We investigated the serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels in a cohort of Chinese patients with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) in relation to clinical disease course and treatment. sNfL and sGFAP levels were determined by ultrasensitive single molecule array (Simoa) assay in patients with NMOSD (n = 102) and MS (n = 98) and healthy controls (HCs; n = 84). Notably, 13 patients with NMOSD and 27 patients with MS were enrolled in the 1-year follow-up cohort. Levels were compared with data such as clinical course, disease duration, Expanded Disability Status Scale (EDSS) score, and lesions on MRI. Higher levels of sNfL and sGFAP were found in subjects with NMOSD and MS than in HCs (sNfL, median 12.11, 17.5 vs. 8.88 pg/ml, p < .05; sGFAP, median 130.2, 160.4 vs. 80.01 pg/ml, p < .05). Moreover, sNfL levels were higher in the relapse phase of MS than in the relapse phase of NMOSD (30.02 vs. 14.57 pg/ml, p < .05); sGFAP levels were higher in the remission phase of MS than in the remission phase of NMOSD (159.8 vs. 124.5 pg/ml, p < .01). A higher sGFAP/sNfL quotient at relapse differentiated NMOSD from MS. Multivariate analyses indicated that sGFAP levels were associated with the EDSS score in NMOSD (p < .05). At the 1-year follow-up, sNfL and sGFAP levels were both decreased in NMOSD patients in remission, while only sNfL levels were decreased in MS patients in remission. sGFAP and sNfL are potential blood biomarkers for diagnosing and monitoring NMOSD and MS.
Abstract Objective To determine the relationship between basal metabolic rate (BMR) and multiple sclerosis (MS) susceptibility, we used genome-wide association study (GWAS) summary statistics data from the International Multiple Sclerosis Genetics Consortium on a total of 115,803 participants of European descent, including 47,429 MS patients and 68,374 controls. Methods We selected 378 independent genetic variants strongly associated with BMR in a GWAS involving 454,874 participants as instrumental variables to examine a potential causal relationship between BMR and MS. Results A genetically predicted higher BMR was associated with a greater risk of MS (odds ratio [OR]: 1.283 per one standard deviation increase in BMR, 95% confidence interval [CI]: 1.108–1.486, P = 0.001). Moreover, we used the lasso method to eliminate heterogeneity (Q statistic = 384.58, P = 0.370). There was no pleiotropy in our study and no bias was found in the sensitivity analysis using the leave-one-out test. Conclusions We provide novel evidence that a higher BMR is an independent causal risk factor in the development of MS. Further work is warranted to elucidate the potential mechanisms.
The historical period from Han to Northern and Southern dynasties was the major duration when Eastern-Western Cao existed. Western Cao and Eastern Cao were administrative organs which, under the jurisdiction of Prime Minister in Western Han initially, took charge of internal and external affairs respectively. Then Eastern-Western Cao administered personnel affairs which were subordinated to Three-Chancellor in Eastern Han dynasty. Western Cao mastered official personnel, while Eastern Cao commanded the most important power of personnel disposal in the feudal political system, and Eastern-Western Cao’s installation scope and the changes of functional state had close connections with realistic politics. The distribution of feudal local authorities in Han-Wei-Jin-Northern and Southern dynasties were all refraction of Eastern-Western Cao’s historical shifts on certain level: the changes of Prime minister’s power, and the relationship between the centralized monarchy and officers of two-thousand-dan rank and military officials. In Eastern Han period, the installation scope of Eastern-Western Cao extended to the military. Especially at the end of Han dynasty, warlords installed Eastern-Western Cao as regime hub generally, Eastern-Western Cao presented unprecedented active appearance. Therefore, after Wei-Jin dynasties, Western Cao and Eastern Cao developped in the directions of decline and fall.
During the Han and Jin Dynasties, the Fu(傅)family of Beidi(北地)was a rather active aristocratic clan in the north. Being invaded by Qiang nationality(羌)and Hu(胡)in the East Han Dynasty, Beidi county moved and its inhabitants migrated to other places. Fu Xian's(傅咸)descendants migrated to Qinghe(清河)in order to seek advantageous living conditions. After the Yongjia(永嘉)turmoil, two branches of the Fu family migrated to the south. The cultural features of the Fu family showed the characteristics of northern aristocratic clans clearly. The Fu family valued patriarchal clan system and kinship, filial piety, and being diligent in achievements and government affairs. The Fu family's styles of education and study were mixed with each other, and tended to be conservative. When the Kingdom of Wei replaced the Han Dynasty, Fu Gan(傅干)rebuked Cao Cao's usurpation of throne. When the SiMa(司马)family usurped the throne in late Wei, Fu Jia(傅嘏)and Fu Xuan(傅玄)joined in the camp of the SiMa family. In the two transformations of the imperial power, the Fu family's political inclination and function were different.
P-type ATPases are integral membrane transporters that play important roles in transmembrane transport in plants. However, a comprehensive analysis of the P-type ATPase gene family has not been conducted in Chinese white pear (Pyrus bretschneideri) or other Rosaceae species. Here, we identified 419 P-type ATPase genes from seven Rosaceae species (Pyrus bretschneideri, Malus domestica, Prunus persica, Fragaria vesca, Prunus mume, Pyrus communis and Pyrus betulifolia). Structural and phylogenetic analyses revealed that P-type ATPase genes can be divided into five subfamilies. Different subfamilies have different conserved motifs and cis-acting elements, which may lead to functional divergence within one gene family. Dispersed duplication and whole-genome duplication may play critical roles in the expansion of the P-type ATPase family. Purifying selection was the primary force driving the evolution of P-type ATPase family genes. Based on the dynamic transcriptome analysis and transient transformation of Chinese white pear fruit, Pbr029767.1 in the P3A subfamily were found to be associated with malate accumulation during pear fruit development. Using a co-expression network, we identified several transcription factors that may have regulatory relationships with the P-type ATPase gene family. Overall, this study lays a solid foundation for understanding the evolution and functions of P-type ATPase genes in Chinese white pear and six other Rosaceae species.
The plant disease resistance system involves a very complex regulatory network in which jasmonates play a key role in response to external biotic or abiotic stresses. As inhibitors of the jasmonic acid (JA) signaling pathway, JASMONATE ZIM domain (JAZ) proteins have been identified in many plant species, and their functions are gradually being clarified. In this study, 26 JAZ genes were identified in tomato. The physical and chemical properties, predicted subcellular localization, gene structure, cis-acting elements, and interspecies collinearity of 26 SlJAZ genes were subsequently analyzed. RNA-seq data combined with qRT-PCR analysis data showed that the expression of most SlJAZ genes were induced in response to Stemphylium lycopersici, methyl jasmonate (MeJA) and salicylic acid (SA). Tobacco rattle virus RNA2-based VIGS vector (TRV2)-SlJAZ25 plants were more resistant to tomato gray leaf spots than TRV2-00 plants. Therefore, we speculated that SlJAZ25 played a negative regulatory role in tomato resistance to gray leaf spots. Based on combining the results of previous studies and those of our experiments, we speculated that SlJAZ25 might be closely related to JA and SA hormone regulation. SlJAZ25 interacted with SlJAR1, SlCOI1, SlMYC2, and other resistance-related genes to form a regulatory network, and these genes played an important role in the regulation of tomato gray leaf spots. The subcellular localization results showed that the SlJAZ25 gene was located in the nucleus. Overall, this study is the first to identify and analyze JAZ family genes in tomato via bioinformatics approaches, clarifying the regulatory role of SlJAZ25 genes in tomato resistance to gray leaf spots and providing new ideas for improving plant disease resistance.
Abstract Background: The BAHD acyltransferase superfamily exhibits various biological roles in plants, including regulation the fruit quality; catalytic synthesis of terpene, phenolic and esters; improvement of stress resistance. However, the copy number, evolutionary history and potential functions of the BAHD superfamily genes in the genome sequenced Rosaceae species remains unclear. Results: Totally, 755 BAHD genes were obtained from the genomes of seven Rosaceae fruit species (Pyrus bretschneideri, Malus domestica, Prunus avium, Prunus persica, Fragaria vesca, Pyrus communis and Rubus occidentalis). Based on the classification results from model plants, we divided the BAHD family genes into seven subgroups (I-a, I-b, II-a, II-b, III-a, IV, V). Based on intra-species synteny analysis, 61 syntenic gene pairs were detected from the six Rosaceae species. Dispersed gene duplication occurred frequently in all investigated species. Different modes of duplicated gene pairs identified in each investigated species show that the Ka/Ks is less than one, indicating they evolved through purifying selection. Based on the correlation analysis between ester content and expression level of BAHD genes at different development stages, we selected five genes to perform qRT-PCR verification, and the results showed that Pbr020016.1, Pbr019034.1, Pbr014028.1 and Pbr029551.1 are the important candidate genes involved in aroma formation during pear fruit development. Conclusion: We have thoroughly annotated the BAHD superfamily genes and made a comprehensive comparative analysis of their colinearity, phylogenetic relationships and gene duplication patterns in the seven Rosaceae species, and also obtained four candidate genes might be involved in the aroma synthesis in the pear fruit. These presented results provide a theoretical basis for the future studies of the specific biological functions of BAHD superfamily members and the improvement of pear fruit quality. Keywords: BAHD, pear, evolution, Rosaceae, transcriptome, volatile esters
Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease of the central nervous system that is manifested as secondary myelin loss. Oligodendrocyte progenitor cells (OPCs) are the principal source of myelinating oligodendrocytes (OLs) and are abundant in demyelinated regions of NMOSD patients, thus possibly representing a cellular target for pharmacological intervention. To explore the therapeutic compounds that enhance myelination due to endogenous OPCs, we screened the candidate drugs in mouse neural progenitor cell (NPC)‐derived OPCs. We identified drug edaravone, which is approved by the Food and Drug Administration (FDA), as a promoter of OPC differentiation into mature OLs. Edaravone enhanced remyelination in organotypic slice cultures and in mice, even when edaravone was administered following NMO‐IgG‐induced demyelination, and ameliorated motor impairment in a systemic mouse model of NMOSD. The results of mechanistic studies in NMO‐IgG‐treated mice and the biopsy samples of the brain tissues of NMOSD patients indicated that the mTORC1 signaling pathway was significantly inhibited, and edaravone promoted OPC maturation and remyelination by activating mTORC1 signaling. Furthermore, pharmacological activation of mTORC1 signaling significantly enhanced myelin regeneration in NMOSD. Thus, edaravone is a potential therapeutic agent that promotes lesion repair in NMOSD patients by enhancing OPC maturation.
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