Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.

Stability improvement of human collagenα1(I)chain using insulin as a fusion partner

To enhance the stability of recombinant human collagen α1(I) chains(rhCOL1 A1) in production and purification stages, a gene fragment fusing COL1 A1 and insulin protein coding domains was synthesized and inserted into the pPIC9 K expression vector. The fusion peptide-expressing Pichia pastoris strain was created by transformation.After optimization of shake flask cultures, the ultimate intracellular expression level of the insulin-collagen α1(I) chain fusion protein(INS-COL1 A1) reached about 300 mg·L^(-1), and no obvious protein degradation was found in the fermentation and purification processes. The His-tagged recombinant fusion protein was detected by western blotting and was effectively purified using Ni^(2+)-chelating chromatography. A prominent improvement in the stability of INS-COL1 A1 was observed compared to rhCOL1 A1 in vitro, and the rhCOL1 A1 released from the fusion protein was studied by LC–MS/MS and in bioassays. The results showed that the purified rhCOL1 A1 was consistent with the native protein in amino acid composition and had a similar biological compatibility. To our knowledge, this is the first study to demonstrate the use of insulin as a fusion protein to improve the stability of easily degradable proteins.

High efficiency production of ginsenoside compound K by catalyzing ginsenoside Rb1 using snailase

The rare ginsenoside Compound K （C-K） is attracting more attention because of its good physiological activity and urgent need. There are many pathways to obtain ginsenoside C-K, including chemical and biological methods. Among these, the conversion of PPD-type ginsenosides by enzymatic hydrolysis is a trend due to its high efficiency and mild conditions. For effectively extracting from the other panaxadiol saponins, the conversion process for ginsenoside C-K was investigated using snailases in this study. The univariate experimental design and response surface methodology were used to determine the optimal hydrolysis conditions for the conversion of ginsenoside Rbl into ginsenoside C-K by snailases. The optimum conditions were as follows： pH 5,12, temperature 51 ℃, ratio of snailase/substrate 0.21, and reaction time 48 h. On the basis of these parameters, the addition of 1.0 mmol· L- 1 ferric ion was found to significantly improve the enzymolysis ofsnailases for the first time. With the above conditions, the maximum conversion rate reached 89.7%, suggesting that the process can obviously increase the yield of ginsenoside C-K. The bioassay tests indicated that the ginsenoside C-K showed anti-tumor activity in a series of tumor cell lines. Based on these results, we can conclude that the process of rare ginsenoside C- K production by enzymolysis with snailase is feasible, efficient, and suitable for the industrial production and application.

Application and progress of techno-economic analysis and life cycle assessment in biomanufacturing of fuels and chemicals

To reduce the dependency on petroleum-based products and emission of greenhouse gas,renewable biofuels and chemicals play an important role to meet the unmatched energy demands of the rapidly growing population.However,most biofuel and chemical products do not reach the commercialization stage,mainly hindered by incomparable economics to petroproducts.Techno-economic assessment(TEA)is a useful tool to estimate eco-nomic performance,and identify bottlenecks for the development of biofuel and chemical production technology,meanwhile,life cycle assessment(LCA)is applied to assess sustainability by reducing the environmental impact of biofuel and chemical production.This present review covers TEA and LCA research progress in the manufacturing of biofuels and biochemical,and discusses the impacts of TEA and LCA results on the development and optimi-zation of biofuel and chemical production.In addition,challenges associated with TEA and LCA of biofuel and biochemical production were briefly overviewed,and potential approaches that may overcome such challenges were discussed enabling viable and sustainable biomanufacturing of fuels and chemicals.Future integrated TEA and LCA studies could significantly promote the economic and sustainable development of the biomanufacturing process.

Construction of multifunctional hydrogel based on the tannic acid-metal coating decorated MoS2 dual nanozyme for bacteria-infected wound healing

Bacterial infection,tissue hypoxia and inflammatory response can hinder the infected wound repair process.To mitigate the above issues,tannic acid-chelated Fe-decorated molybdenum disulfide nanosheets(MoS2@TA/Fe NSs)with dual enzyme activities were developed and anchored to a multifunctional hydrogel.The hydrogel exhibited excellent antibacterial ability owing to the combined effects of photothermal therapy(PTT),glutathione(GSH)loss,and the peroxidase(POD)-like activity(catalyse H2O_(2)into⋅OH under acid condition)of MoS2@TA/Fe NSs.Benefitting from the catalase(CAT)-like activity,the hydrogel could decompose H2O_(2)into O_(2)at neutral pH to relieve hypoxia and supply adequate O_(2).POD-like activity was mainly attributed to MoS2 NSs,while CAT-like activity was primarily due to TA/Fe complex.Moreover,MoS2@TA/Fe NSs endowed the hydrogel with outstanding anti-oxidant ability to scavenge redundant reactive oxygen species(ROS)and reactive nitrogen species(RNS)under neutral environment to maintain the balance of antioxidant systems and prevent inflammation.In addition,the hydrogel could inhibit the release of inflammatory factors for the anti-inflammatory property of TA.TA retained partial phenolic hydroxyl groups,which cross-linked the nanosheets to the network structure of the hydrogel and promoted the adhesion of hydrogels.Due to the dynamic boron ester bonds between polyvinyl alcohol(PVA),dextran(Dex),MoS2@TA/Fe,and borax,the hydrogel demonstrated fast self-healing and rapid shape adaptability.This shape-adaptable adhesive hydrogel could fill the whole wound and closely contact the wound,ensuring that it achieved its functions with maximum efficiency.The MoS2@TA/Fe nanozyme-anchored multifunctional hydrogel showed high potential for bacteria-infected wound healing.

Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing

Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@Cel&INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres con-taining celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@Cel&INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 ◦C) and solid-like elasticity (protect wounds against external forces, approximately 25 ◦C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/ GMs@Cel&INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@Cel&INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.