Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

OBJECTIVE To investigate the expression and clinical significance of microRNA-223(miR-223),mono-cyte chemoattractant protein-1(MCP-1),and basic fibroblast growth factor(bFGF)in patients with colostomy infection after rectal cancer surgery.METHODS One hundred patients with rectal cancer who underwent surgery in Zhejiang Provincial People's Hospital between Jun.2022 and Jun.2024 were chosen retrospectively and divided in-to an infection group(n=27)and a non-infection group(n=73)based on whether colostomy infection occurred within seven days after surgery.The etiological features of postoperative hospital-acquired infection were analyzed,and the differences in serum miR-223,bFGF,and MCP-1 levels between the infected and non-infected groups were detected.The receiver operating characteristic(ROC)curve was used to analyze the predictive values of ser-um miR-223,bFGF,and MCP-1 for postoperative colostomy infection.RESULTS A total of 30 pathogenic strains were isolated from 27 patients in the infection group,including 17 gram-negative bacteria(56.67%),11 gram-positive bacteria(36.67%),and 2 fungi(6.67%),with Escherichia coli being the most common.The serum lev-els of miR-223 and MCP-1 were higher in the infected group than those in the non-infected group,while bFGF was lower in the infected group(P<0.05).The ROC curve analysis showed that the area under the curve(AUC)for the combined detection of serum miR-223,bFGF,and MCP-1 was 0.944,with the sensitivity of 88.88%and spe-cificity of 94.52%.CONCLUSIONS Postoperative colostomy infection in rectal cancer patients is primarily caused by E.coli and is associated with changes in serum miR-223,bFGF and MCP-1 levels.Abnormally high expression of miR-223 and MCP-1 and abnormally low expression of bFGF can predict postoperative colostomy infection in rectal cancer,which can provide an important basis for clinical diagnosis of postoperative infections in the rectal cancer patients.

OBJECTIVE To investigate the expression and clinical significance of microRNA-223(miR-223),mono-cyte chemoattractant protein-1(MCP-1),and basic fibroblast growth factor(bFGF)in patients with colostomy infection after rectal cancer surgery.METHODS One hundred patients with rectal cancer who underwent surgery in Zhejiang Provincial People's Hospital between Jun.2022 and Jun.2024 were chosen retrospectively and divided in-to an infection group(n=27)and a non-infection group(n=73)based on whether colostomy infection occurred within seven days after surgery.The etiological features of postoperative hospital-acquired infection were analyzed,and the differences in serum miR-223,bFGF,and MCP-1 levels between the infected and non-infected groups were detected.The receiver operating characteristic(ROC)curve was used to analyze the predictive values of ser-um miR-223,bFGF,and MCP-1 for postoperative colostomy infection.RESULTS A total of 30 pathogenic strains were isolated from 27 patients in the infection group,including 17 gram-negative bacteria(56.67%),11 gram-positive bacteria(36.67%),and 2 fungi(6.67%),with Escherichia coli being the most common.The serum lev-els of miR-223 and MCP-1 were higher in the infected group than those in the non-infected group,while bFGF was lower in the infected group(P<0.05).The ROC curve analysis showed that the area under the curve(AUC)for the combined detection of serum miR-223,bFGF,and MCP-1 was 0.944,with the sensitivity of 88.88%and spe-cificity of 94.52%.CONCLUSIONS Postoperative colostomy infection in rectal cancer patients is primarily caused by E.coli and is associated with changes in serum miR-223,bFGF and MCP-1 levels.Abnormally high expression of miR-223 and MCP-1 and abnormally low expression of bFGF can predict postoperative colostomy infection in rectal cancer,which can provide an important basis for clinical diagnosis of postoperative infections in the rectal cancer patients.

Objective:To study the feasibility of 3-D reconstruction model in the observation of tetrachlorodibenzo-p-dioxin(TCDD) effected palatal organ development of fetal mouse.Methods:Kunming mice treated 40 ug/kg TCDD by lavage on day 12.5 of pregnancy were used as in the experimental group,isodose corn oil treated in the control group.On day 13.5,14.5 and 15.5 of pregnancy heads of the fetal mice were taken out and fixed.Conventional paraffin serial sections of palatal organ were preparated and dyed by hematoxylin-eosin,images of the palatal organs were collected and photoshop treated,3-D reconstruction of the palatal organ was performed by 3D-DOCTOR software.Results:3-D reconstruction images showed that palatal organs moved from on both sides above the tongue and gradually closed and merged in the control group.In the experimental group,the palatal organs moved from on both sides above the tongue was later than control group,gradually closed,but not merged,formed cleft palate.Conclusion:3D-DOCTOR software reconstruction can be used for the study of the development process effected by TCDD in the pregnant mouse.

Purpurin is a common component ofRubia cordifolia L. The study on its molecular target was useful for elucidating the therapeutic material basis and action mechanism ofR. cordifolia. HT-29 cells were used in the cell culture. The highly expressed G Protein-coupled Receptor-35 (GPR35) agonist was used as target. The label-free optical biosensor cellular assay was used to investigate the agonist activity ofpurpurin at an endogenous receptor. The results showed thatpurpurin can cause DMR response in HT-29 cells. And the DMR response curve type was consistent with zaprinast. Its EC50 was 6.142± 0.189μmol·L-1. In addition,purpurinhad desensitization effect on GPR35 agonist zaprinast in HT-29 cells. GPR35 agonist ML145 blocked the DMR ofpurpurin. It was concluded thatpurpurinwas the GPR35 agonist.