A Curcumin-Decorated Nanozyme with ROS Scavenging and Anti-Inflammatory Properties for Neuroprotection.

Disordered reactive oxygen/nitrogen species are a common occurrence in various diseases, which usually cause cellular oxidative damage and inflammation. Despite the wide range of applications for biomimetic nanoparticles with antioxidant or anti-inflammatory properties, designs that seamlessly integrate these two abilities with a synergistic effect in a simple manner are seldom reported. In this study, we developed a novel PEI-Mn composite nanoparticle (PM NP) using a chelation method, and the curcumin was loaded onto PM NPs via metal-phenol coordination to form PEI-Mn@curcumin nanoparticles (PMC NPs). PMC NPs possessed excellent dispersibility and cytocompatibility, was engineered to serve as an effective nanozyme, and exhibited specific SOD-like and CAT-like activities. In addition, the incorporation of curcumin granted PMC NPs the ability to effectively suppress the expression of inflammatory cytokines in microglia induced by LPS. As curcumin also has antioxidant properties, it further amplified the synergistic efficiency of ROS scavenging. Significantly, PMC NPs effectively scavenged ROS triggered by H2O2 in SIM-A9 microglia cells and Neuro-2a cells. PMC NPs also considerably mitigated DNA and lipid oxidation in Neuro-2a cells and demonstrated an increase in cell viability under various H2O2 concentrations. These properties suggest that PMC NPs have significant potential in addressing excessive ROS and inflammation related to neural diseases.

EVs-mediated delivery of CB2 receptor agonist for Alzheimer's disease therapy.

Alzheimer's disease (AD) is a typical neurodegenerative disease that leads to irreversible neuronal degeneration, and effective treatment remains elusive due to the unclear mechanism. We utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241 (EVs-AM1241) to protect against neurodegenerative progression and neuronal function in AD model mice. According to the results, EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241. The Morris water maze (MWM) and fear conditioning tests revealed that the learning and memory of EVs-AM1241-treated model mice were significantly improved. In vivo electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning. Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloid ß (Aß)-induced neuronal apoptosis were significantly suppressed by EVs-AM1241. Moreover, EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton, indicating that they enhanced neuronal regeneration. RNA sequencing revealed that EVs-AM1241 facilitated Aß phagocytosis, promoted neurogenesis and ultimately improved learning and memory through the calcium-Erk signaling pathway. Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in model mice, indicating that they are very promising particles for treating AD.

Combination therapy with ultrasound and 2D nanomaterials promotes recovery after spinal cord injury via Piezo1 downregulation.

Spinal cord injury (SCI) causes severe neurological dysfunction and currently has no effective treatment. Due to the complex pathophysiological processes associated with SCI and the limited efficacy of single strategies, the need for combined strategies for effective SCI therapy is becoming increasingly apparent. In this study, we evaluated the combined effects of layered double hydroxide-coupled NT3 (MgFe-LDH/NT3) nanoparticles (NPs) and ultrasound (US) both in vitro and in vivo. Combined treatment promoted neural stem cell (NSC) differentiation into neurons and exerted anti-inflammatory effects in vitro. Furthermore, combined therapy promoted behavioural and electrophysiological performance at eight weeks in a completely transected murine thoracic SCI model. Additional RNA sequencing revealed that ultrasonic-induced Piezo1 downregulation is the core mechanism by which combined therapy promotes neurogenesis and inhibits inflammation, and the Piezo1/NF-κB pathways were identified. Hence, the findings of this study demonstrated that the combination of ultrasound and functional NPs may be a promising novel strategy for repairing SCI.

Influence of microplastics on microbial anaerobic detoxification of chlorophenols.

Microplastics (MPs) can absorb halogenated organic compounds and transport them into marine anaerobic zones. Microbial reductive dehalogenation is a major process that naturally attenuates organohalide pollutants in anaerobic environments. Here, we aimed to determine the mechanisms through which MPs affect the microbe-mediated marine halogen cycle by incubating 2,4,6-trichlorophenol (TCP) dechlorinating cultures with various types of MPs. We found that TCP was dechlorinated to 4-chlorophenol in biotic control and polypropylene (PP) cultures, but essentially terminated at 2,4-dichlorophenol in polyethylene (PE) and polyethylene terephthalate (PET) cultures after incubation for 20 days. Oxygen-containing functional groups such as peroxide and aldehyde were enriched on PE and PET after incubation and corresponded to elevated levels of intracellular reactive oxygen species (ROS) in the microorganisms. Adding PE or PET to the cultures exerted limited effects on hydrogenase and ATPase activities, but delayed the expression of the gene encoding reductive dehalogenase (RDase). Considering the limited changes in the microbial composition of the enriched cultures, these findings suggested that microbial dechlorination is probably affected by MPs through the ROS-induced inhibition of RDase synthesis and/or activity. Overall, our findings showed that extensive MP pollution is unfavorable to environmental xenobiotic detoxification.

Carbazole and polyhalogenated carbazoles in the marine environment around the Zhoushan Archipelago: Distribution characteristics, environmental behavior, and sources.

The distribution characteristics and drivers of carbazole (CZ) and polyhalogenated carbazoles are still poorly understood. In this study, 96 samples were collected around the Zhoushan Archipelago, and their distribution characteristics were assessed. The results showed that CZ, 36-CCZ, and 36-BCZ were the top three abundant congeners in most collected samples. The bioaccumulation analysis revealed that marine plants prefer to accumulate CZ and bromocarbazoles rather than chlorocarbazoles. Both the mean concentrations of total carbazole and its derivants (ΣCZDs), as well as individual congeners, are the highest in sediments around the berthing areas of cargo ships and oil tankers. Meanwhile, ΣCZDs of these sediments are significantly influenced by the geo-weighted displacement of ships (r = 0.61; p < 0.05), indicating the ballast water from these ships as potential contributor for marine CZDs. Moreover, the accumulation of CZ in plankton, planktonic origin of sedimentary organic matter, and relationship between CZ and C/N ratio (p < 0.05) in sediments support the scenario that plankton absorbs and takes CZ into the sediments. These findings will promote the understanding of the sources, environmental behaviors, and fates of marine CZDs.

Improved Regional Homogeneity in Chronic Insomnia Disorder After Amygdala-Based Real-Time fMRI Neurofeedback Training.

Background: Chronic insomnia disorder (CID) is a highly prevalent sleep disorder, which influences people's daily life and is even life threatening. However, whether the resting-state regional homogeneity (ReHo) of disrupted brain regions in CID can be reshaped to normal after treatment remains unclear. Methods: A novel intervention real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) was used to train 28 CID patients to regulate the activity of the left amygdala for three sessions in 6 weeks. The ReHo methodology was adopted to explore its role on resting-state fMRI data, which were collected before and after training. Moreover, the relationships between changes of clinical variables and ReHo value of altered regions were determined. Results: Results showed that the bilateral dorsal medial pre-frontal cortex, supplementary motor area (SMA), and left dorsal lateral pre-frontal cortex had decreased ReHo values, whereas the bilateral cerebellum anterior lobe (CAL) had increased ReHo values after training. Some clinical scores markedly decreased, including Pittsburgh Sleep Quality Index, Insomnia Severity Index, Beck Depression Inventory, and Hamilton Anxiety Scale (HAMA). Additionally, the ReHo values of the left CAL were positively correlated with the change in the Hamilton depression scale score, and a remarkable positive correlation was found between the ReHo values of the right SMA and the HAMA score. Conclusion: Our study provided an objective evidence that amygdala-based rtfMRI-NF training could reshape abnormal ReHo and improve sleep in patients with CID. The improved ReHo in CID provides insights into the neurobiological mechanism for the effectiveness of this intervention. However, larger double-blinded sham-controlled trials are needed to confirm our results from this initial study.

Alterations in Gut Microbiota Are Correlated With Serum Metabolites in Patients With Insomnia Disorder.

This study aimed to investigate insomnia-related alterations in gut microbiota and their association with serum metabolites. A total of 24 patients with insomnia disorder and 22 healthy controls were recruited. The fecal and serum samples were collected. The 16s rRNA sequencing and bioinformatics analysis were conducted to explore insomnia-related changes in the diversity, structure, and composition of the gut microbiota. UPLC-MS was performed to identify insomnia-related serum metabolites. Spearman correlation analysis was used to investigate the correlations between insomnia-related gut bacteria and the serum metabolites. Despite the nonsignificant changes in the diversity and structure of gut microbiota, insomnia disorder patients had significantly decreased family Bacteroidaceae, family Ruminococcaceae, and genus Bacteroides, along with significantly increased family Prevotellaceae and genus Prevotella, compared with healthy controls. Genus Gemmiger and genus Fusicatenibacter were dominant in patients with insomnia disorder, whereas genus Coprococcus, genus Oscillibacter, genus Clostridium XI, and family Peptostreptococcaceae were dominant in healthy controls. The UPLC-MS analysis identified 97 significantly decreased metabolites and 74 significantly increased metabolites in the serum samples of patients with insomnia disorder, compared with those of healthy controls. KEGG enrichment analysis revealed 1 significantly upregulated metabolic pathway and 16 downregulated metabolic pathways in patients with insomnia disorder. Furthermore, Spearman correlation analysis unveiled significant correlations among the altered bacteria genus and serum metabolites. Patients with insomnia disorder have differential gut microbiota and serum metabolic profiles compared with healthy controls. The alterations in gut microbiota were correlated with specific serum metabolites, suggesting that some serum metabolites might mediate gut microbiota-brain communication in the pathogenesis of insomnia disorder.

CT-derived abdominal adiposity: Distributions and better predictive ability than BMI in a nationwide study of 59,429 adults in China.

BACKGROUND: Although abdominal adiposity is associated with an altered cardiometabolic risk profile, the specific contribution of abdominal adipose tissue distribution remains not fully understood. Computed tomography (CT) is a well-established and precise method to measure abdominal adipose tissue distribution. The present study investigated abdominal adiposity assessed by CT in a large-scale Chinese population. METHOD: A total of 59,429 adults who underwent a low dose chest CT for lung cancer screening at one of 13 health checkup centers throughout China were evaluated. Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured at the center of the 2nd lumbar vertebra with Mindways quantitative CT software using the existing CT dataset without any additional radiation exposure. The ratio of visceral to total adipose tissue (TAT) areas (VAT/TAT ratio) was calculated and expressed as a percentage. Anthropometric indices including body mass index (BMI) and waist circumference were also obtained. RESULTS: BMI, waist circumference, VAT area, SAT area, and the VAT/TAT ratio were 25.0 ±â€¯3.0 kg/m2, 90 ±â€¯8 cm, 194 ±â€¯77 cm2, 85 ±â€¯41 cm2, and 69.5 ±â€¯9.1%, respectively, in men and 23.3 ±â€¯3.1 kg/m2, 79 ±â€¯8 cm, 120 ±â€¯57 cm2, 123 ±â€¯53 cm2, and 48.9 ±â€¯9.7% in women. With increasing age, VAT area and the VAT/TAT ratio increased in both sexes whereas SAT area decreased in men (P < 0.001 for all). After adjustment for BMI and waist circumference, older individuals showed higher VAT area and higher VAT/TAT ratio than younger subjects (P < 0.001 for all). Adjusted VAT areas in participants aged 75 or older was 45 cm2 (95% confidence interval [CI]: 41 cm2, 50 cm2) higher in men and 43 cm2 (95% CI: 37 cm2, 49 cm2) higher in women compared with participants aged 31-44 years. Additionally, differences in VAT area across age groups increased as BMI or waist circumference increased. VAT and SAT areas, but not the VAT/TAT ratio, were positively associated with BMI and waist circumference in every age group. CONCLUSION: In a nationwide study conducted in China, distributions of CT-derived measures of visceral and subcutaneous adiposity were found to vary significantly between sex and age groups. Our study also revealed that the proportion of VAT (an important driver of cardiometabolic risk) could not be predicted from BMI in a Chinese population.

Opportunistic Screening Using Low-Dose CT and the Prevalence of Osteoporosis in China: A Nationwide, Multicenter Study.

Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L1 -L2 ) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged >50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm3 ) than men (176.6 mg/cm3 ) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm3 ) than men (92.1 mg/cm3 ) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

Influence of a Coronary Artery Disease-Associated Genetic Variant on FURIN Expression and Effect of Furin on Macrophage Behavior.

Objective- Genome-wide association studies have revealed a robust association between genetic variation on chromosome 15q26.1 and coronary artery disease (CAD) susceptibility; however, the underlying biological mechanism is still unknown. The lead CAD-associated genetic variant (rs17514846) at this locus resides in the FURIN gene. In advanced atherosclerotic plaques, furin is expressed primarily in macrophages. We investigated whether this CAD-associated variant alters FURIN expression and whether furin affects monocyte/macrophage behavior. Approach and Results- A quantitative reverse transcription polymerase chain reaction analysis showed that leukocytes from individuals carrying the CAD risk allele (A) of rs17514846 had increased FURIN expression. A chromatin immunoprecipitation assay revealed higher RNA polymerase II occupancy in the FURIN gene in mononuclear cells of individuals carrying this allele. A reporter gene assay in transiently transfected monocytes/macrophages indicated that the CAD risk allele had higher transcriptional activity than the nonrisk allele (C). An analysis of isogenic monocyte cell lines created by CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing showed that isogenic cells with the A/A genotype for rs17514846 had higher FURIN expression levels than the isogenic cells with the C/C genotype. An electrophoretic mobility shift assay exhibited preferential binding of a nuclear protein to the risk allele. Studies of monocytes/macrophages with lentivirus-mediated furin overexpression or shRNA (short hairpin RNA)-induced furin knockdown showed that furin overexpression promoted monocyte/macrophage migration, increased proliferation, and reduced apoptosis whereas furin knockdown had the opposite effects. Conclusions- Our study shows that the CAD-associated genetic variant increases FURIN expression and that furin promotes monocyte/macrophage migration and proliferation while inhibiting apoptosis, providing a biological mechanism for the association between variation at the chromosome 15q26.1 locus and CAD risk.