MEN1 is a regulator of alternative splicing and prevents R-loop-induced genome instability through suppression of RNA polymerase II elongation.

The fidelity of alternative splicing (AS) patterns is essential for growth development and cell fate determination. However, the scope of the molecular switches that regulate AS remains largely unexplored. Here we show that MEN1 is a previously unknown splicing regulatory factor. MEN1 deletion resulted in reprogramming of AS patterns in mouse lung tissue and human lung cancer cells, suggesting that MEN1 has a general function in regulating alternative precursor mRNA splicing. MEN1 altered exon skipping and the abundance of mRNA splicing isoforms of certain genes with suboptimal splice sites. Chromatin immunoprecipitation and chromosome walking assays revealed that MEN1 favored the accumulation of RNA polymerase II (Pol II) in regions encoding variant exons. Our data suggest that MEN1 regulates AS by slowing the Pol II elongation rate and that defects in these processes trigger R-loop formation, DNA damage accumulation and genome instability. Furthermore, we identified 28 MEN1-regulated exon-skipping events in lung cancer cells that were closely correlated with survival in patients with lung adenocarcinoma, and MEN1 deficiency sensitized lung cancer cells to splicing inhibitors. Collectively, these findings led to the identification of a novel biological role for menin in maintaining AS homeostasis and link this role to the regulation of cancer cell behavior.

Role of transcription factor complex OsbHLH156-OsIRO2 in regulating manganese, copper, and zinc transporters in rice.

Iron (Fe), manganese (Mn), copper (Cu), and zinc (Zn) are essential micronutrients that are necessary for plant growth and development, but can be toxic at supra-optimal levels. Plants have evolved a complex homeostasis network that includes uptake, transport, and storage of these metals. It was shown that the transcription factor (TF) complex OsbHLH156-OsIRO2 is activated under Fe deficient conditions and acts as a central regulator on Strategy II Fe acquisition. In this study, the role of the TF complex on Mn, Cu, and Zn uptake was evaluated. While Fe deficiency led to significant increases in shoot Mn, Cu, and Zn concentrations, the increases of these divalent metal concentrations were significantly suppressed in osbhlh156 and osiro2 mutants, suggesting that the TF complex plays roles on Mn, Cu, and Zn uptake and transport. An RNA-sequencing assay showed that the genes associated with Mn, Cu, and Zn uptake and transport were significantly suppressed in the osbhlh156 and osiro2 mutants. Transcriptional activation assays demonstrated that the TF complex could directly bind to the promoters of OsIRT1, OsYSL15, OsNRAMP6, OsHMA2, OsCOPT1/7, and OsZIP5/9/10, and activate their expression. In addition, the TF complex is required to activate the expression of nicotianamine (NA) and 2'-deoxymugineic acid (DMA) synthesis genes, which in turn facilitate the uptake and transport of Mn, Cu, and Zn. Furthermore, OsbHLH156 and OsIRO2 promote Cu accumulation to partially restore the Fe-deficiency symptoms. Taken together, OsbHLH156 and OsIRO2 TF function as core regulators not only in Fe homeostasis, but also in Mn, Cu, and Zn accumulation.

HNRNPA2B1-mediated m6A modification of FOXM1 promotes drug resistance and inhibits ferroptosis in endometrial cancer via regulation of LCN2.

N6-methyladenosine (m6A) methylation is an extensive posttranscriptional RNA modification, and it is associated with various cellular responses, especially in tumor progression. An m6A "reader"-HNRNPA2B1 has been found oncogenic in multiple malignancies. As a key proliferation-related transcription factor, forkhead box protein M1 (FOXM1) is involved in tumorigenesis. Here, we elucidated the underlying mechanism by which HNRNPA2B1-mediated modification of FOXM1 promotes endometrial cancer (EC). The GSE115810 dataset was used to analyze the upregulated gene mRNA in late-stage EC tissues. The expression levels of HNRNPA2B1, FOXM1, and LCN2 in EC samples were shown by western blotting and qPCR. The interaction among HNRNPA2B1, FOXM1, and LCN2 in EC cells was detected using bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down, RNA decay analysis, and luciferase reporter experiments. Cisplatin (DDP)-resistant EC cells were constructed using HEC-1-A and HEC-1-B cells, named HEC-1-A/DDP and HEC-1-B/DDP, respectively. Proliferation, migration, and invasiveness in treated HEC-1-A/DDP and HEC-1-B/DDP cells were detected by EdU, wound healing, and transwell assays. Ferroptosis-resistant gene expression, MDA level, and ROS level were measured. The m6A modification level in EC tissues was elevated. HNRNPA2B1 and FOXM1 levels were upregulated in EC. HNRNPA2B1 expression was positively related to FOXM1 expression in EC samples, and HNRNPA2B1 bound to the 3'UTR of FOXM1 and stabilized FOXM1 mRNA via m6A modification. FOXM1 positively regulated LCN2 expression in EC cells by binding to the LCN2 promotor. Knockdown of FOXM1 downregulated ferroptosis-resistant gene expression and increased MDA and ROS levels in DDP-resistant EC cells. Rescue assays revealed that LCN2 overexpression eliminated the effects mediated by FOXM1 knockdown on the proliferation, migration, invasiveness, and ferroptosis in DDP-resistant EC cells. In conclusion, HNRNPA2B1-mediated mA modification of FOXM1 facilitates drug resistance and inhibits ferroptosis in EC cells by upregulating LCN2 expression.

DNA methylation is involved in acclimation to iron-deficiency in rice (Oryza sativa).

Iron (Fe) is an essential micronutrient in plants, and Fe limitation significantly affects plant growth, yield and food quality. While many studies have reported the transcriptomic profile and pursue molecular mechanism in response to Fe limitation, little is known if epigenetic factors play a role in response to Fe-deficiency. In this study, whole-genome bisulfite sequencing analysis, high-throughput RNA-Seq of mRNA, small RNA and transposable element (TE) expression with root and shoot organs of rice seedlings under Fe-sufficient and Fe-deficient conditions were performed. The results showed that widespread hypermethylation, especially for the CHH context, occurred after Fe-deficiency. Integrative analysis of methylation and transcriptome revealed that the transcript abundance of Fe-deficiency-induced genes was negatively correlated with nearby TEs and positively with the 24-nucleotide siRNAs. The ability of methylation to affect the physiology and molecular response to Fe-deficiency was tested using an exogenous DNA methyltransferase inhibitor (5-azacytidine), and genetically using a mutant for domains rearranged methyltransferase 2 (DRM2), that lacks CHH methylation. Both approaches resulted in decreased growth and Fe content in rice plants. Thus, alterations in specific methylation patterns, directed by siRNAs, play an important role in acclimation of rice to Fe-deficient conditions. Furthermore, comparison with other reports suggests this may be a universal mechanism to acclimate to limited nutrient availability.

SDH mutations confer complex cross-resistance patterns to SDHIs in Corynespora cassiicola.

Succinate dehydrogenase inhibitors (SDHIs) are one of the most frequently used fungicides in cucumber fields in China. Our previous studies indicated that the sensitivity profile of Corynespora cassiicola, the causal agent of Corynespora leaf spot, to different SDHIs varied greatly; however, the underlying mechanism remains unclear. The 50% effective concentration (EC50) values of boscalid, fluopyram, fluxapyroxad and isopyrazam in C. cassiicola collected from 2017 to 2020 shifted, with resistance frequencies of 79.83%, 78.43%, 83.19% and 49.86%, respectively. The sequence alignment of sdhB/C/D of resistant strains revealed that eight single amino acid mutations (B-H278Y/L, B-I280V, C-S73P, C-N75S, C-H134R, D-D95E and D-G109V), and three dual-mutations (B-I280V&C-S73P, B-I280V&C-N75S and C-S73P&C-N75S) conferred various SDHI resistance levels and cross-resistance profiles. The expression level of the sdhB/C/D gene and succinate dehydrogenase (SDH) activity in the mutants were significantly altered by the presence of SDHIs, compared with the wild type strain. Additionally, molecular docking results suggested that the missense mutation influenced the crystal structure of SDH and subsequently interfered with the interaction bonds and bond distances among the target protein and chemicals. In brief, amino acid mutations altered the fungicide response of target gene expression, SDH activity and the binding features of SDH-ligand complexes and subsequently conferred multiple resistance levels and complex cross-resistance patterns to SDHIs in C. cassiicola. The evaluation of C. cassiicola resistance to SDHIs provided a significant foundation for efficient chemical development and integrated CLS management strategies.

Phosphonium ionic liquid-promoted Ce-doped nitrogen-rich TiO2for degradation gaseous pollutant under visible light irradiation.

Altering physicochemical properties of TiO2based on modifying the cation and anion structure of ionic liquids (ILs) is of great interests for environment. Up to date, the research involving IL-assisted synthesis of TiO2was focused on imidazolium IL, and much less attention was devoted to IL with other structures. Hence, strategy for preparation of TiO2in phosphonium IL is presented to control the growth of TiO2nanocrystals. The as-prepared noble cerium-doped nitrogen-rich phosphonium IL-TiO2photocatalyst with assisted by tributyl(propyl)phosphonium tetrafluoroborate exhibits a higher specific surface area and smaller crystallite size, which is conducive to the production of more and faster active substance, such as hydroxyl oxygen. When evaluated for photocatalysis of gaseous toluene under visible light irradiation, the sample manifests high degradation rate and efficiency, as well as excellent recycling performance due to the existence of superoxide radical produced by the Ce3+/Ce4+redox reaction. The introduction of phosphonium IL and Ce greatly enhanced charge separation efficiency and promoted production of active substances. Nitrogen also existed in the form of interstitial nitrogen and substituted nitrogen improves its response to visible light. This work shows promising application of phosphonium IL for highly enhanced TiO2photocatalytic performance.

Toxicity, residue and risk assessment of tetraniliprole in soil-earthworm microcosms.

Maize seed treatment with chemicals to control underground pests is a common agricultural practice, but inappropriate use of insecticides poses a considerable threat to plant development and soil nontarget organisms. In this study, the availability of tetraniliprole seed dressing to control the black cutworm Agrotis ipsilon (Lepidoptera: Noctuidae) in the maize seeding stage and its safety to earthworms (Eisenia fetida) were investigated. The selective toxicity (ST) of tetraniliprole between E. fetida and A. ipsilon was greater than 4000. No significant adverse effect of tetraniliprole seed treatment on the germination of maize seeds was observed at concentrations of 2.4-9.6 g a.i. /kg seed. Compared with the untreated control, seed treatment with tetraniliprole at 9.6 g a.i. /kg seed greatly reduced the percentage of damaged plants from 88.73% to 26.67%, and achieved the highest control effect of 69.91%. Tetraniliprole of 2.4 g a.i. /kg seed can effectively inhibit A. ipsilon until 14 days after seed germination, with the lowest mortality rate of 44.44%. During the entire exposure period, the maximum residual concentration of tetraniliprole detected in the soil (5.86 mg/kg) was considerably lower than the LC50 value of tetraniliprole to E. fetida (>4000 mg/kg). According to the low-tier risk assessment, the highest risk quotient (RQ) of tetraniliprole seed treatment to earthworms at test concentrations was 2.8 × 10-3, which was evaluated as acceptable. This study provided data support for tetraniliprole seed treatment to control underground pests in maize fields.

Evaluation of the antifungal and biochemical activities of mefentrifluconazole against Botrytis cinerea.

Mefentrifluconazole is the first product of a new sub-class of triazoles fungicides, i.e., the isopropanol triazoles, with the broad spectrum and high activity. In this study, the potential and biochemical activities of mefentrifluconazole against Botrytis cinerea were investigated. The frequency distribution of all EC50 values of mefentrifluconazole against mycelial growth and germ tube elongation of 106 isolates formed unimodal curve, with the mean EC50 values of 0.124 ± 0.025 and 0.015 ± 0.008 µg/mL, respectively. The effect of mefentrifluconazole against gray mold was determined on detached leaves of cucumber in vivo, the treatment of mefentrifluconazole at 200 µg/mL provided 100% preventative efficacy and 72.7% curative efficacy. No evident correlation was detected between the sensitivity of B. cinerea to mefentrifluconazole and that to tebuconazole, difenoconazole, myclobutanil, hexaconazole, triadimefon, flusilazole and pyrisoxazole (P > 0.05). Mefentrifluconazole treatment resulted in the increase of mycelium branch, the decrease of ergosterol content and the changes of the permeability of cell membrane. These studies evaluated the potential of mefentrifluconazole to control gray mold and helped us to understand the possible biochemical activity of mefentrifluconazole against B.cinerea.

The Bioactivity and Efficacy of Benzovindiflupyr Against Corynespora cassiicola, the Causal Agent of Cucumber Corynespora Leaf Spot.

Corynespora cassiicola, which causes Corynespora leaf spot, results in considerable yield loss of cucumber grown in greenhouses. Frequent reports of reduced efficacy and control failure of fungicides warrant new, efficient alternative chemistries. In this study, the sensitivity of C. cassiicola to benzovindiflupyr was evaluated using a collection of 81 isolates collected from Shandong, China. The mean EC50 values for mycelial growth, spore germination, and germ tube elongation of C. cassiicola were 0.69 ± 0.44, 0.12 ± 0.063, and 0.13 ± 0.076 µg ml-1, respectively. Benzovindiflupyr treatment led to a reduced respiration rate and ATP production of C. cassiicola and decreased spore pathogenicity by 21.9% on average. Additionally, detached cucumber leaves sprayed with fungicides before or after inoculation were used to assess the efficacy of benzovindiflupyr against C. cassiicola. Benzovindiflupyr (150 µg ml-1) exhibited preventive and curative efficacies of 86.9 and 77.1%, respectively. Benzovindiflupyr at 150 g a.i. ha-1 provided over 70% efficacy in field trials performed in 2018 and 2019, which was significantly higher than that of the reference fungicides fluopyram and fluxapyroxad at the same dose. Furthermore, the yield of commercial cucumber increased as disease incidence decreased. Our findings pave the way for the introduction of benzovindiflupyr in the integrated management of Corynespora leaf spot.

Activity of the Novel Fungicide Mefentrifluconazole Against Colletotrichum scovillei.

The prevalence and destructiveness of anthracnose, caused by Colletotrichum scovillei, in pepper production regions seriously affects pepper yield and quality. Mefentrifluconazole, the first of the isopropanol-azole subgroup of triazole fungicides, was introduced for the control of pepper anthracnose. However, the growth characteristics of pepper fruit and rapid spread of anthracnose suggest that the fungicide application method must be optimized to enhance fungicide efficacy. The sensitivity of C. scovillei to mefentrifluconazole was determined by mycelial growth and germ tube elongation assays using 157 single-spore isolates with mean 50% effective concentration values of 0.462 ± 0.138 and 0.359 ± 0.263 mg/liter, respectively. The in vivo data also showed that mefentrifluconazole had favorable protective and curative effects against pepper anthracnose. Mefentrifluconazole significantly affected C. scovillei infection on pepper by reducing appressorium formation and sporulation, shriveling spores and germ tubes, and causing the abnormal development of appressoria and conidiophores. Mefentrifluconazole could move acropetally, horizontally, and basipetally in pepper plants. Compared with a knapsack sprayer, mefentrifluconazole applied by mist sprayer exhibited significantly better activity against pepper anthracnose. Additionally, as the spray volume increased from 45 to 150 liters/ha, the control efficacy of mefentrifluconazole first increased and then tended to be steady, with an optimal spray volume of 90 liters/ha. The difference in disease control efficacy was related to the deposition and droplet distribution of mefentrifluconazole on the pepper fruit. These results provide scientific guidance for the application of mefentrifluconazole in pepper fields and improved fungicide utilization.

Development of a LAMP method for detecting the N75S mutant in SDHI-resistant Corynespora cassiicola.

The replacement of asparagine with serine at codon 75 of the sdhC gene (N75S) confers succinate dehydrogenase inhibitor resistance in Corynespora cassiicola, which caused by consecutive fungicide application. To rapidly detect the mutation of N75S, a method based on loop-mediated isothermal amplification (LAMP) was developed in this study. The optimal primer set among the six primer sets designed could clearly identify N75S from the wild-type genotype. The detection threshold of the optimized LAMP mixture (10 µL) was 8.8 fg of target DNA at 63 °C within 60 min. This method specifically showed a color change and ladder-like band only when DNA extracted from isolates containing the N75S mutation was added. The results of stability tests suggested a satisfactory repeatability of this method. Additionally, the assay could positively distinguish N75S mutants from crude DNA isolated from conidia and mycelia of C. cassiicola. Given the high efficiency, sensitivity, specificity, repeatability and simplicity of operation, the LAMP method established here could be useful to evaluate the shift in the sensitivity of C. cassiicola to SDHIs and will provide significant data for the management of Corynespora leaf spot.

Evaluation of Sensitivity and Resistance Risk of Corynespora cassiicola to Isopyrazam and Mefentrifluconazole.

Necrotic lesions on leaves caused by Corynespora leaf spot (CLS) seriously threaten the quality and yield of cucumber in China. Corynespora cassiicola has developed different degrees of sensitivity to various fungicides due to its long-term and extensive application. In our work, the effect of isopyrazam and mefentrifluconazole on different life stages of C. cassiicola was examined. To determine the optimal effect of binary mixtures of isopyrazam and mefentrifluconazole, the two fungicides were mixed at different proportions. Furthermore, the disease suppression of isopyrazam, mefentrifluconazole, and their compound mixture against CLS was evaluated in greenhouse experiments. Ultraviolet (UV) mutagenesis and fungicide-selection methods were performed to assess the risk of resistance development. Among the three life stages tested, isopyrazam showed the weakest inhibition on mycelial growth, and mefentrifluconazole showed the strongest inhibition of germ tube elongation. According to Wadley's and cotoxicity coefficient methods, the optimal proportion of the two-component mixture of isopyrazam and mefentrifluconazole was 1:1. Isopyrazam, mefentrifluconazole, and their binary mixture at 1:1 reduced the disease severity of CLS on potted cucumber plants, with protective effects of 31.11, 24.65, and 42.12% and curative effect of 33.90, 37.48, and 42.84%, respectively. Compared with isopyrazam or mefentrifluconazole alone, the binary mixture of the two fungicides at 1:1 did not exert significant influence on the change of C. cassiicola sensitivity. Undoubtedly, such data will greatly facilitate the screening of new fungicides for CLS and resistance management.

Phosphorus sorption behavior on sediments in Sanggou Bay related with their compositions by sequential fractionation.

The surficial sediment samples collected from the Sanggou Bay in China were treated by a sequential extraction procedure. After removal of calcite, organic matter and Fe/Mn oxides, P adsorption onto the sediment residues was then evaluated through kinetic and thermodynamic characteristics. The sorption kinetic curves could be described by a two-compartment first order equation. The sorption isotherms fit well with the Langmuir and Freundlich equations. The HCl-treated sediments with calcite removed showed a rising fraction of the rapid step and a higher P adsorption potential compared with the un-extracted samples. For the clay minerals and silicate residue after NH2OH·HCl treatment, the rapid step fraction was dominant, the sorption capability was prohibited, and the process was much more reversible than the original and previously-generated samples. An increase of temperature was favorable for the sorption. Estimation of thermodynamic parameters showed that the process was spontaneous and endothermic, with an increased randomness at the solid-liquid interface. Compared with the un-extracted sediment, the thermodynamic parameters in our case changed slightly after HCl treatment and NH2OH·HCl treatment.

Residue determination of pyraclostrobin, picoxystrobin and its metabolite in pepper fruit via UPLC-MS/MS under open field conditions.

In this study, a new, high-efficiency and sensitive method was determined to simultaneous analyze the residue of pyraclostrobin, picoxystrobin and its metabolite BF-500-3 in pepper fruit using modified QuEChERS pretreatment combined with ultra performance liquid chromatography-tandem mass spectrometry. The clean-up steps of QuEChERS procedure were optimized using the chemometric tools. Models of stepwise regression and surface response demonstrated that the optimal sorbent mixtures were 40 mg nano-zirconia + 10 mg C18 for pyraclostrobin and picoxystrobin and 30 mg nano-zirconia + 20 mg C18 for BF-500-3. The optimized purification procedures provided satisfactory recoveries for all tested fungicides with rates between 91% and 107% and relative standard deviations between 3.7% and 9.6%. The limits of detection and quantification were in the range of 0.0360-0.272 µg/kg and 0.120-0.910 µg/kg. Based on this method, the dissipation of pyraclostrobin, picoxystrobin and its metabolite in pepper fruit were determined under field conditions. Pyraclostrobin and picoxystrobin degraded rapidly with half-lives of 5.53-7.02 and 5.97-7.82 days and 5.09 and 5.68 days in 2016 and 2017, respectively. The residue levels of BF-500-3 increased first and then decreased. The terminal residues of all fungicides were below the maximum residue limits (MRLs). This research can not only provide guidance for the reasonable usage of pyraclostrobin and picoxystrobin in agriculture but also give a reference for the Chinese government to establish the MRL for pyraclostrobin in pepper.

A bioactivity and biochemical analysis of iminoctadine tris (albesilate) as a fungicide against Corynespora cassiicola.

Iminoctadine tris (albesilate) is a bis-guazatine fungicide, and its specific modes of action and efficacy against C. cassiicola are not yet clear. In this study, baseline sensitivity data for mycelial growth showed that the frequency distribution curve of iminoctadine tris (albesilate) EC50 values is unimodal. The EC50 values ranged from 0.1151 to 1.2101 µg/mL, with a mean of 0.5775 ±â€¯0.2677 µg/mL. Iminoctadine tris (albesilate) affected the morphological development of C. cassiicola, causing increased branching of the mycelium. The significant increase in membrane permeability and malondialdehyde content after iminoctadine tris (albesilate) treatment indicated that this fungicide caused severe damage to the membrane structure. Furthermore, 0.4 µg/mL iminoctadine tris (albesilate) could decrease the spore density of C. cassiicola from 2.6200 × 104 to 1.4967 × 104/cm2 on average in vitro, indicating that the fungicide had great potential to reduce secondary infection with C. cassiicola in the field. Additionally, 120 µg/mL iminoctadine tris (albesilate) provided over 95% curative efficacy and 81.17% preventative efficacy on detached cucumber leaves inoculated with C. cassiicola. In field trials, iminoctadine tris (albesilate) at a dose of 120 g a.i./ha exhibited 72.92% and 80.92% control efficacy in 2017 and 2018, respectively. However, the efficacy supplied by the reference fungicide azoxystrobin at 250 g a.i./ha was only approximately 50% due to the development of fungicide resistance in C. cassiicola. Taken together, the findings above provide a solid foundation for the exploration of the action mechanisms of iminoctadine tris (albesilate) against C. cassiicola and provide overwhelming evidence for the use of iminoctadine tris (albesilate) as an excellent potential alternative fungicide in the management of cucumber Corynespora leaf spot.

Evaluation of bioactivity and control efficacy of tetramycin against Corynespora cassiicola.

Tetramycin is a novel polyene antibiotic that has exhibited excellent inhibitory activity against many plant pathogens. In this study, the sensitivity of Corynespora cassiicola to tetramycin was assessed in vitro using a series of 91 isolates, and its effects on hyphae and conidia were evaluated. Preventive and curative efficacies of tetramycin against Corynespora leaf spot were evaluated using detached cucumber leaves and potted cucumber plants. The control efficacy of tetramycin against the pathogen was also determined under field conditions. Measurement of baseline sensitivity suggested that the frequency distribution of tetramycin fits a unimodal curve. Among several life stages, spore germination was most severely inhibited by tetramycin, whereas mycelial growth was found to be the least sensitive. Microscopy observation revealed that tetramycin treatment leads to abnormal morphological development of C. cassiicola. Overall, tetramycin exhibited excellent curative and preventive activities against C. cassiicola on both cucumber leaves and potted cucumber plants. Furthermore, tetramycin significantly reduced the disease severity of Corynespora leaf spot in the field. The results from this study showed that tetramycin may play an important role in Corynespora leaf spot disease management and promote its introduction into fungicide-application programs.

Baseline Sensitivity and Control Efficacy of Tetramycin Against Phytophthora capsici Isolates in China.

Tetramycin is a new biopesticide that combines high-level and broad-spectrum fungicidal activity, low toxicity, and environmental safety. In this study, 90 Phytophthora capsici isolates obtained from various regions in southern China were characterized for their baseline sensitivity to tetramycin. The protective and curative activities of tetramycin against P. capsici were determined on leaves of pepper, and the control efficacy of tetramycin in greenhouse experiments was also determined. Compared with mycelial growth, the formation of sporangia and the discharge of zoospores were inhibited by lower concentrations of tetramycin, approximately 5 µg ml-1 on V8 media. The frequency distribution curves for the tetramycin sensitivity were unimodal, with mean values for the fungicide concentration that reduced mycelial growth, sporangia formation, and zoospore discharge by 50% compared with the control of 1.18 ± 0.91, 0.64 ± 0.42, and 0.63 ± 0.30 µg ml-1, respectively. In addition, no correlation was observed between tetramycin and other fungicides tested, including mandipropamid, azoxystrobin, mefenoxam, fluazinam, fluopicolide, and famoxadone. Tetramycin exhibited both protective and curative effects against P. capsici in vitro, and its protective activity was better than its curative activity. In greenhouse experiments, tetramycin concentration of 60 and 90 µg ml-1 provided a protective control efficacy of 47.1 to 56.4% and curative efficacy of 43.3 to 52.7%. These results demonstrated that tetramycin could serve as an excellent alternative fungicide to control Phytophthora blight of pepper.

[Effect of Magnesium Sulfate, Nifedipine Tablet Combined Salvia Injection on ET-1/NO, TXA2/PGI2 and Hemorheology of Preeclampsia Patients].

OBJECTIVE: To observe the effect of magnesium sulfate, Nifedipine Tablet (NT) combined Salvia Injection (SI) on endothelin-1 (ET-1), nitric oxide (NO), thromboxane A2(TXA2), prostacyclin I2(PG2), and hemorheology of preeclampsia patients. METHODS: Totally 704 preeclampsia patients were randomly assigned to the treatment group and the control group, 352 cases in each group. All patients were treated with magnesium sulfate combined NT (on the first day: slow intravenous injection of magnesium sulfate 5 g + intravenous dripping of magnesium sulfate injection 10 g + oral administration of NT 30 mg; on the second and third day, intravenous dripping of magnesium sulfate injection 10 g + oral administration of NT 30 mg), while those in the treatment group were dripped with SI additionally at 20 mL per day for 3 consecutive days. Before and after treatment plasma levels of endothelin-1 (ET-1), nitric oxide (NO), TXA2, PGi2, and hemorheology indicators [such as high blood viscosity (HBV), low blood viscosity (LBV), plasma viscosity (PV), erythrocyte rigidity index (ERI), fibrinogen (FIB)] of two groups were detected. RESULTS: Compared with the same group before treatment, serum levels of ET-1, TXA2, HBV, LBV, PV, ERI, and FIB decreased in the two groups after treatment (P <0. 05), but levels of NO and PG2 increased (P <0. 05). Compared with the control group in the same period, levels of ET-1, TXA2, HBV, LBV, PV, ERI, and FIB decreased in the treatment group after treatment (P <0. 05), but levels of NO and PGI2 increased (P <0. 05). CONCLUSION: Magnesium sulfate, NT combined SI could effectively regulate the balance of ET-1/NO and TXA2/PGI2, and improve hemorheology of preeclampsia patients.

Co-exposure to Environmentally Relevant Levels of Molybdenum and Cadmium Induces Oxidative Stress and Ferroptosis in the Ovary of Ducks.

Excessive doses of molybdenum (Mo) and cadmium (Cd) have toxic effects on animals. Nevertheless, the reproductive toxicity elicited by Mo and Cd co-exposure remains obscure. To evaluate the co-induce toxic impacts of Mo and Cd on ovaries, 8-day-old 40 healthy ducks were stochastically distributed to four groups and were raised a basal diet supplemented with Cd (4 mg/kg Cd) and/or Mo (100 mg/kg Mo). In the 16th week, ovary tissues were gathered. The data revealed that Mo and/or Cd decreased GSH content, CAT, T-SOD, and GSH-Px activities and increased MDA and H2O2 levels. Moreover, there was a significant decrease in nuclear Nrf2 protein level and its related downstream factors, while cytoplasmic Nrf2 protein level showed a substantial increase. Additionally, a marked elevation was observed in ferrous ion content and TFRC, GCLC, SLC7A11, ACSL4, and PTGS2 expression levels, while FTH1, FTL1, FPN1, and GPX4 expression levels were conversely reduced. These indicators exhibited more marked changes in the joint exposure group. In brief, our results announced that Mo and/or Cd resulted in oxidative stress and ferroptosis in duck ovaries. Synchronously, the Cd and Mo mixture intensified the impacts.

Molybdenum and cadmium co-induce apoptosis and ferroptosis through inhibiting Nrf2 signaling pathway in duck (Anas platyrhyncha) testes.

Cadmium (Cd) and high molybdenum (Mo) are injurious to the body. Previous research has substantiated that Cd and Mo exposure caused testicular injury of ducks, but concrete mechanism is not fully clarified. To further survey the toxicity of co-exposure to Cd and Mo in testis, 40 healthy 8-day-old Shaoxing ducks (Anas platyrhyncha) were stochasticly distributed to 4 groups and raised with basic diet embracing Cd (4 mg/kg Cd) or Mo (100 mg/kg Mo) or both. At the 16th wk, testis tissues were gathered. The characteristic ultrastructural changes related to apoptosis and ferroptosis were observed in Mo or Cd or both groups. Besides, Mo or Cd or both repressed nuclear factor erythroid 2-related factor 2 (Nrf2) pathway via decreasing Nrf2, Heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), Glutamate-cysteine ligase catalytic subunit (GCLC) and Glutamate-cysteine ligase modifier subunit (GCLM) mRNA expression of and Nrf2 protein expression, then stimulated apoptosis by elevating Bcl-2 antagonist/killer-1 (Bak-1), Bcl-2-associated X-protein (Bax), Cytochrome complex (Cyt-C), caspase-3 mRNA expression, cleaved-caspase-3 protein expression and apoptosis rate, as well as reducing B-cell lymphoma-2 (Bcl-2) mRNA expression and ratio of Bcl-2 to Bax, and triggered ferroptosis by upregulating Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), transferrin receptor (TFR1) and Prostaglandin-Endoperoxide Synthase 2 (PTGS2) expression levels, and downregulating ferritin heavy chain 1 (FTH1), ferritin light chain 1 (FTL1), ferroportin 1 (FPN1), solute carrier family 7 member 11 (SCL7A11) and glutathione peroxidase 4 (GPX4) expression levels. The most obvious changes of these indexes were observed in co-treated group. Altogether, the results announced that Mo or Cd or both evoked apoptosis and ferroptosis by inhibiting Nrf2 pathway in the testis of ducks, and co-exposure to Mo and Cd exacerbated these variations.