Gastric cancer (GC) is the fifth most prevalent malignancy globally. However, its heterogeneity and asymptomatic early-stage development hinder timely diagnosis and effective treatment. Here, we employed single-cell RNA sequencing to delineate the transitional features of pit mucous cells (PMCs) during the gastritis-to-cancer transition and identified 100 core genes. Characterization of the gene set revealed the role of ribosomal protein small subunit and ribosomal protein large subunit in inflammation-to-cancer transition, which promoted ribonucleoprotein complex biogenesis and cytoplasmic translation. External validation using independent cohorts confirmed that this core gene set discriminated disease progression (AUC>0.7) and was significantly enriched in GC tissues (p<0.01). Moreover, we evaluated the therapeutic intervention effects of C. butyricum and synbiotics (Weichanghao®) using a rat model of gastritis and demonstrated the targeted suppression of inflammation-to-cancer transition genes. Our findings establish the basis for early diagnosis of GC through PMC-driven molecular dynamics. Additionally, we propose microbiota-based strategies to prevent the inflammation-to-cancer transition in preneoplastic stages. Furthermore, our results highlight that dysbiosis of the gastric microbiome can be addressed using probiotic supplementations and the core gene set may provide labeling for the evaluation of probiotics-based treatment.

Dicarboxylates are valuable platform compounds with a broad range of applications. The in vitro biosynthetic system used to produce dicarboxylates from ω-amino acids via the natural pathway requires costly cofactors and co-substrates, which restricts its economic feasibility of use. In this study, we designed a cofactor- and co-substrate-free artificial pathway for the production of dicarboxylates from ω-amino acids. Only three enzymes (viz., amine oxidase from Kluyveromyces marxianus DMKU3-1042, xanthine oxidase from bovine milk, and catalase from Aspergillus niger) were required for dicarboxylate production. Succinate (0.79 g g^-1), glutarate (0.83 g g^-1), and adipate (0.77 g g^-1) were produced in high yields from the corresponding ω-amino acids through the in vitro biosynthetic system with the artificial pathway. Glutarate could also be produced from l-lysine by further introducing l-lysine monooxygenase and 5-aminovaleramide amidohydrolase from Pseudomonas putida KT2440 into the in vitro biosynthetic system, with the cofactor- and co-substrate-free system achieving a product yield of 0.63 g g^-1. Considering its desirable characteristics, this artificial pathway-based in vitro biosynthetic system may be a promising alternative for dicarboxylate production from biotechnologically produced ω-amino acids.

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder characterized by debilitating motor and non-motor symptoms. Its etiology is multifactorial, with no single definitive cause identified, although aging is a significant risk factor. Additional risks include genetic predisposition, family history, and environmental factors such as pesticide exposure and Helicobacter pylori infection. Dysbiosis of the gut microbiota, and in particular bacterial imbalances, has been implicated in the disruption of the gut-brain axis, contributing to both systemic and neuroinflammation. Environmental factors such as antibiotic exposure and toxins can precipitate microbial dysregulation, potentially accelerating PD progression. Understanding the mechanisms of the gut-brain axis and identifying strategies to preserve a healthy microbiome are essential for developing novel therapeutic approaches. This review synthesizes current therapeutic strategies and ongoing research focused on restoring gut-brain balance to combat PD. These approaches include fecal microbiota transplantation, dietary interventions, and probiotic therapies, all of which show promise in mitigating both motor and non-motor symptoms. Furthermore, we emphasize the urgent need for continued research into probiotics and innovative therapeutic approaches for gut-brain axis modulation, presenting novel opportunities for effective PD management.

As the understanding of bacteria-mediated cancer therapies deepens, bacteria such as Escherichia coli Nissle 1917 (EcN) have become a promising platform for cancer therapy. However, their potential role in real-time monitoring and visualization tools still needs to be explored and enhanced. In this study, we aimed to screen and optimize EcN visualization systems for non-invasive in vivo bioluminescence imaging in live mice. To this end, we developed three series of recombinant EcN strains expressing Gaussia luciferase (Gluc), Renilla luciferase (Rluc), and NanoLuc (Nluc), along with their respective mutants. These strains exhibited bioluminescence when different coelenterazine (CTZ) substrates were present. As a result, multiple bioluminescent EcN strain-substrate pairs were identified with stronger, longer, or red-shifted bioluminescence, offering multiple effective optical tumor-targeting systems for in vivo studies investigating bacteria-mediated cancer therapy and intestinal diseases.

Engineering microorganisms to withstand extreme temperatures (>80 °C) remains a critical challenge in industrial biotechnology owing to limited genetic tools and poor mechanistic understanding of microbial thermoadaptation. We aimed to develop a novel Geobacillus stearothermophilus strain with remarkable thermal resilience through an integrated approach combining adaptive laboratory evolution and rational genetic engineering. Progressive thermal adaptation (70-80 °C) followed by genome reduction generated a mutant (SL-1-80) with enhanced stability at 80 °C. Subsequent combinatorial overexpression of eight heat-associated genes (murD, cysM, grpE, groES, hsp33, hslO, hrcA, clpE) synergistically extended its survival to 85 °C. Genomic and transcriptomic analyses revealed a triple mechanism: (1) strategic deletion of transposable elements (IS5377/IS4/IS110) reduced genomic instability, (2) co-activation of chaperone systems (GroES-GrpE) and redox homeostasis enzymes (HslO——Hsp33) enhanced protein folding and oxidative stress resistance, and (3) metabolic plasticity (BglG and HTH-domain transcriptional repressor), motility optimization (FliY), and transcriptional reprogramming (Sigma-D, DUF47-family chaperone and HTH-domain transcriptional repressor) facilitated nutrient acquisition and motility-based environmental navigation under stress. Furthermore, we established the first high-efficiency electroporation protocol (10⁴ transformants/µg DNA) for this genus, enabling ATP-enhanced heterologous protein expression under heat stress. This study provided a robust platform organism for high-temperature bioprocessing and a mechanistic blueprint for engineering microbial thermotolerance, addressing key limitations in applications such as microbial-enhanced oil recovery and industrial enzyme production.

A unicellular-colonial cyanobacterium, designated “BRSZ,” was isolated from a neutral-alkaline hot spring in Thailand. Morphological characterization revealed distinctive features consistent with those of the genus Gloeocapsa. Physiological assessments demonstrated that BRSZ is a moderately thermophilic and halotolerant cyanobacterium with the potential for chemoheterotrophic growth in dark conditions. Molecular phylogenetic analysis based on 16S ribosomal RNA (rRNA) gene sequences placed BRSZ within a well-defined Gloeocapsa clade, a finding corroborated by 16S-23S internal transcribed spacer (ITS) rRNA secondary structure analyses. Genome comparisons, including average nucleotide identity (ANI), genome-to-genome distance (GGD), and digital DNA-DNA hybridization (dDDH), between strain BRSZ and closely related taxa showed an ANI value of 95.45 %, near the lower boundary of the species delineation threshold (95-96 %). A GGD of 0.0374 (>0.0258) and dDDH of 69 % (<70 %) further supported genomic differentiation. Genome-based analysis revealed a mycosporine-like amino acid biosynthetic gene cluster likely involved in sunscreen compound production. Cultivation-based production of a UV-absorbing compound confirmed the functional relevance of this gene cluster. These findings expand the described diversity within the Gloeocapsa complex and enhance our understanding of the taxonomy of this group. In addition, they underscored the importance of hot spring environments as sources of novel extremophiles.

Cycloastragenol is a bioactive, high-value triterpenoid derived from Astragalus membranaceus. Conventional plant-based extraction and chemical synthesis methods are expensive. To our knowledge, this is the first report on the de novo biosynthesis of cycloastragenol in yeast. The mevalonate pathway was reconstituted in yeast peroxisomes, and the engineered yeast produced 656.55 mg/L squalene. Further introduction of heterologous enzymes led the engineered yeast to produce 1.04 mg/L cycloastragenol, which demonstrated the yeast production of value-added medicinal molecules.

Staphylococcus aureus is a major public health threat, largely due to its remarkable capacity to develop antimicrobial resistance. Zhang et al. recently demonstrated a highly innovative approach to eradicate chronic methicillin-resistant S. aureus infections by inducing bacterial calcification with antibody-polysialic acid conjugates targeting wall teichoic acids, while simultaneously modulating host immune responses via enhanced calprotectin expression and macrophage activation. Despite limitations, this strategy represents a promising and unconventional therapy to combat resistant S. aureus infections.