Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Objective:To study disease spectrum and genetic profiles of inborn errors of metabolism (IEM) among newborns in selected areas of Nanning city.Methods:From July 2019 to December 2021, neonates born and received IEM screening in our hospital were prospectively enrolled. Heel blood samples were tested using tandem mass spectrometry as IEM screening. Neonates with positive results were called back for recheck. Whole exome sequencing was used to detect possible pathogenic genes in suspected cases and IEM was diagnosed combining clinical manifestations. Sanger sequencing method was used for the diagnosed neonates and their parents to confirm the diagnoses.Results:A total of 16 207 live-birth neonates were enrolled. For initial IEM screening, 1 423 neonates were positive (8.8%) and 1 311 were called back (92.1%). 15 cases were suspected with IEM and 8 were diagnosed. The overall detection rate was 1∶2 026. Among 8 confirmed cases, 4 cases had amino acid metabolism disorders (2 cases of phenylketonuria, 1 case of Citrin deficiency and 1 case of tyrosinemia), 2 cases had organic acid metabolism disorders (1 case of methylmalonic acidemia and 1 case of glutaric acidemia) and 2 cases had fatty acid oxidation disorders (1 case of carnitine palmitotransferaseⅡdeficiency and 1 case of primary carnitine deficiency). 5 cases had homozygous genetic variants (2 in PAH, and 1 in SLC25A13, SLC22A5 and FAH, respectively) and 3 had heterozygous genetic variants (1 in CPT2, MUT, and GCDH, respectively). During follow-up, all 8 cases had normal growth and developmental outcomes after standardized treatment.Conclusions:The overall detection rate of IEM is high, with varied genetic profiles in selected areas of Nanning. Timely genetic testing may lead to early diagnosis and treatment and improve the quality of life of neonates.

Objective:To investigate the effect of Budesonide (BUD) on pulmonary vascular development and the expression of vascular endothelial growth factor (VEGF) and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) in newborn rats with bronchopulmonary dysplasia (BPD) caused by intrauterine infection.Methods:The 15-day-pregnant SD rats were divided into control group and infection group [intraperitoneal injection of 0.35 mg/(kg·d) lipopolysaccharide], and the newborn rats born by the above groups were divided into 3 groups: BUD group (0.5 mg of BUD suspension), normal control group (NC group, equal amount of 9 g/L saline), BPD group (equal amount of 9 g/L saline), with 40 rats in each group, all of them were inhaled twice a day for 14 days.Ten newborn rats were selected at birth, on the 3 rd, 7 th and 14 th day after administration.Pulmonary histopathological changes and radial alveolar counts (RAC) were observed after HE staining, and the thickness of alveolar respiratory membrane was measured; the platelet-endothelial cell adhesion molecule (PECAM-1/CD 31) in lung tissue was detected by immunohistochemistry, and the density of pulmonary microvessels was calculated; the expressions of VEGF, NLRP3 and Caspase-1 were detected by Western blot; and the levels of serum interleukin( IL)-1β and IL-18 were measured by enzyme-linked immunosorbent assay. Results:With the increase of day-old, the lung tissue of newborn rats in NC group was gradually developed and matured, the structure of alveoli was clear, the size was uniform, the count was significantly increased, and no obvious pathological changes were observed.In BPD group, the lung tissue structure was disordered, the alveoli were different in size and few in count, and inflammatory cells were exuded from the alveoli or the alveoli space.Compared with BPD group, the pathological changes of lung tissue in BUD group were significantly reduced.On the 3 rd, 7 th and 14 th day after administration, compared with NC group, the RAC, average integral optical density of CD 31 positive cells, density of pulmonary microvessel and level of VEGF protein in lung tissue of BPD group and BUD group were lower, and the differences were statistically significant (all P<0.05); while the thickness of respiratory membrane, level of NLRP3, Caspase-1 proteins in lung tissue and serum levels of IL-1β, IL-18 were significantly higher, and the differences were statistically significant(all P<0.05). Compared with BPD group, the RAC, average integral optical density of CD 31 positive cells, density of pulmonary microvessel and level of VEGF protein in lung tissue of BPD group and BUD group were significantly higher, and the differences were statistically significant (all P<0.05); while the thickness of respiratory membrane, level of NLRP3, Caspase-1 proteins in lung tissue and serum levels of IL-1β, IL-18 were significantly lower, and the differences were statistically significant (all P<0.05). Conclusions:The occurrence and development of pathological changes of BPD newborn rats caused by intrauterine infection can affect the development of pulmonary vessels through the inflammatory response of lung tissue.BUD can alleviate pathological changes in lung tissues of BPD newborn rats by reducing inflammatory reaction and up-regulating VEGF expression, promoting pulmonary vascular remodeling, and increasing pulmonary microvascular density.