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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.

Alcohol dehydrogenase (ADH) is essential to the formation of aromatic compounds in fruits. However, the evolutionary history and characteristics of ADH gene expression remain largely unclear in Rosaceae fruit species. In this study, 464 ADH genes were identified in eight Rosaceae fruit species, 68 of the genes were from pear and which were classified into four subgroups. Frequent single gene duplication events were found to have contributed to the formation of ADH gene clusters and the expansion of the ADH gene family in these eight Rosaceae species. Purifying selection was the major force in ADH gene evolution. The younger genes derived from tandem and proximal duplications had evolved faster than those derived from other types of duplication. RNA-Seq and qRT-PCR analysis revealed that the expression levels of three ADH genes were closely correlated with the content of aromatic compounds detected during fruit development.

ObjectiveMyelin oligodendrocyte glycoprotein-associated disorders (MOGADs) are a rare new neurological autoimmune disease with unclear pathogenesis. Since a linkage of the disease to the human leucocyte antigen (HLA) has not been shown, we here investigated whether MOGAD is associated with the HLA locus.MethodsHLA genotypes of 95 patients with MOGADs, assessed between 2016 and 2018 from three academic centres, were compared with 481 healthy Chinese Han individuals. Patients with MOGADs included 51 paediatric-onset and 44 adult-onset cases. All patients were seropositive for IgG targeting the myelin oligodendrocyte glycoprotein (MOG).ResultsPaediatric-onset MOGAD was associated with the DQB1*05:02–DRB1*16:02 alleles (OR=2.43; OR=3.28) or haplotype (OR=2.84) of HLA class II genes. The prevalence of these genotypes in patients with paediatric-onset MOGAD was significantly higher than healthy controls (padj=0.0154; padj=0.0221; padj=0.0331). By contrast, adult-onset MOGAD was not associated with any HLA genotype. Clinically, patients with the DQB1*05:02–DRB1*16:02 haplotype exhibited significantly higher expanded disability status scale scores at onset (p=0.004) and were more likely to undergo a disease relapse (p=0.030). HLA–peptide binding prediction algorithms and computational docking analysis provided supporting evidence for the close relationship between the MOG peptide subunit and DQB1*05:02 allele. In vitro results indicated that site-specific mutations of the predicted target sequence reduced the antigen–antibody binding, especially in the paediatric-onset group with DQB1*05:02 allele.ConclusionsThis study demonstrates a possible association between specific HLA class II alleles and paediatric-onset MOGAD, providing evidence for the conjecture that different aetiology and pathogenesis likely underlie paediatric-onset and adult-onset cases of MOGAD.

Preventing relapse by immunosuppressants (ISs) is critical for the prognosis of neuromyelitis optica spectrum disorder (NMOSD); however, the optimal duration of IS treatment is still under discussion. The objective was to explore the optimal duration of IS treatment and the risk of IS discontinuation for NMOSD.This cohort study was conducted at a major neurological center that housed the largest NMOSD database in South China. Eligible participants were patients with NMOSD undergoing IS treatment. The main outcome measures were changes in relapse risk based on IS treatment duration, clinical outcomes and predictors of relapse following IS discontinuation.In total, 343 patients were included in this study. The duration of IS treatment was strongly associated with a decrease in relapse risk (hazard ratio [HR] 0.53, p lt; 0.001). Continuous IS treatment resulted in decreased relapse HRs within 5 years of receiving IS medication, with a mild rebound starting at 5 years. Rituximab reduced the risk of NMOSD relapse to approximately zero within 3 years. The rate of relapse after IS withdrawal was high (77.5%). As opposed to other ISs, a delayed relapse following rituximab withdrawal was observed in this study. Longitudinal extensive transverse myelitis (HR = 2.023, p = 0.006) was associated with a higher risk of relapse after IS discontinuation.Long-term IS medication for NMOSD is generally suitable. Patients with longitudinal extensive transverse myelitis had a higher risk of relapse after IS discontinuation. Future studies should explore individualized strategies of rituximab maintenance treatment.

From the perspective of the role of T follicular helper (Tfh) cells in the destruction of tolerance in disease progression, more attention has been paid to their role in autoimmunity. To address the role of Tfh cells in neuromyelitis optica spectrum disorder (NMOSD) recurrence, serum C-X-C motif ligand 13 (CXCL13) levels reflect the effects of the Tfh cells on B-cell-mediated humoral immunity. We evaluated the immunobiology of the CXCR5+CD4+ Tfh cells in 46 patients with NMOSD, including 37 patients with NMOSD with an annual recurrence rate (ARR) of

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) causes major disability as a consequence of recurrent demyelinating events and neuronal loss. Biomarkers identifying different phenotypes of recurrence or tissue damage might be useful to guide individualized therapy. Herein, we evaluated serum neurofilament light chain (sNfL) as a potential biomarker in both adult and pediatric MOGAD patients. Forty-nine patients with MOGAD (37 adults, 12 children) and 71 healthy controls (HCs) (56 adults, 15 children) were enrolled prospectively from September 2019 to April 2021 at the Third Affiliated Hospital of Sun Yat-sen University and the Children's Hospital, Zhejiang University School of Medicine. sNfL levels were determined using ultrasensitive single-molecule array assay and correlated with clinical parameters. The sNfL levels in MOGAD adults in a relapsed state (median: 31.0 pg/mL) were higher than those in a remission state (8.1 pg/mL, p = 0.001) and in HC adults (10.3 pg/mL, p = 0.004). Similar results were observed in children (relapse: 46.8 pg/mL vs. remission: 13.1 pg/mL, p = 0.001; and vs. HCs: 8.2 pg/mL, p = 0.007) sNfL levels were correlated with recent relapses within 60 days (multivariate: β = 2.02, p = 0.003), seizures (multivariate: β = 2.50, p = 0.021) and brain lesions on magnetic resonance imaging (MRI) of a recent relapse (multivariate: β = 1.72, p = 0.012). Our study showed that sNfL levels are beneficial for identifying recent relapses and seizures and suggest that adult and pediatric MOGAD patients had similar sNfL levels.

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.

Phytophthora infestans (P. infestans) recently caused epidemics of tomato late blight. Our study aimed to identify the function of the SlMYBS2 gene in response to tomato late blight. To further investigate the function of SlMYBS2 in tomato resistance to P. infestans, we studied the effects of SlMYBS2 gene knock out. The SlMYBS2 gene was knocked out by CRISPR-Cas9, and the resulting plants (SlMYBS2 gene knockout, slmybs2-c) showed reduced resistance to P. infestans, accompanied by increases in the number of necrotic cells, lesion sizes, and disease index. Furthermore, after P. infestans infection, the expression levels of pathogenesis-related (PR) genes in slmybs2-c plants were significantly lower than those in wild-type (AC) plants, while the number of necrotic cells and the accumulation of reactive oxygen species (ROS) were higher than those in wild-type plants. Taken together, these results indicate that SlMYBS2 acts as a positive regulator of tomato resistance to P. infestans infection by regulating the ROS level and the expression level of PR genes.

Background Leaves, which are the most important organs of plants, can not only fix carbon sources through photosynthesis, but also absorb nutrients through transpiration. Leaf development directly determines the growth, flowering and fruiting of plants. There are many factors that affect leaf development, such as the growth environment, gene expression, and hormone synthesis. In this study, tomatoes were used to study the role of the transcription factor Solanum lycopersicum salt-related MYB1-like (SlSRM1-like) in the development of tomato leaves. Results Loss-of-function of the SlSRM1-like gene mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) resulted in abnormal tomato leaf morphology, including thinner leaves, wrinkled edges, raised veins, disordered edge veins, and left and right asymmetry. An analysis of the transcription levels of genes related to leaf development revealed that the expression of these genes was significantly altered in the SlSRM1-like mutants (SlSRM1-like-Ms). Moreover, the SlSRM1-like gene was expressed at higher transcription levels in young tissues than in old tissues, and its expression was also induced in response to auxin. In addition, the transcription levels of genes related to the auxin pathway, which regulates tomato growth and development, were severely affected in the SlSRM1-like-Ms. Therefore, it is hypothesized that the SlSRM1-like gene functions in the regulation of tomato leaf development through the auxin-related pathway. Conclusions In this study, we successfully knocked out the SlSRM1-like gene in the tomato variety Ailsa Craig using CRISPR technology and found that knockout of the SlSRM1-like gene resulted in abnormal development of tomato leaves. Further research indicated that SlSRM1-like regulated tomato leaf development through auxin-related pathways. The results provide an important reference for the functional study of other SRM1-like genes in plants and provide new insights into the regulation of leaf development in tomato and other plants.

Background The BAHD acyltransferase superfamily exhibits various biological roles in plants, including regulating fruit quality, catalytic synthesizing of terpene, phenolics and esters, and improving stress resistance. However, the copy numbers, expression characteristics and associations with fruit aroma formation of the BAHD genes remain unclear. Results In total, 717 BAHD genes were obtained from the genomes of seven Rosaceae, (Pyrus bretschneideri, Malus domestica, Prunus avium, Prunus persica, Fragaria vesca, Pyrus communis and Rubus occidentalis). Based on the detailed phylogenetic analysis and classifications in model plants, we divided the BAHD family genes into seven groups, I-a, I-b, II-a, II-b, III-a, IV and V. An inter-species synteny analysis revealed the ancient origin of BAHD superfamily with 78 syntenic gene pairs were detected among the seven Rosaceae species. Different types of gene duplication events jointly drive the expansion of BAHD superfamily, and purifying selection dominates the evolution of BAHD genes supported by the small Ka/Ks ratios. Based on the correlation analysis between the ester content and expression levels of BAHD genes at different developmental stages, four candidate genes were selected for verification as assessed by qRT-PCR. The result implied that Pbr020016.1, Pbr019034.1, Pbr014028.1 and Pbr029551.1 are important candidate genes involved in aroma formation during pear fruit development. Conclusion We have thoroughly identified the BAHD superfamily genes and performed a comprehensive comparative analysis of their phylogenetic relationships, expansion patterns, and expression characteristics in seven Rosaceae species, and we also obtained four candidate genes involved in aroma synthesis in pear fruit. These results provide a theoretical basis for future studies of the specific biological functions of BAHD superfamily members and the improvement of pear fruit quality.

Introduction The aim was to characterize the optical coherence tomography (OCT) angiography measures in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) and to evaluate their disease discrimination capacity. Methods Patients with MS (n = 83) and AQP4‐IgG‐seropositive NMOSD (n = 91) with or without a history of optic neuritis, together with healthy controls (n = 34), were imaged. The main outcome measures were peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell‐inner plexiform layer (GC‐IPL) thickness, macular vessel density (VD), and perfusion density (PD) in the superficial capillary plexus. Diagnostic accuracy was assessed using the area under the receiver operating characteristics curve. Results Compared with patients with MS, those with NMOSD had a significantly smaller average thickness of the pRNFL and GC‐IPL (80.0 [59.0; 95.8] μm versus 92.0 [80.2; 101] μm, p, In summary, our study compared the structure and flow between patients with MS and those with AQP4‐IgG‐positive NMOSD, indicating pathophysiological differences between them and suggesting that OCTA may have an additive effect as a biomarker in conjunction with routine OCT measurements. Combining OCTA and OCT may yield promising diagnostic properties in distinguishing both diseases.

Brain metastases (BM) remains the most cumbersome disease burden in patients with lung cancer. This study aimed to investigate whether serum brain injury biomarkers can indicate BM, to further establish related diagnostic models, or to predict prognosis of BM. This was a prospective study of patients diagnosed with lung cancer with BM (BM group), with lung cancer without BM (NBM group), and healthy participants (control group). Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were detected at baseline. We identified and integrated the risk factors of BM to establish diagnostic models. A total of 158 patients were included (n = 37, 57, and 64 in the BM, NBM, and control groups, respectively). Serum biomarker levels were significantly higher in the NBM group than in the control group. Higher serum NfL and GFAP concentrations were associated with BM (odds ratios, 3.06 and 1.79, respectively). NfL (area under curve [AUC] = 0.77, p

Funder: National Eye Research Centre (UK), Funder: NIHR Biomedical Research Centre, Funder: UK National Institute of Health Research (NIHR), Funder: Fight for Sight (UK), Funder: Isaac Newton Trust (UK), Aims: To compare macular structure and vasculature between neuromyelitis optica spectrum disorder (NMOSD) and primary open angle glaucoma (POAG) using optical coherence tomography angiography. Methods: NMOSD patients (n=124) with/without a history of optic neuritis (ON) (NMO+ON: 113 eyes; NMO-ON: 95 eyes), glaucomatous patients (n=102) with early/advanced glaucoma (G-E: 74 eyes; G-A: 50 eyes) and healthy controls (n=62; 90 eyes) were imaged. The main outcome measures were macular ganglion cell-inner plexiform layer (GC-IPL) thickness, vessel density (VD) and perfusion density (PD) in the superficial capillary plexus, and diagnostic capabilities of the parameters as calculated by area under the curve (AUC). Results: Significant losses in GC-IPL, VD and PD were detected in both patients with NMOSD and POAG. With matched losses in the peripapillary retinal nerve fibre layer, NMOSD group showed significant thinning of GC-IPL in the nasal-superior quadrant, whereas in POAG group, significant thinning was observed in the inferior and temporal-inferior quadrants. GC-IPL thinning was more prominent in the superior, nasal-superior and nasal-inferior quadrants in NMO+ON eyes. In G-A eyes, significant GC-IPL thinning was seen in the temporal-inferior quadrant. The specific structural parameters combining VD and foveal avascular zone (FAZ) indices showed the best diagnostic accuracies. The FAZ area in eyes with NMOSD was significantly smaller than the eyes of healthy controls and POAG. Conclusion: NMOSD and POAG have specific patterns of macular structural and vascular changes associated with pathophysiology. Our results indicate that FAZ could be a sensitive biomarker of macular changes in NMOSD.

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

Improved understanding of the genetic structure and genetic variation patterns in natural populations is an essential element of breeding programs that focus on forest species. Castanopsis fissa is an important, fast-growing evergreen species in southern China, where it is used for reforestation. We sampled 28 different C. fissa populations from three provinces in southern China and investigated their genetic variation and genetic relationship through an analysis of sequence-related amplified polymorphism (SRAP) markers. We acquired 236 electrophoretic bands from the 241 individuals analyzed by SRAP; 195 bands were polymorphic. Analysis of molecular variance (AMOVA) detected significant genetic variation within and among the populations; genetic variation among populations was smaller than variation within populations (p

Serum neurofilament light chain (sNfL) is a promising biomarker for neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS), but there is limited validation data in specific ethnic and disease groups.To investigate the levels of sNfL in a cohort of Chinese patients with NMOSD and compare sNfL levels in patients with different disease courses and treatments.We analysed sNfL levels in 153 Chinese patients with NMOSD (n = 51) and MS (n = 102) using single-molecule array (Simoa) technology. The sNfL levels were compared with those of 71 healthy controls from two centres in southern China. For each disease, we assessed correlations between sNfL and disease phases and treatments.Higher levels of sNfL were found in the patients with NMOSD [17.97 (10.55-27.94) pg/mL] and MS [15.83 (8.92-25.67) pg/mL] compared to healthy controls [10.09 (7.19-13.29) pg/mL, p 0.001]. No significant differences were found between the AQP4-IgG-positive NMOSD group and OCB-positive MS group.sNfL measured by Simoa technology is a potential candidate blood biomarker for the diagnosis and disease monitoring of NMOSD in Chinese patients, warranting further prospective and multicentre studies.

Our previous research confirmed the repression of SMADs signaling pathway inhibits the invasion, migration, and EMT in breast cancer MCF-7 and SKBR-3 cell lines by DNMT1 up-regulating CLDN6, but the mechanism is unclear. Western blot was performed to detect the expression of SMAD2, SMAD3, P-SMAD2, and P-SMAD3. Then RT-PCR was carried out to examine the expression of tight junctions and cell adhesion molecule E-cadherin. According to the gene sequence of Claudin6, shRNA was linked with the green fluorescent protein-expressing eukaryotic expression vector pGC silencer TMΜ6/Neo/GFP, and it was transfected into breast cancer MCF-7 cells and SKBR-3 cells. RT-PCR and western blot were applied to verify the Claudin6 gene-silencing effect. We observed cellular morphology with inverted microscope, analyzed the capacity for clone formation, and detected transepithelial electrical resistance. The level of MMP2, and MMP9 in the cells treated with or without SB431542 and MCF-7-shGFP, MCF-7-shClaudin-6, SKBR-3-shGFP, and SKBR-3-shClaudin-6 cells pretreated with SB431542 were examined by RT-PCR and western blot. The expressions of Claudin-6, occludin, and cell adhesion molecule E-cadherin were enhanced by SB431542. SB431542 transformed mesenchymal cell morphology into epithelial cell morphology, inhibited capacity for clone formation, increased transepithelial electrical resistance, and downregulated the expression of MMP2 and MMP9. Knock down of Claudin6 can abolish SB431542 effects. We conclude that Claudin6 mediates the effects of SB431542 on the biologic phenotypes of the breast cancer cells we studied. We speculate Claudin6-mediated the SB431542 inhibition of invasion, migration, and EMT in breast cancer cells via MMP2/9.

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.

We examined the prevalence of sex with older male partner (SWOMP) and its association with condomless anal intercourse (CAI) with male partners and unrecognized HIV infection among young men who have sex with men (MSM) in Shanghai, China. The analytic sample included 243 MSM who were 18-45 years and HIV negative or of unknown HIV serostatus. Older male partner refers to male sex partner who was at least 10 years older than themselves. Overall, 99 (43.0%) and 50 (20.7%) reported having SWOMP in lifetime and in the last 3 months, respectively. Having any CAI with male partners in the last 3 months was independently associated with SWOMP and sex with stable male partners in the last 3 months. Unrecognized HIV infection was independently associated with being HSV-2 positive and having any CAI with male partners as well as SWOMP in last 3 months. Sex with stable male partner in the last 3 months was also marginally significantly associated with unrecognized infection (p = 0.084). Older partner selection is common among young MSM in China. Prevention programs should incorporate education messages about the HIV risk associated with SWOMP. MSM should be informed that having condomless sex with stable partners may place them at HIV risk.

Additional file 2: Figure S1. Phylogenetic analysis of BAHD from Arabidopsis, Pyrus bretschneideri and Populus. The software MEGA 7.0 was used to construct the phylogenetic tree. The amino-acid sequences of Arabidopsis and Populus were obtained from phytozome (https://phytozome.jgi.doe.gov/pz/portal.html#).

Background Alcohol dehydrogenases (ADHs) are essential to plant growth and the formation of aromatic compounds in fruits. However, the evolutionary history and characteristics of ADH gene expression remain largely unclear in Chinese white pear ( Pyrus bretschneideri ) and other fruit species from the family Rosaceae.Results In this study, 464 ADH genes were identified in eight Rosaceae fruit species and 68 of the genes were from pear. Based on the analyses of phylogeny and conserved motifs, the pear ADH genes were classified into four subgroups (I, II, III, and IV). The chromosomal distribution of the genes was found to be uneven and numerous clusters of physically linked ADH genes were detected. Frequent single-gene duplication events were found to have contributed to the formation of ADH gene clusters and the expansion of the ADH gene family in these eight Rosaceae species. Purifying selection was the major force in ADH gene evolution. The younger genes derived from tandem and proximal duplications had evolved faster than those that derived from other types of duplication. RNA-sequencing and quantitative-real time-PCR analysis revealed that the expression levels of three ADH genes were closely correlated with the content of aromatic compounds that are found during fruit development.Conclusion Comprehensive analyses were conducted in eight Rosaceae species and 464 ADH genes were identified. The results of this study provide new insights into the evolution and expression characteristics of ADH family genes in pear and other Rosaceae species.

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

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.

Few studies have compared radiological features obtained on magnetic resonance imaging (MRI) between myelin oligodendrocyte glycoprotein antibody (MOG-ab)- and aquaporin 4 antibody (AQP4-ab)-positive patients. In this study, 77 MOG-ab and 92 AQP4-ab patients were enrolled. The results demonstrated that the brain MRI-based incidence of subcortical white matter lesions was higher in MOG-ab patients (p < .000) than in AQP4-ab patients and that the former therefore had a higher incidence of periventricular lesions (p = .003). The posterior limb of the internal capsule was more prone to lesions in MOG-ab patients (p = .019). Large lesions and U- or S-shaped lesions were also more frequent in MOG-ab (p < .000 and p = .013, respectively). Half of the MOG-ab patients had spinal cord involvement, and 36.5% presented with longitudinally extensive transverse myelitis (LETM). However, among the MOG-ab and AQP4-ab patients with spinal attack, there was no significant difference in the proportion with LETM (p = .057). In conclusion, a higher proportion of MOG-ab patients than AQP4-ab patients had brain lesions in white matter. Among MOG-ab patients who had an attack in the spinal cord, 65.5% also had LETM during the disease course. Conus medullaris lesions were rare in Chinese MOG-ab patients.

Due to health concerns surrounding the use of cobalt as a binder for tungsten carbide in cemented carbides there is a drive to find an alternative binder. Although there are many publications on ce ...

Sugar is an important component affecting fruit quality and taste and has been studied in many plants. Tomatoes are consumed in very large amounts worldwide, but to date, few reports on the quantitative trait loci (QTLs) for the sugar content in tomato fruits have been published. In this study, we analyzed the genetic model of the soluble sugar content in ripe tomato fruits and the reasons for the differences. We determined that the inheritance of the soluble sugar content in tomato fruits followed a negative dominance pattern, with a predominantly polygenic effect. Moreover, we identified two chromosomal regions by bulked-segregant analysis (BSA) sequencing analysis and initially screened 47 genes that may affect the soluble sugar content of tomato fruits.

Background Delayed multiple sclerosis (MS) diagnoses are not uncommon, an early diagnostic tool is urgently warranted. We aimed to develop an effective tool through electronic health records and machine learning techniques to early recognize MS patients from hospital visitors in China. Methods Two case sets were collected from January 2016 to December 2018. The training set had 239 MS and 1142 controls, and the test set had 23 MS and 92 controls. The utility of Extreme Gradient Boosting (XGBoost), Random Forest (RF), Naive Bayes, K-nearest-neighbor (KNN) and Support Vector Machine (SVM) in early diagnosis of MS was evaluated by the area under curve of receiver operating characteristic, precision, recall, specificity, accuracy and F1 score. Results The XGBoost performed the best and was used to generate the results. Thirty-four variables which were highly relevant to MS diagnosis were set for the XGBoost model, and their relative importance with MS were ranked. The training set recall was 0.632, with a precision of 0.576, and the test set recall was 0.609, with a precision of 0.609. Our study found that 61%, 51%, and 49% of the patients could be diagnosed with MS, 1, 2, and 3 years earlier than their real diagnostic time point, respectively. Conclusions A diagnostic tool for early MS recognition based on the XGBoost model and electronic health records were developed to help reduce diagnostic delays in MS.

CO2 laser annealing of SiGe core, glass-clad optical fibers is a powerful technique for the production of single-crystal cores with spatially varying Ge concentrations. Laser power, laser scan speed and cooling air flow alter the Ge distribution during annealing. In this work, near-single crystal fibers exhibiting a central axial feature with peak Ge concentration ∼15 at% higher than the exterior of the semiconductor core have been prepared. Preferential transmission of near infrared radiation through the Ge-rich region, and spectral data confirm its role as a waveguide within the semiconductor core. This proof-of-concept step toward crystalline double-clad structures is an important advancement in semiconductor core optical fibers made using the scalable molten core method. © 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Genetic parameters for height (H), diameter at breast height (DBH), stem straightness (STR), and under crown clear bole height (CH) of loblolly pine (Pinus taeda L.) were estimated for 255 families (209 open pollinated (OP) and 46 controlled pollinated (CP) families) using a family model and an individual tree model at age 1, 2, 3, 5, 11, and 15 years. Heritability estimates for growth traits of individual trees at age 11 years were the highest (0.17-0.78), and those at age 15 years were the lowest (0.05-0.74). Heritability estimates for DBH, STR, and CH were lower than those for H. Genetic correlations between H and DBH were generally strongly positive, attained a maximum values at age 2 to 3, and declined slightly thereafter. The genetic correlations between CH at age 11 and both H and DBH at different ages were moderate. Age-age genetic correlations for growth traits were moderate to high (0.56-0.91) at age 5 for half-rotation age (15 years), indicating the opportunity exists for early selection. Indirect selection from the age 5 to 11 years for H and DBH could be expected to produce gains of over 50% and 35% respectively, for these two ages, relative to direct selection at age 15. Efficiencies of early selection for H and DBH indicated that growth at maturity could be improved by early selection.

Quantitative trait locus (QTL) detection was carried out for growth traits in 122 F1 progenies of Pinus elliottii var. elliottii (PEE) × P. caribaea var. hondurensis (PCH) hybrid. The PCH male parent linkage map contained 108 markers in 16 linkage groups, while the PEE female parent contained 93 markers in 19 linkage groups. Sequence-related amplified polymorphism (SRAP), microsatellite (SSR), expressed sequence tag polymorphism (ESTP) and inter-simple sequence repeat (ISSR) were selected from an existing linkage map. Growth traits investigated were height at age five (HT05) and six years (HT06), diameter at breast height at age five (DBH05) and six years (DBH06) and annual growth from age five to six years of height (AGHT) and diameter at breast height (AGDBH). Kruskal-Wallis and interval mapping approaches were used to estimate levels of significance, the number of QTLs, the percentage of the phenotypic variation explained by each of QTLs and their positions on the genetic linkage maps. Twenty six QTLs with significance levels p < 0.05 were detected on the parental maps for the six growth traits, which explained more than 15% of the phenotypic variation, suggesting an existence of major-effect genes. Several QTLs had the pleiotropy controlling more than one single growth trait. Overall, the proportion of phenotypic variation explained by QTLs ranged from 5.9% to 40.6% for HT05 and HT06, from 6.6% to 42.0% for DBH05 and DBH06 and from 5.8% to 22.3% for AGHT and AGDBH. The results from this study provide a basis for marker-aided selection (MAS) in PEE × PCH hybrids.