Biomanufacturing has emerged as a crucial driving force for efficient material conversion through engineered cells or cell-free systems. However, the intrinsic spatiotemporal heterogeneity, complexity, and dynamic characteristics of these processes pose significant challenges to systematic understanding, optimization, and regulation. This review summarizes essential methodologies for multi-omics data acquisition and analyses for bioprocesses and outlines modelling approaches based on multi-omics data. Furthermore, we explore practical applications of multi-omics and modelling in fine-tuning process parameters, improving fermentation control, elucidating stress response mechanisms, optimizing nutrient supplementation, and enabling real-time monitoring and adaptive adjustment. The substantial potential offered by integrating multi-omics with computational modelling for precision bioprocessing is also discussed. Finally, we identify current challenges in bioprocess optimization and propose the possible solutions, the implementation of which will significantly deepen understanding and enhance control of complex bioprocesses, ultimately driving the rapid advancement of biomanufacturing.
Fermentation ; Genomics/methods* ; Biotechnology/methods* ; Proteomics/methods* ; Models, Biological ; Metabolomics/methods* ; Bioreactors ; Multiomics

OBJECTIVE: To investigate the expression of citrullinated epitopes in articular cartilage protein and whether its expression is sufficient to induce anti-citrullinated protein antibody (ACPA) response in mice. METHODS: The experimental group was treated with different concentrations of lipopolysaccharide (LPS), heat-inactivated bacteria ( and ) or specific monoclonal antibody against type Ⅱ collagen to induce citrullination of articular cartilage protein, with PBS as the control. Immunohistochemistry with the monoclonal antibody ACC4 (IgG1) that specifically binds to the citrullinated epitope of cartilage protein was performed for detecting the expression of citrullinated protein, with ACC1 (IgG2a) as a positive control antibody and L243 (IgG2a) and Hy2.15 (IgG1) as the negative isotype control. In the in vivo experiment, SD rats were subjected to injection of different doses of LPS in the right knee (with PBS as the controls in the left knee), and 3 days later frozen sections were prepared for immunohistochemical detection of the expression of citrullinated protein. Models of collagen-induced arthritis (CIA) established in different mouse strains were observed for incidence and severity of CIA. Serum samples collected from these models and the sera from rheumatoid arthritis patients were examined for anti-citrullinated protein antibody, and immunohistochemistry was performed to detect the expression of citrullinated protein in the cartilage of the mouse. RESULTS: The citrullinated CII epitope-specific antibody ACC4 did not bind to articular cartilage tissues with different treatments as compared with the positive control antibody ACC1. The ACC4 antibody and the antibodies from patients with rheumatoid arthritis with high titers of anti-citrullinated protein antibody were capable of binding to the synovial tissue around the articular cartilage of the CIA. Luminex analysis showed that the anti-citrullinated protein antibody was lowly expressed in mouse serum, but the anti-type Ⅱ collagen triple helix structure peptide antibody exhibited strong reactivity. CONCLUSIONS Mild acute inflammatory response is not enough to cause citrullination of articular cartilage protein, and the expression of specific epitope requires a high-intensity inflammatory response. Inflammatory articular cartilage protein can express citrullinated epitopes in type Ⅱ collagen-induced arthritis in mice, but the expression of citrullinated epitopes is not sufficient to induce an immune response to anti-citrullinated antibodies. Stronger stimulation signals are required to induce an immune response for producing anti-citrullinated protein antibodies.
Animals ; Arthritis, Experimental ; Autoantibodies ; Cartilage, Articular ; Citrulline ; Humans ; Inflammation ; Mice ; Rats ; Rats, Sprague-Dawley

Objective To evaluate the role of α2A adrenergic receptor (α2AAR) in dexmedetomidine-induced inhibition of TLR4/NF-κB signaling pathway activation during hypoxia-reoxygenation (H/R)caused injury to alveolar type Ⅱ epithelial cells.Methods Type Ⅱ] alveolar epithelial cells of rats RLE6TN cells cultured in vitro were divided into 4 groups (n =6 each) using a random number table method:control group (group C),H/R injury group (group H/R),dexmedetomidine group (group D) and α2A AR small interfering RNA (siRNA) plus dexmedetomidine group (group α2AAR-siRNA+D).H/R was produced by exposing cells to 1％ O2-5％ CO2-94％ N2 for 24 h followed by 4-h reoxygenation.Cells were incubated for 1 h with dexmedetomidine at the final concentration of 1 nmol/L,and then H/R model was established in group D.In group α2AAR-siRNA+D,cells were transfected with 50 nmol/L α2AAR-siRNA,48 h later dexmedetomidine at the final concentration of 1 nmol/L was added,cells were incubated for 1 h,and then H/R model was established.The cell viability was measured using CCK-8 method,cell apoptosis rate was determined by flow cytometry,and the expression of TLR4 and NF-κB was detected by immunofluorescence.Results Compared with group C,the cell viability was significantly decreased,the apoptosis rate was increased,and the expression of TLR4 and NF-κB was up-regulated in group H/R (P＜0.05),and no significant change was found in the parameters mentioned above in group D (P＞0.05).Compared with group H/R,the cell viability was significantly increased,the apoptosis rate was decreased,and the expression of TLR4 and NF-κB was down-regulated in group D (P＜0.05),and no significant change was found in the parameters mentioned above in group α2AAR-siRNA+D (P＞0.05).Compared with group D,the cell viability was significantly decreased,the apoptosis rate was increased,and the expression of TLR4 and NF-κB was up-regulated in group α2AAR-siRNA+D (P＜0.05).Conclusion The mechanism by which dexmedetomidine inhibits TLR4/NF-κB signaling pathway activation may be related to activating α2AAR during H/R-caused injury to alveolar type Ⅱ epithelial cells.