Pancreatic cancer is a devastating disease with a high mortality rate and a lack of effective therapies. The challenges associated with early detection and the highly aggressive nature of pancreatic cancer have limited treatment options, underscoring the urgent need for better disease-modifying therapies. Peptide-based biotherapeutics have become an attractive area of research due to their favorable properties such as high selectivity and affinity, chemical modifiability, good tissue permeability, and easy metabolism and excretion. Phage display, a powerful technique for identifying peptides with high affinity and specificity for their target molecules, has emerged as a key tool in the discovery of peptide-based drugs. Phage display technology involves the use of bacteriophages to express peptide libraries, which are then screened against a target of interest to identify peptides with desired properties. This approach has shown great promise in cancer diagnosis and treatment, with potential applications in targeting cancer cells and developing new therapies. In this comprehensive review, we provide an overview of the basic biology of phage vectors, the principles of phage library construction, and various methods for binding affinity assessment. We then describe the applications of phage display in pancreatic cancer therapy, targeted drug delivery, and early detection. Despite its promising potential, there are still challenges to be addressed, such as optimizing the selection process and improving the pharmacokinetic properties of phage-based drugs. Nevertheless, phage display represents a promising approach for the development of novel targeted therapies in pancreatic cancer and other tumors.

This study used Silibinin as an additive to conduct fermentation experiments, wherein its effects on rumen gas production, fermentation, metabolites, and microbiome were analyzed in vitro. The silibinin inclusion level were 0 g/L (control group), 0.075 g/L, 0.15 g/L, 0.30 g/L, and 0.60 g/L (experimental group). Fermentation parameters, total gas production, carbon dioxide (CO2), methane (CH4), hydrogen (H2), and their percentages were determined. Further analysis of the rumen microbiome’s relative abundance and α/β diversity was performed on the Illumina NovaSeq sequencing platform. Qualitative and quantitative metabolomics analyses were performed to analyze the differential metabolites and metabolic pathways based on non-targeted metabolomics. The result indicated that with an increasing dose of silibinin, there was a linear reduction in total gas production, CO2, CH4, H2 and their respective percentages, and the acetic acid to propionic acid ratio. Concurrent with a linear increase in pH, when silibinin was added at 0.15 g/L and above, the total volatile fatty acid concentration decreased, the acetic acid molar ratio decreased, the propionic acid molar ratio increased, and dry matter digestibility decreased. At the same time, the relative abundance of Prevotella, Isotricha, Ophryoscolex, unclassified_Rotifera, Methanosphaera, Orpinomyces, and Neocallimastix in the rumen decreased after adding 0.60 g/L of silibinin. Simultaneously, the relative abundance of Succiniclasticum, NK4A214_group, Candidatus_Saccharimonas, and unclassified_Lachnospiraceae increased, altering the rumen species composition, community, and structure. Furthermore, it upregulated the ruminal metabolites, such as 2-Phenylacetamide, Phlorizin, Dalspinin, N6-(1,2-Dicarboxyethyl)-AMP, 5,6,7,8-Tetrahydromethanopterin, Flavin mononucleotide adenine dinucleotide reduced form (FMNH), Pyridoxine 5′-phosphate, Silibinin, and Beta-D-Fructose 6-phosphate, affecting phenylalanine metabolism, flavonoid biosynthesis, and folate biosynthesis pathways. In summary, adding silibinin can alter the rumen fermentation parameters and mitigate enteric methane production by regulating rumen microbiota and metabolites, which is important for developing novel rumen methane inhibitors.

ObjectiveTo use genomic analysis to identify Acinetobacter spp. and to explore the distribution characteristics of ß-lactamase oxallicinases (blaOXA) among Acinetobacter species globally.MethodsGenomes of global Acinetobacter spp. were downloaded from GenBank using Aspera batch. After quality check using CheckM and QUAST software, the genomes were annotated using Prokka software to investigate the distribution of blaOXAs across Acinetobacter spp.; a phylogenetic tree was constructed to explore the evolutionary relationship among the blaOXA genes in Acinetobacter spp. Average-nucleotide identification (ANI) was performed to re-type the Acinetobacter spp. BLASTN comparison analysis was implemented to determine the sequence type (ST) of Acinetobacter baumannii strain.ResultsA total of 7,853 genomes were downloaded, of which only 6,639 were left for further analysis after quality check. Among them, 282 blaOXA variants were identified from the genomes of 5,893 Acinetobacter spp.; blaOXA-23 (n = 3,168, 53.8%) and blaOXA-66 (2,630, 44.6%) were the most frequent blaOXAs, accounting for 52.6% (3,489/6639), and the co-carriage of blaOXA-23 and blaOXA-66 was seen in 2223 (37.7%) strains. The 282 blaOXA variants were divided into 27 clusters according to the phylogenetic tree. The biggest clade was blaOXA-51-family carbapenem-hydrolyzing enzymes composed of 108 blaOXA variants. Overall, 4,923 A. baumannii were identified out of the 6,639 Acinetobacter spp. strains and 291 distinct STs were identified among the 4,904 blaOXA-carrying A. baumannii. The most prevalent ST was ST2 (n = 3,023, 61.6%) followed by ST1 (n = 228, 4.6%).ConclusionOXA-like carbapenemases were the main blaOXA-type β-lactamase spread widely across Acinetobacter spp. Both blaOXA-23 and blaOXA-66 were the predominant blaOXAs, among all A. baumannii strains, with ST2 (belonging to CC2) being the main clone disseminated globally.

IntroductionUlcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent and remitting inflammation of the mucosa of the colon and rectum, the incidence of which is on the rise. Glucagon-like peptide-2 (GLP-2) is a newly discovered neurotrophic factor, but its efficacy and mechanism of action in UC remain unclear. In this study, we investigated the protective effects and potential targets of GLP-2 on dextran sodium sulfate (DSS)-induced UC in mice through integrative analysis.MethodsThe effects of GLP-2 on UC were assessed by calculating the disease activity index, colonic mucosal damage index, and pathological histological scores. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the expression of GLP-2, nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3). The 16SrRNA gene was used to detect changes in gut microbiota in mouse colonic tissues, and oral glucose tolerance test (OGTT) blood glucose levels were used to analyze the differences in flora.ResultsThe results showed that GLP-2 could reduce the inflammation of UC mice, which may be achieved by inhibiting the potential targets of NF-κB, and Janus kinase (JAK)/STAT3 inflammatory pathways, regulating sugar metabolism, increasing dominant species, and improving microbial diversity.DiscussionThis study provides new insight into the potential of GLP-2 for achieving more ideal UC treatment goals in future.

Beneficial microorganisms play a pivotal role in the invasion process of exotic plants, including arbuscular mycorrhizal fungi (AMF) and Bacillus. However, limited research exists on the synergistic influence of AMF and Bacillus on the competition between both invasive and native plants. In this study, pot cultures of Ageratina adenophora monoculture, Rabdosia amethystoides monoculture, and A. adenophora and R. amethystoides mixture were used to investigate the effects of dominant AMF (Septoglomus constrictum, SC) and Bacillus cereus (BC), and the co-inoculation of BC and SC on the competitive growth of A. adenophora. The results showed that inoculation with BC, SC, and BC + SC significantly increased the biomass of A. adenophora by 14.77, 112.07, and 197.74%, respectively, in the competitive growth between A. adenophora and R. amethystoides. Additionally, inoculation with BC increased the biomass of R. amethystoides by 185.07%, while inoculation with SC or BC + SC decreased R. amethystoides biomass by 37.31 and 59.70% compared to the uninoculated treatment. Inoculation with BC significantly increased the nutrient contents in the rhizosphere soil of both plants and promoted their growth. Inoculation with SC or SC + BC notably increased the nitrogen and phosphorus contents of A. adenophora, therefore enhancing its competitiveness. Compared with single inoculation, dual inoculation with SC and BC increased AMF colonization rate and Bacillus density, indicating that SC and BC can form a synergistic effect to further enhance the growth and competitiveness of A. adenophora. This study reveals the distinct role of S. constrictum and B. cereus during the invasion of A. adenophora, and provide new clues to the underlying mechanisms of interaction between invasive plant, AMF and Bacillus.

ObjectiveAs a virulence factor, HupB plays important roles in the survival of MTB after infection and modulates the host immune response. In the current study, we aim to explore a new cellular immunological detection method for tuberculosis infection detection based on HupB protein.MethodsHupB was used to stimulate PBMCs extracted from pulmonary tuberculosis (PTB) patients, and secreted cytokines was examined. Then, we constructed a single center and a multi-center clinical trials to collect PBMCs from PTB patients, nPTB patients, or healthy volunteers to verify our findings.ResultsCytokine’s screening illustrated that IL-6 was the only cytokine released after HupB stimulation. Single-center and multi-center clinical trials showed that HupB stimulation significantly increased the level of IL-6 in the supernatant of PBMCs from PTB patients. Then we compared the specificity and sensitivity of HupB induced IL-6 release assay with ESAT-6 and CFP10 induced interferon γ release assay (IGRA), and found in smear positive PTB patients, the specificity and sensitivity of HupB induced IL-6 release assay was better than IGRA, and in smear negative PTB patients, the sensitivity was better. Combination of both assays provided an improved specificity and sensitivity for tuberculosis diagnosis.ConclusionThis study explored an immunological detection method for tuberculosis infection cells based on HupB protein-induced IL-6 release test, which can be used to enhance the diagnosis diagnostic accuracy of TB.