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Recent advancements in sequencing technology have resulted in rapid progress in the study of the major histocompatibility complex (MHC) in non-model avian species. Here, we analyze a global dataset of avian MHC class I and class II sequences (ca. 11,000 sequences from over 250 species) to gain insight into the processes that govern macroevolution of MHC genes in birds. Analysis of substitution rates revealed striking differences in the patterns of diversifying selection between passerine and nonpasserine birds. Non-passerines showed stronger selection at MHC class II, which is primarily involved in recognition of extracellular pathogens, while passerines showed stronger selection at MHC class I, which is involved in recognition of intracellular pathogens. Positions of positively selected amino-acid residues showed marked discrepancies with peptide-binding residues (PBRs) of human MHC molecules, suggesting that using a human classification of PBRs to assess selection patterns at the avian MHC may be unjustified. Finally, our analysis provided evidence that indel mutations can make a substantial contribution to adaptive variation at the avian MHC.

Endothelial cell injury plays a critical part in ischemic acute kidney injury (AKI) and participates in the progression of AKI. Targeting renal endothelial cell therapy may ameliorate vascular injury and further improve the prognosis of ischemic AKI. Here, P‐selectin as a biomarker of ischemic AKI in endothelial cells is identified and P‐selectin binding peptide (PBP)‐engineered extracellular vesicles (PBP‐EVs) with imaging and therapeutic functions are developed. The results show that PBP‐EVs exhibit a selective targeting tendency to injured kidneys, while providing spatiotemporal information for the early diagnosis of AKI by quantifying the expression of P‐selectin in the kidneys by molecular imaging. Meanwhile, PBP‐EVs reveal superior nephroprotective functions in the promotion of renal repair and inhibition of fibrosis by alleviating inflammatory infiltration, improving reparative angiogenesis, and ameliorating maladaptive repair of the renal parenchyma. In conclusion, PBP‐EVs, as an ischemic AKI theranostic system that is designed in this study, provide a spatiotemporal diagnosis in the early stages of AKI to help guide personalized therapy and exhibit superior nephroprotective effects, offering proof‐of‐concept data to design EV‐based theranostic strategies to promote renal recovery and further improve long‐term outcomes following AKI. Endothelial cell (EC) injury is one of the specific features of acute kidney injury (AKI). However, there is no feasible target or effective theranostic strategy for EC‐targeted AKI treatment. In the present study, the authors identify P‐selectin as a biomarker of ischemic AKI and develop P‐selectin binding peptide (PBP)‐engineered extracellular vesicles with imaging and therapeutic functions for the first time.

Background The bovine ephemeral fever virus (BEFV) glycoprotein neutralization site 1 (also referred as G 1 protein), is a critical protein responsible for virus infectivity and eliciting immune-protection, however, binding peptides of BEFV G 1 protein are still unclear. Thus, the aim of the present study was to screen specific polypeptides, which bind BEFV G 1 protein with high-affinity and inhibit BEFV replication. Methods The purified BEFV G 1 was coated and then reacted with the M13-based Ph.D.-7 phage random display library. The peptides for target binding were automated sequenced after four rounds of enrichment biopanning. The amino acid sequences of polypeptide displayed on positive clones were deduced and the affinity of positive polypeptides with BEFV G 1 was assayed by ELISA. Then the roles of specific G 1 -binding peptides in the context of BEFV infection were analyzed. Results The results showed that 27 specific peptide ligands displaying 11 different amino acid sequences were obtained, and the T18 and T25 clone had a higher affinity to G 1 protein than the other clones. Then their antiviral roles of two phage clones (T25 and T18) showed that both phage polypeptide T25 and T18 exerted inhibition on BEFV replication compared to control group. Moreover, synthetic peptide based on T18 (HSIRYDF) and T25 (YSLRSDY) alone or combined use on BEFV replication showed that the synthetic peptides could effectively inhibit the formation of cytopathic plaque and significantly inhibit BEFV RNA replication in a dose-dependent manner. Conclusion Two antiviral peptide ligands binding to bovine ephemeral fever virus G 1 protein from phage display peptide library were identified, which may provide a potential research tool for diagnostic reagents and novel antiviral agents.

The receptor activator of NF-κB ligand (RANKL)-binding peptide, OP3-4, is known to stimulate bone morphogenetic protein (BMP)-2-induced bone formation, but peptides tend to aggregate and lose their bioactivity. Cholesterol-bearing pullulan (CHP) nanogel scaffold has been shown to prevent aggregation of peptides and to allow their sustained release and activity; however, the appropriate design of CHP nanogels to conduct local bone formation needs to be developed. In the present study, we investigated the osteoconductive capacity of a newly synthesized CHP nanogel, CHPA using OP3-4 and BMP-2. We also clarified the difference between perforated and nonperforated CHPA impregnated with the two signaling molecules. Thirty-six, five-week-old male BALB/c mice were used for the calvarial defect model. The mice were euthanized at 6 weeks postoperatively. A higher cortical bone mineral content and bone formation rate were observed in the perforated scaffold in comparison to the nonperforated scaffold, especially in the OP3-4/BMP-2 combination group. The degradation rate of scaffold material in the perforated OP3-4/BMP-2 combination group was lower than that in the nonperforated group. These data suggest that perforated CHPA nanogel could lead to local bone formation induced by OP3-4 and BMP–2 and clarified the appropriate degradation rate for inducing local bone formation when CHPA nanogels are designed to be perforated.

Serum albumin binding moieties (ABMs) such as the Evans blue (EB) dye fragment and the 4-(p-iodophenyl)butyryl (IP) have been used to improve the pharmacokinetic profile of many radiopharmaceuticals. The goal of this work was to directly compare these two ABMs when conjugated to an integrin αvβ6 binding peptide (αvβ6-BP); a peptide that is currently being used for positron emission tomography (PET) imaging in patients with metastatic cancer. The ABM-modified αvβ6-BP peptides were synthesized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA) chelator for radiolabeling with copper-64 to yield [64Cu]Cu DOTA-EB-αvβ6-BP ([64Cu]1) and [64Cu]Cu DOTA-IP-αvβ6-BP ([64Cu]2). Both peptides were evaluated in vitro for serum albumin binding, serum stability, and cell binding and internalization in the paired engineered melanoma cells DX3puroβ6 (αvβ6 +) and DX3puro (αvβ6 −), and pancreatic BxPC-3 (αvβ6 +) cells and in vivo in a BxPC-3 xenograft mouse model. Serum albumin binding for [64Cu]1 and [64Cu]2 was 53–63% and 42–44%, respectively, with good human serum stability (24 h: [64Cu]1 76%, [64Cu]2 90%). Selective αvβ6 cell binding was observed for both [64Cu]1 and [64Cu]2 (αvβ6 (+) cells: 30.3–55.8% and 48.5–60.2%, respectively, vs. αvβ6 (−) cells <3.1% for both). In vivo BxPC-3 tumor uptake for both peptides at 4 h was 5.29 ± 0.59 and 7.60 ± 0.43% ID/g ([64Cu]1 and [64Cu]2, respectively), and remained at 3.32 ± 0.46 and 4.91 ± 1.19% ID/g, respectively, at 72 h, representing a >3-fold improvement over the non-ABM parent peptide and thereby providing improved PET images. Comparing [64Cu]1 and [64Cu]2, the IP-ABM-αvβ6-BP [64Cu]2 displayed higher serum stability, higher tumor accumulation, and lower kidney and liver accumulation, resulting in better tumor-to-organ ratios for high contrast visualization of the αvβ6 (+) tumor by PET imaging.

Gold nanoparticles have numerous applications, many of which are notable in industries. The biosynthesis of gold nanoparticles offers an easy, effective, green, and eco-friendly approach. In organisms capable of synthesizing nanoparticles, enzymes and proteins are responsible for the structural and functional modifications that lead to their formation. These include ABC transporter, peptide-binding proteins, which are dependent on abiotic parameters. This study uses the purified ABC transporter, peptide-binding protein transformed from Thermus scotoductus SA-01 and expressed in mesophilic Escherichia coli BL21 and thermophilic Thermus thermophilus HB27 hosts for the biosynthesis of gold nanoparticles at different concentrations, temperatures, and pH values. Gold nanoparticle formation was evaluated with a range of gold (III) concentrations (0–10 mM), incubated at temperatures ranging from 30–85 ºC and pH levels from 3.6–9.0. Transmission electron microscopy (TEM), energy dispersive X-ray spectrometry (EDX), and UV–Vis absorption spectroscopy were used to characterise the formation of nanoparticles. In all of the protein reactions, UV–Vis absorbance peaks at approximately 520–560 nm confirmed the formation of gold nanoparticles. Optimum nanoparticle synthesis was observed at pH values ranging from 5.5 to 9.0, gold (III) solution (HAuCl 4 ) concentrations from 0.5–2.0 mM, and a maximum temperature of 65ºC in the mesophilic host and 85ºC in the thermophilic host, indicating the significance of temperature in both hosts for the expression and bioactivity of the purified ABC transporter protein. However, the biogenic formation of gold nanoparticles using E. coli and T. thermophilus hosts was not monodispersed, suggesting a necessity for further development of the procedure.

Summary Conversion of nongrain biomass into liquid fuel is a sustainable approach to energy demands as global population increases. Previously, we showed that iron can act as a catalyst to enhance the degradation of lignocellulosic biomass for biofuel production. However, direct addition of iron catalysts to biomass pretreatment is diffusion‐limited, would increase the cost and complexity of biorefinery unit operations and may have deleterious environmental impacts. Here, we show a new strategy for in planta accumulation of iron throughout the volume of the cell wall where iron acts as a catalyst in the deconstruction of lignocellulosic biomass. We engineered CBM‐IBP fusion polypeptides composed of a carbohydrate‐binding module family 11 (CBM11) and an iron‐binding peptide (IBP) for secretion into Arabidopsis and rice cell walls. CBM‐IBP transformed Arabidopsis and rice plants show significant increases in iron accumulation and biomass conversion compared to respective controls. Further, CBM‐IBP rice shows a 35% increase in seed iron concentration and a 40% increase in seed yield in greenhouse experiments. CBM‐IBP rice potentially could be used to address iron deficiency, the most common and widespread nutritional disorder according to the World Health Organization.

Dual Opdivo plus Yervoy immunotherapy, targeting the immune checkpoints PD1 and CTLA‐4, is successful in clinical use. However, it is associated with a high incidence of adverse events, and its therapeutic efficacy needs improving. In this study, polymeric multivalent Fc‐binding peptides (PLG‐Fc‐III‐4C) are employed to fabricate a bispecific antibody (PD1/CTLA‐4 BsAb) to potentiate dual immunotherapy targeting PD1 and CTLA‐4. The PD1/CTLA‐4 BsAb is prepared by mixing PLG‐Fc‐III‐4C with aPD1 and aCTLA‐4 in an aqueous solution for 3 h using the clinically optimal 3:1 proportion of aPD1 to aCTLA‐4. PD1/CTLA‐4 BsAb significantly inhibits tumors in MC38 colon cancer‐bearing mice more effectively than the combination of aPD1 and aCTLA‐4, with tumor suppression rates of 96.8% and 77.3%, respectively. It also induces a higher percentage of CD8+ T cells and increases the secretion of effector cytokines while reducing Treg levels in tumors compared to phosphate‐buffered saline, indicating significant tumor immunity regulation. Mechanistically, a 6.3‐fold increase in PD1/CTLA‐4 BsAb accumulation in tumors due to the tumor targeting ability of aPD1, and the PD1/CTLA‐4 BsAb significantly reduces the adverse colitis event in healthy mice, compared to aPD1 and aCTLA‐4. Thus, these findings provide a novel approach to enhance antitumor therapy using aPD1 and aCTLA‐4. This study investigates an approach to enhance dual immunotherapy targeting PD1 and CTLA‐4 by utilizing a clinically formulated bispecific antibody (PD1/CTLA‐4 BsAb) constructed with polymeric multivalent Fc‐binding peptides. The PD1/CTLA‐4 BsAb significantly improves tumor suppression, boosts CD8+ T cell immune responses, and reduces adverse events, offering a promising strategy for more effective cancer treatment.

Protective cell‐surface coatings with complement‐regulatory activity emerge as promising therapeutic strategies, particularly for preventing thromboinflammatory complications during transplantation. However, their development and in vitro evaluation require specialized assay systems. This study establishes an efficient platform to coat endothelial cells with peptides that recruit the physiological complement regulator factor H (FH) and test their activity. Azide‐groups are introduced into cell‐surface glycans of human and porcine endothelial cells via metabolic glycoengineering to enable covalent attachment of alkyne‐labeled FH‐binding peptides via click chemistry. By optimizing the type and concentration of azido‐sugars, effective incorporation of accessible click handles can be achieved with minimal impact on cell viability. This approach results in uniform, controllable peptide coatings that efficiently recruit FH from purified sources and human serum to endothelial cell surfaces and enhance their resistance to complement‐mediated opsonization. This model not only served as validation for the efficacy of FH‐recruiting peptides but also provides a versatile platform to evaluate and optimize various parameters that define coating efficacy and gain insight into mechanisms of complement activation. As such, it may facilitate the screening of modulators and the development of protective coatings for future applications in biomedical or preclinical research. Metabolic glycoengineering combined with click chemistry efficiently immobilizes clickable factor H (FH)‐binding peptides onto endothelial cell surfaces, creating stable, uniform coatings that recruit FH and enhance resistance to complement‐mediated inflammation. Optimized azido‐sugar incorporation provides precise control over peptide coating and preserves cell viability, offering a versatile platform for evaluating protective coatings and mechanistic studies relevant to (xeno‐)transplantation.

Bio/chemical sensors require high selectivity for specific targets. Carbon nanomaterials, especially graphene-based materials, are preferred in sensors due to their high surface area, superior electrical conductivity, mechanical strength, and flexibility. In this study, DNT-bp (Dinitrotoluene binding peptide) and TNT-bp (Trinitrotoluene binding peptide) were immobilized on LIG (Laser-induced graphene) films through covalent and non-covalent interactions. EDC (1-ethyl-3-3-dimethylaminopropyl carbodiimide hydrochloride) is used to activate carboxylic acid groups, which then react with NHS (N-hydroxysuccinimide) to form NHS esters, facilitating the binding of amine-containing peptides to the LIG surface. XPS analysis of LIG films functionalized with EDC+NHS shows a decrease in COOH (carboxyl) and an increase in C–N/C=N/C–O groups. N1s peak at high-resolution XPS spectrum indicates that DNT-bp immobilization leads to higher elimination of NHS-esters, resulting in fewer N-C=O (amide) functional groups and more protonated nitrogen, which suggests that DNT-bp immobilization is more effective than TNT-bp immobilization. The findings suggest that LIG-based sensors provide a cost-effective platform for the detection of DNT (2,4-dinitrotoluene) and 2,4,6-trinitrotoluene (TNT). Further advancements in LIG-based biosensors may enable their broader application in security, environmental monitoring, and health diagnostics.