First report of leaf blight caused by Stemphylium lycopersici on Salvia splendens in China.

Salvia splendens is a popular ornamental plant in China with extensive potentials, including value in traditional Chinese medicine and in environmental restoration function (Li et al. 2008). In September 2019, leaf blight disease was observed on road side plants of S. splendens in Bayi park, Nanchang city, Jiangxi province, China. The typical symptoms appeared as irregular necrotic spots or leaf blight, accompanied by extensive scorch necrosis or ultimately defoliation. Small segments cut from diseased leaves were surface sterilized in a 2% sodium hypochlorite solution for 2 min and rinsed three times with sterile distilled water. Then, the samples were placed on potato dextrose agar (PDA) plates incubated at 25°C in darkness. Pure cultures were obtained by the hyphal tip method. Morphologically, all 11 colonies were identical to each other on PDA. Two strains, YZU 191468 and YZU 191481, were selected for further study and deposited in the Fungal Herbarium of Yangtze University (YZU), Jingzhou, Hubei, China. The 7-day-old colonies were circular, 53 to 56 mm in diameter, and consisted of white mycelium with a buff margin, and were cinnamon colored in the center of the reverse side. To examine conidial morphology, the mycelium was transferred onto potato carrot agar (PCA) and incubated at 23°C with a period of 8 h light/16 h dark for 7 days. Conidia were normally solitary or two in a chain, ellipsoid or long ellipsoid, beakless, 10 to 23×30 to 60 µm in size (n=50). Based on morphology, the isolates were consistent with Stemphylium lycopersici (Yamamoto 1960). To confirm the identification, genomic DNA was extracted from both isolates and used to amplify the internal transcribed spacer rDNA region (ITS), glyceraldehydes-3-phosphate dehydrogenase (GAPDH) and calmodulin (CAL) genes with primer pairs ITS5/ITS4, gpd1/gpd2, and CALDF1/CALDR2, respectively (Woudenberg et al. 2017). Sequences were deposited in GenBank with accession numbers OP564983 and OP564984 (ITS), OP892529 and OP892530 (GAPDH), OP584970 and OP584971 (CAL). A neighbor-joining tree was constructed with Mega 7.0 based on the combined dataset with 1,000 bootstrap replicates. The resulting phylogenetic tree showed that the strains from S. splendens clustered with S. lycopersici (CBS 122639 and CBS 124980) supported with 100% bootstrap values. The molecular analyses confirmed that the species causing leaf blight symptoms was S. lycopersici. To test pathogenicity, healthy leaves of S. splendens were surface sterilized and inoculated by mycelium blocks (6 mm in diameter) and spore suspension (1×106 spore/mL) of representative strains YZU 191468 and YZU 191481, respectively. Controls were inoculated with blocks of PDA and sterile water. Each strain was inoculated on three leaves of a plant. One clean plant was used as control. The test was replicated three times. After inoculation, the plants were covered with plastic bags and incubated in a greenhouse (25℃, 80 % relative humidity, 8 h light/16 h dark). After 5 days, the inoculated leaves exhibited dark brown spots with white mycelium, followed by withering of necrotic tissues. There were no symptoms observed on the controls. The fungal isolates inoculated leaves had the same morphological characteristics as the strains used for inoculation. S. lycopersici has been found on eggplant and Zinnia elegans in China (He et al. 2019; Yang et al. 2017). To the best of our knowledge, this is the first report of S. lycopersici causing leaf blight on S. splendens in China. This finding offers a new reference for the management and control of S. splendens leaf diseases in China.

The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer's disease continuum participants.

BACKGROUND: Glymphatic dysfunction is a crucial pathway for dementia. Alzheimer's disease (AD) pathologies co-existing with cerebral small vessel disease (CSVD) is the most common pathogenesis for dementia. We hypothesize that AD pathologies and CSVD could be associated with glymphatic dysfunction, contributing to cognitive impairment. METHOD: Participants completed with amyloid PET, diffusion tensor imaging (DTI), and T2 fluid-attenuated inversion-recovery (FLAIR) sequences were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI). White matter hyperintensities (WMH), the most common CSVD marker, was evaluated from T2FLAIR images and represented the burden of CSVD. Amyloid PET was used to assess Aß aggregation in the brain. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, the burden of enlarged perivascular spaces (PVS), and choroid plexus volume to reflect glymphatic function. The relationships between WMH burden/Aß aggregation and these glymphatic markers as well as the correlations between glymphatic markers and cognitive function were investigated. Furthermore, we conducted mediation analyses to explore the potential mediating effects of glymphatic markers in the relationship between WMH burden/Aß aggregation and cognition. RESULTS: One hundred and thirty-three participants along the AD continuum were included, consisting of 40 CN - , 48 CN + , 26 MCI + , and 19 AD + participants. Our findings revealed that there were negative associations between whole-brain Aß aggregation (r = - 0.249, p = 0.022) and WMH burden (r = - 0.458, p < 0.001) with DTI-ALPS. Additionally, Aß aggregation (r = 0.223, p = 0.041) and WMH burden (r = 0.294, p = 0.006) were both positively associated with choroid plexus volume. However, we did not observe significant correlations with PVS enlargement severity. DTI-ALPS was positively associated with memory (r = 0.470, FDR-p < 0.001), executive function (r = 0.358, FDR-p = 0.001), visual-spatial (r = 0.223, FDR-p < 0.040), and language (r = 0.419, FDR-p < 0.001). Conversely, choroid plexus volume showed negative correlations with memory (r = - 0.315, FDR-p = 0.007), executive function (r = - 0.321, FDR-p = 0.007), visual-spatial (r = - 0.233, FDR-p = 0.031), and language (r = - 0.261, FDR-p = 0.021). There were no significant correlations between PVS enlargement severity and cognitive performance. In the mediation analysis, we found that DTI-ALPS acted as a mediator in the relationship between WMH burden/Aß accumulation and memory and language performances. CONCLUSION: Our study provided evidence that both AD pathology (Aß) and CSVD were associated with glymphatic dysfunction, which is further related to cognitive impairment. These results may provide a theoretical basis for new targets for treating AD.

Chromosome-level genome assembly of the Asian citrus psyllid, Diaphorina citri.

Diaphorina citri is a global citrus pest. As a vector insect, it can transmit the causative agents of citrus huanglongbing, causing irreversible losses to the citrus industry. The acquisition of genomic information can provide a molecular genetic basis for effective control of D. citri. Here, the DNBSEQ™ , Oxford Nanopore Technologies, and Hi-C technologies are applied to generate a high-quality chromosome-level genome of D. citri. The genome size of D. citri was 523.78 Mb with a scaffold N50 of 47.05 Mb distributed on 13 chromosomes. A total of 250.64 Mb (47.85%) repeat sequences and 24 048 protein-coding genes were predicted. Genome resequencing of female and male individuals indicated that the sex chromosome system of D. citri is XO. Phylogenetic analysis demonstrated that D. citri and Pachypsylla venusta, which separated from their most recent common ancestor about 336.62 million years ago, were the most closely related. Additionally, we identified genes potentially involved in detoxification metabolism, pathogen transmission, and honeydew secretion for further investigation. The high-quality genome provides an important reference for developing effective management strategies of D. citri.

Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma.

BACKGROUND: Accurate histologic and molecular genetic diagnosis is critical for the pathogenesis study of pediatric patients with lymphoblastic lymphoma (LBL). Optical genome mapping (OGM) as all-in-one process allows the detection of most major genomic risk markers, which addresses some of the limitations associated with conventional cytogenomic testing, such as low resolution and throughput, difficulty in ascertaining genomic localization, and orientation of segments in duplication, inversions, and insertions. Here, for the first time, we examined the cytogenetics of 5 children with LBL using OGM. METHODS: OGM was used to analyze 5 samples of pediatric LBL patients treated according to the modified NHL-BFM95 backbone regimen. Whole-exon Sequencing (WES) was used to confirm the existence of structural variants (SVs) identified by OGM with potentially clinical significance on MGI Tech (DNBSEQ-T7) platform. According to the fusion exon sequences revealed by WES, the HBS1L :: AHI1 fusion mRNA in case 4 was amplified by cDNA-based PCR. RESULTS: In total, OGM identified 251 rare variants (67 insertions, 129 deletions, 3 inversion, 25 duplications, 15 intrachromosomal translocations, and 12 interchromosomal translocations) and 229 copy number variants calls (203 gains and 26 losses). Besides all of the reproducible and pathologically significant genomic SVs detected by conventional cytogenetic techniques, OGM identified more SVs with definite or potential pathologic significance that were not detected by traditional methods, including 2 new fusion genes, HBS1L :: AHI1 and GRIK1::NSDHL , which were confirmed by WES and/or Reverse Transcription-Polymerase Chain Reaction. CONCLUSIONS: Our results demonstrate the feasibility of OGM to detect genomic aberrations, which may play an important role in the occurrence and development of lymphomagenesis as an important driving factor.

Effects of Candidatus Liberibacter asiaticus infection on metagenome of Diaphorina citri gut endosymbiont.

Asian citrus psyllid (Diaphorina citri, D. citri) is the important vector of "Candidatus Liberibacter asiaticus" (CLas), associated with Huanglongbing, the most devastating citrus disease worldwide. CLas can affect endosymbiont abundance of D. citri. Here, we generated the high-quality gut endosymbiont metagenomes of Diaphorina citri on the condition of CLas infected and uninfected. The dataset comprised 6616.74 M and 6586.04 M raw reads, on overage, from CLas uninfected and infected psyllid strains, respectively. Taxonomic analysis revealed that a total of 1046 species were annotated with 10 Archaea, 733 Bacteria, 234 Eukaryota, and 69 Viruses. 80 unique genera in CLas infected D. citri were identified. DIAMOND software was used for complement function research against various functional databases, including Nr, KEGG, eggNOG, and CAZy, which annotated 84543 protein-coding genes. These datasets provided an avenue for further study of the interaction mechanism between CLas and D. citri.

High CO2 - and pathogen-driven expression of the carbonic anhydrase ßCA3 confers basal immunity in tomato.

Atmospheric CO2 concentrations exert a strong influence on the susceptibility of plants to pathogens. However, the mechanisms involved in the CO2 -dependent regulation of pathogen resistance are largely unknown. Here we show that the expression of tomato (Solanum lycopersicum) ß-CARBONIC ANHYDRASE 3 (ßCA3) is induced by the virulent pathogen Pseudomonas syringae pv. tomato DC3000. The role of ßCA3 in the high CO2 -mediated response in tomato and two other Solanaceae crops is distinct from that in Arabidopsis thaliana. Using ßCA3 knock-out and over-expression plants, we demonstrate that ßCA3 plays a positive role in the activation of basal immunity, particularly under high CO2 . ßCA3 is transcriptionally activated by the transcription factor NAC43 and is also post-translationally regulated by the receptor-like kinase GRACE1. The ßCA3 pathway of basal immunity is independent on stomatal- and salicylic-acid-dependent regulation. Global transcriptome analysis and cell wall metabolite measurement implicate cell wall metabolism/integrity in ßCA3-mediated basal immunity under both CO2 conditions. These data not only highlight the importance of ßCA3 in plant basal immunity under high CO2 in a well-studied susceptible crop-pathogen system, but they also point to new targets for disease management strategies in a changing climate.

A Plant Phytosulfokine Peptide Initiates Auxin-Dependent Immunity through Cytosolic Ca2+ Signaling in Tomato.

Phytosulfokine (PSK) is a disulfated pentapeptide that is an important signaling molecule. Although it has recently been implicated in plant defenses to pathogen infection, the mechanisms involved remain poorly understood. Using surface plasmon resonance and gene silencing approaches, we showed that the tomato (Solanum lycopersicum) PSK receptor PSKR1, rather than PSKR2, functioned as the major PSK receptor in immune responses. Silencing of PSK signaling genes rendered tomato more susceptible to infection by the economically important necrotrophic pathogen Botrytis cinerea Analysis of tomato mutants defective in either defense hormone biosynthesis or signaling demonstrated that PSK-induced immunity required auxin biosynthesis and associated defense pathways. Here, using aequorin-expressing tomato plants, we provide evidence that PSK perception by tomato PSKR1 elevated cytosolic [Ca2+], leading to auxin-dependent immune responses via enhanced binding activity between calmodulins and the auxin biosynthetic YUCs. Thus, our data demonstrate that PSK acts as a damage-associated molecular pattern and is perceived mainly by PSKR1, which increases cytosolic [Ca2+] and activates auxin-mediated pathways that enhance immunity of tomato plants to B. cinerea.

YEATS4 promotes the tumorigenesis of pancreatic cancer by activating beta-catenin/TCF signaling.

Beta-catenin/TCF signaling has been reported to promote the growth and metastasis of pancreatic cancer cells. However, the regulation for the beta-catenin/TCF transcriptional complex remains largely unknown. Here, we have found that YEATS4 is a positive regulator for Beta-catenin/TCF signaling. The expression of YEATS4 was elevated in clinical pancreatic cancer samples and pancreatic cancer mouse model. Up-regulation of YEATS4 promoted the growth, migration and invasion of pancreatic cancer cells, while knocking down the expression of YEATS4 inhibited the growth, migration, invasion and metastasis of pancreatic cancer cells. Moreover, the mechanism study revealed that YEATS4 interacted with beta-catenin and activated beta-catenin/TCF signaling. Furthermore, knocking down the expression of YEATS4 impaired the malignant transformation of normal pancreatic cells (HPDE6C7) by the oncogenic Ras. Taken together, our study demonstrated the oncogenic roles of YEATS4 in the progression of pancreatic cancer by activating beta-catenin/TCF signaling and suggested that YEATS4 might be a promising therapeutic target for pancreatic cancer.

Involvement of ubiquitin-conjugating enzyme E2C in proliferation and invasion of prostate carcinoma cells.

Ubiquitin-conjugating enzyme E2C (UBE2C) has been found to participate in the process of several cancers. However, the role of UBE2C in prostate cancer has not been reported. To investigate the function of UBE2C in prostate cancer, several methods were used. UBE2C promoted the proliferation and viability of prostate cancer cells through MTT and colony formation assay and increased the number of invaded or migrated cells in Matrigel or Transwell assay based on its function of inducing EMT. UBE2C also promoted tumor formation in vivo. Our results suggest that UBE2C acts as an oncogene in prostate cancer progression and may be a candidate marker of diagnosis for this disease.

Comparison of MRI and endoscope ultrasound detection in preoperative T/N staging of gastric cancer.

Gastric cancer is a common malignancy and cause of mortality. The aim of this study was to evaluate the accuracy of magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) detection in preoperative clinical T/N staging in gastric cancer. Thirty-eight patients diagnosed with gastric cancer by gastroscopy and pathological examination were included in the study. All 38 patients underwent MRI and EUS detection prior to surgery. The accuracy of MRI, EUS and MRI+EUS was evaluated according to postoperative pathological staging. Results identified the accuracy of EUS, MRI and EUS+MRI in T clinical staging to be 86.64, 73.68 and 89.47%, respectively (MRI vs. EUS+MRI, P=0.035), while the accuracy for N clinical staging was 65.78, 68.42 and 71.05%, respectively (P>0.05). The accuracy rate in EUS and EUS+MRI detection in N0 stage was markedly higher compared with that in MRI (100 vs. 86.67%, P=0.032), whereas the rate in EUS detection in N2 stage was lower compared with that in MRI and EUS+MRI (45.45 vs. 54.54%, P=0.021). Thus, both MRI and EUS had a higher accuracy in preoperative T/N staging. Additionally, the accuracy rate was improved significantly when the two procedures were combined.

EphB4 is overexpressed in papillary thyroid carcinoma and promotes the migration of papillary thyroid cancer cells.

EphB4 tyrosine kinase receptor has been involved in various physiologic and pathologic processes, and the role of the EphB4 in tumorigenesis has recently attracted much interest. However, its function in papillary thyroid carcinoma remains poorly understood. In this study, we explored the function of EphB4 in papillary thyroid carcinoma. We found that the expression of EphB4 was significantly upregulated in clinical samples. Overexpression of EphB4 in papillary thyroid carcinoma cell lines accelerated cell migration. In contrast, downregulation of EphB4 inhibited cell migration and suppressed in vivo tumor metastasis. Furthermore, we showed that EphB4 promoted cell migration by inhibiting the phosphorylation of FAK and paxillin. Moreover, EphB4 promoted cell migration in a kinase-independent manner. Taken together, our findings suggest that EphB4 plays an important role in the progression of papillary thyroid carcinoma by stimulating cell migration and EphB4 might be a potential therapeutic target in papillary thyroid carcinoma.

Effect of mitofusin 2 overexpression on the proliferation and apoptosis of high-glucose-induced rat glomerular mesangial cells.

BACKGROUND: Mitofusin 2 (Mfn2) regulates mitochondrial morphology and associated signaling pathways. However, the role of Mfn2 in kidney disease is not fully understood. The present study aimed to investigate the effects of Mfn2 overexpression on high-glucose-induced cell proliferation and apoptosis. Another objective was to explore the possible underlying signal transduction mechanisms in a rat glomerular mesangial cell (GMC) line. METHODS: After adenovirus-mediated Mfn2 gene transfection, Mfn2 expression was detected by real-time PCR. Time-dependent concentration changes in Mfn2 and relevant proteins induced by high glucose were investigated to define the optimal time for research. The protein expression levels of Mfn2, proliferating cell nuclear antigen (PCNA), p-Akt, p-ERK1/2 and Bcl-2 were examined on Western blots. Cell proliferation was detected by the CCK-8 method. Apoptosis was analyzed by flow cytometry. RESULTS: Mfn2 gene expression was successfully increased via adenovirus mediation. The correlation of Mfn2 expression with p-ERK1/2 and phosphorylated Akt was significant 48 hours after high-glucose stimulation. p-ERK1/2 was increased by high glucose, but was inhibited by overexpressed Mfn2. Changes in the PCNA and GMC proliferative level coincided with p-ERK1/2. Overexpressed Mfn2 significantly inhibited Akt phosphorylation and Bcl-2 expression. The apoptosis rate increased in the AdMfn2 group. CONCLUSIONS: Overexpressed Mfn2 could alleviate GMC proliferation and increase apoptosis. Subsequently, cellular quantity is maintained, which may contribute to reversing early diabetic nephropathy pathological changes. Mfn2 may perform its activities through the MAPK/ERK and PI3K/Akt signal pathways in correlation with proliferation and apoptosis.

Up-regulated miR155 reverses the epithelial-mesenchymal transition induced by EGF and increases chemo-sensitivity to cisplatin in human Caski cervical cancer cells.

The epithelial-mesenchymal transition (EMT) induced by EGF promotes cervical cancer progression; however, the mechanisms underlying the EGF-induced EMT remain unclear. In this study, we reported that miR155 overexpression suppressed EGF-induced EMT, decreased migration/invasion capacities, inhibited cell proliferation and increased the chemo-sensitivity to DDP in human Caski cervical cancer cells. Further, the overexpression of miR155 increased TP53 expression but reduced SMAD2, and CCND1 expression levels. These data suggest that miR155 negatively regulates EGF-induced EMT. We conclude that miR155 does not act as an oncogene but as a tumour suppressor in Caski cells.