Polysaccharides play an anti-fibrotic role by regulating intestinal flora: A review of research progress.

Fibrosis is a common pathological process affecting multiple organs. It refers to an increase in fibrous connective tissue and a decrease in parenchymal cells in damaged tissues or organs. This may lead to structural damage and functional decline or even organ failure. The incidence of fibrosis is increasing worldwide, and the need for safe and effective therapeutic drugs and treatments is pivotal. The intestinal tract has a complex network of exchanging information with various tissues in the body. It contains a sizeable microbial community of which the homeostasis and metabolites are closely related to fibrosis. Polysaccharides are a class of biomolecules present in natural products; they have potential value as anti-fibrotic prebiotics. Recently, polysaccharides have been found to improve fibrosis in different organs by decreasing inflammation and modulating the immune function and intestinal microbiota. In this paper, we reviewed the progress made in research concerning polysaccharides and organ fibrosis in relation to the intestinal microbiota from the pathogenesis of fibrosis to the relationship between the intestinal flora and fibrosis. Furthermore, we provide ideas and references for future polysaccharide-drug discovery and strategies for the treatment of fibrosis.

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus.

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

Polysaccharides from fructus corni: Extraction, purification, structural features, and biological activities.

Fructus Corni, derived from the dried fruit of Cornus officinalis Sieb. Et Zucc., is widely used as a food source and Chinese herb. Fructus Corni, as an indispensable ingredient in Liuwei Dihuang decoction, tonifies the liver and kidneys. As the main component of water decoctions, Fructus Corni polysaccharides demonstrate multifaceted effects, including hypoglycemic, hypolipidemic, antioxidant, anti-aging, sexual function regulation, and anti-epileptic, The ultrasound-assisted extraction method obtained the highest yields of Fructus Corni polysaccharides. However, it has notable shortcomings and lacks further innovation. The homogeneous polysaccharides obtained from Fructus Corni are mostly neutral polysaccharides with relatively limited structure, and the mechanism of their biological activity needs to be further elucidated. In addition, different extraction, isolation and purification methods may change the molecular weight, monosaccharide composition, and biological activity of polysaccharides. Therefore, this study systematically summarized the extraction, purification, structural features, and biological activities of Fructus Corni polysaccharides. This study aimed to provide support for the ongoing development and application of Fructus Corni polysaccharides.

A new insight into Cd exposure-induced hemocyte reduction in Lymantria dispar larvae: Involvement of the ROS-ATF6-ER stress-apoptosis pathway.

Hemocytes are important targets for heavy metal-induced immunotoxicity in insects. This study aimed to investigate the mechanism by which cadmium (Cd) exposure affects the hemocyte count in Lymantria dispar larvae. The results showed that the number of larval hemocytes was significantly decreased under Cd exposure, accompanied by a significant increase in the apoptosis rate and the expression of Caspase-3. The endoplasmic reticulum (ER) of hemocytes in the Cd-treated group showed irregular swelling. Expression levels of ER stress indicator genes (CHOP, Bip1, Bip2, Bip3, and Bip4) were significantly higher in the Cd-treated group. Among the three pathways that potentially mediate ER stress, only the key genes in the ATF6 pathway (ATF6, S1P-1, S1P-2, and WFS1) exhibited differential responses to Cd exposure. Cd exposure significantly increased the levels of reactive oxygen species (ROS) and the expression of oxidative stress-related genes (CNCC, P38, and ATF2) in hemocytes. Studies using inhibitors confirmed that apoptosis mediated the decrease in hemocyte count, ER stress mediated apoptosis, ATF6 pathway mediated ER stress, and ROS or oxidative stress mediated ER stress through the activation of the ATF6 pathway. Taken together, the ROS-ATF6-ER stress-apoptosis pathway is responsible for the reduction in the hemocyte count of Cd-treated L. dispar larvae.

Identification and potential application of key insecticidal metabolites in Tilia amurensis, a low-preference host of Hyphantria cunea.

Developing effective insecticidal strategies is an important means of reducing the spread and host plant damage by Hyphantria cunea. In this study, key metabolites with insecticidal activity against H. cunea were screened by targeted metabolomics in Tilia amurensis, a low-preference host plant. Subsequently, the potential of key metabolites that could be used as botanical pesticides was evaluated. The results showed that coumarin was the key insecticidal metabolite of T. amurensis and had a significant insecticidal effect and weight inhibition effect on H. cunea larvae. Coumarin treatment significantly decreased the larval nutrient content and the gene expression of rate-limiting enzymes in the glycolytic pathway and tricarboxylic acid cycle. A significantly enhanced detoxification enzyme activity (CarE and GST), antioxidant oxidase activity (SOD and CAT), non-enzymatic antioxidant levels (GSH), and total antioxidant capacity were observed in coumarin-treated larvae. Coumarin treatment resulted in a significant increase in the expression levels of detoxification enzyme genes (CarE1, CarE2, CarE3, GST2, and GST3) and antioxidant oxidase genes (SOD1, CAT1, and CAT2) in H. cunea larvae. Coumarin treatment significantly increased the levels of MDA and H2O2 in larvae but did not cause pathological changes in the ultrastructure of the larval midgut. Coumarin solution sprayed directly or as a microcapsule suspension formulation with coumarin as the active ingredient had significant insecticidal activity against the H. cunea larvae. Overall, coumarin, a key anti-insect metabolite identified from T. amurensis, can significantly inhibit the growth and survival of H. cunea larvae and has the potential to be developed as a botanical pesticide.

Development of a green, concise synthesis of nicotinamide derivatives catalysed by Novozym® 435 from Candida antarctica in sustainable continuous-flow microreactors.

An increasing number of studies have shown that many nicotinamide derivatives exhibited extensive biological activities, such as anti-inflammatory and antitumor activity. In this paper, a green, concise synthesis of nicotinamide derivatives in sustainable continuous-flow microreactors catalysed by Novozym® 435 from Candida antarctica has been developed. Application of an easily obtainable and reusable lipase in the synthesis of nicotinamide derivatives from methyl nicotinate and amines/benzylamines reacted for 35 min at 50 °C led to high product yields (81.6-88.5%). Environmentally friendly tert-amyl alcohol was applied as a reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further activity research of novel nicotinamide derivatives.

The exposure risk of heavy metals to insect pests and their impact on pests occurrence and cross-tolerance to insecticides: A review.

Heavy metal (HM) pollution is a severe global environmental issue. HMs in the environment can transfer along the food chain, which aggravates their ecotoxicological effect and exposes the insects to heavy metal stress. In addition to their growth-toxic effects, HMs have been reported as abiotic environmental factors that influence the implementation of integrated pest management strategies, including microbial control, enemy insect control, and chemical control. This will bring new challenges to pest control and further highlight the ecotoxicological impact of HM pollution. In this review, the relationship between HM pollution and insecticide tolerance in pests was analyzed. Our focus is on the risks of HM exposure to pests, pests tolerance to insecticides under HM exposure, and the mechanisms underlying the effect of HM exposure on pests tolerance to insecticides. We infer that HM exposure, as an initial stressor, induces cross-tolerance in pests to subsequent insecticide stress. Additionally, the priming effect of HM exposure on enzymes associated with insecticide metabolism underlies cross-tolerance formation. This is a new interdisciplinary field between pollution ecology and pest control, with an important guidance value for optimizing pest control strategies in HM polluted areas.

Assessment of cytisine as an insecticide candidate for Hyphantria cunea management: Toxicological, biochemical, and control potential insights.

In the present study, the toxicological effects of cytisine on the H. cunea larvae were investigated, and the potential of cytisine as a botanical insecticide through field simulation experiments was evaluated. The results showed that cytisine treatment (0.25-2.5%) exerted significant biotoxic effects on the H. cunea larvae, including diminished weight, disruption of both positive (HcCKS1, HcPLK, HcCCNA) and negative (HcGADD and HcCDKN) regulatory genes associated with larval growth, increased mortality, and heightened oxidative damage (H2O2 and MDA). Cytisine treatment significantly reduced glucose content and inhibited the expression of key rate-limiting enzyme genes (HcPFK, HcPK, HcHK1, HcCS, and HcIDH2) within glycolysis and the tricarboxylic acid cycle pathways. Under cytisine treatment, detoxification enzyme activities (CarE and GST) and expression of detoxification genes (HcCarE1, HcCarE2, HcCarE3, HcGST1, and HcGST3) were inhibited in H. cunea larvae. An increased contents of SOD, CAT, ASA and T-AOC, as well as expression of antioxidant enzyme genes HcSOD1 and HcCAT2, was found in cytisine-treated H. cunea larvae. Simultaneously, this is accompanied by a significant reduction in the expression of four antioxidant enzyme genes (e.g., HcPOD1 and HcPOD2). In the field experiment, a cytisine aqueous solution (25 g/L) with pre-sprayed and directly sprayed ways demonstrated potent insecticidal activity against H. cunea larvae, achieving a mortality rate of 53.75% and 100% at 24 h, respectively. Taken together, cytisine has significantly weight inhibition and lethal toxicity on the H. cunea larvae, and can be developed as a botanical insecticide for H. cunea control.

Digestive Characteristics of Hyphantria cunea Larvae on Different Host Plants.

Digestive physiology mediates the adaptation of phytophagous insects to host plants. In this study, the digestive characteristics of Hyphantria cunea larvae feeding preferences on different host plants were investigated. The results showed that the body weight, food utilization, and nutrient contents of H. cunea larvae feeding on the high-preference host plants were significantly higher than those feeding on the low-preference host plants. However, the activity of larval digestive enzymes in different host plants presented an opposite trend, as higher α-amylase or trypsin activity was observed in the group feeding on the low-preference host plants than that feeding on the high-preference host plants. Upon treatment of leaves with α-amylase and trypsin inhibitors, the body weight, food intake, food utilization rate, and food conversion rate of H. cunea larvae significantly decreased in all host plant groups. Furthermore, the H. cunea comprised highly adaptable compensatory mechanisms of digestion involving digestive enzymes and nutrient metabolism in response to digestive enzyme inhibitors. Taken together, digestive physiology mediates the adaptation of H. cunea to multiple host plants, and the compensatory effect of digestive physiology is an important counter-defense strategy implemented by H. cunea to resist plant defense factors, especially the insect digestive enzyme inhibitors.

Susceptibility of Hyphantria cunea larvae to Beauveria bassiana under Cd Stress: An integrated study of innate immunity and energy metabolism.

Biological control is widely used for integrated pest management. However, there are many abiotic factors that can affect the biocontrol efficiency. In this study, we investigated the susceptibility of Hyphantria cunea larvae to Beauveria bassiana under Cd stress, and the corresponding mechanism was analyzed around innate immunity and energy metabolism. The results showed that mortality of H. cunea larvae treated with Cd and B. bassiana was significantly higher than those treated with B. bassiana alone, and the combined lethal effect exhibited a synergistic effect. Compared with the single fungal treatment group, the total hemocyte count in the combined Cd and fungal treatment group decreased significantly, accompanied by a decrease in phagocytosis, encapsulation, and melanization activity. The expression levels of three phagocytosis-related genes, one encapsulation-promoting gene, and one melanization-regulating gene were significantly lower in the combined treatment group than those in the single fungal treatment group. Furthermore, pathogen recognition ability, signal transduction level, and immune effector expression level were weaker in the combined treatment group than those in the single fungal treatment group. The expression levels of 14 key metabolites and 7 key regulatory genes in glycolysis and tricarboxylic acid cycle pathways were significantly lower in the combined treatment group than those in the single fungal treatment group. Taken together, the weakness of innate immunity and energy metabolism in response to pathogen infection resulted in an increased susceptibility of H. cunea larvae to B. bassiana under Cd pre-exposure. Microbial insecticide is a preferred strategy for pest control in heavy metal-polluted areas. AVAILABILITY OF DATA AND MATERIAL: All the data that support the findings of this study are available in the manuscript.

Cadmium exposure through the food chain reduces the parasitic fitness of Chouioia cunea to Hyphantria cunea pupae: An ecotoxicological risk to pest control.

The toxicity of heavy metals on various trophic levels along the food chain has been extensively investigated, but no studies have focused on parasitic natural enemy insects. Herein, we constructed a food chain consisting of soil-Fraxinus mandshurica seedlings-Hyphantria cunea pupae-Chouioia cunea to analyze the effects of Cd exposure through food chain on the fitness of parasitic natural enemy insects and its corresponding mechanism. The results showed that the transfer of Cd between F. mandshurica leaves and H. cunea pupae and between H. cunea pupae and C. cunea was a bio-minimization effect. After parasitizing Cd-accumulated pupa, the number of offspring larvae, and the number, individual size (body weight, body length, abdomen length) and life span of offspring adults decreased significantly, while the duration of embryo development extended significantly. The contents of malondialdehyde and H2O2 in Cd-exposed offspring wasps increased significantly, accompanied by a significantly decrease in antioxidant capacity. The cellular immunity parameters significantly decreased in Cd-accumulated pupae, including the number of hemocytes, melanization activity and the expression level of cellular immunity genes (e.g. Hemolin-1 and PPO1). The humoral immunity disorder was found in the Cd-accumulated pupae, as evidenced by that the expression level of immune recognition gene (PGRP-SA), signal transduction genes (IMD, Dorsal, and Tube), as well as all antimicrobial peptide genes (e.g. Lysozym and Attacin) decreased significantly. Cd exposure decreased the content of glucose, trehalose, amino acid, and free fatty acid in H. cunea pupae. The expression of Hk2 in glycolysis pathway and the expression of Idh2, Idh3, Cs, and OGDH in TCA cycle pathway were significantly down-regulated in Cd-accumulated pupae. Taken together, exposure to Cd through the food chain causes oxidative damage on the offspring wasps and disrupts energy metabolism of the host insect, ultimately reducing the parasitic fitness of C. cunea to H. cunea pupae.

Transfer of Cd along the food chain: The susceptibility of Hyphantria cunea larvae to Beauveria bassiana under Cd stress.

Heavy metal can affect the bio-control efficiency of entomopathogenic fungi on pests, but this has not been studied in the food chain. Here, the food chain of soil-Fraxinus mandshurica-Hyphantria cunea was constructed to investigate the effect of cadmium (Cd) exposure on the susceptibility of H. cunea larvae to Beauveria bassiana (Bb) and to analyze the corresponding mechanism through larval innate immunity and energy metabolism. Cd through the food chain synergistically enhanced the susceptibility of H. cunea larvae to Bb. Cellular immunity-related parameters decreased when the Cd treatment group was compared with the control group and when the combined treatment group of Cd and Bb was compared with the Bb treatment group. Cd exposure induced hormesis on pathogen recognition and signal transduction genes of humoral immunity, but reduced the expression of effector genes. The expression of the 13 humoral immunity-related genes in the combined treatment group was lower than in the Bb treatment group. Cd exposure decreased the energy storage of H. cunea larvae before Bb infection and aggravated the disorder level of energy metabolism after Bb infection. Taken together, disturbance of innate immunity and energy metabolism improves the susceptibility of H. cunea larvae to Bb in the Cd-polluted food chain.