Predominant Component Research Articles

Spatial-temporal drivers and incidence heterogeneity of hemorrhagic fever with renal syndrome transmission in Shandong Province, China, 2016–2022

BackgroundHemorrhagic fever with renal syndrome (HFRS) signals a recurring risk in Eurasia in recent years owing to its continued rise in case notifications and the extension of geographical distribution. This study was undertaken to investigate the spatiotemporal drivers and incidence heterogeneity of HFRS transmission in Shandong Province.MethodsThe epidemiological data for HFRS, meteorological data and socioeconomic data were obtained from China Information System for Disease Control and Prevention, China Meteorological Data Sharing Service System, and Shandong Statistical Yearbook, respectively. The spatial-temporal multicomponent model was employed to analyze the values of spatial-temporal components and the heterogeneity of HFRS transmission across distinct regions.ResultsThe total effect values of the autoregressive, epidemic, and endemic components were 0.451, 0.187, and 0.033, respectively, exhibiting significant heterogeneity across various cities. This suggested a pivotal role of the autoregressive component in propelling HFRS transmission in Shandong Province. The epidemic component of Qingdao, Weifang, Yantai, Weihai, and Jining declined sharply at the onset of 2020. The random effect identified distinct incidence levels associated with Qingdao and Weifang, signifying regional variations in HFRS occurrence.ConclusionsThe autoregressive component emerged as a significant driver in the transmission of HFRS in Shandong Province. Targeted preventive measures should be strategically implemented across various regions, taking into account the predominant component influencing the epidemic.

Actual and reference evapotranspiration for a natural, temperate zone fen wetland – Upper Biebrza case study

Evapotranspiration is the key and predominant component of the water balance in wetlands. Direct evapotranspiration measurements are challenging in wetlands due to their remoteness and high surface water level. This article describes the actual (ETa and reference evapotranspiration (ET0) from a cultivated wet meadow located in the Biebrza National Park – the largest national park in north-east Poland, Central Europe. The data were sourced from a micrometeorological station equipped with an eddy covariance system to measure heat and vapour fluxes and such meteorological elements as radiation balance components, air temperature and humidity. The values of directly measured ETa were presented daily in the context of available energy and ET0. Daily sums of ETa ranged from below 0.2 mm in winter to 6.5 mm in summer. The share of daily sums of ETa in the ET0 usually ranged from 50 to 60%, with extreme values from 10 to 170%. Aside from giving more insight into Biebrza wetlands’ functioning, the actual data produced in this study may be used instead of indirect methods, which were used the most in modelling wetlands areas.

Hydrogen transfer reaction in butene catalytic cracking over ZSM-5

Hydrogen transfer reaction (HTR) is the pivotal side reaction in the catalytic cracking process of low carbon olefins. The intricate reaction pathways and product diversity of HTR directly impact the selective formation of ethylene and propylene. Therefore, elucidating the key HTR in various reaction pathways and defining the hydrogen transfer index (HTI) as a criterion lay a scientific foundation for precisely regulating HTR during olefin catalytic cracking process. Herein, the influence of the acid strength of ZSM-5 zeolites on the HTR degree was analyzed in butene catalytic cracking. Results showed that isobutane was the predominant component of HTR products, mainly derived from HTR during the dimerization-cracking of pentene (butene primary cracking product). Subsequent pentene catalytic cracking experiments validated this conclusion. Thus, the HTI in butene or pentene cracking process was defined as follows: for butene cracking process, HTI = Si–C4H10/SC5H10; for pentene cracking process, HTI = Si–C4H10/SC4H8. The HTI accurately reflected the extent of HTR with respect to the acid properties of the catalysts. Moreover, the reaction network of butene catalytic cracking process was optimized, providing a comprehensive explanation for the intriguing phenomenon of decreasing butene conversion with increasing reaction temperature when the acid strength of ZSM-5 was weak. Finally, a high-performance butene catalytic cracking catalyst, De-TS-1-0.25%P, was developed, exhibiting high olefin selectivity (92.33 %) and outstanding stability (307 h) in the conversion of butene.

Organic-mineral colloids regulate the migration and fractionation of rare earth elements in groundwater systems impacted by ion-adsorption deposits mining in South China

Ion-adsorption rare earth element (REE) deposits distributed in the subtropics provide a rich global source of REEs, but in situ injection of REEs extractant into the mine can result in leachate being leaked into the surrounding groundwater systems. Due to the lack of understanding of REE speciation distribution, particularly colloidal characteristics in a mining area, the risks of REEs migration caused by in situ leaching of ion-adsorption REE deposits has not been concerned. Here, ultrafiltration and asymmetric flow field-flow fractionation coupled with inductively coupled plasma mass spectrometry (AF4-ICP-MS) were integrated to characterize the size and composition of REEs in leachate and groundwater from mining catchments in South China. Results show that REEs were associated with four fractions: 1) the <1 kDa fraction including dissolved REEs; 2) the 1 – 100 kDa nano-colloidal fraction containing organic compounds; 3) the 100 kDa – 220 nm fine colloids including organic-mineral (Fe, Mn and Al (oxy)hydroxides and clay minerals); 4) the >220 nm coarse colloids and acid soluble particles (ASPs) comprising minerals. Influenced by the ion exchange effect of in situ leaching, REEs in leachate were mostly dissolved (79 %). The pH of the groundwater far from the mine site was increased (5.8 – 7.3), the fine organic-mineral colloids (46 % – 80 %) were the main vectors of transport for REEs. Further analysis by AF4 revealed that the fine colloids can be divided into mineral-rich (F1, 100 kDa – 120 nm) and organic matter-rich (F2, 120 – 220 nm) populations. The main colloids associated with REEs shifted from F1 (64 % ∼ 76 %) to F2 (50 % ∼ 52 %) away from the mining area. For F1 and F2, the metal/C molar ratio decreased away from the mining area and middle to heavy REE enrichment was presented. According to the REE fractionation, organic matter was the predominant component capable of binding REEs in fine colloids. Overall, our results indicate that REEs in the groundwater system shifted from the dissolved to the colloidal phase in a catchment affected by in situ leaching, and organic-mineral colloids play an important role in facilitating the migration of REEs.

Abstract LB297: Toll-like receptor 8 in tumor associated macrophages regulates miR-192-5p expression and drug resistance in neuroblastoma

Abstract MicroRNAs (miRs) are small non-coding RNAs (ncRNAs) with gene expression regulatory functions. MiRs are frequently dys-regulated in human cancers and orchestrate the biology of the disease, and its resistance to chemotherapy. Increasing evidence supports a role of the tumor microenvironment (TME) in promoting cancer growth and resistance to treatments. Tumor Associated Macrophages (TAMs) are a predominant cellular component of the TME of several types of cancers, including neuroblastoma (NB), the most frequent pediatric extra-cranial solid tumor. NB cells secrete miRs within small extracellular vesicles called exosomes, and these miR are shuttled to surrounding TAMs. Our lab was the first to show that cancer-derived exosomal miRs bind to Toll-like receptor 8 (TLR8) in TAMs, triggering an NF-κB-dependent production of TAM-derived miRs, that are then shuttled back to NB cells. Following up on that discovery, we identified a signature of miRs that are up/down-regulated in NB cells when co-cultured with TAMs expressing TLR8 or in which the TLR8 had been deleted with CRISPR/Cas9 engineering. We identified miR-192-5p as significantly down-regulated in NB cells when co-cultured with wild-type TAMs, however miR-192-5p expression was significantly increased in NB cells when co-cultured with TLR8-knock out TAMs, supporting a TLR8-mediated modulation of miR-192-5p in the NB TME. Additionally, we found that over-expression of miR-192-5p in NB cells increased sensitivity of NB cells to temozolomide and cisplatin, two commonly used drugs in the treatment of this malignancy. Overall, these findings support the use of TLR8 inhibitors to up-regulate miR-192-5p and increase sensitivity of NB cells to chemotherapy. Citation Format: Nicolo Toldo, Verena Martinez Rodriguez, Muller Fabbri. Toll-like receptor 8 in tumor associated macrophages regulates miR-192-5p expression and drug resistance in neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB297.

Exploring the Potential of Humoral Immune Response to Commensal Bifidobacterium as a Biomarker for Human Health, including Both Malignant and Non-Malignant Diseases: A Perspective on Detection Strategies and Future Directions.

In this comprehensive review, we explore the pivotal role of commensal Bifidobacterium (c-BIF) as potent non-self-antigens through antigenic mimicry, along with exploring the potential of humoral immune responses for both malignant and non-malignant disease. c-BIF, a predominant component of the human gut microbiome encompassing around 90% of the human genome, has emerged as a pivotal player in human biology. Over recent decades, there has been extensive research elucidating the intricate connections between c-BIF and various facets of human health, with particular emphasis on their groundbreaking impact on anti-cancer effects and the management of non-malignant diseases. The multifaceted role of c-BIF is explored, ranging from enhancing anti-tumor immunity to improving the efficacy of anti-cancer and anti-infectious disease strategies, and serving as predictive biomarkers for various diseases. Recent studies highlight not only c-BIF's promotion of anti-tumor immunity but also their role in enhancing the efficacy of immune checkpoint inhibitors. The review emphasizes the promising avenue of manipulating the gut microbiota, particularly c-BIF, for modulating cancer immunotherapy with targeted effects on tumor cells while minimizing harm to normal tissue. In the context of infectious and inflammatory diseases, the crucial role of c-BIFs in the management of COVID-19 symptoms is examined, emphasizing their impact on the severity of and immune response to COVID-19. Furthermore, c-BIF exhibits preventive and therapeutic effects on Human Papillomaviruses (HPV) and shows promise in improving inflammatory bowel diseases. The potential application of c-BIF as a biomarker for immunotherapy is explored, with a specific emphasis on its predictive and prognostic value in cancer. Suggestions are made regarding the use of humoral immune responses to cytotoxic T lymphocyte (CTL) epitope peptides that share motifs with c-BIF, proposing them as potential markers for predicting overall survival in diverse cancer patients. In conclusion, c-BIF emerges as a crucial and multifaceted determinant of human health, across anti-tumor immunity to infectious and inflammatory disease management. The manipulation of c-BIF and gut microbiota presents a promising avenue for advancing therapeutic strategies, particularly in the realm of cancer immunotherapy. Additionally, this review highlights the significance of c-BIF as potent non-self-antigens via antigenic mimicry, emphasizing the importance of robust humoral immune responses against c-BIF for preventing various diseases, including inflammatory conditions. Elevated levels of circulating antibodies against c-BIF in healthy individuals may serve as potential indicators of lower risks for malignant and non-malignant diseases.

The inherent nature of N/P heteroatoms in Sargassum fusiforme seaweed biochar enhanced the nonradical activation of peroxymonosulfate for acetaminophen degradation in aquatic environments

This study investigated the catalytic activity of biochar materials derived from algal biomass Sargassum fusiforme (S. fusiforme) for groundwater remediation. A facile single-step pyrolysis process was used to prepare S. fusiforme biochar (SFBCX), where x denotes pyrolysis temperatures (600 °C-900 °C). The surface characterization revealed that SFBC800 possesses intrinsic N and P heteroatoms. The optimum experimental condition for acetaminophen (AAP) degradation (>98.70%) was achieved in 60 min using 1.0 mM peroxymonosulfate (PMS), 100 mg L−1 SFBC800, and pH 5.8 (unadjusted). Moreover, the degradation rate constant (k) was evaluated by the pseudo-first-order kinetic model. The maximum degradation (>98.70%) of AAP was achieved within 60 min of oxidation. Subsequently, the k value was calculated to be 6.7 × 10−2 min−1. The scavenger tests showed that radical and nonradical processes are involved in the SFBC800/PMS system. Moreover, the formation of reactive oxygen species (ROS) in the SFBC800/PMS system was confirmed using electron spin resonance (ESR) spectroscopy. Intriguingly, both radical (O2•−, •OH, and SO4•−) and nonradical (1O2) ROS were formed in the SFBC800/PMS system. In addition, electrochemical studies were conducted to verify the electron transfer process of the nonradical mechanism in the SFBC800/PMS system. The scavenger and electron spin resonance (ESR) spectroscopy showed that singlet oxygen (1O2) is the predominant component in AAP degradation. Under optimal condition, the SFBC800/PMS system reached ∼81% mineralization of AAP within 5 min and continued to ∼85% achieved over 60 min of oxidation. Coexisting ions and different aqueous matrices were investigated to examine the feasibility of the catalyst system, and the SFBC800/PMS system was found to be effective in the remediation of AAP-contaminated groundwater, river water, and effluent water obtained from wastewater treatment plants. Moreover, the SFBC800-activated PMS system demonstrated reusability. Our findings indicate that the SFBC800 catalyst has excellent catalytic activity for AAP degradation in aquatic environments.

Initiation mechanism of arcing generated in RF capacitively coupled plasma

In our previous study, we established an arcing generation and measurement system and we observed prior light emission before arcing current development. However, we briefly analyzed those light emissions with strong assumptions without detailed experiment evaluations and thus, the investigation of the formation mechanism in the initiation phase with detailed experiment evaluations has yet to be conducted. In this work, we investigated the initiation mechanism of arcing generated on an arcing inducing probe (AIP) in a radio frequency capacitively coupled plasma (CCP) environment. Here, the AIP is an aluminum rod covered by anodized film and its tip edge is partially stripped to localize arcing on this edge. We measured emission light, voltage, and current waveforms induced by arcing. The spatiotemporal image of the emission light revealed that the tip glow is the brightest intensity and has longest lifetime during arcing, meaning that it is the primary process in whole arcing process. The current waveform induced by arcing corresponds to the time evolution of the tip glow and estimations revealed that the electron emission is the predominant component of the current formation. Furthermore, snapshot images with AIPs having enlarged stripping area exhibited that arcing occurs at the boundary between the alnuminum and anodized film (dielectric), where charging of ions from the CCP on the film surface can induce high-electric field. In addition, we found that the energy relaxation length of emitted electrons for collisions with Ar atoms, which are the background gas, is much larger than the tip glow diameter, meaning that the electon-Ar collision cannot maintain tip glow. This result supports additional source of atoms to sustain the tip glow such as the surface evaporation from arcing spot, of which evidence was speculated our previous study. We estimated minimum aluminum vapor density and surface temperature, which is sufficiently high enough to induce surface vaporization. Combining those experiment results and estimations, that are electron emission, high surface temperature, and surface evaporation, we can speculate that the initiation mechanism of arcing near dielectric surface in radio-frequency CCP environment is the thermionic emission and surface evaporation from arcing spot.

Single nucleotide polymorphism (SNP) chromosomal microarray as a diagnostic tool for mucinous tubular and spindle cell carcinoma: A validation study

Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA).We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays.The cohort was comprised of 8 females and males, each, with an age range of 33–79 years (median, 59), and a tumor size range of 3.4–15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally.Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of CDKN2A/B, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC.MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.

Fruit sugar and organic acid composition and inheritance analysis in an intraspecific cross of Chinese cherry

Chinese cherry is an economically significant fruiting cherry species within Rosaceae family. Soluble sugar and organic acid are crucial factors affecting fruit flavor, while the genetic basis for these traits in Chinese cherry remains largely unknown. In this study, we determined sugar and acid components in 190 and 187 representative hybrids from an intraspecific cross of Chinese cherry over two consecutive years. Fructose and glucose were the major sugars in both progeny and parents, but their contents varied considerably between years. Fructose represented a higher proportion in progeny than in parents. Malic acid was the most predominant component, accounting for a relatively stable proportion (∼70%) for both years. The F1 population exhibited wide phenotypic variations, with coefficient of variation ranging from 6.57% to 108.63%. Regarding inheritance patterns, sugars tended towards smaller values, while malic acid exhibited significant transgressive heterosis. Sugars and acids were primarily governed by 2 MG-AD or 2 MG-EA model. Major gene heritability exceeded 88% for acids but much lower (12%–75%) for sugars. These results suggest that acid contents might be controlled by two major genes, while sugars are mainly governed by polygenes. This study provides a theoretic basis for understanding genetic predisposition underlying sugar-acid fractions in Chinese cherry fruit.

Phyto-pharmacological Evaluation of Pimenta dioica (Linn.) Merill, Essential oil for Anthelmintic and Antimicrobial potential

Pimenta dioica (Linn.) Merill., belongs to the family Myrtaceous, has been used as a spice and is well known for its culinary as well as medicinal values. The aim of the current study was to assess the in vitro antimicrobial, anthelmintic activity and phytochemical composition of the essential oil extracted from Pimenta dioica leaves. The extraction of essential oil was performed with the Clevenger apparatus, by hydro-distillation. Pimenta dioica essential oil yield was 1.03%. The GC-MS analysis of this Pimenta dioica essential oil showed that eugenol (74.72%) was the predominant component. The essential oil showed potent anthelmintic activity assay when analysed by the adult worm’s motility assay. It has shown a comparable paralysis and disintegration profile of the model organism to that of the standard drug albendazole. The essential oil was also found to be effective against common human pathogenic bacteria, including Staphylococcus aureus, Klebsiella, Escherichia coli, Chromobacterium violaceum and Proteus vulgaris. It also showed moderate antifungal activity against Candida albicans and Aspergillus niger. These results proved that Pimenta dioica essential oil could be used as a source of the lead molecule for developing novel anthelmintic or antimicrobial agents.

Expression of fibroblast growth factor receptor 2 (FGFR2) in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma: clinicopathological study

Genetic alterations including fusions in fibroblast growth factor receptor 2 (FGFR2) are detected in 10–20% of intrahepatic cholangiocarcinoma (iCCA), and FGFR2 inhibitors are effective for the treatment of iCCA. We examined a prevalence of FGFR2 genetic alterations and their clinicopathological significance in combined hepatocellular–cholangiocarcinoma (cHCC-CCA). FGFR2 expression, which is a surrogate marker for FGFR2 genetic alterations, was immunohistochemically assessed in the liver sections from 75 patients with cHCC-CCA, 35 with small duct-type iCCA, 30 with large duct-type iCCA, and 35 with hepatocellular carcinoma (HCC). FGFR2 genetic alterations were detected by reverse transcription-PCR and direct sequence. An association of FGFR2 expression with clinicopathological features was investigated in cHCC-CCAs. FGFR2 expression was detected in significantly more patients with cHCC-CCA (21.3%) and small duct-type iCCA (25.7%), compared to those with large duct-type iCCA (3.3%) and HCC (0%) (p < 0.05). FGFR2-positive cHCC-CCAs were significantly smaller size (p < 0.05), with more predominant cholangiolocarcinoma component (p < 0.01) and less nestin expression (p < 0.05). Genetic alterations of ARID1A and BAP1 and multiple genes were significantly more frequent in FGFR2-positive cHCC-CCAs (p < 0.05). 5′/3′ imbalance in FGFR2 genes indicating exon18-truncated FGFR2 was significantly more frequently detected in FGFR2-positive cHCC-CCAs and small duct iCCAs, compared to FGFR2-negative ones (p < 0.05). FGFR2::BICC fusion was detected in a case of cHCC-CCAs. FGFR2 genetic alterations may be prevalent in cHCC-CCAs as well as small duct-type iCCAs, which suggest cHCC-CCAs may also be a possible therapeutic target of FGFR2 inhibitors.Graphical

Problematic Issues of the Legal Regulation of Voluntary Surrender of Narcotic Drugs

Introduction: the Russian Federation is taking effective measures aimed at preventing and solving crimes related to illicit trafficking in narcotic drugs. Most of the measures applied in practice today are not effective enough and need to be significantly improved. Despite the fact that the forces of the state and society are aimed at actively combating drug trafficking, it is necessary to improve the system of countering this type of criminal encroachment against public health. The measures taken should be comprehensive and aimed at a more detailed study of the identity of the drug offender, the search for causes and conditions conducive to the commission of the illegal acts in question. In the paper, some recommendations are made to improve the current criminal legislation in the field of combating drug trafficking and problematic issues of voluntary surrender of narcotic drugs are considered. The purpose of the study is to analyze the controversial issues of voluntary surrender of substances with limited circulation (narcotic drugs); to develop significant proposals and recommendations in the field of law enforcement on the identified issues; as well as countering (preventing) illegal trafficking in narcotic drugs in the criminal law plane, aimed at improving the effectiveness of criminal law counteraction measures. Research methods: the classical methodological concept, which includes the general scientific methods in particular, as well as a set of socio-scientific methods in its predominant component – the statistical method. Results of the study and conclusions: the authors conclude that in order to ensure the unity of the law enforcement approach, it is proposed to make clarifications in the note to Article 228 of the Criminal Code of the Russian Federation, namely, to consolidate the concepts of “a real opportunity to dispose of them in another way” and the moment of detention within the framework of criminal procedural actions.

Insights into atmospheric trace gases, aerosols, and transport processes at a high-altitude station (2623 m a.s.l.) in Northeast Asia

As part of the efforts to understand long-range air pollution transport in Northeast Asia, a comprehensive field measurement campaign was conducted at the top of Changbai Mountain (2623 m a.s.l.) from 25th July to 21st August in 2021. The ambient concentrations of trace gases and chemical characteristics of fine particulate matter (PM2.5) were comparable to those at background or free tropospheric locations in China, but exceeded levels at corresponding sites in Europe and the United States. Well-defined diurnal variations were evident in most air pollutants, including carbon monoxide (CO), sulfur dioxide (SO2), and nitrogen oxide (NOx), reflecting the influence of boundary layer development and local anthropogenic activities. Ozone (O3) exhibited a unique diurnal distribution, with lower concentrations during the daytime and higher levels at nighttime, indicating a pronounced impact of downward transport of O3-rich air from the upper troposphere during the nighttime. During the campaign, organic carbon (OC) constituted the predominant component of PM2.5, comprising 43% of the total, while sulfate (SO42−) was the most abundant secondary inorganic component in PM2.5, accounting for 26%. Combining the analysis of air mass backward trajectories, we found that Changbai Mountain is primarily influenced by air masses originating from North Korea and the Sea of Japan, constituting 62% of the total, and local vegetation biological emissions and anthropogenic emissions in North Korea notably affect the observation site. Conversely, the secondary aerosol components were most abundant in marine air mass originating from the marginal seas of China and the strait between the Korean peninsula and southern Japan. Utilizing the Lagrangian photochemical trajectory model (LPTM), a significant increase in particulate SO42− concentrations was observed when air mass passed through the marginal seas of China, primarily due to SO2 oxidation reaction. This study contributes to an improved understanding of the atmospheric chemistry in the high-altitude regions of Northeast Asia and underscores the substantial role of secondary inorganic aerosol formation during the transport of marine air masses.

Practical considerations in liquefaction numerical simulations calibrated with historical data

The paper details some practical considerations associated with the numerical simulation of liquefaction in Wildlife site in Southern California. Two material constitutive models are implemented in the simulations: a pressure-dependent multi-yield-surface model (PDMY) and PM4Sand, both available in the OpenSees finite elements platform. Both uniaxial as well as biaxial simulations are presented in the paper. The uniaxial simulations only include the predominant horizontal shaking component while the biaxial simulations include both orthogonal horizontal shaking components. Two historical major earthquake events were simulated: the 1987 Superstition Hills and the 2010 El Mayor Cucapah earthquakes. Laboratory experimental data used for calibration of the material models was obtained from historical data published in the 1980's. This data is particularly valuable since they correspond to intact (undisturbed) samples extracted from Wildlife site about two years before occurrence of the 1987 earthquake. In all the simulations, the models were able to capture salient features of the deposit's behavior, such as the magnitude of surface accelerations, and dilative behavior of the soil. However, the excess pore water pressure rises earlier than what the site recordings indicates. This may be attributed to the fact that the constitutive models do not consider the concept of volumetric threshold shear strain below which no excess pore water pressure is generated during cyclic shear loading. It was also found that there was a significant overestimation of the excess pore pressure for the 2010 El Mayor Cucapah earthquake simulations. This may be attributed to the effect of the site shaking history which increased the site resistance to liquefaction. This added resistance was not reflected by the numerical model since it was calibrated with samples extracted about 25 years before the 2010 earthquake.

Study on assessing the impact of evaporation on the natural recharge in the Holocene aquifer of sand dunes in Ben Tre province, Vietnam

On the surface of the terrain in Ben Tre province, sand dunes exist in the form of thin strips running parallel and facing the coastline, with a total distributed area of about 12,179 hectares. These sand dunes vary in size, with widths ranging from 100 to 620 meters and lengths from 1,200 to 7,200 m. The predominant geological component in these sand dunes is fine-grained sand with large pore sizes. The vegetation cover on these sand dunes is sparse, with numerous hours of sunlight throughout the year. The air temperature and surface evaporation are high, creating favourable conditions for the evaporation process from the groundwater surface. This study employs the direct evaporation measurement method using Lysimeter (LS) based on the water balance principle. The LS measuring station is located in Tan Thuy commune, Ba Tri district, Ben Tre province, to monitor the groundwater loss through evaporation, simulating real conditions with groundwater levels at depths of 0.5 and 0.9 m. The monitoring and calculations show that the total groundwater evaporation during the period from 1 June 2022 to 31 May 2023 is approximately 142.5 mm, equivalent to 24.9% of the natural recharge of the aquifer.

A Phase I, Open-Label, Mass Balance Study of [14C]-Iberdomide in Healthy Subjects.

Iberdomide is a novel potent cereblon modulator (CELMoD®) agent, which is currently under clinical development for hematological malignancies. A human mass balance study was conducted to characterize the biotransformation and excretion pathways of iberdomide. After a single dose of radiolabelled [14C]-iberdomide (1 mg) in six healthy subjects. Blood, urine, and fecal samples were collected for pharmacokinetics, mass balance, and clinical laboratory assessments. Results showed that a single oral dose of 1 mg iberdomide was generally well tolerated in healthy subjects. The recovery of [14C]-iberdomide-derived radioactivity in humans was 45.9% in urine and 42.6% in feces. Based on exposure (area under the concentration-time curve [AUC0-24]), iberdomide and M12 (metabolites) accounted for approximately 59% and 14% of circulating total radioactivity (TRA) exposure, respectively. Of the 88.5% TRA excreted, approximately 27% was excreted as unchanged iberdomide and 62% as metabolites, with similar amounts of excreted metabolites in the urine (16%) and feces (11%). Biotransformation of iberdomide in humans included multiple oxidations of the morpholino moiety as well as glutarimide ring hydrolysis of parent and oxidized metabolites and a combination of these pathways. Iberdomide was the predominant component in human plasma, with metabolite M12 being the most prominent circulating metabolite. In excreta, similar iberdomide-derived radioactivity was found in urine and feces. NCT03294603.

Abstract 3719: Fasting-mimicking diet plus 2-DG drives antitumor immunity by targeting EDEM3-induced PD-L1 glycosylation

Abstract The PD-1/PD-L1 axis plays an essential role in immune escape and immunotherapy. Importantly, translated N-linked glycosylation of PD-L1 stabilizes protein, enters the cell membrane binding to PD-1, renders T cells anergic and leads to T-cell exhaustion and dysfunction. Targeting PD-L1 glycosylation as an attractive target by a rational combination of cancer immunotherapies. Cancer-associated fibroblasts (CAFs), a predominant cell component of the tumor microenvironment, exert crucial functions in promoting immune escape and immunotherapy resistance by increasing the tumor PD-L1 expression. However, whether and how CAFs upregulate the glycosylation of PD-L1 has never been reported. This study shows that CAFs can upregulate PD-L1 glycosylation and enhance PD-L1 cell surface expression via glycosyltransferase EDEM3, thus cancer immune evasion. Then, the study delves into the relationship between EDEM3 expression, prognosis and immunogenicity. We demonstrate that EDEM3 plays a role in tumor immunity during tumor progression, as evidenced by EDEM3 expression is only significantly correlated with poor prognosis in the CD8+ T cell-enriched population. In subcutaneous tumor models, we observed high cell-surface PD-L1 expression accompanied by decreased CD8+ T cell infiltration and increased M2 macrophage in immunocompetent mice transplanted with EDEM3 over-expressed CRC cells that promote resistance to PD-1/PD-L1 blockade cancer immunotherapy. By performing bioinformatic analysis, we found that the hexosamine biosynthesis pathway (HBP) is highly affected in EDEM3-upregulated CRC cancer. Subsequently, the production of the UDP-GlcNAc (the end product of HBP metabolic flow), a donor substrate for N-linked glycosylation, is significantly increased in EDEM3 over-expressed CRC cells by LC/MS. Meanwhile, glucose is confirmed to be the primary effector of PD-L1 glycosylation in CRC cells, and the glucose restriction attenuates EDEM3-modified PD-L1 glycosylation by reducing UDP-GlcNAc biosynthesis. Finally, we demonstrate that modulation of glucose metabolism through a fasting-mimicking diet (FMD) in combination with 2-deoxy glucose (2-DG) treatment enhances antitumor immunity, especially in tumors with high-EDEM3 expression that exhibit resistance to immunotherapy. We propose potential therapeutic targets for CRC that inhibit PD-L1 glycosylation through FMD+2-DG and could augment the efficacy of immune checkpoint blockers. Citation Format: Xiaoxia Liu, Shaoyong Peng, Xiaolin Wang, Huichuan Yu, Yanxin Luo. Fasting-mimicking diet plus 2-DG drives antitumor immunity by targeting EDEM3-induced PD-L1 glycosylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3719.

An Investigation into Habits of Mind Prospective Teacher: Do They Have it?

Purpose: The purpose of this study is to obtain a profile of habits of mind among prospective teacher students in the PMIPA (Science, Mathematics, and Environmental Education) Department in Pontianak, Indonesia. Recognizing the importance of habits of mind in shaping learning outcomes and life skills, the research aims to assess the prevalence and distribution of self-regulation, critical thinking, and creative thinking among teacher education students. Methods: The research utilizes a quantitative descriptive approach, conducted across three study programs: Biology Education, Chemistry Education, and Mathematics Education. Purposive sampling is employed to select a sample of 100 prospective teacher students. Data collection involves the administration of a questionnaire comprising three aspects: self-regulation, critical thinking, and creative thinking. The collected data are analyzed using quantitative methods to provide a comprehensive understanding of the habits of mind among PMIPA students. Results and Discussion: The research findings reveal that the habits of mind among PMIPA students are generally categorized as good, with 84% exhibiting favorable habits. Among the three study programs, Biology Education students exhibit the highest percentage of favorable habits, followed by Chemistry Education and Mathematics Education. Self-regulation emerges as the predominant habitual component of the mind, followed by critical thinking, with creative thinking ranking lowest in prevalence. These findings suggest that while PMIPA students demonstrate strengths in self-regulation and critical thinking, there may be opportunities for further development of creative thinking skills. Implications of the Research: The results of this research hold significant implications for universities and lecturers involved in teacher education programs. By providing insights into the habits of mind prevalent among prospective teacher students, the findings can inform the design of appropriate teaching and learning strategies tailored to the needs and strengths of PMIPA students. Additionally, the research outcomes may contribute to the enhancement of teacher education curricula, emphasizing the cultivation of critical thinking and creative thinking skills alongside self-regulation. Originality/Value: This study contributes to the existing literature by offering a detailed examination of habits of mind among prospective teacher students in the PMIPA Department, particularly in the context of teacher education in Pontianak, Indonesia. By focusing on the components of self-regulation, critical thinking, and creative thinking, the research provides valuable insights into the cognitive and metacognitive skills prevalent among PMIPA students. The findings offer a basis for enhancing teacher education programs and fostering the development of well-rounded educators equipped with essential habits of mind for success in teaching and lifelong learning.

Genetic and chemical control of tuberculostearic acid production in Mycobacterium avium subspecies paratuberculosis.

Tuberculostearic acid (TBSA) is a fatty acid unique to mycobacteria and some corynebacteria and has been studied due to its diagnostic value, biofuel properties, and role in membrane dynamics. In this study, we demonstrate that TBSA production can be abrogated either by addition of pivalic acid to mycobacterial growth cultures or by a bfaA gene knockout encoding a flavin adenine dinucleotide (FAD)-binding oxidoreductase. Mycobacterium avium subspecies paratuberculosis (Map) growth and TBSA production were inhibited in 0.5-mg/mL pivalic acid-supplemented cultures, but higher concentrations were needed to have a similar effect in other mycobacteria, including Mycobacterium smegmatis. While Map C-type strains, isolated from cattle and other ruminants, will produce TBSA in the absence of pivalic acid, the S-type Map strains, typically isolated from sheep, do not produce TBSA in any condition. A SAM-dependent methyltransferase encoded by bfaB and FAD-binding oxidoreductase are both required in the two-step biosynthesis of TBSA. However, S-type strains contain a single-nucleotide polymorphism in the bfaA gene, rendering the oxidoreductase enzyme vestigial. This results in the production of an intermediate, termed 10-methylene stearate, which is detected only in S-type strains. Fatty acid methyl ester analysis of a C-type Map bfaA knockout revealed the loss of TBSA production, but the intermediate was present, similar to the S-type strains. Collectively, these results demonstrate the subtle biochemical differences between two primary genetic lineages of Map and other mycobacteria as well as explain the resulting phenotype at the genetic level. These data also suggest that TBSA should not be used as a diagnostic marker for Map.IMPORTANCEBranched-chain fatty acids are a predominant cell wall component among species belonging to the Mycobacterium genus. One of these is TBSA, which is a long-chain middle-branched fatty acid used as a diagnostic marker for Mycobacterium tuberculosis. This fatty acid is also an excellent biolubricant. Control of its production is important for industrial purposes as well as understanding the biology of mycobacteria. In this study, we discovered that a carboxylic acid compound termed pivalic acid inhibits TBSA production in mycobacteria. Furthermore, Map strains from two separate genetic lineages (C-type and S-type) showed differential production of TBSA. Cattle-type strains of Mycobacterium avium subspecies paratuberculosis produce TBSA, while the sheep-type strains do not. This important phenotypic difference is attributed to a single-nucleotide deletion in sheep-type strains of Map. This work sheds further light on the mechanism used by mycobacteria to produce tuberculostearic acid.