Molluscicidal effect mechanism study on metaldehyde to Pomacea canaliculate at low temperature.

BACKGROUND: Metaldehyde is a molluscicide commonly used to control Pomacea canaliculate. Its efficacy is significantly impacted by water temperature, although the underlying mechanisms have not been fully explored. RESULTS: In this study, we systematically investigated the temperature effect and molecular mechanisms of metaldehyde on P. canaliculata. The molluscicidal effect at various temperatures indicated that metaldehyde's molluscicidal activity significantly decreases with a drop in temperature. The LC50 value was only 458.8176 mg/L at 10 °C, while it surged to a high of 0.8249 mg/L at 25 °C. The impact of low temperature (10 °C) on metaldehyde's molluscicidal activity was analyzed via transcriptomics. The results revealed that the effect of low temperature primarily influences immunity, lipid synthesis, and oxidative stress. The expression of stress and immune-related genes, such as MANF, HSP70, Cldf7, HSP60, and PclaieFc, significantly increased. Furthermore, we studied the function of five target genes using RNA interference (RNAi) and discovered that Cldf7 and HSP70 could notably affect metaldehyde's molluscicidal effect. The mortality of P. canaliculata increased by 36.17% (72 h) after Cldf7 interference and by 48.90% (72 h) after HSP70 interference. CONCLUSION: Our findings demonstrate that low temperature can induce the extensive expression of the Cldf7 and HSP70 genes, resulting in a substantial reduction in metaldehyde's molluscicidal activity. © 2024 Society of Chemical Industry.

Sublethal effects of niclosamide on the aquatic snail Pomacea canaliculata.

Pomacea canaliculata is a malignant invasive aquatic snail found worldwide, and niclosamide (NS) is one of the primary agents used for its control. NS applied to water will exist in non-lethal concentrations for some time due to degradation or water exchange, thus resulting in sublethal effects on environmental organisms. To identify sublethal effects of NS on Pomacea canaliculata, we studied the aspects of histopathology, oxygen-nitrogen ratio (RO∶N), enzyme activity determination, and gene expression. After LC30 NS treatment (0.310 g/L), many muscle fibers of the feet degenerated and some acinar vesicles of the hepatopancreas collapsed and dissolved. The oxygen-nitrogen ratio (RO∶N) decreased significantly from 15.0494 to 11.5183, indicating that NS had changed the metabolic mode of Pomacea canaliculata and shifted it primarily to protein catabolism. Transcriptome analysis identified the sublethal effects of LC30 NS on the snails at the transcriptional level. 386, 322, and 583 differentially expressed genes (DEGs) were identified in the hepatopancreas, gills, and feet, respectively. GO (Gene Ontology) functional analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotations showed that DEGs in the hepatopancreas were mainly enriched for sugar metabolism, protein biosynthesis, immune response, and amino acid metabolism functional categories; DEGs in the gills were mainly enriched for ion transport and amino acid metabolism; DEGs in the feet were mainly enriched for transmembrane transport and inositol biosynthesis. In the future, we will perform functional validation of key genes to further explain the molecular mechanism of sublethal effects.

Validation of target protein PcnWAS in Pomacea canaliculata and screening of target-based molluscicidal compounds.

Virtual screening is an efficient way to obtain new drugs, which has become an important method in the field of pesticide research. Protein neural wiskott-Aldrich syndrome isoform X1 (PcnWAS) is a target protein that exists in the haemocytes of Pomacea canaliculata, and in this study, isothermal titration calorimetry (ITC) was used to evaluate the binding ability of protein PcnWAS and pedunsaponin A in vitro. Furthermore, it was set as a receptor, and the design of molluscicidal compounds based on protein PcnWAS was carried out. Results showed that, pedunsaponin A had high binding capacity with protein PcnWAS, and the binding constant (Ka) was 2.98 ± 1.74 × 10-4. A new potential molluscicidal compound thionicotinamide-adenine-dinucleotide (thionicotinamide-DPN) was obtained by virtual screening. In-vivo bioassay indicated that, the LC50 value was 57.7102 mg/L (72 h), and the oxygen consumption rate, ammonia excretion rate, oxygen nitrogen ratio and hemocyanin content of P. canaliculata declined after 60 mg/L thionicotinamide-DPN treated. Furthermore, the treatment of thionicotinamide-DPN also decreased gene expression level of protein PcnWAS. The results of ITC test showed that thionicotinamide-DPN can bind with protein PcnWAS efficiently, which means that it has the same target with pedunsaponin A when interacted with P. canaliculata. All the above results lay a foundation for the development of new molluscicides.

Study on the Synergistic Molluscicidal Effect of Pedunsaponin A and Niclosamide.

Niclosamide (NI) is the main molluscicide used to control Pomacea canaliculata (Lamarck) (Architaenioglossa: Ampullariidae). However, NI failed to inhibit snail climbing during the treatment process. In this study, we examined the effect of NI combined with pedunsaponin A at an ineffective concentration. The molluscicidal effect of Pedunsaponin A on NI was evidently synergistic after 48 h, and the synergism ratio (SR) was 1.82 after treatment for 72 h at 0.8 mg·L-1. Examination of the climbing adhesion effect showed that a high concentration of Pedunsaponin A (0.4 mg·L-1 and 0.8 mg·L-1) combined with NI significantly inhibited the climbing of P. canaliculata. We further studied the synergism mechanism; the results of histopathological observation showed that the siphon appeared cavities, the muscle fibers of the ventricular were severely dissolved, and kidney tubule arrangement was distorted after NI adding Pedunsaponin A. In addition, the hemocyte survival rate and the content of hemocyanin decreased significantly. According to the results of our study, the synergism mechanism may hinder oxygen transport of P. canaliculata, influencing the supply of energy; the ability of immune defense and excretion and metabolic detoxification decreased, prolonging the action time of NI in the body.

Research on the molluscicidal activity and molecular mechanisms of arecoline against Pomacea canaliculata.

Pomacea canaliculata, as an invasive snail in China, can adversely affect agricultural crop yields, ecological environment, and human health. In this paper, we studied the molluscicidal activity and mechanisms of arecoline against P. canaliculata. The molluscicidal activity tests showed that arecoline exhibits strong toxicity against P. canaliculata, and the LC50 value (72 h) was 1.05 mg/L (15 ± 2 mm shell diameter). Additionally, Molluscicidal toxicity were negatively correlated with the size of snails. Snails (25 ± 2 mm shell diameter) were choosed for mechanisms research and the result of microstructure and biochemistry showed that arecoline (4 mg/L, 20 â„ƒ) had strong toxic effect on the gill, and the main signs were the loss of cilia in the gill filaments. Moreover, arecoline significantly decreased the oxygen consumption rate, ammonia excretion rate and inhibited acetylcholinesterase (AChE). Then, the changes in protein expression were studied by iTRAQ, and 526 downregulated proteins were found. Among these, cilia and flagella-associated 157-like (PcCFP) and rootletin-like (PcRoo) were selected as candidate target proteins through bioinformatics analysis, and then RNA interference (RNAi) was adopted to verify the function of PcCFP and PcRoo. The results showed that after arecoline treated, the mortality and the cilia shedding rate of PcRoo RNAi treated group was significantly lower than control group. The above results indicate that arecoline can bind well with protein PcRoo, and then leads to the drop of gill cilia, affect respiratory metabolism, accelerate its entry into hemolymph, inhibit AChE and finally leads to the death of P. canaliculata.

SOFA Score in relation to Sepsis: Clinical Implications in Diagnosis, Treatment, and Prognostic Assessment.

Purpose: To analyze the clinical significance of the sequential organ failure assessment (SOFA) score in the diagnosis, treatment, and prognostic assessment of sepsis. Methods: 140 patients with sepsis from January 2020 to January 2021 were selected as the observation group, and 40 healthy people were selected as the control group. The observation group was divided into mild group, severe group, and septic shock group by single blind grouping according to the condition of the disease, and they were also divided into survival group and death group according to the prognosis. Collect the fasting venous blood of the subjects in each group in the morning, compare the levels of total bilirubin (TBIL), blood creatinine (CR), and platelet count (PLT) in each group, and record and compare the patients' respiratory system oxygen partial pressure/inhaled oxygen concentration (po2/fio2), acute physiology and chronic health scoring system II (APACHE II), sequential organ failure assessment (sofa) score, q-SOFA score, and △SOFA score; Pearson analysis was used to analyze the correlation between SOFA score and other indicators; multivariate logistic regression was used to analyze the prognostic risk factors of patients with sepsis; receiver-operating characteristic curve (ROC) was used to analyze the value of SOFA score alone and in combination in the diagnosis, condition, and prognosis of sepsis. Results: There were significant differences in Apache II score, SOFA score, q-SOFA score map, po2/fio2, PLT, GCS, TBIL, and serum creatinine (SCR) between the control group and the observation group (P < 0.05). There were significant differences in Apache II score, SOFA score, q-SOFA score, mean arterial pressure (map) po2/fio2, PLT, Glasgow Coma Score (GCS), TBIL, SCR, and △SOFA score among patients in mild, severe, and septic shock groups (P < 0.05). There were significant differences in age, Apache II score, SOFA score, q-SOFA score, map, po2/fio2, PLT, GCS, TBIL, SCR, and △SOFA score between survival group and death group (P < 0.05). SOFA score and q-SOFA score were significantly positively correlated with TBIL and SCR and significantly negatively correlated with po2/fio2 and PLT; △SOFA score was significantly negatively correlated with TBIL and SCR and significantly positively correlated with map, po2/fio2, PLT, and GCS. Apache II score, SOFA score, and q-SOFA score were independent risk factors for sepsis patients, and △SOFA score, po2/fio2, and GCS score were protective factors (P < 0.05). ROC curve analysis showed that the AUC of sepsis combined with SOFA score and q-SOFA score was 0.880; the AUC of sepsis assessed by SOFA score, q-SOFA score, and △SOFA score was 0.929; the AUC of sepsis prognosis assessed by SOFA score, q-SOFA score, and △SOFA score was 0.900. Conclusion: SOFA score, q-SOFA score, and △SOFA score were abnormally expressed in patients with sepsis and were risk factors for the severity of the patient's condition and prognosis. The SOFA score, q-SOFA score, and △SOFA score were risk factors for the severity and prognosis of patients with sepsis and had some value in diagnosing sepsis and assessing the condition and prognosis, of which the combined value of the three was higher.

Early Diagnosis and Prediction of Death Risk in Patients with Sepsis by Combined Detection of Serum PCT, BNP, Lactic Acid, and Apache II Score.

In order to investigate the expression levels of procalcitonin (PCT), B-type brain natriuretic peptide (BNP), and lactic acid (Lac) in serum of patients with sepsis, a retrospective analysis is conducted. 80 sepsis patients admitted to the ICU of our hospital from January 2019 to June 2020 are selected, and the application value of these factors combined with Apache II score in early diagnosis and prediction of death risk is analyzed. All patients are classified into survival group (n = 57) and death group (n = 23), and examined by blood routine. Lac, PCT, and BNP, and the serum PCT, BNP, and Lac levels were compared between the nonsepsis group and the control group. Furthermore, Acute Physiology and Chronic Health Status scoring System II (Apache II) is applied to evaluate the score difference between the sepsis group and the control group. The ROC curve demonstrates that PCT, BNP, and Lac combined with Apache II score can obtain high value for early diagnosis of sepsis. Compared with nonsepsis patients, the scores of serum Lac, PCT, and BNP and Apache II are significantly higher in sepsis patients. It is clearly evident that the combined detection of those indicators is valuable for early diagnosis and prediction of death, and will be suitable for widespread clinical application.

Antifungal Effects and Active Components of Ligusticum chuanxiong

The separation of chemical components from wild plants to develop new pesticides is a hot topic in current research. To evaluate the antimicrobial effects of metabolites of Ligusticum chuanxiong (CX), we systematically studied the antimicrobial activity of extracts of CX, and the active compounds were isolated, purified and structurally identified. The results of toxicity measurement showed that the extracts of CX had good biological activities against Botrytis cinerea, Sclerotinia sclerotiorum, Alternaria alternata and Pythium aphanidermatum, and the value of EC50 were 130.95, 242.36, 332.73 and 307.29 mg/L, respectively. The results of in vivo determination showed that under the concentration of 1000 mg/L, the control effect of CX extract on Blumeria graminis was more than 40%, and the control effect on Botrytis cinerea was 100%. The antifungal active components of CX were identified as Senkyunolide A and Ligustilide by mass spectrometry and nuclear magnetic resonance. The MIC (minimum inhibitory concentration) value of Senkyunolide A and Ligustilide against Fusarium graminearum were 7.81 and 62.25 mg/L, respectively. As a new botanical fungicide with a brightly exploitative prospect, CX extract has potential research value in the prevention and control of plant diseases.

Pharmacophore identification, virtual screening and activity verification of pedunsaponin A on target proteins PcAdv and PcnWAS of Pomacea canaliculata.

Target-protein-based pesticide screening has attracted wide-ranging attention on pesticide science. Pedunsaponin A (PA) is a compound isolated from the root of Pueraria peduncularis, and it has a strong toxic effect on Pomacea canaliculata. Previous studies found that Advlin (PcAdv) and neural Wiskott-Aldrich syndrome isoform X1(PcnWAS) are target proteins of PA when interacted with P. canaliculata. In this study, we modeled the two target proteins through I-Tasser and identified the pharmacophore of PA binding to the two target proteins by molecular docking. Furthermore, through virtual screening, potassium alginate was found to strongly bind to the target proteins in theory. In vivo bioassay showed that, similar to PA treatment, potassium alginate was able to induce typical poisoning symptoms on P. canaliculata, which were characterized by abnormal increase of excreta, weakening of climbing capacity, loss of gill cilia and decrease in hemocyanin content, and even cause death of P. canaliculata with a 13.33% mortality rate under 100 mg L-1 concentration. Furthermore, the treatment of potassium alginate also decreased the gene expression level of PcAdv and PcnWAS. These findings indicate that potassium alginate can affect the living state of P. canaliculata, and that it is feasible to develop new molluscicides based on PcAdv and PcnWAS by virtual screening. © 2022 Society of Chemical Industry.

Identification and functional verification of the target protein of pedunsaponin A in the gills of Pomacea canaliculata.

BACKGROUND: Based on previous research indicating that pedunsaponin A (PA) can destroy the gills of Pomacea canaliculata, we chose the gill as the main research object, and identified the target protein of PA in the gills of P. canaliculata through proteomics and RNA interference (RNAi). RESULTS: Proteomics showed that 180 proteins were downregulated after PA treatment in P. canaliculata. Among them, we chose advillin (PcAdv), receptor type tyrosine protein phosphatase (PcRT) and unconventional myosin heavy chain 6 (PcUM) as candidate target proteins through bioinformatics analysis. The small interfering RNA (siRNA) with the best interference effect was identified through further screening. Gene interference rates were 97%, 98% and 82% for PcAdv, PcRT and PcUM, respectively. The results showed that after RNAi treatment, the mortality of P. canaliculata treated with PcAdv (60.0%) was significantly lower than that for the control (93.3%); histological analysis showed that the structure of the gill was intact, cilia shedding was reduced, and the survival rate of hemocytes had increased. CONCLUSION: These findings indicate that, when the protein was absent or suppressed, the channel for entry of PA into the hemocytes of P. canaliculata was blocked, which reduced PA binding to hemocytes, and that there is a close relationship between shedding of gill cilia and PA entry into hemocytes. PcAdv is thus the key protein in PA destruction of gill cilia. Locating the proteins in gills that interact with drugs and investigating their mode of action is of great importance in the development of new molluscicides to control P. canaliculata populations.

Study on the fungicidal mechanism of glabridin against Fusarium graminearum.

Glabridin is a natural plant-derived compound that has been widely used in medicine and cosmetic applications. However, the fungicidal mechanism of glabridin against phytopathogens remains unclear. In this study, we determined the biological activity and physiological effects of glabridin against F. graminearum. Then the differentially expressed proteins of F. graminearum were screened. The EC50 values of glabridin in inhibiting the mycelial growth and conidial germination of F. graminearum were 110.70 mg/L and 40.47 mg/L respectively. Glabridin-induced cell membrane damage was indicated by morphological observations, DiBAC4(3) and PI staining, and measurements of relative conductivity, ergosterol content and respiratory rates. These assays revealed that the integrity of the membrane was destroyed, the content of ergosterol decreased, and the respiratory rate was inhibited. A proteomics analysis showed that 186 proteins were up-regulated and 195 proteins were down-regulated. Mechanically sensitive ion channel proteins related to transmembrane transport and ergosterol biosynthesis ERG4/ERG24, related to ergosterol synthesis were blocked. It is speculated that glabridin acts on ergosterol synthesis-related proteins to destroy the integrity of the cell membrane, resulting in abnormal transmembrane transport and an increased membrane potential. Finally, the morphology of mycelia was seriously deformed, growth and development were inhibited. As a result death was even induced.

Screening and functional verification of the target protein of pedunsaponin A in the killing of Pomacea canaliculata.

Previous study found that pedunsaponin A (PA) influenced the cytoskeleton of Pomacea canaliculata hemocytes, leading to depolarization and haemocyte destruction and eventually to snail death. In this study, we analysed the changes in protein expression by iTRAQ-mediated proteomics and identified 51 downregulated proteins. Among these, we focused on proteins related to cytoskeletal function and identified neural Wiskott-Aldrich syndrome isoform X1 (PcnWAS). The full-length PcnWAS gene contains 9791 bp and includes an open reading frame of 1401 bp that encodes 735 amino acids with a predicted molecular mass of 49.83 kD. PcnWAS exhibited a relatively distant genetic relationship with known species; the closest homologue is Biomphalaria glabrata (57%). RNA interference (RNAi) was adopted to verify the function of PcnWAS after screening the siRNA sequence with an efficiency of 97%. Interference with the gene expression of PcnWAS did not lead to snail death, but the depolarization level increased, which demonstrated that PcnWAS is an important depolarization-related protein. The results of PA treatment of snails subjected to RNAi proved that interfering with PcnWAS gene expression decreased the molluscicidal activity of PA toward P. canaliculata; snail mortality after RNAi was significantly lower (40%) than that in PA-treated snails without RNAi (54%), while the survival rate and depolarization level in haemocytes were not significant, indicating that PcnWAS is only one of the important target proteins of PA in P. canaliculata. This study lays the foundation for further exploration of the molecular mechanism by which PA kills this harmful snail.

Potential Role of Photosynthesis in the Regulation of Reactive Oxygen Species and Defence Responses to Blumeria graminis f. sp. tritici in Wheat.

Photosynthesis is not only a primary generator of reactive oxygen species (ROS) but also a component of plant defence. To determine the relationships among photosynthesis, ROS, and defence responses to powdery mildew in wheat, we compared the responses of the Pm40-expressing wheat line L658 and its susceptible sister line L958 at 0, 6, 12, 24, 48, and 72 h post-inoculation (hpi) with powdery mildew via analyses of transcriptomes, cytology, antioxidant activities, photosynthesis, and chlorophyll fluorescence parameters. The results showed that H2O2 accumulation in L658 was significantly greater than that in L958 at 6 and 48 hpi, and the enzymes activity and transcripts expression of peroxidase and catalase were suppressed in L658 compared with L958. In addition, the inhibition of photosynthesis in L658 paralleled the global downregulation of photosynthesis-related genes. Furthermore, the expression of the salicylic acid-related genes non-expressor of pathogenesis related genes 1 (NPR1), pathogenesis-related 1 (PR1), and pathogenesis-related 5 (PR5) was upregulated, while the expression of jasmonic acid- and ethylene-related genes was inhibited in L658 compared with L958. In conclusion, the downregulation of photosynthesis-related genes likely led to a decline in photosynthesis, which may be combined with the inhibition of peroxidase (POD) and catalase (CAT) to generate two stages of H2O2 accumulation. The high level of H2O2, salicylic acid and PR1 and PR5 in L658 possible initiated the hypersensitive response.

The relationship between BSP mRNA expression and 25(OH)D/OPG in peripheral blood of newly diagnosed T2DM patients with different bone mass.

INTRODUCTION: The objective of the study was to detect the levels of osteoprotegerin (OPG) and 25-hydroxyvitamin D [25(OH)D], as well as the expression of bone sialoprotein (BSP) mRNA, in the peripheral blood of patients with newly diagnosed type 2 diabetes mellitus (T2DM) under different bone mass conditions, and to explore its role and significance in the development process of T2DM combined with osteoporosis (OP). MATERIAL AND METHODS: A total of 225 patients hospitalised in the Endocrinology Department and General Department from May 2017 to May 2018 were enrolled and categorised into five groups: the pure T2DM group (group A, 45 patients), the bone mass reduction group (group B, 45 patients), the T2DM + bone mass reduction group (group C, 45 patients), the OP group (group D, 45 patients), and the T2DM + OP group (group E, 45 patients); meanwhile, age-matched healthy subjects undergoing physical examination in our hospital were collected as the normal control group (group NC, 45 cases). Logistic regression analysis was used to analyse the influencing factors of bone mass in patients with T2DM. RESULTS: Compared with group B, the expression levels of glycated haemoglobin (HbA1c), 25(OH)D, N-terminal propeptide of type I procollagen (PINP), fasting plasma glucose (FPG), fasting plasma insulin (FINS), high-density lipoprotein cholesterol (HDL-C), and BSP mRNA were significantly increased while OPG and b-collagen degradation products (b-CTX) were significantly decreased in group A. CONCLUSION: The expression of BSP mRNA and the decrease of 25(OH)D and OPG in peripheral blood may participate in the development of diabetes and osteoporosis.

Study of the Differentially Expressed Genes in the Pomacea canaliculata Transcriptome after Treatment with Pedunsaponin A.

Transcriptomes, genomes, and proteomes have played important roles in the search for drug targets. To determine the molluscicidal mechanism of pedunsaponin A against Pomacea canaliculata, RNA-seq technology was adopted to analyze the differentially expressed genes (DEGs) in the P. canaliculata transcriptome after treatment with pedunsaponin A. As a result, 533 DEGs were identified, among which 255 genes were significantly upregulated and 278 genes were significantly downregulated. According to the analysis of Gene Ontology (GO) functions, we found that the DEGs were significantly enriched in the viral life cycle, UDP-glucose 4-epimerase activity, guanylate cyclase activity, the cyclic guanosine monophosphate (cGMP) biosynthetic process, and the cGMP metabolic process. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway results showed that the DEGs were mainly involved in the hedgehog signaling pathway, phagosome, cytosolic DNA-sensing pathway, retinoic acid-inducible gene I like (RIG-I-like) receptor signaling pathway, bacterial secretion system, and nuclear factor-kappa B (NF-kappa B) signaling pathway. The above results indicated that pedunsaponin A causes a metabolic disorder, anomalous opening of membrane ion channels, and an imbalance in osmotic pressure between the interior and exterior of cells, eventually resulting in the death of cells involved in immune defense and influencing the immune response of P. canaliculata.

Purinostat Mesylate Is a Uniquely Potent and Selective Inhibitor of HDACs for the Treatment of BCR-ABL-Induced B-Cell Acute Lymphoblastic Leukemia.

PURPOSE: This study was to perform preclinical evaluation of a novel class I and IIb HDAC-selective inhibitor, purinostat mesylate, for the treatment of Ph+ B-cell acute lymphoblastic leukemia (B-ALL). EXPERIMENTAL DESIGN: Biochemical assays were used to test enzymatic activity inhibition of purinostat mesylate. Ph+ leukemic cell lines and patient cells were used to evaluate purinostat mesylate activity in vitro. BL-2 secondary transplantation Ph+ B-ALL mouse model was used to validate its efficacy, mechanism, and pharmacokinetics properties in vivo. BCR-ABL(T315I)-induced primary B-ALL mouse model and PDX mouse model derived from relapsed Ph+ B-ALL patient post TKI treatment were used to determine the antitumor effect of purinostat mesylate for refractory or relapsed Ph+ B-ALL. Long-term toxicity and hERG blockade assays were used to safety evaluation of purinostat mesylate. RESULTS: Purinostat mesylate, a class I and IIb HDAC highly selective inhibitor, exhibited robust antitumor activity in hematologic cancers. Purinostat mesylate at low nanomolar concentration induced apoptosis, and downregulated BCR-ABL and c-MYC expression in Ph+ leukemia cell lines and primary Ph+ B-ALL cells from relapsed patients. Purinostat mesylate efficiently attenuated Ph+ B-ALL progression and significantly prolonged the survival both in BL-2 secondary transplantation model with clinical patient symptoms of Ph+ B-ALL, BCR-ABL(T315I)-induced primary B-ALL mouse model, and PDX model derived from patients with relapsed Ph+ B-ALL post TKI treatment. In addition, purinostat mesylate possesses favorable pharmacokinetics and low toxicity properties. CONCLUSIONS: Purinostat mesylate provides a new therapeutic strategy for patients with Ph+ B-ALL, including those who relapse after TKI treatment.

The Damaging Effects of Pedunsaponin A on Pomacea canaliculata Hemocytes.

Pomacea canaliculata hemocytes are the main functional cells in the immune defense system, and hemocyte destruction disrupts the immune response mechanism of P. canaliculata, resulting in abnormal growth, development, reproduction, and even death. Our previous study found that Pedunsaponin A significantly affects P. canaliculata hemocyte structure. This study further investigated the damaging effects of Pedunsaponin A on P. canaliculata hemocytes. The cell mortality rate results showed that the hemocyte mortality was significantly increased after treatment with Pedunsaponin A, and the mortality rate exhibited a significant positive correlation with treatment time and dose. The membrane potential results showed that the cell membranes of P. canaliculata hemocytes exhibited time-dependent membrane depolarization after 40 mg/L Pedunsaponin A treatment. At 36 h, the cell depolarization rate in the Pedunsaponin A treatment group was 41.43%, which was significantly greater than the control group (6.24%). The cytoskeleton results showed that Pedunsaponin A led to disordered and dispersed arrangement of microfilaments and changes in the cytoskeletal structure. The apoptosis and cell cycle results showed that Pedunsaponin A induced apoptosis and influenced the cell cycle to some extent. These results showed that the cell membrane and cytoskeleton of P. canaliculata hemocytes were damaged after treatment with Pedunsaponin A, which led to an increase in cell mortality, dysfunction, cell cycle abnormalities and apoptosis. This study provides a foundation for further identification of the site of Pedunsaponin A activity on hemocytes.

Comparative Proteomic Analysis of Wheat Carrying Pm40 Response to Blumeria graminis f. sp. tritici Using Two-Dimensional Electrophoresis.

Wheat powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) is considered a major wheat leaf disease in the main wheat producing regions of the world. Although many resistant wheat cultivars to this disease have been developed, little is known about their resistance mechanisms. Pm40 is a broad, effective resistance gene against powdery mildew in wheat line L699. The aim of this study was to investigate the resistance proteins after Bgt inoculation in wheat lines L699, Neimai836, and Chuannong26. Neimai836 with Pm21 was used as the resistant control, and Chuannong26 without any effective Pm genes was the susceptible control. Proteins were extracted from wheat leaves sampled 2, 4, 8, 12, and 24 h after Bgt inoculation, separated by two-dimensional electrophoresis, and stained with Coomassie brilliant blue G-250. The results showed that different proteins were upregulated and downregulated in three wheat cultivars at different time points. For the wheat cultivar L699, a total of 62 proteins were upregulated and 71 proteins were downregulated after Bgt inoculation. Among these, 46 upregulated proteins were identified by mass spectrometry analysis using the NCBI nr database of Triticum. The identified proteins were predicted to be associated with the defense response, photosynthesis, signal transduction, carbohydrate metabolism, energy pathway, protein turnover, and cell structure functions. It is inferred that the proteins are not only involved in defense response, but also other physiological and cellular processes to confer wheat resistance against Bgt. Therefore, the resistance products potentially mediate the immune response and coordinate other physiological and cellular processes during the resistance response to Bgt. The lipoxygenase, glucan exohydrolase, glucose adenylyltransferasesmall, phosphoribulokinase, and phosphoglucomutase are first reported to be involved in the interactions of wheat-Bgt at early stage. The further study of these proteins will deepen our understanding of their detailed functions and potentially develop more efficient disease control strategies.

Compounds from the root of Pueraria peduncularis (Grah. ex Benth.) Benth. and their antimicrobial effects.

BACKGROUND: Pueraria peduncularis belongs to the genus Pueraria DC, and has a wide range of medical and agricultural activities. Previous studies have shown that P. peduncularis extracts have broad bioactivities against phytopathogens. In this paper, we systematically studied the fungicidal activity of root methanol extracts and further isolated the active compounds. RESULTS: The root methanol extract inhibited the mycelial growth of the five tested phytopathogens to different degrees. Among these phytopathogens, the inhibitory effect was greatest against R. solani, with an EC50 value of 324.72 mg L-1 . Eight compounds were subsequently isolated and identified from P. peduncularis. Among them, puercarpan A and medicarpin showed strong fungicidal activity, with MIC values against Rhizoctonia solani of 1.6 and 6.25 mg L-1 , respectively. Puercarpan A is a new compound, and its structure was established as (6aR,6bS,11aR)-6b-hydroxy-3-methoxypterocarpan-10-ene-7-one. CONCLUSION: The P. peduncularis extracts exhibit high antimicrobial activity against R. solani and have great potential value of P. peduncularis as a fungicide. © 2019 Society of Chemical Industry.

Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs).

Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome.