Inhibitors of dermatan sulfate epimerase 1 decreased accumulation of glycosaminoglycans in mucopolysaccharidosis type I fibroblasts.

Genetic deficiency of alpha-L-iduronidase causes mucopolysaccharidosis type I (MPS-I) disease, due to accumulation of glycosaminoglycans (GAGs) including chondroitin/dermatan sulfate (CS/DS) and heparan sulfate (HS) in cells. Currently, patients are treated by infusion of recombinant iduronidase or by hematopoietic stem cell transplantation. An alternative approach is to reduce the L-iduronidase substrate, through limiting the biosynthesis of iduronic acid. Our earlier study demonstrated that ebselen attenuated GAGs accumulation in MPS-I cells, through inhibiting iduronic acid producing enzymes. However, ebselen has multiple pharmacological effects, which prevents its application for MPS-I. Thus, we continued the study by looking for novel inhibitors of dermatan sulfate epimerase 1 (DS-epi1), the main responsible enzyme for production of iduronic acid in CS/DS chains. Based on virtual screening of chemicals towards chondroitinase AC, we constructed a library with 1,064 compounds that were tested for DS-epi1 inhibition. Seventeen compounds were identified to be able to inhibit 27%-86% of DS-epi1 activity at 10 µM. Two compounds were selected for further investigation based on the structure properties. The results show that both inhibitors had a comparable level in inhibition of DS-epi1while they had negligible effect on HS epimerase. The two inhibitors were able to reduce iduronic acid biosynthesis in CS/DS and GAG accumulation in WT and MPS-I fibroblasts. Docking of the inhibitors into DS-epi1 structure shows high affinity binding of both compounds to the active site. The collected data indicate that these hit compounds may be further elaborated to a potential lead drug used for attenuation of GAGs accumulation in MPS-I patients.

Barley yellow dwarf virus-GAV 17K protein disrupts thiamine biosynthesis to facilitate viral infection in plants.

Thiamine functions as a crucial activator modulating plant health and broad-spectrum stress tolerances. However, the role of thiamine in regulating plant virus infection is largely unknown. Here, we report that the multifunctional 17K protein encoded by barley yellow dwarf virus-GAV (BYDV-GAV) interacted with barley pyrimidine synthase (HvTHIC), a key enzyme in thiamine biosynthesis. HvTHIC was found to be localized in chloroplast via an N-terminal 74-amino acid domain. However, the 17K-HvTHIC interaction restricted HvTHIC targeting to chloroplasts and triggered autophagy-mediated HvTHIC degradation. Upon BYDV-GAV infection, the expression of the HvTHIC gene was significantly induced, and this was accompanied by accumulation of thiamine and salicylic acid. Silencing of HvTHIC expression promoted BYDV-GAV accumulation. Transcriptomic analysis of HvTHIC silenced and non-silenced barley plants showed that the differentially expressed genes were mainly involved in plant-pathogen interaction, plant hormone signal induction, phenylpropanoid biosynthesis, starch and sucrose metabolism, photosynthesis-antenna protein, and MAPK signaling pathway. Thiamine treatment enhanced barley resistance to BYDV-GAV. Taken together, our findings reveal a molecular mechanism underlying how BYDV impedes thiamine biosynthesis to uphold viral infection in plants.

A viral protein competitively bound to rice CIPK23 inhibits potassium absorption and facilitates virus systemic infection in rice.

Potassium (K+) plays a crucial role as a macronutrient in the growth and development of plants. Studies have definitely determined the vital roles of K+ in response to pathogen invasion. Our previous investigations revealed that rice plants infected with rice grassy stunt virus (RGSV) displayed a reduction in K+ content, but the mechanism by which RGSV infection subverts K+ uptake remains unknown. In this study, we found that overexpression of RGSV P1, a specific viral protein encoded by viral RNA1, results in enhanced sensitivity to low K+ stress and exhibits a significantly lower rate of K+ influx compared to wild-type rice plants. Further investigation revealed that RGSV P1 interacts with OsCIPK23, an upstream regulator of Shaker K+ channel OsAKT1. Moreover, we found that the P1 protein recruits the OsCIPK23 to the Cajal bodies (CBs). In vivo assays demonstrated that the P1 protein competitively binds to OsCIPK23 with both OsCBL1 and OsAKT1. In the nucleus, the P1 protein enhances the binding of OsCIPK23 to OsCoilin, a homologue of the signature protein of CBs in Arabidopsis, and facilitates their trafficking through these CB structures. Genetic analysis indicates that mutant in oscipk23 suppresses RGSV systemic infection. Conversely, osakt1 mutants exhibited increased sensitivity to RGSV infection. These findings suggest that RGSV P1 hinders the absorption of K+ in rice plants by recruiting the OsCIPK23 to the CB structures. This process potentially promotes virus systemic infection but comes at the expense of inhibiting OsAKT1 activity.

Understanding Citrus Viroid Interactions: Experience and Prospects.

Citrus is the natural host of at least eight viroid species, providing a natural platform for studying interactions among viroids. The latter manifests as antagonistic or synergistic phenomena. The antagonistic effect among citrus viroids intuitively leads to reduced symptoms caused by citrus viroids, while the synergistic effect leads to an increase in symptom severity. The interaction phenomenon is complex and interesting, and a deep understanding of the underlying mechanisms induced during this viroid interaction is of great significance for the prevention and control of viroid diseases. This paper summarizes the research progress of citrus viroids in recent years, focusing on the interaction phenomenon and analyzing their interaction mechanisms. It points out the core role of the host RNA silencing mechanism and viroid-derived siRNA (vd-siRNA), and provides suggestions for future research directions.

Dynamic changes in lysosome-related pathways in APP/PS1 mice with aging.

Senile plaque, composed of amyloid ß protein (Aß) aggregates, is a critical pathological feature in Alzheimer's disease (AD), leading to cognitive dysfunction. However, how Aß aggregates exert age-dependent toxicity and temporal cognitive dysfunction in APP/PS1 mice remains incompletely understood. In this study, we investigated AD pathogenesis and dynamic alterations in lysosomal pathways within the hippocampus of age-gradient male mice using transcriptome sequencing, molecular biology assays, and histopathological analyses. We observed high levels of ß-amyloid precursor protein (APP) protein expression in the hippocampus at an early stage and age-dependent Aß deposition. Transcriptome sequencing revealed the enrichment of differential genes related to the lysosome pathway. Furthermore, the protein expression of ATP6V0d2 and CTSD associated with lysosomal functions exhibited dynamic changes with age, increasing in the early stage and decreasing later. Similar age-dependent patterns were observed for the endosome function, autophagy pathway, and SGK1/FOXO3a pathway. Nissl and Golgi staining in the hippocampal region showed age-dependent neuronal loss and synaptic damage, respectively. These findings clearly define the age-gradient changes in the autophagy-lysosome system, the endosome/lysosome system, and the SGK1/FOXO3a pathway in the hippocampus of APP/PS1 mice, providing new perspectives and clues for understanding the possible mechanisms of AD, especially the transition from compensatory to decompensated state.

Genomics Analysis Reveals the Potential Biocontrol Mechanism of Pseudomonas aeruginosa QY43 against Fusarium pseudograminearum.

Fusarium crown rot (FCR) in wheat is a prevalent soil-borne disease worldwide and poses a significant threat to the production of wheat (Triticum aestivum) in China, with F. pseudograminearum being the dominant pathogen. Currently, there is a shortage of biocontrol resources to control FCR induced by F. pseudograminearum, along with biocontrol mechanisms. In this study, we have identified 37 strains of biocontrol bacteria displaying antagonistic effects against F. pseudograminearum from over 8000 single colonies isolated from soil samples with a high incidence of FCR. Among them, QY43 exhibited remarkable efficacy in controlling FCR. Further analysis identified the isolate QY43 as Pseudomonas aeruginosa, based on its colony morphology and molecular biology. In vitro, QY43 significantly inhibited the growth, conidial germination, and the pathogenicity of F. pseudograminearum. In addition, QY43 exhibited a broad spectrum of antagonistic activities against several plant pathogens. The genomics analysis revealed that there are genes encoding potential biocontrol factors in the genome of QY43. The experimental results confirmed that QY43 secretes biocontrol factor siderophores and pyocyanin. In summary, QY43 exhibits a broad spectrum of antagonistic activities and the capacity to produce diverse biocontrol factors, thereby showing substantial potential for biocontrol applications to plant disease.

Tilletia horrida glycoside hydrolase family 128 protein, designated ThGhd_7, modulates plant immunity by blocking reactive oxygen species production.

Tilletia horrida is an important soilborne fungal pathogen that causes rice kernel smut worldwide. We found a glycoside hydrolase family 128 protein, designated ThGhd_7, caused cell death in Nicotiana benthamiana leaves. The predicted signal peptide (SP) of ThGhd_7 targets it for secretion. However, loss of the SP did not affect its ability to induce cell death. The 23-201 amino acid sequence of ThGhd_7 was sufficient to trigger cell death in N. benthamiana. ThGhd_7 expression was induced and upregulated during T. horrida infection. ThGhd_7 localised to both the cytoplasm and nucleus of plant cells, and nuclear localisation was required to induce cell death. The ability of ThGhd_7 to trigger cell death in N. benthamiana depends on RAR1 (required for Mla12 resistance), SGT1 (suppressor of G2 allele of Skp1), and BAK1/SERK3 (somatic embryogenesis receptor-like kinase 3). Heterologous overexpression of ThGhd_7 in rice reduced reactive oxygen species (ROS) production and enhanced susceptibility to T. horrida. Further research revealed that ThGhd_7 interacted with and destabilised OsSGT1, which is required for ROS production and is a positive regulator of rice resistance to T. horrida. Taken together, these findings suggest that T. horrida employs ThGhd_7 to disrupt ROS production and thereby promote infection.

LATS2 degradation promoted fibrosis damage and rescued by vitamin K3 in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). The limited treatment options for LN increase the economic burdens on patients. Because fibrotic progression leads to irreversible renal damage in LN patients and further progresses to chronic kidney disease (CKD) and the end stage of renal disease (ESRD), developing new targets to prevent LN fibrotic progression could lead to a feasible treatment strategy for LN patients. METHODS: In this study, we examined YAP activation and LATS2 downregulation in LN kidney biopsy samples (LN: n = 8, normal: n = 2) and lupus-prone MRL/lpr mice (n = 8 for each disease stage). The function of LATS2 was further investigated by in situ injection of Ad-LATS2 into mice with LN (n = 6 mice per group). We examined the role of SIAH2-LATS2 regulation by IP-MS and co-IP, and the protective effect of the SIAH2 inhibitor was investigated in mice with LN. RESULTS: Restoring LATS2 by an adenovirus in vivo alleviated renal fibrotic damage in mice with LN. Moreover, we found that LATS2 was degraded by a K48 ubiquitination-proteasome pathway mediated by SIAH2 and promoted YAP activation to worsen fibrosis progression in LN. The H150 region of the substrate binding domain (SBD) is an important site for SIAH2-LATS2 binding. The SIAH2-specific inhibitor vitamin K3 protected against LN-associated fibrotic damage in vivo. CONCLUSION: In summary, we identified the SIAH2-LATS2 axis as an attractive intervention target in LN to alter the resistance to fibrosis.

Abnormal protein post-translational modifications induces aggregation and abnormal deposition of protein, mediating neurodegenerative diseases.

Protein post-translational modifications (PPTMs) refer to a series of chemical modifications that occur after the synthesis of protein. Proteins undergo different modifications such as phosphorylation, acetylation, ubiquitination, and so on. These modifications can alter the protein's structure, function, and interaction, thereby regulating its biological activity. In neurodegenerative diseases, several proteins undergo abnormal post-translational modifications, which leads to aggregation and abnormal deposition of protein, thus resulting in neuronal death and related diseases. For example, the main pathological features of Alzheimer's disease are the aggregation of beta-amyloid protein and abnormal phosphorylation of tau protein. The abnormal ubiquitination and loss of α-synuclein are related to the onset of Parkinson's disease. Other neurodegenerative diseases such as Huntington's disease, amyotrophic lateral sclerosis, and so on are also connected with abnormal PPTMs. Therefore, studying the abnormal PPTMs in neurodegenerative diseases is critical for understanding the mechanism of these diseases and the development of significant therapeutic strategies. This work reviews the implications of PPTMs in neurodegenerative diseases and discusses the relevant therapeutic strategies.

Integrated Genome Sequencing and Transcriptome Analysis Identifies Candidate Pathogenicity Genes from Ustilago crameri.

Ustilago crameri is a pathogenic basidiomycete fungus that causes foxtail millet kernel smut (FMKS), a devastating grain disease in most foxtail-millet-growing regions of the world. Here, we report an assembled high-quality genome sequence of U. crameri strain SCZ-6 isolated from the diseased grains of foxtail millet in Changzhi, Shanxi Province, China. The genome size is 19.55 Mb, consisting of 73 contigs (N50 = 840,209 bp) with a G + C content of 54.09%, and encoding 6576 predicted genes and 6486 genes supported by RNA-seq. Evolutionarily, U. crameri lies close to the barley smut U. hordei, and an obvious co-linearity was observed between these two smut fungi. We annotated the genome of U. crameri strain SCZ-6 using databases, identifying 1827 pathogen-host interaction (PHI)-associated genes, 1324 genes encoding fungal virulence factors, 259 CAZy-related genes, 80 genes encoding transporters, and 206 putative cytochrome P450 genes; their expression profiles at different inoculation time points were also detected. Additionally, 70 candidate pathogen effectors were identified according to their expression patterns and predicted functions. In summary, our results provide important insights into the pathogenic mechanisms of the pathogenesis-related genes of U. crameri and a robust foundation for further investigation.

Activation of MAPK-mediated immunity by phosphatidic acid in response to positive-strand RNA viruses.

Increasing evidence suggests that mitogen-activated protein kinase (MAPK) cascades play a crucial role in plant defense against viruses. However, the mechanisms that underlie the activation of MAPK cascades in response to viral infection remain unclear. In this study, we discovered that phosphatidic acid (PA) represents a major class of lipids that respond to Potato virus Y (PVY) at an early stage of infection. We identified NbPLDα1 (Nicotiana benthamiana phospholipase Dα1) as the key enzyme responsible for increased PA levels during PVY infection and found that it plays an antiviral role. 6K2 of PVY interacts with NbPLDα1, leading to elevated PA levels. In addition, NbPLDα1 and PA are recruited by 6K2 to membrane-bound viral replication complexes. On the other hand, 6K2 also induces activation of the MAPK pathway, dependent on its interaction with NbPLDα1 and the derived PA. PA binds to WIPK/SIPK/NTF4, prompting their phosphorylation of WRKY8. Notably, spraying with exogenous PA is sufficient to activate the MAPK pathway. Knockdown of the MEK2-WIPK/SIPK-WRKY8 cascade resulted in enhanced accumulation of PVY genomic RNA. 6K2 of Turnip mosaic virus and p33 of Tomato bushy stunt virus also interacted with NbPLDα1 and induced the activation of MAPK-mediated immunity. Loss of function of NbPLDα1 inhibited virus-induced activation of MAPK cascades and promoted viral RNA accumulation. Thus, activation of MAPK-mediated immunity by NbPLDα1-derived PA is a common strategy employed by hosts to counteract positive-strand RNA virus infection.

1,2,4-Triazole benzamide derivative TPB against Gaeumannomyces graminis var. tritici as a novel dual-target fungicide inhibiting ergosterol synthesis and adenine nucleotide transferase function.

BACKGROUND: Isopropyl 4-(2-chloro-6-(1H-1,2,4-triazol-1-yl)benzamido)benzoate (TPB) was a 1,2,4-triazole benzoyl arylamine derivative with excellent antifungal activity, especially against Gaeumannomyces graminis var. tritici (Ggt). Its mechanism of action was investigated by transmission electron microscopy (TEM) observation, assays of sterol composition, cell membrane permeability, intracellular ATP and mitochondrial membrane potential, and mPTP permeability, ROS measurement, RNA sequencing (RNA-seq) analysis. RESULTS: TPB interfered with ergosterol synthesis, reducing ergosterol content, increasing toxic intermediates, and finally causing biomembrane disruption such as increasing cell membrane permeability and content leakage, and destruction of organelle membranes such as coarse endoplasmic reticulum and vacuole. Moreover, TPB destroyed the function of adenine nucleotide transferase (ANT), leading to ATP transport obstruction in mitochondria, inhibiting mPTP opening, inducing intracellular ROS accumulation and mitochondrial membrane potential loss, finally resulting in mitochondrial damage including mitochondria swelled, mitochondrial membrane dissolved, and cristae destroyed and reduced. RNA-seq analyses showed that TPB increased the expression of ERG11, ERG24, ERG6, ERG5, ERG3 and ERG2 genes in ergosterol synthesis pathway, interfered with the expression of genes (NDUFS5, ATPeV0E, NCA2 and Pam17) related to mitochondrial structure, and inhibited the expression of genes (WrbA and GST) related to anti-oxidative stress. CONCLUSIONS: TPB exhibited excellent antifungal activity against Ggt by inhibiting ergosterol synthesis and destroying ANT function. So, TPB was a novel compound with dual-target mechanism of action and can be considered a promising novel fungicide for the control of wheat Take-all. The results provided new guides for the structural design of active compounds and powerful tools for pathogen resistance management. © 2023 Society of Chemical Industry.

Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Gypenoside IX restores Akt/GSK-3ß pathway and alleviates Alzheimer's disease-like neuropathology and cognitive deficits.

The main pathological changes of Alzheimer's disease (AD), a progressive neurodegenerative disorder, include senile plaque (deposited by amyloid beta), neurofibrillary tangle (formed by paired helical filaments composed of hyperphosphorylated tau), and massive loss of neurons. Currently there is a lack of ideal drugs to halt AD progression. Gypenosides (GPs), a kind of natural product, possesses potential therapeutic effects for neurodegenerative diseases, including AD. However, the specific role and mechanism of GPs for AD remain unclear. In the current study, we used staurosporine (STP), an inducer of apoptosis and causing tau hyperphosphorylation, to mimic AD models, and explored the role and mechanism of Gypenoside IX (one of the extracts of Gynostemma, GP for short name in our experiments) in STP treated primary hippocampal neurons and rats. We found STP not only increased apoptosis and tau hyperphosphorylation, but also significantly increased Aß production, resulting in synaptic dysfunction and cognitive decline in mimic AD models by STP. GP was found to rescue apoptosis and cognitive impairments caused by STP treatment. Moreover, GP recovered the decreased synaptic proteins PSD95, Synaptophysin and GluR2, and blocked dendritic spine loss. Interestingly, GP decreased the STP induced tau hyperphosphorylation at different sites including S-199, S-202, T-205, T-231, S-262, S-396, and S-404, and at the same time decreased Aß production through down-regulation of BACE1 and PS1. These effects in STP treated primary hippocampal neurons and rats were accompanied with a restoration of AKT/GSK-3ß signaling axis with GP treatment, supporting that dysregulation of AKT/GSK-3ß pathway might be involved in STP related AD pathogenesis. The results from our research proved that GP might be a potential candidate compound to reduce neuronal damage and prevent the cognitive decline in AD.

Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer's Disease and Other Tauopathies.

Tau, a microtubule-associated protein predominantly localized in neuronal axons, plays a crucial role in promoting microtubule assembly, stabilizing their structure, and participating in axonal transport. Perturbations in tau's structure and function are implicated in the pathogenesis of neurodegenerative diseases collectively known as tauopathies, the most common disorder of which is Alzheimer's disease (AD). In tauopathies, it has been found that tau has a variety of post-translational modification (PTM) abnormalities and/or tau is cleaved into a variety of fragments by some specific proteolytic enzymes; however, the precise contributions of these abnormal modifications and fragments to disease onset and progression remain incompletely understood. Herein, we provide an overview about the involvement of distinctive abnormal tau PTMs and different tau fragments in the pathogenesis of AD and other tauopathies and discuss the involvement of proteolytic enzymes such as caspases, calpains, and asparagine endopeptidase in mediating tau cleavage while also addressing the intercellular transmission role played by tau. We anticipate that further exploration into PTMs and fragmented forms of tau will yield valuable insights for diagnostic approaches and therapeutic interventions targeting AD and other related disorders.

Low-molecular weight sulfated marine polysaccharides: Promising molecules to prevent neurodegeneration in mucopolysaccharidosis IIIA?

Mucopolysaccharidosis IIIA is a hereditary disease caused by mutations in the sulfamidase enzyme that participates in catabolism of heparan sulfate (HS), leading to HS fragment accumulation and multisystemic failure. No cure exists and death occurs around the second decade of life. Two low molecular weight highly sulfated compounds derived from marine diabolican and infernan exopolysaccharides (A5_3 and A5_4, respectively) with heparanase inhibiting properties were tested in a MPSIIIA cell line model, resulting in limited degradation of intracellular HS. Next, we observed the effects of intraperitoneal injections of the diabolican derivative A5_3 from 4 to 12 weeks of age on MPSIIIA mice. Brain metabolism and microstructure, levels of proteins and genes involved in MPSIIIA brain pathophysiology were also investigated. 1H-Magnetic Resonance Spectroscopy (MRS) indicated deficits in energetic metabolism, tissue integrity and neurotransmission at both 4 and 12 weeks in MPSIIIA mice, with partial protective effects of A5_3. Ex-vivo Diffusion Tensor Imaging (DTI) showed white matter microstructural damage in MPSIIIA, with noticeable protective effects of A5_3. Protein and gene expression assessments displayed both pro-inflammatory and pro-apoptotic profiles in MPSIIIA mice, with benefits of A5_3 counteracting neuroinflammation. Overall, derivative A5_3 was well tolerated and was shown to be efficient in preventing brain metabolism failure and inflammation, resulting in preserved brain microstructure in the context of MPSIIIA.

The Great Game between Plants and Viruses: A Focus on Protein Homeostasis.

Plant viruses are tiny pathogenic obligate parasites that cause significant damage to global crop production. They exploit and manipulate the cellular components of host plants to ensure their own survival. In response, plants activate multiple defense signaling pathways, such as gene silencing and plant hormone signaling, to hinder virus propagation. Growing evidence suggests that the regulation of protein homeostasis plays a vital role in the ongoing battle between plants and viruses. The ubiquitin-proteasome-degradation system (UPS) and autophagy, as two major protein-degradation pathways, are widely utilized by plants and viruses in their arms race. One the one hand, these pathways act as essential components of plant's antiviral defense system by facilitating the degradation of viral proteins; on the other hand, viruses exploit the UPS and autophagy to create a favorable intracellular environment for viral infection. This review aims to provide a comprehensive summary of the events involved in protein homeostasis regulation during viral infection in plants. Gaining knowledge in this area will enhance our understanding of the complex interplay between plants and viruses.

A Putative Zn(II)2Cys6-Type Transcription Factor FpUme18 Is Required for Development, Conidiation, Cell Wall Integrity, Endocytosis and Full Virulence in Fusarium pseudograminearum.

Fusarium pseudograminearum is one of the major fungal pathogens that cause Fusarium crown rot (FCR) worldwide and can lead to a substantially reduced grain yield and quality. Transcription factors play an important role in regulating growth and pathogenicity in plant pathogens. In this study, we identified a putative Zn(II)2Cys6 fungal-type domain-containing transcription factor and named it FpUme18. The expression of FpUME18 was induced during the infection of wheat by F. pseudograminearum. The ΔFpume18 deletion mutant showed defects in growth, conidial production, and conidial germination. In the responses to the cell wall, salt and oxidative stresses, the ΔFpume18 mutant inhibited the rate of mycelial growth at a higher rate compared with the wild type. The staining of conidia and mycelia with lipophilic dye FM4-64 revealed a delay in endocytosis when FpUME18 was deleted. FpUME18 also positively regulated the expression of phospholipid-related synthesis genes. The deletion of FpUME18 attenuated the pathogenicity of wheat coleoptiles. FpUME18 also participated in the production of the DON toxin by regulating the expression of TRI genes. Collectively, FpUme18 is required for vegetative growth, conidiation, stress response, endocytosis, and full virulence in F. pseudograminearum.

Design, Synthesis, and Antifungal Activity of Polyacetylenic Alcohol Derivatives and Stereoisomers against Phytopathogenic Fungi.

Falcarindiol is active against phytopathogenic fungi. In the present study, racemic falcarindiol analogs (8a-8q) were designed, synthesized, and tested for their activities against eight economically significant phytopathogenic fungal species. The compound 8o displayed the best antifungal activities and up to 54.6-fold in vitro potency improvement against Phytophthora capsici than the natural product stipudiol. Its half-maximum effective concentrations ranged from 4 to 23 µg/mL against all tested fungal species. Racemic 8o was 195-fold more potent than the fungicide carbendazim against P. capsici in vitro. The isomer (1S, 6S)-8o exhibited an EC50 of 1.10 and 2.70 µg/mL against Monilia fructigena and P. capsici, respectively, which was 47 and 11 times lower than (1R, 6S)-8o and (1S, 6R)-8o. In addition, in vivo bioassay results showed that (1S, 6S)-8o had high antifungal activity against infection of M. fructigena and P. capsici to apricot and pepper fruits and pepper plants, which the efficacy was similar or better than carbendazim. The high potency and selectivity of 8o stereoisomers against the phytopathogens warrant an interest in elucidating the molecular target for fungicide development.

A comparison of the mineral element content of 70 different varieties of pear fruit (Pyrus ussuriensis) in China.

Background: Pyrus ussuriensis (Maxim.) is a unique pear tree that grows in northern China. The tree has strong cold resistance and can withstand low temperatures from -30 °C to -35 °C. Due to its unique growth environment, its fruit is rich in minerals and has much higher levels of minerals such as K, Ca and Mg than the fruit of Pyrus pyrifolia (Nakai.) and Pyrus bretschneideri (Rehd.) on the market, and many say the ripe fruit tastes better than other varieties. A comprehensive analysis of the characteristics of mineral elements in the fruits of different varieties of P. ussuriensis will provide a valuable scientific basis for the selection, breeding and production of consumer varieties of P. ussuriensis, and provide a more complete understanding of nutritional differences between fruit varieties. Methods: In this study, 70 varieties of wild, domesticated and cultivated species of P. ussuriensis from different geographical locations were compared. Targeting four main mineral elements and eight trace mineral elements contained in the fruit, the differences in mineral content in the peel and pulp of different varieties of P. ussuriensis were analyzed, compared and classified using modern microwave digestion ICP-MS. Results: The mineral elements in the fruit of P. ussuriensis generally followed the following content pattern: K > P > Ca > Mg > Na > Al > Fe > Zn > Cu > Cr > Pb > Cd. The mineral element compositions in the peel and pulp of different fruits were also significantly different. The four main mineral elements in the peel were K > Ca > P > Mg, and K > P > Mg > Ca in the pulp. The mineral element content of wild fruit varieties was higher than that of cultivated and domesticated varieties. Correlation analysis results showed that there was a significant positive correlation between K, P and Cu in both the peel and pulp of P. ussuriensis fruit (P < 0. 01). Cluster analysis results showed that the 70 varieties of P. ussuriensis could be divided into three slightly different categories according to the content of the peel or pulp. According to the contents of the fruit peel, these varieties were divided into: (1) varieties with high Na, Mg, P, K, Fe and Zn content, (2) varieties with high Ca content and (3) varieties with medium levels of mineral elements. According to the fruit pulp content, these varieties were divided into: (1) varieties with high Mg, P and K content, (2) varieties with low mineral element content, and (3) varieties with high Na and Ca content. The comprehensive analysis of relevant mineral element content factors showed that 'SSHMSL,' 'QYL,' 'SWSL' and 'ZLTSL-3' were the best varieties, and could be used as the focus varieties of future breeding programs for large-scale pear production.