Exploring the environmental contamination toxicity and potential carcinogenic pathways of perfluorinated and polyfluoroalkyl substances (PFAS): An integrated network toxicology and molecular docking strategy.

The objective of this study was to investigate the potential carcinogenic toxicity and mechanisms of PFAS in thyroid, renal, and testicular cancers base on network toxicology and molecular docking techniques. Structural modeling was performed to predict relevant toxicity information, and compounds and cancer-related targets were screened in multiple databases. The interaction of PFAS with three cancers and their key protein targets were explored by combining protein network analysis, enrichment analysis and molecular docking techniques. PFOA, PFOS, and PFHXS exhibited significant carcinogenic and cytotoxic effects. These compounds may induce cancer by mediating active oxygen metabolism and the transduction of phosphatidylinositol 3-kinase/protein kinase B signaling pathway through genes such as ALB, mTOR, MDM2, and ERBB2. Furthermore, the underlying toxic mechanisms may be linked to the pathways in cancer, chemical carcinogenesis through reactive oxygen species/receptor activation, and the FoxO signaling pathway. The results contribute to a comprehensive understanding of the effects of these environmental pollutants on genes, proteins, and metabolic pathways in living organisms. It revealed their toxicity mechanisms in inducing thyroid, renal, and testicular cancers, and provided a solid theoretical foundation for designing new environmental control strategies and drug screening initiatives. Additionally, the integrated application of network toxicology and molecular docking technology can enhance our understanding of the toxicity and mechanisms of unknown environmental pollutants, which is beneficial for protecting the environment and human health.

Advancements in Nanomaterial Dispersion and Stability and Thermophysical Properties of Nano-Enhanced Phase Change Materials for Biomedical Applications.

Phase change materials (PCMs) are materials that exhibit thermal response characteristics, allowing them to be utilized in the biological field for precise and controllable temperature regulation. Due to considerations of biosafety and the spatial limitations within human tissue, the amount of PCMs used in medical applications is relatively small. Therefore, researchers often augment PCMs with various materials to enhance their performance and increase their practical value. The dispersion of nanoparticles to modify the thermophysical properties of PCMs has emerged as a mature concept. This paper aims to elucidate the role of nanomaterials in addressing deficiencies and enhancing the performance of PCMs. Specifically, it discusses the dispersion methods and stabilization mechanisms of nanoparticles within PCMs, as well as their effects on thermophysical properties such as thermal conductivity, latent heat, and specific heat capacity. Furthermore, it explores how various nano-additives contribute to improved thermal conductivity and the mechanisms underlying enhanced latent heat and specific heat. Additionally, the potential applications of PCMs in biomedical fields are proposed. Finally, this paper provides a comprehensive analysis and offers suggestions for future research to maximize the utilization of nanomaterials in enhancing the thermophysical properties of PCMs for biomedical applications.

Expert consensus on endodontic therapy for patients with systemic conditions.

The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Magnesium implantation as a continuous hydrogen production generator for the treatment of myocardial infarction in rats.

Molecular hydrogen is an emerging broad-spectrum antioxidant molecule that can be used to treat myocardial infarction (MI). However, with hydrogen inhalation, the concentration that can be reached within target organs is low and the duration of action is short, which makes it difficult to achieve high dose targeted delivery of hydrogen to the heart, seriously limiting the therapeutic potential of hydrogen for MI. As a result of reactions with the internal environment of the body, subcutaneous implantation of magnesium slices leads to continuous endogenous hydrogen production, leading to a higher hydrogen concentration and a longer duration of action in target organs. In this study, we propose magnesium implant-based hydrogen therapy for MI. After subcutaneous implantation of magnesium slices in the dorsum of rats, we measured hydrogen production and efficiency, and evaluated the safety of this approach. Compared with hydrogen inhalation, it significantly improved cardiac function in rats with MI. Magnesium implantation also cleared free radicals that were released as a result of mitochondrial dysfunction, as well as suppressing cardiomyocyte apoptosis.

Effects of low-tube voltage coronary CT angiography on plaque and pericoronary fat assessment: intraindividual comparison.

OBJECTIVES: To investigate the effects of low tube voltage on coronary plaques and pericoronary fat assessment, and to compare their extent among various levels of low voltage. MATERIALS AND METHODS: Patients were recommended for high-pitch low-tube voltage coronary computed tomography angiography (CCTA), and they were included if they had poor image quality and were referred to a conventional CCTA. The patients were classified into a low-voltage group (with 70-kV, 80-kV, and 90-kV subgroups) and a conventional group (100/120 kV). Their total plaque and subcomponent volumes and pericoronary fat attenuation index (FAI) were measured. RESULTS: A total of 1002 image slices (from 65 patients and 74 plaques) were included, including 21, 31, 13, 4, and 61 patients in the 70-kV, 80-kV, 90-kV, 100-kV, and 120-kV groups respectively. The CT values of noncalcified plaques in the conventional and low-voltage groups were 54.6 ± 21.3 HU and 31.5 ± 22.6 HU, respectively (p < 0.05). Compared with the conventional group, the necrotic core and calcification volume were increased, and the fibrolipid volume, periplaque, and right coronary artery FAI were decreased in the low-voltage group and its subgroups (p < 0.001). The magnitude of changes in fibrous and calcification volumes increased in the 70-kV subgroup compared with that in the 90-kV subgroup (p < 0.05). CONCLUSION: Low tube voltages, particularly of 70 kV, have a significant effect on coronary plaque and FAI. The effect of low voltage on plaque composition is characterized by a polarization pattern, i.e., a decrease in fibrolipid (medium density) and an increase in necrotic core (low density) and calcification (high density). CLINICAL RELEVANCE STATEMENT: Our results highlight the comparability and repeatability of plaque and pericoronary fat assessments facilitated by the same or a similar tube voltage. It is necessary to carry out studies on the specificity threshold of low tube voltage at each level. KEY POINTS: • Low tube voltage had a significant effect on coronary plaque and pericoronary fat, particularly 70 kV. • The effect of low tube voltage on plaque composition shows the shift from medium-density mixed components to low- and high-density components. • It is necessary to correct the specificity threshold or attenuation difference for low tube voltage at each level.

Multibarrier-penetrating drug delivery systems for deep tumor therapy based on synergistic penetration strategy.

Nanotherapies, valued for their high efficacy and low toxicity, frequently serve as antitumor treatments, but do not readily penetrate deep into tumor tissues and cells. Here we developed an improved tumor-penetrating peptide (TPP)-based drug delivery system. Briefly, the established TPP iNGR was modified to generate a linear NGR peptide capable of transporting nanotherapeutic drugs into tumors through a CendR pathway-dependent, neuropilin-1 receptor-mediated process. Although TPPs have been reported to reach intended tumor targets, they often fail to penetrate cell membranes to deliver tumoricidal drugs to intracellular targets. We addressed this issue by harnessing cell penetrating peptide technology to develop a liposome-based multibarrier-penetrating delivery system (mbPDS) with improved synergistic drug penetration into deep tumor tissues and cells. The system incorporated doxorubicin-loaded liposomes coated with nona-arginine (R9) CPP and cyclic iNGR (CRNGRGPDC) molecules, yielding Lip-mbPDS. Lip-mbPDS tumor-targeting, tumor cell/tissue-penetrating and antitumor capabilities were assessed using CD13-positive human fibrosarcoma-derived cell (HT1080)-based in vitro and in vivo tumor models. Lip-mbPDS evaluation included three-dimensional layer-by-layer confocal laser scanning microscopy, cell internalization/toxicity assays, three-dimensional tumor spheroid-based penetration assays and antitumor efficacy assays conducted in an animal model. Lip-mbPDS provided enhanced synergistic drug penetration of multiple biointerfaces for potentially deep tumor therapeutic outcomes.

Comparison of an interpretable extreme gradient boosting model and an artificial neural network model for prediction of severe acute pancreatitis.

INTRODUCTION: Acute pancreatitis (AP) that progresses to persistent organ failure is referred to as severe acute pancreatitis (SAP). It is a condition associated with a relatively high mortality. A prediction model that would facilitate early recognition of patients at risk for SAP is crucial for improvement of patient prognosis. OBJECTIVES: The aim of this study was to evaluate the accuracy of extreme gradient boosting (XGBoost) and artificial neural network (ANN) models for predicting SAP. PATIENTS AND METHODS: A total of 648 patients with AP were enrolled. XGBoost and ANN models were developed and validated in the training (519 patients) and test sets (129 patients). The accuracy and predictive performance of the XGBoost and ANN models were evaluated using both the area under the receiver operating characteristic curves (AUCs) and the area under the precision­recall curves (AUC­PRs). RESULTS: A total of 15 variables were selected for model construction through a univariable analysis. The AUCs of the XGBoost and ANN models in 5­fold cross­validation of the training set were 0.92 (95% CI, 0.87-0.97) and 0.86 (95% CI, 0.78-0.92), respectively, whereas the AUCs for the test set were 0.93 (95% CI, 0.85-1) and 0.87 (95% CI, 0.79-0.96), respectively. The XGBoost model outperformed the ANN model in terms of both diagnostic accuracy and AUC­PR. Individual predictions of the XGBoost model were explained using a local interpretable model­agnostic explanation plot. CONCLUSIONS: An interpretable XGBoost model showed better discriminatory efficiency for predicting SAP than the ANN model, and could be used in clinical practice to identify patients at risk for SAP.

Expert consensus on difficulty assessment of endodontic therapy.

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

MNTZNN for Solving Hybrid Double-Deck Dynamic Nonlinear Equation System Applied to Robot Manipulator Control.

Compared with conventional dynamic nonlinear equation systems, a hybrid double-deck dynamic nonlinear equation system (H3DNES) not only has multiple layers describing more different tasks in practice, but also has a hybrid nonlinear structure of solution and its derivative describing their nonlinear constraints. Its characteristics lead to the ability to describe more complicated problems involving multiple constraints, and strong nonlinear and dynamic features, such as robot manipulator tracking control. Besides, noises are inevitable in practice and thus strong robustness of models solving H3DNES is also necessary. In this work, a multilayered noise-tolerant zeroing neural network (MNTZNN) model is proposed for solving H3DNES. MNTZNN model has strong robustness and it solves H3DNES successfully even when noises exist in both the two layers of H3DNES. In order to develop the MNTZNN model, a new zeroing neural network (ZNN) design formula is proposed. It not only enables equations with respect to solutions to become equations with respect to the second-order derivatives of solutions but also makes the corresponding model have strong robustness. The robustness of the MNTZNN model is proved when parameters in the model satisfy a loose constraint and the error bounds are programmable via setting appropriate parameter values. Finally, the MNTZNN model is applied to the tracking control of the six-link planar robot manipulator and PUMA560 robot manipulator with hybrid nonlinear constraints of joint angle and velocity.

Understanding the effect of foreign atoms occupation on the metamagnetic behaviors in MnCoSi-based alloys: taking Pt-doping as an example.

Present research on TiNiSi-type MnCoSi-based alloys focuses on finding a suitable doping element to effectively reduce the critical magnetic field (µ0Hcri) required to induce a metamagnetic transition. This paper provides a guide to achieve this goal through an experimental investigation of Mn1-xPtxCoSi and MnCo1-xPtxSi alloys. In Mn1-xPtxCoSi, asxincreases,µ0Hcriat room temperature decreases, while in MnCo1-xPtxSi, it increases. This phenomenon can be attributed to the fact that larger Pt atoms prefer Co sites over Mn sites, as predicted by our density-functional theory. Consequently, in Mn1-xPtxCoSi, larger Co atoms are extruded into the Mn atoms chain, increasing the nearest Mn-Mn distance and resulting in a reducedµ0Hcri. This finding suggests that transition-metal atoms with more valence electrons preferably occupy the Co site, while those with fewer valence electrons preferably occupy the Mn site. Adhering to this rule, one can easily obtain a lowµ0Hcriand large magnetostrain under a low magnetic field by selecting a suitable foreign element and chemical formula, as demonstrated by the Mn1-xPtxCoSi alloy.

"Magnet" Based on Activated Silver Nanoparticles Adsorbed Bacteria to Predict Refractory Apical Periodontitis Via Surface-Enhanced Raman Scattering.

Refractory apical periodontitis (RAP) is an endodontic apical inflammatory disease caused by Enterococcus faecalis (E. faecalis). Bacterial detection using surface-enhanced Raman scattering (SERS) technology is a hot research topic, but the specific and direct detection of oral bacteria is a challenge, especially in real clinical samples. In this paper, we develop a novel SERS-based green platform for label-free detection of oral bacteria. The platform was built on silver nanoparticles with a two-step enhancement way using NaBH4 and sodium (Na+) to form "hot spots," which resulted in an enhanced SERS fingerprint of E. faecalis with fast, quantitative, lower-limit, reproducibility, and stability. In combination with machine learning, four different oral bacteria (E. faecalis, Porphyromonas gingivalis, Streptococcus mutans, and Escherichia coli) could be intelligently distinguished. The unlabeled detection method emphasized the specificity of E. faecalis in simulated saliva, serum, and even real samples from patients with clinical root periapical disease. In addition, the assay has been shown to be environmentally friendly and without secondary contamination through antimicrobial assays. The proposed label-free, rapid, safe, and green SERS detection strategy for oral bacteria provided an innovative solution for the early diagnosis and prevention of RAP and other perioral diseases.

External Field-Responsive Ternary Non-Noble Metal Oxygen Electrocatalyst for Rechargeable Zinc-Air Batteries.

Despite the increasing effort in advancing oxygen electrocatalysts for zinc-air batteries (ZABs), the performance development gradually reaches a plateau via only ameliorating the electrocatalyst materials. Herein, a new class of external field-responsive electrocatalyst comprising Ni0.5Mn0.5Fe2O4 stably dispersed on N-doped Ketjenblack (Ni0.5Mn0.5Fe2O4/N-KB) is developed via polymer-assisted strategy for practical ZABs. Briefly, the activity indicator ΔE is significantly decreased to 0.618 V upon photothermal assistance, far exceeding most reported electrocatalysts (generally >0.680 V). As a result, the photothermal electrocatalyst possesses comprehensive merits of excellent power density (319 mW cm-2), ultralong lifespan (5163 cycles at 25 mA cm-2), and outstanding rate performance (100 mA cm-2) for liquid ZABs, and superb temperature and deformation adaptability for flexible ZABs. Such improvement is attributed to the photothermal-heating-enabled synergy of promoted electrical conductivity, reactant-molecule motion, active area, and surface reconstruction, as revealed by operando Raman and simulation. The findings open vast possibilities toward more-energy-efficient energy applications.

Color-Tunable Perovskite Nanomaterials with Intense Circularly Polarized Luminescence and Tailorable Compositions.

The ability to design halide perovskite nanocrystals (PNCs) with circularly polarized luminescence (CPL) offers exceptional potential in photonic technologies. Despite recent inspiring advances, the creation of PNCs with full-color tailorablity, outstanding CPL, and long-term stability remains a substantial challenge. Herein, a robust strategy to craft CPL-active PNCs is reported, exhibiting appealing full-color tunable wavelengths, enhanced CPL, and prolonged stability. In contrast to conventional methodologies, this strategy utilizes chiral nematic mesoporous silica (CNMS) as host to render in situ confined growth of diverse achiral PNCs. By strategically engineering photonic bandgap, adjusting loading amount of PNCs, and manipulating cations/anion compositions of PNCs, robust CPL responses with tunable wavelength and intensity are successfully obtained. The resulting PNCs-CNMS achieves stable CPL emissions with full-color tunability and impressive luminescent dissymmetric factors up to -0.17. Remarkably, silica-based hosts as a protective barrier confer exceptional resistance to humidity, photodegradation, and thermal stability, even up to 95 °C. Furthermore, the ability to achieve reversible CPL switching within PNCs-CNMS is attainable by leveraging the responsiveness of CNMS matrix or dynamic behavior of impregnated PNCs. Additionally, circularly polarized light-emitting diode devices based on PNCs-CNMS can be conveniently fabricated. This research affords a powerful platform for designing functional chiroptical materials.

Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS: ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 µg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1ß, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.

Porous Organic Materials in Tissue Engineering: Recent Advances and Applications for Severed Facial Nerve Injury Repair.

The prevalence of facial nerve injury is substantial, and the restoration of its structure and function remains a significant challenge. Autologous nerve transplantation is a common treatment for severed facial nerve injury; however, it has great limitations. Therefore, there is an urgent need for clinical repair methods that can rival it. Tissue engineering nerve conduits are usually composed of scaffolds, cells and neurofactors. Tissue engineering is regarded as a promising method for facial nerve regeneration. Among different factors, the porous nerve conduit made of organic materials, which has high porosity and biocompatibility, plays an indispensable role. This review introduces facial nerve injury and the existing treatment methods and discusses the necessity of the application of porous nerve conduit. We focus on the application of porous organic polymer materials from production technology and material classification and summarize the necessity and research progress of these in repairing severed facial nerve injury, which is relatively rare in the existing articles. This review provides a theoretical basis for further research into and clinical interventions on facial nerve injury and has certain guiding significance for the development of new materials.

The impact of COVID-19 pandemic on healthcare workers under the "Ten New Guidelines" in Taizhou, China.

Purpose: We explored the influence of the "Ten new guidelines" on healthcare workers' preparedness, work impact, personal life impact, concerns, and support in Taizhou, China. Methods: A hospital-based self-administered online survey was conducted to investigate the levels of COVID-19 related experience among healthcare workers in December 2022. In total, 472 out of 2080 healthcare workers (22.7 % response rate) completed the questionnaires with valid responses. Stepwise linear regression was used to investigate the independence of factors associated with preparedness, work impact, personal life impact, concerns, and support. Results: The results revealed that working position (p < 0.001), pressure (p = 0.005), and negative affect (p < 0.001) were significantly associated with preparedness. Working position (p = 0.015), number of children (p = 0.040), working years (p = 0.019), COVID-19 risk perception (p < 0.001), work overload (p < 0.001), and negative affect (p < 0.001) were significantly associated with work impact. In addition, COVID-19 risk perception (p < 0.001), work overload (p < 0.001), pressure (p = 0.002), history of COVID-19 infection (p = 0.008), and awareness of possible infectious time (p = 0.031) were significantly associated with personal life impact. COVID-19 risk perception (p < 0.001), negative affect (p < 0.001), and work overload (p = 0.020) were significantly associated with concerns. Sex (p = 0.020) and negative affect (p = 0.016) were significantly associated with support. Conclusion: Negative affect was the most significant factor associated with COVID-19 related questions among healthcare workers under "Ten new guidelines" during COVID-19 pandemic.

6-Shogaol prevents benzo (A) pyrene-exposed lung carcinogenesis via modulating PRDX1-associated oxidative stress, inflammation, and proliferation in mouse models.

In this study, we have investigated the chemopreventive role of 6-shogaol (6-SGL) on benzopyrene (BaP) exposed lung carcinogenesis by modulating PRDX1-associated oxidative stress, inflammation, and proliferation in Swiss albino mouse models. Mice were exposed to BaP (50 mg/kg b.wt) orally twice a week for four consecutive weeks and maintained for 16 weeks, respectively. 6-SGL (30 mg/kg b.wt) were orally administered to mouse 1 h before BaP exposure for 16 weeks. After the experiment's termination, 6-SGL (30 mg/kg b.wt) prevented the loss in body weight, increased lung weight, and the total number of tumors in the mice. Moreover, we observed that 6-SGL treatment reverted the activity of BaP-induced lipid peroxidation and antioxidants in mice. Also, 6-SGL impeded the phosphorylation of MAPK family proteins such as Erk1, p38, and Jnk1 in BaP-exposed mice. PRDX1 is an essential antioxidant protein that scavenges toxic radicals and enhances several antioxidant proteins. Overexpression of PRDX1 substantially inhibits MAPKs, proliferation, and inflammation signaling axis. Hence, PRDX1 is thought to be a novel targeting protein for preventing BaP-induced lung cancer. In this study, we have obtained the 6-SGL treatment in a mouse model that reverted BaP-induced depletion of PRDX1 expression. Moreover, pretreatment of 6-SGL (30 mg/kg b.wt) significantly inhibited enhanced proinflammatory cytokines (TNF-α, IL-6, IL-ß1, IL-10) and proliferative markers (Cyclin-D1, Cyclin-D2, and PCNA) in BaP-exposed mice. The histopathological studies also confirmed that 6-SGL effectively protected the cells with less damage. Thus, the study demonstrated that 6-SGL could be a potential phytochemical and act as a chemopreventive agent in BaP-induced lung cancer by enhancing PRDX1 expression.

Preclinical Development of PNT6555, a Boronic Acid-Based, Fibroblast Activation Protein-α (FAP)-Targeted Radiotheranostic for Imaging and Treatment of FAP-Positive Tumors.

The overexpression of fibroblast activation protein-α (FAP) in solid cancers relative to levels in normal tissues has led to its recognition as a target for delivering agents directly to tumors. Radiolabeled quinoline-based FAP ligands have established clinical feasibility for tumor imaging, but their therapeutic potential is limited due to suboptimal tumor retention, which has prompted the search for alternative pharmacophores. One such pharmacophore is the boronic acid derivative N-(pyridine-4-carbonyl)-d-Ala-boroPro, a potent and selective FAP inhibitor (FAPI). In this study, the diagnostic and therapeutic (theranostic) potential of N-(pyridine-4-carbonyl)-d-Ala-boroPro-based metal-chelating DOTA-FAPIs was evaluated. Methods: Three DOTA-FAPIs, PNT6555, PNT6952, and PNT6522, were synthesized and characterized with respect to potency and selectivity toward soluble and cell membrane FAP; cellular uptake of the Lu-chelated analogs; biodistribution and pharmacokinetics in mice xenografted with human embryonic kidney cell-derived tumors expressing mouse FAP; the diagnostic potential of 68Ga-chelated DOTA-FAPIs by direct organ assay and small-animal PET; the antitumor activity of 177Lu-, 225Ac-, or 161Tb-chelated analogs using human embryonic kidney cell-derived tumors expressing mouse FAP; and the tumor-selective delivery of 177Lu-chelated DOTA-FAPIs via direct organ assay and SPECT. Results: DOTA-FAPIs and their natGa and natLu chelates exhibited potent inhibition of human and mouse sources of FAP and greatly reduced activity toward closely related prolyl endopeptidase and dipeptidyl peptidase 4. 68Ga-PNT6555 and 68Ga-PNT6952 showed rapid renal clearance and continuous accumulation in tumors, resulting in tumor-selective exposure at 60 min after administration. 177Lu-PNT6555 was distinguished from 177Lu-PNT6952 and 177Lu-PNT6522 by significantly higher tumor accumulation over 168 h. In therapeutic studies, all 3 177Lu-DOTA-FAPIs exhibited significant antitumor activity at well-tolerated doses, with 177Lu-PNT6555 producing the greatest tumor growth delay and animal survival. 225Ac-PNT6555 and 161Tb-PNT6555 were similarly efficacious, producing 80% and 100% survival at optimal doses, respectively. Conclusion: PNT6555 has potential for clinical translation as a theranostic agent in FAP-positive cancer.

Effect of Morinda citrifolia juice on the bonding strength and nanoleakage of crowns dentin / 口腔疾病防治

Objective@#To explore the effect of Morinda citrifolia juice (MCJ) combined with ethylene diamine tetraacetic acid (EDTA) on premolar bonding strength and nanoleakage and compare the results with those of the most commonly used root canal irrigation solution, sodium hypochlorite (NaClO), to provide a reference for clinical application.@*Methods@#This study was approved by the ethics review committee. Sixty-three human premolars extracted for orthodontic treatment were randomly divided into a control group (distilled water group) and 6 experimental groups according to the different rinsing solutions used after the surface enamel was removed. The experimental groups included Group A (2.5% NaClO), Group B (5.25% NaClO), Group C (6% MCJ), Group D (2.5% NaClO-17% EDTA), Group E (5.25% NaClO-17% EDTA), and Group F (6% MCJ-17% EDTA) (n = 9). After soaking in the corresponding rinsing solution for 20 minutes, they were layered and stacked on their surfaces to form 4 mm × 4 mm × 3 mm Z350 resin blocks. Six samples from each group were cut into 1 mm × 1 mm × 8 mm specimen strips for microtensile bonding strength testing. The fracture type was determined under a stereomicroscope, and the remaining 3 samples from each group were aged and cut into 1 mm thick slices for interface nanoleakage testing and scanning electron microscopy observation of the resin dentin bonding interface.@*Results@#There were significant differences in the microtensile bonding strength among the groups (P<0.05), and the control group had the highest bonding strength. Among experimental groups, Group B had the lowest bonding strength, mainly bonding interface fracture, and Group F had the highest bonding strength, mainly mixed fracture. There were significant differences in nanoleakage among all groups (P<0.05), and the control group had the lowest nanoleakage value. Among experimental groups, Group B had the highest nanoleakage, with resin protrusions being unaltered, and Group F had the lowest nanoleakage value, with resin protrusions being thick and dense.@*Conclusion@#The higher the concentration of NaClO was, the worse the bonding strength and edge sealing of the crown dentin were. The effects of root canal irrigation with MCJ and EDTA on the adhesive strength and edge sealing of crown dentin were less pronounced than those of root canal irrigation with NaClO and EDTA.