Selective adsorption of anionic dyes by a macropore magnetic lignin-chitosan adsorbent.

Dyes pollution is well known for their hazardous impacts on human health and the environment. The removal of dyes from wastewater has become an important issue. In this study, magnetic micrometer-sized particles AL-CTS@MNPs were synthesized from alkaline lignin (AL) and chitosan (CTS) by "one-pot method". The adsorbent presented higher selectivity adsorption effect on anionic dyes than amphoteric and cationic dyes, and even no adsorption effect on cationic methylene blue (MB), which showed that the anionic dyes could be better separated from the other two types of dyes. The adsorption isotherms of the dyes were highly consistent with the Langmuir model, and the maximum adsorption capacity was 329.50 mg/g for methyl orange (MO) and 20.00 mg/g for rhodamine B (RhB). AL-CTS@MNPs showed good adsorption of anionic dyes (MO) in the pH range of 3-9. Meanwhile, the adsorbent AL-CTS@MNPs were also characterized, showing rough surface with specific surface areas of 37.38 m2/g, pore diameter of 95.8 nm and porosity of 17.62 %. The particle sizes were ranged from 800 µm to 1300 µm. The electrostatic attraction and π-π* electron donor-acceptor interactions were the main forces between the adsorbent and anionic dyes. While the electrostatic repulsive force between the adsorbent and the cationic dyes resulted in the non-absorption of MB by AL-CTS@MNPs. Subsequently, the adsorbent maintained a removal rate of >95 % after five adsorption-desorption cycles, demonstrating its excellent stability and recoverability. Ultimately, the prepared AL-CTS@MNPs illuminated good prospect on complex components dyes wastewater treatment.

Solid-state fermentation of corn straw using synthetic microbiome to produce fermented feed: The feed quality and conversion mechanism.

Straw is a typical biomass resource which can be converted into high nutritional value feed via microbial fermentation. The degradation and conversion of straw using a synthetic microbial community (SMC-8) was functionally investigated to characterise its nitrogen conversion and carbon metabolism. Four species of bacteria were found to utilise >20 % of the inorganic nitrogen within 15 h, and the ratio of the diameter of fungal transparent circles (D) to the diameter of the colony (d) of the four fungal species was >1. Solid-state fermentation of corn straw increased the total amino acid (AA) content by 41.69 %. The absolute digestibility of fermented corn straw dry weight (DW) and true protein was 34.34 % and 45.29 %, respectively. Comprehensive analysis of functional proteins revealed that Aspergillus niger, Trichoderma viride, Cladosporium cladosporioides, Bacillus subtilis and Acinetobacter johnsonii produce a complex enzyme system during corn straw fermentation, which plays a key role in the degradation of lignocellulose. This study provided a new insight in utilizing corn straw.

Long-Chain Bio-Based Nylon 514 Salt: Crystal Structure, Phase Transformation, and Polymerization.

Nylon 514 is one of the new long-chain bio-based nylon materials; its raw material, 1,5-pentanediamine (PDA), is prepared by biological techniques, using biomass as the raw material. The high-performance monomer of nylon 514, 1,5-pentanediamine-tetradecanedioate (PDA-TDA) salt, was obtained through efficient crystallization methods. Here, two crystal forms of PDA-TDA, anhydrous and dihydrate, were identified and studied in this paper. From the characterization data, their crystal structures and thermal behaviors were investigated. Lattice energy was calculated to gain further insight into the relationship between thermal stability and crystal structures. The contribution of hydrogen bonds and other intermolecular interactions to the crystal structure stability have been quantified according to detailed Hirshfeld and IRI analyses. Additionally, the transformation mechanism of the anhydrate and dihydrate was established through a series of well-designed stability experiments, in which the temperature and water activity play a significant role in the structural stability of crystalline forms. Eventually, we obtained nylon 514 products with good thermal stability and low absorption using stable dihydrate powders as monomers. The properties of nylon 514 products prepared by different polymerization methods were also compared.

Properties of Ophioglossum vulgatum L. extract Pickering emulsion stabilized by carbon dots and its potential use in cosmetics.

Ophioglossum vulgatum L. (O. vulgatum) is a species of fern used in traditional Chinese medicine, however, its application in cosmetics has not yet been studied. This study obtained O. vulgatum extract using 70% ethanol solution and evaporation. Fourier Transform Infrared Spectrometer (FTIR) analysis identified many active components in O. vulgatum extract, such as polyols, amino acids, and flavonoids. A Pickering emulsion of O. vulgatum extract was also prepared, stabilized by a type of carbon dot based on l-arginine (CDs-Arg). The prepared Pickering emulsion was characterized by metallographic microscope and contact angle measurement. The results demonstrated that it was a pH-responsive O/W emulsion. Facial cleanser was then created using the prepared Pickering emulsion as the main component. When squeezed onto hands, the cleanser produced many delicate foams and caused no skin irritation. The prepared Pickering emulsion facilitated the use of O. vulgatum in facial cleanser.

Multiple medicinal chemistry strategies of targeting KRAS: State-of-the art and future directions.

KRAS is the most frequently mutated oncogene and drives the development and progression of malignancies, most notably non-small cell lung cancer (NSCLS), pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). However, KRAS proteins have maintained the reputation of being "undruggable" due to the lack of suitable deep pockets on its surface. One major milestone for KRAS inhibition was the discovery of the covalent inhibitors bond to the allosteric switch-II pocket of the KRASG12C protein. To date, the FDA has approved two KRASG12C inhibitors, sotorasib and adagrasib, for the treatment of patients with KRASG12C-driven cancers. Researchers have paid close attention to the development of inhibitors for other KRAS mutations and upstream regulatory factors. The KRAS targeted drug discovery has entered a state of rapid development. This article has aimed to present the current state of the art of drug development in the KRAS field. We systematically summarize recent advances in the discovery and optimization processes of direct KRAS inhibitors (including KRASG12C, KRASG12D, KRASG12A and KRASG12R inhibitors), indirect KRAS inhibitors (SOS1 and SHP2 inhibitors), pan-KRAS inhibitors, as well as proteolysis-targetingchimeras degrades and molecular chaperone modulators from the perspective of medicinal chemistry. We also discuss the current challenges and opportunities of KRAS inhibition and hope to shed light on future KRAS drug discovery.

DNA flexible chain modified MOFs as a versatile platform for chemoenzymatic cascade reactions in glucose catalysis.

Glucose oxidase (GOD) is widely used in the pharmaceutical industry, fermentation products and glucose biosensors for its essential role in catalyzing the conversion of glucose to gluconic acid and hydrogen peroxide (H2O2). As H2O2 is the by-product and will have a toxic effect on glucose oxidase, so introducing another enzyme that could consume H2O2 to form an enzymatic cascade reaction is a practical solution. However, this decision will lead to extra expenses and complex condition optimization such as the specific mass ratio, temperature and pH to improve the activity, stability and recyclability. Herein, we describe a mild and versatile strategy by anchoring GOD on carboxyl-activated MOF (Cu-TCPP(Fe)) through DNA-directed immobilization (DDI) technology. Robust MOF nanosheets were utilized as not only the carrier for the immobilization of GOD, but also a peroxidase-like catalyst for the decomposition of H2O2 to reduce its harmful impacts. In this work, the immobilized GOD retained 55.78% of its initial activity after being used for 7 times. More than 60% of the immobilized enzyme's catalytic activity was still maintained after 96 h of being stored at 50 â„ƒ. This study provides a new idea for preparing immobilized enzymes with enhanced stability, fast diffusion and high activity, which can be used in fields such as biocatalysis and biotechnology.

Synthesis of 3-Phenylserine by a Two-enzyme Cascade System with PLP Cofactor.

A two-enzyme cascade system containing ω-transaminase (ω-TA) and L-threonine aldolase (L-ThA) was reported for the synthesis of 3-Phenylserine starting from benzylamine, and PLP was utilized as the only cofactor in these both two enzymes reaction system. Based on the transamination results, benzylamine was optimized as an advantageous amino donor as confirmed by MD simulation results. This cascade reaction system could not only facilitate the in situ removal of the co-product benzaldehyde, enhancing the economic viability of the reaction, but also establish a novel pathway for synthesizing high-value phenyl-serine derivatives. In our study, nearly 95 % of benzylamine was converted, yielding over 54 % of 3-Phenylserine under the optimized conditions cascade reaction.

Single-cell RNA sequencing indicates cordycepin remodels the tumor immune microenvironment to enhance TIGIT blockade's anti-tumor effect in colon cancer.

Both preclinical and clinical studies have extensively proven the effectiveness of TIGIT inhibitors in tumor immunotherapy. However, it has been discovered that the presence of CD226 on tumor-infiltrating lymphocytes is crucial for the effectiveness of both anti-TIGIT therapy alone and when combined with anti-PD-1 therapy for tumors. In our investigation, we observed that cordycepin therapy significantly augmented the expression of the Cd226 gene. As a result, it was hypothesized that cordycepin therapy could enhance the effectiveness of anti-TIGIT therapy. By employing single-cell RNA sequencing analysis of immune cells in the MC38 tumor model, we discovered that cordycepin combined with anti-TIGIT therapy led to a significant increase in the proportion of NK cells within the tumor immune microenvironment. This increased NK cell activity and decreased the expression of inhibitory receptors and exhaustion marker genes. In the combination therapy group, CD8+ T cells had lower exhaustion state scores and increased cytotoxicity, indicating a better immune response. The combination therapy group increased DCs in the tumor immune microenvironment and promoted cellular interaction with CD4+ T cell and CD8+ T cell populations while decreasing Treg cell interactions. In conclusion, cordycepin with anti-TIGIT therapy in colon cancer could reshape the tumor immune microenvironment and have notable anticancer effects.

Xylan cinnamoylation for reinforcing poly (butylene adipate-co-terephthalate): Molecule design and interaction optimization.

PBAT composites with biomass fillers have gained considerable attention as alternatives to non-biodegradable plastics. This work employed xylan derivatives as fillers for PBAT composites. Xylan was modified by introducing cinnamoyl side groups which limit the hydrogen bonding and construct π-π stacking interactions with PBAT chains. The resultant xylan cinnamates (XCi) show degree of substitution (DS) of 0.55-1.89, glass-transition temperatures (Tg) of 146.5-175.0 °C and increased hydrophobicity, which can be simply controlled by varying the molar ratio of reactants. NMR results demonstrate that the C3-OH of xylopyranosyl unit is more accessible to cinnamoylation. XCi fillers (30-50 wt%) were incorporated into PBAT through melt compounding. The filler with a DS of 0.97 exhibited the optimal reinforcing effect, showing superior tensile strength (19.4 MPa) and elongation at break (330.9 %) at a high filling content (40 wt%), which is even beyond the neat PBAT. SEM and molecular dynamics simulation suggest improved compatibility and strengthened molecular interaction between XCi and PBAT, which explains the suppressed melting/crystallization behavior, the substantial increase in Tg (-34.5 â†’ -1.8 °C) and the superior mechanical properties of the composites. This research provides valuable insights into the preparation of high-performance composites by designing the molecular architecture of xylan and optimizing the associated interactions.

Cordycepin remodels the tumor microenvironment of colorectal cancer by down-regulating the expression of PD-L1.

PURPOSE: Colorectal cancer, as a common malignant tumor, poses a serious threat to human life. Cordycepin, derived from Cordyceps militaris extract, which was established as a capable inhibitor of tumor growth. Nevertheless, the precise antitumor mechanism of cordycepin in colorectal cancer cells remains elusive. METHODS: Herein, our initial focus was to explore the tumor-suppressive impact of cordycepin through its influence on various biological functions in murine colorectal cancer cells, conducted by an in vitro setting. First, we investigated the tumor-suppressive effect of cordycepin on the regulation of biological functions in murine colorectal cancer cells in vitro. Furthermore, we evaluated the in vivo antitumor potential of cordycepin using a mouse preclinical tumor model, and further explored the antitumor mechanism. RESULTS: Our findings revealed that cordycepin effectively inhibit the proliferation, invasion, and migration of murine colon cancer cells. Moreover, there is a substantial reduction in the expression of PD-L1 observed in tumor cells, in response to cordycepin treatment. Collectively, these results demonstrate the significant tumor-suppressive attributes of cordycepin against colorectal cancer. Consequently, our study lays a solid foundation for the potential clinical utilization of cordycepin in cancer therapy. CONCLUSION: Cordycepin inhibits the biological functions of colorectal cancer cells and suppresses tumor growth by reducing the expression of PD-L1.

Pretreatment of Luzhou distiller's grains for feed protein production using crude enzymes produced by a synthetic microbial consortium.

Chinese distillers' grains (CDGs) have low fermentation efficiency due to the presence of lignocellulosic components, such as rice husk. In this study, a microbial consortium synthesized was used based on the "functional complementarity" principle to produce lignocellulolytic crude enzyme. The crude enzyme was used to hydrolyze CDGs. After enzymatic hydrolysis, lignocellulose was damaged to varying degrees and the crystallinity decreased. Subsequently, the feed protein was produced using yeast through two pathways. The results showed that the crude enzyme produced by the microbial consortium (comprising Trichoderma reesei, Aspergillus niger, and Penicillium) exhibited excellent enzymatic efficiency, yielding 27.88%, 19.64%, and 10.88% of reducing sugar, cellulose, and hemicellulose. The true protein content of CDGs increased by 53.49% and 48.35% through the first and second pathways, respectively. Notably, the second pathway demonstrated higher economic benefits to produce feed protein. This study provides a pathway for high-quality utilization of CDGs.

Recent Advances of Lignin Functionalization for High-Performance and Advanced Functional Rubber Composites.

The biomass lignin is the only large-volume renewable feedstock that is composed of aromatics but has been largely underutilized and is sought for valorization as a value-added material. Recent research has highlighted lignin as a promising alternative to traditional petrol-based reinforcements and functional additives for rubber composites. This review summarized the recent advances in the functionalization of lignin for a variety of rubber composites, as well as the compounding techniques for effectively dispersing lignin within the rubber matrix. Significant progress has been achieved in the development of high-performance and advanced functional rubber/lignin composites through carefully designing the structure of lignin-based additives and the optimization of interfacial morphologies. This Review discussed the effect of lignin on composite properties, including mechanical reinforcement, dynamic properties, antiaging performance, and oil resistance, and also the advanced stimuli-responsive performance in detail. A critical analysis for the future development of rubber/lignin composites is presented as concluding remarks.

Construction of a synthetic microbial community based on multiomics linkage technology and analysis of the mechanism of lignocellulose degradation.

The efficient degradation of lignocellulose is a bottleneck for its integrated utilization. This research performed species analysis and made functional predictions in various ecosystems using multiomics coupling to construct a core synthetic microbial community with efficient lignocellulose degradation function. The synthetic microbial community was employed to degrade corn straw via solid-state fermentation. The degradation mechanisms were resolved using proteomics. The optimum culture conditions included 10% inoculum level (w/v), 4% nitrogen source ratio and a fermentation time of 23 d. Under these conditions, the degradation rates of cellulose, hemicellulose, and lignin were 34.91%, 45.94%, and 23.34%, respectively. Proteomic analysis revealed that lignin 1,4-ß-xylanase, ß-xylosidase and endo-1,4-ß-xylanase were closely related to lignocellulose degradation. The metabolic pathways involved in lignocellulose degradation and the functional roles of eight strains were obtained. The synthesis of a microbial community via multiomics linkage technology can effectively decompose lignocellulose, which is useful for their further utilization.

Cordycepin synergizes with CTLA-4 blockade to remodel the tumor microenvironment for enhanced cancer immunotherapy.

The strategy of using immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, leading to remarkable clinical outcomes. However, certain cancer types and patient demographics continue to face unique challenges. As a result, it is vital to investigate combination therapies that involve ICIs to boost therapeutic efficacy. Cordycepin, an adenosine derivative composed of adenine and pentose, holds immense promise for treating inflammation and cancer. Our recent research has demonstrated that the combined treatment of cordycepin and the anti-CD47 antibody significantly curtails tumor growth and extends the lifespan of tumor-bearing mice. In the current study, we showed that the combination of cordycepin and CTLA-4 blockade had a profound impact on suppressing tumor growth. We utilized the MC38 and CT26 tumor models to evaluate the therapeutic effect of cordycepin, CTLA-4 blockade, and their combined approach. Flow cytometry results unveiled that cordycepin, when combined with CTLA-4 blockade, considerably augmented the presence of tumor-infiltrating CD8+T cells and diminished the population of Foxp3+Tregs within the tumor microenvironment (TME). Additionally, we employed single-cell analysis to examine the TME's reconfiguration upon the combined treatment of anti-CTLA-4 and cordycepin. We observed a significant impact on inhibiting tumor growth and substantially extended survival in tumor-bearing mice. Our data also demonstrated an increased proportion of effector CD8+T cells in the combined treatment group compared to all other groups, while exhausted CD8+T cells diminished in the combined group compared to the anti-CTLA-4 treatment alone. In conclusion, our findings supported the idea that combining cordycepin and CTLA-4 blockade could modify the effector and exhaustion status of CD8+T cells, thereby bolstering CD8+T-cell-mediated anti-tumor immunity in the TME. Collectively, our current study successfully established a combination therapeutic strategy utilizing cordycepin and CTLA-4 blockade. This strategy demonstrated a significant synergistic effect against cancer, highlighting its importance in cancer treatment.

Modulated Arabinose Uptake and cAMP Signaling Synergistically Improve Glucose and Arabinose Consumption in Recombinant Yeast.

During the production of ethanol from lignocellulose-derived sugars, recombinant yeasts tend to utilize xylose and arabinose after glucose exhaustion. So far, many glucose-insensitive pentose transporters have been reported to counteract this phenomenon, but few studies have described intracellular factors. In this study, the combination of adaptive evolution, comparative genomics, and genetic complementation revealed that the hexokinase-deficient (Hxk0) arabinose-fermenting Saccharomyces cerevisiae requires the arabinose transporter variant Gal2-N376T and the mutations of guanine nucleotide exchange factor Cdc25 to overcome glucose restriction during arabinose assimilation. The results showed that the Hxk0 recombinant yeasts could lower the metabolic/physiological threshold of cell proliferation by downregulating the intracellular cAMP levels, resulting in smaller cells and increased arabinose assimilation under glucose restriction. In the medium containing 80 g/L glucose and 20 g/L arabinose, the evolved strain restoring the hexokinase activity completed fermentation at 22 h, compared to 24 h for the parental strain. Overall, the experimental results provide new insights into glucose repression of biorefinery yeasts.

Engineering Saccharomyces cerevisiae for improved biofilm formation and ethanol production in continuous fermentation.

BACKGROUND: Biofilm-immobilized continuous fermentation has the potential to enhance cellular environmental tolerance, maintain cell activity and improve production efficiency. RESULTS: In this study, different biofilm-forming genes (FLO5, FLO8 and FLO10) were integrated into the genome of S. cerevisiae for overexpression, while FLO5 and FLO10 gave the best results. The biofilm formation of the engineered strains 1308-FLO5 and 1308-FLO10 was improved by 31.3% and 58.7% compared to that of the WT strain, respectively. The counts of cells adhering onto the biofilm carrier were increased. Compared to free-cell fermentation, the average ethanol production of 1308, 1308-FLO5 and 1308-FLO10 was increased by 17.4%, 20.8% and 19.1% in the biofilm-immobilized continuous fermentation, respectively. Due to good adhering ability, the fermentation broth turbidity of 1308-FLO5 and 1308-FLO10 was decreased by 22.3% and 59.1% in the biofilm-immobilized fermentation, respectively. Subsequently, for biofilm-immobilized fermentation coupled with membrane separation, the engineered strain significantly reduced the pollution of cells onto the membrane and the membrane separation flux was increased by 36.3%. CONCLUSIONS: In conclusion, enhanced biofilm-forming capability of S. cerevisiae could offer multiple benefits in ethanol fermentation.

Construction of co-immobilized multienzyme systems using DNA-directed immobilization technology and multifunctionalized nanoparticles.

The multienzyme co-immobilization systems with high cascade catalytic efficiency and selectivity have attracted considerable attention. In this study, through DNA-directed immobilization (DDI) technology, two model enzymes, glucose oxidase (GOD) and horseradish peroxide (HRP) were co-immobilized on the multifunctional silica nanoparticles (DDI enzyme). In addition to the directional distribution promoted by DNA complementary chains, the multienzyme system allowed the control of the stoichiometric ratio of the enzymes by adjusting the ratio of amino/carboxyl groups. The optimal mole ratio of GOD/HRP was 1:2, while the protein loading amount could reach 8.06 mg·g-1. Compared with the conventional direct adsorption, the catalytic activity of the DDI enzyme was 2.49 times higher. Moreover, with the enhancement of thermal and mechanical stability, the DDI enzyme could still retain at least 50% of its initial activity after 12 cycles. Accompanied by an excellent response and good selectivity, the constructed multienzyme systems simultaneously showed the potential as a glucose detector. Therefore, based on the DDI technology, the highly efficient multienzyme co-immobilization system could be further extended for a wider range of research fields.

Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer.

Cordycepin is widely considered a direct tumor-suppressive agent. However, few studies have investigated as the effect of cordycepin therapy on the tumor microenvironment (TME). In our present study, we demonstrated that cordycepin could weaken the function of M1-like macrophages in the TME and also contribute to macrophage polarization toward the M2 phenotype. Herein, we established a combined therapeutic strategy combining cordycepin and an anti-CD47 antibody. By using single-cell RNA sequencing (scRNA-seq), we showed that the combination treatment could significantly enhance the effect of cordycepin, which would reactivate macrophages and reverse macrophage polarization. In addition, the combination treatment could regulate the proportion of CD8+ T cells to prolong the progression-free survival (PFS) of patients with digestive tract malignancies. Finally, flow cytometry validated the changes in the proportions of tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs). Collectively, our findings suggested that the combination treatment of cordycepin and the anti-CD47 antibody could significantly enhance tumor suppression, increase the proportion of M1 macrophages, and decrease the proportion of M2 macrophages. In addition, the PFS in patients with digestive tract malignancies would be prolonged by regulating CD8 + T cells.

Biofilm-Based Biocatalysis for Galactooligosaccharides Production by the Surface Display of ß-Galactosidase in Pichia pastoris.

Galactooligosaccharides (GOS) are one of the most important functional oligosaccharide prebiotics. The surface display of enzymes was considered one of the most excellent strategies to obtain these products. However, a rough industrial environment would affect the biocatalytic process. The catalytic process could be efficiently improved using biofilm-based fermentation with high resistance and activity. Therefore, the combination of the surface display of ß-galactosidase and biofilm formation in Pichia pastoris was constructed. The results showed that the catalytic conversion rate of GOS was up to 50.3% with the maximum enzyme activity of 5125 U/g by screening the anchorin, and the number of the continuous catalysis batches was up to 23 times. Thus, surface display based on biofilm-immobilized fermentation integrated catalysis and growth was a co-culture system, such that a dynamic equilibrium in the consolidated integrative process was achieved. This study provides the basis for developing biofilm-based surface display methods in P. pastoris during biochemical production processes.