Dysbiosis, departure of the gut microbiome from a healthy state, has been suggested to be a powerful biomarker of disease incidence and progression
. Diagnostic applications have been proposed for ...inflammatory bowel disease diagnosis and prognosis
, colorectal cancer prescreening
and therapeutic choices in melanoma
. Noninvasive sampling could facilitate large-scale public health applications, including early diagnosis and risk assessment in metabolic
and cardiovascular diseases
. To understand the generalizability of microbiota-based diagnostic models of metabolic disease, we characterized the gut microbiota of 7,009 individuals from 14 districts within 1 province in China. Among phenotypes, host location showed the strongest associations with microbiota variations. Microbiota-based metabolic disease models developed in one location failed when used elsewhere, suggesting that such models cannot be extrapolated. Interpolated models performed much better, especially in diseases with obvious microbiota-related characteristics. Interpolation efficiency decreased as geographic scale increased, indicating a need to build localized baseline and disease models to predict metabolic risks.
The type 2 cannabinoid receptor (CB2R) was initially regarded as a peripheral cannabinoid receptor. However, recent technological advances in gene detection, alongside the availability of transgenic ...mouse lines, indicate that CB2Rs are expressed in both neurons and glial cells in the brain under physiological and pathological conditions, and are involved in multiple functions at cellular and behavioral levels. Brain CB2Rs are inducible and neuroprotective via up-regulation in response to various insults, but display species differences in gene and receptor structures, CB2R expression, and receptor responses to various CB2R ligands. CB2R transcripts also differ between the brain and spleen. In the brain, CB
is the major transcript isoform, while CB
and CB
transcripts are present at higher levels in the spleen. These new findings regarding brain versus spleen CB2R isoforms may in part explain why early studies failed to detect brain CB2R gene expression. Here, we review evidence supporting the expression and function of brain CB2R from gene and receptor levels to cellular functioning, neural circuitry, and animal behavior.
Proprotein convertase subtilisin/kexin type‐9 (PCSK9), a member of the proprotein convertase family, is an important drug target because of its crucial role in lipid metabolism. Emerging evidence ...suggests a direct role of localized PCSK9 in the pathogenesis of vascular diseases. With this in our consideration, we reviewed PCSK9 physiology with respect to recent development and major studies (clinical and experimental) on PCSK9 functionality in vascular disease. PCSK9 upregulates low‐density lipoprotein (LDL)‐cholesterol levels by binding to the LDL‐receptor (LDLR) and facilitating its lysosomal degradation. PCSK9 gain‐of‐function mutations have been confirmed as a novel genetic mechanism for familial hypercholesterolemia. Elevated serum PCSK9 levels in patients with vascular diseases may contribute to coronary artery disease, atherosclerosis, cerebrovascular diseases, vasculitis, aortic diseases, and arterial aging pathogenesis. Experimental models of atherosclerosis, arterial aneurysm, and coronary or carotid artery ligation also support PCSK9 contribution to inflammatory response and disease progression, through LDLR‐dependent or ‐independent mechanisms. More recently, several clinical trials have confirmed that anti‐PCSK9 monoclonal antibodies can reduce systemic LDL levels, total nonfatal cardiovascular events, and all‐cause mortality. Interaction of PCSK9 with other receptor proteins (LDLR‐related proteins, cluster of differentiation family members, epithelial Na+ channels, and sortilin) may underlie its roles in vascular disease. Improved understanding of PCSK9 roles and molecular mechanisms in various vascular diseases will facilitate advances in lipid‐lowering therapy and disease prevention.
Proprotein convertase subtilisin/kexin type‐9 (PCSK9) gain‐of‐function mutations have been confirmed as a novel genetic mechanism for familial hypercholesterolemia. Elevated serum PCSK9 levels in patients with vascular diseases may contribute to coronary artery disease, atherosclerosis, cerebrovascular diseases, vasculitis, aortic diseases, and arterial aging pathogenesis. Experimental models of atherosclerosis, arterial aneurysm, and coronary or carotid artery ligation support PCSK9 contribution to inflammatory response and disease progression, through low‐density lipoprotein receptor (LDLR)‐dependent or ‐independent mechanisms.
Comprehensive studies on the size effect in nanozyme (i. e., nanomaterials with enzyme‐like activities)‐based catalysis have rarely been reported. In this work, we systematically investigated the ...size effect in nanozymes by using Pd−Ir core‐shell nanoparticles with peroxidase‐like activities as a model system. Pd−Ir nanoparticles with four different sizes (3.3, 5.9, 9.8 and 13.0 nm), but identical shapes and surface structures, were designed and synthesized. We found that the catalytic activity for individual nanozymes increased with particle size. The area‐specific catalytic activity was similar for nanoparticles of 3.3–9.8 nm, but decreased slightly when particle size reached 13.0 nm. By using an enzyme‐linked immunosorbent assay (ELISA) as a model platform, the size effect of Pd−Ir nanoparticles in biosensing applications was investigated; smaller nanoparticles were found to offer lower detection limits. This work not only demonstrates the size effect, but also provides an effective strategy to enhance the performance of nanozymes in certain applications.
Size matters: Size effect in nanozyme was studied by using Pd−Ir core‐shell nanoparticles of different sizes that possess peroxidase‐like properties as a model system. Over a size range of 3.3–13.0 nm, the nanoparticles showed size‐dependent catalytic activities. Their performance in immunoassays was also found to have a dependence on particle size.
Microglia play critical roles in tissue homeostasis and can also modulate neuronal function and synaptic connectivity. In contrast to astrocytes and oligodendrocytes, which arise from multiple ...progenitor pools, microglia arise from yolk sac progenitors and are widely considered to be equivalent throughout the CNS. However, little is known about basic properties of deep brain microglia, such as those within the basal ganglia (BG). Here, we show that microglial anatomical features, lysosome content, membrane properties, and transcriptomes differ significantly across BG nuclei. Region-specific phenotypes of BG microglia emerged during the second postnatal week and were re-established following genetic or pharmacological microglial ablation and repopulation in the adult, indicating that local cues play an ongoing role in shaping microglial diversity. These findings demonstrate that microglia in the healthy brain exhibit a spectrum of distinct functional states and provide a critical foundation for defining microglial contributions to BG circuit function.
•We provide an extensive definition of basic properties of basal ganglia microglia•Microglia in the healthy brain exist along a spectrum of functional states•Midbrain microglia differ significantly from their cortical counterparts•Region-specific phenotypes reemerge following microglial ablation and repopulation
De Biase et al. show that microglia in different basal ganglia nuclei exhibit region-specific phenotypes, with distinct anatomical features, lysosome content, membrane properties, and transcriptomes. Local regulatory cues guide establishment and maintenance of this regional specialization.
Bromodomain‐containing protein 4 (BRD4), a chromatin‐binding protein, is involved in the development of various tumors. Recent evidence suggests that BRD4 also plays a significant role in ...cardiovascular diseases, such as ischemic heart disease, hypertension, and cardiac hypertrophy. This review summarizes the roles of BRD4 as a potential regulator of various pathophysiological processes in cardiovascular diseases, implicating that BRD4 may be a new therapeutic target for cardiovascular diseases in the future.
This review summarizes the roles of BRD4 as a potential regulator of various pathophysiological processes in cardiovascular diseases, implicating that BRD4 may be a new therapeutic target for cardiovascular diseases in the future.
Visualization software provides powerful numerical calculations for the 3D mathematical modeling process. This paper uses optical motion capture mathematical modeling technology to track and detect ...dancers’ dance movements in segments in real-time. The research results found that the visual dance choreography system proposed in the article improves the efficiency of posture analysis and real-time analysis improves the quality of teaching. This has played an important role in the digital teaching of dance movements and the development of science.
Substance use disorder (SUD) is a major public health crisis worldwide, and effective treatment options are limited. During the past 2 decades, researchers have investigated the impact of a variety ...of pharmacological approaches to treat SUD, one of which is the use of medical cannabis or cannabinoids. Significant progress was made with the discovery of rimonabant, a selective CB1 receptor (CB1R) antagonist (also an inverse agonist), as a promising therapeutic for SUDs and obesity. However, serious adverse effects such as depression and suicidality led to the withdrawal of rimonabant (and almost all other CB1R antagonists/inverse agonists) from clinical trials worldwide in 2008. Since then, much research interest has shifted to other cannabinoid-based strategies, such as peripheral CB1R antagonists/inverse agonists, neutral CB1R antagonists, allosteric CB1R modulators, CB2R agonists, fatty acid amide hydrolase (FAAH) inhibitors, monoacylglycerol lipase (MAGL) inhibitors, fatty acid binding protein (FABP) inhibitors, or nonaddictive phytocannabinoids with CB1R or CB2R-binding profiles, as new therapeutics for SUDs. In this article, we first review recent progress in research regarding the endocannabinoid systems, cannabis reward versus aversion, and the underlying receptor mechanisms. We then review recent progress in cannabinoid-based medication development for the treatment of SUDs. As evidence continues to accumulate, neutral CB1R antagonists (such as AM4113), CB2R agonists (JWH133, Xie2-64), and nonselective phytocannabinoids (cannabidiol, β-caryophyllene, ∆
-tetrahydrocannabivarin) have shown great therapeutic potential for SUDs, as shown in experimental animals. Several cannabinoid-based medications (e.g., dronabinol, nabilone, PF-04457845) that entered clinical trials have shown promising results in reducing withdrawal symptoms in cannabis and opioid users.
Substance use disorder (SUD) is a serious public health problem worldwide for which available treatments show limited effectiveness. Since the legalization of cannabis and the approval of cannabidiol ...(CBD) by the US Food and Drug Administration, therapeutic potential of CBD for the treatment of SUDs and other diseases has been widely explored. In this mini-review article, we first review the history and evidence supporting CBD as a potential pharmacotherapeutic. We then focus on recent progress in preclinical research regarding the pharmacological efficacy of CBD and the underlying receptor mechanisms on addictive-like behavior. Growing evidence indicates that CBD has therapeutic potential in reducing drug reward, as assessed in intravenous drug self-administration, conditioned place preference and intracranial brain-stimulation reward paradigms. In addition, CBD is effective in reducing relapse in experimental animals. Both in vivo and in vitro receptor mechanism studies indicate that CBD may act as a negative allosteric modulator of type 1 cannabinoid (CB1) receptor and an agonist of type 2 cannabinoid (CB2), transient receptor potential vanilloid 1 (TRPV1), and serotonin 5-HT
receptors. Through these multiple-receptor mechanisms, CBD is believed to modulate brain dopamine in response to drugs of abuse, leading to attenuation of drug-taking and drug-seeking behavior. While these findings suggest that CBD is a promising therapeutic candidate, further investigation is required to verify its safety, pharmacological efficacy and the underlying receptor mechanisms in both experimental animals and humans.
Designing highly active and more durable oxygen electrocatalysts for regenerative metal-air batteries and water splitting is of practical significance. Herein, an advanced Co/N–C-800 catalyst ...composed of abundant Co–N x structures and carbon defects derived from cobalt phthalocyanine is synthesized. Remarkably, this catalyst exhibits favorable catalytic performance toward the oxygen evolution reaction (OER) with a receivable overpotential of 274 mV in an alkaline medium achieving a current density of 10 mA cm–2 and a Tafel slope of 43.6 mV decade–1, outperforming the commercial RuO2 catalyst. It further displays a high half-wave potential (0.82 V) for the oxygen reduction reaction in 0.1 M KOH. Theoretical calculations reveal that the Co–N x active sites along with the carbon defects can decrease the adsorption energy of intermediates (OH*, O*, and OOH*) and enhance the electron-transfer ability, thus boosting the OER process.
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