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On December 14, 2022, the U.S. Food and Drug Administration (FDA) approved revisions to the United States Prescribing Information (USPI) for capecitabine that revised existing indications and dosage regimens, added new indications and their recommended dosage regimens, revised safety information, updated the description of the risk of capecitabine in patients with dihydropyrimidine dehydrogenase (DPD) deficiency, and edited other sections of the USPI to conform with FDA's current labeling guidance. These supplements were reviewed and approved under Project Renewal, a public health initiative established by the FDA's Oncology Center of Excellence that aims to update the prescribing information of certain older oncology drugs to ensure information is clinically meaningful and scientifically up to date. This article summarizes the FDA approach that supported revisions to the capecitabine USPI within the context of Project Renewal.

Purpose: To investigate the prevalence and characteristics of late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) and its prognostic value in patients with Takayasu arteritis (TA)., Materials and Methods: Sixty TA patients with a CMR examination were retrospectively included. All TA patients were divided into with LGE-positive and LGE-negative groups. Bi-ventricular function and location, distribution, and pattern of left ventricular (LV) LGE were evaluated in both LGE-positive and LGE-negative groups. Primary outcome was defined as a composite of cardiovascular death, hospitalization for heart failure, coronary artery revascularization, and stroke. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the association between variables and primary outcomes., Results: Sixty consecutive TA patients were enrolled in this study. The mean age was 38.2 ± 13.8 years and 54 patients (54/60, 90.0%) were female. LGE-positive was observed in twenty-one (21/60, 35%) patients in the total patients with TA. LGE was predominantly distributed in the middle wall and subendocardial. The patchy and infarcted LGE patterns were the most common. Compared with the LGE-negative group, the LGE-positive group had reduced LV ejection fraction ( P  = 0.033), elevated LV end-diastolic volume index ( P  = 0.008), LV end-systolic volume index ( P  = 0.012), and LV mass ( P  = 0.008). During a median follow-up period of 1,892 days (interquartile range: 1,764-1,988 days), the primary outcomes occurred in thirteen patients. In the univariate analysis, LGE-positive (hazard ratio [HR] = 4.478, 95% confidence interval [CI]: 1.376-14.570; P  = 0.013) were independently associated with the primary outcomes. However, LGE-positive did not retain its value as an independent predictor of primary outcomes in the multivariate analysis. Instead, LVMI (HR = 1.030, 95%CI: 1.013-1.048; P  = 0.001) was the strongest independent predictor of primary outcomes in patients with TA. The Kaplan-Meier plot revealed that patients with LVMI ≥ 57.5 g/m 2 have a worse prognosis., Conclusion: LGE-positive detected by CMR was observed in 35% of total TA patients with different distributions and patterns. LGE is associated with adverse LV remodeling and worsen cardiac function. However, LVMI rather than LGE can provide independent prognostic information in patients with TA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Tang, Wei, Zhao, Liu, Liu, Qin, Pan, Zhang and Wen.)

Background: The prevalence of online altruistic behaviors among the college students has attracted widespread attention. However, the factors influencing this are still unclear. The objective of this study was to explore the relationship and mechanism of online interpersonal trust, moral identity, online social support and online altruistic behavior among college students., Methods: The survey was conducted among 986 Chinese college students using the Interpersonal Trust Scale for the Internet, Moral Identity Scale, The Internet Social Support Questionnaire for College Students and The Internet Altruistic Behavior Questionnaire for College Students., Results: Moral identity, online social support, online interpersonal trust and online altruistic behavior were significantly positively correlated ( r  = 0.09-0.39, p  < 0.01). Online social support plays a partial mediating role in the relation between online interpersonal trust and online altruistic behavior, accounting for 33.76% of the total effect, while moral identity and online social support play a chain mediating role in the relation between online interpersonal trust and online altruistic behavior, accounting for 2.23% of the total effect., Conclusion: Online interpersonal trust not only directly affects college students' online altruistic behavior, but also indirectly influences it through moral identity and online social support., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Lin, Liao and Pan.)

Anaplastic lymphoma kinase (ALK) fusion genes promote a variety of human malignancies. Although several ALK inhibitors have significantly improved disease prognosis in patients with ALK positive cancers, the persistent emergence of acquired drug-resistant mutations remain the major problem in clinic treatment. Adoption of new therapeutic strategies such as proteolysis targeting chimera (PROTAC) to overcome drug resistance in BTK/AR-related cancers have shown promising prospect. Herein, we reported the integrate ALK PROTACs through overall optimization of linker, revealed that subtle structural differences can lead to significant activity difference, indicating the key role of conformation of PROTACs in inducing the formation of E3-PROTAC-target protein ternary complexes. A series of rigid ALK PROTACs were developed through conjugation of Ceritinib and thalidomide, orally bioavailable PROTAC 4B (F = 14.22 %) was obtained by overall optimization of molecular properties. 4B effectively induced long lasting degradation of ALK fusion proteins and strong repression of downstream pathway in Karpas 299 cells (DC 50  = 119.33 nM, Dmax = 97.1 %) and showed comparable anti-proliferative activity to Ceritinib (IC 50  = 3.11 ± 0.08 nM vs IC 50  = 1.31 ± 0.43 nM). Furthermore, 4B significantly inhibited the growth of Karpas 299 xenografts in vivo with TGI of 49.5 % and showed superior anti-proliferative activity against G1202R mutation to Ceritinib (IC 50  = 52.82 nM vs IC 50  = 109.5 nM). Overall, 4B is expected to be a potential treatment for ALK-driven malignancies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Emerging fields, such as wearable electronics, digital healthcare, the Internet of Things, and humanoid robots, highlight the need for flexible devices capable of recording signals on curved surfaces and soft objects. In particular, flexible magnetosensitive devices garner significant attention owing to their ability to combine the advantages of flexible electronics and magnetoelectronic devices, such as reshaping capability, conformability, contactless sensing, and navigation capability. Several key challenges must be addressed to develop well-functional flexible magnetic devices. These include determining how to make magnetic materials flexible and even elastic, understanding how the physical properties of magnetic films change under external strain and stress, and designing and constructing flexible magnetosensitive devices. In recent years, significant progress is made in addressing these challenges. This study aims to provide a timely and comprehensive overview of the most recent developments in flexible magnetosensitive devices. This includes discussions on the fabrications and mechanical regulations of flexible magnetic materials, the principles and performances of flexible magnetic sensors, and their applications for wearable electronics. In addition, future development trends and challenges in this field are discussed., (© 2024 Wiley‐VCH GmbH.)

Background: Pulmonary artery involvement (PAI) is not rare in Takayasu arteritis (TA). Persistently elevated pulmonary arterial pressure in TA-PAI patients leads to pulmonary hypertension (PH), and eventually cardiac death. Thus, the early detection of right ventricular dysfunction before the onset of PH is important., Purpose: To explore the potential of right ventricular global peak longitudinal and circumferential strain (RVGLS and RVGCS, respectively) in detecting right ventricular myocardial damage in TA-PAI patients without PH., Study Type: Retrospective., Population: One hundred and six TA patients (39.6 ± 13.9 years), of whom 52 were non-PAI and 54 were PAI patients (36 without PH and 18 with PH), along with 58 sex- and age-matched healthy volunteers (HVs) (36.7 ± 13.2 years). The involved arteries were validated by aorta magnetic resonance (MR) angiography and pulmonary artery computed tomography angiography., Field Strength/sequence: 3 T/Cine imaging sequence with a steady-state free precession readout., Assessment: Cardiac MRI-derived parameters measured by two radiologists independently were compared among HVs, and TA patients with and without PAI. In addition, these indices were further compared among HVs, and TA-PAI patients with and without PH., Statistical Tests: Student's t test, one-way ANOVA analysis, Pearson and Spearman correlation analysis, and reproducibility analysis. A P-value of <0.05 was considered statistically significant., Results: Although the TA-PAI patients without PH had a similar RV ejection fraction (RVEF) with HV (P = 0.348), RVGLS (non-PH 20.6 ± 3.7% vs. HV 24.0 ± 3.1%) was significantly lower and RVGCS (non-PH 14.8 ± 3.9% vs. HV 13.0 ± 2.7%) higher. The TA-PAI patients with PH had significantly poorer RVGLS (PH 13.5 ± 3.8% vs. non-PH 20.6 ± 3.7%) and RVGCS (PH 10.9 ± 3.2% vs. non-PH 14.8 ± 3.9%) than those without PH., Data Conclusion: Right ventricular dysfunction was detected in the TA-PAI patients without PH. MR-feature tracking may be an effective method for detecting early cardiac damage in the TA-PAI patients without PH., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 3., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: The predictive importance of IKZF1 del in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has shown variability across different studies. Thus, the optimal treatment approach for children with IKZF1 del BCP-ALL remains contentious, with the ongoing debate surrounding the use of IKZF1 del -based high-risk stratification versus a minimal residual disease (MRD)-guided protocol., Methods: IKZF1 status was reliably determined in 804 patients using multiplex ligation-dependent probe amplification (MLPA) data obtained from four hospitals in Fujian, a province of China. In the Chinese Children Leukemia Group (CCLG)-ALL 2008 cohort, IKZF1 status was included in the risk assignment, with all IKZF1 del patients receiving a high-risk regimen. Conversely, in the Chinese Children's Cancer Group (CCCG)-ALL 2015 cohort, IKZF1 del was not incorporated into the risk assignment, and patients were treated based on an MRD-guided risk stratification protocol., Results: IKZF1 del was found in 86 patients (86/804, 10.7%) overall and in 30 (30/46, 65.2%) BCR::ABL1-positive patients. Overall, IKZF1 del was a poor prognostic predictor for patients, though the significance diminished upon age adjustment, white blood cell (WBC) count at diagnosis, treatment group, and MRD status. In the CCLG-ALL 2008 cohort, IKZF1 del conferred a notably lower 5-year overall survival (OS) and event-free survival (EFS) and a significantly higher 5-year cumulative incidence of relapse (CIR) than IKZF1 wt . In the CCLG-ALL 2015 cohort, IKZF1 del conferred a lower 5-year OS and EFS and a higher 5-year CIR than IKZF1 wt , but the differences were insignificant. The IKZF1 del patients treated with higher intensity chemotherapy (CCLG-ALL 2008 high-risk regimen) had a markedly lower 5-year OS and EFS compared with those treated with the MRD-guided protocol (CCCG-ALL 2015 protocol). Furthermore, patients treated with the CCLG-ALL 2008 high-risk regimen experienced a higher frequency of serious adverse events (SAEs), especially infection-related SAEs, compared with those treated with the CCCG-ALL 2015 MRD-guided protocol., Conclusions: The prognostic effect of IKZF1 del may vary in different protocols. Compared with higher intensity chemotherapy, the MRD-guided protocol may be a more effective approach to treating BCP-ALL with IKZF1 del in children., (© 2024. The Author(s).)

On November 15, 2023, the U.S. Food and Drug Administration (FDA) granted traditional approval to repotrectinib (Augtyro, Bristol Myers Squibb Corporation) for the treatment of adult patients with locally advanced or metastatic receptor tyrosine kinase encoded by the ROS1 gene (ROS1)-positive non-small cell lung cancer (NSCLC). The approval was based on TRIDENT-1, a single-arm trial with multiple cohorts of patients with ROS1 fusion-positive (hereafter "ROS1-positive") NSCLC (NCT03093116), who were either treatment naïve or had received prior ROS1 tyrosine kinase inhibitor (TKI) and/or platinum-based chemotherapy. The primary efficacy outcome measure is objective response rate (ORR) assessed by blinded independent central review (BICR) using response evaluation criteria in solid tumors version 1.1. ORR was assessed in 71 patients who were ROS1 TKI naïve and 56 patients who had received a prior ROS1 TKI. Among the 71 patients who were ROS1 TKI naïve, the ORR was 79% (95% CI, 68-88), median duration of response was 34.1 months (95% CI, 26-NE). In patients who had received a prior ROS1 TKI and no prior chemotherapy, the ORR was 38% (95% CI, 25-52). The median duration of response was 14.8 months (95% CI, 7.6-NE); BICR-assessed responses were observed in CNS metastases in patients in both cohorts and in patients who developed resistance mutations following prior TKI therapy. The most common (>20%) adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. A unique feature of this ROS1 TKI approval is the inclusion of robust evidence of efficacy in patients with ROS1-positive NSCLC who had progressed on prior ROS1 TKIs., (©2024 American Association for Cancer Research.)

On August 11, 2022, FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd, ENHERTU, Daiichi Sankyo) for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. The approval was based on a prespecified interim analysis of DESTINY-Lung02 (Study U206), a multi-center, randomized, dose-optimization trial in patients with NSCLC harboring activating HER2-mutations. At the approved dose of 5.4 mg/kg given intravenously every 3 weeks, the overall response rate (ORR) was 58% (95% confidence interval [CI]: 43, 71). The median duration of response was 8.7 months (95% CI: 7.1, not estimable). These results were consistent with response rates observed at the 6.4 mg/kg dose level. The most common (≥ 20%) adverse reactions were nausea, constipation, decreased appetite, vomiting, fatigue, and alopecia. The rate of interstitial lung disease (ILD) or pneumonitis was 6% at the 5.4 mg/kg dose level and 14% at the 6.4 mg/kg dose level. In the setting of similar efficacy and reduced toxicity, approval was granted for the 5.4 mg/kg dose level. The applicant conducted a randomized, dose-optimization study with guidance from the FDA Oncology Center of Excellence's Project Optimus. This is the first approval of a targeted therapy for HER2-mutated NSCLC., (Published by Oxford University Press 2024.)

Targeting receptor-interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [ 11 C]CNY-10 is reported, which may enable brain RIPK1 imaging. [ 11 C]CNY-10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [ 11 C]CNY-10 is characterized by PET imaging in rodents and a non-human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [ 11 C]CNY-10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [ 11 C]CNY-10-based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [ 11 C]CNY-10 for AD and potentially other RIPK1-related human studies., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objectives: The aim of this study was to investigate the predictive value of uric acid (UA) in prognosis of pulmonary artery involvement (PAI) in patients with Takayasu's arteritis (TAK)., Methods: A total of 166 TAK patients were enrolled in the study, including 76 with PAI and 90 without. Outcomes of 144 TAK patients were followed up and recorded. The possible associations between serum UA levels and incidence of PAI in TAK and PAI-related prognosis of TAK patients were examined using different statistical models., Results: The serum UA levels were significantly higher in TAK patient with PAI than TAK patients without PAI. Multivariate logistic regression analysis indicated that serum UA level ≥284.5 umol/L was associated with an increasing incidence of PAI in TAK (OR: 2.108, 95% CI: 1.063 to 4.180; p=0.033). Kaplan-Meier survival analysis showed that TAK patients with serum UA level ≥328.1 umol/L had a significantly higher cumulative incidence of PAI-related adverse events compared to TAK patients with serum UA level <328.1 umol/L (p=0.008). Multivariate Cox proportional hazard regression analysis revealed that serum UA level ≥328.1 umol/L (HR: 2.595, 95% CI: 1.198 to 5.622; p=0.016) was a PAI-related prognostic risk factor for TAK., Conclusions: Elevation of serum UA level was associated with an increasing risk of PAI and PAI-related adverse event in patients with TAK, indicating its potential as a predictor for identification of PAI onset and worsening in TAK patients.

Background: Dexmedetomidine, an α 2 -adrenergic receptor (α 2 -AR) agonist, is extensively used in clinical and animal studies owing to its sedative, analgesic, and anxiolytic effects. The diverse range of research domains associated with dexmedetomidine poses challenges in defining pivotal research directions. Therefore, this study aimed to conduct a qualitative and quantitative bibliometric study in the field of dexmedetomidine over the past decade to establish current research trends and emerging frontiers., Methods: Relevant publications in the field of dexmedetomidine between 2014 and 2023 were extracted from the Web of Science Core Collection database. The bibliometric analysis, incorporating statistical and visual analyses, was conducted using CiteSpace (6.1.R6) and R (4.3.1)., Results: The present study encompassed a total of 5,482 publications, exhibiting a consistent upward trend over the past decade. The United States and its institutions had the highest centrality. Ji, Fuhai, and Ebert, Thomas J. were identified as the most productive author and the most cited author, respectively. As anticipated, the most cited journal was Anesthesiology . Moreover, cluster analysis of cited references and co-occurrence of keywords revealed that recent studies were primarily focused on sedation, delirium, and opioid-free anesthesia. Finally, a timeline view of keywords clusters and keywords burst demonstrated that primary research frontiers were stress response, neuroinflammation, delirium, opioid-free anesthesia, peripheral nerve block, and complications., Conclusion: Current research trends and directions are focused on sedation, delirium, and opioid-free anesthesia, as evidenced by our results. The frontier of future research is anticipated to encompass basic investigations into dexmedetomidine, including stress response and neuroinflammation, as well as clinical studies focusing on delirium, opioid-free anesthesia, peripheral nerve block, and associated complications., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 Chen et al.)

Background: The heart can be involved in immunoglobulin (Ig)-G4-related disease (IgG4-RD). This study aimed to summarize the clinical features and efficacy of treatment for IgG4-RD patients with heart involvement., Methods: We conducted a retrospective study enrolling 42 IgG4-RD patients with heart involvement from the IgG4-RD cohorts of the Peking Union Medical College Hospital and Beijing An Zhen Hospital, from 2010 to 2022. Clinical, laboratory, radiological data were collected, and treatment responses to glucocorticoids and immunosuppressants were analyzed., Results: IgG4-related cardiac involvement is a rare part of the IgG4-RD spectrum. The incidences of coronary periarteritis and pericarditis were 1.2%(13/1075) and 3.1%(33/1075), respectively in our cohort. Valvular disease possibly related to IgG4-RD was detected in two patients. None of the patients with myocardial involvement were identified. The average age was 58.2 ± 12.8 years, with a male predominance (76.7%). Coronary artery CT revealed that mass-like and diffuse wall-thickening lesions were the most frequently observed type of coronary periarteritis. Pericarditis presented as pericardial effusion, localized thickening, calcification and mass. After treatment with glucocorticoid and immunosuppressants, all patients achieved a reduced IgG4-RD responder index score and achieved radiological remission. Two patients with coronary peri-arteritis experienced clinical relapses during the maintenance period., Conclusions: Cardiac involvement in IgG4-RD is rare and easily overlooked since many patients are asymptomatic, and the diagnosis relies on imaging. Patients showed a satisfactory response to glucocorticoid based treatment., (© 2024. The Author(s).)

Objective: The goal of the present study was to investigate the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and disease remission in Takayasu arteritis (TAK) patients., Methods: This retrospective study included 59 patients in the study group and 80 patients in the validation cohort with TAK. After 6 months of therapy, patients were re-evaluated, and serum 25(OH)D levels were compared before and after treatment. Correlations between changes in 25(OH)D levels and changes in disease activity scores (NIH, ITAS2010, ITAS.A) were analyzed. Additionally, a predictive cut-off value for disease remission was determined., Results: After 6 months of therapy, serum 25(OH)D levels in TAK patients significantly increased compared to baseline [(18.33 ± 7.25)µg/L vs (11.77 ± 4.14) µg/L] (P < 0.001). Positive correlations were observed between the increasing changes in the 25(OH)D level and the decreasing changes in the reduced NIH, ITAS2010, and ITAS.A scores (r = 0.455, P < 0.001; r = 0.495, P < 0.001; and r = 0.352 P = 0.006, respectively). A change of 8.45 µg/L in 25(OH)D level was identified as the predictive cut-off value for TAK remission (sensitivity 54.1%, specificity 90.9%, area under the curve = 0.741). Similarly for patients with normal baseline ESR, sensitivity is 68.0%, specificity is 92.3%, and area under the curve is 0.831, and for patients with normal baseline CRP, sensitivity is 58.3%, specificity is 90.0%, and area under the curve is 0.748. Validation in an additional 80 patients demonstrated a higher remission rate in those with a 25(OH)D level change > 8.45 µg/L., Conclusion: Serum 25(OH)D levels significantly increased after treatment in TAK patients, and an increase of ≥ 8.45 µg/L was predictive of disease remission, especially in individuals with normal baseline ESR and/or CRP levels. Key Points • Following treatment, there was a significant increase in serum 25(OH)D levels among TAK patients. • The elevated changes in 25(OH)D levels before and after treatment demonstrated a positive correlation with the reduction in disease activity scores. • In patients with TAK before and after treatment, an elevation in serum 25(OH)D levels exceeding 8.45 µg/L serves as an indicator for disease remission, particularly prominent in individuals with normal baseline ESR and/or CRP levels., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Dielectric elastomers, such as thermoplastic polyurethanes (TPUs), are widely used as the dielectric layer, encapsulation layer, and substrate of flexible and stretchable devices. To construct capacitors and actuators that work stably upon deformation, it has become urgent to investigate the evolution of dielectricity under stress and strain. However, the lack of effective methods for estimating the dielectric constant of elastomers under strain poses a big challenge. This study reports a device for the in situ measurement of the dielectric constant of TPU under strain. It is found that upon stretching TPU to a strain of 400%, its dielectric constant decreases from 8.02 ± 0.01 to 2.88 ± 0.25 (at 1 MHz). In addition, combined Fourier-transform infrared spectroscopy, the X-ray scattering technique, and atomic force microscopy were utilized to characterize the evolution of the microstructure under strain. The investigation under tensile strain reveals a decreased density and average size of polarized hard domains, along with a tendency of the molecular chains to align in parallel with the tensile stress. The evolution of the microstructures results in a reduction in the measured dielectric constant in TPU., Competing Interests: The authors declare no conflicts of interest.

Objectives: Coronary artery calcification (CAC) is frequently observed in Takayasu's arteritis (TAK). Our objective is to calculate the prevalence and severity of CAC in TAK, while evaluating the influence of traditional cardiovascular risk factors, glucocorticoid exposure, and disease activity on CAC., Methods: This retrospective study involved 155 TAK patients. We measured the Agatston score by coronary computed tomography angiography (CCTA) and categorised all patients into groups with or without CAC (41 vs. 114) to compare clinical characteristics and ancillary findings between the two groups., Results: Among the TAK patients, a total of 41 TAK patients (26.45%) exhibited CAC. Age of onset, disease duration, history of hypertension, history of hyperlipidaemia, Numano V and glucocorticoid use emerged as the independent risk factors for developing CAC in TAK (OR [95% CI] 1.084[1.028-1.142], p=0.003; 1.005 [1.001-1.010], p=0.020; 4.792 [1.713-13.411], p=0.003; 4.199 [1.087-16.219], p=0.037; 3.287 [1.070-10.100], p=0.038; 3.558[1.269-9.977], p=0.016). Nonetheless, CAC was not associated with disease activity. Moreover, the extent of calcification score in TAK showed a positive correlation with the number of traditional cardiovascular risk factors., Conclusions: We recommend CCTA screening for Numano V classified TAK patients. Glucocorticoid usage significantly escalates the risk of CAC. Therefore, in cases of effectively controlled disease, the inclusion of immunosuppressants aimed at reducing glucocorticoid dosage is advisable.

Introduction: Improved understanding of the prognostic biomarkers associated with childhood acute lymphoblastic leukemia (ALL) is needed for accurate risk group stratification. This study aimed to identify potential long-non coding RNA (lncRNA) markers and evaluate their prognostic value in children with ALL., Methods: We selected 50 children with newly diagnosed ALL and 20 age-matched patients with idiopathic immune thrombocytopenia (controls). RNA sequencing was performed to identify differentially expressed lncRNAs between the ALL and control groups. Correlation analysis was performed to determine the relationships between candidate lncRNAs, clinical features, and the risk of leukemogenesis., Results: A total of 1,019 differentially expressed lncRNAs were identified between the ALL and control groups. Reverse-transcriptase (RT-qPCR) revealed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 were significantly upregulated in patients with ALL. Furthermore correlation analysis showed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 represent potential predictors of leukemogenesis; however, only lncRNA RP11-252C15.1 was associated with clinical features and outcome in children with B-cell precursor ALL (BCP-ALL). In vitro experiments confirmed that lncRNA RP11-252C15.1 was significantly overexpressed in BCP-ALL cell lines and promoted proliferation, and repressed apoptosis in MHH-CALL-3 cells., Conclusion: LncRNA RP11-252C15.1 is a potential oncogene in BCP-ALL pathogenesis and a prognostic biomarker in children with BCP-ALL., (S. Karger AG, Basel.)

Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Familial acute myeloid leukemia (AML) pedigrees with germline CCAAT/enhancer-binding protein-α (CEBPA) mutation have been rarely reported due to insufficient knowledge of their clinical features. Here, we report two Chinese families with multiple AML cases carrying germline CEBPA mutations, one of which had 11 cases spanning four consecutive generations. Additionally, we collected clinical data of 57 AML patients from 22 families with germline CEBPA mutations, with 58.3% of them harboring double CEBPA mutations. The first mutation frequently occurred at the N-terminal of CEBP/α (78.6%), resulting in an exclusive expression of p30 of CEBPA (CEBPA p30 ). The second mutation was mostly found at the C-terminal of CEBP/α (CEBPA others ). Germline CEBPA p30 carriers had higher incidences of AML (80.36% vs. 42.86%) and earlier onset of AML (18 vs. 38.5 years old) compared to germline CEBPA others carriers. Despite the high rates of relapse, most familial AML cases exhibited favorable overall survival (OS), with germline CEBPA p30 carriers having better survival outcomes (>25 years vs. 11 years for CEBPA others carriers). Among the 27 healthy germline CEBPA-mutated carriers, we detected a pre-leukemia clone harboring a pathogenic IDH2 variant (R140Q)in one individual. These findings should aid in the genetic counseling and management of AML patients and healthy carriers with germline CEBPA mutations., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The canonical correlation analysis (CCA) has attracted wide attention in fault detection (FD). To improve the detection performance, we propose a new joint sparse constrained CCA (JSCCCA) model that integrates the l 2,0 -norm joint sparse constraints into classical CCA. The key idea is that JSCCCA can fully exploit the joint sparse structure to determine the number of extracted variables. We then develop an efficient alternating minimization algorithm using the improved iterative hard thresholding and manifold constrained gradient descent method. More importantly, we establish the convergence guarantee with detailed analysis. Finally, we provide extensive numerical studies on the simulated dataset, the benchmark Tennessee Eastman process, and a practical cylinder-piston process. In some cases, the computing time is reduced by 600 times, and the FD rate is increased by 12.62% compared with classical CCA. The results suggest that the proposed approach is efficient and fast.

Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans -cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo , with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC.

Objective: Depression is a common complication in Takayasu arteritis (TA). Disorders of the immune system play an important role in both diseases. This study aimed to clarify the feature of cytokines in TA patients with depression., Methods: In this cross-sectional study, serum cytokines were tested in 40 TA patients and 11 healthy controls using the Bio-Plex Magpix System (Bio-Rad ® ). The state of depression was measured by the Zung Self-Rating Depression Scale (SDS) in TA patients. Logistic regression analysis was performed to find the risk factors of depression in patients with TA., Results: TA patients with depression had higher ESR, hsCRP, NIH, and ITAS.A than patients without depression (16.00 [10.00, 58.50]mm/H vs. 7.50 [4.50, 17.75]mm/H, p  = 0.013; 7.60 [2.32, 46.52]mg/L vs. 0.71 [0.32, 4.37]mg/L, p  = 0.001; 2.00 [2.00, 3.00] vs. 1.00 [0.00, 2.00], p  = 0.007; 7.00 [4.00, 9.50] vs. 1.50 [0.00, 5.75], p  = 0.012, respectively). Additionally, the lower age of onset and levels of IL-4, IL-13, eotaxin, and IP-10 were observed in the depressed group compared with the non-depressed (23.50 [19.25, 32.50]pg./ml vs. 37.00 [23.25, 42.50]pg./ml, p  = 0.017; 2.80 [2.17, 3.18]pg./ml vs. 3.51 [3.22, 4.66]pg./ml, p  < 0.001; 0.66 [0.60, 1.12]pg./ml vs. 1.04 [0.82, 1.25]pg./ml, p  = 0.008; 46.48 [37.06, 61.75]pg./ml vs. 69.14 [59.30, 92.80]pg./ml, p  = 0.001; 184.50 [138.23, 257.25]pg./ml vs. 322.32 [241.98, 412.60]pg./ml, p  = 0.005, respectively). The lower level of IL-4 and age of onset were the independent risk factors for depression in TA patients (OR [95% CI] 0.124 [0.018, 0.827], p  = 0.031; 0.870 [0.765, 0.990], p  = 0.035, respectively)., Conclusion: Our data suggested that lower cytokine levels, especially IL-4, might be involved in the development of TA patients with depression. Clinicians can probably use serum IL-4 level testing as a potential indicator of depression in TA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Yang, Fan, Du, Gao, Pan and Li.)

Here we describe a cost-effective and simplified cell sorting method using tetrazine bioorthogonal chemistry. We successfully isolated SKOV3 cells from complex mixtures, demonstrating efficacy in separating mouse lymphocytes expressing interferon and HeLa cells expressing virally transduced green fluorescent protein post-infection.

Elsinochrome A (EA) is a naturally occurring photosensitizer with potential applications in photodynamic therapy (PDT) for various malignancies. Despite its promising therapeutic properties, the poor solubility of EA hampers its effective utilization in clinical settings. To circumvent this limitation, we engineered four distinct nano-formulations: PLGA/EA nanoparticles (NPs), CMC-PLGA/EA NPs, mPEG-PCL/EA nanomicelles (NMs), and LHP-CHOL/EA nanoliposomes (NLs), all designed to enhance the solubility of EA. A comparative evaluation of these formulations, based on metrics such as particle size, Zeta potential, drug loading efficiency, and encapsulation efficiency, identified PLGA/EA NPs and mPEG-PCL/EA NMs as the most efficacious candidates. Subsequent in vitro investigations into the drug release kinetics under varying pH conditions and the impact on cell viability and apoptosis in A549 and MCF-7 cell lines were conducted. Remarkably, the maximum drug release for PLGA/EA NPs and mPEG-PCL/EA NMs was recorded at 62.5% and 70.8% in an acidic environment (pH 5.7), respectively. Upon exposure to 460 nm light, PLGA/EA NPs induced a significant reduction in A549 cell viability to 13.8% and an apoptosis rate of 93.8%, whereas mPEG-PCL/EA NMs elicited a decrease in MCF-7 cell viability to 12.8% and an apoptosis rate of 73.0%., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Prompt response to induction chemotherapy is a prognostic factor in pediatric acute myeloid leukemia. In this study, we aimed to evaluate the prognostic significance of multiparametric flow cytometry-minimal residual disease (MFC-MRD), assessed at the end of the first and second induction courses., Methods: MFC-MRD was performed at the end of the first induction (TP1) in 524 patients and second induction (TP2) in 467 patients who were treated according to the modified Medical Research Council (UK) acute myeloid leukemia 15 protocol., Results: Using a 0.1% cutoff level, patients with MFC-MRD at the two time points had lower event-free survival and overall survival. Only the TP2 MFC-MRD level could predict the outcome in a separate analysis of high and intermediate risks based on European LeukemiaNet risk stratification and KMT2A rearrangement. The TP2 MFC-MRD level could further differentiate the prognosis of patients into complete remission or non-complete remission based on morphological evaluation. Multivariate analysis indicated the TP2 MFC-MRD level as an independent adverse prognostic factor for event-free survival and overall survival. When comparing patients with MFC-MRD ≥ 0.1%, those who underwent hematopoietic stem cell transplant during the first complete remission had significantly higher 5-year event-free survival and overall survival and lower cumulative incidence of relapse than those who only received consolidation chemotherapy., Conclusions: The TP2 MFC-MRD level can predict the outcomes in pediatric patients with acute myeloid leukemia and help stratify post-remission treatment., (© 2024. The Author(s).)

Atherosclerosis is a significant contributor to global cardiovascular disease. Reducing the formation of atherosclerotic plaque effectively can lead to a decrease in cardiovascular diseases. Therefore, controlling macrophage function is crucial. This study presents the creation of a bifunctional nanoparticle that is specific to macrophages to achieve intracellular and extracellular synergistic therapy for restoring macrophage functions. The nanoparticle is conjugated with anti-CD47 antibody to modulate extracellular CD47-SIRPα phagocytic signaling axis on the outer surface of macrophages and encapsulates the NLRP3 inhibitor (CY-09) to regulate intracellular inflammation response of macrophages. The results showed that the nanoparticles accumulate in the atherosclerotic plaque, alter macrophage phagocytosis, inhibit NLRP3 inflammasome activation, and decrease the plaque burden in Apoe -/- mice whilst ensuring safety. Examination of single-cell RNA sequencing indicates that this multifunctional nanoparticle decreases the expression of genes linked to inflammation and manages inflammatory pathways in the plaque lesion. This study proposes a synergistic therapeutic approach that utilizes a bifunctional nanoparticle, conjugated with anti-CD47, to regulate the microenvironment of plaques., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

Objective: The primary aim of this study is to assess the diagnostic efficacy of elastography and contrast-enhanced ultrasound (CEUS) in the identification of breast lesions subsequent to the optimization and correction of the BI-RADS category 4 classification obtained through conventional ultrasound. The objective is to augment both the specificity and accuracy of breast lesion diagnosis, thereby establishing a reliable framework for reducing unnecessary biopsies in clinical settings., Methods: A cohort comprising 50 cases of breast lesions classified under BI-RADS category 4 was collected during the period from November 2022 and November 2023. These cases were examined utilizing strain elastography (SE), shear wave elastography (SWE), and CEUS. Novel scoring methodologies for ultrasonic elastography (UE) and CEUS were formulated for this investigation. Subsequently, the developed UE and CEUS scoring systems were used to refine and optimize the conventional BI-RADS classification, either in isolation or in conjunction. Based on the revised classification, the benign group was classified as category 3 and the suspected malignant group was classified as category 4a and above, with pathological results serving as the definitive reference standard. The diagnostic efficacy of the optimized UE and CEUS, both independently and in combination, was meticulously scrutinized and compared using receiver operating characteristic (ROC) curve analysis, with pathological findings as the reference standard., Results: Within the study group, malignancy manifested in 11 cases. Prior to the implementation of the optimization criteria, 78% (39 out of 50) of patients underwent biopsies deemed unnecessary. Following the application of optimization criteria, specifically a threshold of≥8.5 points for the UE scoring method and≥6.5 points for the CEUS scoring method, the incidence of unnecessary biopsies diminished significantly. Reduction rates were observed at 53.8% (21 out of 39) with the UE protocol, 56.4% (22 out of 39) with the CEUS protocol, and 89.7% (35 out of 39) with the combined UE and CEUS optimization protocols., Conclusion: The diagnostic efficacy of conventional ultrasound BI-RADS category 4 classification for breast lesions is enhanced following optimized correction using UE and CEUS, either independently or in conjunction. The application of the combined protocol demonstrates a notable reduction in the incidence of unnecessary biopsies.

Objective: To investigate the prognostic value of serum albumin (SA) levels before chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) after receiving chemotherapy., Methods: This is a retrospective study, and 127 patients with DLBCL including 71 males (55.9%) and 56 females (44.1%) were included. Patients' gender, age, Ann Arbor staging, eastern cooperative oncology group (ECOG) score, treatment options, international prognostic index, response rate, overall survival (OS), and progression-free survival (PFS) were obtained for statistical analysis., Results: Univariate analysis showed that SA≤34 g/L, Ann Arbor III-IV, B symptoms, ECOG≥2, and bone marrow involvement suggest a poor prognosis in patients with DLBCL. Patients with persistent SA>34 g/L had significantly longer OS than patients with persistent SA≤34 g/L (P=0.020). Multivariate analysis showed that SA≤34 g/L (HR=0.48, 95% CI=0.26-0.90, P=0.022) and R-CHOP-like treatment regimen (HR=0.43, 95% CI=0.24-0.76, P=0.004) are independent factors that could affect the prognosis of patients with DLBCL., Conclusion: SA can be used as an indicator of prognosis in patients with DLBCL before the first chemotherapy. DLBCL patients with SA≤34 g/L are associated with short OS and poor prognosis, which may potentially provide guidance for the clinician to pay more attention to this population before the first chemotherapy.

Platelet parameters have been recognized as important markers for disease severity in various types of diseases. The aim of our study was to investigate whether platelet count could be used as a potential predictor of refractory Takayasu arteritis (TAK). In this retrospective study, fifty-seven patients were selected as development data group to identify the associated risk factors and potential predictors of refractory TAK. Ninety-two TAK patients were included in the validation data group to verify the predictive value of platelet count for refractory TAK. Refractory TAK patients had higher levels of platelet (PLT) than non-refractory TAK patients (305.5 vs. 272.0 × 10 9 /L, P = 0.043). For PLT, the best cut-off value was 296.5 × 10 9 /L to predict refractory TAK. Elevated PLT (> 296.5 × 10 9 /L) was found to be statistically related to refractory TAK (OR [95%CI] 4.000 [1.233-12.974], p = 0.021). In the validation data group, the proportion of refractory TAK in patients with elevated PLT was significantly higher than that in patients with non-elevated PLT (55.6% vs. 32.2%, P = 0.037). The 1-, 3- and 5-year cumulative incidence of refractory TAK were 37.0%, 44.4% and 55.6% in patients with elevated PLT, respectively. Elevated PLT (p = 0.035, hazard ratio (HR) 2.106) was identified as a potential predictor of refractory TAK. Clinicians should pay close attention to platelet levels in patients with TAK. For TAK patients with PLT greater than 296.5 × 10 9 /L, closer monitoring of the disease and comprehensive assessment of disease activity are recommended to be alert to the occurrence of refractory TAK., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Takayasu arteritis (TAK) is an inflammatory disease of blood vessels, and its pathogenesis is not clear at present. In this study, we explored the immunological characteristics of T cell receptor (TCR) α-chain complementarity-determining region 3 (CDR3) in patients with TAK., Methods: Five untreated patients with TAK were collected from June 2019 to December 2019. Four healthy blood samples were matched as the control group. The blood mononuclear cells were separated, and RNA was extracted for reverse transcription to obtain complementary DNA. Then high-throughput sequencing was performed. The quality of samples was evaluated by principal component analysis. We compared the diversity and expression of TCR α-chain between TAK group and control group. R software was used for statistical analysis and drawing, and Mann-Whitney U test was used to analyze the differences between the two groups., Results: The results showed that there was a significant difference in the diversity of TCR α-chain CDR3 between the two groups. Three V region genes expression significantly higher in the TAK patients than in the control group. A total of 196 VJ rearrangement genes are significantly different between the two groups, of which 149 rearrangement genes in the TAK group are lower than those in the control group, and 47 rearrangement genes in the TAK group are higher than those in the control group., Conclusion: Patients with TAK have a unique TCR α-chain CDR3 library. These characteristic genes may be a marker for early diagnosis and provide a new theoretical basis for treating TAK., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer with major challenges in both prevention and therapy. Metformin, adenosine monophosphate-activated protein kinase (AMPK) activator, has been suggested to reduce the incidence of HCC when used for patients with diabetes in preclinical and clinical studies. However, the possible effects of metformin and their mechanisms of action in non-diabetic HCC have not been adequately investigated., Methods: Fah -/-  mice were used to construct a liver-injury-induced non-diabetic HCC model for exploring hepatocarcinogenesis and therapeutic potential of metformin. Changes in relevant tumour and biochemical indicators were measured. Bulk and single-cell RNA-sequencing analyses were performed to validate the crucial role of proinflammatory/pro-tumour CD8 + T cells. In vitro and in vivo experiments were performed to confirm Cyp26a1-related antitumour mechanisms of metformin., Results: RNA-sequencing analysis showed that chronic liver injury led to significant changes in AMPK-, glucose- and retinol metabolism-related pathways in Fah -/- mice. Metformin prevented the formation of non-diabetic HCC in Fah -/- mice with chronic liver injury. Cyp26a1 ddexpression in hepatocytes was significantly suppressed after metformin treatment. Moreover, downregulation of Cyp26a1 occurred in conjunction with increased levels of all-trans-retinoic acid (atRA), which is involved in the activation of metformin-suppressed hepatocarcinogenesis in Fah-/- mice. In contrast, both CD8 +  T-cell infiltration and proinflammatory/pro-tumour cytokines in the liver were significantly upregulated in Fah -/- mice during chronic liver injury, which was notably reversed by either metformin or atRA treatment. Regarding mechanisms, metformin regulated the decrease in Cyp26a1 enzyme expression and increased atRA expression via the AMPK/STAT3/Gadd45β/JNK/c-Jun pathway., Conclusions: Metformin inhibits non-diabetic HCC by upregulating atRA levels and downregulating CD8 + T cells. This is the first reporting that the traditional drug metformin regulates the metabolite atRA via the Cyp26a1-involved pathway. The present study provides a potential application of metformin and atRA in non-diabetic HCC., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

This study aimed to investigate the influence of recombinant human erythropoietin (rHuEPO) on pentylenetetrazol (PTZ)-induced neuronal apoptosis in epilepsy rats, and to explore the signaling pathways related to the action. Healthy Sprague-Dawley rats aged 8 weeks old were randomly divided into 5 groups, namely, control group, PTZ model group, PTZ + rHuEPO intervention group, PTZ + SB431542 + rHuEPO intervention group and PTZ + SB431542 (TGF-β/Smad inhibitor) intervention group. The expressions of apoptotic proteins [tumor necrosis factor receptor 1 (TNFR1) and caspase-3] and the transforming growth factor-beta (TGF-β)/Smad signaling pathway-related proteins [phosphorylated smad3 (p-smad3) and TGF-β1] in the brain tissues were determined via Western blotting (WB). Epilepsy was successfully induced by PTZ in the rats. The results of the TUNEL assay showed that the intervention with rHuEPO could remarkably reduce the number of PTZ-induced apoptotic neurons in the hippocampus, while SB431542 inhibitor could attenuate the protective effect of rHuEPO against neuronal apoptosis (P<0.05). In addition, the intraperitoneal injection of 50 μg/kg rHuEPO could activate the TGF-β/Smad signaling pathway, markedly up-regulate the expressions of TGF-β1 and p-smad3 (P<0.05), down-regulate the expressions of apoptotic proteins TNFR1 and caspase-3 (P<0.01) and reduce neuronal apoptosis. Moreover, SB431542 was able to notably repress the protective effect of rHuEPO against neuronal apoptosis, and down-regulate the expressions of p-smad3 and TGF-β1 (P<0.01). In conclusion, the inhibitory effect of rHuEPO on nerve cell apoptosis in epilepsy rats may be realized by activating the TGF-β/Smad signaling pathway, thus relieving neuronal apoptosis and ameliorating the symptoms of epilepsy.

This study tested the hypothesis that recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances polymorphonuclear neutrophils (PMNs) via interleukin (IL)-1β to improve the prognosis of secondary infection in sepsis. The latter stage of sepsis is prone to induce immunosuppression, resulting in secondary fatal infections. Recombinant GM-CSF has become a way for sepsis-induced immunosuppression due to its immunomodulatory effect. However, the functional impact of GM-CSF on PMNs in sepsis remains obscure. This study aimed to study the role of recombinant GM-CSF on the bactericidal ability of PMNs in septic mice, assessing its effect on the prognosis of secondary pneumonia, and explore the mechanism of recombinant GM-CSF by intervening PMNs in patients with sepsis. The C57BL/6J sepsis mouse model was induced by cecal ligation and puncture. Recombinant murine GM-CSF (rmGM-CSF) was used in vivo when mice developed immunosuppression, which was characterized by abnormal bactericidal function of PMNs in peripheral blood. rmGM-CSF improved the prognosis of secondary pneumonia and reversed the function of PMNs. PMNs isolated by Percoll from septic patients were treated by recombinant human GM-CSF (rhGM-CSF) in vitro. The expression of CD11b, reactive oxygen species, phagocytosis, and neutrophil extracellular trap release in PMNs were enhanced by rhGM-CSF treatments. Whole-transcriptomic sequencing of mouse PMNs indicated that recombinant GM-CSF increased the expression of Il1b gene in PMNs. Blocking and inhibiting IL-1β release effectively counteracted the enhancing effect of GM-CSF on the bactericidal function of PMNs. rmGM-CSF enhances the bactericidal function of PMNs in vivo and improves the prognosis of secondary pneumonia in septic mice, and recombinant GM-CSF increases IL-1β precursor reserves, which, if stimulated, can rapidly enhance the bactericidal capacity of PMNs., Competing Interests: Conflict of interest statement. The authors have no financial conflicts of interest., (Published by Oxford University Press on behalf of Society for Leukocyte Biology 2023.)

Individualized positive end-expiratory pressure (PEEP) combined with recruitment maneuvers improves intraoperative oxygenation in individuals undergoing robot-assisted prostatectomy. However, whether electrical impedance tomography (EIT)-guided individualized PEEP without recruitment maneuvers can also improve intraoperative oxygenation is unknown. To test this, fifty-six male patients undergoing elective robot-assisted laparoscopic prostatectomy were randomly assigned to either individualized PEEP (Group PEEP IND , n = 28) or a control with a fixed PEEP of 5 cm H 2 O (Group PEEP 5 , n = 28). Individualized PEEP was guided by EIT after placing the patients in the Trendelenburg position and performing intraperitoneal insufflation. Patients in Group PEEP IND maintained individualized PEEP without intermittent recruitment maneuvers, and those in Group PEEP 5 maintained a PEEP of 5 cm H 2 O intraoperatively. Both groups were extubated in a semi-sitting position once the extubation criteria were met. The primary outcome was arterial oxygen partial pressure (PaO 2 )/inspiratory oxygen fraction (FiO 2 ) prior to extubation. Other outcomes included intraoperative driving pressure, plateau pressure and dynamic, respiratory system compliance, and the incidence of postoperative hypoxemia in the post-operative care unit (PACU). Our results showed that the intraoperative median for PEEP IND was 16 cm H 2 O (ranging from 12 to 18 cm H 2 O). EIT-guided PEEP IND was associated with higher PaO 2 /FiO 2 before extubation compared to PEEP 5 (71.6 ± 10.7 vs. 56.8 ± 14.1 kPa, p = 0.003). Improved oxygenation extended into the PACU with a lower incidence of postoperative hypoxemia (3.8% vs. 26.9%, p = 0.021). Additionally, PEEP IND was associated with lower driving pressures (12.0 ± 3.0 vs. 15.0 ± 4.4 cm H 2 O, p = 0.044) and better compliance (44.5 ± 12.8 vs. 33.6 ± 9.1 mL/cm H 2 O, p = 0.017). Our data indicated that individualized PEEP guided by EIT without intraoperative recruitment maneuvers also improved perioperative oxygenation in patients undergoing robot-assisted laparoscopic radical prostatectomy, which could benefit patients with the risk of intraoperative hemodynamic instability caused by recruitment maneuvers. Trial registration: China Clinical Trial Registration Center Identifier: ChiCTR2100053839. This study was registered on 1 December 2021. The first patient was recruited on 15 December 2021.

Background: The imaging of somatostatin receptors (SSTRs) plays a significant role in imaging neuroendocrine tumors (NETs). However, there has been no clear definition on whether it is necessary to withdraw somatostatin analogs (SSAs) before SSTRs imaging. We aimed to assess whether nonradioactive SSAs affect the uptake of radiolabeled SSAs on imaging for NETs patients., Methods: The databases of PubMed, Embase, and Web of Science (WoS) were searched until March 12, 2022 to identify eligible studies. Maximum standardized uptake values (SUVmax) in tumor and normal tissues were extracted, pooled, and compared before and after SSAs treatment. The change of tumor-to-background/liver ratio was also described. The quality of each study was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool., Results: A total of 9 articles involving 285 patients were included and 5 studies using Gallium-68-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid]-D-Phe 1 -Tyr 3 -Thr 8 -octreotide ( 68 Ga-DOTATATE) were used for pooled evaluation. We found a significantly decreased SUVmax in the liver (9.56±2.47 vs. 7.62±2.12, P=0.001) and spleen (25.74±7.14 vs. 20.39±6.07, P=0.006) after SSAs treatment whereas no significant differences were observed in the uptake of thyroid, adrenal, and pituitary gland. For either primary tumor sites or metastases, the SUVmax did not change significantly before and after SSAs treatment. The tumor-to-liver/background ratio increased following SSAs therapy. High heterogeneity was observed across the studies, mainly due to inherent diversity of study design, sample size, and scanning technique., Conclusions: Based on current evidence, long-acting SSAs therapy before imaging has no effect on the uptake of radiolabeled SSAs at tumor primary sites and metastatic lesions, but results in a significant reduction of uptake in the liver and spleen. These findings may implicate the unnecessary discontinuation of SSAs before radiolabeled SSAs imaging., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-477/coif). The authors report that this work was supported by the National Natural Science Foundation of China (No. 81901776) and the Post-Doctor Research Project, West China Hospital, Sichuan University (No. 2023HXBH075)., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: The clinical value of pericoronary adipose tissue in assessing Takayasu arteritis (TAK) with coronary artery involvement (CAI) is yet to be determined. The purpose of this study was to investigate the characteristics of pericoronary fat attenuation index (FAI) derived from coronary computed tomography angiography (CTA) in patients with TAK., Methods: This is a retrospective study involving enrollment of 111 consecutive patients (mean age, 33.92±12.48 years) who were diagnosed as TAK, of which 52 patients had coronary artery involvement (TAK-CAI) and 59 patients without coronary artery involvement (TAK-nonCAI). Based on the extent of coronary artery lesion, the TAK-CAI group was further classified into localized group (n=25) and diffused group (n=27). Furthermore, patients with TAK were divided into active group (n=33) and inactive group (n=78). Meanwhile, 51 gender-matched individuals with normal appearance in coronary CTA examination were enrolled as the control group. The pericoronary FAI was quantitatively evaluated on each coronary CTA examination groups. The diagnostic value of pericoronary FAI was determined using the area under the curve (AUC) of the receiver operating characteristic., Results: A higher pericoronary FAI was found in TAK-nonCAI group than control group with normal coronary arteries (P<0.001). Multivariate analysis showed that the FAI is an independent risk factor for coronary involvement in TAK patients [odds ratio (OR): 1.23, 95% confidence interval (CI): 1.13-1.35, P<0.001]. With the best cut-off value of -86.50, the pericoronary FAI identified coronary involvement with 67.8% sensitivity and 74.5% specificity (AUC: 0.794, 95% CI: 0.713-0.875, P<0.001). Multivariate analysis showed that the pericoronary FAI is an independent risk factor for determination of active TAK patients (OR: 1.57, 95% CI: 1.25-1.97, P<0.001). With the best cut-off value of -79.50, the pericoronary FAI identified active inflammation with 93.9% sensitivity and 74.4% specificity (AUC: 0.911, 95% CI: 0.860-0.962, P<0.001)., Conclusions: Coronary CTA-derived FAI is significantly increased in patients with TAK and can be used as a reliable biomarker to distinguish TAK patients from those with normal coronary arteries, and determine the extent of TAK inflammation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-419/coif). ZS serves as an unpaid associate editor of Quantitative Imaging in Medicine and Surgery. The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Due to the magnetoelastic coupling, the magnetic properties of many flexible magnetic films (such as Fe, Co, and Ni) are sensitive to mechanical stress, which deteriorates the performance of flexible magnetoelectronic devices. We show that by stacking Co and Pt alternatively to form multilayers with strong perpendicular magnetic anisotropy (PMA), both magnetic hysteresis and magnetic domain measurements reveal robust PMA against external stress. As the PMA weakens at increased Co thickness, the magnetic anisotropy is vulnerable to external stress. These results were understood based on a micromagnetic model, which suggests that the strength of magnetoelastic anisotropy with respect to initial effective magnetic anisotropy affects the stress-stability of the film. Although the stress coefficient of magnetoelastic anisotropy is enhanced at reduced Co thickness, the concomitant increase of initial effective magnetic anisotropy guarantees a robust PMA against external stress. Our results provide a route to constructing flexible magnetoelectronic devices with enhanced stress stability.

Elsinochrome A (EA) is a perylene quinone natural photosensitizer, photosensitizer under light excitation generates reactive oxygen species (ROS) to induce apoptosis, so can be used for treating tumors, that is so-called photodynamic therapy (PDT). However, the molecular mechanism, especially related to apoptosis and autophagy, is still unclear. In this study, we aimed to explore the mechanism of EA-PDT-induced B16 cells apoptosis and autophagy. The action of EA-PDT on mitochondrial permeability transition pore (MPTP), mitochondrial membrane potential (MMP) and the mitochondrial function were researched by fluorescence technique and Extracellular Flux Analyzer. Illumina sequencing, tandem mass tags Quantitative Proteomics and Western Blot studied the mechanism at the gene and protein levels. The results indicated that EA-PDT had excellent phototoxicity in vitro. EA could bind to the mitochondria. EA-PDT for 5 min caused MPTP opening, MMP decreasing and abnormal mitochondrial function with a concentration-dependent characteristic. EA-PDT resulted in an increase intracellular ROS and the number of autophagosomes. Caspase2, caspase9 and tnf were upregulated, and bcl2, prkn, atg2, atg9 and atg10 were downregulated. Our results indicated that EA-PDT induced cell apoptosis and autophagy through the mediation of ROS/Atg/Parkin. This study can provide enlightenment for exploring potential targets of drug development for the PDT of melanoma., (© 2023 Wiley Periodicals LLC.)

Introduction: The aim of this study was to analyse the effect of perioperative dexmedetomidine (DEX) application on stress response, post-operative pain and prognosis in patients undergoing gynaecologic laparoscopy., Patients and Methods: One hundred and sixty-eight patients admitted for gynaecologic laparoscopic surgery from May 2020 to November 2022 were included in the study. The patients were randomly divided into pre-operative DEX group (n = 56), intraoperative DEX group (n = 56) and post-operative DEX group (n = 56) according to the application of DEX in the perioperative period. The visual analogue scale (VAS), time awake, extubation time, pneumoperitoneum time, post-anaesthesia care unit (PACU) stay time and Richmond agitation-sedation scale score (RASS) were recorded., Results: Patients in both the pre-operative and intraoperative DEX groups had substantially shorter wakeup and extubation times than those in the post-operative DEX group. Patients in the pre-operative DEX group had considerably shorter wakeup and extubation times than those in the intraoperative DEX group, and their pneumoperitoneum time was significantly shorter than that of the post-operative DEX group (P < 0.001). The RASS scores of the pre-operative DEX group and intraoperative DEX group were significantly lower than those of the post-operative DEX group at 1 h, 6 h and 12 h after surgery. Meanwhile, at all time periods, the RASS scores of patients in the pre-operative DEX group were considerably lower than those in the intraoperative DEX group (P < 0.01). The VAS scores of patients in the pre-operative DEX group and intraoperative DEX group were evidently lower than those in the post-operative DEX group at 0.5 h, 2 h and 12 h postoperatively, and the VAS scores of patients in the pre-operative DEX group were markedly lower than those in the intraoperative DEX group (P < 0.001). The incidence of nausea and vomiting was significantly lower in the pre-operative DEX group than in the intraoperative DEX group and the post-operative DEX group at 0-2 h, >2-12 h and >12-24 h postoperatively (P < 0.001). The incidence of nausea and vomiting in the intraoperative DEX group was significantly lower than that in the post-operative DEX group from 0 to 2 h after surgery (P < 0.05). The incidence of adverse reactions was not significantly different amongst the three groups of patients (P > 0.05)., Conclusion: Pre-operative and intraoperative application of DEX can help reduce post-operative pain and stress responses, help patients recover quickly after surgery and improve patient prognosis, especially the pre-operative application of DEX., Competing Interests: None

Classical local anesthetics are unsuitable to treat regional pain lasting several days due to their limited duration and systemic toxicity. Self-delivery nano systems without excipients were designed for long-term sensory blocks. 1a self-assembled into different vehicles with different fractions of intermolecular π-π stacking, transported itself into nerve cells, and released single molecules slowly to achieve long-term duration for rats' sciatic nerve block for 11.6 h in water, 12.1 h in water with CO 2 and 3.4 h in NS (normal saline). After the counter ions were changed to SO 4 2- , 1e can self-assemble into vesicles and prolong the duration to 43.2 h, which was much longer than the 3.8 h led by ( s )-bupivacaine hydrocloride (0.75%). This was mainly caused by the enhancement of self-release and counter ion exchange inside nerve cells, which were affected by the gemini surfactant structure, p K a of the counter ions and π-π stacking interactions.

Background: The implication of the monocyte-to-high-density lipoprotein ratio (MHR) in Takayasu arteritis (TAK) remains unclear., Objective: We aimed to assess the predictive value of the MHR to identify coronary involvement with TAK and determine the patient prognosis., Methods: In this retrospective study, 1,184 consecutive patients with TAK were collected and assessed, and those who were initially treated and with coronary angiography were enrolled and classified according to coronary involvement or no involvement. Binary logistic analysis was performed to assess coronary involvement risk factors. Receiver-operating characteristic analysis was used to determine the MHR value to predict coronary involvement in TAK. Major adverse cardiovascular events (MACEs) were recorded in patients with TAK and coronary involvement within a 1-year follow-up, and Kaplan-Meier survival curve analysis was conducted to compare MACEs between them stratified by the MHR., Results: A total of 115 patients with TAK were included in this study, and 41 of them had coronary involvement. A higher MHR was found for TAK with coronary involvement than for TAK without coronary involvement ( P = 0.014). Multivariate analysis showed that the MHR is an independent risk factor for coronary involvement in TAK (odds ratio: 92.718, 95% confidence interval ( CI ): 2.813-3056.291, P = 0.011). With the best cut-off value of 0.35, the MHR identified coronary involvement with 53.7% sensitivity and 68.9% specificity [area under the curve (AUC): 0.639, 95% CI : 0.544-0.726, P= 0.010] and identified left main disease and/or three-vessel disease (LMD/3VD) with 70.6% sensitivity and 66.3% specificity (AUC: 0.704, 95% CI : 0.612-0.786, P = 0.003) in TAK. Combined with other variables, the MHR identified coronary involvement with 63.4% sensitivity and 90.5% specificity (AUC: 0.852, 95% CI : 0.773-0.911, P < 0.001), and identified LMD/3VD with 82.4% sensitivity and 78.6% specificity (AUC: 0.827, 95% CI : 0.720-0.934, P < 0.001) in TAK. A total of 39 patients with TAK and coronary involvement were followed up for 1 year, and 5 patients suffered a MACE. Those with an MHR >0.35 had a higher MACE incidence than their counterparts with an MHR ≤0.35 (χ 2  =   4.757, P = 0.029)., Conclusions: The MHR could be a simple, practical biomarker for identifying coronary involvement and LMD/3VD in TAK and predicting a long-term prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ci, Wan, Han, Zou, Ge, Pan and Jin.)

Competing Interests: Disclosures None.

Background: Norepinephrine transporter inhibitors that can alter the level of neurotransmitter in the brain are used to treat neurological disorders. However, a number of studies have reported their limited significance as a result of their slow onset of action and moderate efficacy., Objectives: To determine the effects of norepinephrine reuptake inhibitors (NRIs), reboxetine and atomoxetine on schizophrenia and attention deficit hyperactivity disorder (ADHD)., Material and Methods: Relevant articles published between 2000 and 2022 were searched in the MEDLINE, CINAHL (via Ebsco), Web of Science and Scopus databases. Among the various NRIs, studies concerning the 2 potent drugs - reboxetine and atomoxetine - were selected for analysis. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated, along with the exploration of heterogeneity and publication bias, using RevMan software., Results: A total of 14 eligible studies with a combined sample size of 970 patients were included. Using a random effects model, an OR of 0.55 (0.32-0.94), a Tau2 value of 0.23, a ÷2 value of 12.31, 8 degrees of freedom (df), an I2 of 35%, a Z value of 2.19, and a p-value of 0.03 were recorded for reboxetine. Atomoxetine had an OR of 0.35 (0.13-0.97), a Tau2 value of 0.58, a ÷2 value of 7.31, 4 df, an I2 of 45%, a Z value of 1.53, and a p-value of 0.04. All results were statistically significant with a low risk of publication bias, as was evident from the p-values >0.05 derived from the Egger's test and the Begg's test. These drugs provided comparable changes to control drugs in Hamilton Depression Rating Scale (HAM-D) scores, Positive and Negative Syndrome Scale (PANSS) scores and ADHD ratings. This confirms the efficacy of reboxetine for the treatment of schizophrenia and atomoxetine for the treatment of ADHD., Conclusion: The present meta-analysis suggests that NRIs are efficacious and therefore they are potential candidate drugs for the treatment of schizophrenia and ADHD.

Background: Takayasu arteritis (TAK) is a large-vessel vasculitis with high relapse rate. Longitudinal studies identifying risk factors of relapse are limited. We aimed to analyze the associated factors and develop a risk prediction model for relapse., Methods: We analyzed the associated factors for relapse in a prospective cohort of 549 TAK patients from the Chinese Registry of Systemic Vasculitis cohort between June 2014 and December 2021 using univariate and multivariate Cox regression analyses. We also developed a prediction model for relapse, and stratified patients into low-, medium-, and high-risk groups. Discrimination and calibration were measured using C-index and calibration plots., Results: At a median follow-up of 44 (IQR 26-62) months, 276 (50.3%) patients experienced relapses. History of relapse (HR 2.78 [2.14-3.60]), disease duration <24 months (HR 1.78 [1.37-2.32]), history of cerebrovascular events (HR 1.55 [1.12-2.16]), aneurysm (HR 1.49 [1.10-2.04], ascending aorta or aortic arch involvement (HR 1.37 [1.05-1.79]), elevated high-sensitivity C-reactive protein level (HR 1.34 [1.03-1.73]), elevated white blood cell count (HR 1.32 [1.03-1.69]), and the number of involved arteries ≥6 (HR 1.31 [1.00-1.72]) at baseline independently increased the risk of relapse and were included in the prediction model. The C-index of the prediction model was 0.70 (95% CI 0.67-0.74). Predictions correlated with observed outcomes on the calibration plots. Compared to the low-risk group, both medium and high-risk groups had a significantly higher relapse risk., Conclusions: Disease relapse is common in TAK patients. This prediction model may help to identify high-risk patients for relapse and assist clinical decision-making., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier B.V.)

With the merits of high sensitivity, high stability, high flexibility, low cost, and simple manufacturing, flexible magnetic field sensors have potential applications in various fields such as geomagnetosensitive E-Skins, magnetoelectric compass, and non-contact interactive platforms. Based on the principles of various magnetic field sensors, this paper introduces the research progress of flexible magnetic field sensors, including the preparation, performance, related applications, etc. In addition, the prospects of flexible magnetic field sensors and their challenges are presented.

Objective. Skin lesion segmentation plays an important role in the diagnosis and treatment of melanoma. Existing skin lesion segmentation methods have trouble distinguishing hairs, air bubbles, and blood vessels around lesions, which affects the segmentation performance. Approach. To clarify the lesion boundary and raise the accuracy of skin lesion segmentation, a joint attention and adversarial learning network (JAAL-Net) is proposed that consists of a generator and a discriminator. In the JAAL-Net, the generator is a local fusion network (LF-Net) utilizing the encoder-decoder structure. The encoder contains a convolutional block attention module to increase the weight of lesion information. The decoder involves a contour attention to obtain edge information and locate the lesion. To aid the LF-Net generate higher confidence predictions, a discriminant dual attention network is constructed with channel attention and position attention. Main results. The JAAL-Net is evaluated on three datasets ISBI2016, ISBI2017 and ISIC2018. The intersection over union of the JAAL-Net on the three datasets are 90.27%, 89.56% and 80.76%, respectively. Experimental results show that the JAAL-Net obtains rich lesion and boundary information, enhances the confidence of the predictions, and improves the accuracy of skin lesion segmentation. Significance. The proposed approach effectively improves the performance of the model for skin lesion segmentation, which can assist physicians in accurate diagnosis well., (© 2023 Institute of Physics and Engineering in Medicine.)

Abstract: Prostate cancer was newly diagnosed in a 73-year-old man. He underwent bone scintigraphy to assess any skeletal involvement. No abnormal uptake was observed in the skeletal system, whereas intense radioactivity was seen in the bilateral axillary regions. Physical examination found large amounts of sweat. Repeat images revealed no axillary activity after washing. This case illustrated axillary accumulation of 99m Tc-MDP due to perspiration., Competing Interests: Conflicts of interest and sources of funding: The authors have no conflicts to report. This article was supported by the Natural Science Foundation of Sichuan Province (grant 2022NSFSC1391)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Disorders of humoral immunity in Takayasu's arteritis (TAK) have not been well explored. This study describes the characteristics of B cells and immunoglobulin (Ig) profile in patients with TAK., Methods: Peripheral B cell populations assessed using flow cytometry and serum Ig levels assessed using a biochemical analyser in 98 newly diagnosed patients with TAK were analysed and compared with those of 31 patients with systemic lupus erythematosus (SLE) and 60 healthy controls (HCs). CD19+ B cell and IgG infiltration to the aortic tissue was evaluated by immunohistochemical staining., Results: The proportion of peripheral CD3-CD19+ B cells and levels of serum IgG in TAK were lower than those in SLE, but higher than those in HCs. CD3-CD19+ B cell counts were higher in TAK than in HCs. Serum IgG and IgG1 levels were higher in active TAK than in non-active TAK. In TAK, positive correlations of serum IgG levels with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Kerr score, and Indian Takayasu Clinical Activity Score (ITAS2010, ITAS-A) were observed before immunotherapy. After 6 months of immunotherapy, serum Ig levels significantly decreased. Positive correlations between the changes in IgG levels and values of ESR, CRP, Kerr score, and ITAS-A were detected. Immunohistochemical staining confirmed CD19+ B cell and IgG infiltration to the aortic wall in patients with TAK., Conclusions: Enhanced B cells might contribute to the pathogenesis of TAK, and serum IgG levels could serve as a simple, useful biomarker to assess disease activity and monitor treatment response in TAK.

Fibroblast activation protein (FAP) is regarded as a promising target for the diagnosis and treatment of tumors as it was overexpressed in cancer-associated fibroblasts. FAP inhibitors bearing a quinoline scaffold have been proven to show high affinity against FAP in vitro and in vivo , and the scaffold has been radio-labeled for the imaging and treatment of FAP-positive tumors. However, currently available FAP imaging agents both contain chelator groups to enable radio-metal labeling, making those tracers more hydrophilic and not suitable for the imaging of lesions in the brain. Herein, we report the synthesis, radio-labeling, and evaluation of a 18 F-labeled quinoline analogue ([ 18 F] 3 ) as a potential FAP-targeted PET tracer, which holds the potential to be blood-brain barrier-permeable. [ 18 F] 3 was obtained by one-step radio-synthesis via a copper-mediated S N A R reaction from a corresponding boronic ester precursor. [ 18 F] 3 showed moderate lipophilicity with a log D 7.4 value of 1.11. In cell experiments, [ 18 F] 3 showed selective accumulation in A549-FAP and U87 cell lines and can be effectively blocked by the pre-treatment of a cold reference standard. Biodistribution studies indicated that [ 18 F] 3 was mainly excreted by hepatic clearance and urinary excretion, and it may be due to its moderate lipophilicity. In vivo PET imaging studies indicated [ 18 F] 3 showed selective accumulation in FAP-positive tumors, and specific binding was confirmed by blocking studies. However, low brain uptake was observed in biodistribution and PET imaging studies. Although our preliminary data indicated that [ 18 F] 3 holds the potential to be developed as a blood-brain barrier penetrable FAP-targeted PET tracer, its low brain uptake limits its application in the detection of brain lesions. Herein, we report the synthesis and evaluation of [ 18 F] 3 as a novel small-molecule FAPI-targeted PET tracer, and our results suggest further structural optimizations would be needed to develop a BBB-permeable PET tracer with this scaffold., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Pan, Pan, Diao, Su, Huang, Yang, Li, Qi, Zhang and Wu.)