Abstract
Black holes can amplify incoming bosonic waves via rotational superradiance, inducing bound states of ultralight bosons around them. This phenomenon has the potential to confine the ...parameter spaces of new bosons. Axions and axion-like particles (ALPs) are candidate beyond-standard-model particles that can form such clouds around supermassive black holes (SMBHs) and impact the polarization signal in a similar fashion to Faraday rotation via axion–photon coupling. Prior efforts have used polarized images from the Event Horizon Telescope (EHT) M87 2017 observations to limit the dimensionless axion–photon coupling to previously unexplored regions. However, with the novel calibration-insensitive quantities, closure traces, and conjugate closure trace products, it is possible to constrain the existence of axion clouds while avoiding the dominant sources of systematic uncertainties, e.g., station gains and polarization leakages. We utilize a simple geometric model for the polarization map of M87* to fit the model parameters with both simulated and real data sets and reach a comparable level of constraint in the accuracy with which an axion cloud may be excluded in M87. Future applications of our approach include subsequent M87* and Sgr A* observations by EHT and the next-generation EHT that are expected to produce stronger constraints across a wider range of axion and ALP masses. Because it does not require imaging, closure trace analyses may be applied to target active galactic nuclei for which imaging is marginal, extending the number of SMBHs from which axion limits may be obtained significantly.
A novel series of clioquinol-moracin hybrids were designed and synthesized by fusing the pharmacophores of clioquinol and moracin M, and their activities as multitarget-directed ligands against ...Alzheimer’s disease were evaluated. Biological activity results demonstrated that these hybrids possessed significant inhibitory activities against phosphodiesterase 4D (PDE4D) and Aβ aggregation as well as remarkable antioxidant effects and excellent blood–brain barrier permeability. The optimal compound, 18d (WBQ5187), exhibited excellent PDE4D inhibitory potency (IC50 = 0.32 μM), significant antioxidant effects, appropriate biometal chelating functions, and interesting properties that modulated self- and metal-induced Aβ aggregation. Two-dimensional NMR studies revealed that 18d had significant interactions with Aβ1–42 at the R5, H6, H14, Q15, and F20 residues. Furthermore, this typical hybrid possessed preeminent neuroprotective effects against inflammation in microglial cells. Most importantly, oral administration of 18d·HCl demonstrated marked improvements in cognitive and spatial memory in a rat model of Alzheimer’s disease and protected hippocampal neurons from necrosis.
The microbiota–gut–brain axis plays a critical role in the pathogenesis of major depressive disorder (MDD) and related subclinical symptoms. However, studies on the gut microbiota in MDD are ...inconsistent, and data on MDD's effects on sleep are lacking. This study aimed to analyze the gut microbiota composition and sleep quality of patients with MDD. We performed 16S rRNA sequencing of stool samples from 36 patients with MDD and 45 healthy controls (HC). Sleep quality was assessed using the Pittsburgh Sleep Quality Index, depressive severity with the Hamilton Depression Scale, and insomnia severity using the Insomnia Severity Index. Forty-eight microbiota targets showed significant differences between MDD and HC. In MDD, six microbiota targets were associated with the severity of depression, 11 with sleep quality, and 3 with sleep severity. At the genus level,
Dorea
was simultaneously related to depression and sleep quality, while
Intestinibacter
was more closely related to sleep problems.
Coprococcus
and
Intestinibacter
were associated with sleep quality independent of the severity of depression. In conclusion, the present findings enable a better understanding of the relationship between gut microbiota and MDD-related symptoms. Gut microbiota alterations may become potential biomarkers and/or treatment targets for sleep quality in MDD.
Over the past several decades, liposomes have been extensively developed and used for various clinical applications such as in pharmaceutical, cosmetic, and dietetic fields, due to its versatility, ...biocompatibility, and biodegradability, as well as the ability to enhance the therapeutic index of free drugs. However, some challenges remain unsolved, including liposome premature leakage, manufacturing irreproducibility, and limited translation success. This article reviews various aspects of liposomes, including its advantages, major compositions, and common preparation techniques, and discusses present U.S. FDA-approved, clinical, and preclinical liposomal nanotherapeutics for treating and preventing a variety of human diseases. In addition, we summarize the significance of and challenges in liposome-enabled nanotherapeutic development and hope it provides the fundamental knowledge and concepts about liposomes and their applications and contributions in contemporary pharmaceutical advancement.
A novel series of quinoline–indole derivatives were synthesized and evaluated as multitarget-directed ligands for the treatment of Alzheimer’s disease (AD). Biological evaluation revealed that the ...derivatives had multifunctional profiles including antioxidant effects, blood–brain barrier (BBB) penetration, biometal chelation, Aβ aggregation modulation, neurotrophic and neuroprotective properties. Moreover, several representative target derivatives demonstrated hippocampal cell proliferation in living adult mice by intracerebroventricular (icv) injection or oral administration. Further drug-like property analysis demonstrated that the optimized compound, 8d (WI-1758), had liver microsomal metabolic stability, was well tolerated (>2000 mg/kg), and had a rational pharmacokinetic profile, as well as an oral bioavailability of 14.1% and a positive log BB (−0.19) to cross the BBB in vivo. Pharmacodynamics studies demonstrated that chronic oral administration of 8d·HCl substantially ameliorated the cognitive and spatial memory deficits in APP/PS1 AD mice and noticeably reduced overall cerebral β-amyloid deposits.
Background
Depressive disorder is a chronic mental illness that is vulnerable to relapse, imposes a huge economic burden on society and patients, and is a major global public health problem. ...Depressive disorders are characterized by depressed mood, decreased energy and interest, and suicidal ideation and behavior in severe cases. They can be treated through pharmacotherapy and psychotherapy or physical treatments such as electroconvulsive therapy (ECT). In patients with suicidal ideation, behavior, or refractory depressive disorder ECT has a faster onset of action and better efficacy than pharmacotherapy. This study used bibliometric and visual analyses to map the current state of global research on ECT for depressive disorder and to predict future research trends in this area.
Materials and methods
A literature search was performed for studies on ECT and depressive disorder in the Web of Science Core Collection (WoSCC) database. All studies considered for this paper were published between 2012 and 2021. Bibliometric and co-occurrence analyses were performed using the CiteSpace software.
Results
In total, 2,184 publications were retrieved. The number of publications on ECT and depressive disorder have been increasing since 2012, with China being a emerging hub with a growing influence in the field. Zafiris J. Daskalakis is the top author in terms of number of publications, and
The Journal of ECT
is not only the most published journal but also the most co-cited journal in the field. Co-occurrence analysis showed that electroconvulsive therapy, treatment-resistant depression, bipolar disorder, hippocampus, efficacy, and electrode placement are current research hotspots. Molecular biomarkers, neuroimaging predictors, and late-life depression will become research hotspots in the future.
Conclusion
Our analysis made it possible to observe an important growth of the field since 2012, to identify key scientific actors in this growth and to predict hot topics for future research.
Cholesterol (Chol) fortifies packing and reduces fluidity and permeability of the lipid bilayer in vesicles (liposomes)-mediated drug delivery. However, under the physiological environment, Chol is ...rapidly extracted from the lipid bilayer by biomembranes, which jeopardizes membrane stability and results in premature leakage for delivered payloads, yielding suboptimal clinic efficacy. Herein, we report a Chol-modified sphingomyelin (SM) lipid bilayer via covalently conjugating Chol to SM (SM-Chol), which retains membrane condensing ability of Chol. Systemic structure activity relationship screening demonstrates that SM-Chol with a disulfide bond and longer linker outperforms other counterparts and conventional phospholipids/Chol mixture systems on blocking Chol transfer and payload leakage, increases maximum tolerated dose of vincristine while reducing systemic toxicities, improves pharmacokinetics and tumor delivery efficiency, and enhances antitumor efficacy in SU-DHL-4 diffuse large B-cell lymphoma xenograft model in female mice. Furthermore, SM-Chol improves therapeutic delivery of structurally diversified therapeutic agents (irinotecan, doxorubicin, dexamethasone) or siRNA targeting multi-drug resistant gene (p-glycoprotein) in late-stage metastatic orthotopic KPC-Luc pancreas cancer, 4T1-Luc2 triple negative breast cancer, lung inflammation, and CT26 colorectal cancer animal models in female mice compared to respective FDA-approved nanotherapeutics or lipid compositions. Thus, SM-Chol represents a promising platform for universal and improved drug delivery.
The success of targeted drug therapies for treating cancer patients has attracted broad attention both in the academic community and social society. However, rapidly developed acquired resistance is ...becoming a newly recognized major challenge to the continuing efficiency of these therapies. Metformin is a well‐known natural compound with low toxicity derived from the plant French lilac. Our previous work has highlighted research progress of the combination of clinically applied chemotherapies and metformin by different mechanisms. We have also launched a study to combine metformin with the small molecule targeted drug gefitinib to treat bladder cancer using intravesical administration. Thus, in this minireview, we summarize recent achievements combining metformin with various targeted therapies. This work directs the potential clinical future by selecting available cancer patients and providing precise medicine by the combination of metformin and targeted drugs to overcome resistance and enhance therapeutic efficacies.
This work highlights the recent achievements combining metformin with various targeted therapies and discusses the detailed mechanisms. This work predicts the potential clinical application of metformin by selecting available cancer patients and providing precise medicine by its combination with targeted drugs to overcome resistance and enhance therapeutic efficacies.
Global research hotspots and future research trends in the neurobiological mechanisms of late-life depression (LLD) as well as its diagnosis and treatment are not yet clear.
This study profiled the ...current state of global research on LLD and predicted future research trends in the field.
Literature with the subject term LLD was retrieved from the Web of Science Core Collection, and CiteSpace software was used to perform econometric and co-occurrence analyses. The results were visualized using CiteSpace, VOSviewer, and other software packages.
In total, 10,570 publications were included in the analysis. Publications on LLD have shown an increasing trend since 2004. The United States and the University of California had the highest number of publications, followed consecutively by China and England, making these countries and institutions the most influential in the field. Reynolds, Charles F. was the author with the most publications. The
was the journal with the most articles and citations. According to the co-occurrence analysis and keyword/citation burst analysis, cognitive impairment, brain network dysfunction, vascular disease, and treatment of LLD were research hotspots.
Late-life depression has attracted increasing attention from researchers, with the number of publications increasing annually. However, many questions remain unaddressed in this field, such as the relationship between LLD and cognitive impairment and dementia, or the impact of vascular factors and brain network dysfunction on LLD. Additionally, the treatment of patients with LLD is currently a clinical challenge. The results of this study will help researchers find suitable research partners and journals, as well as predict future hotspots.
Objective
This research examines the intestinal‐associated flora of patients with depression compared with healthy volunteers to identify the characteristics and differences of flora associated with ...depression. It provides a theoretical basis for the prevention and treatment of depression through intestinal micro‐ecological regulation.
Methods
We recruited 30 patients with depression to participate in the patient group (PG), and 30 volunteers were recruited for the healthy control group (HG) from the Beijing Hui‐long‐guan Hospital. Thereafter, the 16S rRNA high‐throughput sequencing method, using the Hamilton Depression Scale, was applied to analyze patient and healthy groups.
Results
PG and HG microflora were different regarding phylum, Family, Genus, and Order. The results showed that Barnesiella was the dominant flora in depression patients, while Lachnospiraceae and Alloprevotella were the dominant bacteria in healthy participants. The proportion of Betaproteobateria (Proteobacteria), Alcaligenaceae (proinflammatory), Peptostreptococcaceae, Catenibacterium, Romboutsia, Sutterella, and Burkholderiales in the anxiety‐negative depressed group was significantly higher than in the anxiety‐positive group; and the proportion of Anaerostipes (inflammation) and Faecalibacterium (anti‐inflammatory) bacteria was significantly lower than that of patients with anxiety.
Conclusion
Results showed there were differences in intestinal micro‐ecology between patients with depression and healthy volunteers. We found that the level of inflammation‐related bacteria in anxiety‐positive patients was lower than that in anxiety‐negative patients. These results enrich the knowledge of relationships between depression and intestinal flora and provide a theoretical basis for probiotics to assist in the treatment of depression.
This research examines the intestinal‐associated flora of patients with depression compared with healthy volunteers to identify the characteristics and differences of flora associated with depression. It provides a theoretical basis for the prevention and treatment of depression through intestinal micro‐ecological regulation
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