Oral matrine alleviates CCl4-induced liver fibrosis via preserved HSP72 from modulated gut microbiota.

Hepatic fibrosis is intricately associated with dysregulation of gut microbiota and host metabolomes. Our previous studies have demonstrated that matrine can effectively reduce hepatosteatosis and associated disorders. However, it is poorly understood whether the gut microbiota involved in the attenuation of liver fibrosis by matrine. Herein we explored a novel mechanism of how oral administration of matrine alleviates liver fibrosis by modulating gut microbiota. Administration of matrine not only potently ameliorated liver fibrosis in carbon tetrachloride (CCl4)-induced mice, but also significantly preserved hepatic heat shock protein 72 (HSP72) in vivo and in vitro. Matrine was failed to reduce liver fibrosis when HSP72 upregulation was blocked by the HSP72 antagonist VER-155008. Also, consumption of matrine significantly alleviated gut dysbiosis and fecal metabonomic changes in CCl4-treated mice. Transplanted the faces of matrine-treated mice induced a remarkable upregulation of HSP72 and remission of fibrosis in liver in CCl4-exposed mice and inhibition of TGF-ß1-induced inflammatory response and epithelial-mesenchymal transition (EMT) in AML-12 cells. Furthermore, deficiency of HSP72 partly reversed the intestinal microbial composition that prevented matrine from reducing CCl4-induced liver fibrosis in mice. This study reveals the "gut microbiota-hepatic HSP72" axis as a key mechanism of matrine in reducing liver fibrosis and suggest that this axis may be targeted for developing other new therapies for liver fibrosis.

Crosstalk between ethylene and melatonin activates isoflavone biosynthesis and antioxidant systems to produce high-quality soybean sprouts.

Isoflavone, which are mainly found in soybeans, are a secondary metabolite with a variety of physiological functions. In recent years, increasing the isoflavone content of soybeans has received widespread attention. Although ethephon treatment significantly increased isoflavone content in soybean sprouts, it also had a certain inhibitory effect on the growth of sprouts. Melatonin (MT), as a new type of plant hormone, not only alleviated the damage caused by abiotic stress to plants, but also promoted the synthesis of secondary metabolites. In this study, we aimed to elucidate the mechanism of exogenous MT in regulating the growth and development, and the metabolism of isoflavone in soybean sprouts under ethephon treatment. The results indicated that MT alleviated the adverse effects of ethephon treatment on soybean sprouts by increasing the activities of superoxide dismutase, peroxidase, catalase, and the expression of their corresponding genes, as well as decreased the content of malondialdehyde and hydrogen peroxide. In addition, MT further increased the isoflavone content by up-regulating the expression level of isoflavone synthesis genes and increased the activities of phenylalanine ammonia-lyase and cinnamic acid 4-hydroxylase under ethephon treatment. This study provided technical support and reference value for the production of high-quality soybean sprouts to a certain extent.

Methyl Jasmonate and Zinc Sulfate Induce Secondary Metabolism and Phenolic Acid Biosynthesis in Barley Seedlings.

This study aimed to reveal the impact of MeJA and ZnSO4 treatments on the physiological metabolism of barley seedlings and the content of phenolic acid. The results showed that MeJA (100 µM) and ZnSO4 (4 mM) treatments effectively increased the phenolic acid content by increasing the activities of phenylalanine ammonia-lyase and cinnamate-4-hydroxylase (PAL) and cinnamic acid 4-hydroxylase (C4H) and by up-regulating the expression of genes involved in phenolic acid synthesis. As a result of the MeJA or ZnSO4 treatment, the phenolic acid content increased by 35.3% and 30.9% at four days and by 33.8% and 34.5% at six days, respectively, compared to the control. Furthermore, MeJA and ZnSO4 treatments significantly increased the malondialdehyde content, causing cell membrane damage and decreasing the fresh weight and seedling length. Barley seedlings responded to MeJA- and ZnSO4-induced stress by increasing the activities of antioxidant enzymes and controlling their gene expression levels. Meanwhile, MeJA and ZnSO4 treatments significantly upregulated calcium-adenosine triphosphate, calmodulin-dependent protein kinase-related kinase, and calmodulin-dependent protein genes in barley seedlings. This suggested that Ca2+ may be the signaling molecule that promotes phenolic acid synthesis under MeJA and ZnSO4 treatment. This study deepens the understanding of the phenolic acid enrichment process in barley seedlings under MeJA and ZnSO4 treatments.

Melatonin mediates phenolic acids accumulation in barley sprouts under MeJA stress.

Phenolic acids are secondary metabolites in higher plants, with antioxidant, anticancer, and anti-aging effects on the human body. Therefore, foods rich in phenolic acids are popular. Methyl jasmonate (MeJA) promoted phenolic acids accumulation but also inhibited sprout growth. Melatonin (MT) was a new type of plant hormone that not only alleviated plants' abiotic stress, but also promoted the synthesis of plant-stimulating metabolism. This study aimed to elucidate the mechanism of exogenous MT on the growth and development, and phenolic acids metabolism of barley sprouts under MeJA treatment. The results showed that MT increased the phenolic acids content in sprouts by increasing the activities of phenylalanine ammonia-lyase and cinnamic acid 4-hydroxylase, and up-regulating the gene expression of phenylalanine ammonia-lyase, cinnamic acid 4-hydroxylase, 4-coumarate: coenzyme a ligase, and ferulic acid-5-hydroxylase. MT attenuated the growth inhibition of barley sprouts under MeJA stress by increasing the activities of regulated antioxidant enzymes and the expression of their corresponding genes. Furthermore, MT increased the NO content and induced Ca2+ burst in barley sprouts under MeJA stress. These events were inhibited by DL-4-Chlorophenylalanine. These results suggested that MT ameliorated growth inhibition and promoted the biosynthesis of phenolic acids in barley sprouts under MeJA stress.

Leveraging microalgae as a sustainable ingredient for meat analogues.

As the world's population and income levels continue to rise, there is a substantial increase in the demand for meat, which poses significant environmental challenges due to large-scale livestock production. This review explores the potential of microalgae as a sustainable protein source for meat analogues. The nutritional composition, functional properties, and environmental advantages of microalgae are analyzed. Additionally, current obstacles to large-scale microalgal food production are addressed, such as strain development, contamination risks, water usage, and downstream processing. The challenges associated with creating meat-like textures and flavors using techniques like extrusion and emulsion formation with microalgae are also examined. Lastly, considerations related to consumer acceptance, marketing, and regulation are summarized. By focusing on improvements in cultivation, structure, sensory attributes, and affordability, microalgae demonstrate promise as a transformative and eco-friendly protein source to enhance the next generation of meat alternatives.

Enrichment of Flavonoids in Short-Germinated Black Soybeans (Glycine max L.) Induced by Slight Acid Treatment.

Exogenous abiotic stimulant treatments are a straightforward and effective method for enhancing secondary metabolites in plants. In this study, the response surface optimization method was used to optimize the conditions for enriching flavonoids in short-germinated black soybeans under a slight acid treatment, and the mechanism of flavonoid accumulation during black soybean germination was explored. The results show that the use of a 126.2 mM citric acid-sodium citrate buffer (pH 5.10) as a slight acid treatment resulted in the highest flavonoid content when the black soybeans were germinated for 24 h. Under these conditions, the isoflavonoid (glycitin, daidzein, and genistein) increased significantly, and the flavonoid content reached 2.32 mg/g FW. The microacidified germination treatment significantly increased the activities and relative gene expression levels of key enzymes involved in flavonoid metabolism (4-coumarate-CoA ligase and cinnamic acid 4-hydroxylase, etc.). However, the slight acid treatment inhibited the growth of the black soybeans and caused damage to their cells. This was evidenced by significantly higher levels of malondialdehyde, superoxide anion, and hydrogen peroxide compared to the control group. Furthermore, the antioxidant system in the short-germinated soybeans was activated by the slight acid treatment, leading to a significant increase in the activities and relative gene expression levels of catalase and peroxidase. The results above show that a slight acid treatment was beneficial in inducing the accumulation of flavonoids during the growth of black soybean sprouts. This lays a technical foundation for producing black soybean products that are rich in flavonoids.

Fabrication of flexible chitosan film reinforced with pulping by-product lignosulfonates for cherry-tomato preservation.

The massive production of food waste and plastic pollution necessitates innovative solutions. This study reports the first fabrication of a flexible chitosan (CH) film reinforced with lignosulfonate (LS) derived from pulping byproduct as a sustainable alternative to synthetic food packaging. The CH/LS composite film was prepared by a simple casting method with varying LS contents of 1 % and 2 %. Compared to CH film, the addition of 2 % LS increased the tensile strength by over 4 times and decreased water vapor permeability by 11 %. Moreover, the CH/LS film exhibited excellent UV-shielding properties. This novel use of LS to reinforce CH film presents an eco-friendly active packaging material. When used to package cherry tomatoes for 2 weeks, the CH/LS film effectively maintained fruit freshness and hardness while minimizing weight loss. This work provides new scientific evidence on the optimized preparation and application of CH/LS composite films from renewable resources for food preservation.

Salicylic acid promotes phenolic acid biosynthesis for the production of phenol acid-rich barley sprouts.

BACKGROUND: Phenolic acid exhibits a variety of well-known physiological functions. In this study, optimal germination conditions to ensure total phenolic acid enrichment in barley sprouts induced by salicylic acid treatment and its effects on sprout physiology and activity, as well as the gene expression of key enzymes for phenolic acid biosynthesis, were investigated. RESULTS: When sprouts were treated with 1 mmol L-1 salicylic acid during germination and germinated at 25 °C for 4 days, the phenolic acid content was 1.82 times that of the control, reaching 1221.54 µg g-1 fresh weight. Salicylic acid significantly increased the activity of phenylalanine aminolase and cinnamic acid-4-hydroxylase and the gene expression of phenylalanine aminolase, cinnamic acid-3-hydroxylase, cinnamic acid-4-hydroxylase, 4-coumaric acid-coenzyme A, caffeic acid O-methyltransferase, and ferulate-5-hydroxylase in barley sprouts. However, salicylic acid treatment significantly increased malondialdehyde and H2O2 content, H2O2 and O2 - fluorescence intensity, as well as significantly decreasing sprout length and fresh weight. Salicylic acid treatment markedly increased the activity of peroxidase and catalase and the gene expression of peroxidase, catalase, and ascorbate peroxidase in barley sprouts. CONCLUSION: Salicylic acid treatment during barley germination significantly promoted the enrichment of total phenolic acid by increasing the activities and gene expression levels of enzymes involved in the phenolic acid biosynthesis pathway. Salicylic acid induced the accumulation of reactive oxygen species, inhibited sprout growth, and activated the antioxidant system. This study provides a basis for the future development of functional foods using phenol acid-rich plants as raw materials. © 2024 Society of Chemical Industry.

Exogenous methyl jasmonate promotes the biosynthesis of endogenous melatonin in mustard sprouts.

The present study investigated the effects regulating melatonin (MT) biosynthesis under methyl jasmonate (MeJA) treatment in mustard sprouts. The results revealed that MeJA significantly increased the MT content in the sprouts to 11.43 times that of the control. However, MeJA treatment had an inhibitory effect on growth. Tryptophan decarboxylase and tryptamine 5-hydroxylase gene expression were significantly induced by MeJA. Moreover, 156 differential abundance proteins (DAPs) were detected in 4-day-old sprouts using quantitative proteomic methods. These DAPs were divided into 13 functional groups, and the vast majority of DAPs involved in defense/stress, energy, signal transduction, and secondary metabolism increased. MeJA treatment significantly enriched 15 pathways, including glutathione metabolism, biosynthesis of secondary metabolites, and tryptophan metabolism. In particular, the abundance of three DAPs (myrosinase 1, cytosolic sulfotransferase 16, and glutamate-glyoxylate aminotransferase 2) in the tryptophan metabolism pathway, a substrate for MT biosynthesis, increased significantly. In summary, MeJA induces endogenous MT biosynthesis in mustard sprouts by promoting the genes expression of MT synthetase and increasing the abundance of tryptophan-related proteins.

Exogenous methyl jasmonate combined with Ca2+ promote resveratrol biosynthesis and stabilize sprout growth for the production of resveratrol-rich peanut sprouts.

Promoting resveratrol accumulation in plants and utilizing resveratrol-rich plants as raw materials for the development of functional foods is a promising development direction. The effects of methyl jasmonate (MeJA), in combination with CaCl2 and Ca2+ inhibitors, on physiological metabolism and resveratrol enrichment of peanut sprouts were investigated. MeJA combined with CaCl2 increased Ca2+ content, calmodulin content, and Ca2+- adenosine triphosphatase activity, as well as upregulated calcium-binding proteinase expression levels. Treatment with MeJA plus CaCl2 significantly increased peroxidase and superoxide dismutase activities and antioxidant capacities, significantly decreased the content of malondialdehyde and hydrogen peroxide, which resulted in a significantly increased in sprout length and fresh weight, and alleviated the inhibition of sprout growth. MeJA plus CaCl2 significantly increased the activities of phenylalanine ammonia-lyase and 4-coumarate coenzyme A ligase and upregulated the expression levels of phenylalanine ammonia-lyase, cinnamic acid 4-hydroxylase, and resveratrol synthase, thus significantly increasing resveratrol content. However, MeJA combined with Ca2+ antagonists reversed these effects. These results indicate that MeJA interacts with Ca2+ to promote resveratrol synthesis in peanut sprouts and to improve sprout stress tolerances.

Mitigation of oxidative stress damage caused by abiotic stress to improve biomass yield of microalgae: A review.

Microalgae have been recognized as emerging cell factories due to the high value-added bio-products. However, the balance between algal growth and the accumulation of metabolites is always the main contradiction in algal biomass production. Hence, the security and effectiveness of regulating microalgal growth and metabolism simultaneously have drawn substantial attention. Since the correspondence between microalgal growth and reactive oxygen species (ROS) level has been confirmed, improving its growth under oxidative stress and promoting biomass accumulation under non-oxidative stress by exogenous mitigators is feasible. This paper first introduced ROS generation in microalgae and described the effects of different abiotic stresses on the physiological and biochemical status of microalgae from these aspects associated with growth, cell morphology and structure, and antioxidant system. Secondly, the role of exogenous mitigators with different mechanisms in alleviating abiotic stress was concluded. Finally, the possibility of exogenous antioxidants regulating microalgal growth and improving the accumulation of specific products under non-stress conditions was discussed.

Proteome reveals the mechanism of selenium-sulfur interaction in regulating isothiocyanate biosynthesis and the physiological metabolism of broccoli sprouts.

Broccoli sprouts have a strong ability to accumulate isothiocyanate and selenium. In this study, the isothiocyanate content increased significantly as a result of ZnSO4 stress. Particularly, based on the isothiocyanate content is not affected, the combined ZnSO4 and Na2SeO3 treatment alleviated the inhibition of ZnSO4 and induced selenium content. Gene transcription and protein expression analyses revealed the changes in isothiocyanate and selenium metabolite levels in broccoli sprouts. ZnSO4 combined with Na2SeO3 was proven to activate a series of isothiocyanate metabolite genes (UGT74B1, OX1, and ST5b) and selenium metabolite genes (BoSultr1;1, BoCOQ5-2, and BoHMT1). The relative abundance of the total 317 and 203 proteins, respectively, in 4-day-old broccoli sprouts varied, and the metabolic and biosynthetic pathways for secondary metabolites were significantly enriched in ZnSO4/control and ZnSO4 combined Na2SeO3/ZnSO4 comparisons. The findings demonstrated how ZnSO4 combined with Na2SeO3 treatment reduced stress inhibition and the accumulation of encouraged selenium and isothiocyanates during the growth of broccoli sprouts.

Ethephon promotes isoflavone accumulation in germinating soybeans by its acceleration of isoflavone biosynthetic pathway.

Soybeans have medicinal value and are an oil crop with medicinal and food properties. The present work investigated two aspects of isoflavone accumulation in soybean. First, germination conditions for exogenous-ethephon-mediated accumulation of isoflavone were optimised through response surface methodology. Second, various influences of ethephon on the growth of germinating soybeans and isoflavone metabolism were investigated. The findings of the research led to the conclusion that exogenous ethephon treatment effectively facilitated the enrichment of isoflavones in soybeans during germination. Optimal germination conditions were obtained through a response surface optimization test, which yielded the following criteria: a germination time of 4.2 d, an ethephon concentration of 102.6 µM, and a germination temperature of 30.2 °C. The maximum isoflavone content was 544.53 µg/sprout FW. Relative to the control, the addition of ethephon significantly inhibited sprout growth. Exogenous ethephon treatment led to the phenomenon that peroxidase, superoxide dismutase, and catalase activities and their gene expression increased significantly in germinating soybeans. Meanwhile, the expression of genes related to ethylene synthetase increase under the effect of ethephon promoting ethylene synthesis. Ethylene multiplied the total flavonoid content of soybean sprouts relying on the increase in activity and gene expression of crucial isoflavone biosynthesis-related enzymes (phenylalanine ammonia-lyase and 4-coumarate coenzyme A ligase) during germination.

AFP deletion leads to anti-tumorigenic but pro-metastatic roles in liver cancers with concomitant CTNNB1 mutations.

HCC remains one of the most prevalent and deadliest cancers. Serum AFP level is a biomarker for clinical diagnosis of HCC, instead the contribution of AFP to HCC development is clearly highly complex. Here, we discussed the effect of AFP deletion in the tumorigenesis and progression of HCC. AFP deletion in HepG2 cells inhibited the cell proliferation by inactivating PI3K/AKT signaling. Surprisingly, AFP KO HepG2 cells appeared the increasing metastatic capacity and EMT phenotype, which was attributed to the activation of WNT5A/ß-catenin signal. Further studies revealed that the activating mutations of CTNNB1 was closely related with the unconventional pro-metastatic roles of AFP deletion. Consistently, the results of DEN/CCl4-induced HCC mouse model also suggested that AFP knockout suppressed the growth of HCC primary tumors, but promoted lung metastasis. Despite the discordant effect of AFP deletion in HCC progression, a drug candidate named OA showed the potent suppression of HCC tumor growth by interrupting AFP-PTEN interaction and, importantly, reduced the lung metastasis of HCC via angiogenesis suppression. Thus, this study demonstrates an unconventional effect of AFP in HCC progression, and suggests a potent candidate strategy for HCC therapy.

iTRAQ-Based Proteomic Analyses of Regulation of Isothiocyanate and Endogenous Selenium Metabolism in Broccoli Sprouts by Exogenous Sodium Selenite.

Broccoli sprouts have high isothiocyanate and selenium accumulation capacity. This study used a combination of methods, including physiological and biochemical, gene transcription and proteomic, to investigate the isothiocyanate and endogenous selenium accumulation mechanisms in broccoli sprouts under exogenous sodium selenite treatment during germination. Compared with the control, the sprouts length of broccoli sprouts under exogenous selenium treatment was significantly lower, and the contents of total phenol and malondialdehyde in 6-day-old broccoli sprouts were substantially higher. The contents of isothiocyanate and sulforaphane in 4-day-old were increased by up-regulating the relative expression of genes of UGT74B1, OX-1, and ST5b. The relative expression of BoSultr1;1, BoSMT, BoHMT1, and BoCOQ5-2 genes regulating selenium metabolism was significantly up-regulated. In addition, 354 proteins in 4-day-old broccoli sprouts showed different relative abundance compared to the control under selenium treatment. These proteins were classified into 14 functional categories. It was discovered that metabolic pathways and biosynthetic pathways of secondary metabolites were significantly enriched. The above results showed that exogenous selenium was beneficial in inducing the accumulation of isothiocyanate and selenium during the growth of broccoli sprouts.

Effects of methyl jasmonate and NaCl treatments on the resveratrol accumulation and defensive responses in germinated peanut (Arachis hypogaea L.).

In this study, the effects of methyl jasmonate (MeJA) and sodium chloride (NaCl) treatments on the resveratrol biosynthesis and physiology of peanuts during germination were investigated. The results showed that MeJA (150 µM) and NaCl (150 mM) treatments significantly promoted resveratrol biosynthesis in germinated peanuts. MeJA and NaCl treatments promoted resveratrol accumulation by regulating the activities of phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H) and 4-coumarate coenzyme A ligase (4CL) and their gene expression levels in cotyledons and non-cotyledons. In addition, both MeJA and NaCl treatments inhibited peanut sprout growth, as evidenced by shorter sprout length, increased malondialdehyde content, and accumulation of reactive oxygen species in cotyledons and non-cotyledons. Both treatments' germinated peanuts responded to the environmental stimuli by raising the activities of antioxidant enzymes and controlling the levels of their gene' expression. Meanwhile, MeJA and NaCl treatments promoted Ca2+ aggregation in the root tips. Therefore, it can be deduced that Ca2+ may help improve the plant's resistance to adversity. In conclusion, treatment with MeJA (150 µM) or NaCl (150 mM) during germination is an effective way to enrich the resveratrol content of peanuts. Germinated peanuts enhance adaptation to the external environment by promoting resveratrol biosynthesis and enhancing antioxidant systems.

Nitric oxide mediates melatonin-induced isoflavone accumulation and growth improvement in germinating soybeans under NaCl stress.

The involvement of nitric oxide (NO) in exogenous melatonin (MT)-induced isoflavone accumulation and growth improvement in NaCl-stressed soybeans was investigated in this study. The results demonstrated that MT increased the activity of nitrate reductase (NR) and upregulated the relative expression of NR1, NR2, and nitric oxide synthase1, which subsequently led to an increase in NO content. MT and sodium nitroprusside (SNP, as an NO donor) markedly increased isoflavone content by enhancing the activities of cinnamic acid 4-hydroxylase (C4H) and phenylalanine ammonia lyase (PAL), and by upregulating gene expression of C4H, Isoflavone synthase, PAL, and Chalcone isomerase 1A, which are involved in isoflavone biosynthesis. Moreover, MT, as well as SNP, improved the growth and biomass of NaCl-treated soybeans by increasing the activities of superoxide dismutase, catalase, and peroxidase, and reducing the accumulation of H2O2 and O2•- in soybeans under NaCl stress. These MT-induced responses were entirely reversed by the supply of 4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO, a specific scavenger of NO), which in turn considerably decreased endogenous NO content. These results suggest that NO acts as an important downstream signal molecule, mediating MT-induced isoflavone accumulation and growth improvement in NaCl-stressed soybeans.

Mechanism of calcium in melatonin enhancement of functional substance-phenolic acid in germinated hulless barley.

Phenolic acid is a physiologically active substance that has a variety of effects on humans. Barley sprouts are often used as food ingredients to enrich phenolic acids and to further produce functional foods rich in phenolic acids. In this study, the mechanism of Ca2+ involvement in regulating phenolic acid biosynthesis and plant growth in barley by melatonin (MT) under NaCl stress was investigated. According to the studies, MT (25 µM) increased total calcium content, induced Ca2+ burst, and up-regulated the gene expression of calcium-regulated protein-dependent protein kinase and calcium-binding protein transcription-activating protease in NaCl-stressed (60 mM) barley. Exogenous MT and its combined CaCl2 (0.4 mM) significantly promoted phenolic acid biosynthesis by increasing the activity of C4H and PAL, and induced gene expression of PAL and F5H. The addition of exogenous CaCl2 and MT caused systemic tolerance in NaCl-stressed barley, as determined by a decrease in the fluorescence intensity of hydrogen peroxide and oxygen radical anions as well as an enhancement in the antioxidant enzyme, thus significantly increasing sprout length and fresh weight. In addition, combined use of MT with Ca2+ antagonists (lanthanum chloride or ethylene glycol tetraacetic acid), impaired all impacts as mentioned above. These findings imply that Ca2+ participated in MT-induced phenolic acid biosynthesis and growth improvement in NaCl-stressed barley.

Metal-Cyclic Dinucleotide Nanomodulator-Stimulated STING Signaling for Strengthened Radioimmunotherapy of Large Tumor.

Combined treatment of immunotherapy and radiotherapy shows promising therapeutic effects for the regression of a variety of cancers. However, even multi-modality therapies often fail to antagonize the regression of large tumors due to the extremely immunosuppressive tumor microenvironment (TME). Here, a radioimmunotherapeutic paradigm based on stimulator of interferon genes (STING)-dependent signaling is applied to preclude large tumor progression by utilizing the metal-cyclic dinucleotide (CDN) nanoplatform, which integrates STING agonist c-di-AMP and immunomodulating microelement manganese (II) within the tannic acid nanostructure (TMA-NPs). As observed by magnetic resonance imaging, the localized administration of TMA-NPs effectively relieves hypoxia within TME and causes radical oxygen species overproduction and apoptosis in cancer cells after exposure to X-ray irradiation. The DNA fragments released from the apoptotic cells after the combined treatment augment the production of endogenous CDNs in cancer cells, hence significantly activating the STING-mediated pathway for stronger anti-tumor immunity. The localized therapy of TMA-NPs + X-ray not only inhibits the primary large tumor progression but also retards distant tumor growth by promoting dendritic cell maturation and activating cytotoxic immune cells whil suppressing immunosuppressive cells. Therefore, this work represents the combinatorial potency of TMA-NPs and X-rays on large tumor regression through strengthened STING-mediated radioimmunotherapeutics.

Exogenous melatonin stimulated isoflavone biosynthesis in NaCl-stressed germinating soybean (Glycine max L.).

Melatonin (MT) has gained increasing attention due to its pleiotropic effects. In this study, the function of exogenous MT on the response to NaCl stress and isoflavone biosynthesis in germinating soybeans was investigated. Results showed the exogenous MT (100 µM) application neutralised the negative effects of NaCl stress (60 mM), induced sprout growth, biomass and fluorescence intensity of intracellular free calcium, decreased malondialdehyde, H2O2 content and fluorescence intensity of O2•-, and enhanced superoxide dismutase, catalase and peroxidas activities of germinating soybeans. Meanwhile, total flavonoids and different forms of isoflavone content were enhanced by MT application, not only companied by the up-regulated relative gene expression of cinnamic acid 4-hydroxylase chalcone reductase, chalcone isomerase 1A, isoflavone reductase and isoflavone synthase 1 that involved in isoflavone biosynthesis, but also increased activities of phenylalanine ammonia lyase and 4-coumarate coenzyme A ligase. Given the evidence from the present study, it's proposed that the exogenous MT could relieve NaCl stress and stimulate isoflavone biosynthesis in germinating soybeans.