Enhanced Cd2+ removal from aqueous solution using olivine and magnesite combination: New insights into the mechanochemical synergistic effect.

In this study, an efficient stabilizer material for cadmium (Cd2+) treatment was successfully prepared by simply co-milling olivine with magnesite. Several analytical methods including XRD, TEM, SEM and FTIR, combined with theoretical calculations (DFT), were used to investigate mechanochemical interfacial reaction between two minerals, and the reaction mechanism of Cd removal, with ion exchange between Cd2+ and Mg2+ as the main pathway. A fixation capacity of Cd2+ as high as 270.61 mg/g, much higher than that of the pristine minerals and even the individual/physical mixture of milled olivine and magnesite, has been obtained at optimized conditions, with a neutral pH value of the solution after treatment to allow its direct discharge. The as-proposed Mg-based stabilizer with various advantages such as cost benefits, green feature etc., will boosts the utilization efficiency of natural minerals over the elaborately prepared adsorbents.

Unveiling the Promoting Mechanism of H2 Activation on CuFeOx Catalyst for Low-Temperature CO Oxidation.

The effect of H2 activation on the performance of CuFeOx catalyst for low-temperature CO oxidation was investigated. The characterizations of XRD, XPS, H2-TPR, O2-TPD, and in situ DRIFTS were employed to establish the relationship between physicochemical property and catalytic activity. The results showed that the CuFeOx catalyst activated with H2 at 100 °C displayed higher performance, which achieved 99.6% CO conversion at 175 °C. In addition, the H2 activation promoted the generation of Fe2+ species, and more oxygen vacancy could be formation with higher concentration of Oα species, which improved the migration rate of oxygen species in the reaction process. Furthermore, the reducibility of the catalyst was enhanced significantly, which increased the low-temperature activity. Moreover, the in situ DRIFTS experiments revealed that the reaction pathway of CO oxidation followed MvK mechanism at low temperature (<175 °C), and both MvK and L-H mechanism was involved at high temperature. The Cu+-CO and carbonate species were the main reactive intermediates, and the H2 activation increased the concentration of Cu+ species and accelerated the decomposition carbonate species, thus improving the catalytic performance effectively.

Natural Killer-Based Therapy: A Prospective Thought for Cancer Treatment Related to Diversified Drug Delivery Pathways.

Immunotherapy has been a research hotspot due to its low side effects, long-lasting efficacy, and wide anti-tumor spectrum. Recently, NK cell-based immunotherapy has gained broad attention for its unique immunological character of tumor identification and eradication and low risk of graft-versus-host disease and cytokine storm. With the cooperation of a drug delivery system (DDS), NK cells activate tumoricidal activity by adjusting the balance of the activating and inhibitory signals on their surface after drug-loaded DDS administration. Moreover, NK cells or NK-derived exosomes can also be applied as drug carriers for distinct modification to promote NK activation and exert anti-tumor effects. In this review, we first introduce the source and classification of NK cells and describe the common activating and inhibitory receptors on their surface. Then, we summarize the strategies for activating NK cells in vivo through various DDSs. Finally, the application prospects of NK cells in tumor immunotherapy are also discussed.

Automated Radiosynthesis of [18F]FluoFAPI and Its Dosimetry and Single Acute Dose Toxicological Evaluation.

BACKGROUND: Cancer-associated fibroblasts have become a new target for therapy. Fibroblasts present within malignancies express the fibroblast activation protein (FAP). Inhibitors to FAP (FAPI) are small molecules recently developed as a theranostic agents for imaging and radiotherapy. All currently used FAPI rely on a linker-chelator complex attached to the 'inhibitor'. We describe a new automated method of the direct attachment of the radioisotope to the inhibitor, resulting in a >50% MW reduction with the hope of an improved tumor-to-background ratio and tumor uptake. METHODS: [18F]FluroFAPI was developed from a Sn precursor. This allowed for subsequent automated radioflourination. We obtained the biodistribution of [18F]FluroFAPI in rats, performed estimated human radiation dosimetry, and performed a 100× expected single dose toxicology analysis for eventual first-in-human experiments. RESULTS: The synthesis of the Sn precursor for FluorFAPI and the automated synthesis of [18F]FluroFAPI was demonstrated. [18F]FluroFAPI had favorable estimated human radiation dosimetry, and demonstrated no adverse effects when injected at a dose of 100× that planned for [18F]FluroFAPI. CONCLUSIONS: With the successful development of an automated synthesis of [18F]FluroFAPI, first-in-human testing can be planned with the hope of an improved tumor-to-background performance compared to other FAPI agents.

Assessing the Post-Activation Performance Enhancement of Upper Limbs in Basketball Athletes: A Sensor-Based Study of Rapid Stretch Compound and Blood Flow Restriction Training.

OBJECTIVE: This study introduces a novel methodology combining rapid stretch compound training with blood flow restriction (BFR) to investigate post activation performance enhancement (PAPE) in basketball players, a field that has been predominantly explored for lower limbs. We aimed to assess the efficacy of this combined approach on upper limb muscle performance in athletes. METHODS: We employed a randomized, self-controlled crossover trial with ten male basketball players. The bench press throw (BPT) served as the primary metric, with players undergoing four interventions post-baseline: (1) STR-plyometric training; (2) BFR-blood flow restriction; (3) COMB-STR integrated with BFR; and (4) CON-control. Innovatively, we utilized an intelligent tracking sensor to precisely measure peak power (PP), peak velocity (PV), mean power (MP), and mean velocity (MV) at 4, 8, and 12 min post-intervention, providing a detailed temporal analysis of PAPE. RESULTS: The COMB intervention demonstrated superior PAPE effects at 4 min, significantly outperforming STR and BFR alone and the control group across all measured indices (p < 0.05). Notably, the COMB group maintained these improvements for PV, PP, and H up to 12 min post-intervention, suggesting a prolonged effect. CONCLUSION: (1) The COMB stimulation has been shown to successfully induce PAPE more effectively than STR and BFR modality alone. (2) It appears that the optimal effects of PAPE are achieved within 4 min of exercising under this COMB. By the 12 min mark, only the COMB group continued to show significant improvements in PV, PP, and H compared to both the baseline and the CON group, while the effects in the STR and BFR groups further diminished. This suggests that although the PAPE effect is maintained over time, its optimal performance may peak at the 4 min mark and then gradually weaken as time progresses.

High-Performance Binocular Disparity Prediction Algorithm for Edge Computing.

End-to-end disparity estimation algorithms based on cost volume deployed in edge-end neural network accelerators have the problem of structural adaptation and need to ensure accuracy under the condition of adaptation operator. Therefore, this paper proposes a novel disparity calculation algorithm that uses low-rank approximation to approximately replace 3D convolution and transposed 3D convolution, WReLU to reduce data compression caused by the activation function, and unimodal cost volume filtering and a confidence estimation network to regularize cost volume. It alleviates the problem of disparity-matching cost distribution being far away from the true distribution and greatly reduces the computational complexity and number of parameters of the algorithm while improving accuracy. Experimental results show that compared with a typical disparity estimation network, the absolute error of the proposed algorithm is reduced by 38.3%, the three-pixel error is reduced to 1.41%, and the number of parameters is reduced by 67.3%. The calculation accuracy is better than that of other algorithms, it is easier to deploy, and it has strong structural adaptability and better practicability.

Single Image Super-Resolution via Wide-Activation Feature Distillation Network.

Feature extraction plays a pivotal role in the context of single image super-resolution. Nonetheless, relying on a single feature extraction method often undermines the full potential of feature representation, hampering the model's overall performance. To tackle this issue, this study introduces the wide-activation feature distillation network (WFDN), which realizes single image super-resolution through dual-path learning. Initially, a dual-path parallel network structure is employed, utilizing a residual network as the backbone and incorporating global residual connections to enhance feature exploitation and expedite network convergence. Subsequently, a feature distillation block is adopted, characterized by fast training speed and a low parameter count. Simultaneously, a wide-activation mechanism is integrated to further enhance the representational capacity of high-frequency features. Lastly, a gated fusion mechanism is introduced to weight the fusion of feature information extracted from the dual branches. This mechanism enhances reconstruction performance while mitigating information redundancy. Extensive experiments demonstrate that the proposed algorithm achieves stable and superior results compared to the state-of-the-art methods, as evidenced by quantitative evaluation metrics tests conducted on four benchmark datasets. Furthermore, our WFDN excels in reconstructing images with richer detailed textures, more realistic lines, and clearer structures, affirming its exceptional superiority and robustness.

Positional Analysis of Assisting Muscles for Handling-Assisted Exoskeletons.

In order to better design handling-assisted exoskeletons, it is necessary to analyze the biomechanics of human hand movements. In this study, Anybody Modeling System (AMS) simulation was used to analyze the movement state of muscles during human handling. Combined with surface electromyography (sEMG) experiments, specific analysis and verification were carried out to obtain the position of muscles that the human body needs to assist during handling. In this study, the simulation and experiment were carried out for the manual handling process. A treatment group and an experimental group were set up. This study found that the vastus medialis muscle, vastus lateralis muscle, latissimus dorsi muscle, trapezius muscle, deltoid muscle and triceps brachii muscle require more energy in the process of handling, and it is reasonable and effective to combine sEMG signals with the simulation of the musculoskeletal model to analyze the muscle condition of human movement.

Macrophage Activation Syndrome in Viral Sepsis.

Macrophage activation syndrome (MAS) is a life-threatening systemic hyperinflammatory syndrome triggered by various infections, particularly viral infections, autoimmune disorders, and malignancy. The condition is characterized by an increased production of proinflammatory cytokines resulting in a cytokine storm and has been associated with poor clinical outcomes. During the COVID-19 pandemic, patients with severe manifestations developed features similar to those of MAS, although these characteristics remained well defined within the lung. Additionally, other viral infections including EBV, the herpes family of viruses, hepatitis viruses, influenza, HIV, and hemorrhagic fevers can be complicated by MAS. The diagnosis and management of the condition remain challenging due to the lack of consensus on specific guidelines, especially among the adult population. Currently, therapeutic options primarily rely on medications that are typically used to treat primary hemophagocytic lymphohistiocytosis, such as corticosteroids and etoposide. In addition, cytokine-targeted therapies present promising treatment options. The objective of this review is to discuss the emergence of MAS in the context of viral infections including, but not limited to, its occurrence in COVID-19.

Facilitating the Hydrogen Evolution Reaction on Basal-Plane S Sites on MoS2@Ni3S2 by Dual Ti and N Plasma Treatment.

Atomic engineering of the basal plane active sites in MoS2 holds great promise to boost the electrocatalytic activity for hydrogen evolution reactions (HER), yet the performance optimization and mechanism exploration are still not satisfactory. Herein, we proposed a dual-plasma engineering strategy to implant Ti and N heteroatoms into the basal plane of MoS2 supported by Ni3S2 nanorods on nickel foam (MSNF) for efficient electrocatalysis of HER. Owing to the low formation energy of Ti dopants in MoS2 and the extra charge carriers introduced by N dopants, the optimally codoped samples N1.0@Ti500-MSNF demonstrate significant morphology changes from nanorods to urchin-like nanospheres with the surface active areas increased by seven-fold, as well as enhanced electrical conductivity in comparison with the nondoped counterparts. The HER performance of N1.0@Ti500-MSNF is comparable with the Pt-based catalyst: overpotential of 26 mV at 20 mA cm-2, Tafel slope of 35.6 mV dec-1, and long-term stability over 50 h. First-principles calculation reveals that N doping accelerates the dissociation of water molecules while Ti doping activates the adjacent S sites for hydrogen adsorption by lowering the Gibbs free energy, resulting in excellent HER activity. This work thus provides an effective strategy for basal plane engineering of MoS2 heterostructures toward high-performance HER and sustainable energy supply at reasonable costs.

Utility of OLIG2 immunostaining in pediatric brain tumors with embryonal morphology.

This study evaluates the diagnostic utility of OLIG2 immunohistochemistry for distinguishing between pediatric high-grade gliomas (pHGG) and embryonal tumors (ETs) of the CNS. Utilizing a retrospective pediatric cohort (1990-2021) of 56 CNS tumors, classified initially as primitive neuroectodermal tumors or CNS ET, we reclassified the cases based on WHO CNS5 criteria after comprehensive review and additional molecular testing that included next-generation sequencing and DNA methylation profiling. Our results indicate that OLIG2 immunopositivity was negative or minimal in a significant subset of pHGG cases (6 out of 11). At the same time, it showed diffuse expression in all cases of CNS neuroblastomas with FOXR2 activation (5/5), demonstrating its limited specificity in differentiating between pHGG and ET. Variable OLIG2 expression in other ETs, ATRT, and ETMR suggests the broader diagnostic implications of the marker. Furthermore, incidental findings of OLIG2 positivity in cases traditionally expected to be negative, such as medulloblastoma and ependymoma, introduce an additional layer of complexity. Together, these findings highlight the challenges of relying solely on OLIG2 immunostaining for accurate tumor classification in pediatric CNS neoplasms and underscore the importance of an integrated diagnostic approach.

Near-field detection and peak frequency metric for substrate and activation mapping of ventricular tachycardias in two- and three-dimensional circuits.

AIMS: Successful ventricular arrhythmia (VA) ablation requires identification of functionally critical sites during contact mapping. Estimation of the peak frequency (PF) component of the electrogram (EGM) may improve correct near-field (NF) annotation to identify circuit segments on the mapped surface. In turn, assessment of NF and far-field (FF) EGMs may delineate the three-dimensional path of a ventricular tachycardia (VT) circuit. METHODS AND RESULTS: A proprietary NF detection algorithm was applied retrospectively to scar-related re-entry VT maps and compared with manually reviewed maps employing first deflection (FDcorr) for VT activation maps and last deflection (LD) for substrate maps. Ventricular tachycardia isthmus location and characteristics mapped with FDcorr vs. NF were compared. Omnipolar low-voltage areas, late activating areas, and deceleration zones (DZ) in LD vs. NF substrate maps were compared. On substrate maps, PF estimation was compared between isthmus and bystander sites. Activation mapping with entrainment and/or VT termination with radiofrequency (RF) ablation confirmed critical sites. Eighteen patients with high-density VT activation and substrate maps (55.6% ischaemic) were included. Near-field detection correctly located critical parts of the circuit in 77.7% of the cases compared with manually reviewed VT maps as reference. In substrate maps, NF detection identified deceleration zones in 88.8% of cases, which overlapped with FDcorr VT isthmus in 72.2% compared with 83.3% overlap of DZ assessed by LD. Applied to substrate maps, PF as a stand-alone feature did not differentiate VT isthmus sites from low-voltage bystander sites. Omnipolar voltage was significantly higher at isthmus sites with longer EGM durations compared with low-voltage bystander sites. CONCLUSION: The NF algorithm may enable rapid high-density activation mapping of VT circuits in the NF of the mapped surface. Integrated assessment and combined analysis of NF and FF EGM-components could support characterization of three-dimensional VT circuits with intramural segments. For scar-related substrate mapping, PF as a stand-alone EGM feature did not enable the differentiation of functionally critical sites of the dominant VT from low-voltage bystander sites in this cohort.

The role of basophil activation test in venom immunotherapy: comparative evaluation with specific IgE and skin prick tests, innovative approaches.

Summary: Background. In diagnosing insect venom allergy and making immunotherapy decisions, clinical history, skin tests, and specific serum IgE levels are commonly utilized. This study aims to emphasize the clinical significance of using the basophil activation test in accurately identifying sensitivities in individuals with insect venom allergy and to compare its effectiveness with other testing methods. Methods. This study included a total of 43 patients, who experienced at least one systemic allergic reaction following insect stings and were deemed suitable for immunotherapy.Basophil activation test, specific serum IgE levels, and skin prick test results utilized in making immunotherapy treatment decisions were recorded. Results. Our study determined that the overall clinical sensitivities of the basophil activation test (BAT), specific serum IgE (spIgE), and skin prick test (SPT) for apis mellifera were 95.5%, 95.7%, and 48.4% respectively, while for vespula vulgaris, they were 83.3%, 100%, and 33.3%. Based on these results, the prediction of systemic reactions to bee stings is ordered as spIgE > BAT > SPT. Additionally, early-stage skin prick tests showed a sensitivity of 67% and specificity of 50% at a cut-off value of 1.5 mm, and 33% sensitivity and 83% specificity at 2.5 mm. Conclusions. This study demonstrates that the basophil activation test (BAT) can provide a high positive predictive value in immunotherapy treatment decisions and offer significant insights in clinical practices.

Functional characterization of complete and immunodominant epitopes of a novel pollen allergen from Parthenium hysterophorus.

Summary: .Background. Parthenium hysterophorus pollen induces chronic clinical conditions such as allergic rhinitis and bronchial asthma. Among the plethora of proteins in the pollens, only few were reported to induce allergy. Currently sensitization to P. hysterophorus pollen allergen is diagnosed by skin prick test (SPT) using the entire pollen extract instead of using the specific allergen. Methods. In P. hysterophorus sensitized patients, SPT was done using the crude pollen extract, 40 kDa allergenic pollen protein and two commercially synthesized allergen epitopes (17 and 24) of P. hysterophorus. Dot-blot of allergen epitopes was done using P. hysterophorus sensitized sera. Crude pollen extract (1, 1.25, 2.5, 5 and 10 µg/mL), 40 kDa allergenic protein (3 µg/mL), and allergen epitopes (3µg/mL) were used to perform Basophil Activation Test (BAT). Results. Crude pollen extract at 2.5, 5, 10 µg/mL and 40 kDa allergenic protein at 3µg/mL concentrations induced wheal and flare reaction by around 15 minutes, whereas commercially synthesized allergen epitopes at 3µg/mL induced wheal and flare reactions in less than 10 minutes. Allergen epitopes (3 µg/mL) revealed strong reactivity with sensitized patient's IgE in dot-blot analysis. Basophil activation Test using crude pollen extract (2.5, 5, 10 µg/mL), 40 kDa allergenic protein (3 µg/mL), and allergenic epitopes (3µg/mL) indicated significant basophil activation (as measured by CD63 expression) in sensitized patients. Conclusions. The 40 kDa allergenic protein and its allergenic epitopes (17 and 24) induced phenotypic and cellular immune responses in P. hysterophorus sensitized individuals. The tested allergenic epitopes (17 and 24) induced faster wheal and flare reactions in comparison with the crude extract and the 40 kDa allergenic protein. The novel 40kDa allergenic protein and its allergen epitopes identified here may be useful for the development of component-resolved diagnosis (CRD) while also serving as a potential therapeutic lead for desensitization treatment for P. hysterophorus pollen induced allergy.

The role of saliency maps in enhancing ophthalmologists' trust in artificial intelligence models.

PURPOSE: Saliency maps (SM) allow clinicians to better understand the opaque decision-making process in artificial intelligence (AI) models by visualising the important features responsible for predictions. This ultimately improves interpretability and confidence. In this work, we review the use case for SMs, exploring their impact on clinicians' understanding and trust in AI models. We use the following ophthalmic conditions as examples: (1) glaucoma, (2) myopia, (3) age-related macular degeneration, and (4) diabetic retinopathy. METHOD: A multi-field search on MEDLINE, Embase, and Web of Science was conducted using specific keywords. Only studies on the use of SMs in glaucoma, myopia, AMD, or DR were considered for inclusion. RESULTS: Findings reveal that SMs are often used to validate AI models and advocate for their adoption, potentially leading to biased claims. Overlooking the technical limitations of SMs, and the conductance of superficial assessments of their quality and relevance, was discerned. Uncertainties persist regarding the role of saliency maps in building trust in AI. It is crucial to enhance understanding of SMs' technical constraints and improve evaluation of their quality, impact, and suitability for specific tasks. Establishing a standardised framework for selecting and assessing SMs, as well as exploring their relationship with other reliability sources (e.g. safety and generalisability), is essential for enhancing clinicians' trust in AI. CONCLUSION: We conclude that SMs are not beneficial for interpretability and trust-building purposes in their current forms. Instead, SMs may confer benefits to model debugging, model performance enhancement, and hypothesis testing (e.g. novel biomarkers).

Activity flow under the manipulation of cognitive load and training.

Flexible cognitive functions, such as working memory (WM), usually require a balance between localized and distributed information processing. However, it is challenging to uncover how local and distributed processing specifically contributes to task-induced activity in a region. Although the recently proposed activity flow mapping approach revealed the relative contribution of distributed processing, few studies have explored the adaptive and plastic changes that underlie cognitive manipulation. In this study, we recruited 51 healthy volunteers (31 females) and investigated how the activity flow and brain activation of the frontoparietal systems was modulated by WM load and training. While the activation of both executive control network (ECN) and dorsal attention network (DAN) increased linearly with memory load at baseline, the relative contribution of distributed processing showed a linear response only in the DAN, which was prominently attributed to within-network activity flow. Importantly, adaptive training selectively induced an increase in the relative contribution of distributed processing in the ECN and also a linear response to memory load, which were predominantly due to between-network activity flow. Furthermore, we demonstrated a causal effect of activity flow prediction through training manipulation on connectivity and activity. In contrast with classic brain activation estimation, our findings suggest that the relative contribution of distributed processing revealed by activity flow prediction provides unique insights into neural processing of frontoparietal systems under the manipulation of cognitive load and training. This study offers a new methodological framework for exploring information integration versus segregation underlying cognitive processing.

Associations of cognitive appraisal and patient activation on disability and mental health outcomes: a prospective cohort study of patients undergoing spine surgery.

BACKGROUND: With the increased use of patient-reported outcomes measures (PROMs) to assess spine surgery outcomes, it is important to understand how patients interpret their health changes over time. The measurement of cognitive-appraisal processes enables the quantification of how individuals think about quality of life (QOL). This study examined how appraisal processes were associated with patients' views of their role in managing their health-patient activation. METHODS: This longitudinal cohort study from August 2019 to January 2022 included 222 adults undergoing spine surgery for cervical (n = 107) and/or lumbar (n = 148) pathology at an academic medical center. PROMs assessed disability (Neck Disability Index for cervical or Oswestry Disability Index for lumbar) and mental health (PROMIS-29 v2.0), cognitive-appraisal processes (QOLAPv2-SF), and patient activation (Patient Activation Measure). ANOVA models were used to examine the relationships between QOL and cognitive appraisal processes before and after surgery, overall and stratified by patient-activation stage. Effect sizes facilitated interpretation. RESULTS: There were significant improvements in pain-related disability and mental health following surgery. Cognitive appraisal processes explained substantial amounts of variance, particularly with changes in mental health (45% before surgery, 75% at three months, and 63%, at 12-months after surgery). With respect to physical disability, less disability was associated with a lesser focus on negative aspects of QOL. Appraisal explained the most variance before surgery for high-activation patients. At 12-months post-surgery, however, appraisal explained the most variance for the low-activation patients. Appraisal explained similar amounts of variance in mental health at baseline and three-months post-surgery for all activation groups, but substantially more variance in the low-activation group at 12-months post-surgery. There were differences in the direction of appraisal-outcome associations by activation group in selected appraisal items/domains. CONCLUSIONS: Cognitive-appraisal processes demonstrate a significant relationship with QOL among spine surgery patients. These processes explain substantial variance in pain-related disability and mental health, especially among those high in activation before surgery and those low in activation at 12-months post-surgery. Our findings suggest that patients' ways of thinking about their health may be effective targets of motivational coaching, to help them become more engaged over the recovery trajectory.

Modeling collisional kinetic energy damping, heating, and cooling of ions in mass spectrometers: a tutorial perspective.

Many powerful methods in mass spectrometry rely on activation of ions by high-energy collisions with gas particles. For example, multiple Collision Induced Dissociation (CID) has been used for many years to determine structural information for ions ranging from small organics to large, native-like protein complexes. More recently, Collision Induced Unfolding (CIU) has proved to be a very powerful method for understanding high-order protein structure and detecting differences between similar proteins. Quantifying the thermochemistry underlying dissociation/unfolding in these experiments can be quite challenging without reliable models of ion heating and cooling. Established physical models of CID are valuable in predicting ion heating but do not explicitly include mechanisms for cooling, which may play a large part in CID/CIU in modern instruments. Ab initio and Molecular Dynamics methods are extremely computationally expensive for modeling CID/CIU of large analytes such as biomolecular ions. In this tutorial perspective, limiting behaviors of ion kinetic energy damping, heating, and cooling set by "extreme" cases are explored, and an Improved Impulsive Collision Theory and associated software ("Ion Simulations of the Physics of Activation", IonSPA) are introduced that can model all of these for partially inelastic collisions. Finally, examples of modeled collisional activation of native-like protein ions under realistic experimental conditions are discussed, with an outlook toward the use of IonSPA in accessing the thermochemical information hidden in CID breakdown curves and CIU fingerprints.

In vitro and in vivo analyses of eFAP: a novel FAP-targeting small molecule for radionuclide theranostics and other oncological interventions.

BACKGROUND: Fibroblast activation protein (FAP), a transmembrane serine protease overexpressed by cancer-associated fibroblasts in the tumor stroma, is an interesting biomarker for targeted radionuclide theranostics. FAP-targeting radiotracers have demonstrated to be superior to [18F]FDG PET/CT in various solid cancers. However, these radiotracers have suboptimal tumor retention for targeted radionuclide therapy (TRT). We aimed to develop a novel FAP-targeting pharmacophore with improved pharmacokinetics by introducing a substitution at the 8-position of (4-quinolinoyl)-glycyl-2-cyanopyrrolidine, which allows for conjugation of a chelator, dye, or other payloads. RESULTS: Here we showed the synthesis of DOTA-conjugated eFAP-6 and sulfo-Cyanine5-conjugated eFAP-7. After chemical characterization, the uptake and specificity of both tracers were determined on FAP-expressing cells. In vitro, [111In]In-eFAP-6 demonstrated a superior affinity and a more rapid, although slightly lower, peak uptake than gold standard [111In]In-FAPI-46. Confocal microscopy demonstrated a quick FAP-mediated internalization of eFAP-7. Studies with HT1080-huFAP xenografted mice confirmed a more rapid uptake of [177Lu]Lu-eFAP-6 vs. [177Lu]Lu-FAPI-46. However, tumor retention at 24 h post injection of [177Lu]Lu-eFAP-6 was lower than that of [177Lu]Lu-FAPI-46, hereby currently limiting its use for TRT. CONCLUSION: The superior affinity and faster tumor accumulation of eFAP-6 over FAPI-46 makes it a suitable compound for radionuclide imaging. After further optimization, the eFAP series has great potential for various oncological interventions, including fluorescent-guided surgery and effective targeted radionuclide theranostics.

Water-mediated active conformational transitions of lipase on organic solvent interfaces.

When it comes to enzyme stability and their application in organic solvents, enzyme biocatalysis has emerged as a popular substitute for conventional chemical processes. However, the demand for enzymes exhibiting improved stability remains a persistent challenge. Organic solvents can significantly impacts enzyme properties, thereby limiting their practical application. This study focuses on Lipase Thermomyces lanuginose, through molecular dynamics simulations and experiments, we quantified the effect of different solvent-lipase interfaces on the interfacial activation of lipase. Revealed molecular views of the complex solvation processes through the minimum distance distribution function. Solvent-protein interactions were used to interpret the factors influencing changes in lipase conformation and enzyme activity. We found that water content is crucial for enzyme stability, and the optimum water content for lipase activity was 35 % in the presence of benzene-water interface, which is closely related to the increase of its interfacial activation angle from 78° to 102°. Methanol induces interfacial activation in addition to significant competitive inhibition and denaturation at low water content. Our findings shed light on the importance of understanding solvent effects on enzyme function and provide practical insights for enzyme engineering and optimization in various solvent-lipase interfaces.