly following 12 h treatment with 19.5 mM D-glucose. Additionally, following an addition of 100 μM necrostatin-1 in 19.5 mM D-glucose medium for RGCs treatment 12 h, the protein expression of RIPK1 and RIPK3 was decreased markedly, and the number of Nissl bodies in cells was increased substantially. The findings of the present study indicated that high glucose could induce the expression of RIPK1/RIPK3, and necrostatin-1 could effectively protect RGCs from D-glucose-induced cell necrosis.

ABSTRACTAtrial fibrosis plays a significant role in the development of atrial fibrillation (AF). Previously, we showed that mitsugumin 53 (MG53) regulates TGF-β1 signaling pathway-induced atrial fibrosis. Recent studies have shown that caveolin-1 (CAV1) is an important anti-fibrosis signaling mediator that inhibits the TGF-β1 signaling pathway. Here, we further study the mechanism underlying the related action of MG53 and CAV1. We demonstrate that CAV1 expression was decreased while MG53 expression was increased in atrial tissue from AF patients. In cultured atrial fibroblasts, MG53 depletion by siRNA caused CAV1 upregulation and TGF-β1/SMAD2 signaling pathway downregulation, while MG53 overexpression via adenovirus had the opposite effect. CAV1 inactivated the TGF-β1/SMAD2 signaling pathway. In addition, using an Ang II–induced fibrosis model, we show that MG53 regulates TGF-β1 signaling via CAV1. Therefore, CAV1 is critical for the MG53 regulation of TGF-β1 signaling pathway-induced atrial fibrosis in AF. These findings reveal the related underlying mechanism of action of MG53 and CAV1 and provide a potential therapeutic target for fibrosis and AF.

Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However, intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetration is commonly overlooked. Therefore, in this study, taking fluorescent labeled PLGA (poly (lactic-co-glycolic acid)) nanoparticles as a tool, the influence of anionic and nonionic surfactants on mucus penetration ability of nanoparticles and their mucus barrier regulating ability were studied. The movement of PLGA nanoparticles in mucus was tracked by multiple particles tracking method (MPT). Alteration of mucus properties by addition of surfactants was evaluated by rheology and morphology study. Rat intestinal villus penetration study was used to further evaluate penetration enhancement of nanoparticles. The effective diffusivities of the nanoparticles in surfactants pretreated mucus were increased by 2–3 times and the mucus barrier regulating capacity was also surfactant type dependent. Sodium dodecyl sulfate (SDS) increased the complex viscosity and viscoelastic properties of mucus, but poloxamer presented a decreased trend. Tween 80 maintained the rheological property of the mucus. With the mucus barrier regulated by surfactants, the penetration of nanoparticles in intestinal villus was obviously increased. In summary, the mucus penetration ability of nanoparticles could be enhanced by altering mucus microenvironment with surfactants. Tween 80 which largely retains the original mucus rheology and morphology properties may be a promising candidate for facilitating nanoparticle penetration through the mucus barrier with good safety profile.

In this paper, we theoretically explore the motivation and behaviors of the excited‐state intramolecular proton transfer (ESIPT) reaction for a novel white organic light‐emitting diode (WOLED) material 4‐tert‐butyl‐2‐(5‐(5‐tert‐butyl‐2‐methoxyphenyl)thiazolo[5,4‐d]thiazol‐2‐yl)‐phenol (t‐MTTH). The “atoms in molecules” (AIM) method is adopted to verify the formation and existence of the hydrogen bond OH···N. By analyzing the excited‐state hydrogen bonding behaviors via changes in the chemical bonding and infrared (IR) vibrational spectra, we confirm that the intramolecular hydrogen bond OH···N should be getting strengthened in the first excited state in four kinds of solvents, thus revealing the tendency of ESIPT reaction. Further, the role of charge‐transfer interaction is addressed under the frontier molecular orbitals (MOs), which depicts the nature of the electronic excited state and supports the ESIPT reaction. Also, the electron distribution confirms the ESIPT tendency once again. The scanned and optimized potential energy curves according to variational OH coordinate in the solvents demonstrate that the proton transfer reaction should occur in the S1state, and the potential energy barriers along with ESIPT direction support this reaction. Based on the excited‐state behaviors reported in this work, the experimental spectral phenomenon has been reasonably explained. Charge redistribution and photoexcitation induce the strengthening of the intramolecular hydrogen bond in the S1state and facilitate the excited‐state intramolecular proton transfer (ESIPT) process in the 4‐tert‐butyl‐2‐(5‐(5‐tert‐butyl‐2‐methoxyphenyl)thiazolo[5,4‐d]thiazol‐2‐yl)‐phenol system. Potential energy curves of both S0and S1states reveal the ESIPT mechanism in four kinds of solvents, which reasonably explains the experimental phenomenon.

Terson syndrome refers to intraocular haemorrhage that occurs due to subarachnoid bleeding associated with an acute increase in intracranial pressure. No previous study has reported a delayed macular hole (MH) secondary to Terson syndrome. A 17-year-old boy visited our department and presented with vitreous bleeding and a history of subarachnoid haemorrhage. Sub-internal limiting membrane (ILM) haemorrhage with ILM detachment and intraretinal haemorrhage were detected during pars plana vitrectomy. Additionally, a delayed MH was detected 1 week after the surgery. There was no sign of MH closure during a 2-month follow-up. Subsequently, an MH massage was performed to close the MH. Our findings suggest that a delayed MH can occur secondary to Terson syndrome. Elevated hydrodynamic pressure and hydrostatic pressure, which are caused by sub-ILM and intraretinal haemorrhages of the fovea, contribute to the formation of an MH. Additionally, ILM peeling may cause damage to the macula and facilitate the formation of MHs. Although the MH may close by itself, early surgical intervention is recommended when there is no sign that the MH will close spontaneously because a prolonged MH can lead to retinal damage.

Ozone reaction with human surfaces is an important source of ultrafine particles indoors. However, 1–20 nm particles generated from ozone–human chemistry, which mark the first step of particle formation and growth, remain understudied. Ventilation and indoor air movement could have important implications for these processes. Therefore, in a controlled-climate chamber, we measured ultrafine particles initiated from ozone–human chemistry and their dependence on the air change rate (ACR, 0.5, 1.5, and 3 h–1) and operation of mixing fans (on and off). Concurrently, we measured volatile organic compounds (VOCs) and explored the correlation between particles and gas-phase products. At 25–30 ppb ozone levels, humans generated 0.2–7.7 × 1012of 1–3 nm, 0–7.2 × 1012of 3–10 nm, and 0–1.3 × 1012of 10–20 nm particles per person per hour depending on the ACR and mixing fan operation. Size-dependent particle growth and formation rates increased with higher ACR. The operation of mixing fans suppressed the particle formation and growth, owing to enhanced surface deposition of the newly formed particles and their precursors. Correlation analyses revealed complex interactions between the particles and VOCs initiated by ozone–human chemistry. The results imply that ventilation and indoor air movement may have a more significant influence on particle dynamics and fate relative to indoor chemistry.

The measurement of maximum cerebral blood flow in collateral vessels within the Sylvian fissure is an independent predictor for both hemorrhagic transformation and good outcome.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

AimsWe sought to investigate the risk factors of blood-brain barrier (BBB) disruption, and its potential impact on 90-day clinical outcome in acute ischemic stroke (AIS) patients after reperfusion therapy.MethodsConsecutive acute anterior circulation AIS patients imaged with computed tomographic perfusion (CTP) before reperfusion therapy were included. Tmax >6 s was used for the volumetric measurement of the hypoperfusion area. BBB permeability (BBBP) was calculated as the average relative permeability-surface area product (rPS) within the hypoperfusion region (rPShypo-i) and its contralateral mirror region (rPShypo-c) on CTP-derived PS color maps. Modified Rankin Scale (mRS) score was obtained at 90-day post-stroke.ResultsA total of 187 patients were included, among whom the median age was 73 (61–80) years and 76 (40.6%) were women. Median baseline NIHSS score was 12 (7– 16). Ninety-eight (52.4%) patients had mRS score >2. Increased rPShypo-iand rPShypo-cwere both independently associated with males and large infarct volume. The increased rPShypo-iwas also independently associated with a history of atrial fibrillation and high NIHSS score. Multivariable analysis showed higher rPShypo-cwas independently associated with higher mRS (OR: 1.064, 95% CI 1.011 to 1.121; P=0.018).ConclusionBBBP in both the hypoperfusion region and its contralateral mirror region are associated with stroke severity, but only increased BBBP in the contralateral mirror hypoperfusion region relates to worse outcome after reperfusion therapy.

Supplemental Digital Content is available in the text.

Human and mouse orthologs are expected to have similar biological functions; however, many discrepancies have also been reported. We systematically compared human and mouse orthologs in terms of alternative splicing patterns and expression profiles. Human-mouse orthologs are divergent in alternative splicing, as human orthologs could generally encode more isoforms than their mouse orthologs. In early embryos, exon skipping is far more common with human orthologs, whereas constitutive exons are more prevalent with mouse orthologs. This may correlate with divergence in expression of splicing regulators. Orthologous expression similarities are different in distinct embryonic stages, with the highest in morula. Expression differences for orthologous transcription factor genes could play an important role in orthologous expression discordance. We further detected largely orthologous divergence in differential expression between distinct embryonic stages. Collectively, our study uncovers significant orthologous divergence from multiple aspects, which may result in functional differences and dynamics between human-mouse orthologs during embryonic development.

Posttranslational modifications of proteins critically regulate the function, localization, and stability of target proteins. Histone modification is one of the regulatory mechanisms that modulate the chromatin structure and thereby affect various DNA-templated processes, such as gene transcription, DNA replication, DNA recombination, and DNA repair in cells. These molecular processes contribute to basic cellular functions, including cell cycle, cell growth, and apoptosis. Histone modifications consist of acetylation, methylation, phosphorylation, ubiquitination, sumoylation biotination, citrullination, poly-ADPribosylation, and N-glycosylation. The modification status of histone is balanced by two enzyme families with opposing catalytic activities: histone modifying and de-modifying enzymes. Recent studies have shown that dysfunction of histone modification enzymes is a major cause for human cancer initiation and progression. In this review, we will summarize the functions of histone modification enzymes in cancer, and the mechanisms that histone modification enzymes use to drive or suppress human malignancies.

Most natural gas hydrate (NGH) reservoirs have poor permeability characteristics, which is unfavorable to fluid flow and gas production. To enhance gas production, a new method of radial water jet slotting and grouting (RWJSG) was proposed to reconstruct the formation around horizontal wellbores of a horizontal well. To evaluate the effectiveness of the proposed method, a three-dimensional (3D) gas production model was constructed with reference to the NGH reservoir at the SH2 site in the South China Sea (SCS). The results show that RWJSG can effectively enhance the gas recovery of the horizontal well. Compared with an unreconstructed case, the hydrate dissociation efficiency, cumulative gas production, and average ratio of gas to water production in the RWJSG case are increased by 121.0, 116.3 and 46.1%, respectively, during the 720-day production period. RWJSG can enlarge reservoir exposed area, promote pressure drop transfer, and improve gas/water flow near the wellbore. In addition, the effect of increasing production mainly depends on the slot radius and number. Within a certain range, the decrease in slot spacing and increase in slot filler permeability have positive effects. For the reservoir at SH2 site, the scheme with a radius of 5 m, a spacing of 5 m, a number of 5 and a permeability of 500 mD could achieve remarkable stimulation effect. This work provides ideas and guidance for stimulation of horizontal wells in NGH reservoirs by RWJSG.

The Lund project (1992) recommended treatment with clonidine (2-adrenergic agonist) and metoprolol (1-adrenergic antagonist) to improve recovery after brain trauma, and discouraged use of the V1 agonist vasopressin (ADH). Brain effects of these drugs and the ability of a post-traumatic elevation of extracellular K concentrations ([K]o) to activate mechanism(s) leading to secondary cytotoxic (cellular) edema were then virtually unknown. Now, it is established that interactions occur between effects on astrocytes by high [K]o and vasopressin or 2- and 1-adrenergic agonists and antagonists, and that the effects modify edema and thus intracranial pressure. In mouse astrocytes in primary cultures, reliably expressing characteristics of their in vivo counterparts, high [K]o and each of the transmitters agonists activate a signal mechanism, transactivation, in which Ca2 entry through depolarization-mediated channel opening or stimulation of Gq- or Gi/o protein-coupled receptors via PKC-, Ca2- and metalloproteinase-mediated signaling leads to release of an epidermal growth factor (EGF) receptor agonist. Minor, but important, differences exist between individual pathways. The agonist released by dexmedetomidine decreases neuronal vulnerability to oxidative damage by a paracrine effect, and in all cases the released EGF receptor agonist has autocrine effects. These include mitogen-activated protein (MAP) kinase-mediated phosphorylation of astrocytic extracellular-regulated kinase (ERK), and with high [K]o also the cotransporter NKCC1, accumulating Na and K together with 2 Cl- and water, causing edema. This effect, exerted specifically on astrocytes, is enhanced by 1-adrenergic or vasopressinergic V1 signaling, explaining the beneficial effect of 1-adrenergic antagonists and why vasopressin should be omitted in edema treatment after brain trauma.

Pancreatic cancer is a serious disease worldwide for its high mortality. Gemcitabine has become the frontline option for the treatment of this disease since its approval. However, resistance to the drug has been on the rise in recent years. Searching for other chemotherapeutic agents therefore has attracted much attention. Cucurbitacin B (CuB) is a member of the triterpenoid family and has shown inhibitory effect on various cancer cells. In this study, we have assessed the effect of CuB on pancreatic cancer cells.

By virtue of its binding to cyclophilin, the cellular receptor for cyclosporine (CsA), we could identify a new compound D-43787 [N-[(1-tert-butyloxycarbonyl)-indolin-2-(S)-carbonyl]-indolin-2-(S)-carbonacid-[N-ε-benzyloxycarbonyl)-2-(S)-lysin methylester]-amide] exhibiting immunomodulating properties. It inhibited cell proliferation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA)/ionomycin and anti-CD3/CD28 with an IC50of 0.3 μM. The protein phosphatase calcineurin, which is the target of the CsA-cyclophilin complex, is not inhibited by D-43787. It inhibited T helper cell (Th) 2 cytokines interleukin (IL)-4, -5, and -13 more effectively than the Th1 cytokine interferon (IFN)-γ in human primary T cells. The IC50for IL-5 and IL-13 in TPA/ionomycin-stimulated peripheral blood mononuclear cells (PBMC) is 0.7 ± 0.1 and 0.5 ± 0.1 μM, respectively, whereas the IC50for IFN-γ is 2.0 ± 0.4 μM. When PBMC were stimulated with anti-CD3/CD28, the IC50for IL-4, -5, and -13 were 1.5 ± 0.2, 1.8 ± 0.2, and 1.9 ± 0.4 μM, respectively. IFN-γ was only partially inhibited under these conditions. This effect was even more pronounced in pure CD4+T cells. Pretreatment of human monocytes with D-43787 inhibited lipopolysaccharide-induced proinflammatory cytokines IL-6 and TNFα with an IC50of 1.2 ± 0.1 and 4.7 ± 0.9 μM, respectively. In vivo, D-43787 potently inhibited late-phase eosinophilia in actively sensitized and challenged guinea pigs (10 mg/kg, i.p.: 51%) and Brown-Norway rats (1 mg/kg, intrapulmonary: 66% 30 mg/kg, i.p.: 50%). In adjuvant-induced arthritis, D-43787 (10–40 mg/kg, b.i.d., i.p.) dose dependently reduced edema development on both hind paws. The potency of D-43787 was comparable with that of indomethacin and dexamethasone. In conclusion, we characterized a novel Th2 selective immunosuppressive drug with possible anti-asthmatic/anti-inflammatory effects. Its mode of action is distinct from that of CsA.

•Most of EVs are used as low-speed and close-range commuters in Shanghai.•Charging EVs at low night time is beneficial to both EV owners and the power grid.•PHEVs charge in the morning to meet the return trip, which is unfriendly to the grid.•The actual energy efficiency of EVs is higher than that provided by manufacturers.•It is necessary to optimize the layout of charging piles and orderly charging of EVs.