Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

AIM:To investigate the effects and mechanism of long noncoding RNA PCED1B antisense strand 1(lncRNA PCED1B-AS1)on the proliferation,migration,invasion and apoptosis of papillary thyroid carcinoma(PTC)cells.METHODS:Human PTC cells were cultured in vitro.The expression of PCED1B-AS1 and fused in sarcoma(FUS)was measured by RT-qPCR.The effects of knockdown/overexpression of PCED1B-AS1/FUS on the migration and invasion of PTC cells were detected via Transwell assay.The effects of knockdown/overexpression of PCED1B-AS1/FUS on PTC cell proliferation were analysed via CCK-8 and plate colony assay.The effect of knockdown PCED1B-AS1 on PTC cell apoptosis was determined by flow cytometry.The target binding of PCED1B-AS1 and FUS was determined with bioin-formatics and RNA immunoprecipitation(RIP)experiments.Fluorescence in situ hybridization experiment was performed to verify whether PCED1B-AS1 colocalises with FUS.The mitogen-activated protein kinase(MAPK)signaling pathway-re-lated proteins were detected via Western blot.RESULTS:(1)PCED1B-AS1 expression was significantly higher and FUS expression was significantly lower in PTC cells compared with normal thyroid Nthy-ori3-1 cell(P<0.05).(2)Knockdown of PCED1B-AS1 and overexpression of FUS inhibited PTC cell migration,invasion and proliferation,and promoted apopto-sis(P<0.05).(3)Bioinformatics analysis and RIP assay verified the existence of targeted binding of PCED1B-AS1 to FUS(P<0.05).(4)PCED1B-AS1 and FUS colocalised in the cytoplasm.(5)Inhibition of PCED1B-AS1 decreased the expression of MAPK signaling pathway-related proteins p-ERK 1/2,p-JNK and p-P38(P<0.05).CONCLUSION:ln-cRNA PCED1B-AS1 inhibits the proliferation,migration and invasion,and promotes the apoptosis of PTC cells,and its mechanism may be related to the expression of FUS and the MAPK signaling pathway.

BACKGROUND: With the increase of lung cancer screening, more and more patients have been diagnosed as sub-centimeter (≤1 cm) lung adenocarcinoma. Sub-centimeter lung adenocarcinoma is mostly early stage lung cancer, but the research on sub-centimeter lung adenocarcinoma is still insufficient. This study analyzed the clinical characteristics and prognosis of patients with sub-centimeter lung adenocarcinoma in order to provide the basis for the diagnosis and treatment of such patients. METHODS: A retrospective study was performed to analyze patients with sub-centimeter lung adenocarcinoma who underwent VATS in Peking University People's Hospital from January 2012 to December 2016. Patients were divided into pure ground-glass nodules (pGGN) group, mixed ground-glass nodules (mGGN) group and solid nodules (SN) group according to the features of nodular imaging. The clinical characteristics of the three groups were compared and the subgroup analysis of nodules in different diameter was performed. We also performed multivariate logistic regression analyses to identify the risk factors for sub-centimeter lung invasive adenocarcinoma. RESULTS: The study included 182 patients (57 men and 125 women) with a median age of 54 (27-75) years. Female sub-centimeter lung adenocarcinoma patients had a significantly lower proportion of non-smoking history than males (P<0.001). All patients with 1 mm-10 mm pGGN, 1 mm-5 mm mGGN and 1 mm-5 mm SN had no other pathologically positive findings except for the primary lesion. Of the 46 patients with 6 mm-10 mm mGGN, 3 had pleural invasion and 1 had vascular tumor thrombus. Of the 39 patients with 6 mm-10 mm SN, 5 had pleural invasion, 2 had vascular tumor thrombus and 2 had lymph node metastasis. The pathological type in each patient with pleural invasion, vascular tumor thrombus or lymph node metastasis was invasive adenocarcinoma. Logistic regression analysis indicated that smoking history (OR=4.727, P=0.009), previous tumor history (OR=3.408, P=0.015), mGGN (OR=3.735, P=0.004), SN (OR=8.921, P<0.001) and tumor diameter >5 mm (OR=4.241, P=0.001) were independent risk factors for sub-centimeter lung invasive adenocarcinoma. The median follow-up time was 44 (22-82) months. The 5-year recurrence-free survival rate was 100.0% and the overall survival rate was 98.9%. CONCLUSIONS Patients with sub-centimeter lung adenocarcinoma have a relatively earlier onset age. Sub-centimeter lung invasive adenocarcinoma patients with 6 mm-10 mm mGGN and 6 mm-10 mm SN may be involved in pleural invasion or lymph node metastasis. Smoking history, previous tumor history, mGGN, SN and tumor diameter >5 mm are independent risk factors for sub-centimeter lung invasive adenocarcinoma. For patients with sub-centimeter lung adenocarcinoma, early detection and appropriate surgical intervention can lead to a good prognosis.

Objective To study the correlations between the genetic polymorphism of brain-derived neurotrophic factor (BDNF) and the postpartum depression (PPD) in cesarean section parturient. Methods Three hundred and sixty parturients, who underwent cesarean section under spinal anesthesia from Feb. 2014 to Feb. 2015 in Third Xiangya Hospital of Central South University or Hunan Maternal and Child Health Hospital, were selected as subjects. The general information of parturients was recorded and Edinburgh Postnatal Depression Scale (EPDS) was used to evaluate the depression condition of parturients at the prenatal 1 day and the 42th day postpartum, and with a cut-off point of 12/13 for identifying PPD. The genotypes of BDNF gene locus G712A, rs56164415, rs11030100, rs11030101 and rs6265 were measured by Sequenom? Mass Array SNP. Finally, the correlations of PPD to different genotypes and general information of parturients were statistically analyzed. Results The incidence of PPD among the selected subjects was 7.2%. Pregnancy mental stress, poor pregnancy mood, perinatal elevated monocyte count, prenatal depression mood and BDNF gene locus rs6265 mutation all could affect the incidence of PPD in cesarean section parturients (P<0.05). No statistically significant difference existed between BDNF gene G712A, rs11030101, rs11030100 and rs56164415 locus mutation and PPD (P>0.05), and their haploid forms were not related to PPD also. Conclusion BDNF rs6265CC genotype, pregnancy mental stress, poor pregnancy mood, perinatal elevated monocyte count and prenatal depression mood are the risk factors for postpartum depression.