Curcumin: An innovative approach for postharvest control of Alternaria alternata induced black rot in cherry tomatoes.

Curcumin, a natural bioactive compound derived from Curcuma longa, has been widely recognized for its antifungal properties. In this study, we investigated the effects of curcumin on the phytopathogenic fungus Alternaria alternata and its pathogenicity in cherry tomato fruit. The results demonstrated that curcumin treatment significantly inhibited mycelial growth and spore germination of A. alternata in a dose-dependent manner. Scanning electron microscopy revealed alterations in the morphology of A. alternata mycelia treated with curcumin. Furthermore, curcumin treatment led to an increase in malondialdehyde and hydrogen peroxide contents, indicating cell membrane damage in A. alternata. Moreover, curcumin exhibited a remarkable inhibitory effect on the incidence and lesion diameters of black rot caused by A. alternata in cherry tomato fruit. Gene expression analysis revealed upregulation of defense-related genes (POD, SOD, and CAT) in tomato fruit treated with curcumin. Additionally, curcumin treatment resulted in decreased activity of exocellular pathogenic enzymes (polygalacturonase, pectin lyase, and endo-1,4-ß-d-glucanase) in A. alternata. Overall, our findings highlight the potential of curcumin as an effective antifungal agent against A. alternata, providing insights into its inhibitory mechanisms on mycelial growth, spore germination, and pathogenicity in cherry tomato fruit.

Development and External Validation of a Gait Test Based Diagnostic Model for Detecting Mild Cognitive Impairment.

OBJECTIVE: To address the lack of large-scale screening tools for mild cognitive impairment (MCI), this study aimed to assess the discriminatory ability of several gait tests for MCI and develop a screening tool based on gait test for MCI. DESIGN: A diagnostic case-control test. SETTING: The general community. PARTICIPANTS: We recruited 134 older adults (≥65 years) for the derivation sample, comprising -69 individuals in the cognitively normal group and -65 in the MCI group (N=134). An additional 70 participants were enrolled for the validation sample. INTERVENTIONS: All participants completed gait tests consisting of a single task (ST) and 3 dual tasks (DTs): counting backwards, serial subtractions 7, and naming animals. MAIN OUTCOME MEASURES: Binary logistic regression analyses were used to develop models, and the efficacy of each model was assessed using receiver operating characteristic (ROC) curve and area under the curve (AUC). The best effective model was the final diagnostic model and validated using ROC curve and calibration curve. RESULTS: The DT gait test incorporating serial subtractions 7 as the cognitive task demonstrated the highest efficacy with the AUC of 0.906 and the accuracy of 0.831 in detecting MCI with "years of education" being adjusted. Furthermore, the model exhibited consistent performance across different age and sex groups. In external validation, the model displayed robust discrimination (AUC=0.913) and calibration (calibrated intercept=-0.062, slope=1.039). CONCLUSIONS: The DT gait test incorporating serial subtractions 7 as the cognitive task demonstrated robust discriminate ability for MCI. This test holds the potential to serve as a large-scale screening tool for MCI, aids in the early detection and intervention of cognitive impairment in older adults.

A Sensitive Ultra-performance Liquid Chromatography-Tandem Mass Spectrometric Method for Determination of Secalonic Acid F in Rat Plasma and Its Application to Pharmacokinetic Study.

Secalonic acid F (SAF) is a fungal secondary metabolite exhibited interesting pharmacological effect. In this study, a simple and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed and validated for the determination of SAF in rat plasma. Emodin was selected as the internal standard (IS), and plasma samples were prepared by liquid-liquid extraction with ethyl acetate. Chromatographic separation was operated on an Agilent SB-C18 column, and the mobile phase was a mixture of 0.5% formic acid in water and methanol (V:V = 20:80) at a flow rate of 0.3 mL/min. Detection was carried out with a 6460 triple-quadrupole mass spectrometer using electrospray ionization in the multiple-reaction monitoring mode. The MS/MS ion transitions monitored were m/z 639.3 â†’ 415.4 and 269.0 â†’ 225.1 for SAF and IS, respectively. Results showed the calibration curve of SAF was linear in the range of 2-500 ng·mL-1 with the correlation coefficient > 0.99. The matrix effect, extraction recovery, dilution effect, intraday and inter-day precision and accuracy were all in acceptable limits. The analytes were also stable under different conditions. The validated method was successfully applied to a pharmacokinetic study after oral administration in Sprague-Dawley rats at a dose of 10 mg/kg.

Alkaloid diversity expansion of a talent fungus Penicillium raistrichii through OSMAC-based cultivation.

Introduction: Alkaloidal natural products are attractive for their broad spectrum of pharmaceutical bioactivities. In the present work, the highly productive saline soil derived fungus, Penicillium raistrichii, was subjected to the strategy of OSMAC (one strain many compounds) with changes of cultivation status. Then, the work-flow led to the expansion of the alkaloid chemical diversity and subsequently induced the accumulation of four undescribed alkaloids, named raistrimides A-D (1-4), including three ß-carbolines (1-3), one 2-quinolinone (4), and one new natural product, 2-quinolinone (5), along with five known alkaloid chemicals (6-10). Methods: A set of NMR techniques including 1H, 13C, HSQC and HMBC, along with other spectroscopic data of UV-Vis, IR and HRESIMS, were introduced to assign the plain structures of compounds 1-10. The absolute configuration of 1-3 were elucidated by means of X-ray crystallography or spectroscopic analyses on optical rotation values and experimental electronic circular dichroism (ECD) data. In addition, it was the first report on the confirmation of structures of 6, 7 and 9 by X-ray crystallography data. The micro-broth dilution method was applied to evaluate antimicrobial effect of all compounds towards Staphylococcus aureus, Escherichia coli, and Candida albicans. Results and discussion: The results indicated compounds 1, 3 and 4 to be bioactive, which may be potential for further development of anti-antimicrobial agents. The finding in this work implied that OSMAC strategy was a powerful and effective tool for promotion of new chemical entities from P. raistrichii.

Spatio-temporal divergence and influencing factors of agritourism integration development in Xinjiang, China.

Exploring the coupling and coordination relationship between agriculture and tourism industry plays an important role in formulating differentiated integration development policies and promoting regional economic development. We adopt 14 prefectures and cities in Xinjiang, China as examples, and use a coupling coordination model and generalized method of moments estimation to explore the spatial differentiation characteristics and influencing factors between agriculture and tourism industries in various prefectures and cities in Xinjiang from 2009 to 2018. The results indicate: (1) The combined development levels of agriculture and tourism in Xinjiang exhibited a similar development trend over the period, and despite fluctuations in individual years, the overall trend is still increasing. (2) The coupling degree and coordination of agriculture and tourism in various regions presented significant spatial differentiation characteristics. (3) Human capital, residents' consumption level, and coupling coordination degree are positively correlated, while service capacity, government support, industrial foundation, and market supply and coupling coordination degree are significantly negatively correlated. Finally, based on our results, we present corresponding suggestions on how to improve the level of integrated development of agriculture and tourism in Xinjiang.

Differences in the influence of daily behavior on health among older adults in urban and rural areas: evidence from China.

Background: As the population of older adult in China keeps growing, the degree of aging is becoming increasingly serious and the health of older adults is a growing concern. Comparing the personal characteristics and health levels of urban and rural older adults and determining the relationship between these factors are of great significance in maintaining their health. In addition, exploring how these relationships differ between urban and rural areas is important. Method: This study conducted a literature review to examine the impact of various factors on the physical and mental health of older adults in urban and rural areas in China. Moreover, based on cross-sectional data from the 2017 Chinese General Social Survey (CGSS), urban-rural differences in the factors' degree of influence on the perceived health of older adults were studied using multiple logistic regression. Results: Regular physical exercise had a powerful protective effect on urban older adults' physical and mental health, whereas regular participation in social activities had a positive impact on rural older adults' health. Low income, low educational level, low social trust, lack of a partner, and having more than one child negatively affected the physical health of rural older people. Low socioeconomic status had a negative impact on rural people's health both in mind and body. Overall, the rural adults' health status was found to be relatively low and deserves more attention. Conclusion: This study demonstrated that older people's physical and mental health levels can be significantly affected by the frequency of daily activities and individual and family characteristics. Furthermore, urban-rural differences were observed. These findings could provide feasible suggestions for governments, communities, and older adults' family members to help alleviate health inequality.

Genome-wide characterization of SOS1 gene family in potato (Solanum tuberosum) and expression analyses under salt and hormone stress.

Salt Overly Sensitive 1 (SOS1) is one of the members of the Salt Overly Sensitive (SOS) signaling pathway and plays critical salt tolerance determinant in plants, while the characterization of the SOS1 family in potato (Solanum tuberosum) is lacking. In this study, 37 StSOS1s were identified and found to be unevenly distributed across 10 chromosomes, with most of them located on the plasma membrane. Promoter analysis revealed that the majority of these StSOS1 genes contain abundant cis-elements involved in various abiotic stress responses. Tissue specific expression showed that 21 of the 37 StSOS1s were widely expressed in various tissues or organs of the potato. Molecular interaction network analysis suggests that 25 StSOS1s may interact with other proteins involved in potassium ion transmembrane transport, response to salt stress, and cellular processes. In addition, collinearity analysis showed that 17, 8, 1 and 5 of orthologous StSOS1 genes were paired with those in tomato, pepper, tobacco, and Arabidopsis, respectively. Furthermore, RT-qPCR results revealed that the expression of StSOS1s were significant modulated by various abiotic stresses, in particular salt and abscisic acid stress. Furthermore, subcellular localization in Nicotiana benthamiana suggested that StSOS1-13 was located on the plasma membrane. These results extend the comprehensive overview of the StSOS1 gene family and set the stage for further analysis of the function of genes in SOS and hormone signaling pathways.

Structural characterization and partial properties of dextran produced by Leuconostoc mesenteroides RSG7 from pepino.

Exopolysaccharides (EPSs) produced by lactic acid bacteria possess various bioactivities and potential attractions for scientific exploration and commercial development. An EPS-producing bacterial strain, RSG7, was previously isolated from the pepino and identified as Leuconostoc mesenteroides. Based on the analyses of high-performance size exclusion chromatography, high-performance ion chromatography, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and methylation, the RSG7 EPS was identified as a dextran with a molecular weight of 5.47 × 106 Da and consisted of α-(1→6) glycosidic linkages as backbone and α-(1→2), α-(1→3), α-(1→4), and α-(1→6) glycosidic linkages as side chains. Scanning electron microscopy observed a honeycomb-like porous structure of RSG7 dextran, and this dextran formed aggregations with irregular hill-shaped lumps according to atomic force microscopy analysis. Physical-chemical investigations suggested that RSG7 dextran possessed excellent viscosity at high concentration, low temperature, and high pH; showed a superior emulsifying capacity of tested vegetable oils than that of hydrocarbons; and owned the maximal flocculating activity (10.74 ± 0.23) and flocculating rate (93.46 ± 0.07%) in the suspended solid of activated carbon. In addition, the dextran could coagulate sucrose-supplemented milk and implied potential probiotics in vitro. Together, these results collectively describe a valuable dextran with unique characteristics for exploitation in food applications.

Characteristics of starch from rice seeds modified by T-DNA insertion of ascorbate peroxidase 2.

Starch is the main storage carbohydrate in rice seed. The amylose and amylopectin content differ among varieties. A transgenic rice line was obtained by T-DNA insertion of ascorbate peroxidase 2 (apx2), resulting in decrease of thousand kernel weight. In this study, starches were isolated from apx2 and wild type seeds. Morphology, physical and chemical properties of starch granules were analyzed. The seed micro-surface in apx2 showed distinct textures, compared with that of wild type. The morphology of starch granules in apx2 exhibited irregular shapes, while the wild type starch granules presented regular polyhedral shapes. Additionally, the length and width of starch granules in apx2 were significantly decreased, compared with that of wild type. Further analysis found that apx2 starch showed low crystallinity and high amylose with the methods of X-ray diffraction pattern, iodine binding and blue value analysis, fourier transform infrared (FT-IR) spectrum and thermogravimetric investigation. This study broadened our knowledge of relationship between antioxidant enzyme and rice seed starch formation.

Polyarginine-Mediated siRNA Delivery: A Mechanistic Study of Intracellular Trafficking of PCL-R15/siRNA Nanoplexes.

As a cell-penetrating peptide, polyarginine is widely used in drug delivery systems based on its membrane permeation ability. Previously, we developed the mPEG-PLA-b-polyarginine(R15) triblock copolymer, which exhibited a high siRNA delivery efficiency both in vitro and in vivo. As a continued effort, here the amphiphilic diblock polymer PCL-R15 was synthesized as a simplified model to further elucidate the structure-activity relationship of arginine-based amphiphilic polymers as siRNA delivery systems, and the cellular trafficking mechanisms of the PCL-R15/siRNA nanoplexes were investigated to understand the interaction patterns between the nanoplexes and cells. Compared to the R15/siRNA complexes, the introduction of PCL moiety was found to result in the stronger interactions with cells and the enhanced transfection efficiency after the formation of condensed nanoplexes. Caveolae-mediated endocytosis and clathrin-mediated endocytosis were major routes for the internalization of PCL-R15/siRNA nanoplexes. The intracellular release of siRNA from nanoplexes was confirmed by fluorescence resonance energy transfer assay. It was also noticed that the internalized PCL-R15/siRNA nanoplexes were transported through digestive routes and trapped in lysosomes, which may be the bottleneck for efficient siRNA delivery of PCL-R15/siRNA nanoplexes. This study investigated the relationship between the polymer structure of PCL-R15 and the cellular interaction patterns, which may render implications on the rational design of polyarginine-based siRNA delivery systems.

Iizukines C-E from a saline soil fungus Aspergillus iizukae.

Three new alkaloids, iizukines C-E (1-3), including two aspochalasins (1 and 2), and one brasiliamide derivative (3), along with two known aspochalasins, rosellichalasin (4) and cytochalasin Z17 (5), were isolated from the culture of Aspergillus iizukae. Compound 1 was the first aspochalasin uniquely featuring a 1,2,4-triazole functionality, and 3 showed a pair of NMR signals in CDCl3 with a ratio of about 2:1 due to the existence of conformational isomers. Their structures were determined by extensive spectroscopic analyses and single-crystal X-ray diffractions. In particular, the 1,2,4-triazole moiety in 1 was assigned on the basis of extremely valuable 1H-15N HMBC spectrum. Compound 1 exhibited cytotoxic effect towards HL-60 and A549 cell lines with IC50 values of 3.8 and 7.2 µM, respectively.

New Butenolides and Cyclopentenones from Saline Soil-Derived Fungus Aspergillus Sclerotiorum.

Three new γ-hydroxyl butenolides (1-3), a pair of new enantiomeric spiro-butenolides (4a and 4b), a pair of enantiomeric cyclopentenones (5a new and 5b new natural), and six known compounds (6-11), were isolated from Aspergillus sclerotiorum. Their structures were established by spectroscopic data and electronic circular dichroism (ECD) spectra. Two pairs of enantiomers [(+)/(-)-6c and (+)/(-)-6d] obtained from the reaction of 6 with acetyl chloride (AcCl) confirmed that 6 was a mixture of two pairs of enantiomers. In addition, the X-ray data confirmed that 7 was also a racemate. The new metabolites (1-5) were evaluated for their inhibitory activity against cancer and non-cancer cell lines. As a result, compound 1 exhibited moderate cytotoxicity to HL60 and A549 with IC50 values of 6.5 and 8.9 µM, respectively, and weak potency to HL-7702 with IC50 values of 17.6 µM. Furthermore, compounds 1-9 were screened for their antimicrobial activity using the micro-broth dilution method. MIC values of 200 µg/mL were obtained for compounds 2 and 3 towards Staphylococcus aureus and Escherichia coli, while compound 8 exhibited a MIC of 50 µ/mL towards Candida albicans.

Analysis of Comparative Proteomic and Potent Targets of Peniciketal A in Human Acute Monocytic Leukemia.

BACKGROUND: Peniciketal A (Pe-A), a spiroketal compound, shows potent anticancer activities in human acute monocytic leukemia. However, the detailed mechanisms and potent targets of Pe-A remain largely unexplored. Here, we investigated the differentially expressed proteins between the Pe-A-treated group and the control group on human acute monocytic leukemia cell line THP-1. METHODS: The DEPs were analyzed by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) with TMT label. The function and feature of the identified proteins were analyzed by the bioinformatic analysis. Western blotting was used to evaluate protein expression. RESULTS: The DEPs were primarily sub located in the cytoplasm and the nucleus by regulating 21 pathways enriched through the Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, we preliminarily demonstrated that glucose-6-phosphate 1-dehydrogenase (G6PD), prolow-density lipoprotein receptor-related protein 1 (LRP1) and Calreticulin (CALR) might be the potent targets of Pe-A on death induction of THP-1 cells. CONCLUSION: Collectively, this study not only provides a global proteomic profile as the supplementary data of our previous studies but also provides interesting information that Pe-A may exert more bio-activities.

Effects of a spiroketal compound Peniciketal A and its molecular mechanisms on growth inhibition in human leukemia.

Peniciketal A (Pe-A), a spiroketal compound, is isolated from the saline soil-derived fungus Penicillium raistrickii. However, the underlying molecular mechanistic basis for the effects of Pe-A on leukemia is poorly understood. Here, we investigated that Pe-A reduced cell proliferation in three leukemia cell lines (THP-1, K562 and HL60). Importantly, Pe-A showed little cytotoxicity in primary mouse embryonic fibroblast (MEF) cells in a long-duration treatment. For the mechanistic research, we identified 3449 differentially expressed Pe-A-induced proteins through liquid chromatography-tandem mass spectrometry (LC-MS/MS) with TMT label in THP-1 cells. Results showed that many identified proteins were involved in apoptosis and/or autophagy. Then, we confirmed that Pe-A induced not only apoptosis via the mitochondrial pathway but also cytoprotective autophagy by activating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway indeed. In addition, Pe-A also arrested the cell cycle at the G0-G1 phase by regulating the expressions of checkpoint protein. Collectively, these results provide new insights into the mechanisms that Pe-A may target autophagy-related or apoptosis-related pathways to suppress the development of human leukemia.

Potential Antiviral Xanthones from a Coastal Saline Soil Fungus Aspergillus iizukae.

Five new (1⁻5) and two known xanthones (6 and 7), one of the latter (6) obtained for the first time as a natural product, together with three known anthraquinones, questin, penipurdin A, and questinol, were isolated from the coastal saline soil-derived Aspergillus iizukae by application of an OSMAC (one strain many compounds) approach. Their structures were determined by interpretation of nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, as well as comparison of these data with those of related known compounds. Antiviral activity of xanthones 1-7 was evaluated through the cytopathic effect (CPE) inhibition assay, and compound 2 exhibited distinctly strong activity towards influenza virus (H1N1), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) with IC50 values of 44.6, 21.4, and 76.7 µM, respectively, which indicated that it was worth to further investigate it as a potential lead compound. The preliminary structure-activity relationship of the xanthones is discussed.

Raistrickiones A-E from a Highly Productive Strain of Penicillium raistrickii Generated through Thermo Change.

Three new diastereomers of polyketides (PKs), raistrickiones A−C (1⁻3), together with two new analogues, raistrickiones D and E (4 and 5), were isolated from a highly productive strain of Penicillium raistrickii, which was subjected to an experimental thermo-change strategy to tap its potential of producing new secondary metabolites. Metabolites 1 and 2 existed in a diastereomeric mixture in the crystal packing according to the X-ray data, and were laboriously separated by semi-preparative HPLC on a chiral column. The structures of 1⁻5 were determined on the basis of the detailed analyses of the spectroscopic data (UV, IR, HRESIMS, 1D, and 2D NMR), single-crystal X-ray diffractions, and comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 1⁻5 represented the first case of 3,5-dihydroxy-4-methylbenzoyl derivatives of natural products. Compounds 1⁻5 exhibited moderate radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH).

Peniciketal A, A Novel Spiroketal Compound, Exerts Anticancer Effects by Inhibiting Cell Proliferation, Migration and Invasion of A549 Lung Cancer Cells.

BACKGROUND: Peniciketal A (Pe-A) is a spiroketal compound isolated from saline soil-derived fungus Penicillium raistrickii. However, its role for biological processes has not been clarified. In this study, we for the first time investigated the anticancer effects and the underlying mechanisms of Pe-A in A549 lung cancer cells. Metheds: Cell proliferation was tested by MTT assay and colony formation assay. Flow cytometry was performed to examine the cell cycle, apoptosis and mitochondrial membrane potential. Invasion and migration were analyzed using transwell assay and wound healing analysis. Immunofluorescence staining and western blotting were used to evaluate the protein expression. RESULTS: Pe-A effectively inhibited proliferation, with IC50 values was 22.33 µM for 72 h. Mechanistic studies revealed that Pe-A caused cell cycle arrest at the G0-G1 phase by decreasing cyclinD1 expression and induced apoptosis through accelerating the mitochondrial apoptotic pathway. Moreover, Pe-A significantly inhibited A549 cell migration and invasion by reducing the protein levels of MMP-2 and MMP-9, while the Epithelial- Mesenchymal Transition (EMT) property was also changed. Importantly, Pe-A exhibited much lower toxicity towards L02, normal liver cells, and MRC5, normal fibroblast cells, compared to A549 cells. CONCLUSION: Collectively, the current results indicate that Pe-A may offer effective potentials and insights for lung cancer treatment and drug design.

Pyran Rings Containing Polyketides from Penicillium raistrickii.

Five new pyran rings containing polyketides, penicipyrans A-E (1-5), together with the known pestapyrone A (6), were isolated from the saline soil-derived Penicillium raistrickii. Their structures were determined by interpretation of NMR and HRESIMS data. The absolute configurations of compounds 4 and 5 were established by the modified Mosher's method and single-crystal X-ray diffraction analysis, respectively. These compounds possessed high structural diversity including two α-pyrones (1, 2), three isocoumarins (3, 4, 6), and one dihydropyran derivative (5). Among them, Compound 5 exhibited cytotoxicity against HL-60 and K562 cell lines with IC50 values of 4.4 and 8.5 µM, respectively.

Systemic delivery of siRNA by T7 peptide modified core-shell nanoparticles for targeted therapy of breast cancer.

Systemic delivery of siRNA is the most challenging step to transfer RNAi to clinical application for breast cancer therapy. In this study, the tumor targeted, T7 peptide modified core-shell nanoparticles (named as T7-LPC/siRNA NPs) were constructed to achieve effective systemic delivery of siRNA. The core-shell structure of T7-LPC/siRNA NPs enables them to encapsulate siRNA in the core and protect it from RNase degradation during circulation. In vitro cellular uptake and gene silencing experiments demonstrated that T7-LPC/siEGFR NPs could deliver EGFR siRNA into breast cancer cells through receptor mediated endocytosis and effectively down-regulate the EGFR expression. In vivo distribution study proved the T7-LPC/siRNA NPs could deliver fluorescence labeled siRNA to the tumor site more efficiently than the non-targeted PEG-LPC/siRNA NPs after intravenous administration. Furthermore, the experiments of in vivo tumor therapy confirmed that intravenous administration of T7-LPC/siEGFR NPs led to an effective EGFR down-regulation and an obvious inhibition of breast tumor growth, with little activation of immune responses and negligible body weight loss. These results suggested that T7-LPC/siRNA NPs could be an effective and safe systemic siRNA delivery system for RNAi-based breast cancer therapy.

Diphenyl derivatives from coastal saline soil fungus Aspergillus iizukae.

Two new diphenyl derivatives, named iizukines A (1) and B (2), along with nine known compounds were isolated from coastal saline soil derived fungus Aspergillus iizukae. The structures were determined by extensive spectroscopic analysis. Their cytotoxicities were preliminarily evaluated on HL-60, BEL-7402 and A-549 cell lines by the MTT assay.