Abstract
Alkynes generally serve as C
2
synthons in transition‐metal‐catalyzed C−H annulations, herein, exploiting electron‐deficient alkynes as unconventional C
1
synthons, the chemo‐ and ...regiospecific synthesis of functionalized 1
H
‐imidazo1,5‐
a
indol‐3(2
H
)‐ones via a redox‐neutral rhodium(III)‐catalyzed 4+1 annulation of
N
‐carbamoyl indoles has been achieved. This process is characterized by high chemo‐ and regioselectivity, broad substrate scope, good tolerance of functional groups, moderate to high yields and mild redox‐neutral conditions, thus affording a robust approach to access valuable 1
H
‐imidazo1,5‐
a
indol‐3(2
H
)‐ones.
magnified image
In the present study, the structural, mechanical, electronic and optical properties of all-inorganic vacancy-ordered double perovskites A2Sn1−xTixY6 (A = K, Rb, Cs; Y = Cl, Br, I) are explored by ...density functional theory. The structural and thermodynamic stabilities are confirmed by the tolerance factor and negative formation energy. Moreover, by doping Ti ions into vacancy-ordered double perovskite A2SnY6, the effect of Ti doping on the electronic and optical properties was investigated in detail. Then, according to the requirement of practical applications in photovoltaics, the optimal concentration of Ti ions and the most suitable halide element are determined to screen the right compositions. In addition, the mechanical, electronic and optical properties of the selected compositions are discussed, exhibiting the maximum optical absorption both in the visible and ultraviolet energy ranges; thus, the selected compositions can be considered as promising materials for application in solar photovoltaics. The results suggest a great potential of A2Sn1−xTixY6 (A = K, Rb, Cs; Y = Cl, Br, I) for further theoretical research as well as experimental research on the photovoltaic performance of stable and toxic-free perovskite solar cells.
Central post-stroke pain (CPSP) is a disabling condition in stroke patients. It is a type of neuropathic pain for which the mechanism and relevant drug pathways remain unknown. Inflammatory response ...and central disinhibition have been suggested recently. Our previous research has shown targeting P2X4 receptors (P2X4R) may be effective in the treatment of CPSP, but the downstream pathway of the P2X4R has not been studied. In this study, we found the increase in tumor necrosis factor alpha (TNF-α) level and endocytosis of surface gamma-aminobutyric acid a receptors (GABAaR) in CPSP, and these effects were inhibited by blocking P2X4R. Furthermore, antagonizing TNF-α can increase surface GABAaR expression and mechanical pain threshold. Meanwhile, knocking down TNFR1 but not TNFR2 reversed the endocytosis of surface GABAaR and alleviated mechanical allodynia. Thus, the neuropathic pain was mediated, in part, through P2X4R/TNF-α/TNFR1/GABAaR signaling, which was induced after stroke. PERSPECTIVE: P2X4R regulates the pathophysiological mechanism of CPSP through central disinhibition mediated by TNF-α/TNFR1. Our results suggest that modulation of P2X4R-TNF-α/TNFR1-GABAaR signaling could provide a new therapeutic strategy to treat CPSP.
Research into kappa opioid receptor (KOR) agonists with attenuated central-nervous-system side effects is a critical focus for developing productive and safe analgesics. Herein, a series of
...-substituted
-cyclopropylmethyl-7α-phenyl-6,14-
ethano-tetrahydronorthebaines were designed, synthesized, and subjected to bioassays. Compound
exhibited high subtype selectivity and potent agonistic activity toward KOR (KOR,
= 3.9 nM, MOR/KOR = 270, DOR/KOR = 1075;
SGTPγS binding, EC
= 3.4 nM). Additionally, this compound exhibited robust and persistent antinociceptive effects in rodent models with different animal strains (hot plate test, ED
= 0.20-0.30 mg/kg, i.p.; abdominal constriction test, ED
= 0.20-0.60 mg/kg, i.p.), with its KOR-mediated mechanism for antinociception firmly established. Notably, compound
, unlike conventional KOR agonists, displayed minimal sedation and aversion at the antinociceptive ED
dose. This feature addresses a crucial limitation in existing KOR agonists, positioning compound
as a promising novel therapeutic agent.
Research into kappa opioid receptor (KOR) agonists with attenuated central-nervous-system side effects is a critical focus for developing productive and safe analgesics. Herein, a series of ...ortho-substituted N-cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaines were designed, synthesized, and subjected to bioassays. Compound 7a exhibited high subtype selectivity and potent agonistic activity toward KOR (KOR, K i = 3.9 nM, MOR/KOR = 270, DOR/KOR = 1075; 35SGTPγS binding, EC50 = 3.4 nM). Additionally, this compound exhibited robust and persistent antinociceptive effects in rodent models with different animal strains (hot plate test, ED50 = 0.20–0.30 mg/kg, i.p.; abdominal constriction test, ED50 = 0.20–0.60 mg/kg, i.p.), with its KOR-mediated mechanism for antinociception firmly established. Notably, compound 7a, unlike conventional KOR agonists, displayed minimal sedation and aversion at the antinociceptive ED50 dose. This feature addresses a crucial limitation in existing KOR agonists, positioning compound 7a as a promising novel therapeutic agent.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly around the world, posing a major threat to human health and the ...economy. Currently, long-term data on viral shedding and the serum antibody responses in COVID-19 patients are still limited. Herein, we report the clinical features, viral RNA loads, and serum antibody levels in a cohort of 112 COVID-19 patients admitted to the Honghu People’s Hospital, Hubei Province, China. Overall, 5.36% (6/112) of patients showed persistent viral RNA shedding (> 45 days). The peak viral load was higher in the severe disease group than in the mild group (median cycle threshold value, 36.4 versus 31.5;
P
= 0.002). For most patients the disappearance of IgM antibodies occurred approximately 4–6 weeks after symptoms onset, while IgG persisted for over 194 days after the onset of symptoms, although patients showed a 46% reduction in antibodies titres against SARS-CoV-2 nucleocapsid protein compared with the acute phase. We also studied 18 asymptomatic individuals with RT-qPCR confirmed SARS-CoV-2 infection together with 17 symptomatic patients, and the asymptomatic individuals were the close contacts of these symptomatic cases. Delayed IgG seroconversion and lower IgM seropositive rates were observed in asymptomatic individuals. These data indicate that higher viral loads and stronger antibody responses are related to more severe disease status in patients with SARS-CoV-2 infection, and the antibodies persisted in the recovered patient for more than 6 months so that the vaccine may provide protection against SARS-CoV-2 infection.
•Methanogen pretreatment changed remarkably pyrolysis product distribution in bio-oil.•After biopretreatment, the phenols content increased from 42.25% to 79.32%.•Methanogen pretreatment improved the ...pyrolysis selectivity of CS for 4-VP.•Biopretreatment increased the 4-VP content from 28.6% to 60.9% in bio-oil.•Effects of biopretreated time on pyrolysis product distribution were insignificant.
After pretreated by methanogen for 5, 15 and 25days, corn stalk (CS) were pyrolyzed at 250, 300, 350, 400, 450 and 500°C by Py–GC/MS and product distribution in bio-oil was analyzed. Results indicated that methanogen pretreatment changed considerably the product distribution: the contents of sugar and phenols increased; the contents of linear carbonyls and furans decreased; the contents of linear ketones and linear acids changed slightly. Methanogen pretreatment improved significantly the pyrolysis selectivity of CS to phenols especially 4-VP. At 250°C, the phenols content increased from 42.25% for untreated CS to 79.32% for biopretreated CS for 5days; the 4-VP content increased from 28.6% to 60.9%. Increasing temperature was contributed to convert more lignin into 4-VP, but decreased its content in bio-oil due to more other chemicals formed. The effects of biopretreatment time on the chemicals contents were insignificant.
Both optimal stereoacuity and integration time to achieve that are impaired in patients with intermittent exotropia. The deterioration of stereoacuity is more revealing since it correlates well with ...exotropia control score.
Despite the periodic misalignment of two eyes, some intermittent exotropia (IXT) patients exhibit normal stereoacuity, particularly when evaluated with static tests. It is not clear if the temporal integration process of stereopsis is altered in IXT patients, thus warranting further research.
IXT patients (
= 29) and age-matched normal controls (
= 36) were recruited. Static stereopsis was measured with the Titmus stereoacuity test. In computer-generated random dots tests, stereoacuity was measured with a stimuli presentation duration varying from 100 to 1,200 ms. And the relationship between stereoacuity and stimuli duration was fitted into a quadratic model. Optimal stereoacuity was achieved when fitted curve flattened and the critical integration time was the duration needed to achieve optimal stereoacuity.
IXT patients were not found to differ significantly from control subjects under the Titmus test, while the Random Dots stereotest showed significantly worse optimal stereoacuity and significantly longer critical integration time. Multiple regression analysis showed that age (
= -4.83;
= 0.04) had statistically significant negative correlation on the critical integration time, age (
= -6.45;
= 0.047) and exotropia control scores (
= 60.71;
= 0.007) had statistically significant effects on optimal stereoacuity.
The temporal integration for stereopsis is impaired in IXT patients, requiring longer critical integration time to achieve elevated optimal stereoacuity.
Abstract
The Quasi-Analytical Algorithm (QAA) is effective in retrieving water inherent optical properties (IOPs) from remote sensing spectral reflectance and has wider applications in studies of the ...open ocean and coastal waters than of inland waters. This research aimed to modify the QAA model based on measured field spectral reflectance and absorption coefficients to render it applicable to studies of Daihai Lake, China. The improvements mainly included the reference wavelength selection, the power index of the particle backscattering coefficient and the exponential slope of the absorption coefficient of the colored detrital matter estimation. The average relative error between the inverse and measured absorption coefficients was less than 20%. A linear model was established between the phytoplankton absorption coefficient at a wavelength of 674 nm (aph(674)) and the chlorophyll-a (Chl-a) concentration, with a determination coefficient of 0.88. Additionally, the modified Quasi-Analytical Algorithm (MQAA) model was applied to the Ocean and Land Color Instrument (OLCI) data aboard the Sentinel-3 satellite. Finally, a spatial distribution map for the Chl-a concentrations in Daihai Lake on August 10, 2017, was drawn and the mid-eutrophication area was found to occur in the north and border.
Alkynes generally serve as C2 synthons in transition‐metal‐catalyzed C−H annulations, herein, exploiting electron‐deficient alkynes as unconventional C1 synthons, the chemo‐ and regiospecific ...synthesis of functionalized 1H‐imidazo1,5‐aindol‐3(2H)‐ones via a redox‐neutral rhodium(III)‐catalyzed 4+1 annulation of N‐carbamoyl indoles has been achieved. This process is characterized by high chemo‐ and regioselectivity, broad substrate scope, good tolerance of functional groups, moderate to high yields and mild redox‐neutral conditions, thus affording a robust approach to access valuable 1H‐imidazo1,5‐aindol‐3(2H)‐ones.
PDF
