MicroPET Imaging of Riboflavin Transporter 3 Expression in Myocardial Infarction/Reperfusion Rat Models with Radiofluorinated Riboflavin.

Riboflavin transporter 3 (RFVT3) represents a potential cardioprotective biotarget in energetic metabolism reprogramming after myocardial infarction/reperfusion (MI/R). This study investigated the feasibility of noninvasive real-time quantification of RFVT3 expression after MI/R with an radiolabeled probe 18F-RFTA in a preclinical rat model of MI/R. The tracer 18F-RFTA was radio-synthesized manually and characterized on the subjects of radiolabeling yield, radiochemical purity, and stability in vivo. MI/R and sham-operated rat models were confirmed by cardiac magnetic resonance imaging (cMRI) and single-photon-emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium-99m sestamibi (99mTc-MIBI). Positron emission tomography (PET) imaging of MI/R and sham-operated rat models were conducted with 18F-RFTA. Ex vivo autoradiography and RFVT3 immunohistochemical (IHC) staining were conducted to verify the RFVT3 expression in infarcted and normal myocardium. 18F-RFTA injection was prepared with high radiochemical purity (>95%) and kept stable in vitro and in vivo. 18F-RFTA PET revealed significant uptake in the infarcted myocardium at 8 h after reperfusion, as confirmed by lower 99mTc-MIBI perfusion and decreased intensity of cMRI. Conversely, there were only the tiniest uptakes in the normal myocardium and blocked infarcted myocardium, which was further corroborated by ex vivo autoradiography. The RFVT3 expression was further confirmed by IHC staining in the infarcted and normal myocardium. We first demonstrate the feasibility of imaging RFVT3 in infarcted myocardium. 18F-RFTA is an encouraging PET probe for imaging cardioprotective biotarget RFVT3 in mitochondrial energetic metabolism reprogramming after myocardial infarction. Noninvasive imaging of cardioprotective biotarget RFVT3 has potential value in the diagnosis and therapy of patients with MI.

Development and Evaluation of DOTA-FAPI-Maleimide as a Novel Radiotracer for Tumor Theranostic with Extended Circulation.

This study aimed to evaluate a novel albumin-binding strategy for addressing the challenge of insufficient tumor retention of fibroblast activation protein inhibitors (FAPIs). Maleimide, a molecule capable of covalent binding to free thiol groups, was modified to conjugate with FAPI-04 in order to enhance its binding to endogenous albumin, resulting in an extended blood circulation half-life and increased tumor uptake. DOTA-FAPI-maleimide was prepared and radiolabeled with Ga-68 and Lu-177, followed by cellular assays, pharmacokinetic analysis, PET/CT, and SPECT/CT imaging to assess the probe distribution in various tumor-bearing models. Radiolabeling of the modified probe was successfully achieved with a radiochemical yield of over 99% and remained stable for 144 h. Cellular assays showed that the ligand concentration required for 50% inhibition of the probe was 1.20 ± 0.31 nM, and the Kd was 0.70 ± 0.07 nM with a Bmax of 7.94 ± 0.16 fmol/cell, indicative of higher specificity and affinity of DOTA-FAPI-maleimide compared to other FAPI-04 variants. In addition, DOTA-FAPI-maleimide exhibited a persistent blood clearance half-life of 7.11 ± 0.34 h. PET/CT images showed a tumor uptake of 2.20 ± 0.44%ID/g at 0.5 h p.i., with a tumor/muscle ratio of 5.64 in HT-1080-FAP tumor-bearing models. SPECT/CT images demonstrated long-lasting tumor retention. At 24 h p.i., the tumor uptake of [177Lu]Lu-DOTA-FAPI-maleimide reached 5.04 ± 1.67%ID/g, with stable tumor retention of 3.40 ± 1.95%ID/g after 4 days p.i. In conclusion, we developed and evaluated the thiol group-attaching strategy, which significantly extended the circulation and tumor retention of the adapted FAPI tracer. We envision its potential application for clinical cancer theranostics.

Alcohol Advertising Exposure and Drinking Habits Among Chinese Adolescents in 2021: A National Survey.

Objectives. To assess the exposure of Chinese adolescents to proalcohol advertising and explore its association with alcohol consumption. Methods. A nationally and regionally representative school-based survey was conducted in mainland China in 2021 among students in grades 7 through 12, aged 13 to 18 years. We assessed adolescent exposure to proalcohol advertising and its association with alcohol consumption. Results. A total of 57 336 students participated in the survey, and the exposure percentage of proalcohol advertising was 66.8%, with no difference between boys and girls or between urban and rural areas. The top 3 exposure channels were television (51.8%), the Internet (43.6%), and outdoor billboards (42.0%). The exposure was higher among students who had consumed alcohol in the past 30 days (80.1% vs 65.1%; adjusted odds ratio [AOR] = 1.29) and in the past 12 months (77.3% vs 61.7%; AOR = 1.30). However, no significant correlation was observed between advertising exposure and drunkenness. Conclusions. Approximately two thirds of Chinese adolescents have been exposed to proalcohol advertising in the past 30 days, with television, the Internet, and outdoor billboards being the most prevalent channels. Exposure to proalcohol advertising exhibits a positive correlation with drinking. (Am J Public Health. 2024;114(8):814-823. https://doi.org/10.2105/AJPH.2024.307680).

The Trend of Smoking-Related Cognition and Its Association with Smoking Behaviors Among Junior High School Students - China, 2013-2021.

What is already known about this topic?: In 2013, 31.61% of students perceived quitting smoking as difficult, 61.73% considered smoking less attractive, and 73.89% believed that secondhand smoke is definitely harmful to health. What is added by this report?: The percentage of students who perceived quitting smoking as difficult increased from 31.61% in 2013 to 38.83% in 2021, while the percentage of students who found smoking less attractive rose from 61.73% to 69.40%. Conversely, there was a decrease in the percentage of students who perceived secondhand smoke as harmful, from 73.89% to 68.46%. An increased awareness of the hazards of secondhand smoke was associated with a reduction in smoking behaviors. What are the implications for public health practice?: It is imperative to enhance health education efforts that aim to raise awareness of the hazards of secondhand smoke.

Cigarette Use and Secondhand Smoke Exposure Among Secondary School Students - China, 2023.

What is already known about this topic?: In 2021, the prevalence of experimental and current cigarette use among secondary school students in China stood at 16.7% and 4.7%, respectively. Additionally, 39.9% of these students were exposed to secondhand smoke at school. What is added by this report?: In comparison to 2021, the prevalence of current cigarette use remained unchanged at 4.2% in 2023, whereas experimental use declined to 13.7%. Notably, rates were significantly higher among vocational senior high school (VSHS) students relative to their peers in senior high school (SHS) and junior high school (JHS). Furthermore, exposure to secondhand smoke in schools decreased to 35.4% in 2023 from previously recorded levels, with more pronounced reductions observed in JHS and SHS populations and no notable change among VSHS students. What are the implications for public health practice?: Targeted tobacco control policies are imperative for secondary school students, including the establishment of smoke-free school environments. Additionally, it is crucial to pay close attention to the needs of VSHS students.

Progressive Optimization of Lanthanide Nanoparticle Scintillators for Enhanced Triple-Activated Radioluminescence Imaging.

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency. Benefiting from the favorable host matrix and the luminescence-protective effect of core-shell engineering, NaGdF4 : 15 %Eu@NaLuF4 nanoparticle scintillators with tailored structures emerged as the top candidates. Living imaging experiments based on optimal LnNP scintillators validated the feasibility of laser-free continuous RL activated by clinical radiopharmaceuticals for tumor multiplex visualization. This research provides unprecedented insights into the rational design of LnNP scintillators, which would enable efficient energy conversion from Cerenkov luminescence, γ-radiation, and ß-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics.

A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy.

BACKGROUND: Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics. RESULTS: To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68Ga or 177Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [68Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [177Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [68Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [68Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [177Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [177Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [177Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection. CONCLUSION: In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics.

Synthesis, preclinical, and initial clinical evaluation of integrin αVß3 and gastrin-releasing peptide receptor (GRPR) dual-targeting radiotracer [68Ga]Ga-RGD-RM26-03.

Integrin receptor αvß3 and gastrin-releasing peptide receptor (GRPR) expression of tumors could be detected using PET imaging with radiolabeled Arg-Gly-Asp (RGD) and the antagonistic bombesin analog RM26, respectively. The purpose of this study was to investigate the dual receptor-targeting property of the heterodimer RGD-RM26-03 (denoted as LNC1015), demonstrate the tumor diagnostic value of [68Ga]Ga-LNC1015 in preclinical experiments, and evaluate its preliminary clinical feasibility. METHODS: LNC1015 was designed and synthesized by linking cyclic RGD and the RM26 peptide. Preclinical pharmacokinetics were detected in a PC3 xenograft model using microPET and biodistribution studies. The clinical feasibility of [68Ga]Ga-LNC1015 PET/CT was performed in patients with breast cancer, and the results were compared with those of 18F-fluorodeoxyglucose (FDG). RESULTS: [68Ga]Ga-LNC1015 had good stability in saline for at least 2 h, and favorable binding affinity and specificity were demonstrated in vitro and in vivo. The tumor uptake and retention of [68Ga]Ga-LNC1015 during PET imaging were improved compared with its monomeric counterparts [68Ga]Ga-RGD and [68Ga]Ga-RM26 at all the time points examined. In our initial clinical studies, the tumor uptake and tumor-to-background ratio (TBR) of primary and metastatic lesions in [68Ga]Ga-LNC1015 PET/CT were significantly higher than those in [18F]FDG PET/CT, resulting in high lesion detection rate and tumor delineation. CONCLUSION: The dual targeting radiotracer [68Ga]Ga-LNC1015 showed significantly improved tumor uptake and retention, as well as lower liver uptake than [68Ga]Ga-RGD and [68Ga]Ga-RM26 monomer. The first-in-human study showed high TBRs in patients, suggesting favorable pharmacokinetics and high clinical feasibility for PET/CT imaging of cancer.

Development of small-molecular-based radiotracers for PET imaging of PD-L1 expression and guiding the PD-L1 therapeutics.

PURPOSE: Programmed cell death protein ligand 1 (PD-L1) is a crucial biomarker for immunotherapy. However, nearly 70% of patients do not respond to PD-L1 immune checkpoint therapy. Accurate monitoring of PD-L1 expression and quantification of target binding during treatment are essential. In this study, a series of small-molecule radiotracers were developed to assess PD-L1 expression and direct immunotherapy. METHODS: Radiotracers of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were designed based on a 2-methyl-3-biphenyl methanol scaffold and successfully synthesized. Cellular experiments and molecular docking assays were performed to determine their specificity for PD-L1. PD-L1 status was investigated via positron emission tomography (PET) imaging in MC38 tumor models. PET imaging of [68Ga]Ga-D-pep-PMED was performed to noninvasively quantify PD-L1 blocking using an anti-mouse PD-L1 antibody (PD-L1 mAb). RESULTS: The radiosyntheses of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were achieved with radiochemical yields of 87 ± 6%, 82 ± 4%, and 79 ± 9%, respectively. In vitro competition assays demonstrated their high affinities (the IC50 values of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were 90.66 ± 1.24, 160.8 ± 1.35, and 51.6 ± 1.32 nM, respectively). At 120 min postinjection (p.i.) of the radiotracers, MC38 tumors displayed optimized tumor-to-muscle ratios for all radioligands. Owing to its hydrophilic modification, [68Ga]Ga-D-pep-PMED had the highest target-to-nontarget (T/NT) ratio of approximately 6.2 ± 1.2. Interestingly, the tumor/liver ratio was hardly affected by different concentrations of the inhibitor BMS202. We then evaluated the impacts of dose and time on accessible PD-L1 levels in the tumor during anti-mouse PD-L1 antibody treatment. The tumor uptake of [68Ga]Ga-D-pep-PMED significantly decreased with increasing PD-L1 mAb dose. Moreover, after 8 days of treatment with a single antibody, the uptake of [68Ga]Ga-D-pep-PMED in the tumor significantly increased but remained lower than that in the saline group. CONCLUSION: PET imaging with [68Ga]Ga-D-pep-PMED, a small-molecule radiotracer, is a promising tool for evaluating PD-L1 expression and quantifying the target blockade of PD-L1 to assist in the development of effective therapeutic regimens.

In Vivo Comparative Study of Radioiodinated Folate Receptor Targeting Albumin Probes for Atherosclerosis Plaque Imaging.

The objective of this study is to compare a series of albumin-based folate radiotracers for the potential imaging of folate receptor (FR) positive macrophages in advanced atherosclerotic plaques. Diversified radioiodinated FR-targeting albumin-binding probes ([131I]IBAbHF, [131I]IBNHF, and [131I]HF) were developed through various strategies. Among the three radiotracers, [131I]IBAbHF and [131I]IBNHF showed excellent in vitro stability (>98%) in saline and PBS 7.4 for 24 h. Also, good stability of [131I]IBNHF in mouse serum albumin was monitored using an HSA ELISA kit. The experiments in Raw264.7 macrophages activated by ox-LDL confirmed the specificity of tracers for FR-ß. Biodistribution studies of radiotracers were performed to verify the prolonged blood half-life. Prolonged blood half-lives of [131I]IBAbHF, [131I]HF, and [131I]IBNHF were 17.26 ± 4.29, 6.33 ± 2.64, and 5.50 ± 1.26 h, respectively. SPECT-CT imaging of ApoE-/- mice at different stages was performed to evaluate the progression and monitor the prognosis of AS. Evident [131I]IBNHF uptake in atherosclerotic lesions could be observed along with a low background signal. In summary, we demonstrated a proof-of-concept of albumin-based radioligands for FR-targeting atherosclerosis imaging and found that different incorporation of radioiodinated groups resulted in different pharmacokinetic properties. Among these candidate compounds, [131I]IBNHF would be a satisfactory radiotracer for SPECT imaging of atherosclerosis.

Utilization of Smoking Cessation Support Among Adults - 18 PLADs, China, 2020.

What is already known about this topic?: In 2018, unassisted smoking cessation (USC) was the predominant method for quitting smoking among Chinese adult smokers, accounting for 90.1% of cases. The utilization of professional smoking cessation support was comparatively low in this population. What is added by this report?: In 2020, the prevalence of USC methods increased to 93.1%. Concurrently, there was a slight increase in the utilization of pharmaceuticals (from 4.6% in 2018 to 5.5% in 2020) and counseling and quit line services (from 3.2% in 2018 to 7.5% in 2020). On the other hand, the use of e-cigarettes as a cessation aid decreased from 14.9% in 2018 to 9.8% in 2020. Smokers aged 15-24 years old were more likely to rely on pharmaceutical interventions (7.9%), and less likely to choose USC methods (79.0%). What are the implications for public health practice?: The promotion of professional cessation support is essential for enhancing smoking cessation rates.

Development of [177Lu]Lu-LNC1003 for radioligand therapy of prostate cancer with a moderate level of PSMA expression.

PURPOSE: Evans blue as an albumin binder has been widely used to improve pharmacokinetics and enhance tumor uptake of radioligands, including prostate-specific membrane antigen (PSMA) targeting agents. The goal of this study is to develop an optimal Evans blue-modified radiotherapeutic agent that could maximize the absolute tumor uptake and tumor absorbed dose thus the therapeutic efficacy to allow treatment of tumors even with moderate level of PSMA expression. METHODS: [177Lu]Lu-LNC1003 was synthesized based on PSMA-targeting agent and Evans blue. Binding affinity and PSMA targeting specificity were verified through cell uptake and competition binding assay in 22Rv1 tumor model that has moderate level of PSMA expression. SPECT/CT imaging and biodistribution studies in 22Rv1 tumor-bearing mice were performed to evaluate the preclinical pharmacokinetics. Radioligand therapy studies were conducted to systematically assess the therapeutic effect of [177Lu]Lu-LNC1003. RESULTS: LNC1003 showed high binding affinity (IC50 = 10.77 nM) to PSMA in vitro, which was comparable with that of PSMA-617 (IC50 = 27.49 nM) and EB-PSMA-617 (IC50 = 7.91 nM). SPECT imaging of [177Lu]Lu-LNC1003 demonstrated significantly improved tumor uptake and retention as compared with [177Lu]Lu-EB-PSMA and [177Lu]Lu-PSMA-617, making it suitable for prostate cancer therapy. Biodistribution studies further confirmed the remarkably higher tumor uptake of [177Lu]Lu-LNC1003 (138.87 ± 26.53%ID/g) over [177Lu]Lu-EB-PSMA-617 (29.89 ± 8.86%ID/g) and [177Lu]Lu-PSMA-617 (4.28 ± 0.25%ID/g) at 24 h post-injection. Targeted radioligand therapy results showed noteworthy inhibition of 22Rv1 tumor growth after administration of a single dose of 18.5 MBq [177Lu]Lu-LNC1003. There was no obvious antitumor effect after [177Lu]Lu-PSMA-617 treatment under the same condition. CONCLUSION: In this study, [177Lu]Lu-LNC1003 was successfully synthesized with high radiochemical purity and stability. High binding affinity and PSMA targeting specificity were identified in vitro and in vivo. With greatly enhanced tumor uptake and retention, [177Lu]Lu-LNC1003 has the potential to improve therapeutic efficacy using significantly lower dosages and less cycles of 177Lu that promises clinical translation to treat prostate cancer with various levels of PSMA expression.

Trends in Exposure to Secondhand Smoke Among Adolescents in China From 2013-2014 to 2019: Two Repeated National Cross-sectional Surveys.

BACKGROUND: It is well-known that secondhand smoke exposure in childhood or adolescence is positively associated with morbidity and mortality. However, less is known about the current status of and most recent trends in secondhand smoke exposure among adolescents in China. OBJECTIVE: We aimed to assess recent changes in the prevalence of secondhand smoke exposure among adolescents in China using nationally representative data. METHODS: We used data from 2 repeated national cross-sectional surveys conducted in 2013-2014 and 2019. A total of 155,117 students (median age 13.5 years) in 2013-2014 and 147,270 students (median age 13.1 years) in 2019 were included in this study. Sociodemographic factors and secondhand smoke exposure information were collected via a standardized questionnaire. Exposure was defined as secondhand smoke exposure ≥1 day during the past 7 days at home or in public places. Other frequencies of secondhand smoke exposure (ie, ≥3 days, ≥5 days, and every day) during the past 7 days were also assessed. The weighted prevalence of secondhand smoke exposure was calculated according to the complex sample design for surveys. RESULTS: The prevalence of secondhand smoke exposure in any place (home or public places ≥1 day during the past 7 days) decreased from 2013-2014 (72.9%, 95% CI 71.5%-74.3%) to 2019 (63.2%, 95% CI 62%-64.5%), as did exposure at home (2013-2014: 44.4%, 95% CI 43.1%-45.7%; 2019: 34.1%, 95% CI 33.1%-35.2%) and in public places (2013-2014: 68.3%, 95% CI 66.9%-69.6%; 2019: 57.3%, 95% CI 56%-58.6%). The prevalence of secondhand smoke exposure decreased with increased gross domestic product per capita in each of the 2 survey years irrespective of exposure frequency or location. The prevalence of exposure at other frequencies (ie, ≥3 days, ≥5 days, or every day during the past 7 days) also decreased in any place, at home, and in public places. Secondhand smoke exposure was associated with higher school grade level (ninth vs seventh grade: odds ratio [OR] 1.76, 95% CI 1.68-1.84), gender (boys vs girls: OR 1.18, 95% CI 1.15-1.22), urban status (urban vs rural: OR 1.10, 95% CI 1.01-1.19), and cigarette smoking (yes vs no: OR 6.67, 95% CI 5.83-7.62). CONCLUSIONS: Although the prevalence of secondhand smoke exposure among Chinese adolescents declined from 2013-2014 to 2019, it remains unacceptably high. More effective strategies and stronger action are needed in China to further, and dramatically, curb secondhand smoke exposure among adolescents.

Synthesis and Preclinical Evaluation of a 68Ga-Labeled Pyridine-Based Benzamide Dimer for Malignant Melanoma Imaging.

Benzamide (BZA), a small molecule that can freely cross cell membranes and bind to melanin, has served as an effective targeting group for melanoma theranostics. In this study, a novel pyridine-based BZA dimer (denoted as H-2) was labeled with 68Ga ([68Ga]Ga-H-2) for positron emission tomography (PET) imaging of malignant melanomas. [68Ga]Ga-H-2 was obtained with high radiochemical yield (98.0 ± 2.0%) and satisfactory radiochemical purity (>95.0%). The specificity and affinity of [68Ga]Ga-H-2 were confirmed in melanoma B16F10 cells and in vivo PET imaging of multiple tumor models (B16F10 tumors, A375 melanoma, and lung metastases). Monomeric [68Ga]Ga-H-1 was prepared as a control radiotracer to verify the effects of the molecular structure on pharmacokinetics. The values of the lipid-water partition coefficient of [68Ga]Ga-H-2 and [68Ga]Ga-H-1 demonstrated hydrophilicity with log P = -2.37 ± 0.07 and -2.02 ± 0.09, respectively. PET imaging and biodistribution showed a higher uptake of [68Ga]Ga-H-2 in B16F10 primary and metastatic melanomas than that in A375 melanomas. However, the relatively low uptake of monomeric [68Ga]Ga-H-1 in B16F10 tumors and high accumulation in nontarget organs resulted in poor PET imaging quality. This study demonstrates the synthesis and preclinical evaluation of the novel pyridine-based BZA dimer [68Ga]Ga-H-2 and indicates that the dimer tracer has promising applications in malignant melanoma-specific PET imaging because of its high uptake and long-time retention in malignant melanoma.

Alternative splicing of a carboxyl/choline esterase gene enhances the fenpropathrin tolerance of Tetranychus cinnabarinus.

Detoxification plays a crucial role in agricultural pests to withstand pesticides, and cytochrome P450s, carboxyl/choline esterases (CCEs), and glutathione-S-transferases are the main proteins responsible for their detoxification ability. The activity of CCEs can be upregulated, downregulated, or modified by mutation. However, few studies have examined the role of alternative splicing in altering the properties of CCEs. We identified 2 variants of TcCCE23 in Tetranychus cinnabarinus: a long version (CCE23-V1) and a short version that is 18 nucleotides shorter than CCE23-V1 (CCE23-V2). Whether splicing affects the activity of TcCCE23 remains unclear. Overexpression of CCE23-V2 in fenpropathrin-resistant T. cinnabarinus revealed that splicing affected the detoxification of fenpropathrin by CCE23-V2. The mortality of mites was significantly higher when the expression of CCE23-V2 was knocked down (43.2% ± 3.3%) via injection of CCE23-dsRNA (double-stranded RNA) compared with the control group injected with green fluorescent protein-dsRNA under fenpropathrin exposure; however, the downregulation of CCE23-V1 (61.3% ± 6.3%) by CCE23-small interfering RNA had no such effect, indicating CCE23-V2 plays a greater role in xenobiotic metabolism than CCE23-V1. The tolerance of flies overexpressing CCE23-V2 to fenpropathrin (50% lethal dose [LD50 ] = 19.47 µg/g) was significantly higher than that of Gal4/UAS-CCE23-V1 transgenic flies (LD50  = 13.11 µg/g). Molecular docking analysis showed that splicing opened a "gate" that enlarges the substrate binding cavity of CCE23-V2, might enhance the ability of CCE23-V2 to harbor fenpropathrin molecules. These findings suggest that splicing might enhance the detoxifying capability of TcCCE23. Generally, our data improve the understanding of the diversity and complexity of the mechanisms underlying the regulation of CCEs.

Longitudinal MicroSPECT Imaging of Systemic Sclerosis Model Mice with [99mTc]Tc-HYNFA via Folate Receptor Targeting.

Noninvasive single-photon emission computed tomography (SPECT) imaging with [99mTc]Tc-HYNFA via folate receptor (FR) targeting was proposed to assess the inflammation and therapeutic effect of systemic sclerosis (SSc) in model mice. The radiochemical yield and purity of [99mTc]Tc-HYNFA were over 95%, with a specific activity of about 9.36 ± 0.17 MBq/nmol. At the end of induction, the uptake ratios of bleomycin-injected regions on the back-to-muscle (R/M) and lung-to-muscle (L/M) derived from SPECT images were 7.27 ± 0.50 and 4.25 ± 0.15, respectively. The radioactivity uptakes could be blocked by excessive folic acid (FA), and R/M and L/M obviously decreased to 2.78 ± 0.57 and 2.51 ± 0.79, respectively. R/M (2.22 ± 0.71) and L/M (1.62 ± 0.28) decreased very close to those of the control mice group (R/M = 1.99 ± 0.36, L/M = 1.50 ± 0.14) when macrophages had been depleted in advance. After being treated with cyclophosphamide (CTX) or methotrexate (MTX), R/M and L/M decreased to 3.58 ± 0.52 and 2.03 ± 0.32 (CTX treatment) or 2.48 ± 0.64 and 1.83 ± 0.06 (MTX treatment). R/M and L/M were highly correlated with pathological changes. The trend of hydroxyproline content in lungs at the later non-inflammatory phase of each group was similar to the uptake values of the lung in the 4th week from the beginning of induction. [99mTc]Tc-HYNFA had an ideal uptake in SSc lesions. R/M and L/M had a high consistency with pathological changes. SPECT imaging-targeted FR could monitor the therapeutic effect of CTX and MTX. It is expected to be an effective means to evaluate SSc.

Association between e-cigarette use and susceptibility to tobacco product use: findings from the 2019 China National Youth Tobacco Survey.

Background: There is an ongoing debate about whether e-cigarettes act as a gateway to tobacco smoking or contribute to smoking cessation, and relevant studies are limited among Chinese adolescents. This cross-sectional study therefore aimed to explore the relationship between e-cigarette use and susceptibility to tobacco product use among Chinese high school students. Methods: The study population comprised 107,633 never smokers and 19,377 former smokers, generated from the 2019 China National Youth Tobacco Survey. The primary independent variables of interest were ever e-cigarette use, current e-cigarette use, and the frequency of current e-cigarette use. The main outcome was the susceptibility to tobacco product use. Multilevel logistic regression was used to estimate the association between the primary independent variables of interest and the outcome variable. Moreover, two additional multilevel logistic regression models were fitted using two alternative definitions of the outcome as the sensitivity analyses. Results: Among never smokers, students who ever used e-cigarettes were more likely to be susceptible to tobacco product use compared to students who never used e-cigarettes (AOR = 2.83, 95%CI = 2.59-3.08). Students who currently used e-cigarettes were more likely to be susceptible to tobacco product use than those who did not currently use e-cigarettes (AOR = 3.89, 95%CI = 3.21-4.72). Among former smokers, with the same settings of modeling, the AORs were 1.76 (95%CI = 1.62-1.91) and 3.16 (95%CI = 2.52-3.97), respectively. Similar results were obtained from the two sensitivity analyses. Conclusion: Among Chinese high school students, both never smokers and former smokers, e-cigarette use, especially current e-cigarette use, was positively associated with susceptibility to tobacco product use. It is recommended to strengthen the monitoring of e-cigarettes and to provide targeted health education to adolescents.

Prevalence and Determinants of Secondhand Smoke Exposure Among Adolescent Girls - China, 2019.

What is already known about this topic?: The rate of secondhand smoke (SHS) exposure among female junior high students in 2013-2014 in China was 69.9%. What is added by this report?: The rate of SHS among adolescent girls in 2019 in China was 62.8%, with 60.8% in junior high and 65.3% in senior high school, meanwhile, higher SHS exposure was correlated to higher grade levels, senior high school over junior high school, urban areas, those with more pocket money, those who've attempted smoking, exposure to tobacco advertisements, those with parents who smoke, those with close friends who smoke, use of e-cigarettes, and belief that SHS exposure is detrimental to health. What are the implications for public health practice?: The rate of SHS exposure among adolescent girls in China still remains extraordinarily high. Targeted public health initiatives to curb SHS exposure among adolescent girls are urgently needed in China.

Cigarette availability and affordability among Chinese youth smokers: Findings from the 2019 China Youth Tobacco Survey.

INTRODUCTION: Preventing youth from tobacco use is a priority for tobacco control in China, and the government has taken many measures such as introducing tobacco control in the health education curriculum, banning smoking in school, promoting smoke-free household, and advocacy campaigns. The objective of this study was to understand the availability and affordability of cigarettes for middle school (MS) and high school (HS) students in China. METHODS: The data were extracted from the 2019 China National Youth Tobacco Survey, which was a school-based cross-sectional survey with a nationally representative sample of 288192 MS and HS students. The survey employed a randomized multistage stratified cluster sampling design with probability proportional to size sampling method and used an anonymous self-administrated questionnaire to collect data. The availability and affordability of cigarettes were analyzed, and all parameter estimates were weighted to account for the complex sampling design. RESULTS: In 2019, an estimated 80.5% of current smokers who were aged <18 years bought cigarettes in the past 30 days. Among them, 83.3% (83.0% of males and 85.2% of females; and 76.5% in MS and 87.6% in HS) had not been refused purchase of cigarettes because they were underage, with 84.1% in urban and 82.9% in rural areas, and 87.3% in central, 83.4% in eastern, and 80.5% in western regions of China. Among current smokers who bought cigarettes in the past 30 days, 77.3% had bought a pack of cigarettes (20 cigarettes) costing >10 RMB and at least 61.4% had more pocket money per week than the cost of a pack of cigarettes. Although 84.2% of current smokers bought cigarettes by the pack, 9.2% of current smokers reported that they bought cigarettes as sticks. CONCLUSIONS: Although the youth smoking rate dropped down from 2014 to 2019, the proportion of youth smokers that bought cigarettes was still high in China. Due to the high amount of pocket money, the current cigarette price was not an effective price barrier to prevent youth smoking. Selling cigarettes by the stick worsens the situation. Strengthening the enforcement of the 2021 Law on the Protection of Minors, increasing tobacco taxes and prices, and forbidding the selling of cigarette sticks, might assist the progress in youth tobacco control.

Synthesis, preclinical evaluation and radiation dosimetry of a dual targeting PET tracer [68Ga]Ga-FAPI-RGD.

To enhance tumor uptake and retention, we designed and developed bi-specific heterodimeric radiotracers targeting both FAP and αvß3, [68Ga]Ga-FAPI-RGD. The present study aimed to evaluate the specificity, pharmacokinetics, and dosimetry of [68Ga]Ga-FAPI-RGD by preclinical and preliminary clinical studies. Methods: FAPI-RGD was designed and synthesized with the quinoline-based FAPI-02 and the cyclic RGDfK peptide. Preclinical pharmacokinetics were determined in Panc02 xenograft model using microPET and biodistribution experiments. The safety and effective dosimetry of [68Ga]Ga-FAPI-RGD was evaluated in 6 cancer patients, and compared with 2-[18F]FDG imaging. Results: The [68Ga]Ga-FAPI-RGD had good stability in saline for at least 4 h, and showed favorable binding affinity and specificity in vitro and in vivo. Compared to [68Ga]Ga-FAPI-02 and [68Ga]Ga-RGDfK, the tumor uptake and retention of [68Ga]Ga-FAPI-RGD were very much enhanced than its monomeric counterparts at all the time points examined by microPET imaging. A total of 6 patients with various malignant tumors were prospectively enrolled. The effective dose of [68Ga]Ga-FAPI-RGD was 1.94E-02 mSv/MBq. The biodistribution of [68Ga]Ga-FAPI-RGD from 0 to 2 h after injection demonstrated rapid and high tumor uptake, prolonged tumor retention, and high tumor-to-background ratios (TBRs) which further increased over time. No significant difference in mean SUVmax of [68Ga]Ga-FAPI-RGD and 2-[18F]FDG was present in primary tumors (8.9±3.2 vs. 10.3 ± 6.9; p = 0.459). Conclusion: The dual targeting PET tracer [68Ga]Ga-FAPI-RGD showed significantly improved tumor uptake and retention, as well as cleaner background over 68Ga-labeled FAPI and RGD monospecific tracers. The first-in-human biodistribution study showed high TBRs over time, suggesting high diagnostic performance and favorable tracer kinetics for potential therapeutic applications.