Ring finger protein 216 loss-of-function induces white matter hyperintensities by inhibiting oligodendroglia proliferation.

White matter hyperintensities (WMHs) refer to a group of diseases with numerous etiologies while oligodendrocytes remain the centerpiece in the pathogenesis of WMHs. Ring Finger Protein 216 (RNF216) encodes a ubiquitin ligase, and its mutation begets WMHs, ataxia, and cognitive decline in patients. Yet no study has revealed the function of RNF216 in oligodendroglia and WHIs before. In this study, we summarized the phenotypes of RNF216-mutation cases and explored the normal distribution of RNF216 in distinct brain regions and neuronal cells by bioinformatic analysis. Furthermore, MO3.13, a human oligodendrocyte cell line, was applied to study the function alteration after RNF216 knockdown. As a result, WMHs were the most common symptom in RNF216-mutated diseases, and RNF216 was indeed relatively enriched in corpus callosum and oligodendroglia in humans. The downregulation of RNF216 in oligodendroglia remarkably hampered cell proliferation by inhibiting the Akt pathway while having no significant effect on cell injury and oligodendrocyte maturation. Combining clinical, bioinformatical, and experimental evidence, our study implied the pivotal role of RNF216 in WMHs which might serve as a potent target in the therapy of WMHs.

A multicenter study: predicting KRAS mutation and prognosis in colorectal cancer through a CT-based radiomics nomogram.

PURPOSE: To establish a CT-based radiomics nomogram for preoperative prediction of KRAS mutation and prognostic stratification in colorectal cancer (CRC) patients. METHODS: In a retrospective analysis, 408 patients with confirmed CRC were included, comprising 168 cases in the training set, 111 cases in the internal validation set, and 129 cases in the external validation set. Radiomics features extracted from the primary tumors were meticulously screened to identify those closely associated with KRAS mutation. Subsequently, a radiomics nomogram was constructed by integrating these radiomics features with clinically significant parameters. The diagnostic performance was assessed through the area under the receiver operating characteristic curve (AUC). Lastly, the prognostic significance of the nomogram was explored, and Kaplan-Meier analysis was employed to depict survival curves for the high-risk and low-risk groups. RESULTS: A radiomics model was constructed using 19 radiomics features significantly associated with KRAS mutation. Furthermore, a nomogram was developed by integrating these radiomics features with two clinically significant parameters (age, tumor location). The nomogram achieved AUCs of 0.834, 0.813, and 0.811 in the training set, internal validation set, and external validation set, respectively. Additionally, the nomogram effectively stratified patients into high-risk (KRAS mutation) and low-risk (KRAS wild-type) groups, demonstrating a significant difference in overall survival (P < 0.001). Patients categorized in the high-risk group exhibited inferior overall survival in contrast to those classified in the low-risk group. CONCLUSIONS: The CT-based radiomics nomogram demonstrates the capability to effectively predict KRAS mutation in CRC patients and stratify their prognosis preoperatively.

AX·(H2SeO3)n (A = K, Cs; X = Cl, Br; n = 1, 2): A Series of Ionic Cocrystals as Promising UV Birefringent Materials with Large Birefringence and Wide Band Gap.

The design and syntheses of new birefringent crystals will be of great importance in commercial applications and materials science. A series of ultraviolet (UV) birefringent crystals, AX·(H2SeO3)n (A = K, Cs; X = Cl, Br; n = 1, 2), with large sizes up to 23 × 6 × 3 mm3, was successfully synthesized by simple aqueous solution method. These four compounds belong to three different space groups. Isomorphic KCl·(H2SeO3)2 and CsCl·(H2SeO3)2 crystallize in the P1¯ space group, while CsBr·(H2SeO3)2 and CsCl·H2SeO3 crystallize in the P21/m and P21/c space groups, respectively. They exhibit cocrystal structures composed of [2(H2SeO3)]∞ and [AX]∞ frameworks, ingeniously inheriting the large optical anisotropy of selenite and the wide band gap of alkali metal halide. And it proves that these compounds indeed possess large birefringence (0.1-0.17 at 532 nm) and short UV cutoff edges (227-239 nm), achieving a balance of optical properties. This research affords a simple and viable strategy for the design and syntheses of new UV birefringent crystals. Besides, it is also found that the n value and ionic size (A and X ions) have important influences on the crystal structures and optical properties of AX·(H2SeO3)n. And this will promote further understanding of the alkali metal halide selenite family.

Microglial histone deacetylase 2 is dispensable for functional and histological outcomes in a mouse model of traumatic brain injury.

The Class-I histone deacetylases (HDACs) mediate microglial inflammation and neurological dysfunction after traumatic brain injury (TBI). However, whether the individual Class-I HDACs play an indispensable role in TBI pathogenesis remains elusive. HDAC2 has been shown to upregulate pro-inflammatory genes in myeloid cells under brain injuries such as intracerebral hemorrhage, thereby worsening outcomes. Thus, we hypothesized that HDAC2 drives microglia toward a pro-inflammatory neurotoxic phenotype in a murine model of controlled cortical impact (CCI). Our results revealed that HDAC2 expression was highly induced in CD16/CD32+ pro-inflammatory microglia 3 and 7d after TBI. Surprisingly, microglia-targeted HDAC2 knockout (HDAC2 miKO) mice failed to demonstrate a beneficial phenotype after CCI/TBI compared to their wild-type (WT) littermates. HDAC2 miKO mice exhibited comparable levels of grey and white matter injury, efferocytosis, and sensorimotor and cognitive deficits after CCI/TBI as WT mice. RNA sequencing of isolated microglia 3d after CCI/TBI indicated the elevation of a panel of pro-inflammatory cytokines/chemokines in HDAC2 miKO mice over WT mice, and flow cytometry showed further elevated brain infiltration of neutrophils and B cells in HDAC2 miKO mice. Together, this study does not support a detrimental role for HDAC2 in microglial responses after TBI and calls for investigation into alternative mechanisms.

The Role of Indoor Microbiome and Metabolites in Shaping Children's Nasal and Oral Microbiota: A Pilot Multi-Omic Analysis.

Maintaining a diverse and well-balanced nasal and oral microbiota is vital for human health. However, the impact of indoor microbiome and metabolites on nasal and oral microbiota remains largely unknown. Fifty-six children in Shanghai were surveyed to complete a questionnaire about their personal and environmental characteristics. The indoor microbiome and metabolites from vacuumed indoor dust were profiled via shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS). The nasal and oral microbiota in children was characterized using full-length 16S rRNA sequencing from PacBio. Associations between personal/environmental characteristics and the nasal/oral microbiota were calculated using PERMANOVA and regression analyses. We identified 6247, 431, and 342 microbial species in the indoor dust, nasal, and oral cavities, respectively. The overall nasal and oral microbial composition showed significant associations with environmental tobacco smoke (ETS) exposure during pregnancy and early childhood (p = 0.005 and 0.03, respectively), and the abundance of total indoor flavonoids and two mycotoxins (deoxynivalenol and nivalenol) (p = 0.01, 0.02, and 0.03, respectively). Notably, the abundance of several flavonoids, such as baicalein, eupatilin, isoliquiritigenin, tangeritin, and hesperidin, showed positive correlations with alpha diversity and the abundance of protective microbial taxa in nasal and oral cavities (p < 0.02), suggesting their potential beneficial roles in promoting nasal/oral health. Conversely, high carbohydrate/fat food intake and ETS exposure diminished protective microorganisms while augmenting risky microorganisms in the nasal/oral cavities. Further, potential microbial transfer was observed from the indoor environment to the childhood oral cavity (Moraxella catarrhalis, Streptococcus mitis, and Streptococcus salivarius), which could potentially increase virulence factors related to adherence and immune modulation and vancomycin resistance genes in children. This is the first study to reveal the association between the indoor microbiome/metabolites and nasal/oral microbiota using multi-omic approaches. These findings reveal potential protective and risk factors related to the indoor microbial environment.

Chiral Skeletons of Mesoporous Silica Nanospheres to Mitigate Alzheimer's ß-Amyloid Aggregation.

Chiral mesoporous silica (mSiO2) nanomaterials have gained significant attention during the past two decades. Most of them show a topologically characteristic helix; however, little attention has been paid to the molecular-scale chirality of mSiO2 frameworks. Herein, we report a chiral amide-gel-directed synthesis strategy for the fabrication of chiral mSiO2 nanospheres with molecular-scale-like chirality in the silicate skeletons. The functionalization of micelles with the chiral amide gels via electrostatic interactions realizes the growth of molecular configuration chiral silica sols. Subsequent modular self-assembly results in the formation of dendritic large mesoporous silica nanospheres with molecular chirality of the silica frameworks. As a result, the resultant chiral mSiO2 nanospheres show abundant large mesopores (∼10.1 nm), high pore volumes (∼1.8 cm3·g-1), high surface areas (∼525 m2·g-1), and evident CD activity. The successful transfer of the chirality from the chiral amide gels to composited micelles and further to asymmetric silica polymeric frameworks based on modular self-assembly leads to the presence of molecular chirality in the final products. The chiral mSiO2 frameworks display a good chiral stability after a high-temperature calcination (even up to 1000 °C). The chiral mSiO2 can impart a notable decline in ß-amyloid protein (Aß42) aggregation formation up to 79%, leading to significant mitigation of Aß42-induced cytotoxicity on the human neuroblastoma line SH-ST5Y cells in vitro. This finding opens a new avenue to construct the molecular chirality configuration in nanomaterials for optical and biomedical applications.

Blood-brain barrier endothelial cells in neurodegenerative diseases: Signals from the "barrier".

As blood-brain barrier (BBB) disruption emerges as a common problem in the early stages of neurodegenerative diseases, the crucial roles of barrier-type brain endothelial cells (BECs), the primary part of the BBB, have been reported in the pathophysiology of neurodegenerative diseases. The mechanisms of how early vascular dysfunction contributes to the progress of neurodegeneration are still unclear, and understanding BEC functions is a promising start. Our understanding of the BBB has gone through different stages, from a passive diffusion barrier to a mediator of central-peripheral interactions. BECs serve two seemingly paradoxical roles: as a barrier to protect the delicate brain from toxins and as an interface to constantly receive and release signals, thus maintaining and regulating the homeostasis of the brain. Most previous studies about neurodegenerative diseases focus on the loss of barrier functions, and far too little attention has been paid to the active regulations of BECs. In this review, we present the current evidence of BEC dysfunction in neurodegenerative diseases and explore how BEC signals participate in the pathogenesis of neurodegenerative diseases.

Microbial Virulence Factors, Antimicrobial Resistance Genes, Metabolites, and Synthetic Chemicals in Cabins of Commercial Aircraft.

Passengers are at a higher risk of respiratory infections and chronic diseases due to microbial exposure in airline cabins. However, the presence of virulence factors (VFs), antimicrobial resistance genes (ARGs), metabolites, and chemicals are yet to be studied. To address this gap, we collected dust samples from the cabins of two airlines, one with textile seats (TSC) and one with leather seats (LSC), and analyzed the exposure using shotgun metagenomics and LC/MS. Results showed that the abundances of 17 VFs and 11 risk chemicals were significantly higher in TSC than LSC (p < 0.01). The predominant VFs in TSC were related to adherence, biofilm formation, and immune modulation, mainly derived from facultative pathogens such as Haemophilus parainfluenzae and Streptococcus pneumoniae. The predominant risk chemicals in TSC included pesticides/herbicides (carbofuran, bromacil, and propazine) and detergents (triethanolamine, diethanolamine, and diethyl phthalate). The abundances of these VFs and detergents followed the trend of TSC > LSC > school classrooms (p < 0.01), potentially explaining the higher incidence of infectious and chronic inflammatory diseases in aircraft. The level of ARGs in aircraft was similar to that in school environments. This is the first multi-omic survey in commercial aircraft, highlighting that surface material choice is a potential intervention strategy for improving passenger health.

A novel inflammasome-related gene nomogram predicts survival in hepatocellular carcinoma.

Inflammasomes are closely associated with the progression of multiple cancers. We established an inflammasome-related gene (IRG)-based model to predict the survival of patients with hepatocellular carcinoma (HCC). The RNA-sequencing data and clinical information of HCC patients were downloaded from the cancer genome atlas-liver hepatocellular carcinoma database, and the differentially expressed inflammasome-related gene were screened. Seven prognostic differentially expressed inflammasome-related genes were identified by univariate Cox analysis and incorporated into the risk model using least absolute shrinkage and selection operator-Cox algorithm. The predictive accuracy of the risk model was evaluated through the Kaplan-Meier, receiver operating characteristic and Cox regression analyses. The performance of the model was verified in the International Cancer Genome Consortium-Liver Cancer - RIKEN, JP cohort. A nomogram was constructed to predict the 1-, 2-, 3- ,and 5-year survival of HCC patients, and its performance was evaluated using calibration curves. The significantly enriched gene ontology terms, Kyoto encyclopedia of genes and genomes pathways and infiltrating immune cell populations associated with the IRG model were also analyzed to explore of the potential molecular mechanisms and immunotherapeutic targets. An independent and highly accurate prognostic model consisting of 7 IRGs was established and verified in 2 independent HCC cohorts. The IRG model was significantly associated with cell division and cell cycle. In addition, the high-risk group was more likely to have greater infiltration of immune cells and higher expression of immune checkpoint-related genes compared to the low-risk group. An IRG-based model was established to predict 1-, 2-, 3-, and 5-year survival rate in individual HCC patients, which provides new insights into the role of inflammasomes in HCC.

Extracellular Vesicle-Based Therapeutics in Neurological Disorders.

Neurological diseases remain some of the major causes of death and disability in the world. Few types of drugs and insufficient delivery across the blood-brain barrier limit the treatment of neurological disorders. The past two decades have seen the rapid development of extracellular vesicle-based therapeutics in many fields. As the physiological and pathophysiological roles of extracellular vesicles are recognized in neurological diseases, they have become promising therapeutics and targets for therapeutic interventions. Moreover, advanced nanomedicine technologies have explored the potential of extracellular vesicles as drug delivery systems in neurological diseases. In this review, we discussed the preclinical strategies for extracellular vesicle-based therapeutics in neurological disorders and the struggles involved in their clinical application.

([2.2.2]Cryptand)potassium (4-methyl-benzene-thiol-ato)[5,10,15,20-tetra-kis-(4-chloro-phen-yl)porphyr-inato]manganate(II) tetra-hydro-furan disolvate.

Single crystals of the title compound, [K(C18H36N2O6)][Mn(C44H24Cl4N4)(C7H7S)]·2C4H8O, were obtained by the solvent evaporation method. The MnII cation is coordinated by four pyrrole N atoms (Np) of the porphyrin ring and one S atom of the apical 4-methyl-benzene-thiol-ate ligand with the average Mn-Np and the apical Mn-S bond lengths being 2.160 (9) and 2.4642 (8) Å, respectively. Two tetra-hydro-furan solvent mol-ecules and a potassium cation chelated inside a [2.2.2]cryptand (4,7,13,16,21,24-hexa-oxa-1,10-di-aza-bicyclo[8.8.8]hexa-cosa-ne) are also present.

Acne caused by ziprasidone in a young patient with bipolar disorder: A case report.

Background: Ziprasidone is a second-generation antipsychotic drug commonly used to treat schizophrenia and bipolar disorder. Acne is a common inflammatory disease of sebaceous glands in adolescents that is often co-morbid with anxiety and depression, which may reduce treatment compliance. Through unknown mechanisms, ziprasidone may cause a range of inflammatory responses. Whether ziprasidone can cause acne in young patients with bipolar disorder has not been reported. Case summary: We report a 23-year-old woman with a 5-year history of bipolar disorder who experienced acne during use of ziprasidone. She was admitted to our hospital during 1-month aggravation of her symptoms and was diagnosed with bipolar I disorder (current or most recent episode of depression) with psychotic features. She was given ziprasidone and soon developed acne, which she never had before; the rash worsened substantially when the ziprasidone dose was increased. At the same time, levels of inflammatory factors increased. The rash resolved after ziprasidone therapy was stopped. Conclusion: When prescribing ziprasidone to young people with bipolar disorder, clinicians should consider the potential for adverse skin reactions. It may be useful to assay levels of inflammatory markers during ziprasidone therapy and adjust the dose if necessary in order to ensure treatment compliance.

Aberrant gene expression pattern in the glycolysis-cholesterol synthesis axis is linked with immune infiltration and prognosis in prostate cancer: A bioinformatics analysis.

Aberrant lipid metabolism is an early event in tumorigenesis and has been found in a variety of tumor types, especially prostate cancer (PCa). Therefore, We hypothesize that PCa can be stratified into metabolic subgroups based on glycolytic and cholesterogenic related genes, and the different subgroups are closely related to the immune microenvironment. Bioinformatics analysis of genomic, transcriptomic, and clinical data from a comprehensive cohort of PCa patients was performed. Datasets included the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) dataset, GSE70768, our previously published PCa cohort. The unsupervised cluster analysis was employed to stratify PCa samples based on the expression of metabolic-related genes. Four molecular subtypes were identified, named Glycolytic, Cholesterogenic, Mixed, and Quiescent. Each metabolic subtype has specific features. Among the 4 subtypes, the cholesterogenic subtype exhibited better median survival, whereas patients with high expression of glycolytic genes showed the shortest survival. The mitochondrial pyruvate carriers (MPC) 1 exhibited expression difference between PCa metabolic subgroups, but not for MPCs 2. Glycolytic subtypes had lower immune cell scores, while Cholesterogenic subgroups had higher immune cell scores. Our results demonstrated that metabolic classifications based on specific glycolytic and cholesterol-producing pathways provide new biological insights into previously established subtypes and may guide develop personalized therapies for unique tumor metabolism characteristics.

First-episode olfactory hallucination in a patient with anxiety disorder: A case report.

Background: Olfactory hallucination refers to olfactory perception in the absence of chemical stimuli. Although it has been associated with many neurological and psychotic disorders, it has rarely been reported as the first and only symptom in patients with anxiety disorder, and its treatment remains inadequate. Case summary: A 66-year-old woman who had been experiencing gradually worsening olfactory hallucinations for almost 4 years was diagnosed with generalized anxiety disorder. Olfactory hallucination disappeared after treatment with anti-anxiety drugs. Conclusion: Olfactory hallucination can be the first and only symptom in patients with anxiety disorder and may be effectively treated with anti-anxiety medication. In fact, it can precede the diagnosis of anxiety disorder by several years.

Hiccups induced by aripiprazole combined with sertraline in an adolescent with olfactory reference disorder: A case report.

Background: Hiccup can cause significant distress to patients and affect medication compliance. Individuals with olfactory reference disorder (ORD) who might develop persistent hiccups when treated with a combination of antidepressant and antipsychotic, leading to significant distress and impairment. Case summary: We report a rare case of an adolescent with ORD who was treated with aripiprazole combined with sertraline and who began to hiccup persistently after 6 days on this treatment. He stopped hiccupping after the aripiprazole had been suspended for 12 h. After discharge, the patient continued on sertraline alone and reported no hiccupping at 1-month follow-up. Conclusion: Clinicians should consider that the combination of aripiprazole and sertraline can induce hiccups during the acute administration period in adolescents with ORD.

Two-Dimensional-on-Three-Dimensional Metal-Organic Frameworks for Photocatalytic H2 Production.

A MOF-on-MOF heterostructure is attractive in material science because of its potential combined effects in catalysis. However, precisely controlling the growth pattern at the metal-organic framework (MOF) nucleation stage to manipulate the metallic composition and structure dimensionality remain a challenge. Herein, we introduce a polyvinylpyrrolidone-assist kinetic-control strategy to achieve the "anti-epitaxial growth" pattern of a foreign MOF nucleus on the (111) facets of UiO-66-NH2 octahedron seeds, and construct diverse two-dimensional-on-three-dimensional (2D-on-3D) MOF heterostructures (2D-on-3D Cu, Zn, Cd, Co, and Ni). Notably, the 2D-on-3D Cu exhibits a unique "dimensionality-hybrid" effect in photocatalysis which led to a significant photoactivity enhancement over those of the traditional "dimensionality-identical" 2D, 3D and 3D-on-3D MOF structures.

SSA-Net: Spatial self-attention network for COVID-19 pneumonia infection segmentation with semi-supervised few-shot learning.

Coronavirus disease (COVID-19) broke out at the end of 2019, and has resulted in an ongoing global pandemic. Segmentation of pneumonia infections from chest computed tomography (CT) scans of COVID-19 patients is significant for accurate diagnosis and quantitative analysis. Deep learning-based methods can be developed for automatic segmentation and offer a great potential to strengthen timely quarantine and medical treatment. Unfortunately, due to the urgent nature of the COVID-19 pandemic, a systematic collection of CT data sets for deep neural network training is quite difficult, especially high-quality annotations of multi-category infections are limited. In addition, it is still a challenge to segment the infected areas from CT slices because of the irregular shapes and fuzzy boundaries. To solve these issues, we propose a novel COVID-19 pneumonia lesion segmentation network, called Spatial Self-Attention network (SSA-Net), to identify infected regions from chest CT images automatically. In our SSA-Net, a self-attention mechanism is utilized to expand the receptive field and enhance the representation learning by distilling useful contextual information from deeper layers without extra training time, and spatial convolution is introduced to strengthen the network and accelerate the training convergence. Furthermore, to alleviate the insufficiency of labeled multi-class data and the long-tailed distribution of training data, we present a semi-supervised few-shot iterative segmentation framework based on re-weighting the loss and selecting prediction values with high confidence, which can accurately classify different kinds of infections with a small number of labeled image data. Experimental results show that SSA-Net outperforms state-of-the-art medical image segmentation networks and provides clinically interpretable saliency maps, which are useful for COVID-19 diagnosis and patient triage. Meanwhile, our semi-supervised iterative segmentation model can improve the learning ability in small and unbalanced training set and can achieve higher performance.

A systematic review on antibiotics misuse in livestock and aquaculture and regulation implications in China.

China is one of the largest producers and consumers of antibiotics, and China is a larger producer of livestock farming and aquaculture in the world. The livestock farming and aquaculture industry is a major area of antibiotic misuse, which has caused serious antibiotic residues and environment pollution. The antibiotic residues exceeding the standard may lead to antibiotic resistances in animals or human bodies, which poses a threat to human health. In this context, this study tries to systematically review the current situation of antibiotic misuse in livestock and aquaculture in China, and put forward corresponding regulatiory measures for the central government. Based on the status quo of livestock farming and aquaculture in China, this study reviewed antibiotic misuse in livestock farming and aquaculture and antibiotic resistance in China, introduced China's current policies on antibiotic regulation and the gap between China and developed countries, and analyzed the implications of current regulatory policies on animal health and productivity. At last, we put forward suggestions for the future antibiotic regulation, including strictly implementing the relevant laws and regulations, formulating specific supporting measures, encouraging the research and development of antibiotic substitutes, introducing advanced technologies for supervision and regulation, strengthening the publicity of science popularization and enhancing the public's awareness of the rational use of antibiotics. If these policy recommendations can be implemented, they will significantly promote the regulation of antibiotic abuse.

Dl-3-n-Butylphthalide Alleviates Demyelination and Improves Cognitive Function by Promoting Mitochondrial Dynamics in White Matter Lesions.

White matter lesions (WMLs) are a type of cerebrovascular disorder accompanied by demyelination and cognitive decline. Dl-3-n-butylphthalide (D1-NBP) is a neuroprotective drug used for the treatment of ischemic cerebrovascular diseases, although the function of DI-NBP on WML is still not clear. This study aims to investigate whether DI-NBP affects cognitive function and ameliorates demyelination in a model of WML. The bilateral carotid artery stenosis (BCAS) mouse model and in vitro brain slice cultures with low glucose and low oxygen (LGLO) treatment were adopted. The Dl-NBP was administered intragastrically for 28 days after BCAS or added at a dose of 50 µm for 48 h after LGLO. Spatial learning and memory were evaluated by an eight-arm radial maze. Demyelination was detected using a TEM. Mitochondrial dynamics were assessed by time-lapse imaging in the cultured brain slices. The function of the synapse was evaluated by the patch clamp technique. In BCAS mice, obvious demyelination and cognitive decline were observed, while both were significantly relieved by a high-dose D1-NBP treatment (100 mg/kg). Along with demyelination, mitochondrial accumulation in the axons was significantly increased in the BCAS mice model, but with the treatment of a high-dose D1-NBP, mitochondrial accumulation was mitigated, and the anterograde/retrograde transport of mitochondria was increased. Following the improved anterograde/retrograde transport of mitochondria, the synapse activity was significantly upregulated while the reactive oxygen species (ROS) generation was remarkably decreased in the cultured brain slices. In addition, we identified syntaphilin (SNPH) as the downstream target of D1-NBP. The overexpression of SNPH mediated the effects of D1-NBP in mitigating axonal mitochondrial accumulation. In conclusion, the D1-NBP treatment significantly relieved demyelination and improved spatial learning and memory in the WML model by promoting mitochondrial dynamics. These neuroprotective effects of D1-NBP were mediated by inhibiting the mitochondrial arching protein, SNPH, which provided a potential therapeutic target for WML.