The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations.
We conducted a multicenter, prospective, open-label, randomized ...trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization.
A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis.
In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading Shanghai and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).
The intermarriage of neutral and tripodal imidazole ligand, tris(4‐(1H‐imidazol‐1‐yl)phenyl)amine (TIPA), with zinc phosphite yields two hybrid phosphites, Zn2(HPO3)2(TIPA)⋅2 H2O (1) and ...Zn3(HPO3)3(TIPA)⋅6 H2O (2). Compound 1 has a hybrid sheet with neutral zinc‐phosphite chains as supramolecular building blocks (SBBs), whereas 2 exhibits a 3D hybrid architecture with other neutral zincophosphite chains as supramolecular building blocks. The structural discrepancy between 1 and 2 is mainly due to the distinct linkage modes between organic TIPA ligands and inorganic zincophosphite chains. Interestingly, compounds 1 and 2 feature fast photochromism in response to UV light irradiation under ambient conditions. The discrepancy of photochromic performance between 1 and 2 is mainly due to the different geometrical configuration of the TIPA ligand. Different to majority of reported hybrid photochromic compounds driven by photochromic active units, the photochromism in 1 and 2 is derived from the electron transfer (ET) between phosphite and non‐photochromic triimidazole‐derivative ligand TIPA. Compared with the widely explored nonphotochromic polypyridine‐derivative as electron acceptors (EAs), our work provides a new EA model for the design of hybrid photochromic materials based on the ligand‐to‐ligand ET mechanism. A multiple anti‐counterfeiting application based on 1 and 2 was investigated.
A new electron‐acceptor: We provide a new category of electron acceptors (EAs), the tri(imidazole)‐derivative moiety, for the design of crystalline hybrid photochromic materials. The new unit differs clearly from other broadly investigated photoactive units and that are being explored as EAs for nonphotoactive polypyridine‐derivative units.
Summary In this Series paper, we examine how mass incarceration shapes inequality in health. The USA is the world leader in incarceration, which disproportionately affects black populations. Nearly ...one in three black men will ever be imprisoned, and nearly half of black women currently have a family member or extended family member who is in prison. However, until recently the public health implications of mass incarceration were unclear. Most research in this area has focused on the health of current and former inmates, with findings suggesting that incarceration could produce some short-term improvements in physical health during imprisonment but has profoundly harmful effects on physical and mental health after release. The emerging literature on the family and community effects of mass incarceration points to negative health impacts on the female partners and children of incarcerated men, and raises concerns that excessive incarceration could harm entire communities and thus might partly underlie health disparities both in the USA and between the USA and other developed countries. Research into interventions, policies, and practices that could mitigate the harms of incarceration and the post-incarceration period is urgently needed, particularly studies using rigorous experimental or quasi-experimental designs.
Doxorubicin (DOX) is an anthracycline chemotherapy drug used in the treatment of various types of cancer. However, short-term and long-term cardiotoxicity limits the clinical application of DOX. ...Currently, dexrazoxane is the only approved treatment by the United States Food and Drug Administration to prevent DOX-induced cardiotoxicity. However, a recent study found that pre-treatment with dexrazoxane could not fully improve myocardial toxicity of DOX. Therefore, further targeted cardioprotective prophylaxis and treatment strategies are an urgent requirement for cancer patients receiving DOX treatment to reduce the occurrence of cardiotoxicity. Accumulating evidence manifested that Sirtuin 1 (SIRT1) could play a crucially protective role in heart diseases. Recently, numerous studies have concentrated on the role of SIRT1 in DOX-induced cardiotoxicity, which might be related to the activity and deacetylation of SIRT1 downstream targets. Therefore, the aim of this review was to summarize the recent advances related to the protective effects, mechanisms, and deficiencies in clinical application of SIRT1 in DOX-induced cardiotoxicity. Also, the pharmaceutical preparations that activate SIRT1 and affect DOX-induced cardiotoxicity have been listed in this review.
Lysine (Lys) residues in proteins undergo a wide range of reversible post-translational modifications (PTMs), which can regulate enzyme activities, chromatin structure, protein-protein interactions, ...protein stability, and cellular localization. Here we discuss the “writers,” “erasers,” and “readers” of some of the common protein Lys PTMs and summarize examples of their major biological impacts. We also review chemical biology approaches, from small-molecule probes to protein chemistry technologies, that have helped to delineate Lys PTM functions and show promise for a diverse set of biomedical applications.
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Zhipeng Wang and Philip Cole review major types of chemical modifications of the amino acid lysine in proteins and how they are added and removed. They also discuss a number of chemical approaches and how they have been applied to clarify the roles of lysine modifications in biology and medicine.
AIMS: The aim of this study was to characterize anaerobic ammonium oxidation (anammox) community in sediments of the Dongjiang River, a drinking water source of Hong Kong. METHODS AND RESULTS: The ...diversity and distribution of the anammox community were investigated based on a comparative analyses of 16S rRNA and hydrazine oxidation (hzo) genes of anammox bacteria. Candidatus Brocadia and two new anammox bacterial clusters were detected based on phylogenetic analysis of 16S rRNA genes. In contrast, the targeting of hzo genes indicated the presence of only Candidatus Jettenia with four different clusters. It was found that the sequence diversities of hzo genes were higher than those of the 16S rRNA genes. The abundance of anammox bacteria varied significantly among the sediment samples based on qPCR. Pearson correlation analysis indicated that nitrite concentration was the key factor influencing the abundance of anammox bacteria. The redundance analysis (RDA) confirmed that the combination of the contents of nitrite and nitrate, and the ratio of total nitrogen vs total carbon (TN/TC) had significant impact on the anammox bacterial community structure. CONCLUSIONS: The results revealed that the diverse anammox bacteria were present in sediments of the Dongjiang River, and the community structures were associated with varied environmental factors caused by urban pollutant invasion. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report about the distribution of anammox bacterial community in sediments of the Dongjiang River, which provides helpful information of anammox niche specificity and influencing factors in the river ecosystem.
Although it is known that the expression and activity of sirtuin 1 (SIRT1) significantly decrease in doxorubicin (DOX)-induced cardiomyopathy, the role of interaction between SIRT1 and sestrin 2 ...(SESN2) is largely unknown. In this study, we investigated whether SESN2 could be a crucial target of SIRT1 and the effect of their regulatory interaction and mechanism on DOX-induced cardiac injury. Here, using DOX-treated cardiomyocytes and cardiac-specific Sirt1 knockout mice models, we found SIRT1 deficiency aggravated DOX-induced cardiac structural abnormalities and dysfunction, whereas the activation of SIRT1 by resveratrol (RES) treatment or SIRT1 overexpression possessed cardiac protective effects. Further studies indicated that SIRT1 exerted these beneficial effects by markedly attenuating DOX-induced oxidative damage and apoptosis in a SESN2-dependent manner. Knockdown of Sesn2 impaired RES/SIRT1-mediated protective effects, while upregulation of SESN2 efficiently rescued DOX-induced oxidative damage and apoptosis. Most importantly, SIRT1 activation could reduce DOX-induced SESN2 ubiquitination possibly through reducing the interaction of SESN2 with mouse double minute 2 (MDM2). The recovery of SESN2 stability in DOX-impaired primary cardiomyocytes by SIRT1 was confirmed by Mdm2-siRNA transfection. Taken together, our findings indicate that disrupting the interaction between SESN2 and MDM2 by SIRT1 to reduce the ubiquitination of SESN2 is a novel regulatory mechanism for protecting hearts from DOX-induced cardiotoxicity and suggest that the activation of SIRT1-SESN2 axis has potential as a therapeutic approach to prevent DOX-induced cardiotoxicity.
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•DOX-induced cardiotoxicity is based on decreased SIRT1 and SESN2 levels.•SIRT1 activation improves DOX-induced cardiac oxidative stress and apoptosis.•The benefits of SIRT1 in DOX-impaired cardiac function require the activation of SESN2.•SIRT1 reduces ubiquitination and degradation of SESN2 via MDM2.
In order to find a new way to slow down the release of drugs and to solve the burst release problem of drugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium ...alginate/hydroxyapatite (SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in the beads during the sol-gel transition process of SA. The SA/HA nanocomposites were characterized by Fourier transform IR spectroscopy, X-ray fluorescence spectrometry, scanning electron microscopy and field emission SEM in order to reveal their composition and surface morphology as well as the role that the in situ generated HA micro-particles play. The factors influencing the swelling behavior, drug loading and controlled release behavior of the SA/HA nanocomposite beads were also investigated using diclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the nanocomposites, which could contract and restrict the movability of the SA polymer chains, and then change the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency of DS was improved, and the burst release of DS was overcome. The factors (including concentration of Ca(2+), reaction time and temperature) affecting the growth of HA micro-particles have a clear influence on the entrapment efficiency and release rate of DS. In this work, the nanocomposite beads prepared under optimum condition could prolong the release of DS for 8h more compared with the pristine SA hydrogel beads.
Abstract
The intertwining between spin, charge, and lattice degrees of freedom can give rise to unusual macroscopic quantum states, including high-temperature superconductivity and quantum anomalous ...Hall effects. Recently, a charge density wave (CDW) has been observed in the kagome antiferromagnet FeGe, indicative of possible intertwining physics. An outstanding question is that whether magnetic correlation is fundamental for the spontaneous spatial symmetry breaking orders. Here, utilizing elastic and high-resolution inelastic x-ray scattering, we observe a c-axis superlattice vector that coexists with the 2
$$\times$$
×
2
$$\times$$
×
1 CDW vectors in the kagome plane. Most interestingly, between the magnetic and CDW transition temperatures, the phonon dynamical structure factor shows a giant phonon-energy hardening and a substantial phonon linewidth broadening near the c-axis wavevectors, both signaling the spin-phonon coupling. By first principles and model calculations, we show that both the static spin polarization and dynamic spin excitations intertwine with the phonon to drive the spatial symmetry breaking in FeGe.
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