Mingyuan Xu

The interaction between endophytic fungi and medicinal plants plays a crucial role in the production of secondary metabolites; however, the metabolic inter

Objective: This study investigates the physiological and biochemical responses of E. senticosus leaves to varying concentrations of P. oxalicum . Methods: Spore suspensions of P. oxalicum at 10 ³ (CL), 10 ⁴ (CM), and 10 ⁵ (CH) CFU/mL were applied via foliar spraying of E. senticosus leaves. Growth indices (fresh weight, dry weight, and Leaf drying rate), photosynthetic pigments (chlorophyll a, chlorophyll b, and carotenoids), carbohydrate metabolites (soluble sugars and starch), antioxidant enzyme activities, and chlorophyll fluorescence parameters were quantified. Additionally, total phenolic and flavonoid contents were measured. Results: CM treatment significantly increased leaf biomass, whereas CL treatment increased pigment accumulation, photosynthetic efficiency, and antioxidant enzyme activities. The contents of soluble sugars, starch, proteins, chlorophyll fluorescence, phenolics, and flavonoids also increased. In contrast, CH treatment suppressed several parameters. Conclusion: P. oxalicum induced a concentration-dependent biphasic response in E. senticosus . Lower concentrations promoted growth, photosynthetic function, and antioxidant capacity, whereas higher concentrations led to physiological inhibition. These findings emphasize the critical ability of spore concentration to modulate physiological processes and offer insights into strategies that can help improve the quality of medicinal plants.

Melatonin (MLT), a conserved small indole compound, exhibits anti‐inflammatory and antioxidant properties, contributing to its cardioprotective effects. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) is associated with atherosclerosis disease risk, and is known as an atherosclerosis risk biomarker. This study aimed to investigate the impact of MLT on Lp‐PLA2 expression in the atherosclerotic process and explore the underlying mechanisms involved. In vivo, ApoE ^−/− mice were fed a high‐fat diet, with or without MLT administration, after which the plaque area and collagen content were assessed. Macrophages were pretreated with MLT combined with ox‐LDL, and the levels of ferroptosis‐related proteins, NRF2 activation, mitochondrial function, and oxidative stress were measured. MLT administration significantly attenuated atherosclerotic plaque progression, as evidenced by decreased plaque area and increased collagen. Compared with those in the high‐fat diet (HD) group, the levels of glutathione peroxidase 4 (GPX4) and SLC7A11 (xCT, a cystine/glutamate transporter) in atherosclerotic root macrophages were significantly increased in the MLT group. In vitro, MLT activated the nuclear factor‐E2‐related Factor 2 (NRF2)/SLC7A11/GPX4 signaling pathway, enhancing antioxidant capacity while reducing lipid peroxidation and suppressing Lp‐PLA2 expression in macrophages. Moreover, MLT reversed ox‐LDL‐induced ferroptosis, through the use of ferrostatin‐1 (a ferroptosis inhibitor) and/or erastin (a ferroptosis activator). Furthermore, the protective effects of MLT on Lp‐PLA2 expression, antioxidant capacity, lipid peroxidation, and ferroptosis were decreased in ML385 (a specific NRF2 inhibitor)‐treated macrophages and in AAV‐sh‐NRF2 treated ApoE ^−/− mice. MLT suppresses Lp‐PLA2 expression and atherosclerosis processes by inhibiting macrophage ferroptosis and partially activating the NRF2 pathway.

Engineering dynamic control of gene expression is desirable because many engineered functions interfere with endogenous cellular processes that have evolved to facilitate growth and survival. Minimizing conflict between growth and production phases can therefore improve product titers in microbial cell factories. We developed an autoinduced gene expression system by rewiring the Saccharomyces cerevisiae pheromone response pathway. To ameliorate growth reduction due to the early onset response at low population densities, α-pheromone of Kluyveromyces lactis (Kα) instead of S. cerevisiae (Sα) was expressed in mating type "a" yeast. Kα-induced expression of pathway genes was further enhanced by the transcriptional activator Gal4p expressed under the control of the pheromone-responsive FUS1 promoter (P_fus1). As a demonstration, the engineered circuit combined with the deletion of the endogenous galactose metabolic pathway genes was applied to the production of human milk oligosaccharides, 2'-fucosyllactose (2'-FL) and 3-fucosllactose (3-FL). The engineered strains produced 3.37 g/L 2'-FL and 2.36 g/L 3-FL on glucose with a volumetric productivity of 0.14 and 0.03 g/L·h^-1 in batch flask cultivation, respectively. These represented 147 and 153% increases over the control strains on galactose wherein the respective pathway genes are expressed under GAL promoters only. Further fed-batch fermentation achieved titers of 32.05 and 20.91 g/L for 2' and 3-FL, respectively. The genetic program developed here thus represents a promising option for implementing dynamic regulation in yeast and could be used for the production of biochemicals that may place a heavy metabolic burden on cell growth.

Coexisting salt and alkaline stresses seriously threaten plant survival. Most studies have focused on halophytes; however, knowledge on how plants defend against saline–alkali stress is limited. This study investigated the role of Taraxacum mongolicum in a Puccinellia tenuiflora community under environmental saline–alkali stress to analyse the response of elements and metabolites in T. mongolicum, using P. tenuiflora as a control. The results show that the macroelements Ca and Mg are significantly accumulated in the aboveground parts (particularly in the stem) of T. mongolicum. Microelements B and Mo are also accumulated in T. mongolicum. Microelement B can adjust the transformation of sugars, and Mo contributes to the improvement in nitrogen metabolism. Furthermore, the metabolomic results demonstrate that T. mongolicum leads to decreased sugar accumulation and increased amounts of amino acids and organic acids to help plants resist saline–alkali stress. The resource allocation of carbon (sugar) and nitrogen (amino acids) results in the accumulation of only a few phenolic metabolites (i.e., petunidin, chlorogenic acid, and quercetin-3-O-rhamnoside) in T. mongolicum. These phenolic metabolites help to scavenge excess reactive oxygen species. Our study primarily helps in understanding the contribution of T. mongolicum in P. tenuiflora communities on coping with saline–alkali stress.

Effective drug intervention is the most important method to improve the prognosis, improve the quality of life, and prolong the life of patients with heart failure. This study aimed to explore the protective effect of astragaloside IV on myocardial cell injury induced by oxidized low-density lipoprotein (OxLDL) and its regulatory mechanism on the increase of brain natriuretic peptide (BNP) caused by myocardial cell injury. The model of myocardial cell injury, protection, and histone deacetylase (HDAC) inhibition in HL-1 mice was established by OxLDL treatment, astragaloside IV intervention, and UF010 coincubation. The effects of OxLDL and astragaloside IV on apoptosis were detected by flow cytometry. The expression level of BNP mRNA and protein in cells was investigated by real-time fluorescence quantification, western blot, and enzyme-linked immunosorbent assay. HDAC activity in nucleus was calibrated by fluorescence absorption intensity. Enzyme-linked immunosorbent assay (ELISA) was applied to test eNOS level in myocardial cells. OxLDL significantly promoted apoptosis, upregulated BNP mRNA, increased BNP protein level inside and outside cells, and decreased eNOS level. Compared with OxLDL treatment group, apoptosis decreased, BNP mRNA expression level decreased, BNP protein concentration decreased, and eNOS level increased significantly combined with low and high concentration astragaloside IV treatment group. HDAC activity significantly increased in OxLDL treatment group and significantly decreased after combined incubation with low and high concentrations of astragaloside IV. Inhibition of HDAC significantly increased eNOS level and decreased BNP protein level. In conclusion, astragaloside IV can reverse the low level of eNOS caused by OxLDL by regulating HDAC activity to protect myocardial cells from oxide damage, which is manifested by the decrease of BNP concentration.

Background: Mechanical damage is an unavoidable threat to the growth and survival of plants. Although a wound to senescing (lower) leaves improves plant vitality, a wound to younger (upper) leaves often causes damage to or death of the whole plant. Source-sink models are often used to explain how plants respond to biotic or abiotic stresses. In this study, a source-sink model was used to explain the difference in the metabolic mechanism of mechanical damage to young and senescing leaves of Catharanthus roseus. Results: In our study, GC-MS and LC-QTOF-MS metabolomics techniques were used to explore the differences in source-sink allocation and metabolic regulation in different organs of Catharanthus roseus after mechanical damage to the upper/lower leaves (WUL/WLL). Compared with that of the control group, the energy supplies of the WUL and WLL groups were increased and delivered to the secondary metabolic pathway through the TCA cycle. The two treatment groups adopted different secondary metabolic response strategies. The WLL group increased the input to the defense response after damage by increasing the accumulation of phenolics. A source-sink model was applied to the defensive responses to local (damaged leaves) and systemic (whole plant) damage. In the WUL group, the number of sinks increased due to damage to young leaves, and the tolerance response was emphasized. Conclusion: The accumulation of primary and secondary metabolites was significantly different between the two mechanical damage treatments. Catharanthus roseus uses different trade-offs between tolerance (repair) and defense to respond to mechanical damage. Repairing damage and chemical defenses are thought to be more energetically expensive than growth development, confirming the trade-offs and allocation of resources seen in this source-sink model.

Eleuthero (Eleutherococcus senticosus [Ruprecht & Maximowicz] Maximowicz is an important understory species as well as a source of natural products in Asia. The natural source of Eleuthero has been over exploited for pharmacological use, but the manual restoration to rehabilitate its natural distribution has not yet been established. The root is one of the main underground organs in Eleuthero for the acquisition of pharmaceutical ingredients. Root growth also determines the seedling quality of this species for ecological restoration. In this study, Eleuthero seedlings were cultured for one growing cycle with chitosan oligosaccharide (CO) addition at rates of 0 and 25 ppm under artificial lightings by high-pressure sodium (HPS) lamps and two light-emitting diodes (LEDs) with photosynthetic photon flux density set to 94±5 μmol m-2. Light spectra of red (R): green (G): blue (B) ratios were measured to be 43.7:54.6:1.7, 43.8:47:9.2, and 72.7:13.3:14 for the HPS, LED-1, and LED-2 treatments, respectively. In autumn, no interactive effect was found between CO addition and light spectra treatments on any root parameters. Compared to the HPS treatment, the LED-1 treatment resulted in a greater root dry weight and morphology by over 30%. The CO addition caused an increase of root growth by 40-70%. Fine roots in diameter between 0-0.4 mm were the main root part that contributed to the length, surface area, and root tip number. Therefore, LED lighting with the R/G/B spectrum of 43.8:47:9.2 was suggested for the culture of Eleuthero seedlings with the purpose of promoting dry weight and morphology of fine roots.

An ultra-performance liquid chromatography-electrospray ionization-mass spectrometry targeted metabolomics strategy was applied to analyze protocatechuate, syringin, eleutheroside E, isofraxidin, hyperoside, kaempferol, and oleanolic acid, the active compounds in 3-year-old, 5-year-old, and 9-year-old Acanthopanax senticosus. Then, targeted metabolomics was conducted with 3 growth year plants to identify 19 phenolic metabolites related to the above-mentioned active compounds, including 9 C₆C₃C₆-type, 6 C₆C₃-type, and 4 C₆C₁-type. Multivariate statistical analysis was applied to the bioactive metabolite data, and targeted metabolic profiling was used for marker compound classification and characterization. The results showed that 7 active compounds in the roots and stems in the 3 growth year plants differed. The principal component “Q” values showed that the total contents of 7 active compounds in 5-year-old roots and stems were higher than in other growth years. Results of targeted metabolomics profiling of 19 phenolic metabolites showed that the C₆C₁-type compounds accumulated in 9-year-old plants, the C₆C₃-type in 3-year-old plants, and the C₆C₃C₆-type in 5-year-old plants. The stems had the greatest accumulations of the phenolic metabolites. C₆C₁ and C₆C₃-type metabolites are the most abundant in both roots and stems. In conclusion, the active compounds and pharmacological effects of A. senticosus in different growth years are different. The best harvest age for A. senticosus roots and stems was 5 years. The accumulation of 19 phenolic metabolites in different growth years also showed significant differences.

Chlorpyrifos (CPF) and cadmium (Cd) are widespread environmental pollutants, which are often present in drinking water and foods. However, the combined effects of CPF and Cd were not entirely clear at present. There was also no biomarker available to diagnose the poisoning of the two chemicals at low dose for long-term exposures. In this study, we investigated the change of serum metabolites of rats with subchronic exposure to CPF, Cd, and CPF plus Cd using gas chromatography-mass spectrometer-based metabolomics approach. We performed a stepwise optimization algorithm based on receiver operating characteristic to identify serum metabolite biomarkers for toxic diagnosis of the chemicals at different doses after 90-day exposure. We found that aminomalonic acid was the biomarker for the toxicity of Cd alone administration, and serine and propanoic acid were unique biomarkers for the toxicities of CPF plus Cd administrations. Our results suggest that subchronic exposure to CPF and Cd alone, or in combination at their low doses, could cause disturbance of energy and amino acid metabolism. Overall, we have shown that analysis of serum metabolomics can make exceptional contributions to the understanding of the toxic effects following long-term low-dose exposure of the organophosphorus pesticide and heavy metal.