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.

Humans ; Breast ; Neoplasms, Muscle Tissue/surgery*

Humans ; Ulcer/pathology* ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Skin Diseases

Humans ; Breast/pathology* ; Cystadenocarcinoma/pathology* ; Cystadenocarcinoma, Mucinous/pathology* ; Female

OBJECTIVE: To measure the burden of hepatitis C-associated diseases in China from 1990 to 2019, and to predict its changes from 2020 to 2044, so as to provide insights into formulation of the targeted hepatitis C control strategy. METHODS: The total burden due to hepatitis C-associated diseases in China from 1990 to 2019 were extracted from the Global Burden of Disease 2019 (GBD 2019) data resources, and the trends in age-standardized prevalence, incidence, mortality and disability-adjusted life years (DALYs) rate of hepatitis C-associated acute hepatitis C (AHC), chronic liver diseases (CLD) and liver cancer in China from 1990 to 2019 were evaluated in China from 1990 to 2019 using estimated annual percentage change (EAPC). In addition, the changes in the burden of hepatitis C-associated diseases were predicted in China from 2020 to 2044 using a Bayesian model. RESULTS: The prevalence, incidence, mortality and DALY rate of hepatitis C-associated diseases all appeared an overall tendency towards a decline in China from 1990 to 2019 (EAPC = -2.64%, -2.24%, -3.81% and -3.90%, respectively); however, there was a minor rise in the incidence and prevalence of hepatitis C-associated diseases from 2015 to 2019. The overall prevalence of hepatitis C-associated diseases reduced from 2 152.7/10⁵ in 1990 to 1 254.1/10⁵ in 2019 in China, with a reduction of 41.7%. The overall incidence reduced from 87.9/10⁵ in 1990 to 55.0/10⁵ in 2019 in China, with a reduction of 37.4%, and the highest incidence was seen for AHC, followed by CLD and liver cancer. The overall mortality and DALY rate of hepatitis C-associated diseases was 4.0/10⁵ and 100.8/10⁵ in China from 1990 to 2019, with CLD showing the largest contributions to the gross mortality and DALY. The mortality and DALY rate of hepatitis C-associated diseases were 5.5/10⁵ and 142.4/10⁵ among men in China in 2019, which were both much higher than among women (2.8/10⁵ and 60.3/10⁵, respectively), and the overall prevalence (1 604.9/10⁵), mortality (30.2/10⁵) and DALYs (437.1/10⁵) of hepatitis C-associated diseases were all highest among patients at ages of 70 years and older, and the highest incidence was seen among patients at ages of 0 to 9 years (167.3/10⁵). The incidence of hepatitis C-associated diseases was predicted to rise in China from 2020 to 2044; however, the DALY rate was projected to appear a tendency towards a decline. CONCLUSIONS Although the burden of hepatitis C-associated diseases showed a tendency towards a decline in China from 1990 to 2019, the burden remained high, and was predicted to slightly rise from 2020 to 2044. High attention should be paid to screening of hepatitis C among infants and treatment among adults.
Male ; Adult ; Infant ; Humans ; Female ; Bayes Theorem ; Quality-Adjusted Life Years ; Hepatitis C/epidemiology* ; Liver Neoplasms/epidemiology* ; China/epidemiology* ; Incidence

Faculty ; Female ; Humans ; Kidney ; Lipids ; Male ; Physical Fitness ; Universities

Hearing Loss, High-Frequency ; Hearing Loss, Noise-Induced/epidemiology* ; Humans ; Manufacturing Industry ; Noise, Occupational/adverse effects* ; Occupational Exposure

Hearing ; Hearing Loss, Noise-Induced/etiology* ; Humans ; Male ; Manufacturing Industry ; Noise, Occupational/adverse effects* ; Occupational Exposure/adverse effects* ; Surveys and Questionnaires

Humans ; Interior Design and Furnishings ; Manufacturing Industry ; Noise, Occupational ; Occupational Exposure ; Textile Industry

Objective: To analyze the burden of disease (BOD) on diabetes attributable to high BMI in China from 1990 to 2016. Methods: Data based on population of the 2016 Global Burden of Disease Study for China were used to analyze the attributable fractions (PAF) of BOD for diabetes attributable to high BMI. Measurements for attributable BOD of diabetes included disability adjusted life years (DALY), years of lost life (YLL), years living with disability (YLD), death number and mortality rate. The average world population from 2010 to 2035 was used as a reference. Results: In 2016, death number of diabetes attributable to high BMI was 40 310, which was significantly higher than that in 1990 (15 008). Age-standardized death rate of diabetes attributable to high BMI increased from 2.01/100 000 in 1990 to 2.60/100 000 in 2016, which showed a more significant increasing trend in both males and people aged 15-49 years. DALYs of diabetes attributable to high BMI increased from 1.09 million person years to 3.30 million person years. YLL and YLD also showed increasing trends. The highest increasing rate of YLD was in people aged 15-49 years. High BMI was responsible for 26.01% of the diabetes deaths in 2016 in China, an increase of 39.39% compared with that in 1990 (18.66%). Most provinces in China experienced a sharp increase of DALY of diabetes attributable to high BMI from 1990 to 2016. Inner Mongolia, Xinjiang, Zhejiang, Macao SAR, Sichuan and Qinghai had the most significant increase tendency in terms of DALY rate during this period. Conclusions: There was a rapid increase of the deaths and mortality rate of diabetes attributable to high BMI, causing a heavy disease burden, in China from 1990 to 2016. The BOD varied in both different age and gender groups. More attention should be paid to males and people aged 15-49 years in the prevention and control programs of diabetes.
Adolescent ; Adult ; Body Mass Index ; China/epidemiology* ; Cost of Illness ; Diabetes Mellitus/ethnology* ; Disabled Persons ; Humans ; Macau ; Male ; Middle Aged ; Quality-Adjusted Life Years ; Sickness Impact Profile ; Young Adult