Integrated transcriptome and metabolome profiling reveals mechanisms underlying the infection of Cytospora mali in "Jin Hong" branches.

Introduction: Valsa canker, caused by Cytospora mali, is a destructive disease in apple production. However, the mechanism by which apple defend against C. mali infection remains unclear. Methods: In this study, the integrative transcriptional and metabolic analysis were used to investigate the responses of the 'Jin Hong' apple branches to the invasion of C. mali. Results and Discussion: Results showed that the differentially expressed genes were mainly enriched in the pathways of carbon metabolism, photosynthesis-antenna proteins, and biosynthesis of amino acids pathways. Additionally, the differentially accumulated metabolites were significantly enriched in aminoacyl-tRNA biosynthesis, fructose and mannose metabolism, and alanine, aspartate, and glutamate metabolism pathways. Conjoint analysis revealed that C. mali infection significantly altered 5 metabolic pathways, 8 highly relevant metabolites and 15 genes of apples. Among which the transcription factors WRKY and basic domain leucine zipper transcription family were induced, the α-linolenic acid and betaine were significantly accumulated in C. mali infected apple stems. This work presents an overview of the changes in gene expression and metabolic profiles in apple under the inoculation of C. mali, which may help to further screen out the mechanism of plant-pathogen interaction at the molecular level.

Arthroscopic Treatment of Popliteal Cyst Through the Posterior Portal: A Comprehensive Clinical Study.

BACKGROUND A popliteal cyst, often perceived as benign, poses potential harm and symptoms. This study focused on arthroscopic treatment through the posterior knee portal at our medical center, aiming to assess its efficacy, safety, and long-term outcomes compared to traditional methods. MATERIAL AND METHODS A retrospective analysis of 20 patients (9 males and 11 females) with symptomatic popliteal cysts (January 2020 to December 2022) undergoing arthroscopic treatment via the posterior knee portal was conducted. Data on demographics, clinical presentation, preoperative imaging, surgical techniques, intraoperative findings, and postoperative Rauschning and Lindgren scores were collected and analyzed. RESULTS With a mean follow-up of 13.6 months (range: 12 to 36 months), all patients had associated intra-articular lesions and were treated. Degenerative cartilage damage was most common (65.0% of cases). The Rauschning and Lindgren score significantly improved after surgery (P<0.05), with no recurrence evident on MRI in any patients. CONCLUSIONS Arthroscopic treatment through the posterior knee portal has good potential for popliteal cyst management. This minimally invasive approach offers benefits such as direct visualization, precise cyst excision, and concurrent treatment of intra-articular pathologies.

Overexpression of RAD54L attenuates osteoarthritis by suppressing the HIF-1α/VEGF signaling pathway: Bioinformatics analysis and experimental validation.

Osteoarthritis (OA) is a widespread chronic, progressive, degenerative joint disease that causes pain and disability. Current treatments for OA have limited effectiveness and new biomarkers need to be identified. Bioinformatics analysis was conducted to explore differentially expressed genes and DNA repair/recombination protein 54 L (RAD54L) was selected. We firstly overexpressed RAD54L in interleukin-1ß (IL-1ß)-induced human articular chondrocytes or in OA rats to investigate its effect on OA. Chondrocyte viability and apoptotic rate were measured by Cell Counting Kit-8 and flow cytometry, respectively. Then we evaluated OA severity in vivo by Hematoxylin-eosin staining and Osteoarthritis Research Society International standards. The expression of inflammatory mediators was tested by enzyme-linked immunosorbent assay. Finally, western blot was performed to determine the relative expression level of hypoxia-inducible factors 1α (HIF-1α) and vascular endothelial growth factor (VEGF). Overexpression of RAD54L promoted cell viability and attenuated apoptosis in IL-1ß-induced human chondrocytes. A lower Osteoarthritis Research Society International score and a remarkable alleviation of chondrocyte disordering and infiltration of inflammatory cells were found in cartilage tissues of OA rats after overexpressing RAD54L. The inflammatory response induced by OA was decreased by RAD54L overexpression in vitro and in vivo. In addition, RAD54L overexpression decreased the relative expression level of HIF-1α and VEGF. Overexpression of RAD54L could attenuate OA by suppressing the HIF-1α/VEGF signaling pathway, indicating that RAD54L may be a potential treatment target for OA.

Distinctive presentation of neurobrucellosis as myelitis: A case report and literature review.

ABSTRACT: Brucellosis is a zoonotic infectious allergic disease caused by Brucella that is widely distributed throughout the world. Brucella can invade various systems of the human body, such as the joints, the reproductive system, the spine, and the nervous system. Among patients with brucellosis, neurobrucellosis (NB) mainly manifests as nervous system symptoms in only 1.7-10% of patients and can cause a misdiagnosis. We reported a case of NB that presented as myelitis as the main clinical presentation and reviewed the relevant literature. It is suggested that clinicians should consider NB, especially atypical neurological symptoms, when there is a suspicious contact history.

Mechanism of Dendrobium Nobile Polysaccharide Inhibition of Ferroptosis in Rats with Spinal Cord Injury.

BACKGROUND: It has been reported that ferroptosis participates in the pathophysiological mechanism of spinal cord injury (SCI). Our preliminary experiments verified that dendrobium nobile polysaccharide (DNP) improved the behavioral function of SCI rats. Therefore, the purpose of this study was to examine the role of DNP on ferroptosis and its neuroprotective mechanism in SCI rats. METHODS: Adult female sprague dawley (SD) rats were exposed to SCI by Allen's method, followed by an intragastric injection of 100 mg/kg DNP per day for 2 weeks. Behavioral features were verified by the Basso-Beattie-Bresnahan (BBB) scale and footprint evaluation. Iron content and glutathione (GSH) were assessed spectrophotometrically. Mitochondrial morphology was examined by transmission electron microscopy. The expression of ferroptosis-related genes, including System Xc- light chain (xCT), G-rich RNA sequence binding Factor 1 (GRSF1) and glutathione peroxidase 4 (Gpx4), was examined by real-time polymerase chain reaction (PCR) and western blot. The spinal cavity was defined using hematoxylin-eosin (HE) staining, and neuronal modifications were detected by immunofluorescence. RESULTS: Compared with the SCI group, the BBB score of rats in the DNP group increased at 7 d, 14 d, 21 d, and 28 d. The differences between the two groups were statistically significant. At 12 h post-injury the iron content began to decrease. At 24 h post-injury the iron content decreased significantly in the DNP group. The morphological changes of the mitochondrial crest and membrane in the DNP group were ameliorated within 24 h. Compared with the sham group, the expression of xCT, GSH, Gpx4, and GRSF1 were significantly reduced after SCI. After DNP treatment, the expression of xCT, Gpx4, and GSH were higher. The tissue cavity area was significantly reduced and the amount of NeuN+ cells was increased in the DNP group at 14 d and 28 d after SCI. CONCLUSIONS: DNP facilitated the post-injury recovery in SCI rats via the inhibition of ferroptosis.

First Report of Powdery Mildew caused by Erysiphe astragali on Sphaerophysa salsula.

Sphaerophysa salsula (Pall.) DC., also known as Yang Liao Pao, belongs to the Leguminosae family and is the only existing species in the Sphaerophysa genus. S. salsula is tolerance to cold, high salt, and alkaline soil, it is widely cultivated in China as a forage crop, and used as a Chinese folk medicine to treat hypertension (Ma et al., 2002). In 2023, signs and symptoms similar to powdery mildew were found on S. salsula planted in Tumd left (40.515°N, 110.424°E), Baotou City, Inner Mongolia Autonomous Region, China. The white powdery substance covered 90% of the leaf area, and the infected plants showed weak growth and senescence. More than 80% of plants (n=200) had these powdery mildew-like symptoms. Hyphal appressoria are solitary, conidiophores have few branches and septa. Conidia are cylindrical to clavate, 25-32 µm long and 8-15 µm wide (n=30), conidia form single subapical germ tubes, straight to curved-sinuous, with swollen apex or distinctly lobed conidial appressorium. Based on these morphological characteristics, the fungus was tentatively identified as an Erysiphe sp. (Schmidt and Braun 2020). Fungal structures were isolated from diseased leaves, and genomic DNA of the pathogen was extracted using the method described by Zhu et al. (2022). The internal transcribed spacer (ITS) region was amplified by PCR using the primers PMITS1/PMITS2 (Cunnington et al. 2003) and the amplicon sequenced by Invitrogen (Shanghai, China). The powdery mildew strain, named as KMD (GenBank accession no.: PP267067), showed an identity of 100% (645/645bp) with Erysiphe astragali, a powdery mildew reported on Astragalus glycyphyllos in Golestan, Iran (GenBank: OP806834) and identity of 99.6% (643/645bp) with Erysiphe astragali (GenBank: MW142495), a powdery mildew reported on A. scaberrimus in Inner Mongolia, China (Sun et al. 2023). Pathogenicity tests were conducted by brushing the conidia from infected S. salsula leaves onto leaves of four healthy plants, while four control plants were brushed in the same manner. All the treated plants were placed in separate growth chambers maintained at 19°C and 65% humidity, with a 16 h light/8 h dark photoperiod. Nine days after inoculation, the treated plants showed powdery mildew symptoms, while the control plants remained asymptomatic. The same results were obtained for two repeated pathogenicity experiments. The powdery mildew fungus was reisolated and identified as E. astragali based on morphological and molecular analysis, thereby fulfilling Koch's postulates. No report on the occurrence of powdery mildew on S. salsula plants has been found previously. The occurrence of this destructive powdery mildew may adversely affect the cultivation of S. salsula. Identifying the pathogen of powdery mildew will support future efforts to control and manage powdery mildew on S. salsula.

Exposure to heavy metal elements may significantly increase serum prostate-specific antigen levels with overdosed dietary zinc.

BACKGROUND: Serum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa. METHOD: Data on a total of 5089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003-2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (µmol/L), cadmium (nmol/L), and mercury (µmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models. RESULTS: Regression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P = 0.0268, P for interaction=0.0249). CONCLUSIONS: With high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa.

PDK4 inhibits osteoarthritis progression by activating the PPAR pathway.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease caused by the deterioration of cartilage. However, the underlying mechanisms of OA pathogenesis remain elusive. METHODS: Hub genes were screened by bioinformatics analysis based on the GSE114007 and GSE169077 datasets. The Sprague-Dawley (SD) rat model of OA was constructed by intra-articular injection of a mixture of papain and L-cysteine. Hematoxylin-eosin (HE) staining was used to detect pathological changes in OA rat models. Inflammatory cytokine levels in serum were measured employing the enzyme-linked immunosorbent assay (ELISA). The reverse transcription quantitative PCR (RT-qPCR) was implemented to assess the hub gene expressions in OA rat models. The roles of PDK4 and the mechanism regulating the PPAR pathway were evaluated through western blot, cell counting kit-8 (CCK-8), ELISA, and flow cytometry assays in C28/I2 chondrocytes induced by IL-1ß. RESULTS: Six hub genes were identified, of which COL1A1, POSTN, FAP, and CDH11 expressions were elevated, while PDK4 and ANGPTL4 were reduced in OA. Overexpression of PDK4 inhibited apoptosis, inflammatory cytokine levels (TNF-α, IL-8, and IL-6), and extracellular matrix (ECM) degradation protein expressions (MMP-3, MMP-13, and ADAMTS-4) in IL-1ß-induced chondrocytes. Further investigation revealed that PDK4 promoted the expression of PPAR signaling pathway-related proteins: PPARA, PPARD, and ACSL1. Additionally, GW9662, an inhibitor of the PPAR pathway, significantly counteracted the inhibitory effect of PDK4 overexpression on IL-1ß-induced chondrocytes. CONCLUSION: PDK4 inhibits OA development by activating the PPAR pathway, which provides new insights into the OA management.

Molecular Characteristics of Bean Common Mosaic Virus Occurring in Inner Mongolia, China.

Bean common mosaic virus (BCMV) was detected on common bean (Phaseolus vulgaris) plants showing wrinkled and/or narrow leaves, curling, shrinking and chlorosis of leaves, dwarfing of plants, and mottled pods in Inner Mongolia and named BCMV-22Huhe. Its genome has a size of 10,062 bp and was deposited in GenBank under the accession number OR778613. It is closely related to BCMV-Az (GenBank accession no. KP903372, in China) in the lineage of AzBMV. A recombination event was detected for BCMV-22Huhe among the 99 BCMV isolates published in the NCBI GenBank database, showing that BCMV-CJ25 (MK069986, found in Mexico) was a potential major parent, and the minor parent is unknown. This work is the first description of the occurrence of BCMV in Inner Mongolia, China.

First Report of Leek Yellow Stripe Virus Infecting Allium cepa in China.

Onion (Allium cepa), a member of the genus Allium, is widely cultivated throughout the world including China (Zhang et al. 2022). In July 2022, stunted onion (A. cepa 'Weiwang') plants showing typical symptoms of yellow stripe and leaves distortion (Fig. S1) were observed in a vegetable garden in Hohhot, Inner Mongolia, China. The garden is approximately 0.24 ha with around 20,000 onion plants, out of which 140 plants were symptomatic. Diagnosis of the symptomatic plants using negative stain electron microscopy revealed the association of long flexuous virus particles measuring about 11 to 12 nm × 820 to 1000 nm (Fig. S2), which was suggestive of the presence of potyvirus (Chen et al. 2002). Subsequently, the pathogen was identified as the leek yellow stripe virus through RT-PCR combined with Sanger sequencing as described below. The total RNA of each sample was extracted using the MiniBEST plant RNA extraction kit (TaKaRa, Dalian, China), serving as template for synthesis of cDNA using the ABScriptIII RT master mix (ABclonal Biotechnology, Wuhan, China). We then amplified a fragment at the 3' terminus of LYSV using a M5 Hiper superluminal mix (Mei5 Biotechnology, Beijing, China) with the primer pair LYSV-F / LYSV-R (Santosa and Ertunc 2020) which flank the partial NIb gene, the complete coat protein gene and partial 3' untranslated region of LYSV. A unique PCR product of about 1 kb was seen for 10 out of the 140 samples. Five out of the 10 PCR products were randomly selected and cloned using a Zero Background pTOPO-TA cloning kit (Aidlab Technologies, Beijing, China) and E. coli JM109 competent cells were then transformed. Positive colonies were screened by PCR detection of the insert fragments using the primers LYSV-F/-R, and the inserts were sequenced at BGI Genomics (Beijing) using the M13(-21) Forward and M13 Reverse primers. All the obtained sequences were 1032 nt in length, and shared nucleotide sequence identities of 99.2% to 100% (two out of the five sequences were identical to each other). The query sequences were submitted to BLASTn to retrieve homologous sequences from NCBI GenBank databases, and the results showed that the four sequences were homologous to LYSV, suggesting the occurrence of LYSV on onions in Inner Mongolia, China. The sequences were then deposited in GenBank under accession numbers of OQ969953-56, named LYSV isolate Hohhot-1, -2, -3, and -4. In comparison with other published LYSV isolates, the LYSV Hohhot-1, -2, -3, and -4 had the highest nucleotide sequence identity of 87.23%, 86.97%, 87.33%, and 87.23% with LYSV G66 (GenBank accession no. MN059493), respectively, which infects garlic in China. Phylogeny analysis was performed based on 41 complete sequences of the CP gene of LYSV, including the four in this work and another 37 from GenBank of which six isolates were discovered in onions in Turkey (MN070124, MN070126, MN070130, MN070131, MN864794 and MN864795) and the others 31 isolates were from garlics or leeks in 15 different countries (Argentina, Australia, Brazil, China, Ethiopia, Germany, India, Iran, Japan, Mexico, Netherlands, New Zealand, Serbia, South Korea, and Spain), while the CP gene of onion yellow dwarf virus (AJ510223) was employed as an outgroup reference. The tree was reconstructed using the neighbor-joining method of MEGA11 with a bootstrap value of 1,000 replicates. On the tree (Fig. S3), the LYSV Hohhot-1, -2, -3, and -4 were closely related to each other and were distinct from other LYSV isolates including the six isolates in onions in Turkey, suggesting a specific genetic variation of the LYSV isolates in Hohhot. According to Santosa et al. (2023), LYSV Hohhot-1, -2, -3, and -4 were within the S-type lineage. This was the first record of LYSV infecting onions in China, expanding the natural host range of LYSV in China, which offered important information for the management of onion diseases.

ITGB1 alleviates osteoarthritis by inhibiting cartilage inflammation and apoptosis via activating cAMP pathway.

OBJECTIVE: We aimed to screen novel biomarkers for osteoarthritis (OA) using bioinformatic methods and explore its regulatory mechanism in OA development. METHODS: Differentially expressed genes were screened out from GSE98918 and GSE82107 datasets. Protein-protein interaction network and enrichment analysis were employed to search for hub gene and regulatory pathway. Hematoxylin-eosin, Safranin O-Fast green staining, and immunohistochemistry were performed to assess pathological damage. TNF-α, IL-1ß, and IL-6 concentrations were determined by enzyme-linked immunosorbent assay. Real-time quantitative PCR was applied to verify expression of hub genes in OA model. The expression of key protein and pathway proteins was determined by western blot. Furthermore, Cell Counting Kit-8 and flow cytometry were conducted to explore the role of hub gene in chondrocytes. RESULTS: We identified 6 hub genes of OA, including ITGB1, COL5A1, COL1A1, THBS2, LAMA1, and COL12A1, with high prediction value. ITGB1 was screened as a pivotal regulator of OA and cAMP pathway was selected as the key regulatory pathway. ITGB1 was down-regulated in OA model. ITGB1 overexpression attenuated pathological damage and apoptosis in OA rats with the reduced levels of TNF-α, IL-1ß and IL-6. ITGB1 overexpression activated cAMP pathway in vivo and vitro models. In vitro model, ITGB1 overexpression promoted cell viability, while inhibited apoptosis. ITGB1 overexpression also caused a decrease of TNF-α, IL-1ß, and IL-6 concentrations. cAMP pathway inhibitor reversed the positive effect of ITGB1 on OA cell model. CONCLUSION: ITGB1 is a novel biomarker for OA, which inhibits OA development by activating the cAMP pathway.

Identification and Genome Characterization of a Dahlia Common Mosaic Virus Isolate from China.

Dahlia (Dahlia variabilis) is a widely cultivated ornamental and medicinal plant in China. Recently, dahlia plants with symptoms of leaf mottling and distortion were collected in Hohhot, Inner Mongolia, China. The presence of dahlia common mosaic virus (DCMV), an unassigned species in the genus Caulimovirus, was confirmed by high-throughput sequencing. Three fragments of DCMV Inner Mongolia isolate (DCMV-IN) were PCR-amplified with specific primers, sequenced and assembled into the complete genome sequence with a GenBank accession number of OR494328. The double-stranded circular DNA genome of DCMV-IN consists of 7949 bp and contains six open reading frames (ORFs). Sequence analysis showed that DCMV-IN shared high sequence identities with other DCMV isolates available in the GenBank database. Phylogenetic analysis of DCMV isolates and other representative caulimoviruses based on genome sequence clustered four DCMV isolates to a single branch which was closest to dahlia mosaic virus (DMV). No recombination event was detected among the four DCMV isolates.

High-mobility spin-polarized two-dimensional electron gas at the interface of EuTiO3/SrTiO3heterostructures.

Spin polarization of two-dimensional electron gas (2DEG) at the interface of EuTiO3/SrTiO3(STO) heterostructures has been theoretical predicted and experimentally observed via x-ray magnetic circular dichroism and polarized x-ray absorption spectroscopy, which, however, is lack of magnetotransport evidence. Here, we report the fabrication of high-quality EuTiO3/STO heterostructures by depositing antiferromagnetic insulating EuTiO3thin films onto STO substrates. Shubnikov-de Haas oscillation, Hall, and magnetoresistance (MR) measurements show that the interface is not only highly conducting, with electron mobility up to5.5×103cm2V-1s-1at 1.8 K, but also shows low-field hysteretic MR effects. MR of ∼9% is observed at 1.8 K and 20 Oe, which is one order of magnitude higher than those observed in other spin-polarized 2DEG oxide systems. Moreover, the heterostructures show ferromagnetic hysteresis loops. These results demonstrate that the high-mobility 2DEG is spin polarized, whose origin is attributed to the interfacial Ti3+-3dstates due to oxygen deficiency and the exchange interactions between interfacial Eu spins and itinerant Ti-3delectrons.

Occurrence of Powdery Mildew Caused by Erysiphe astragali on Astragalus scaberrimus in Inner Mongolia, China.

Astragalus scaberrimus Bunge, a perennial herb, is widely distributed in North and central China, Russia, and Mongolia (POWO, 2023). Due to its tolerance to drought, cold, high salt, low nutrients and alkaline soil, this plant is widely cultivated in China as a forage crop, for water and soil conservation, and for its medicinal properties (Meng, 2015). In 2022, powdery mildew-like signs and symptoms were seen on leaves of A. scaberrimuns cultivated on the campus of Inner Mongolia Agricultural University, Hohhot, Inner Mongolia China. White powder-like masses covered up to 99% of the leaf area with infected plants showing weak growth and senescence. More than 70% of plants (n = 180) exhibited these powdery mildew-infected symptoms. Conidiophores were 70-120 µm long (n = 20) and composed of a basal foot cell, followed by two cells and a conidium. Cylindrical- or ovoid-shaped conidia were 30-45µm long by 9-15 µm wide (n = 20). Brown or light-brown chasmothecia were 100-140 µm in diameter, with flexuous appendages. Based on these morphological characteristics, the fungus was tentatively identified as an Erysiphe sp. (Braun and Cook, 2012; Schmidt and Braun, 2020). Fungal structures were isolated from diseased leaves and genomic DNA of the pathogen was extracted utilizing the method described by Zhu et al. (2022). The internal transcribed spacer (ITS) region was amplified by PCR employing the primers PMITS1/PMITS2 (Cunnington et al., 2003) and the amplicon sequenced by Invitrogen (Shanghai, China). The sequence for the powdery mildew fungus (GenBank accession no.: MW142495) showed 100% identity (645/645 bp) with Erysiphe astragali, which was reported on A. glycyphyllos in Golestan province, Iran (accession no. OP806834). Pathogenicity tests were conducted by brushing the conidia from infected A. scaberrimus leaves onto leaves of four healthy plants, while, the four control plants were brushed in the same manner. All the treated plants were placed in separate growth chambers maintained at 19℃, 65% humidity, with 16 h light/8 h dark photoperiod. Nine days post inoculation, powdery mildew disease signs appeared on inoculated plants, whereas control plants remained asymptomatic. The same results were obtained for two repeated pathogenicity experiments. The powdery mildew fungus was reisolated and identified as E. astragali based on morphological and molecular analysis, thereby fulfilling Koch's postulates. E. astragali causing powdery mildew on A. glycyphyllus were previously reported in Germany with Genbank accesion number of MZ265150 and MZ265151 (Bradshaw et al., 2022). This, to our knowledge, is the first report of powdery mildew caused by E. astragali on A. scaberrimus. The severe occurrence of this destructive powdery mildew disease on A. scaberrimus may adversely affect the utility of the plant for soil conservation or cultivation for medicinal purposes. Identifying the causal agent of powdery mildew will support efforts for the future control and management of diseases on A. scaberrimus.

Low level TGF-ß1-treated Umbilical mesenchymal stem cells attenuates microgliosis and neuropathic pain in chronic constriction injury by exosomes/lncRNA UCA1／miR-96-5p／FOXO3a.

Neuropathic pain is a chronic pain state that usually caused by injuries in peripheral or central nerve. Inhibition of spinal microglial response is a promising treatment of neuropathic pain caused by peripheral nerve injury. In recent years, mesenchymal stem cells (MSCs) that characterized with multipotent ability have been widely studied for disease treatment. TGF-ß1 is a well-known regulatory cytokine that participate in the response to cell stress and is closely correlated with the function of nerve system as well as MSC differentiation. This work aimed to determine the effects of exosomes that extracted from TGF-ß1-induced umbilical mesenchymal stem cells (hUCSMCs) on the neuropathic pain. In this work, we established a rat model of chronic constriction injury (CCI) of the sciatic nerve and LPS-induced microglia cell model. The hUCSMCs cell surface biomarker was identified by flow cytometry. Exosomes that extracted from TGF-ß1-treated hUCSMCs were characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) and used for treatment. We observed that TGF-ß1 upregulates the level of lncRNA UCA1 (UCA1) in hUCMSC-derived exosomes. Treatment with exosomal lncRNA UCA1 (UCA1) alleviated the neuropathic pain, microgliosis, and production of inflammatory mediator both in vivo and in vitro. UCA1 directly interact with the miR-96-5p, and the miR-96-5p acts as sponge of FOXO3a. Knockdown of UCA1 upregulated the level of miR-96-5p and downregulated the FOXO3a expression, which could be recovered by inhibition of miR-96-5p. In summary, the TGF-ß1-stimulated exosomal UCA1 from hUCMSCs alleviates the neuropathic pain and microgliosis. These findings may provide novel evidence for treatment of neuropathic pain caused by chronic constriction injury.

Genomic characterization of a novel torradovirus infecting Arctium lappa L. in China.

Burdock (Arctium lappa L.) is not only a popular vegetable crop but also an important medicinal plant. In burdock plants with symptoms of leaf mosaic, a novel torradovirus tentatively named "burdock mosaic virus" (BdMV) was identified by high-throughput sequencing. The complete genomic sequence of BdMV was further determined using RT-PCR and the rapid amplification of cDNA ends (RACE) method. The genome is composed of two positive-sense single-stranded RNAs. RNA1 (6991 nt) encodes a polyprotein of 2186 aa, and RNA2 (4700 nt) encodes a protein of 201 aa and a polyprotein of 1212 aa that is predicted to be processed into one movement protein (MP) and three coat proteins (CPs). The Pro-Pol region of RNA1 and the CP region of RNA2 shared the highest amino acid sequence identity of 74.0% and 70.6%, respectively, with the corresponding sequences of lettuce necrotic leaf curl virus (LNLCV) isolate JG3. Phylogenetic analysis based on the amino acid sequences of the Pro-Pol and CP regions showed that BdMV clustered with other non-tomato-infecting torradoviruses. Taken together, these results suggest that BdMV is a new member of the genus Torradovirus.

Antiviral activity of the HSP90 inhibitor VER-50589 against enterovirus 71.

Enterovirus 71 (EV71) is the major pathogen responsible for hand, foot, and mouth disease (HFMD) outbreaks; to date, there is no specific anti-EV71 agent. HSP90 is a crucial host factor for the viral life cycle and an ideal therapeutic target for limiting viral proliferation. However, the specific role of HSP90 in EV71-related signaling pathways and anti-EV71 agents targeting HSP90 remains unclear. This study aimed to verify the role of HSP90 in signaling pathways involved in EV71 replication and investigate the antiviral effects of a small molecule of VER-50589, a potent HSP90 inhibitor, against EV71 both in vitro and in vivo. Viral plaque assay, western blotting, and qPCR results showed that VER-50589 diminished the plaque formation induced by EV71 and inhibited EV71 mRNA and protein synthesis. A single daily dose of VER-50589 treatment significantly improved the survival rate of EV71-infected mice (p < 0.005). Interestingly, VER-50589 also exhibits activities against a series of human enteroviruses, including Coxsackievirus B3 (CVB3), Coxsackievirus B4-5 (CVB4-5), Coxsackievirus B4-7 (CVB4-7), and Echovirus 11 (Echo11). EV71 infection activated the AKT and ERK signaling pathways, and phosphorylation of AKT and RAF/MEK/ERK was weakened by VER-50589 administration. Thus, VER-50589 exhibits robust antiviral activity by inhibiting HSP90 and mediating the AKT and RAF/MEK/ERK signaling pathways. Considering that there are no effective antivirals or vaccines for the prevention and cure of HFMD in a clinical setting, the development of an anti-EV71 agent would be a straightforward and feasible therapeutic approach.

Integrated transgene and transcriptome reveal the molecular basis of MdWRKY87 positively regulate adventitious rooting in apple rootstock.

For most fruit and forest species vegetative propagated from elite genotypes, adventitious rooting is essential. The ability to form adventitious roots significantly decreased during the juvenile to adult phase change. Apart from the miR156-SPL pathway, whether there is another regulation mechanism controlling age-dependent adventitious rooting ability remained largely unknown. In the present study, we showed that MdWRKY87 expression level was positively correlation with adventitious rooting ability. In addition, over-expressing of MdWRKY87 in tobacco leads to enhanced adventitious rooting ability, more adventitious root number and accelerated adventitious rooting process. Comparative transcriptome profiling indicated that MdWRKY87 overexpression can activate the expression of adventitious rooting-induced genes, such as WOX11 and AIL. In addition, MdWRKY87 overexpression can inhibit the transcription of adventitious rooting-repressed genes, such as AUX/IAAs and type-B cytokinin RRs. Collectively, here we demonstrated that higher expression level of MdWRKY87 contributes to age-dependent adventitious rooting-competent in juvenile apple rootstock.

DNA methylation variation is crucial to restore adventitious rooting ability during in vitro shoot culture-induced rejuvenation in apple rootstock.

In vitro shoot culture has been widely used for restoring adventitious rooting ability in rooting recalcitrant woody perennial species for the past few decades, but its molecular mechanism is largely uncovered. DNA methylation is an essential epigenetic mark that participates in many biological processes. Recent reports suggested a role of DNA methylation in vitro culture in plants. In this study, we characterized the single-base resolution DNA methylome and transcriptome of adult and in vitro shoot culture-induced rejuvenation cuttings of apple rootstock M9T337. We found a global decrease in DNA methylation during rejuvenation, which may be correlated with increased expression of DNA demethylase genes and decreased expression of DNA methyltransferase genes. We additionally documented DNA hypomethylation in 'T337'_R in gene protomer associated with higher transcript levels of several adventitious rooting-related genes. The application of a DNA methylation inhibitor (5-azacytidine) enhanced the adventitious rooting ability and the expression level of adventitious rooting-related genes, such as, MdANT, MdMPK3, MdABCB21, MdCDC48, MdKIN8B, pri-MdMIR156a5 and pri-MdMIR156a12. Together, the DNA hypomethylation is critical for the rejuvenation-dependent adventitious rooting ability in apple rootstock. In addition, increased DNA methylation was also found in thousands of genes in 'T337'_R. We additionally documented that DNA hypermethylation is required for inhibition of adventitious rooting-repressed genes, such as MdGAD5a, encoding glutamate decarboxylase, which can catalyze glutamate decarboxylated to form γ-aminobutyric acid (GABA). Our results revealed that in vitro shoot culture-dependent DNA methylation variation plays important roles in adventitious rooting in apple rootstock.

Efficacy of mesenchymal stromal cells intraspinal transplantation for patients with different degrees of spinal cord injury: A systematic review and meta-analysis.

BACKGROUND AIMS: Several studies have reported that mesenchymal stromal cells (MSCs) may improve neurological functions in patients with spinal cord injury (SCI). In this study, we conducted a systematic review and meta-analysis to summarize the effects of MSC treatment on different degrees of severity of SCI. METHODS: Systematic searching of studies reporting outcomes of MSCs on specific injury severities of patients with SCI was performed in The National Library of Medicine (MEDLINE), Embase and Cochrane for published articles up to the 6 July 2022. Two investigators independently reviewed the included studies and extracted the relevant data. The standardized mean differences of American Spinal Injury Association (ASIA) motor score, ASIA light touch scores, ASIA pinprick scores and the Barthel index between baseline and follow-ups were pooled. RESULTS: A total of eight studies were included. A large majority focused on patients with ASIA grade A classification. The pooled mean differences of ASIA motor scores, ASIA light touch scores, ASIA pinprick scores and the Barthel index were -2.78 (95% confidence interval [CI] -5.12 to -0.43, P = 0.02), -18.26 (95% CI -26.09 to -10.43, P < 0.01), -17.08 (95% CI -24.10 to -10.07, P < 0.01) and -4.37 (95% CI -10.96 to 2.22, P = 0.19), respectively. CONCLUSIONS: MSC transplantation was a significantly effective therapy for patients with SCI with ASIA grade A. In the future, further studies are warranted to confirm the potential beneficial effects of MSC therapy.