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This study analyzed the role of G1 to S phase transition 1 protein (GSPT1) in promoting progression of liver cancer cells.A bioinformatics database was used to analyze the expression levels of GSPT1 in liver cancer tissues and the prognosis of patients. Subsequently, Western blotting and quantitative PCR were used to verify the expression levels of GSPT1 between normal hepatocytes and hepatoma cells. We used a CRISPR/Cas9 system to construct knockouts of GSPT1 in HepG2 and HCCLM9 liver cancer cells. The effect of GSPT1 on liver cancer cell migration and invasion was analyzed using flow cytometry, migration, and tumor formation assays.The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset indicated that GSPT1 expression was upregulated in liver cancer cell lines, and patients with liver cancer had poor prognosis. Knockout of GSPT1 in cells significantly inhibited tumor proliferation, cell migration, and growth in vivo.In this study, we found that GSPT1 promotes the migration and invasion of liver cancer cells.

Lung metastasis is a major factor affecting long-term survival in patients with adenoid cystic carcinoma. Here, we showed that the long noncoding RNA (lncRNA) MRPL23 antisense RNA 1 (MRPL23-AS1) was highly expressed and correlated with lung metastasis and overall survival in patients with salivary adenoid cystic carcinoma (SACC). MRPL23-AS1 positively regulated epithelial–mesenchymal transition by forming an RNA–protein complex with enhancer of zeste homolog 2 (EZH2). MRPL23-AS1 increased the binding of EZH2 and H3K27me3 on the E-cadherin promoter region. Moreover, MRPL23-AS1 levels were higher in exosomes isolated from the blood plasma of patients with SACC, and exosomal MRPL23-AS1 affected pulmonary microvascular endothelial cells in an “exosomecrine” manner. MRPL23-AS1–enriched exosomes increased microvascular permeability and facilitated the metastasis of SACC in vivo. Collectively, these findings highlight a molecular mechanism of lung metastasis in SACC. MRPL23-AS1 may represent a biomarker and target for clinical intervention to control this intractable disease.Significance:This study identifies a novel metastasis-promoting lncRNA MRPL23-AS1, which mediates the transcriptional silencing of E-cadherin through forming an RNA–protein complex with EZH2.

Supplementary Data

charateritics of 84 HNSCC patients

S1. Identification of RARS-MAD1L1 by RNA-Seq. S2. RARS-MAD1L1 promotes the proliferation and colony-formation ability of p53-/- MEFs and S26 cells. S3. RARS-MAD1L1 enhances CSC properties in NPC cells. S4. Knockdown of endogenous RARS-MAD1L1 reduces the CSC characteristics of C666-1 cells. S5. Knockdown of RARS-MAD1L1 reduces the oncogenic function of S26 cells induced by RARS-MAD1L1. S6. RARS-MAD1L1 overexpression presents a stronger oncogenic function than wild-type RARS in NPC cells. S7. Knockdown of c-Myc reduces the expression of ABCG2 S8. Schematic illustration of the mechanism through which RARS-MAD1L1 induces cancer stem cell properties and therapeutic resistance through the FBP1/c-Myc axis.

Purpose: Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC.Experimental Design: RNA sequencing (RNA-seq) was applied to look for interchromosome translocation in NPC. PCR, FISH, and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies. MTT assay, colony formation assay, sphere formation assay, co-immunoprecipitation, chromatin immunoprecipitation assay, and in vivo chemoresistance assay were applied to explore the function of RARS-MAD1L1 in NPC.Results: We demonstrated that RARS-MAD1L1 was present in 10.03% (35/349) primary NPC biopsies and 10.7% (9/84) in head and neck cancer (HNC) samples. RARS-MAD1L1 overexpression increased cell proliferation, colony formation, and tumorigenicity in vitro, and the silencing of endogenous RARS-MAD1L1 reduced cancer cell growth and colony formation in vitro. In addition, RARS-MAD1L1 increased the side population (SP) ratio and induced chemo- and radioresistance. Furthermore RARS-MAD1L1 interacted with AIMP2, which resulted in activation of FUBP1/c-Myc pathway. The silencing of FUBP1 or the administration of a c-Myc inhibitor abrogated the cancer stem cell (CSC)-like characteristics induced by RARS-MAD1L1. The expression of c-Myc and ABCG2 was higher in RARS-MAD1L1–positive HNC samples than in negative samples.Conclusions: Our findings indicate that RARS-MAD1L1 might contribute to tumorigenesis, CSC-like properties, and therapeutic resistance, at least in part, through the FUBP1/c-Myc axis, implying that RARS-MAD1L1 might serve as an attractive target for therapeutic intervention for NPC. Clin Cancer Res; 24(3); 659–73. ©2017 AACR.

Supplemental Methods and Materials

RARS-MAD1L1 gDNA fusion sequence by Sanger Sequencing

RARS-MAD1L1 sequence

Cell Line authentication

supplemental figure legend

Phosphorus effect on ash fouling deposition produced during combustion process of sewage sludge solid fuel is a very important factor. Previous studies have only focused on decrease of the ash melting temperature and increase of slagging and sintering by phosphorus content. Therefore, research regarding combustion fouling formation and its effect on temperature reduction of deposit surface by phosphorus content is insufficient. Ash fouling is an important factor, because ash in the combustion boiler process deposits on the surface of heat exchanger and interferes with heat exchange efficiency. In particular, temperature reduction of heat exchanger surface via fouling should be considered together with fouling deposition, because this is related to the heat exchanger efficiency. Synthetic ash, phosphorus vaporization, and drop tube furnace experiments were performed to investigate effect of phosphorus on ash fouling formation and temperature reduction of deposit surface under combustion condition. Phosphorus was highly reactive and reacted with ash minerals to produce mineral phosphate, which promoted ash fouling deposition during the combustion experiments. In contrast, the occurrence of sintering on deposited fouling resulted in formation of a large hollow structure, which alleviated the temperature reduction on the deposit surface. Phosphorus content had a substantial correlation with fouling deposition behavior and influenced reduction in the surface temperature of the heat exchanger, because it led to generating low temperature mineral phases.

A novel nocardioform strain, CICC 11023T, was isolated from a tissue biopsy of neck lesions of a patient with primary cutaneous nocardiosis and characterized to establish its taxonomic position. The morphological, biochemical, physiological and chemotaxonomic properties of strain CICC 11023T were consistent with classification in the genus Nocardia . Whole-cell hydrolysates were rich in meso-diaminopimelic acid, galactose, arabinose and fructose. Mycolic acids were present. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and two unidentified lipids, and the predominant menaquinone was cyclo MK-8 (H4, ω-cyclo). The main fatty acids (>5 %) were C18 : 0 10-methyl (TBSA), C16 : 0, summed feature 4 (C16 : 1 trans 9/C15 : 0 iso 2OH), C15 : 0 and C17 : 0 10-methyl. Phylogenetic analyses based on 16S rRNA gene sequences revealed that the isolate is most closely related (>98 % similarity) to the type strains Nocardia ninae OFN 02.72T, Nocardia iowensis UI 122540T and Nocardia alba YIM 30243T, and phylogenetic analysis of gyrB gene sequences showed similarity (89.1–92.2 %) to Nocardia vulneris NBRC 108936T, Nocardia brasiliensis IFM 0236T and Nocardia exalbida IFM 0803T. DNA–DNA hybridization results for strain CICC 11023T compared to Nocardia type strains ranged from 20.4 to 35.4 %. The genome of strain CICC 11023T was 8.78 Mbp with a G+C content of 67.4 mol% overall. The average nucleotide identity (ANI) values between strain CICC 11023T and N. alba YIM 30243T were low (OrthoANIu=77.47 %), and the ANI values between strain CICC 11023T and N. vulneris NBRC 108936 T were low (OrthoANIu=83.75 %). Consequently, strain CICC 11023T represents a novel Nocardia species on the basis of this polyphasic study, for which the name Nocardia colli sp. nov. is proposed. The type strain is CICC 11023T (=KCTC 39837T).

BACKGROUND Ovarian hyperstimulation syndrome (OHSS), a life-threatening complication occurring in stimulated ovarian cycles, arises from treatment with gonadotropin for inducing follicular maturation. OBJECTIVES The aim of this study was to compare the risk factors between patients with severe OHSS and those without OHSS after in vitro fertilization by intracytoplasmatic sperm injection/embryo transfer (IVF-ICSI/ET). Identifying the associated risk factors may provide guidance for clinicians on how to prevent OHSS. MATERIAL AND METHODS The retrospective study involved patients who had completed IVF-ICSI/ET cycles. The difference in markers for predicting the occurrence of OHSS between groups was compared. The potential protective and risk factors, as well as the predictive markers, were identified. RESULTS Patients with OHSS were younger (p = 0.015), had higher basal antral follicle counts (AFC) (p < 0.001) and lower total dosages of gonadotropin (Gn) (p = 0.011). On the day of human chorionic gonadotropin (hCG) administration, significantly higher total numbers of follicles (p < 0.001), serum estradiol (E2) (p < 0.001) and progestrone (Pg) (p = 0.001) levels, numbers of oocytes (p < 0.001) and metaphase II (MII) oocytes (p < 0.001) were also observed in the OHSS group when compared to the non-OHSS group. A univariate regression analysis revealed that age (OR = 0.898, 95% CI = 0.822-0.981) and total dosage of Gn (OR = 0.999, 95% CI = 0.999-1.000) were protective factors, whereas AFC (OR = 1.090, 95% CI = 1.051-1.131) and, on the day of hCG injection, the number of follicles (OR = 1.185, 95% CI = 1.027-1.230), serum E2 (OR = 1.000, 95% CI = 1.000-1.000) and Pg (OR = 2.773, 95% CI = 0.510-3.370) levels, the number of oocytes (OR = 1.254, 95% CI = 0.894-1.472) and MII oocytes (OR = 1.238, 95% CI = 0.747-1.217) were risk factors for OHSS. However, a multivariate regression analysis showed that the total number of follicles (OR = 1.124, 95% CI = 1.027-1.230) was the only predictive factor for the occurrence of OHSS. CONCLUSIONS The study demonstrated that the follicle count measured on the day of hCG administration was the only predictive factor for the occurrence of OHSS. This provides basic guidance to clinicians on the prevention of the complication when using assisted reproductive technologies (ART).

High-producing dairy cows are easily affected by left displacement of the abomasum (LDA) within 4 weeks postpartum. Although LDA is highly associated with metabolic disturbances, the related information on comprehensive metabolic changes, with the exception of some blood biochemical parameters, remains limited. In this study, the changes in plasma metabolites and in the metabolic profile of postpartum dairy cows with LDA were investigated through liquid chromatography coupled with quadrupole time of flight mass spectrometry (LC-Q/TOF-MS)-based metabolomics, and the metabolic networks related to LDA were constructed through metabolomics pathway analysis (MetPA). An obvious change in the metabolic profile was reflected by significant variations in 68 plasma metabolites in postpartum dairy cows with LDA, and these variations consequently altered 13 metabolic pathways (histidine metabolism, tyrosine metabolism, valine, leucine and isoleucine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, tryptophan metabolism, synthesis and degradation of ketone bodies, linoleic acid metabolism, arachidonic acid metabolism, citrate cycle, butanoate metabolism, vitamin B6 metabolism and pyrimidine metabolism). This study shows that the more detailed information obtained by LC-Q/TOF-MS-based metabolomics and MetPA might contribute to a better understanding of the disordered metabolic networks in postpartum dairy cows with LDA.

A series of new pyrene-based sulfides were synthesized by the reaction between 4-methylbenzenethiol and R-bromopyrene (R = 1( 1 ), 4( 2 ), 2( 3 )). These compounds were structurally characterized and their properties were analyzed by spectroscopy, single crystal X-ray diffraction, electrochemistry and theoretical studies. Significant effect of substituted positions on photophysical properties were observed. The p -methylphenylthio group in 1- and 4-position significantly increases the absolute fluorescence quantum yield ( Ф F ) in solid state, decreases the Ф F in solution and almost does not change the Ф F in film state compared to that of pyrene. However, this substituent in 2-position keeps the high Ф F in solution, almost does not contribute to the Ф F in solid state and significantly decreases the Ф F in film state compared to that of pyrene. Moreover, compounds 1 , 2 and 3 exhibit typical aggregation-induced emission (AIE) properties that were proved by time-resolved photoluminescence.

To explore the impacts on weight reduction effect treated with acupoint thread embedding therapy at different tissue levels under ultrasonic guidance.A total of 70 patients with overweight or obesity were randomized into a shallow-tissue thread embedding group (35 cases, 5 cases dropped off) and a deep-tissue thread embedding group (35 cases, 4 cases dropped off). Under ultrasonic guidance, the thread was embedded in the shallow tissue level and the deep tissue level respectively. The acupoints were Zhongwan (CV 12), Xiawan (CV 10), Shuifen (CV 9), Zhongji (CV 3), etc. The thread embedding therapy was exerted once every 2 weeks, totally for 3 times. Before and 2 weeks after treatment, body mass, body mass index (BMI), waist circumference and hip circumference were recorded in the patients of the two groups separately. After each treatment, the number and the property of blood vessels under each acupoint were detected by ultrasound. Besides, the needling sensation and the intensity were scored and the adverse events were observed after thread embedding therapy.After treatment, the reduction range of body mass, BMI and waist circumference in the deep-tissue thread embedding group were larger than those in the shallow-tissue thread embedding group successively (The deep-tissue thread embedding therapy achieves the stronger

Three new phenazine metabolites, strepphenazine A-C (1-3), along with a known compound baraphenazine E 4 were isolated from the culture broth of a Streptomyces strain YIM PH20095. The structures were elucidated based on the spectral data. Compounds 1-4 showed different antifungal activity against Fusarium oxysporum, Plectosphaerella cucumerina, Alternaria panax, and Phoma herbarum, which caused root-rot disease of Panax notoginseng with minimal inhibitory concentrations (MICs) of 16-64 μg/mL; compared with compound 4, compounds 1-3 showed better antifungal activity against some of these pathogenic fungi with MICs of 16-32 μg/mL, while compound 4 showed antifungal activity against F. oxysporum, P. cucumerina, and A. panax with the same MICs of 64 μg/mL. Thus, strain YIM PH20095 provides new sources for the development of biological control agents to prevent the infection of pathogenic fungi of P. notoginseng.

A direct and highly specific chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) method for monitoring chloramphenicol (CAP) in cosmetics has been developed. The anti-chloramphenicol antibody (mAb) adopted in this work for direct immunoassay could bind to CAP specifically, with negligible cross-reactivity (CR) (less than 0.01%) with most CAP analogues, including structurally related thiamphenicol (TAP) and florfenicol (FF). The limit of detection (LOD), measured by IC10, was 0.0021 ng mL−1. The detection range (IC20-IC80) was ranged from 0.00979 to 0.12026 ng mL−1. In spiked cosmetics samples, mean recoveries ranged from 82.7% to 99.6%, with intraday and interday variation less than 9.8 and 8.2%, respectively. Moreover, with the help of HRP-labeled anti-CAP mAb, the method could be processed in fast direct immunoreaction mode. This CL-ELISA method could be applied for specific, rapid, semiquantitative, and quantitative detection of CAP in cosmetics, facilitating the precise quality control of CAP contamination.

Phosphorylated AKT is highly expressed or overexpressed in chemoresistant tumor samples. However, the precise molecular mechanism involved in AKT phosphorylation-related chemoresistance in breast cancer is still elusive. The present research was designed to estimate the effect of AKT phosphorylation on cell viability and chemoresistance in breast cancer. We utilized MCF-7 and MDA-MB468 human breast cancer cell lines and developed multidrug-resistant MCF-7/MDR and cisplatin-resistant MDA-MB-468 cells. Immunofluorescence analysis and Western blotting were employed to test the level of glycogen synthase kinase 3 beta (GSK3β), phosphorylated phosphatase and tension homologue (p-PTEN) and phosphorylated AKT (p-AKT) in MCF-7/MDR and MDA-MB468 cells. Xenograft assays in nude mice were performed with MCF-7/MDR cells to verify chemoresistance and the signaling pathway upstream of phosphatidylinositide 3-kinase (PI3K)/AKT. An increase in GSK3β, p-PTEN and p-AKT expression was strongly induced in MCF-7/MDR and cisplatin-resistant MDA-MB-468 cells, and augmented GSK3β phosphorylation and PTEN inactivation enhanced AKT signaling. The elevation in GSK3β, p-PTEN and p-AKT was associated with cell viability based on a CCK-8 assay. The results of in vivo and in vitro assays indicated that GSK3β knockdown with lentiviral shRNA (shRNA-GSK3β) promoted apoptosis and suppressed the migration of cisplatin-resistant MCF-7/MDR cells, while these effects were reversed by activating p-AKT with the PTEN inhibitor bpV(pic). AKT phosphorylation mediated by GSK3β and PTEN were correlated with cell viability, migration and apoptosis, which may promote chemoresistance in breast cancer. Furthermore, GSK3β can regulate cell viability through the PTEN/PI3K/AKT signaling pathway and induce chemoresistance, serving as a valuable molecular strategy for breast cancer therapy.

Demyelination in white matter is the end product of numerous pathological processes. This study was designed to evaluate the neuroprotective effect of l -serine and the underlying mechanisms against the demyelinating injury of white matter. A model of focal demyelinating lesions (FDL) was established using the two-point stereotactic injection of 0.25% lysophosphatidylcholine (LPC, 10 μg per point) into the corpus callosum of mice. Mice were then intraperitoneally injected with one of three doses of l -serine (114, 342, or 1026 mg/kg) 2 h after FDL, and then twice daily for the next five days. Behavior tests and histological analysis were assessed for up to twenty-eight days post-FDL induction. Electron microscopy was used for ultrastructural investigation. In vitro, we applied primary co-cultures of microglia and oligodendrocytes for oxygen glucose deprivation (OGD). After establishing FDL, l -serine treatment: 1) improved spatial learning, memory and cognitive ability in mice, and relieved anxiety for 4 weeks post-FDL induction; 2) reduced abnormally dephosphorylated neurofilament proteins, increased myelin basic protein, and preserved anatomic myelinated axons; 3) inhibited microglia activation and reduced the release of inflammatory factors; 4) promoted recruitment and proliferation of oligodendrocyte progenitor cells, and the efficiency of subsequent remyelination on day twenty-eight post-FDL induction. In vitro experiments, showed that l -serine not only directly protected against oligodendrocytes from OGD damage, but also provided an indirect protective effect by regulating microglia. In our study, l -serine offered long-lasting behavioral and oligodendrocyte protection and promoted remyelination. Therefore, l -serine may be an effective clinical treatment aganist white matter injury.

Circular RNAs(circRNA) are recently demonstrated to have a close relationship with tumors.To investigate the role of circular RNA in the pathogenesis of salivary adenoid cystic carcinoma(SACC), ten SACC tissues and paired normal submandibular gland(SMG) tissues were collected as the tumor group and the control group. Total RNA was extracted and then measured using ceRNA microarray (including mRNA, lncRNA, and circRNA) and miRNA microarray. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis were performed in order to investigate the function of the differential expressing genes. The ceRNA regulatory network was constructed to find the core circRNAs. Then the role of circRNA on proliferation was examined in the SACC cell line SACC-83 using CCK-8,qRT-PCR and western blotting, and its roles on migration and invasion were examined using wound healing assay and transwell assay. The results of the microarrays showed that 3792 mRNAs, 7649 lncRNAs, 11553 circRNAs, and 132 miRNAs expressed differentially. The ceRNA regulatory network analysis showed that hsa_circ_0059655 and other 14circRNAs derived from PYGB target on several similar genes by miR-338-3p.Among the 15 circRNAs derived from PYGB, hsa_circ_0059655has the most relationships in the ceRNA network. Furthermore, after hsa_circ_0059655 was knocked down in SACC-83 cells, the expression of hsa-miR-338-3p was up-regulated while CCND1was down-regulated. The proliferation, migration, and invasion of SACC-83 cells also decreased after hsa_circ_0059655 knock-downed.Taken together, the circRNAs derived from PYGB may regulate the tumorigenesis and development of SACC through competing with miR-338-3p.

Background and aim We previously identified forkhead box (FOX) O4 mRNA as a predictor in gastric cancer (GC). However, the underlying mechanism has yet to be elucidated. We aimed to illustrate the mechanism by which FOXO4 regulated glycolysis under hypoxia in GC. Methods FOXO4 protein expression was investigated by immunohistochemical staining of 252 GC and their normal adjacent tissues. We restored or silenced FOXO4 expression in GC cell lines to explore the underlying mechanisms. Results FOXO4 was downregulated in GC. Loss of FOXO4 expression was validated in univariate and multivariate survival analysis as an independent prognostic predictor for overall survival (P, FOXO4 was frequently downregulated in gastric cancer and may serve as a biomarker for prognosis. FOXO4 expression was associated with glycolysis rate both in vitro and in vivo. Mechanistically, FOXO4 impaired glycolysis by transcriptional inhibiting glycolytic enzyme LDHA, and FOXO4 itself was directly by HIF‐1α.

The eukaryotic release factor 3a (eRF3a), a member of the eukaryotic peptide chain release factor family, is overexpressed in several types of cancer. This study aims to investigate the biological role and mechanism of eRF3a in the progression of liver cancer.Western blotting and RT-qPCR were used to detect the expression level of eRF3a in normal liver cells and liver cancer cells. The cell transfection experiments were performed to overexpress eRF3a levels in liver cancer cells HCCLM9 and Huh7, and then cell cycle and apoptosis experiments, Cell Counting Kit-8 (CCK8), plate cloning, and Transwell experiments were done to evaluate the function of eRF3a in the progression of liver cancer. The Western blotting was done to explore the mechanism of eRF3a promoting the development of liver cancer. Western blotting and RT-qPCR were used to detect the expression level of eRF3a in normal liver cells and liver cancer cells. The cell transfection experiments were performed to overexpress eRF3a levels in liver cancer cells HCCLM9 and Huh7, and then cell cycle and apoptosis experiments, Cell Counting Kit-8 (CCK8), plate cloning, and Transwell experiments were done to evaluate the function of eRF3a in the progression of liver cancer. The Western blotting was done to explore the mechanism of eRF3a promoting the development of liver cancer.eRF3a was significantly highly expressed in liver cancer cells, and its expression level was negatively correlated with the clinical prognosis of patients. In addition, in vitro experiments showed that eRF3a could promote the proliferation and migration of liver cancer cells through the ERK and JNK signaling pathways.This study suggests that eRF3a may be a potential prognostic marker for liver cancer and act as an oncogene by activating JNK and ERK signaling; therefore, eRF3a may be a new target for the treatment of liver cancer.

Disruption of remyelination contributes to neurodegeneration and cognitive impairment in chronically disabled patients. Valproic acid (VPA) inhibits histone deacetylase (HDAC) function and probably promotes oligodendrocyte progenitor cell (OPC) proliferation and differentiation; however, the relevant molecular mechanisms remain unknown. Here, focal demyelinating lesions (FDLs) were generated in mice by two-point stereotactic injection of lysophosphatidylcholine (LPC) into the corpus callosum. Cognitive functions, sensorimotor abilities and histopathological changes were assessed for up to 28 days post-injury with or without VPA treatment. Primary OPCs were harvested and used to study the effect of VPA on OPC differentiation under inflammatory conditions. VPA dose-dependently attenuated learning and memory deficits and robustly protected white matter after FDL induction, as demonstrated by reductions in SMI-32 and increases in myelin basic protein staining. VPA also promoted OPC proliferation and differentiation and increased subsequent remyelination efficiency by day 28 post-FDL induction. VPA treatment did not affect HDAC1, HDAC2 or HDAC8 expression but reduced HDAC3 protein levels. In vitro, VPA improved the survival of mouse OPCs and promoted their differentiation into oligodendrocytes following lipopolysaccharide (LPS) stimulation. LPS caused OPCs to overexpress HDAC3, which translocated from the cytoplasm into the nucleus, where it directly interacted with the nuclear transcription factor PPAR-γ and negatively regulated PPAR-γ expression. VPA decreased the expression of HDAC3 and promoted remyelination and functional neurological recovery after FDL. These findings may support the use of strategies modulating HDAC3-mediated regulation of protein acetylation for the treatment of demyelination-related cognitive dysfunction.