Genetic analysis and QTL mapping for pericarp thickness in maize (Zea mays L.).

Proper pericarp thickness protects the maize kernel against pests and diseases, moreover, thinner pericarp improves the eating quality in fresh corn. In this study, we aimed to investigate the dynamic changes in maize pericarp during kernel development and identified the major quantitative trait loci (QTLs) for maize pericarp thickness. It was observed that maize pericarp thickness first increased and then decreased. During the growth and formation stages, the pericarp thickness gradually increased and reached the maximum, after which it gradually decreased and reached the minimum during maturity. To identify the QTLs for pericarp thickness, a BC4F4 population was constructed using maize inbred lines B73 (recurrent parent with thick pericarp) and Baimaya (donor parent with thin pericarp). In addition, a high-density genetic map was constructed using maize 10 K SNP microarray. A total of 17 QTLs related to pericarp thickness were identified in combination with the phenotypic data. The results revealed that the heritability of the thickness of upper germinal side of pericarp (UG) was 0.63. The major QTL controlling UG was qPT1-1, which was located on chromosome 1 (212,215,145-212,948,882). The heritability of the thickness of upper abgerminal side of pericarp (UA) was 0.70. The major QTL controlling UA was qPT2-1, which was located on chromosome 2 (2,550,197-14,732,993). In addition, a combination of functional annotation, DNA sequencing analysis and quantitative real-time PCR (qPCR) screened two candidate genes, Zm00001d001964 and Zm00001d002283, that could potentially control maize pericarp thickness. This study provides valuable insights into the improvement of maize pericarp thickness during breeding.

High preseason temperature variability drives convergence of xylem phenology in the Northern Hemisphere conifers.

Wood growth is key to understanding the feedback of forest ecosystems to the ongoing climate warming. An increase in spatial synchrony (i.e., coincident changes in distant populations) of spring phenology is one of the most prominent climate responses of forest trees. However, whether temperature variability contributes to an increase in the spatial synchrony of spring phenology and its underlying mechanisms remains largely unknown. Here, we analyzed an extensive dataset of xylem phenology observations of 20 conifer species from 75 sites over the Northern Hemisphere. Along the gradient of increase in temperature variability in the 75 sites, we observed a convergence in the onset of cell enlargement roughly toward the 5th of June, with a convergence in the onset of cell wall thickening toward the summer solstice. The increase in rainfall since the 5th of June is favorable for cell division and expansion, and as the most hours of sunlight are received around the summer solstice, it allows the optimization of carbon assimilation for cell wall thickening. Hence, the convergences can be considered as the result of matching xylem phenological activities to favorable conditions in regions with high temperature variability. Yet, forest trees relying on such consistent seasonal cues for xylem growth could constrain their ability to respond to climate warming, with consequences for the potential growing season length and, ultimately, forest productivity and survival in the future.

Pilots' Spatial Visualization Ability Assessment Based on Virtual Reality.

BACKGROUND: The aim of this study was to investigate the effectiveness of the mental rotation test (MRT) based on virtual reality (VR) in predicting pilots' spatial visualization ability (SVA).METHODS: Based on VR, 118 healthy pilots' SVA were evaluated by MRT. The pilot flight ability evaluation scale was used as the criterion of test validity. According to the scale score, pilots were divided into high, middle, or low spatial ability groups pursuant to the 27% allocation principle. Differences in reaction time (RT), correct rate (CR), and correct number per second (CNPS) of MRT between groups were compared. Correlations between scale scores and MRT scores were analyzed. RT, CR, and CNPS of MRT among different age groups and between genders were also compared.RESULTS: The RT of the high spatial ability group was remarkably slower than that of the low spatial ability group (363.4 ± 140.2 s, 458.1 ± 151.7 s). The CNPS of the high spatial ability group was dramatically higher than that of the low spatial ability group (0.111 ± 0.045 s, 0.086 ± 0.001 s). There were no significant differences in RT, CR, and CNPS between different genders. Pilots in the 29-35 yr old age group had considerably slower RT than those in the 22-28 yr old age group (330.8 ± 140.3 s, 417.2 ± 132.7 s). Pilots in the 29-35 yr old age group had conspicuously higher CNPS than pilots in the 22-28 yr old age group (0.119 ± 0.040 s, 0.096 ± 0.036 s). All pilots' scale scores were positively correlated with CNPS (r = 0.254) and negatively correlated with RT (r = -0.234).DISCUSSION: MRT based on VR has a good discrimination efficacy for SVA of pilots and is a good indicator for the SVA component measurement.Zhang M, Wang M, Feng H, Liu X, Zhai L, Xu X, Jin Z. Pilots' spatial visualization ability assessment based on virtual reality. Aerosp Med Hum Perform. 2023; 94(6):422-428.

Kirenol inhibits inflammation challenged by lipopolysaccharide through the AMPK-mTOR-ULK1 autophagy pathway.

Kirenol is a bioactive substance isolated from Herba Siegesbeckiae. Although the anti-inflammatory activity of kirenol has been well documented, its role in autophagy remains unknown. The present study aimed to investigate the protective role of kirenol on inflammation challenged by lipopolysaccharide (LPS) in acute lung injury (ALI) cell and mouse models and unravel the underlying mechanisms, with a particular focus on autophagy. For this purpose, an ALI cell and mouse models were established, and the effects of kirenol on the expression of molecules related to inflammation and autophagy were examined. The present results revealed that kirenol could significantly inhibit inflammatory cytokines secretion in cells and in the mice injured by LPS; this effect may be attributed to enhanced autophagy as evidenced by the up-regulation of LC3-II and the down-regulation of p62 both in vitro and in vivo. Phosphorylated AMPK and ULK1 increased, while phosphorylated mTOR decreased in the kirenol-treated ALI cell model. Moreover, inhibition of autophagy using AMPK inhibitor or 3-MA or chloroquine (CQ) reversed the anti-inflammatory and autophagy-enhancement effects of kirenol exposure in vitro, indicating that kirenol could enhance autophagy by activating the AMPK-mTOR-ULK1 pathway. The results of RNA sequencing suggested that kirenol was strongly related to the biological functions of acute inflammatory response and the AMPK signaling pathway. Further in vivo ALI mouse model studies demonstrated the protective role of kirenol against lung inflammation, such as improved histopathology, decreased lung edema, and leukocyte infiltration were abolished by 3-MA. These findings implicate that kirenol can inhibit LPS-induced inflammation via the AMPK-mTOR-ULK1 autophagy pathway.

A critical thermal transition driving spring phenology of Northern Hemisphere conifers.

Despite growing interest in predicting plant phenological shifts, advanced spring phenology by global climate change remains debated. Evidence documenting either small or large advancement of spring phenology to rising temperature over the spatio-temporal scales implies a potential existence of a thermal threshold in the responses of forests to global warming. We collected a unique data set of xylem cell-wall-thickening onset dates in 20 coniferous species covering a broad mean annual temperature (MAT) gradient (-3.05 to 22.9°C) across the Northern Hemisphere (latitudes 23°-66° N). Along the MAT gradient, we identified a threshold temperature (using segmented regression) of 4.9 ± 1.1°C, above which the response of xylem phenology to rising temperatures significantly decline. This threshold separates the Northern Hemisphere conifers into cold and warm thermal niches, with MAT and spring forcing being the primary drivers for the onset dates (estimated by linear and Bayesian mixed-effect models), respectively. The identified thermal threshold should be integrated into the Earth-System-Models for a better understanding of spring phenology in response to global warming and an improved prediction of global climate-carbon feedbacks.

TM9SF1 knockdown decreases inflammation by enhancing autophagy in a mouse model of acute lung injury.

TM9SF1 is a member of the TM9SF (Transmembrane 9 Superfamily Member) family, which usually has a long N-terminal extracellular region and nine transmembrane domains. TM9SF1's biological function and mechanisms in inflammation are yet unknown. Tm9sf1 was shown to be upregulated in the lung tissues of mice suffering from LPS-induced acute lung injury (ALI). Tm9sf1 knockout mice were studied, and it was shown that Tm9sf1 knockout significantly alleviated LPS-induced ALI, as evidenced by higher survival rate, improved pulmonary vascular permeability, decreased inflammatory cell infiltration, and downregulated inflammatory cytokines. TM9SF1 was also demonstrated to be a negative regulator of autophagy in the LPS-induced ALI model in vitro and in vivo. The autophagy inhibitor 3-MA could counteract the beneficial effects of Tm9sf1 knockout on ALI. Therefore, we discover for the first time the role and mechanism of TM9SF1 in LPS-induced ALI and establish a relationship between TM9SF1 regulated autophagy and ALI progression, which may provide novel targets for the treatment of ALI.

Variations in the TAS2R38 gene among college students in Hubei.

BACKGROUND: The bitter taste receptor gene TAS2R38 is a member of the human TAS2R gene family. Polymorphisms in TAS2R38 affect the ability to taste the bitterness of phenylthiourea (PTC) compounds, thus affecting an individual's food preference and health status. METHODS: We investigated polymorphisms in the TAS2R38 gene and the sensitivity to PTC bitterness among healthy Chinese college students in Hubei province. The association of TAS2R38 polymorphisms and PTC sensitivity with body mass index (BMI), food preference, and health status was also analyzed. A total of 320 healthy college students were enrolled (male: 133, female: 187; aged 18-23 years). The threshold value method was used to measure the perception of PTC bitterness, and a questionnaire was used to analyze dietary preferences and health status. Polymerase chain reaction (PCR) was used to analyze polymorphisms at three common TAS2R38 loci (rs713598, rs1726866, and rs10246939). RESULTS: In our study population, 65.00% of individuals had medium sensitivity to the bitterness of PTC; in contrast, 20.94% were highly sensitive to PTC bitterness, and 14.06% were not sensitive. For the TAS2R38 gene, the PAV/PAV and PAV/AAI diplotypes were the most common (42.19% and 40.63%, respectively), followed by the homozygous AVI/AVI (8.75%) and PAV/AVI (5.00%) diplotypes. CONCLUSION: There was a significant correlation between the sensitivity to PTC bitterness and sex, but there was no correlation between the common diplotypes of TAS2R38 and gender. Polymorphisms in the TAS2R38 gene were associated with the preference for tea, but not with one's native place, BMI, health status, or other dietary preferences. There was no significant correlation between the perception of PTC bitterness and one's native place, BMI, dietary preference, or health status. We hope to find out the relationship between PTC sensitivity and TAS2R38 gene polymorphisms and dietary preference and health status of Chinese population through this study, providing relevant guidance and suggestions for dietary guidance and prevention of some chronic diseases in Chinese population.

Equilibrium and Vestibular Safety of Modafinil in Healthy Volunteers.

BACKGROUND: Modafinil, as a wake-promoting agent, is commonly used to relieve fatigue during military operations. However, there is a lack of clarity regarding the effects of modafinil on the equilibrium and vestibular organs, especially when prescribing this drug to flight crewmembers. The objective of this study was to evaluate the equilibrium- and vestibular-related safety effects of modafinil.METHODS: In a randomized, double-blind, placebo-controlled, crossover study, 10 healthy male volunteers received a single 200-mg oral dose of modafinil or placebo. Equilibrium and vestibular functions were assessed 2 h after oral administration by the sensory organization test (SOT), adaptation test (ADT), and video head impulse test (v-HIT).RESULTS: There was no change in the equilibrium scores of the six SOT conditions or the composite scores between the modafinil and placebo groups. Statistically significant differences were not observed for the sway energy score (SES) in the toe-down test. In the toe-up test, the SES decreased by 16.7% in the modafinil group relative to the placebo group in trial 2, while the differences in other trials were not statistically significant. In the v-HIT, there was no significant difference in the gain of each semicircular canal between the two groups.DISCUSSION: A single 200-mg dose of modafinil did not cause any impairment to vestibular function, equilibrium ability, or adaptive balance response; in fact, modafinil might have a positive effect on adaptation function in healthy volunteers. These findings preliminarily suggest that there is no hidden risk of vestibular dysfunction among aviation employees using modafinil.Liu F, Zhang M, Chen T, Zhai L, Zhang Z, Xue J. Equilibrium and vestibular safety of modafinil in healthy volunteers. Aerosp Med Hum Perform. 2022; 93(6):487-492.

Circular RNAs Acting as miRNAs' Sponges and Their Roles in Stem Cells.

Circular RNAs (circRNAs), a novel type of endogenous RNAs, have become a subject of intensive research. It has been found that circRNAs are important players in cell differentiation and tissue homeostasis, as well as disease development. Moreover, the expression of circRNAs is usually not correlated with their parental gene expression, indicating that they are not only a steady-state by-product of mRNA splicing but a product of variable splicing under novel regulation. Sequence conservation analysis has also demonstrated that circRNAs have important non-coding functions. CircRNAs exist as a covalently closed loop form in mammalian cells, where they regulate cellular transcription and translation processes. CircRNAs are built from pre-messenger RNAs, and their biogenesis involves back-splicing, which is catalyzed by spliceosomes. The splicing reaction gives rise to three different types of intronic, exotic and exon-intron circular RNAs. Due to higher nuclease stability and longer half lives in cells, circRNAs are more stable than linear RNAs and have enormous clinical advantage for use as diagnostic and therapeutic biomarkers for disease. In recent years, it has been reported that circRNAs in stem cells play a crucial role in stem cell function. In this article, we reviewed the general feature of circRNAs and the distinct roles of circRNAs in stem cell biology, including regulation of stem cell self-renewal and differentiation. CircRNAs have shown unique expression profiles during differentiation of stem cells and could serve as promising biomarkers of these cells. As circRNAs play pivotal roles in stem cell regulation as well as the development and progression of various diseases, we also discuss opportunities and challenges of circRNA-based treatment strategies in future effective therapies for promising clinical applications.

[Comparative study on the clinical features of familial clustered and sporadic vestibular migraine].

Objective:To compare and analyze the clinical features of family clustered vestibular migraine（FCVM） and sporadic vestibular migraine（SVM）. Methods:A total of 118 patients with vestibular migraine were selected and divided into FCVM group（66 cases） and SVM group（52 cases）, and the clinical features such as age, the form of symptoms, provoking and relieving factors, audiological manifestations, sequelae and complications, were compared and analyzed. Results:The onset of headache in FCVM group was earlier than that in SVM group （[23.88±11.45] years old and [28.77±11.85] years old, χ²=2.267, P=0.025） with a longer interval between headache and vertigo attack （[13.11±10.08] years old and [8.50±9.26] years old, χ²=2.554, P=0.012）.Patients with positional vertigo in the FCVM group were more than those in the SVM group （12[18.2%] and 0[0], χ²=3.171, P=0.002）. Mental anxiety（P<0.001）, neck stiffness（P=0.028）, and concentration difficulties（P=0.001） were more common in patients with FCVM at the end of the episode than in patients with SVM. Comorbid primary motion sickness combined was more common in FCVM group than in SVM group（49 cases[74.2%] and 25 cases[48.1%], χ²=2.906, P=0.004）. Conclusion:The onset of FCVM is earlier and the prognosis is often poor. Primary motion sickness can be used as a reference for the early diagnosis of FCVM.

Genome-Wide Identification and Characterization of Actin-Depolymerizing Factor (ADF) Family Genes and Expression Analysis of Responses to Various Stresses in Zea Mays L.

Actin-depolymerizing factor (ADF) is a small class of actin-binding proteins that regulates the dynamics of actin in cells. Moreover, it is well known that the plant ADF family plays key roles in growth, development and defense-related functions. Results: Thirteen maize (Zea mays L., ZmADFs) ADF genes were identified using Hidden Markov Model. Phylogenetic analysis indicated that the 36 identified ADF genes in Physcomitrella patens, Arabidopsis thaliana, Oryza sativa japonica, and Zea mays were clustered into five groups. Four pairs of segmental genes were found in the maize ADF gene family. The tissue-specific expression of ZmADFs and OsADFs was analyzed using microarray data obtained from the Maize and Rice eFP Browsers. Five ZmADFs (ZmADF1/2/7/12/13) from group V exhibited specifically high expression in tassel, pollen, and anther. The expression patterns of 13 ZmADFs in seedlings under five abiotic stresses were analyzed using qRT-PCR, and we found that the ADFs mainly responded to heat, salt, drought, and ABA. Conclusions: In our study, we identified ADF genes in maize and analyzed the gene structure and phylogenetic relationships. The results of expression analysis demonstrated that the expression level of ADF genes was diverse in various tissues and different stimuli, including abiotic and phytohormone stresses, indicating their different roles in plant growth, development, and response to external stimulus. This report extends our knowledge to understand the function of ADF genes in maize.

Genome-wide identification, phylogenetic and expression analysis of the maize HECT E3 ubiquitin ligase genes.

HECT (homologous to the E6AP carboxyl terminus) ubiquitin ligase genes (E3s) are enzymes with diverse functions influencing plant growth, development, and responses to abiotic stresses. However, there is relatively little information available regarding the maize HECT E3 gene family. In the present study, 12 maize HECT E3 genes (ZmUPL1 to ZmUPL12) were identified at the whole-genome level. The phylogenetic relationships, structures, and expression levels of the maize HECT E3 genes were then analyzed. On the basis of the constructed maximum likelihood phylogenetic tree, the HECT E3 genes were divided into six groups. The quantitative real-time polymerase chain reaction assay results revealed that all of the maize ZmUPL genes were expressed in most of the examined tissues and were responsive to three abiotic stresses. Considered together, the study results may provide a useful foundation for future investigations of maize stress-tolerance genes as well as functional analyses of the E3 enzymes in diverse agriculturally important crop species.

Prescription Value-Based Automatic Optimization of Importance Factors in Inverse Planning.

OBJECTIVE: An automatic method for the optimization of importance factors was proposed to improve the efficiency of inverse planning. METHODS: The automatic method consists of 3 steps: (1) First, the importance factors are automatically and iteratively adjusted based on our proposed penalty strategies. (2) Then, plan evaluation is performed to determine whether the obtained plan is acceptable. (3) If not, a higher penalty is assigned to the unsatisfied objective by multiplying it by a compensation coefficient. The optimization processes are performed alternately until an acceptable plan is obtained or the maximum iteration Nmax of step (3) is reached. RESULTS: Tested on 2 kinds of clinical cases and compared with manual method, the results showed that the quality of the proposed automatic plan was comparable to, or even better than, the manual plan in terms of the dose-volume histogram and dose distributions. CONCLUSIONS: The proposed algorithm has potential to significantly improve the efficiency of the existing manual adjustment methods for importance factors and contributes to the development of fully automated planning. Especially, the more the subobjective functions, the more obvious the advantage of our algorithm.

Genome-wide identification of AGO18b-bound miRNAs and phasiRNAs in maize by cRIP-seq.

BACKGROUND: Argonaute proteins (AGOs) are important players in the regulation of plant development by directing sRNAs to target mRNAs. In maize (Zea mays), AGO18b is a tassel-enriched and grass-specific AGO. Previous studies have shown that AGO18b is highly expressed in tassels during meiosis and negatively regulates determinacy of spikelet meristems. However, binding profile on RNAs and acting mechanisms of AGO18b remain unknown. RESULTS: In this study, we explored the binding profile of AGO18b in maize tassel by UV cross-linking RNA immunoprecipitation, followed by deep sequencing of these cDNA libraries (cRIP-seq), and systematically studied AGO18b-associated small RNAs and mRNAs by bioinformatics analysis. By globally analyzing the phased small-interfering RNA (phasiRNA) and miRNA abundance bound by AGO18b, we found AGO18b primarily binds to 21-nt phasiRNAs/miRNAs with a 5'-uridine and binds less strongly to 24-nt phasiRNAs with a 5'-adenosine in the premeiotic tassels. The abundance profile of AGO18b-associated miRNAs was different from their expression profile. Moreover, AGO18b strongly binds to miR166a-3p. We then obtained the AGO18b-bound mRNA targets of miR166a-3p by cRIP-seq, and confirmed the molecular function of AGO18b in regulating spikelet meristems. CONCLUSIONS: Our results indicated that AGO18b binds to phasiRNAs with obvious 5 prime end bias under different sRNA length. MiRNAs and their target mRNAs associated with AGO18b indicated the molecular mechanisms of AGO18b as a negative regulator of inflorescence meristem and tassel development through integrating both phasiRNAs and miRNA pathways, which extended our view of sRNA regulation in flower development and provided potential methods to control pollination in the future.

Expression analysis of Argonaute genes in maize (Zea mays L.) in response to abiotic stress.

BACKGROUND: Argonaute (AGO) protein is a kind of RNA binding protein that plays an integral role in the gene-silencing pathways guided by small RNAs. But there are few studies about the regulation of AGO genes responded to diverse abiotic stress in maize. RESULTS: In this study, we analyzed the expression of seventeen ZmAGO genes under heat, cold, salinity, drought and ABA treatments using quantitative PCR (qPCR). All ZmAGOs showed differential expression modes under various abiotic stress treatments. Two ZmAGOs (ZmAGO1a and ZmAGO5d) and other fifteen ZmAGOs exhibited specific up-regulation in response to heat separately. Several ZmAGO genes are very sensitive to cold stress, but many ZmAGO genes are slow to respond to NaCl treatment. Nine ZmAGO genes (ZmAGO1f, ZmAGO2b, ZmAGO4, ZmAGO5a/b/c, ZmAGO7, ZmAGO9 and ZmAGO18a/b) presented definite up-regulation in response to drought, which were similar to the pattern of gene regulation under abscisic acid (ABA) treatment. CONCLUSIONS: Various ZmAGO genes respond to different abiotic stress treatments. These results provide fundamental information and insights for the further study on the role of abiotic stress resistance genes in maize and provide basis for further study on the function of AGO genes in response to abiotic stress in maize.

[Progress in bHLH transcription factors regulating the response to iron deficiency in plants].

Iron is one of the essential mineral micronutrients for plants. Low concentrations of effective iron in soil can easily increase risk of plant iron deficiency. Several members of bHLH transcription factors family participate in the response to iron deficiency and play an important role in iron regulation of plants. In order to better understand the mechanism of iron deficiency response, an overview of the structure, classification, function and regulatory mechanism of bHLH transcription factors was given in this review as well as signaling pathway triggered by iron deficiency. It will provide theoretical basis and design strategies for cultivating iron deficiency tolerant or iron-rich crops using bHLH transcription factors.

Intra-annual wood formation of subtropical Chinese red pine shows better growth in dry season than wet season.

China's subtropical forests play a vital role in sequestering global carbon; therefore, it is critical to conduct a precise investigation of intra-annual wood formation in these ecosystems to clarify the mechanisms behind this. Two field experiments were established in Chinese subtropical forests to monitor weekly the intra-annual xylem formation of Pinus massoniana Lamb. from January to December 2015, using the recently developed micro-sampling approach. The effects of climate on wood formation were also assessed using linear or mixed models. Results indicate that there is an inactive period that might be semi-dormancy in subtropical pine ecosystems in January compared with the complete dormancy in temperate and boreal ecosystems and the fully active or short-term dormancy in tropical ecosystems. The duration of xylem formation of Chinese red pine in subtropical China in 2015 was 4-6 months longer than temperate and boreal forests. Moreover, trees were found to grow better during the dry season than the wet season, indicating that the Chinese red pine ecosystem is more strongly regulated by net energy than by environmental factors. Our findings indicate that China's subtropical pine forests may benefit from the expected longer dry seasons, possibly leading to better forest growth and improved carbon sequestration under continued climate warming.

Contributions of insects and droughts to growth decline of trembling aspen mixed boreal forest of western Canada.

Insects, diseases, fire and drought and other disturbances associated with global climate change contribute to forest decline and mortality in many parts of the world. Forest decline and mortality related to drought or insect outbreaks have been observed in North American aspen forests. However, little research has been done to partition and estimate their relative contributions to growth declines. In this study, we combined tree-ring width and basal area increment series from 40 trembling aspen (Populus tremuloides Michx.) sites along a latitudinal gradient (from 52° to 58°N) in western Canada and attempted to investigate the effect of drought and insect outbreaks on growth decline, and simultaneously partition and quantify their relative contributions. Results indicated that the influence of drought on forest decline was stronger than insect outbreaks, although both had significant effects. Furthermore, the influence of drought and insect outbreaks showed spatiotemporal variability. In addition, our data suggest that insect outbreaks could be triggered by warmer early spring temperature instead of drought, implicating that potentially increased insect outbreaks are expected with continued warming springs, which may further exacerbate growth decline and death in North America aspen mixed forests.

Neural Stem Cell-Based Regenerative Approaches for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, and demyelinating disorder of the central nervous system (CNS), which ultimately leads to axonal loss and permanent neurological disability. Current treatments for MS are largely comprised of medications that are either immunomodulatory or immunosuppressive and are aimed at reducing the frequency and intensity of relapses. Neural stem cells (NSCs) in the adult brain can differentiate into oligodendrocytes in a context-specific manner and are shown to be involved in the remyelination in these patients. NSCs may exert their beneficial effects not only through oligodendrocyte replacement but also by providing trophic support and immunomodulation, a phenomenon now known as "therapeutic plasticity." In this review, we first provided an update on the current knowledge regarding MS pathogenesis and the role of immune cells, microglia, and oligodendrocytes in MS disease progression. Next, we reviewed the current progress on research aimed toward stimulating endogenous NSC proliferation and differentiation to oligodendrocytes in vivo and in animal models of demyelination. In addition, we explored the neuroprotective and immunomodulatory effects of transplanted exogenous NSCs on T cell activation, microglial activation, and endogenous remyelination and their effects on the pathological process and prognosis in animal models of MS. Finally, we examined various protocols to generate genetically engineered NSCs as a potential therapy for MS. Overall, this review highlights the studies involving the immunomodulatory, neurotrophic, and regenerative effects of NSCs and novel methods aiming at stimulating the potential of NSCs for the treatment of MS.