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The shikimate pathway is a necessary pathway for the synthesis of aromatic compounds. The intermediate products of the shikimate pathway and its branching pathway have promising properties in many fields, especially in the pharmaceutical industry. Many important compounds, such as shikimic acid, quinic acid, chlorogenic acid, gallic acid, pyrogallol, catechol and so on, can be synthesized by the shikimate pathway. Among them, shikimic acid is the key raw material for the synthesis of GS4104 (Tamiflu®), an inhibitor of neuraminidase against avian influenza virus. Quininic acid is an important intermediate for synthesis of a variety of raw chemical materials and drugs. Gallic acid and catechol receive widespread attention as pharmaceutical intermediates. It is one of the hotspots to accumulate many kinds of target products by rationally modifying the shikimate pathway and its branches in recombinant strains by means of metabolic engineering. This review considers the effects of classical metabolic engineering methods, such as central carbon metabolism (CCM) pathway modification, key enzyme gene modification, blocking the downstream pathway on the shikimate pathway, as well as several expansion pathways and metabolic engineering strategies of the shikimate pathway, and expounds the synthetic biology in recent years in the application of the shikimate pathway and the future development direction.

Liver cancer is the second leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma is the most common type. The pathogenesis of hepatocellular carcinoma is concealed, its progress is rapid, its prognosis is poor, and the mortality rate is high. Therefore, novel molecular targets for hepatocellular carcinoma early diagnosis and development of targeted therapy are critically needed. Glypican-3, a cell-surface glycoproteins in which heparan sulfate glycosaminoglycan chains are covalently linked to a protein core, is overexpressed in HCC tissues but not in the healthy adult liver. Thus, Glypican-3 is becoming a promising candidate for liver cancer diagnosis and immunotherapy. Up to now, Glypican-3 has been a reliable immunohistochemical marker for hepatocellular carcinoma diagnosis, and soluble Glypican-3 in serum has becoming a promising marker for liquid biopsy. Moreover, various immunotherapies targeting Glypican-3 have been developed, including Glypican-3 vaccines, anti- Glypican-3 immunotoxin and chimeric-antigen-receptor modified cells. In this review, we summarize and analyze the structure and physicochemical properties of Glypican-3 molecules, then review their biological functions and applications in clinical diagnosis, and explore the diagnosis and treatment strategies based on Glypican-3.

The performance of an advanced research version of the Weather Research and Forecasting Model (WRF) in predicting near-surface atmospheric temperature and wind conditions under various terrain and weather regimes is examined. Verification of 2-m temperature and 10-m wind speed and direction against surface Mesonet observations is conducted. Three individual events under strong synoptic forcings (i.e., a frontal system, a low-level jet, and a persistent inversion) are first evaluated. It is found that the WRF model is able to reproduce these weather phenomena reasonably well. Forecasts of near-surface variables in flat terrain generally agree well with observations, but errors also occur, depending on the predictability of the lower-atmospheric boundary layer. In complex terrain, forecasts not only suffer from the model's inability to reproduce accurate atmospheric conditions in the lower atmosphere but also struggle with representative issues due to mismatches between the model and the actual terrain. In addition, surface forecasts at finer resolutions do not always outperform those at coarser resolutions. Increasing the vertical resolution may not help predict the near-surface variables, although it does improve the forecasts of the structure of mesoscale weather phenomena. A statistical analysis is also performed for 120 forecasts during a 1-month period to further investigate forecast error characteristics in complex terrain. Results illustrate that forecast errors in near-surface variables depend strongly on the diurnal variation in surface conditions, especially when synoptic forcing is weak. Under strong synoptic forcing, the diurnal patterns in the errors break down, while the flow-dependent errors are clearly shown.

Pyruvate is a hub of various endogenous metabolic pathways, including glycolysis, TCA cycle, amino acid, and fatty acid biosynthesis. It has also been used as a precursor for pyruvate-derived compounds such as acetoin, 2,3-butanediol (2,3-BD), butanol, butyrate, and L-alanine biosynthesis. Pyruvate and derivatives are widely utilized in food, pharmaceuticals, pesticides, feed additives, and bioenergy industries. However, compounds such as pyruvate, acetoin, and butanol are often chemically synthesized from fossil feedstocks, resulting in declining fossil fuels and increasing environmental pollution. Metabolic engineering is a powerful tool for producing eco-friendly chemicals from renewable biomass resources through microbial fermentation. Here, we review and systematically summarize recent advances in the biosynthesis pathways, regulatory mechanisms, and metabolic engineering strategies for pyruvate and derivatives. Furthermore, the establishment of sustainable industrial synthesis platforms based on alternative substrates and new tools to produce these compounds is elaborated. Finally, we discuss the potential difficulties in the current metabolic engineering of pyruvate and derivatives and promising strategies for constructing efficient producers.

l-Valine is one of the three branched-chain amino acids (valine, leucine, and isoleucine) essential for animal health and important in metabolism; therefore, it is widely added in the products of food, medicine, and feed. l-Valine is predominantly produced through microbial fermentation, and the production efficiency largely depends on the quality of microorganisms. In recent years, continuing efforts have been made in revealing the mechanisms and regulation of l-valine biosynthesis in Corynebacterium glutamicum, the most utilitarian bacterium for amino acid production. Metabolic engineering based on the metabolic biosynthesis and regulation of l-valine provides an effective alternative to the traditional breeding for strain development. Industrially competitive l-valine-producing C. glutamicum strains have been constructed by genetically defined metabolic engineering. This article reviews the global metabolic and regulatory networks responsible for l-valine biosynthesis, the molecular mechanisms of regulation, and the strategies employed in C. glutamicum strain engineering.

Background The bHLH transcription factor is prevalent across the plant kingdom and is crucial for various abiotic stress responses in different plant species. Tritipyrum , an octoploid created from an intergeneric cross between Triticum aestivum (AABBDD) and Thinopyrum elongatum (EE), serves as a significant source of germplasm, facilitating the incorporation of desirable traits from Th. elongatum into T. aestivum . With the recent availability of the complete genome sequences of T. aestivum and Th. elongatum , it has become feasible to investigate the organization and expression patterns of bHLH genes within the Tritipyrum genome. Results In this study, a total of 398 bHLH genes ( TtbHLH ) were identified within the Tritipyrum genome. These genes were classified into twenty major groups based on evolutionary analysis, indicating that they share conserved motif compositions. The TtbHLH genes are distributed across 28 chromosomes and include 67 duplication events. Synteny analysis suggests a common ancestral lineage for the bHLH gene family. Transcriptome data and quantitative polymerase chain reaction (qPCR) expression profiling identified 29 TtbHLH genes with significantly elevated expression levels in response to various salt-stress conditions and recovery treatments. Notably, Tel1E01T336100 ( TtbHLH310 ) demonstrated a pronounced sensitivity to salt stress and is phylogenetically related to the salt-tolerant gene AtbHLH6 in Arabidopsis thaliana . Additionally, Pearson correlation analysis revealed 485 genes that exhibited a strong positive correlation ( R  > 0.9) with TtbHLH310 expression, which was enriched in pathways related to metabolic activities, cellular processes, stimulus responses, and biological regulation. Further analysis through real-time PCR confirmed that TtbHLH310 is highly expressed in the roots, stems, and leaves under salt-stress conditions. Conclusions The findings indicate that TtbHLH310 may play a pivotal role in enhancing salt stress tolerance in plants. Its strong expression in response to salt stress highlights its potential as a valuable foreign gene for improving salt tolerance in wheat. These insights contribute to our understanding of the molecular mechanisms underpinning abiotic stress responses in Tritipyrum and may aid in the development of more resilient wheat varieties.

Recombinant human collagen (rhCol) holds broad potential in biomedical and industrial applications due to its high purity and low immunogenicity. However, large-scale production of structurally stable and functionally active rhCol remains challenging. A novel strategy integrating collagen sequence optimization and microbial prolyl-4-hydroxylase (P4H) screening was developed to enable efficient production of triple-helical rhCol in Komagataella phaffii . Five Type III collagen variants (ColP1 ~ ColP5) were rationally designed based on interchain salt-bridge engineering to improve structural stability and biological activity, with ColP2 showing superior expression and functionality. A systematic evaluation of four microbial P4Hs identified Bacillus megaterium P4H (BmP4H) as the most effective catalyst for proline hydroxylation, enabling stable triple-helix formation. Combined with strain optimization, promoter and signal peptide screening, and 5-L scale fermentation, this approach achieved a high rhCol yield of 2.54 g/L with confirmed triple-helical structure. These results demonstrate an integrated and scalable platform for high-level production of functional recombinant collagen, providing a promising foundation for its industrial and clinical applications. Key Points • Co-expression of BmP4H enables stable triple-helical collagen in yeast. • Strain X-33, promoter P AOX1 , and a-factor leader optimize collagen secretion. • Scale-up in 5L bioreactor achieves 2.54 g/L rhCol production.

An emulsifier with a targeted antioxidant effect was prepared using the inclusion complexes of octenyl succinic anhydride (OSA)-modified cassava amylose (CA) and quercetin (Q). The designed emulsifier, a carbohydrate polymer-flavonoid complex, exhibited both amphiphilic and antioxidant properties. To investigate the physical and oxidation stabilities of the prepared emulsion, three types of emulsions were prepared: primary emulsions stabilized by enzyme-modified starch, secondary emulsions stabilized by OSA-CA, and tertiary emulsions stabilized by Q-encapsulated complexes (OSA-CA/Q). The structural characteristics of CA, OSA-CA, and OSA-CA/Q were investigated by scanning electron microscopy, Fourier transform infrared spectrometry, and small-angle X-ray scattering analysis. The stabilities of the emulsions were evaluated based on their particle size distribution, zeta potential, creaming stability, and peroxide value. The results showed that the secondary and tertiary emulsions exhibited a relatively narrower particle size distribution than the primary emulsions, but the particle size distribution of the tertiary emulsions was the narrowest (10.42 μm). Moreover, the secondary and tertiary emulsions had lower delamination indices than the primary emulsions after 7 days of storage. The results obtained from the antioxidant experiments indicated that OSA-CA/Q exhibited good oxidation stability for application in emulsion systems.

ABSTRACT Purpose The focus of this research was to formulate and evaluate a theranostic liposomal delivery system using indocyanine green (ICG) as a photosensitizer, triggered by near infrared (NIR) irradiation, for in vivo photodynamic therapy (PDT) of breast cancer. Methods Cytotoxicity of PDT using liposomal ICG (LPICG) as well as free ICG (FRICG) was evaluated in the human MDA-MB-468 triple-negative breast cancer (TNBC) cell line. NIR irradiation-induced increase in temperature was also monitored both in vitro and in vivo . Quantitative pharmacokinetic profile and fluorescence imaging-based biodistribution patterns of both formulations were obtained using the human TNBC xenograft model in nude mice. Overall safety, tolerability, and long-term anti-tumor efficacy of LPICG versus FRICG-mediated PDT was evaluated. Results Significant loss of cell viability was achieved following photoactivation of LPICG via NIR irradiation. Temperatures of irradiated LPICG increased with increasing concentrations of loaded ICG, which correlated with significant rise of temperature compared to PBS in vivo (p < 0.01) . Pharmacokinetic assessment revealed a significant increase in systemic distribution and circulation half-life of LPICG, and NIR fluorescence imaging demonstrated enhanced accumulation of liposomes within the tumor region. Tumor growth in mice treated with LPICG followed by NIR irradiation was significantly reduced compared to those treated with FRICG, saline, and irradiation alone. Conclusions In vivo photodynamic therapy using LPICG demonstrated targeted biodistribution and superior anti-tumor efficacy in a human TNBC xenograft model compared to FRICG. In addition, this unique delivery system exhibited a promising role in NIR image-guided delivery and real-time biodistribution monitoring of formulation with ICG serving as the fluorescent probe.

Anthocyanins biosynthesized from the flavonoid pathway are types of pigments that are involved in the protection of poplar from biotic and abiotic stresses. Previous researchers studying anthocyanin-related transcription factors and structural genes in poplar have made significant discoveries. However, little is known about the regulatory role of microRNAs in anthocyanin biosynthesis in poplar. Here, we overexpressed miR156 in poplar to study the comprehensive effects of the miR156- SPL module on the biosynthesis of anthocyanins. Small RNA sequencing analysis revealed 228 microRNAs differentially expressed in transgenic poplar plants with dramatically increased miR156 levels. Furthermore, integrated microRNAomic and transcriptomic analysis suggested that two microRNAs, miR160h, and miR858, have the potential to affect anthocyanin accumulation in poplar by regulating auxin response factors and MYB transcription factors, respectively. Additionally, the accumulation of miR160h and miR858 displayed a positive correlation with miR156 levels, suggesting a possible interaction between the miR156- SPL module and these microRNAs in poplar. Last, metabolomics analysis revealed that the levels of anthocyanins, flavones, and flavonols were substantially elevated in transgenic poplar plants overexpressing miR156 compared with the wild type, whereas the total lignin content was reduced in the transgenic plants. Taken together, our results indicate that miR156 can fine tune the anthocyanin biosynthetic pathway via multiple factors, including microRNAs, transcription factors, and the levels of structural genes, in poplar. This provides additional clues for understanding the complex regulatory network of anthocyanin biosynthesis in woody plants.