The first Pd(II)-catalyzed enantioselective alkynylation of unbiased methylene β-C(sp3)–H bonds is reported. The readily accessible and tunable BINOL derivatives are used as chiral ligands in C–H ...activation for the first time. 3,3′-Fluorinated-BINOL proved crucial in determining both the reactivity and enantioselectivity. A wide range of carboxylic acid derivatives are well tolerated with high enantioselectivities (up to 96% ee). Mechanistic studies suggest that multiple ligands may participate in the stereodetermining C–H palladation step, and a chiral amplification effect is observed.
The incorporation of new modalities into chemotherapy greatly enhances the anticancer efficacy combining the merits of each treatment, showing promising potentials in clinical translations. Herein, a ...hybrid nanomedicine (Au/FeMOF@CPT NPs) is fabricated using metal–organic framework (MOF) nanoparticles and gold nanoparticles (Au NPs) as building blocks for cancer chemo/chemodynamic therapy. MOF NPs are used as vehicles to encapsulate camptothecin (CPT), and the hybridization by Au NPs greatly improves the stability of the nanomedicine in a physiological environment. Triggered by the high concentration of phosphate inside the cancer cells, Au/FeMOF@CPT NPs effectively collapse after internalization, resulting in the complete drug release and activation of the cascade catalytic reactions. The intracellular glucose can be oxidized by Au NPs to produce hydrogen dioxide, which is further utilized as chemical fuel for the Fenton reaction, thus realizing the synergistic anticancer efficacy. Benefitting from the enhanced permeability and retention effect and sophisticated fabrications, the blood circulation time and tumor accumulation of Au/FeMOF@CPT NPs are significantly increased. In vivo results demonstrate that the combination of chemotherapy and chemodynamic therapy effectively suppresses the tumor growth, meantime the systemic toxicity of this nanomedicine is greatly avoided.
A hybrid nanomedicine (Au/FeMOF@CPT NPs) consisting of metal–organic framework nanoparticles (MOF NPs) and Au NPs is developed for cancer chemo/chemodynamic therapy. MOF NPs are used as vehicles to encapsulate camptothecin (CPT). H2O2 from the oxidation of intracellular glucose by Au NPs is further utilized as fuel for the Fenton reaction, thus realizing the synergistic anticancer efficacy.
Accurate calculation of protein–protein binding free energy is of great importance in biological and medical science, yet it remains a hugely challenging problem. In this work, we develop a new ...strategy in which a screened electrostatic energy (i.e., adding an exponential damping factor to the Coulombic interaction energy) is used within the framework of the molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) method. Our results show that the Pearson correlation coefficient in the modified MM/PBSA is over 0.70, which is much better than that in the standard MM/PBSA, especially in the Amber14SB force field. In particular, the performance of the standard MM/PBSA is very poor in a system where the proteins carry like charges. Moreover, we also calculated the mean absolute error (MAE) between the calculated and experimental ΔG values and found that the MAE in the modified MM/PBSA was indeed much smaller than that in the standard MM/PBSA. Furthermore, the effect of the dielectric constant of the proteins and the salt conditions on the results was also investigated. The present study highlights the potential power of the modified MM/PBSA for accurately predicting the binding energy in highly charged biosystems.
Abstract
One of the purposes of taking spectra for millions of stars through the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) medium-resolution survey (MRS) is to obtain the ...elemental abundances, so that one can trace the origin and evolution for the element of interests. Lithium is one of such elements of great importance, which exhibits many puzzling behaviors. Investigating the lithium abundances to a uniquely large sample of stars is essential to understand its origin and evolution. In this paper, we present the lithium abundances obtained from the LAMOST MRS spectra calculated by the template-matching method. Our data set consists of 294,857 spectra that corresponds to 165,479 stars with a resolution power of Δ
λ
/
λ
∼ 7500. We compared the lithium abundances derived from our work with those using the high-resolution spectra and found a good consistence. The errors of lithium abundances are discussed. Our results suggest that the distribution of lithium abundances show two clear peaks at +2.6 and +1.0 dex, respectively. This sample is potentially important for investigating physical mechanisms occurring inside stars that alter the surface lithium abundance.
In patients with preserved ejection fraction or right bundle branch block (RBBB) pattern requiring a high percentage of ventricular pacing, His‐bundle pacing (HBP) might be an alternative to ...biventricular pacing, although the high threshold occasionally occurs. We provided a case of the intrinsic RBBB correction by capturing intra‐Hisian left bundle branch (LBB) or distal His‐bundle with different output settings. LBB pacing had the advantage of a much lower threshold while remained most synchrony as HBP. LBB pacing might be a promisingly safe and effective procedure for patients with high‐grade atrioventricular (AV) block and RBBB pattern.
Galectin-3, a microglia/macrophage-derived inflammatory mediator, plays a role in the stroke progression. In this single-center prospective study, we included 288 consecutive patients with a ...first-ever acute ischemic stroke to assess the association between galectin-3 serum level and clinical severity at admission and outcome at discharge by univariate and multivariate logistic regression. The results were presented as odds ratios (OR) and 95% confidence intervals (CI). Patients with high severity and poor outcomes had higher serum levels of galectin-3 (P<0.001 and P<0.001). Multivariate analysis suggested that a galectin-3 serum level in the highest quartile (The lowest three quartilesQ1-3 as the reference) was associated with poor functional outcome (OR, 3.15; 95% CI, 2.44-3.87). The AUC (standard error) for the NIHSS and the combined model were 0.764 (0.031) and 0.823 (0.027), corresponding to a difference of 0.059 (0.004). This study shows that higher serum levels of galectin-3 are associated with stroke severity at admission and stroke prognosis at discharge in ischemic stroke.
Abstract
The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) Low Resolution Spectroscopic Survey (LRS) provides massive spectroscopic data on M-type stars, and the derived stellar ...parameters could bring vital help to various studies. We adopt the ULySS package to perform
χ
2
minimization with model spectra generated from the MILES interpolator and determine the stellar atmospheric parameters for the M-type stars from LAMOST LRS Data Release 8. Comparison with the stellar parameters from the APOGEE Stellar Parameter and Chemical Abundance Pipeline (ASPCAP) suggests that most of our results have good consistency. For M dwarfs, we achieve dispersions better than 74 K, 0.19 dex, and 0.16 dex for
T
eff
,
log
g
, and Fe/H, while for M giants, the internal uncertainties are 58 K, 0.32 dex, and 0.26 dex, respectively. Compared to ASPCAP we also find a systematic underestimation of Δ
T
eff
= −176 K for M dwarfs and a systematic overestimation of
Δ
log
g
= 0.30 dex for M giants. However, such differences are less significant when we make a comparison with common stars from other literature, which indicates that systematic biases exist in the difference between ASPCAP and other measurements. A catalog of 763,136 spectra corresponding to 616,314 M-type stars with derived stellar parameters is presented. We determine the stellar parameters for stars with
T
eff
higher than 2900 K, with
log
g
from −0.24 dex to 5.9 dex. The typical precisions are 45 K, 0.25 dex, and 0.22 dex, for
T
eff
,
log
g
, and Fe/H, respectively, which are estimated from duplicate observations of the same stars.
Cardiac arrhythmias associated with intracellular calcium inhomeostasis are refractory to antiarrhythmic therapy. We hypothesized that late sodium current (I
) contributed to the calcium-related ...arrhythmias. Monophasic action potential duration at 90% completion of repolarization (MAPD
) was significantly increased and ventricular arrhythmias were observed in hearts with increased intracellular calcium concentration (Ca
) by using Bay K 8644, and the increase became greater in hearts treated with a combination of ATX-II and Bay K 8644 compared to Bay K 8644 alone. The prolongations caused by Bay K 8644 and frequent episodes of ventricular tachycardias, both in absence and presence of ATX-II, were significantly attenuated or abolished by late I
inhibitors TTX and eleclazine. In rabbit ventricular myocytes, Bay K 8644 increased I
density, calcium transient and myocyte contraction. TTX and eleclazine decreased the amplitude of late I
, the reverse use dependence of MAPD
at slower heart rate, and attenuated the increase of intracellular calcium transient and myocyte contraction. TTX diminished the phosphorylation of CaMKII-δ and Na
1.5 in hearts treated with Bay K 8644 and ATX-II. In conclusion, late I
contributes to ventricular arrhythmias and its inhibition is plausible to treat arrhythmias in hearts with increased Ca
.
SUMMARY Ischemic stroke classification is critical in conducting basic research and clinical practice. A precise analysis of stroke subtypes requires the integration of clinical features, findings ...from diagnostic tests, and knowledge about potential etiologic factors by competent diagnostic investigators. We performed a literature review of the published stroke classification systems and examined each for its benefits and limitations in the evaluation of the stroke etiology. Two major approaches to etiologic classifications of ischemic stroke are currently being used: the causative and phenotypic subtyping. The most widely used causative system is the Trial of Org 10172 in acute stroke treatment (TOAST) classification. With the advances in modern diagnostic technology, new stroke subclassification systems, such as the causative classification system (CCS) and Chinese ischemic stroke subclassification (CISS) system, have been developed to enhance the accuracy of TOAST. The A‐S‐C‐O (Atherosclerosis, Small‐vessel disease, Cardiac source, Other cause) phenotypic classification system makes efforts to identify the most likely etiology but not neglecting the possibility of other potential multiple causes. We conclude that the ideal stroke classification system needs to be valid, easy to use, evidence‐based, and incorporate new information as it emerges.
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