Specific Activity Levels Research Articles

Enhanced Peroxidase-like Activity of Ruthenium-Modified Single-Atom-Thick A Layers in MAX Phases for Biomedical Applications.

Nanozymes have demonstrated significant potential as promising alternatives to natural enzymes in biomedical applications. However, their lower catalytic activity compared to that of natural enzymes has limited their practical utility. Addressing this challenge necessitates the development of innovative enzymatic systems capable of achieving specific activity levels of natural enzymes. In this study, we focus on enhancing the catalytic performance of nanozymes by introducing Ru atoms into the single-atom-thick A layer of the V2SnC MAX phase, resulting in the formation of V2(Sn0.8Ru0.2)C with Ru single-atom sites. The V2(Sn0.8Ru0.2)C MAX phase demonstrated an exceptional peroxidase-like specific activity of up to 1792.6 U mg-1, surpassing the specific activity of a previously reported horseradish peroxidase (HRP). Through X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) investigations, it has been revealed that both the V2C atom layers and single-atom-thick Sn readily accept a negative charge from Ru, leading to a reduction of the energy barrier for H2O2 adsorption. This discovery has enabled the successful application of V2(Sn0.8Ru0.2)C in the development of a lateral flow immunoassay for heart failure biomarkers, achieving a detection sensitivity of 4 pg mL-1. Additionally, V2(Sn0.8Ru0.2)C demonstrated exceptional broad-spectrum antibacterial efficacy. This study lays the groundwork for the precise design of MAX phase-based nanozymes with high specific activity, offering a viable alternative to natural enzymes for various applications.

Tritium content in water bodies in regions of peaceful nuclear explosions

Sites of peaceful nuclear explosions pose a potential radiation hazard to the territories of the Russian Federation, primarily due to the possible release of radioactivity from the explosion cavity into aquifers and onto the earth's surface. Therefore, it is essential to conduct regular monitoring of anthropogenic radionuclides in drinking water sources in settlements located near the sites of peaceful nuclear explosions. Tritium serves as an indicator of the potential release of other anthropogenic radionuclides. Monitoring its levels in water bodies in regions where peaceful nuclear explosions were perfomed, and comparing this data with that from Roshydromet across the Russian Federation, allows for an assessment of the reliability of the engineering barriers between the central explosion zone and the environment with respect to preventing radionuclide migration into aquifers. One method for evaluating the reliability of these barriers is the assessment of tritium specific activity in drinking water sources. This article presents results of the study involving 220 water samples collected from drinking water sources (wells, boreholes, springs, central water supply systems) and surface waters within 167 settlements across 17 subjects of the Russian Federation, where 50 peaceful nuclear explosions were conducted between 1965 and 1988. The samples were collected between May and September 2024 in the settlements within a 30 km radius of a peaceful nuclear explosion site. Measurements of tritium specific activity were performed using the Quantulus 1220-003 alpha-beta spectrometric radiometer. The research revealed that the specific activity of tritium in underground water sources is significantly lower (Student's test p<0,05) than in surface waters. The average specific activity levels of tritium in boreholes, rivers, and lakes were 3.0, 3.45, and 4.31 Bq/kg, respectively. The specific activity of tritium in drinking water sources within the regions of peaceful nuclear explosions was found to be at the background levels recorded by Roshydromet, ranging from 1.1 to 5 Bq/kg.

Measurement of radioactivity and hazard index of Gonadal dose in selected Cement samples in Iraq.

Given the importance of cement as a basic material in construction, this study was undertaken to evaluate the level of radioactivity in a selected group of cement samples most used in construction to determine whether they are safe for human health. In this investigative study, nine samples of cement, both domestic and imported, that are often used in construction projects in Iraq were gathered. A NaI (Tl) gamma-ray spectrometer (3"x3") was used to measure the radioactivity in the samples. The average specific activity levels in the tested cement samples were 11.373±0.522, 5.795 ± 0.230, and 179.123±2.207 Bq/Kg, respectively. Also calculated was the average of the radium, which was equivalent to 33.449±1.022 Bq/kg. As for the risk indicators, the internal risk coefficient was 0.121±0.004 and external risk coefficient was 0.090 ±0.002. While studying the radiation doses, the values of effective annual internal dose was 0.080 mSv/y, external dose rates were 0.020 mSv/y, absorbed dose ratio was 16.321±0.476 nGy/h, and gamma index was 0.253±0.007. In the end, and depending on what was studied from various variables, with an average of 115.59 Sv/y, the annual gonadal equivalent dose risk (AGED) was calculated. The world average values were used to compare all the results. Finally, it was discovered that the radiation parameter levels of none of the samples had a detrimental effect on human health.

External redox couple enhanced anammox sludge activity at low temperature: Insight into intracellular resource synthesis

Anaerobic ammonium oxidation (anammox), an energy-efficient deamination biotechnology, faces operational challenges in low-temperature environments. Enhancing the metabolic activity of anammox bacteria (AnAOB) is pivotal for advancing its application in mainstream municipal wastewater treatment. Inspired by the metabolic adaptability of AnAOB and based on our previous findings, this work investigated the enhancement of intracellular ATP and NADH synthesis through the exogenous supply of reduced humic acid (HAred) and H2O2 redox couple, aiming to augment AnAOB activity under low-temperature conditions. Our experimental setup involved continuous dosing of 0.0067 μmol g-1 volatile suspended solid of H2O2 and 10 mg g-1 volatile suspended solid of HAred into a mainstream anammox reactor operated at 15 °C with an influent TN content of 60 mg/L. The results showed that HAred / H2O2 couple succeeded in maintaining the effluent TN at 10.72 ± 0.91 mg l-1. The specific anammox activity, ATP and NADH synthesis levels of sludge increased by 1.34, 2.33 and 6.50 folds, respectively, over the control setup devoid of the redox couple. High-throughput sequencing analysis revealed that the relative abundance of Candidatus Kuenenia after adding HAred / H2O2 couple reached 3.65 % at the end of operation, which was 5.14 folds higher than that of the control group. Further metabolomics analysis underscored an activation in the metabolism of amino acids, nucleotides, and phospholipids, which collectively enhanced the availability of ATP and NADH for the respiratory processes. These findings may provide guidance on strategy development for improving the electron transfer efficiency of AnAOB and underscore the potential of using redox couples to promote the mainstream application of anammox technology.

Calculate the Rate of Natural Radioactivity in the Soil of Some Schools Using the NaI(Tl) Detector in the City of Hilla-Iraq

Activities and risk markers in 15-20 cm soil samples from Hilla City schools were thoroughly examined. This was made possible by the NaI(Tl) detector. The results indicated that the specific activity values for 238U from 2.244±0.06 Bqkg-1 to 23.637±0.60 Bqkg-1, with an average value of 11.70±0.39 Bqkg-1. Similar to 232Th, the average specific activity level was 8.53±0.31 Bqkg-1, ranging between 1.603±0.09 Bqkg-1 and 21.503±0.56 Bqkg-1. For 40K, its specific activity range was 222.96±2.72 to 441.824±2.78 Bqkg-1, with an average of 375.32±2.71 Bqkg-1. The average radiative forcing of the radium equivalent (Raeq) was calculated to be 52.80 Bqkg-1. The external risk index (Hex) was 0.14, and the internal risk index (Hin) was 0.17. The gamma risk index (Iγ) was determined to be 0.41. Also, the average outdoor absorbed dose level Dout is 26.35 nGyh-1, while the average indoor absorbed dose level Din is 50.54 nGyh-1. The average annual values of effective dose equivalents (internal and external) are 0.03 and 0.25 nGyh-1. The additional lifetime cancer risk ELCR(t) due to natural radioactivity in the models was 0.93x10-3. Note that the global average permissible nuclide concentration was 30, 32, and 420, and the danger index values were 1, 1, 6, 59, 84, 0.4, 0.07, and 1.45, respectively, based on the report of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). After carefully comparing the study results with permissible global averages, they fit well within the recommended range.

A Methodology to Evaluate the Real-Time Stability of Submarine Slopes under Rapid Sedimentation

Rapid sedimentation is widely recognized as a crucial factor in initiating the instability of submarine slopes. Once the slope fails, the subsequent landslide poses a significant threat to the safety of underwater infrastructures and potentially leads to severe damage to seabed pipelines, offshore foundations, and oil and gas exploitation wells. However, there is currently a lack of numerical methods to effectively assess the real-time stability of submarine slopes under rapid sedimentation. This study firstly employs a calibrated finite element (FE) model-change approach to reproduce the rapid sedimentation processes and proposes a concise method to calculate the safety factors for the real-time stability of sedimenting submarine slopes. Further, a parametric analysis is carried out to evaluate the effect of varying sedimentation rates on slope stability, and the critical sedimentation rate is numerically solved. Moreover, the effect of seismic events with different occurring times on the stability of rapidly sedimenting slopes is investigated in depth, and the most critical seismic loading pattern among various acceleration combinations is achieved. The results indicate that the presence of weak layers during sedimentation is a critical factor contributing to slope instability. The introduced rate of decrease in the safety factor proves valuable in assessing slope safety over a specific period. As the occurrence time of seismic events is delayed, the seismic resistance of the slope decreases, increasing the likelihood of shallower sliding surfaces. The findings offer insights into the mechanisms by which rapid sedimentation influences the stability of submarine slopes and provide valuable insights for predicting the potential instability of rapidly sedimenting slopes under specific seismic activity levels.

Comprehensive Analysis of Contaminants in Powdered Milk Samples Using an HPGe for γ Radiation.

Aims: This study aimed to assess the activity concentrations and cancer risk assessments of 232Th and 40K in powdered milk samples collected from various suppliers in Pakistan, considering the increasing concern about cancer risks associated with environmental radiological effects related to food consumption. Subjects and Methods: Specific activity concentrations were determined using a high-resolution, high-purity germanium γ-spectroscopy system. Results: The specific activity levels of 40K and 232Th in the analyzed powdered milk samples were found to be 230.86 and 6.87 Bq/kg, respectively, well within the safe limits recommended by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). The hazard index (0.074 Bq/kg) and radium equivalent (27.58 Bq/kg) were calculated as indicators of radiation hazard, along with absorbed dose (26.26 nGy/h), annual effective dose (0.13 nGy/h), and excess lifetime cancer risk (0.45). These parameters provide insights into the potential health risks associated with powdered milk consumption. Conclusions: The findings collectively affirm the radiological safety of the analyzed powdered milk samples, providing valuable insights into the potential health risks associated with their consumption.

BRAIN AND CREATIVITY

Great ideas seem to come out of nowhere. Now we are one step closer to understanding how they appear. The areas responsible for language and creativity are thought to compete in the brain, which may explain why some people with brain damage suddenly become artists. Originality - or the ability to think of new ideas that do not occur to many people - is the key aspect of creativity. Researchers are trying to determine the mechanism by which originality is established. While creativity is generated by the right hemisphere of the brain, it is suppressed by language-specific processes in the left hemisphere: “Language regions may compete with the right hemisphere's ability to produce creative ideas.” This would explain why when areas responsible for language processing are affected, originality appears to increase. A brilliant idea is not enough to qualify a person as creative. Creativity is among the human characteristics whose mysteries we are still trying to understand. It seems almost impossible to find a clear definition for it, and it is equally difficult to look for its origins in the human brain. Many researchers define creativity as a special performance that is both new and appropriate. If we look at creativity as a concept rather than a trait, a number of factors must be considered. For example, an ingenious idea must be realized in such a way that it is visible and useful to others. Only a person who succeeds in this can truly be called creative. Creativity is a complex process that requires the activation of several areas of the brain. So far it is not clear whether creativity requires a specific neural architecture or not. At the root of all thoughts, emotions and behaviors is communication between neurons. Brain waves are the products of synchronized electrical impulses resulting from the communication of masses of neurons. The speed of brain waves is measured in Hz and are divided into categories that delineate slow, moderate and fast waves. They change according to activities or feelings. The electroencephalograph measures brain waves of different frequencies in the brain by using sensors placed on the scalp, the frequency representing the recurrence of a wave in one second. If any of these frequencies are deficient, excessive or difficult to access, psychic performance can suffer. Learning about brain waves and brain wave frequencies is key to understanding how to navigate and reprogram the mind, and to access deeper levels of consciousness. In neuroscience, there are five distinct brainwave frequencies, namely Beta waves, Alpha waves, Theta waves, Delta waves, and Gamma waves. Each frequency has its own set of characteristics representing a specific level of brain activity and a corresponding unique state of consciousness.

Accumulation of Technogenic and Natural Radionuclides in the Don Delta Sediments

The study of current sedimentation processes and radioactive contamination in the total area of the Don Delta is the research goal. The presented paper contains data analysis of radioecological and lithologic studies on bottom sediments, sampled in the northern part of the Don Delta in 2022. Based on the research results obtained, the authors provide the characteristics of the current conditions of sedimentation and specific activity of artificial and natural radionuclides in fluvial deposits, as well as indicate that similar in characteristics sandy-silty aleurites and sandy aleurite-clayish silts with inclusions of plant and shell detritus compose the bottom sediments of numerous braided channels. The authors determined the zonal accumulation character of both 137Cs technogenic and 226Ra, 40K, and 232Th natural radionuclides which conditions their accumulation and content increase from the lower delta to the upper delta areas. The velocity of currents in the braided channels (bayous) and related sedimentation conditions of suspended matter, as well as the lithotype of the bottom ground determine the indicated regularity. We assume that unlike 137Cs the distribution of natural radionuclides (40K, 226Ra, and 232Th) mainly depends on the mineral content of sediments entering the delta with the river runoff. Relatively low indices – on average ca. 9 Bq/kg of dry weight (d.w.) – characterise the current range of 137Cs radioisotope concentrations in the sediments of the Northern Don Delta. Such a level of specific activity is of no danger to the regional ecosystem.

Characterization of Extracellular Chitinase from Bacillus cereus SAHA 12.13 and Its Potency as a Biocontrol of Curvularia affinis

Bacillus cereus SAHA 12.13 can produce chitinase, an enzyme that digests chitin in the main compounds of cell walls, mycelia, and spores in pathogenic fungi that cause leaf spots on oil palm plants such as Curvularia affinis. This study aims to determine the properties of the chitinase enzyme B. cereus SAHA 12.13 that can inhibit the growth of C. affinis. Chitinase enzyme production and characterization were measured using the Spindler method. Antagonism test against pathogenic fungi using dual culture method by testing cell culture and enzyme crude extract. This result showed that the isolate produced a high level of specific chitinase activity at 37 °C for 45 h of incubation with 8.45 U mg-1 proteins with a growth rate (k) of 0.25 generation/h, and the generation time was 3.96 h/generation. The optimum chitinase activity was achieved at pH 7.0 and 45 °C and was stable for 3 h with a half-life (t1/2) of 770 min. The crude enzyme and cell culture of strain can inhibit the growth of C. affinis by 36.27±0.043% and 34.25±0.041%, respectively. These characteristics indicate that B. cereus strain SAHA12.13 can be used to inhibit C. affinis, which causes leaf blight of oil palm, under varying pH and temperature conditions.

Conversion of the CG specific M.MpeI DNA methyltransferase into an enzyme predominantly methylating CCA and CCC sites.

We used structure guided mutagenesis and directed enzyme evolution to alter the specificity of the CG specific bacterial DNA (cytosine-5) methyltransferase M.MpeI. Methylation specificity of the M.MpeI variants was characterized by digestions with methylation sensitive restriction enzymes and by measuring incorporation of tritiated methyl groups into double-stranded oligonucleotides containing single CC, CG, CA or CT sites. Site specific mutagenesis steps designed to disrupt the specific contacts between the enzyme and the non-substrate base pair of the target sequence (5'-CG/5'-CG) yielded M.MpeI variants with varying levels of CG specific and increasing levels of CA and CC specific MTase activity. Subsequent random mutagenesis of the target recognizing domain coupled with selection for non-CG specific methylation yielded a variant, which predominantly methylates CC dinucleotides, has very low activity on CG and CA sites, and no activity on CT sites. This M.MpeI variant contains a one amino acid deletion (ΔA323) and three substitutions (N324G, R326G and E305N) in the target recognition domain. The mutant enzyme has very strong preference for A and C in the 3' flanking position making it a CCA and CCC specific DNA methyltransferase.

Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation.

In the mammalian liver, hepatocytes exhibit diverse metabolic and functional profiles based on their location within the liver lobule. However, it is unclear whether this spatial variation, called zonation, is governed by a well-defined gene regulatory code. Here, using a combination of single-cell multiomics, spatial omics, massively parallel reporter assays and deep learning, we mapped enhancer-gene regulatory networks across mouse liver cell types. We found that zonation affects gene expression and chromatin accessibility in hepatocytes, among other cell types. These states are driven by the repressors TCF7L1 and TBX3, alongside other core hepatocyte transcription factors, such as HNF4A, CEBPA, FOXA1 and ONECUT1. To examine the architecture of the enhancers driving these cell states, we trained a hierarchical deep learning model called DeepLiver. Our study provides a multimodal understanding of the regulatory code underlying hepatocyte identity and their zonation state that can be used to engineer enhancers with specific activity levels and zonation patterns.

Radiation dangers in Iranian ceramic samples in local markets

This research aims to determine the exact levels of activity for Uranium-238, Thorium-232, and Potassium-40 in Iranian pottery samples acquired from the marketplaces of Al-Najaf governorate. The study also seeks to evaluate possible radiological dangers, such as absorbed dose rate, yearly effective dose (indoors), and the related cancer risk from these samples. The current work used NaI(Tl) gamma-ray spectroscopy with a “3× 3” dimension. The mean specific activity levels of Uranium-238, Thorium-232, and Potassium-40 were 30.44±5.22 Bq/kg, 6.35±1.11 Bq/kg, and 278.42±51.83 Bq/kg, respectively. The absorbed radiation rate, yearly effective dose (indoor), and cancer risk×10-3 were measured to be 29.51±4.86 nGy/h, 0.14±0.02 mSv/y, and 0.50±0.08, respectively. The activity levels of Uranium-238, Thorium-232, and Potassium-40 are generally lower than the global average, as reported by UNSCEAR 2008. However, there are a few samples where Uranium-238 activity exceeds the global average. All samples have radiological dangers below acceptable levels, as stated in the radiation protection publications UNSCEAR2000 and ICRP1994. Hence, the research findings are within the internationally accepted permitted limits, ensuring safety.

Effects of additional functional strength training on mobility in children with hemiplegic cerebral palsy

Background: Cerebral palsy (CP) affects the mobility and functional strength of children which leads to a decline in the quality of life of children. Functional strength training may considered objective-oriented to achieve some specific activity level and improve the overall performance of children. Objective: To determine the effects of additional functional strength training on mobility in Children with Hemiplegic Cerebral Palsy (HCP). Method: A single-blind randomized control trial (NCT05878756) was conducted on (n=40) children with hemiplegic cerebral palsy (HCP) at the National Institute of Rehabilitation Science, Islamabad. Children who can follow commands, not using assistive devices, and are not being treated in any other rehabilitation services were included. Children aged 4-12 years were recruited through a non-probability convenient sampling technique and a total of n=40 participants were randomly divided into Group A (n=20) which received conventional therapy along with functional strength training for 4 weeks, while Group B (n=20) only received conventional physical therapy. Both groups received intervention for 4weeks. The tools, Gross Motor Function Measure (GMFM) used for the severity of mobility and, five times sit to stand (FTSST) to assess functional lower extremity strength, transitional movement balance, and fall risk in older adults, were used at baseline and post-treatment assessment. Results: Both groups had improvements in strength and mobility but there was significant improvement in strength and mobility in Group A after 4th week (p≤ 0.05). However, no significant increase in the dimension of lying and kneeling was observed. Comparison between both groups (pre and post-treatment) for dimensions of walking, running, and jumping in both groups showed significant improvement (p=0.045). According to the result of GMFM scoring, a significant improvement in the interventional group (A) as compared to Group B (p=0.003). So, there is a considerable increase in GMFM score for Group A than Group B group. Conclusion: It is concluded that additional functional therapy has a better outcome as compared to conventional therapy on mobility and strength of children with CP. Keywords Cerebral palsy; functional strength training; mobility; Gross Motor Function Measure; Gross Motor Function Classification System

Serine protease homolog pairs CLIPA4-A6, A4-A7Δ, and A4-A12 act as cofactors for proteolytic activation of prophenoloxidase-2 and -7 in Anopheles gambiae

Phenoloxidase (PO) catalyzed melanization and other insect immune responses are mediated by serine proteases (SPs) and their noncatalytic homologs (SPHs). Many of these SP-like proteins have a regulatory clip domain and are called CLIPs. In most insects studied so far, PO precursors are activated by a PAP (i.e., PPO activating protease) and its cofactor of clip-domain SPHs. Although melanotic encapsulation is a well-known refractory mechanism of mosquitoes against malaria parasites, it is unclear if a cofactor is required for PPO activation. In Anopheles gambiae, CLIPA4 is 1:1 orthologous to Manduca sexta SPH2; CLIPs A5−7, A12–14, A26, A31, A32, E6, and E7 are 11:4 orthologous to M. sexta SPH1a, 1b, 4, and 101, SPH2 partners in the cofactors. Here we produced proCLIPs A4, A6, A7Δ, A12, and activated them with CLIPB9 or M. sexta PAP3. A. gambiae PPO2 and PPO7 were expressed in Escherichia coli for use as PAP substrates. CLIPB9 was mutated to CLIPB9Xa by including a Factor Xa cleavage site. CLIPA7Δ was a deletion mutant with a low complexity region removed. After PAP3 or CLIPB9Xa processing, CLIPA4 formed a high Mr complex with CLIPA6, A7Δ or A12, which assisted PPO2 and PPO7 activation. High levels of specific PO activity (55−85 U/μg for PO2 and 1131−1630 U/μg for PO7) were detected in vitro, indicating that cofactor-assisted PPO activation also occurs in this species. The cleavage sites and mechanisms for complex formation and cofactor function are like those reported in M. sexta and Drosophila melanogaster. In conclusion, these data suggest that the three (and perhaps more) SPHI-II pairs may form cofactors for CLIPB9-mediated activation of PPOs for melanotic encapsulation in A. gambiae.

Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor.

89Zr-iPET has been widely used for preclinical and clinical immunotherapy studies to predict patient stratification or evaluate therapeutic efficacy. In this study, we prepared and evaluated 89Zr-DFO-anti-PD-L1-mAb tracers with varying chelator-to-antibody ratios (CARs), including 89Zr-DFO-anti-PD-L1-mAb_3X (tracer_3X), 89Zr-DFO-anti-PD-L1-mAb_10X (tracer_10X), and 89Zr-DFO-anti-PD-L1-mAb_20X (tracer_20X). The DFO-anti-PD-L1-mAb conjugates with varying CARs were prepared using a random conjugation method and then subjected to quality control. The conjugates were radiolabeled with 89Zr and evaluated in a PD-L1-expressing CT26 tumor-bearing mouse model. Next, iPET imaging, biodistribution, pharmacokinetics, and ex vivo pathological and immunohistochemical examinations were conducted. LC-MS analysis revealed that DFO-anti-PD-L1-mAb conjugates were prepared with CARs ranging from 0.4 to 2.0. Radiochemical purity for all tracer groups was >99% after purification. The specific activity levels of tracer_3X, tracer_10X, and tracer_20X were 2.2 ± 0.6, 8.2 ± 0.6, and 10.5 ± 1.6 μCi/μg, respectively. 89Zr-iPET imaging showed evident tumor uptake in all tracer groups and reached the maximum uptake value at 24 h postinjection (p.i.). Biodistribution data at 168 h p.i. revealed that the tumor-to-liver, tumor-to-muscle, and tumor-to-blood uptake ratios for tracer_3X, tracer_10X, and tracer_20X were 0.46 ± 0.14, 0.58 ± 0.33, and 1.54 ± 0.51; 4.7 ± 1.3, 7.1 ± 3.9, and 14.7 ± 1.1; and 13.1 ± 5.8, 19.4 ± 13.8, and 41.3 ± 10.6, respectively. Significant differences were observed between tracer_3X and tracer_20X in the aforementioned uptake ratios at 168 h p.i. The mean residence time and elimination half-life for tracer_3X, tracer_10X, and tracer_20X were 25.4 ± 4.9, 24.2 ± 6.1, and 25.8 ± 3.3 h and 11.8 ± 0.5, 11.1 ± 0.7, and 11.7 ± 0.6 h, respectively. No statistical differences were found between-tracer in the aforementioned pharmacokinetic parameters. In conclusion, 89Zr-DFO-anti-PD-L1-mAb tracers with a CAR of 1.4-2.0 may be better at imaging PD-L1 expression in tumors than are traditional low-CAR 89Zr-iPET tracers.

Abstract C112: L1CAM targeting antibody-based therapy as a novel approach for L1CAM positive lymphomas

Abstract Background. L1CAM (L1 Cell Adhesion Molecule) is a glycoprotein identified as a key mediator of the metastatic process in many different tumor types. It facilitates the detachment of tumor cells from the primary tumor and their entry into the circulation. By promoting cell-cell interactions, it also directly stimulates the colonization of distant organs by circulating tumor cells. The expression and role of L1CAM in B and T cell lymphomas is poorly explored. The aim of this project was to evaluate L1CAM expression in different subtypes of lymphoma and its role as novel therapeutic target. Methods. RNA was extracted with Monarch Total RNA Miniprep Kit and qPCR performed with QuantiFast SYBR Green RT-PCR. For flow cytometry (FACS), cells were stained either with anti-L1CAM antibody or isotype control at a dilution of 1:1000. For immunohistochemistry (IHC) samples were stained for 20 minutes at a dilution of 1:100. For direct killing assay, cells were exposed six days to compounds, followed by MTT assay. Antibody dependent cellular cytotoxicity (ADCC) was performed with ADCC Reporter Bioassay (Promega). Results. L1CAM mRNA expression was assessed in 59 lymphoma cell lines. Whereas expression in most cell lines appeared low, a subgroup of cells displayed high to very high expression of L1CAM. Surface L1CAM expression was confirmed by FACS. L1CAM mRNA and protein expression levels correlated well across the cell lines and revealed that Sezary syndrome (SS) cell lines displayed the highest expression, followed by mantle cell lymphoma (MCL) and activated B cell diffuse large B cell lymphoma (ABC DLBCL) cell lines. By IHC L1CAM expression was assessed on different tissue microarrays covering multiple lymphoma subtypes; L1CAM expression was observed especially in a subset of cutaneous T-cell lymphoma and MCL. The data confirmed the findings in lymphoma cell lines. Anti-L1CAM monoclonal antibody (mAb) and four L1CAM targeting antibody drug conjugates (ADCs) (ADC1, ADC4, ADC5, ADC6), differing for the linker and payload, were tested in L1CAM positive and negative cell lines. mAB did not show any sign of direct antitumoral activity. Among ADCs, highest activity was observed with ADC6 (SG3199 payload), followed by ADC4 (MMAE payload). ADC1 and ADC5 (also containing MMAE as payload) showed limited activity. ADC6 showed the best correlation between killing activity and L1CAM expression levels, indicating a high level of target specific activity. The in vitro activity of ADC4 and ADC6 was validated in an in vivo xenograft using the MCL cell line Z138. Finally, mAb and a bispecific anti-CD3/L1CAM antibody were tested for their ability to induce ADCC. Both induced strong intracellular signaling in the reporter cell line upon co-incubation with L1CAM expressing lymphoma cells, indicative of the induction of killing activity in effector cells. Conclusions. In summary, we have demonstrated the in vitro and in vivo activity of anti-L1CAM antibody-based therapeutic approach as novel treatment for L1CAM positive lymphomas. Citation Format: Filippo Spriano, Giulio Sartori, Luca Aresu, Luciano Cascione, Elisa Civanelli, Afua A. Mensah, Chiara Tarantelli, Stefano Pileri, Flavio Mehli, Gunther Spohn, Francesco Bertoni. L1CAM targeting antibody-based therapy as a novel approach for L1CAM positive lymphomas [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C112.

Synergistic Hydrolysis of Soy Proteins Using Immobilized Proteases: Assessing Peptide Profiles.

Because of the health benefits and economic opportunities, extracting bioactive peptides from plant proteins, often food processing by-products, garners significant interest. However, the high enzyme costs and the emergence of bitter peptides have posed significant challenges in production. This study achieved the immobilization of Alcalase and Flavorzyme using cost-effective SiO2 microparticles. Mussel-inspired chemistry and biocompatible polymers were employed, with genipin replacing glutaraldehyde for safer crosslinking. This approach yielded an enzyme loading capacity of approximately 25 mg/g support, with specific activity levels reaching around 180 U/mg for immobilized Alcalase (IA) and 35 U/mg for immobilized Flavorzyme (IF). These immobilized proteases exhibited improved activity and stability across a broader pH and temperature range. During the hydrolysis of soy proteins, the use of immobilized proteases avoided the thermal inactivation step, resulting in fewer peptide aggregates. Moreover, this study applied peptidomics and bioinformatics to profile peptides in each hydrolysate and identify bioactive ones. Cascade hydrolysis with IA and IF reduced the presence of bitter peptides by approximately 20%. Additionally, 50% of the identified peptides were predicted to have bioactive properties after in silico digestion simulation. This work offers a cost-effective way of generating bioactive peptides from soy proteins with reducing potential bitterness.

Integrating perceived physical environments and the theory of planned behaviors when explaining adherence to 24-hour movement guidelines in Chinese adolescents.

Most adolescents worldwide do not meet 24-h movement guidelines, which recommend specific level of physical activity, sedentary behavior, and sleep for optimal health. Nevertheless, there remains a lack of understanding regarding how social cognitive and physical environmental factors influence adolescents' compliance with these guidelines. This prospective study aimed to examine the associations between perceived physical environments, constructs of the theory of planned behavior (TPB), habit strength, and adherence to 24-h movement guidelines in Chinese adolescents over a three-month period. A total of 629 Chinese adolescents (Mage = 14.59 years, SD = 0.64) completed a set of questionnaires comprising perceived physical environmental characteristics, constructs of the TPB, habit strength, and 24-h movement behaviors at baseline and 3 months later. Data analysis was conducted using variance-based structural equation modeling. Attitude, subjective norm, and perceived behavioral control had a direct effect on intention and intention had a direct effect on number of the guidelines being met. Habit strength was a significant predictor of adherence to the guidelines, although its moderating effect on the intention-behavior relationship was not significant. Perceived neighborhood facility accessibility, school facility availability, and home physical activity equipment had significant indirect effects on intention through attitude, subjective norm, and perceived behavioral control. However, constructs of the TPB did not serve as mediators in the relationship between perceived physical environments and the number of guidelines being met. This study offers preliminary evidence supporting the integration of perceived physical environments and the TPB in predicting adolescents' adherence to 24-h movement guidelines. Future research should consider using experimental study designs with rigorous measures of 24-h movement behaviors to establish causal relationships.

FusionDiff: Multi-focus image fusion using denoising diffusion probabilistic models

Multi-focus image fusion (MFIF) is an image enhancement technology with broad application prospects that can effectively extend the depth-of-field of optical lenses. This paper presents a novel MFIF method, named FusionDiff, based on denoising diffusion probabilistic models (DDPM). FusionDiff uses DDPM to fuse two source images by iteratively performing multiple denoising operations. To predict noise accurately and train the model efficiently, a lightweight U-Net architecture is designed as the conditional noise predictor. FusionDiff does not depend on any specific activity level measurement method, fusion rule or complex feature extraction network. It overcomes many algorithm design and training difficulties in existing image fusion methods. FusionDiff is noise-resistant and can still produce outstanding fusion results from source images with noise interference. In addition, FusionDiff is a few-shot learning method, which makes it suitable for image fusion tasks where training samples are relatively scarce. Experiments show that FusionDiff outperforms representative state-of-the-art methods in both visual perception and quantitative metrics. The code is available at https://github.com/lmn-ning/ImageFusionhttps://github.com/lmn-ning/ImageFusion