Bladder cancer is common and widespread, and its incidence is increasing. Many new diagnostic methods combined with state-of-the-art technology have been introduced in cystoscopy to collect real-time images of the bladder mucosa for diagnosis, but often miss inconspicuous early-stage tumors. Fluorophore-labeled peptides with high sensitivity and specificity for cancer would be a desirable tool for the detection and treatment of tiny or residual bladder tumors. Phage display and the human non-muscle-invasive bladder cancer cell line BIU-87 were used to identify a peptide. The isolated phage display peptide (CSSPIGRHC, named NYZL1) was tested in vitro for its binding specificity and affinity. Accumulation into xenograft tumors in a nude mouse model was analyzed with FITC-labeled NYZL1. NYZL1, with strong tumor‑homing ability, was identified by in vivo phage library selection in the bladder cancer model. The NYZL1 phage and synthetic FITC-labeled NYZL1 peptides bound to tumor tissues and cells, but were hardly detected in normal control organs. Notably, accumulation of FITC-NYZL1 in bladder tumor cells was time-dependent. Biodistribution studies of xenografts of BIU-87 cells showed accumulation of injected FITC-NYZL1 in the tumors, and the bound peptide could not be removed by perfusion after 24 h. The mouse model of bladder tumor showed increased fluorescence intensity in the tumor-bearing bladder in comparison with normal bladder tissues after 4-6 h. In conclusion, NYZL1 may represent a lead peptide structure applicable in the development of optical molecular imaging.

Despite being the most common form of chronic liver disease, there are still no approved drugs for thetreatment of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to elucidate the therapeutic effects and possible mechanisms of hydrogen (H2) inhalation in mice with NAFLD. Male C57BL/6 mice (6 weeks old) were fed either a 60% fat diet (high-fat diet [HFD]) or a 10% fat diet (normal diet) for 11 weeks. Then, H2 was administered to random HFD-fed mice for another 11 weeks before they were euthanized. Biochemical analysis of serum samples, histological analysis of liver and ileum samples, 16S rRNA sequencing analysis of stool samples, and analysis of the expression levels of related factors by enzyme-linked immunosorbent assay were conducted to determine the effect of H2 intervention on NAFLD. H2 inhalation alleviated hyperglycemia and impaired glucose tolerance; decreased the serum concentrations of triglycerides, cholesterol, alanine aminotransferase, aspartate aminotransferase, lipopolysaccharide, and tumor necrosis factor-alpha; and ameliorated liver injury by a HFD, although no weight loss was observed. Interestingly, H2 inhalation increased the relative abundance of Akkermansia muciniphila and decreased the Firmicutes-to-Bacteroidia ratio in the intestinal tract of NAFLD mice. These data indicate that H2 alleviated the symptoms of NAFLD by increasing the abundance of A. muciniphila in the intestine. Thus, H2 may be a new potential treatment strategy for patients with NAFLD.

非小细胞肺癌（non-small cell lung cancer, NSCLC）是最常见的肺癌组织学类型，也是病死率最高的恶性肿瘤之一。多肽作为光学分子成像探针的主体可以实现肿瘤的早期筛查及诊断，提高患者存活率。本研究旨在利用体内噬菌体展示技术筛选与人NSCLC细胞NCI-H1299高度结合的小分子多肽并通过体外实验鉴定其结合特异性。 制备NCI-H1299细胞荷瘤裸鼠模型，用噬菌体展示环七肽库进行3轮体内筛选后随机挑取噬菌体克隆，免疫组织化学法及酶联免疫吸附法（enzyme-linked immunosorbent assay, ELISA）鉴定噬菌体克隆对NCI-H1299细胞的亲和力。提取阳性单克隆噬菌体DNA测序获得外源多肽氨基酸序列，将重复率最高的序列化学合成多肽并进行异硫氰酸荧光素（fluorescein, FITC）标记，制备光学分子探针，初步鉴定其对NCI-H1299细胞的特异性。 经3轮体内筛选后噬菌体富集率是首轮的341.3倍；免疫组织化学染色显示随着筛选次数增加，肿瘤组织中结合的噬菌体不断增加，且结合量明显高于正常组织；ELISA结果显示随机挑取的30个噬菌体克隆中20个为阳性克隆，经测序后将重复率最高的序列合成多肽并命名为NSP1；四甲基偶氮唑盐比色法（methyl thiazolyl tetrazolium assay, MTT）、细胞划痕实验表明NSP1不会影响细胞增殖、迁移；流式细胞术、细胞免疫荧光结果表明NSP1可与NCI-H1299细胞特异性结合。 利用体内噬菌体展示技术成功得到了与肺癌NCI-H1299细胞特异性结合的多肽NSP1，为NSCLC的早期诊断及靶向治疗奠定了研究基础。

Introduction. The distribution of micro-organisms in healthy organisms remains a subject of debate. Emerging evidence revealed the colonization of microbial communities in multiple anatomical sites previously considered sterile under homeostatic conditions. However, the mechanistic relationship between compromised intestinal epithelial barrier integrity and subsequent translocation of gut-resident bacteria into systemic circulation has yet to be comprehensively elucidated. Hypothesis/Gap Statement. Under intestinal leakage, gut micro-organisms can break through the intestinal barrier and then translocate to other organs. Aim. This study investigates the distribution of micro-organisms in healthy organisms to determine whether gut bacteria translocate to sterile organs only under the condition of intestinal leakage using GFP-labelled Escherichia coli (GFP-E. coli) tracing. Methodology. Female C57BL/6 mice (5 weeks old) were administered either a glacial acetic acid enema [inflammatory bowel disease (IBD) group] or a sterile normal saline enema [normal control (NC) group]. All mice were subsequently gavaged with GFP-E. coli. HE staining and Alcian blue staining were performed to evaluate the colon injury. The expression levels of intestinal tight junction proteins (ZO-1 and occludin) were tested by reverse transcription quantitative PCR and immunofluorescence staining. The distribution of GFP-E. coli in multiple organs was assessed through bacterial culture, confocal microscopy and PCR. Results. In the IBD mice, mucopolysaccharide accumulation levels (P<0.01) and tight junction proteins ZO-1 (P<0.001) and occludin (P<0.01) in the colon were significantly decreased compared with the NC group. Bacterial culture showed that there was no GFP-E. coli in the blood, heart, liver, spleen, lungs, kidneys or oviducts of normal mice, while the number of GFP-E. coli colonies in the blood (219 c.f.u. ml⁻¹), liver (2.39×10⁵ c.f.u. ml⁻¹) and lungs (2.50×10⁸ c.f.u. ml⁻¹) of the IBD mice was significantly higher than that of the NC group. The confocal microscopy and PCR results also showed that the number of GFP-E. coli in the liver and lungs of the IBD group was significantly higher than that of the NC group (P<0.001). Conclusion. Healthy mice maintain a sterile microenvironment in the blood, heart, liver, spleen, lungs, kidneys and oviducts. However, compromised intestinal barrier integrity facilitates microbial translocation from the intestinal lumen into the blood, liver and lungs. This study advances our understanding of endogenous infections caused by IBD, demonstrating the crucial role of intestinal permeability in bacterial infections.