High-Coupled Magnetic-Levitation Hybrid Nanogenerator with Frequency Multiplication Effect for Wireless Water Level Alarm.

Hybrid nanogenerators (HNGs) represent a promising avenue for water energy harvesting, yet their commercial viability faces hurdles such as limited power output, poor coupling, and constrained operational lifespans. Here, a highly coupled triboelectric-electromagnetic magnetic-levitation hybrid nanogenerator (ML-HNG) is introduced that shows great potential for water energy harvesting. The ML-HNG fulfills the challenges of high power output, strong coupling, and long operational lifespans. During the contact-separation process of the triboelectric nanogenerator (TENG), the changing magnetic flux in the electromagnetic generator's coils generates a potential difference between the coils and Cu electrodes. The unique design of the ML-HNG employs a shared coil electrode configuration, which enhances the coupling without adding extra volume. This integration allows the ML-HNG to achieve multi-frequency vibrations and multiple output cycles per external longitudinal movement, a phenomenon known as the frequency multiplication effect. With an average power density of 1.69 W m-3 in water, the ML-HNG provides continuous power for a thermo-hygrometer and can quickly drive a wireless water level alarm system within a minute. This groundbreaking hybrid nanogenerator design holds significant promise for the efficient and consistent harvesting of low-frequency ocean wave energy, marking a substantial advancement in blue energy technology.

An Accesss to 4,5,6-Trisubstituted Pyrimidines from 2H-Azirines and α-Isocyanoacetates or α-Isocyanoacetamides Enabled by 1,3-Dipolar [3 + 2] Cycloaddition/Ring-Expanding/Oxidative Aromatization Process.

The products containing pyrimidine scaffolds exhibit various important physiological and biological activities. To date, the strategies to generate 4,5,6-trisubstituted pyrimidines were not reported. Here, a copper-catalyzed reaction of 2H-azirines with α-isocyanoacetates or α-isocyanoacetamides has been developed, rapidly preparing 4,5,6-trisubstituted pyrimidines. The mechanistic results reveal that this strategy underwent a formal 1, 3-dipolar [3 + 2] cycloaddition/ring-expanding/oxidative aromatization procedure to construct the desired pyrimidines.

Cu(I)-Catalyzed Three-Component Annulation for the Synthesis of 3-Acyl Imidazo[1, 5-a]Pyridines from 2-Pyridinyl-Substituted p-Quinone Methides, Terminal Alkynes, and TsN3 Using O2 as the Oxygen Source.

Currently, most conventional methods to achieve imidazo[1,5-a]pyridines have limitations for the synthesis of 3-acyl imidazo[1,5-a]pyridines. Herein, a novel and efficient Cu(I)-catalyzed three-component annulation method for the synthesis of valuable 3-acyl imidazo[1,5-a]pyridines by the reaction of 2-pyridinyl-substituted p-QMs, terminal alkynes, and TsN3 in the presence of O2 under mild conditions have successfully been developed. The investigation indicated that molecular oxygen (O2) and TsN3, respectively, serving as oxygen and nitrogen sources, were essential for the successful completion of the reaction system.

One-pot formal [3 + 2] annulation of 2-pyridinyl-substituted p-quinone methides and arynes for the synthesis of 3-aryl pyrido[1,2-a]indoles.

An efficient and metal-free method for the synthesis of 3-aryl pyrido[1,2-a]indoles from aryne intermediates and 2-pyridinyl-substituted p-QMs was successfully developed under ambient conditions. The reaction offered a novel and practical protocol to access some diverse functional molecules in good to excellent yields. The proposed mechanism indicated that the reaction proceeded via a formal [3 + 2] cycloaddition step.

Elastic Self-Recovering Hybrid Nanogenerator for Water Wave Energy Harvesting and Marine Environmental Monitoring.

To achieve large-scale development of triboelectric nanogenerators (TENGs) for water wave energy harvesting and powering the colossal sensors widely distributed in the ocean, facile and scalable TENGs with high output are urgently required. Here, an elastic self-recovering hybrid nanogenerator (ES-HNG) is proposed for water wave energy harvesting and marine environmental monitoring. The elastic skeletal support of the ES-HNG is manufactured using three-dimensional (3D) printing technology, which is more conducive to the large-scale integration of the ES-HNG. Moreover, the combination of a TENG and an electromagnetic generator (EMG) optimizes the utilization of device space, leading to enhanced energy harvesting efficiency. Experimental results demonstrate that the TENG achieves a peak power output of 42.68 mW, and the EMG reaches a peak power output of 4.40 mW. Furthermore, various marine environment monitoring sensors, such as a self-powered wireless meteorological monitoring system, a wireless alarm system, and a water quality monitoring pen, have been successfully powered by the sophisticated ES-HNG. This work introduces an ES-HNG for water wave energy harvesting, which demonstrates potential in marine environment monitoring and offers a new solution for the sustainable development of the marine internet of things.

Clostridium butyricum inhibits epithelial-mesenchymal transition of intestinal carcinogenesis through downregulating METTL3.

Colorectal cancer (CRC) is related to gut microbiota dysbiosis, especially butyrate-producing bacteria reduction. Our previous study suggested that administration of Clostridium butyricum, a butyrate-producing bacterium, exerts a crucial effect against CRC, however the potential mechanism is not clear. We first found that methyltransferase-like 3 (METTL3) showed a positive correlation with proliferation, epithelial-mesenchymal transition (EMT), DNA repair, metastasis, and invasion in a database analysis. The expression of METTL3 gradually increased from human normal colon tissue, to adenoma, and carcinoma, and was positively correlated with E-cadherin and CD34 levels. Overexpression of METTL3 promoted the proliferation, migration, and invasion of CRC cells and induced vasculogenic mimicry (VM) formation. Clostridium butyricum could downregulate METTL3 expression in CRC cells and decrease the expression of vimentin and vascular endothelial growth factor receptor 2 to reduce EMT and VM formation. Clostridium butyricum alleviated the pro-oncogenic effect of METTL3 overexpressing plasmid in CRC cells. The anti-EMT effect on METTL3 reduction of C. butyricum could be blunted by knocking down G-protein coupled receptor 43. Moreover, C. butyricum prevented EMT and VM and inhibited tumor metastasis in nude mice. Accordingly, C. butyricum could inhibit EMT and VM formation of intestinal carcinogenesis through downregulating METTL3. These findings broaden our understanding of probiotics supplement in CRC prevention and treatment.

Lotus Leaf Derived NiS/Carbon Nanofibers/Porous Carbon Heterogeneous Structures for Strong and Broadband Microwave Absorption.

Developing composite materials with the synergistic effects of heterogeneous structures and multiple components is considered as a promising strategy to achieve high-performance electromagnetic wave (EMW) absorbers. To further satisfy the demand of broadband and strong microwave absorption, a novel NiS/carbon nanofibers (CNFs)/porous carbon composite is successfully synthesized by hydrothermal and chemical vapor deposition using lotus leaves as a biomass carbon source. A few carbon nanotubes (CNTs) and uniformly dispersed Ni nanocrystals have also been found in the hybrid. Benefiting from the porous structure derived from lotus leaves, the combination of dielectric NiS, conductive carbon nanomaterials, and magnetic Ni nanoparticles, together with the three-dimensional conductive network of CNFs and CNTs, the remarkable EMW absorption properties with a minimum reflection loss up to -67.65 dB have been achieved at merely 2.32 mm. Besides, the widest effective absorption band can reach 5.9 GHz with a thin thickness of 2.07 mm, covering almost the entire Ku band. In addition, under the incident angle of 31°, the radar cross-section reduction value of LNSF-600 can reach 42.88 dBm2. Therefore, this work provides an efficient and facile method for manufacturing outstanding biomass-derived EMW absorbers.

Auxin biosynthesis maintains embryo identity and growth during BABY BOOM-induced somatic embryogenesis.

Somatic embryogenesis is a type of plant cell totipotency where embryos develop from nonreproductive (vegetative) cells without fertilization. Somatic embryogenesis can be induced in vitro by auxins, and by ectopic expression of embryo-expressed transcription factors like the BABY BOOM (BBM) AINTEGUMENTA-LIKE APETALA2/ETHYLENE RESPONSE FACTOR domain protein. These different pathways are thought to converge to promote auxin response and biosynthesis, but the specific roles of the endogenous auxin pathway in somatic embryogenesis induction have not been well-characterized. Here we show that BBM transcriptionally regulates the YUCCA3 (YUC3) and YUC8 auxin biosynthesis genes during BBM-mediated somatic embryogenesis in Arabidopsis (Arabidopsis thaliana) seedlings. BBM induced local and ectopic YUC3 and YUC8 expression in seedlings, which coincided with increased DR5 auxin response and indole-3-acetic acid (IAA) biosynthesis and with ectopic expression of the WOX2 embryo reporter. YUC-driven auxin biosynthesis was required for BBM-mediated somatic embryogenesis, as the number of embryogenic explants was reduced by ca. 50% in yuc3 yuc8 mutants and abolished after chemical inhibition of YUC enzyme activity. However, a detailed YUC inhibitor time-course study revealed that YUC-dependent IAA biosynthesis is not required for the re-initiation of totipotent cell identity in seedlings. Rather, YUC enzymes are required later in somatic embryo development for the maintenance of embryo identity and growth. This study resolves a long-standing question about the role of endogenous auxin biosynthesis in transcription factor-mediated somatic embryogenesis and also provides an experimental framework for understanding the role of endogenous auxin biosynthesis in other in planta and in vitro embryogenesis systems.

Multidimensional stitching method with wavelength tuned interferometry and unconstrained support tooling for large-thin parallel plate.

Limited by measurement methods, measuring the surfaces and thickness of large thin parallel plates has been challenging. In this paper, we propose a multi-dimensional stitching method using thickness alignment (MSuTA), which use the sub-aperture stitching method based on the phenomenon of parallel plate self-interference with wavelength-tuned interferometer (WTI) for measuring the surfaces and thickness of large thin parallel plates. We establish the stitching correction model based on Legendre polynomial to separate the aberrations caused by the elastic deformation of the thin plate in the unconstrained support tooling by analyzing the influence of the stress state of the thin plate with unconstrained three-point support. The stitching experiment has carried out on 6.3 mm thick, 6-inch parallel plates that the stitching residual is better than 0.35 nm RMS. Compared with 12-inch vertical interferometer, the surfaces and thickness deviation are better than 0.8 nm RMS, and the 36 standard Legendre polynomial coefficient deviation are better than 2.5 nm. Moreover, MSuTA can improves the lateral resolution of the measurement by nearly four times, allowing for a display of more comprehensive surface information. The stitching method proposed in this paper will be widely applied in the manufacture and measurement of large thin parallel plates, and provide reference for the elastic deformation analysis of the thin optical elements in the unconstrained support tooling.

One-Step Protocol for the Synthesis of Cyanoacrylates Promoted by Elemental Sulfur from p-Quinone Methides and Cyanoacetates under Basic Conditions.

Cyanoacrylates have a wide range of biological activities and are extensively applied in production and daily life. Classic synthetic routes to cyanoacrylates have many limitations. Herein, we demonstrate an elemental sulfur-promoted method for the synthesis of ß,ß-diaryl cyanoacrylates by a tandem 1,6-Michael addition/oxidation/elimination process from p-QMs and cyanoacetates under optimal conditions. The effective protocol has good substrate scopes and yields, and the ratio of inseparable E/Z isomers of cyanoacrylates is also determined by 1HNMR.

Lewis Acid-Catalyzed Remote Site-Selective Ring Deconstruction of Cyclobuteno[a]naphthalene-4-ones to Access Unsymmetric 1,1-Diarylated Olefins.

A catalytic site-selective ring deconstruction of cyclobuteno[a]naphthalene-4-ones with alcohols is reported, enabling the direct production of a wide range of unsymmetric 1,1-diarylated olefins with good yields and complete regioselectivity. The late-stage application of these resulting terminal olefins demonstrates great possibilities to apply this strategy to complex molecules. The protocol features good functional group compatibility, broad substrate scope, and controllable site selectivity.

DMSO-promoted direct δ-selective arylation of p-quinone methenylpiperidine bearinides to generate fuchsones under metal-free conditions by employing p-QMs themselves or substituted phenols as aryl sources.

Fuchsones have wide applications in modern society. Present methods for generating fuchsones have many disadvantages and there are significant limitations for further exploration of fuchsone applications. Herein, we describe a DMSO-promoted direct δ-selective arylation of p-QMs to synthesize symmetrical and unsymmetrical fuchsones under metal-free conditions by employing p-QMs themselves or substituted phenols as aryl sources. As unprecedented methods, these novel strategies present a great advantage and significance for further exploration of fuchsones and the development of new applications.

Mitofusin-2 mediates cannabidiol-induced neuroprotection against cerebral ischemia in rats.

Cannabidiol (CBD) reportedly exerts protective effects against many psychiatric disorders and neurodegenerative diseases, but the mechanisms are poorly understood. In this study, we explored the molecular mechanism of CBD against cerebral ischemia. HT-22 cells or primary cortical neurons were subjected to oxygen-glucose deprivation insult followed by reoxygenation (OGD/R). In both HT-22 cells and primary cortical neurons, CBD pretreatment (0.1, 0.3, 1 µM) dose-dependently attenuated OGD/R-induced cell death and mitochondrial dysfunction, ameliorated OGD/R-induced endoplasmic reticulum (ER) stress, and increased the mitofusin-2 (MFN2) protein level in HT-22 cells and primary cortical neurons. Knockdown of MFN2 abolished the protective effects of CBD. CBD pretreatment also suppressed OGD/R-induced binding of Parkin to MFN2 and subsequent ubiquitination of MFN2. Overexpression of Parkin blocked the effects of CBD in reducing MFN2 ubiquitination and reduced cell viability, whereas overexpressing MFN2 abolished Parkin's detrimental effects. In vivo experiments were conducted on male rats subjected to middle cerebral artery occlusion (MCAO) insult, and administration of CBD (2.5, 5 mg · kg-1, i.p.) dose-dependently reduced the infarct volume and ER stress in the brains. Moreover, the level of MFN2 within the ischemic penumbra of rats was increased by CBD treatment, while the binding of Parkin to MFN2 and the ubiquitination of MFN2 was decreased. Finally, short hairpin RNA against MFN2 reversed CBD's protective effects. Together, these results demonstrate that CBD protects brain neurons against cerebral ischemia by reducing MFN2 degradation via disrupting Parkin's binding to MFN2, indicating that MFN2 is a potential target for the treatment of cerebral ischemia.

Electroencephalographic slowdowns during sleep are associated with cognitive impairment in patients who have obstructive sleep apnea but no dementia.

OBJECTIVES: To research the relationship between quantitative electroencephalogram (qEEG) and impaired cognitive function patients who have obstructive sleep apnea (OSA) but no dementia. METHODS: Subjects who complained of snoring between March 2020 and April 2021 in the Sleep Medicine Center of Weihai Municipal Hospital were included. All subjects underwent overnight in-laboratory polysomnography (PSG) and were assessed using a neuropsychological scale. Standard fast fourier transform (FFT) was used to obtain the electroencephalogram (EEG) power spectral density curve, and to calculate the delta, theta, alpha, and beta relative power and the ratio between slow and fast frequencies. Binary logistic regression was used to assess the risk factors for cognitive impairment in patients who had OSA but no dementia. Correlation analysis was performed to determine the relationship between qEEG and cognitive impairment. RESULTS: A total of 175 participants without dementia who met the inclusion criteria were included in this study. There were 137 patients with OSA, including 76 with mild cognitive impairment (OSA + MCI), 61 without mild cognitive impairment (OSA-MCI), and 38 participants without OSA (non-OSA). The relative theta power in the frontal lobe in stage 2 of non-rapid eye movement sleep (NREM 2) in OSA + MCI was higher than that in OSA-MCI (P = 0.038) and non-OSA (P = 0.018). Pearson correlation analysis showed that the relative theta power in the frontal lobe in NREM 2 was negatively correlated with Mini-Mental State Examination (MMSE) scores, Montreal Cognitive Assessment (MoCA) Beijing version scores, and MoCA subdomains scores (visual executive function, naming, attention, language, abstraction, delayed recall and orientation) outside language. CONCLUSIONS: In patients who had OSA but no dementia, the EEG slower frequency power increased. The relative theta power in the frontal lobe in NREM 2 was associated with MCI of patients with OSA. These results suggest that the slowing of theta activity may be one of the neurophysiological changes in the early stage of cognitive impairment in patients with OSA.

Transglutaminase, glucono-δ-lactone, and citric acid-induced whey protein isolation-milk fat emulsion gel embedding lutein and its application in processed cheese.

In this study, transglutaminase (TG), glucono-δ-lactone (GDL), and citric acid (CA) were used to induce the formation of whey protein isolate (WPI)-milk fat emulsion gels to embed lutein, and the emulsion gels induced in different ways were used for the preparation of processed cheese. The protective effect of emulsion gels induced in different ways on lutein was investigated, and the stability of lutein in emulsion gels and processed cheese was analyzed. The results showed that the acidification rate of CA was higher than that of GDL, which was the key step in acid-induced gels, and that the difference in acidification rate led to differences in gel structure. Compared with the 2 acid inducers (GDL and CA), TG exhibited greater potential for forming gel structures with high strength. The TG-induced emulsion gels showed the best physical stability and the highest embedding efficiency for lutein. After heat treatment (85°C), the GDL-induced emulsion gels had higher retention rate of lutein and showed good thermal stability compared with the CA-induced emulsion gels. The processed cheese added with the TG-induced emulsion gel had higher hardness and springiness compared with the processed cheese added with the other 2 kinds of emulsion gels, whereas the processed cheese added with the CA-induced emulsion gel had a lower density of network structure, showing porosity and a larger aggregated structure, but the highest bioavailability of lutein. These results provide valuable information for the formation of cold-set emulsion gel and provide the possibility for the application of emulsion gel embedding active substances in processed cheese.

Effects of a Nonwearable Digital Therapeutic Intervention on Preschoolers With Autism Spectrum Disorder in China: Open-Label Randomized Controlled Trial.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause difficulty with communication and social interactions as well as complicated family dynamics. Digital health interventions can reduce treatment costs and promote healthy lifestyle changes. These therapies can be adjunctive or replace traditional treatments. However, issues with cooperation and compliance prevent preschool patients with ASD from applying these tools. In this open-label, randomized controlled trial, we developed a nonwearable digital therapy called virtual reality-incorporated cognitive behavioral therapy (VR-CBT). OBJECTIVE: The aim of this study was to assess the adjunctive function of VR-CBT by comparing the effects of VR-CBT plus learning style profile (LSP) intervention with those of LSP-only intervention in preschool children with ASD. METHODS: This trial was performed in China on 78 preschool children (age 3-6 years, IQ>70) diagnosed with ASD who were randomized to receive a 20-week VR-CBT plus LSP intervention (intervention group, 39/78, 50%) or LSP intervention only (control group, 39/78, 50%). The primary outcome was the change of scores from baseline to week 20, assessed by using the parent-rated Autism Behavior Checklist (ABC). Secondary outcomes included the Childhood Autism Rating Scale (CARS), Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV), and behavioral performance data (accuracy and reaction time) in go/no-go tasks. All primary and secondary outcomes were analyzed in the intention-to-treat population. RESULTS: After the intervention, there was an intervention effect on total ABC (ß=-5.528; P<.001) and CARS scores (ß=-1.365; P=.02). A similar trend was observed in the ABC subscales: sensory (ß=-1.133; P=.047), relating (ß=-1.512; P=.03), body and object use (ß=-1.211; P=.03), and social and self-help (ß=-1.593; P=.03). The intervention also showed statistically significant effects in improving behavioral performance (go/no-go task, accuracy, ß=2.923; P=.04). Moreover, a significant improvement of ADHD hyperactivity-impulsivity symptoms was observed in 53 children with comorbid ADHD based on ADHD-RS-IV (ß=-1.269; P=.02). No statistically significant intervention effect was detected in the language subscale of ABC (ß=-.080; P=.83). Intervention group girls had larger improvements in ABC subscales, that is, sensory and body and object use and in the CARS score and accuracy of go/no-go task (all P<.05) than the control group girls. Statistically significant intervention effects could be observed in hyperactivity-impulsivity symptoms in the intervention group boys with comorbid ADHD compared with those in the control group boys (ß=-1.333; P=.03). CONCLUSIONS: We found potentially positive effects of nonwearable digital therapy plus LSP on core symptoms associated with ASD, leading to a modest improvement in the function of sensory, motor, and response inhibition, while reducing impulsivity and hyperactivity in preschoolers with both ASD and ADHD. VR-CBT was found to be an effective and feasible adjunctive digital tool. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100053165; http://www.chictr.org.cn/showproj.aspx?proj=137016.

Stitching method based on dual quaternion for cylindrical mirrors.

In this study, a stitching method based on dual quaternion is proposed. The application of a dual quaternion in sub-aperture stitching interferometry is analyzed in detail, and a calculation method for sub-aperture stitching based on a dual quaternion is deduced. The experimental results demonstrate the accuracy of the stitching method proposed in this study (residuals of overlapping area approximately 0.22 nm RMS). Finally, the residual differences of 0.79 nm RMS between the figure errors are acquired with a stitching by parts algorithm based on the dual quaternion and long trace profiler (FSP at HEPS). The high-accuracy and high-efficiency stitching method proposed in this study will expand its application in the metrology and manufacture of long cylindrical mirrors.

Roflupram attenuates α-synuclein-induced cytotoxicity and promotes the mitochondrial translocation of Parkin in SH-SY5Y cells overexpressing A53T mutant α-synuclein.

We have previously shown that inhibition of cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4) protects against cellular toxicity in neuronal cells. Since α-synuclein (α-syn) toxicity contributes to the neurodegeneration of Parkinson's disease (PD). The aim of this study was to explore the effects and mechanisms of PDE4 on α-syn-induced neuronal toxicity. Using mutant human A53T α-syn overexpressed SH-SY5Y cells, we found that PDE4B knockdown reduced cellular apoptosis. Roflupram (ROF, 20 µM), a selective PDE4 inhibitor, produced similar protective effects and restored the morphological alterations of mitochondria. Mechanistic studies identified that α-syn enhanced the phosphorylation of Parkin at Ser131, followed by the decreased mitochondrial translocation of Parkin. Whereas both PDE4B knockdown and PDE4 inhibition by ROF blocked the effects of α-syn on Parkin phosphorylation and mitochondrial translocation. Moreover, PDE4 inhibition reversed the increase in the phosphorylation of p38 mitogen-activated protein kinase (MAPK) induced by α-syn. ROF treatment also reduced the binding of p38 MAPK to Parkin. Consistently, overexpression of PDE4B blocked the roles of ROF on p38 MAPK phosphorylation, Parkin phosphorylation, and the subsequent mitochondrial translocation of parkin. Furthermore, PDE4B overexpression attenuated the protective role of ROF, as evidenced by reduced mitochondria membrane potential and increased cellular apoptosis. Interestingly, ROF failed to suppress α-syn-induced cytotoxicity in the presence of a protein kinase A (PKA) inhibitor H-89. Our findings indicate that PDE4 facilitates α-syn-induced cytotoxicity via the PKA/p38 MAPK/Parkin pathway in SH-SY5Y cells overexpressing A53T mutant α-synuclein. PDE4 inhibition by ROF is a promising strategy for the prevention and treatment of α-syn-induced neurodegeneration.

Deformable mirror based optimal PSF engineering for 3D super-resolution imaging.

Point spread function (PSF) engineering is an important technique to encode the properties (e.g., 3D positions, color, and orientation) of a single molecule in the shape of the PSF, often with the help of a programmable phase modulator. A deformable mirror (DM) is currently the most widely used phase modulator for fluorescence detection as it shows negligible photon loss. However, it relies on careful calibration for precise wavefront control. Therefore, design of an optimal PSF not only relies on the theoretical calculation of the maximum information content, but also the physical behavior of the phase modulator, which is often ignored during the optimization process. Here, we develop a framework for PSF engineering which could generate a device specific optimal PSF for 3D super-resolution imaging using a DM. We use our method to generate two types of PSFs with depths of field comparable to the widely used astigmatism and tetrapod PSFs, respectively. We demonstrate the superior performance of the DM specific optimal PSF over the conventional astigmatism and tetrapod PSF both theoretically and experimentally.

Mitofusin 2 confers the suppression of microglial activation by cannabidiol: Insights from in vitro and in vivo models.

Currently, there is increasing attention on the regulatory effects of cannabidiol (CBD) on the inflammatory response and the immune system. However, the mechanisms have not yet been completely revealed. Mitofusin 2 (Mfn2) is a mitochondrial fusion protein involved in the inflammatory response. Here, we investigated whether Mfn2 confers the anti-inflammatory effects of CBD. We found that treatment with CBD decreased the levels of tumor necrosis factor α, interleukin 6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and ionized calcium-binding adaptor molecule-1 (Iba1) in lipopolysaccharide (LPS)-challenged microglia. CBD also significantly suppressed the increase in reactive oxygen species (ROS) and the decline of mitochondrial membrane potential in BV-2 cells subjected to LPS. Interestingly, CBD treatment increased the expression of Mfn2, while knockdown of Mfn2 blocked the effect of CBD. By contrast, overexpression of Mfn2 reversed the increase in the levels of iNOS, COX-2, and Iba1 induced by Mfn2 small interfering RNA. In mice challenged with LPS, we found that CBD ameliorated the anxiety responses and cognitive deficits, increased the level of Mfn2, and decreased the expression of Iba1. Since neuro-inflammation and microglial activation are the common events that are observed in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, we treated EAE mice with CBD. Mice that received CBD showed amelioration of clinical signs, reduced inflammatory response, and increased myelin basic protein level. Most importantly, the adeno-associated virus delivery of short hairpin RNA against Mfn2 reversed the protective effects of CBD. Altogether, these results indicate that Mfn2 is an essential immunomodulator conferring the anti-inflammatory effects of CBD. Our results also shed new light on the mechanisms underlying the protective effects of CBD against inflammatory diseases including multiple sclerosis.