bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear Medicine and Cancer Theragnostics: Basic Concepts
Authors: Zoi Vasiliki , Giannakopoulou Maria , Alexiou George A. , Bouziotis Penelope , Thalasselis Savvas , Tzakos Andreas G. , Fotopoulos Andreas , Papadopoulos Athanassios N. , Kyritsis Athanassios P. , Sioka Chrissa
Published: September 2023

Cancer theragnostics is a novel approach that combines diagnostic imaging and radionuclide therapy. It is based on the use of a pair of radiopharmaceuticals, one optimized for positron emission tomography imaging through linkage to a proper radionuclide, and the other bearing an alpha- or beta-emitter isotope that can induce significant damage to cancer cells. In recent years, the use of theragnostics in nuclear medicine clinical practice has increased considerably, and thus investigation has focused on the identification of novel radionuclides that can bind to molecular targets that are typically dysregulated in different cancers. The major advantages of the theragnostic approach include the elimination of multi-step procedures, reduced adverse effects to normal tissues, early diagnosis, better predictive responses, and personalized patient care. This review aims to discuss emerging theragnostic molecules that have been investigated in a series of human malignancies, including gliomas, thyroid cancer, neuroendocrine tumors, cholangiocarcinoma, and prostate cancer, as well as potent and recently introduced molecular targets, like cell-surface receptors, kinases, and cell adhesion proteins. Furthermore, special reference has been made to copper radionuclides as theragnostic agents and their radiopharmaceutical applications since they present promising alternatives to the well-studied gallium-68 and lutetium-177.
DB-Tracker: Multi-Object Tracking for Drone Aerial Video Based on Box-MeMBer and MB-OSNet
Authors: Yuan Yubin , Wu Yiquan , Zhao Langyue , Chen Jinlin , Zhao Qichang
Published: September 2023

Drone aerial videos offer a promising future in modern digital media and remote sensing applications, but effectively tracking several objects in these recordings is difficult. Drone aerial footage typically includes complicated sceneries with moving objects, such as people, vehicles, and animals. Complicated scenarios such as large-scale viewing angle shifts and object crossings may occur simultaneously. Random finite sets are mixed in a detection-based tracking framework, taking the object’s location and appearance into account. It maintains the detection box information of the detected object and constructs the Box-MeMBer object position prediction framework based on the MeMBer random finite set point object tracking. We develop a hierarchical connection structure in the OSNet network, build MB-OSNet to get the object appearance information, and connect feature maps of different levels through the hierarchy such that the network may obtain rich semantic information at different sizes. Similarity measurements are computed and collected for all detections and trajectories in a cost matrix that estimates the likelihood of all possible matches. The cost matrix entries compare the similarity of tracks and detections in terms of position and appearance. The DB-Tracker algorithm performs excellently in multi-target tracking of drone aerial videos, achieving MOTA of 37.4% and 46.2% on the VisDrone and UAVDT data sets, respectively. DB-Tracker achieves high robustness by comprehensively considering the object position and appearance information, especially in handling complex scenes and target occlusion. This makes DB-Tracker a powerful tool in challenging applications such as drone aerial videos.
UAV-Assisted Wideband Terahertz Wireless Communications with Time-Delay Phased UPA under Beam Squint
Authors: Huang Hao , Zheng Qinghe , Sari Hikmet
Published: September 2023

Future Unmanned Aerial Vehicle (UAV)-assisted wireless communication systems are expected to utilize wide bandwidths available at terahertz (THz) frequencies to enhance system throughput. To compensate for the severe path loss in the THz band, it is essential to have a multitude of antennas in the UAV to generate narrow beams for directional transmission. However, narrow beams severely limit its spatial coverage, which greatly affects the efficiency of large-scale access UAV-assisted THz systems. Moreover, the combination of massive antennas and large bandwidth at THz makes the misalignment of the beams caused by beam squint non-negligible and also high energy consumption. UAV-assisted communication technology can effectively increase spatial coverage and provide reliable LoS communication links. In addition, reducing the number of radio frequency (RF) chains while ensuring the number of transmitted data streams and space division multiplexing capability is also an effective way to reduce energy consumption in the UAV communication. In this paper, a single RF chain uniform planar array (UPA) with true-time-delays (TTDs) is equipped on the UAV to achieve two dimensional (2D) beams and split spatial beams to improve transmission efficiency. We analyze the 2D beam squint of the UPA and design a time-delay phased UPA for UAV-assisted THz communication systems. By introducing TTDs between the single RF chain and phase shifters, the beam squint can be controlled flexibly by introducing the delay between each antenna. When TTDs are arranged in both the horizontal and vertical dimensions, the coverage of the beams becomes more complicated compared to uniform linear arrays (ULA). Simulation results show that the proposed time-delay phased UPA can achieve better performance in both single-beam and multi-beam modes for single user and multi-user scenarios compared with conventional phased UPA, respectively. In addition, we propose frequency division beam multiple access (FDBMA) multi access technology, which achieves more efficient multi access by reusing resources from different frequency beam pairs. Finally, the results also show that the enlargement of the beamwidth through the proposed FDBMA strategy can also increase the performance in multi-user scenarios.
A Three-Dimensional Full-Coverage Operation Path Planning Method for Plant Protection Unmanned Aerial Vehicles Based on Energy Consumption Modeling
Authors: Yu Shaomeng , Zhu Jianxi , Shen Jiansheng , Yang Xin , Wang Pengfei
Published: September 2023

With the rapid development of precision agriculture technology worldwide, plant protection unmanned aerial vehicles (UAVs) have been widely applied in the prevention and control of agricultural pests and diseases due to their advantages such as unrestricted terrain, strong maneuverability, hover capability, and high operational efficiency. In view of the fact that most of the current path planning methods for plant protection UAVs are mainly applicable to large fields with relatively flat terrain, and there is a lack of three-dimensional path planning methods applicable to hilly orchards, as well as a lack of intuitive evaluation of the advantages and disadvantages of the paths by utilizing the amount of energy consumption, this paper proposes a three-dimensional (3D) path planning method for plant protection UAVs in hilly orchards. The method utilizes the three-dimensional (3D) coordinates of the operational area obtained from a realistic 3D model of the area, and determines the 3D operational path through the use of Boustrophedon Cellular Decomposition and the height variations of the operational area. Based on the induced power used by the plant protection UAV for flight and the power needed to overcome wind resistance, combined with the change of the load of the plant protection UAV and the supply situation, the relative energy consumption model of the plant protection UAV is constructed. Then, by optimizing the operational heading angle (1–180°), the 3D path with the minimum relative energy consumption is obtained. Through a simulation test, it is demonstrated that the path with the minimum relative energy consumption (operational heading angle of 133°) reduces the average relative energy consumption by 62.44% and 47.21% compared to the path with the maximum relative energy consumption (operational heading angle of 51°) and the average relative energy consumption, respectively. This proves the feasibility of the proposed path planning method in hilly orchard environments and provides a reference for the application of plant protection UAVs in such orchards.
IEC61131-3 Instruction List Language Processor for FPGAs
Authors: Hajduk Zbigniew
Published: September 2023

This paper presents the architecture and field-programmable gate array (FPGA) implementation of a 32-bit central processing unit (CPU) dedicated to programmable logic controllers (PLCs). The CPU instruction set directly matches the instructions of the IEC 61131-3 standard Instruction List (IL) language. The designed IL processor is capable of handling 1-bit, 8-bit, 16-bit, and 32-bit data types. Apart from integer arithmetic operations, the IL processor also performs single precision floating-point operations included in the IEC 61131-3 IL language specification. It also directly performs instructions with a parenthesis modifier for all supported data types and facilitates the fast execution of a code containing Boolean expressions. This paper also presents the performance evaluation results of the developed IL processor. Although the IL processor executed the test algorithms substantially faster than industrial PLCs (e.g., Siemens S7-1200 and Fanux VersaMax), it turned out to be significantly slower than high-performance programmable automation controllers (PACs).
Biotic Factors Drive Woody Plant Species Diversity across a Relative Density Gradient of Quercus aliena var. acuteserrata Maxim. in the Warm–Temperate Natural Oak Forest, Central China
Authors: Yu Chenyi , Ren Siyuan , Huang Yudie , Wang Guanjie , Liu Shengyun , Li Zhenjiang , Yuan Yabo , Huang Xin , Wang Ting
Published: September 2023

Woody plants are crucial components of forest ecosystems and play critical roles in regulating community succession and ecosystem function. Studying woody plant diversity and its influencing factors is thus important for understanding and protecting forest ecosystems. Quercus aliena var. acutiserrata is an important deciduous broadleaf species in the warm–temperate forest of central China. Multiple regression and structural equation modelling were used to discuss the effect of biotic and soil factors on tree species diversity across seven relative density gradients of Q. aliena var. acutiserrata trees in this zone. Our results showed that the following: (1) Species diversity showed significant decreasing trends with increasing relative density of Q. aliena var. acutiserrata. (2) As the relative density of the oak tree increased, some biotic factors (canopy density, and mean DBH) and soil factors (Soil SOC, AP, and AK) all showed significantly increasing trends, whereas the DBH variation (CVD) and soil pH displayed decreasing trends. (3) Biotic factor (e.g., mean DBH, CVD, and competition interaction) had strong direct effect on species diversity, and soil factors exerted indirect roles on tree diversity via biotic factors. Our results provide insight into biodiversity protection and scientific management in this warm–temperate natural oak forest.
Use of Theil for a Specific Duality Economy: Assessing the Impact of Digital Inclusive Finance on Urban-Rural Income Gap in Chongqing
Authors: Aik Nai Chiek , Zhang Qiurui
Published: September 2023

This study uses panel data from 2016 to 2020 to examine the impact of digital financial inclusion on income inequality in the urban-rural divide of Chongqing, China. The results suggest that increasing access to digital financial services could help narrow the income gap between urban and rural areas. However, the impact becomes significantly positive when controlling for other variables with the Random Effects regression model. Among the control variables, the urbanization rate and government expenditure are found to be significant determinants of income inequality in Chongqing. These findings offer insights for policymakers on the potential benefits of targeted interventions to promote financial inclusion and sustainable urbanization, while ensuring effective allocation of government spending to reduce income inequality.
Climate Change May Impact Nile Tilapia, Oreochromis niloticus (Linnaeus, 1758) Distribution in the Southeastern Arabian Peninsula through Range Contraction under Various Climate Scenarios
Authors: Esmaeili Hamid Reza , Eslami Barzoki Zohreh
Published: September 2023

Climate change is expected to affect freshwater water bodies worldwide, especially those located in semiarid and arid regions, including the Arabian Peninsula. Species distribution modeling has been widely used to predict the effects of climate changes on aquatic species. Occurrence records of the cichlid fish Nile tilapia, Oreochromis niloticus, were geographically mapped, followed by the implementation of species distribution models to delineate its range within the sensitive inland water system of the southeastern Arabian Peninsula. The analysis encompassed the examination of species presence data in the context of environmental variables, leading to the development of an ensemble model for habitat suitability, combining four distinct species distribution models. The findings indicated that the mean diurnal range and precipitation seasonality emerged as the most influential factors in predicting the suitability of habitats for O. niloticus. The response curve analysis indicated that the presence probability of O. niloticus decreased with increasing mean diurnal range and decreasing precipitation seasonality. The suitable distribution ranges for O. niloticus in the studied area were mainly distributed in the northeast of this region, where native/endemic fish diversity is high. The ensemble model results specified a significant impact of climate change on O. niloticus distribution, so highly suitable areas for this species will be reduced, while areas with low to moderate suitability increase slightly or remain unchanged. While O. niloticus is anticipated to display resilience and prosper under the influence of climate change, it remains paradoxical that its habitats are at risk of being compromised by climate-induced alterations. Consequently, even this resilient species stands susceptible to the repercussions of climate change. Due to the worldwide severe impacts of Nile tilapia, regular monitoring of freshwater ecosystems and fish fauna—especially in the northeast of the Arabian Peninsula, which has currently been invaded by this alien species—and protecting the region from key anthropogenic stressors are recommended to successfully conserve the freshwater fishes, which include about 22 recognized fish species in 16 genera, 10 families, 7 orders, and a class including 20 natives (7 endemic) species, out of which 13 species co-occur in sympatricity with O. niloticus.
Numerical Simulation of the Conjugate Heat Transfer of a “Fluid–Solid Body” System on an Unmatched Grid Interface
Authors: Korotkov Aleksey , Kozelkov Andrey , Kurkin Andrey , Giniyatullin Robert , Lashkin Sergey
Published: September 2023

Recently, when modeling transient problems of conjugate heat transfer, the independent construction of grid models for fluid and solid subdomains is increasingly being used. Such grid models, as a rule, are unmatched and require the development of special grid interfaces that match the heat fluxes at the interface. Currently, the most common sequential approach to modeling problems of conjugate heat transfer requires the iterative matching of boundary conditions, which can significantly slow down the process of the convergence of the solution in the case of modeling transient problems with fast processes. The present study is devoted to the development of a direct method for solving conjugate heat transfer problems on grid models consisting of inconsistent grid fragments on adjacent boundaries in which, in the general case, the number and location of nodes do not coincide. A conservative method for the discretization of the heat transfer equation by the direct method in the region of inconsistent interface boundaries between liquid and solid bodies is proposed. The proposed method for matching heat fluxes at mismatched boundaries is based on the principle of forming matched virtual boundaries, proposed in the GGI (General Grid Interface) method. A description of a numerical scheme is presented, which takes into account the different scales of cells and the sharply different thermophysical properties at the interface between liquid and solid media. An algorithm for constructing a conjugate matrix, the form of matrix coefficients responsible for conjugate heat transfer, and methods for calculating them are described. The operability of the presented method is demonstrated by the example of calculating conjugate heat transfer problems, the grid models of which consist of inconsistent grid fragments. The use of the direct conjugation method makes it possible to effectively solve both stationary and non-stationary problems using inconsistent meshes, without the need to modify them in the conjugation region within a single CFD solver.
A Genome-Wide Identification and Comparative Analysis of the Heavy-Metal-Associated Gene Family in Cucurbitaceae Species and Their Role in Cucurbita pepo under Arsenic Stress
Authors: Flores-Iga Gerardo , Lopez-Ortiz Carlos , Gracia-Rodriguez Celeste , Almeida Aldo , Nimmakayala Padma , Reddy Umesh K. , Balagurusamy Nagamani
Published: September 2023

The heavy-metal-associated (HMA) proteins are a class of PB1-type ATPases related to the intracellular transport and detoxification of metals. However, due to a lack of information regarding the HMA gene family in the Cucurbitaceae family, a comprehensive genome-wide analysis of the HMA family was performed in ten Cucurbitaceae species: Citrullus amarus, Citrullus colocynthis, Citrullus lanatus, Citrullus mucosospermus, Cucumis melo, Cucumis sativus, Cucurbita maxima, Cucurbita moschata, Cucurbita pepo, and Legenaria siceraria. We identified 103 Cucurbit HMA proteins with various members, ranging from 8 (Legenaria siceraria) to 14 (Cucurbita pepo) across species. The phylogenetic and structural analysis confirmed that the Cucurbitaceae HMA protein family could be further classified into two major clades: Zn/Co/Cd/Pb and Cu/Ag. The GO-annotation-based subcellular localization analysis predicted that all HMA gene family members were localized on membranes. Moreover, the analysis of conserved motifs and gene structure (intron/exon) revealed the functional divergence between clades. The interspecies microsynteny analysis demonstrated that maximum orthologous genes were found between species of the Citrullus genera. Finally, nine candidate HMA genes were selected, and their expression analysis was carried out via qRT-PCR in root, leaf, flower, and fruit tissues of C. pepo under arsenic stress. The expression pattern of the CpeHMA genes showed a distinct pattern of expression in root and shoot tissues, with a remarkable expression of CpeHMA6 and CpeHMA3 genes from the Cu/Ag clade. Overall, this study provides insights into the functional analysis of the HMA gene family in Cucurbitaceae species and lays down the basic knowledge to explore the role and mechanism of the HMA gene family to cope with arsenic stress conditions.
Tissue-Specific Tumour Suppressor and Oncogenic Activities of the Polycomb-like Protein MTF2
Authors: Ngubo Mzwanele , Moradi Fereshteh , Ito Caryn Y. , Stanford William L.
Published: September 2023

The Polycomb repressive complex 2 (PRC2) is a conserved chromatin-remodelling complex that catalyses the trimethylation of histone H3 lysine 27 (H3K27me3), a mark associated with gene silencing. PRC2 regulates chromatin structure and gene expression during organismal and tissue development and tissue homeostasis in the adult. PRC2 core subunits are associated with various accessory proteins that modulate its function and recruitment to target genes. The multimeric composition of accessory proteins results in two distinct variant complexes of PRC2, PRC2.1 and PRC2.2. Metal response element-binding transcription factor 2 (MTF2) is one of the Polycomb-like proteins (PCLs) that forms the PRC2.1 complex. MTF2 is highly conserved, and as an accessory subunit of PRC2, it has important roles in embryonic stem cell self-renewal and differentiation, development, and cancer progression. Here, we review the impact of MTF2 in PRC2 complex assembly, catalytic activity, and spatiotemporal function. The emerging paradoxical evidence suggesting that MTF2 has divergent roles as either a tumour suppressor or an oncogene in different tissues merits further investigations. Altogether, our review illuminates the context-dependent roles of MTF2 in Polycomb group (PcG) protein-mediated epigenetic regulation. Its impact on disease paves the way for a deeper understanding of epigenetic regulation and novel therapeutic strategies.
The Expression and Activation of the NF-κB Pathway Correlate with Methotrexate Resistance and Cell Proliferation in Acute Lymphoblastic Leukemia
Authors: Canevarolo Rafael Renatino , Cury Nathalia Moreno , Yunes José Andrés
Published: September 2023

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Although its prognosis continually improves with time, a significant proportion of patients still relapse from the disease because of the leukemia’s resistance to therapy. Methotrexate (MTX), a folic-acid antagonist, is a chemotherapy agent commonly used against ALL and as an immune-system suppressant for rheumatoid arthritis that presents multiple and complex mechanisms of action and resistance. Previous studies have shown that MTX modulates the nuclear factor kappa B (NF-κB) pathway, an important family of transcription factors involved in inflammation, immunity, cell survival, and proliferation which are frequently hyperactivated in ALL. Using a gene set enrichment analysis of publicly available gene expression data from 161 newly diagnosed pediatric ALL patients, we found the Tumor necrosis factor α (TNF-α) signaling pathway via NF-κB to be the most enriched Cancer Hallmark in MTX-poor-responder patients. A transcriptomic analysis using a panel of ALL cell lines (six B-cell precursor acute lymphoblastic leukemia and seven T-cell acute lymphoblastic leukemia) also identified the same pathway as differentially enriched among MTX-resistant cell lines, as well as in slowly dividing cells. To better understand the crosstalk between NF-κB activity and MTX resistance, we genetically modified the cell lines to express luciferase under an NF-κB-binding-site promoter. We observed that the fold change in NF-κB activity triggered by TNF-α (but not MTX) treatment correlated with MTX resistance and proliferation across the lines. At the individual gene level, NFKB1 expression was directly associated with a poorer clinical response to MTX and with both an increased TNF-α-triggered NF-κB activation and MTX resistance in the cell lines. Despite these results, the pharmacological inhibition (using BAY 11-7082 and parthenolide) or stimulation (using exogenous TNF-α supplementation) of the NF-κB pathway did not alter the MTX resistance of the cell lines significantly, evidencing a complex interplay between MTX and NF-κB in ALL.
Preserving Fragile History: Assessing the Feasibility of Segmenting Digitized Historical Documents with Modulation Depth Analysis
Authors: Zippert Patrick , Binder Felix , Hausotte Tino
Published: September 2023

Historical documents are often severely damaged, making it impossible to open them manually without causing further damage. To address this challenge, computed tomography (CT) has emerged as a non-destructive method to explore the inside in a different way. However, the use of ionising radiation in CT scanning raises concerns about its impact on fragile historical documents. This study presents a methodology that uses a test object to conduct preliminary investigations to evaluate the capability of a CT scanner for digital preservation of historical documents. By assessing the feasibility and determining the setting parameters in advance, the X-ray exposure to historical documents can be minimised. For this purpose, a large dataset of inter-page distances was obtained from CT scans of a specially developed test object. The results obtained show a consistent correlation between the page-to-page distances and the derived modulation depths. This method offers great potential for assessing the separability of the pages of historical documents even before they are exposed to radiation for digitisation. Overall, this study helps to reduce the impact of X-ray radiation on sensitive historical documents during digitisation using CT, with the aim of preserving this fragile cultural heritage for future generations.
Exploring the Potential of Sunflowers: Agronomy, Applications, and Opportunities within Bio-Circular-Green Economy
Authors: Puttha Ratchanee , Venkatachalam Karthikeyan , Hanpakdeesakul Sayomphoo , Wongsa Jittimon , Parametthanuwat Thanya , Srean Pao , Pakeechai Kanokporn , Charoenphun Narin
Published: September 2023

The present review article is intended to provide comprehensive insights into the techniques of sunflower cultivation, methods of processing, and opportunities for value addition through a variety of applications. Sunflower (Helianthus annuus L.) is an economically valuable crop, admired for its vibrant yellow flowers and seeds rich in high-quality oil. The oil derived from sunflower seeds is nutritionally valued for its high content of unsaturated fatty acids, such as linolenic and linoleic acids, which help to reduce cholesterol levels and prevent arterial fat clots. Moreover, it contains essential vitamins A, D, E, and K. Sunflower cultivation primarily occurs in warm regions, aligning with the plant’s climatic preferences. As a short-lived plant, sunflowers demonstrate drought resilience due to their deep root system. In recent years, the use of sunflowers has significantly expanded, driving economic growth. The demand for products derived from sunflowers, including sprouts, roasted seeds, seed oil, and even sunflower-based agricultural tourism, has increased exponentially. Notably, sunflower seeds and their oil hold particular importance as they form the basis for integrated production systems, contributing to the creation of various food and non-food products. By presenting this information, we aim to provide a comprehensive guide for those interested in enhancing the utilization of sunflowers across various sectors.
Reusing Coir-Based Substrates for Lettuce Growth: Nutrient Content and Phytonutrients Accumulation
Authors: Machado Rui , Alves-Pereira Isabel , Alves Inês , Ferreira Rui , Gruda Nazim
Published: September 2023

This research aimed to assess the influence of reusing coir-based substrates on growth, nutrient content, and phytonutrients accumulation in lettuce. The experiment included a new coir pith and four coir-based mixes (1) coir, biochar, and perlite; (2) coir, compost, and perlite; (3) coir, biochar, and pine bark; and (4) coir, compost, and pine bark. All mixes had been previously utilized to grow transplanted spinach and possessed identical ratios of 78:12:10% (v/v) among their components. Lettuce (Lactuca sativa L. cv. ‘Godzilla’) seedlings were transplanted into Styrofoam plant boxes. Each day, the planting boxes received a nutrient solution via drip irrigation. Plants grown in reused mixes had similar macronutrient concentrations as those grown in coir for the first time, except for N and K in the third mix. Plants grown in reused mixtures had similar yields as those in new coir. Lettuce heads yielded 4.6–4.9 kg/m2, while plants grown in reused mixtures had equal or higher total phenols than those in new coir. Ascorbic acid content was higher in plants cultivated in reused mixes. Coir-based growing media can be reused for another short-cycle crop, like lettuce, without yield loss or phytonutrients decrease.
Arginine Expedites Erastin-Induced Ferroptosis through Fumarate
Authors: Guo Xinxin , Guo Yubo , Li Jiahuan , Liu Qian , Wu Hao
Published: September 2023

Ferroptosis is a newly characterized form of programmed cell death. The fundamental biochemical feature of ferroptosis is the lethal accumulation of iron-catalyzed lipid peroxidation. It has gradually been recognized that ferroptosis is implicated in the pathogenesis of a variety of human diseases. Increasing evidence has shed light on ferroptosis regulation by amino acid metabolism. Herein, we report that arginine deprivation potently inhibits erastin-induced ferroptosis, but not RSL3-induced ferroptosis, in several types of mammalian cells. Arginine presence reduces the intracellular glutathione (GSH) level by sustaining the biosynthesis of fumarate, which functions as a reactive α,β-unsaturated electrophilic metabolite and covalently binds to GSH to generate succinicGSH. siRNA-mediated knockdown of argininosuccinate lyase, the critical urea cycle enzyme directly catalyzing the biosynthesis of fumarate, significantly decreases cellular fumarate and thus relieves erastin-induced ferroptosis in the presence of arginine. Furthermore, fumarate is decreased during erastin exposure, suggesting that a protective mechanism exists to decelerate GSH depletion in response to pro-ferroptotic insult. Collectively, this study reveals the ferroptosis regulation by the arginine metabolism and expands the biochemical functionalities of arginine.
A Blue Light-Responsive Strong Synthetic Promoter Based on Rational Design in Chlamydomonas reinhardtii
Authors: Chen Chen , Chen Jun , Wu Guangxi , Li Liling , Hu Zhangli , Li Xiaozheng
Published: September 2023

Chlamydomonas reinhardtii (C. reinhardtii) is a single-cell green alga that can be easily genetically manipulated. With its favorable characteristics of rapid growth, low cost, non-toxicity, and the ability for post-translational protein modification, C. reinhardtii has emerged as an attractive option for the biosynthesis of various valuable products. To enhance the expression level of exogenous genes and overcome the silencing of foreign genes by C. reinhardtii, synthetic promoters such as the chimeric promoter AR have been constructed and evaluated. In this study, a synthetic promoter GA was constructed by hybridizing core fragments from the natural promoters of the acyl carrier protein gene (ACP2) and the glutamate dehydrogenase gene (GDH2). The GA promoter exhibited a significant increase (7 times) in expressing GUS, over the AR promoter as positive control. The GA promoter also displayed a strong responsiveness to blue light (BL), where the GUS expression was doubled compared to the white light (WL) condition. The ability of the GA promoter was further tested in the expression of another exogenous cadA gene, responsible for catalyzing the decarboxylation of lysine to produce cadaverine. The cadaverine yield driven by the GA promoter was increased by 1–2 times under WL and 2–3 times under BL as compared to the AR promoter. This study obtained, for the first time, a blue light-responsive GDH2 minimal fragment in C. reinhardtii, which delivered a doubling effect under BL when used alone or in hybrid. Together with the strong GA synthetic promoter, this study offered useful tools of synthetic biology to the algal biotechnology field.
Exploring Tumor–Immune Interactions in Co-Culture Models of T Cells and Tumor Organoids Derived from Patients
Authors: Jeong So-Ra , Kang Minyong
Published: September 2023

The use of patient-derived tumor tissues and cells has led to significant advances in personalized cancer therapy and precision medicine. The advent of genomic sequencing technologies has enabled the comprehensive analysis of tumor characteristics. The three-dimensional tumor organoids derived from self-organizing cancer stem cells are valuable ex vivo models that faithfully replicate the structure, unique features, and genetic characteristics of tumors. These tumor organoids have emerged as innovative tools that are extensively employed in drug testing, genome editing, and transplantation to guide personalized therapy in clinical settings. However, a major limitation of this emerging technology is the absence of a tumor microenvironment that includes immune and stromal cells. The therapeutic efficacy of immune checkpoint inhibitors has underscored the importance of immune cells, particularly cytotoxic T cells that infiltrate the vicinity of tumors, in patient prognosis. To address this limitation, co-culture techniques combining tumor organoids and T cells have been developed, offering diverse avenues for studying individualized drug responsiveness. By integrating cellular components of the tumor microenvironment, including T cells, into tumor organoid cultures, immuno-oncology has embraced this technology, which is rapidly advancing. Recent progress in co-culture models of tumor organoids has allowed for a better understanding of the advantages and limitations of this novel model, thereby exploring its full potential. This review focuses on the current applications of organoid-T cell co-culture models in cancer research and highlights the remaining challenges that need to be addressed for its broader implementation in anti-cancer therapy.
Comparative Analysis of the Complete Mitochondrial Genomes of Apium graveolens and Apium leptophyllum Provide Insights into Evolution and Phylogeny Relationships
Authors: Li Xiaoyan , Li Mengyao , Li Weilong , Zhou Jin , Han Qiuju , Lu Wei , Luo Qin , Zhu Shunhua , Xiong Aisheng , Tan Guofei , Zheng Yangxia
Published: September 2023

The genus Apium, belonging to the family Apiaceae, comprises roughly 20 species. Only two species, Apium graveolens and Apium leptophyllum, are available in China and are both rich in nutrients and have favorable medicinal properties. However, the lack of genomic data has severely constrained the study of genetics and evolution in Apium plants. In this study, Illumina NovaSeq 6000 and Nanopore sequencing platforms were employed to identify the mitochondrial genomes of A. graveolens and A. leptophyllum. The complete lengths of the mitochondrial genomes of A. graveolens and A. leptophyllum were 263,017 bp and 260,164 bp, respectively, and contained 39 and 36 protein-coding genes, five and six rRNA genes, and 19 and 20 tRNA genes. Consistent with most angiosperms, both A. graveolens and A. leptophyllum showed a preference for codons encoding leucine (Leu). In the mitochondrial genome of A. graveolens, 335 SSRs were detected, which is higher than the 196 SSRs found in the mitochondrial genome of A. leptophyllum. Studies have shown that the most common RNA editing type is C-to-U, but, in our study, both A. graveolens and A. leptophyllum exhibited the U-C editing type. Furthermore, the transfer of the mitochondrial genomes of A. graveolens and A. leptophyllum into the chloroplast genomes revealed homologous sequences, accounting for 8.14% and 4.89% of the mitochondrial genome, respectively. Lastly, in comparing the mitochondrial genomes of 29 species, it was found that A. graveolens, A. leptophyllum, and Daucus carota form a sister group with a support rate of 100%. Overall, this investigation furnishes extensive insights into the mitochondrial genomes of A. graveolens and A. leptophyllum, thereby enhancing comprehension of the traits and evolutionary patterns within the Apium genus. Additionally, it offers supplementary data for evolutionary and comparative genomic analyses of other species within the Apiaceae family.
Development of Engineered-U1 snRNA Therapies: Current Status
Authors: Gonçalves Mariana , Santos Juliana Inês , Coutinho Maria Francisca , Matos Liliana , Alves Sandra
Published: September 2023

Splicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression. The majority of human genes that encode proteins undergo alternative pre-mRNA splicing and mutations that affect splicing are more prevalent than previously thought. Targeting aberrant RNA(s) may thus provide an opportunity to correct faulty splicing and potentially treat numerous genetic disorders. To that purpose, the use of engineered U1 snRNA (either modified U1 snRNAs or exon-specific U1s—ExSpeU1s) has been applied as a potentially therapeutic strategy to correct splicing mutations, particularly those affecting the 5′ splice-site (5′ss). Here we review and summarize a vast panoply of studies that used either modified U1 snRNAs or ExSpeU1s to mediate gene therapeutic correction of splicing defects underlying a considerable number of genetic diseases. We also focus on the pre-clinical validation of these therapeutic approaches both in vitro and in vivo, and summarize the main obstacles that need to be overcome to allow for their successful translation to clinic practice in the future.
On the Efficiency of the Density Functional Theory (DFT)-Based Computational Protocol for 1H and 13C Nuclear Magnetic Resonance (NMR) Chemical Shifts of Natural Products: Studying the Accuracy of the pecS-n (n = 1, 2) Basis Sets
Authors: Rusakov Yuriy Yu. , Semenov Valentin A. , Rusakova Irina L.
Published: September 2023

The basis set issue has always been one of the most important factors of accuracy in the quantum chemical calculations of NMR chemical shifts. In a previous paper, we developed new pecS-n (n = 1, 2) basis sets purposed for the calculations of the NMR chemical shifts of the nuclei of the most popular NMR-active isotopes of 1–2 row elements and successfully approbated these on the DFT calculations of chemical shifts in a limited series of small molecules. In this paper, we demonstrate the performance of the pecS-n (n = 1, 2) basis sets on the calculations of as much as 713 1H and 767 13C chemical shifts of 23 biologically active natural products with complicated stereochemical structures, carried out using the GIAO-DFT(PBE0) approach. We also proposed new alternative contraction schemes for our basis sets characterized by less contraction depth of the p-shell. New contraction coefficients have been optimized with the property-energy consistent (PEC) method. The accuracies of the pecS-n (n = 1, 2) basis sets of both the original and newly contracted forms were assessed on massive benchmark calculations of proton and carbon chemical shifts of a vast variety of natural products. It was found that less contracted pecS-n (n = 1, 2) basis sets provide no noticeable improvement in accuracy. These calculations represent the most austere test of our basis sets as applied to routine calculations of the NMR chemical shifts of real-life compounds.
Forensic Proteomics for the Discovery of New post mortem Interval Biomarkers: A Preliminary Study
Authors: Marrone Alessandro , La Russa Daniele , Barberio Laura , Murfuni Maria Stella , Gaspari Marco , Pellegrino Daniela
Published: September 2023

Estimating the time since death (post mortem interval, PMI) represents one of the most important tasks in daily forensic casework. For decades, forensic scientists have investigated changes in post mortem body composition, focusing on different physical, chemical, or biological aspects, to discover a reliable method for estimating PMI; nevertheless, all of these attempts remain unsuccessful considering the currently available methodical spectrum characterized by great inaccuracies and limitations. However, recent promising approaches focus on the post mortem decomposition of biomolecules. In particular, significant advances have been made in research on the post mortem degradation of proteins. In the present study, we investigated early post mortem changes (during the first 24 h) in the proteome profile of the pig skeletal muscle looking for new PMI specific biomarkers. By mass spectrometry (MS)-based proteomics, we were able to identify a total of nine potential PMI biomarkers, whose quantity changed constantly and progressively over time, directly or inversely proportional to the advancement of post mortem hours. Our preliminary study underlines the importance of the proteomic approach in the search for a reliable method for PMI determination and highlights the need to characterize a large number of reliable marker proteins useful in forensic practice for PMI estimation.
Phytocannabinoids Reduce Inflammation of Primed Macrophages and Enteric Glial Cells: An In Vitro Study
Authors: Cohen Gal , Gover Ofer , Schwartz Betty
Published: September 2023

Intestinal inflammation is mediated by a subset of cells populating the intestine, such as enteric glial cells (EGC) and macrophages. Different studies indicate that phytocannabinoids could play a possible role in the treatment of inflammatory bowel disease (IBD) by relieving the symptoms involved in the disease. Phytocannabinoids act through the endocannabinoid system, which is distributed throughout the mammalian body in the cells of the immune system and in the intestinal cells. Our in vitro study analyzed the putative anti-inflammatory effect of nine selected pure cannabinoids in J774A1 macrophage cells and EGCs triggered to undergo inflammation with lipopolysaccharide (LPS). The anti-inflammatory effect of several phytocannabinoids was measured by their ability to reduce TNFα transcription and translation in J774A1 macrophages and to diminish S100B and GFAP secretion and transcription in EGCs. Our results demonstrate that THC at the lower concentrations tested exerted the most effective anti-inflammatory effect in both J774A1 macrophages and EGCs compared to the other phytocannabinoids tested herein. We then performed RNA-seq analysis of EGCs exposed to LPS in the presence or absence of THC or THC-COOH. Transcriptomic analysis of these EGCs revealed 23 differentially expressed genes (DEG) compared to the treatment with only LPS. Pretreatment with THC resulted in 26 DEG, and pretreatment with THC-COOH resulted in 25 DEG. To evaluate which biological pathways were affected by the different phytocannabinoid treatments, we used the Ingenuity platform. We show that THC treatment affects the mTOR and RAR signaling pathway, while THC-COOH mainly affects the IL6 signaling pathway.
NET Formation Was Reduced via Exposure to Extremely Low-Frequency Pulsed Electromagnetic Fields
Authors: Linnemann Caren , Sahin Filiz , Chen Yangmengfan , Falldorf Karsten , Ronniger Michael , Histing Tina , Nussler Andreas K. , Ehnert Sabrina
Published: September 2023

Fracture-healing is a highly complex and timely orchestrated process. Non-healing fractures are still a major clinical problem and treatment remains difficult. A 16 Hz extremely low-frequency pulsed electromagnetic field (ELF-PEMF) was identified as non-invasive adjunct therapy supporting bone-healing by inducing reactive oxygen species (ROS) and Ca2+-influx. However, ROS and Ca2+-influx may stimulate neutrophils, the first cells arriving at the wounded site, to excessively form neutrophil extracellular traps (NETs), which negatively affects the healing process. Thus, this study aimed to evaluate the effect of this 16 Hz ELF-PEMF on NET formation. Neutrophils were isolated from healthy volunteers and exposed to different NET-stimuli and the 16 Hz ELF-PEMF. NETs were quantified using Sytox Green Assay and immunofluorescence, Ca2+-influx and ROS with fluorescence probes. In contrast to mesenchymal cells, ELF-PEMF exposure did not induce ROS and Ca2+-influx in neutrophils. ELF-PEMF exposure did not result in basal or enhanced PMA-induced NET formation but did reduce the amount of DNA released. Similarly, NET formation induced by LPS and H2O2 was reduced through exposure to ELF-PEMF. As ELF-PEMF exposure did not induce NET release or negatively affect neutrophils, the ELF-PEMF exposure can be started immediately after fracture treatment.
Regulatory Mechanism of the IL-33–IL-37 Axis via Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis
Authors: Tsuji Gaku , Yamamura Kazuhiko , Kawamura Koji , Kido-Nakahara Makiko , Ito Takamichi , Nakahara Takeshi
Published: September 2023

Interleukin (IL)-33 and IL-37 have been identified as novel cytokines involved in various inflammatory diseases. However, their specific roles remain largely unknown. Recent studies have shown that IL-33, which triggers inflammation, and IL-37, which suppresses it, cooperatively regulate the balance between inflammation and anti-inflammation. IL-33 and IL-37 are also deeply involved in the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. Furthermore, a signaling pathway by which aryl hydrocarbon receptor (AHR), a receptor for dioxins, regulates the expression of IL-33 and IL-37 has been revealed. Here, we outline recent findings on the mechanisms regulating IL-33 and IL-37 expression in AD and psoriasis. IL-33 expression is partially dependent on mitogen-activated protein kinase (MAPK) activation, and IL-37 has a role in suppressing MAPK in human keratinocytes. Furthermore, IL-33 downregulates skin barrier function proteins including filaggrin and loricrin, thereby downregulating the expression of IL-37, which colocalizes with these proteins. This leads to an imbalance of the IL-33–IL-37 axis, involving increased IL-33 and decreased IL-37, which may be associated with the pathogenesis of AD and psoriasis. Therefore, AHR-mediated regulation of the IL-33–IL-37 axis may lead to new therapeutic strategies for the treatment of AD and psoriasis.
The Association of APOE ε4 Allele with Retinal Layer Thickness and Microvasculature in Older Adults: Optic Nerve Decline and Cognitive Change Study
Authors: Sheriff Samran , Shen Ting , Saks Danit , Schultz Angela , Francis Heather , Wen Wei , Jiang Jiyang , Mirzaei Mehdi , Gupta Veer , Fiatarone Singh Maria , Sachdev Perminder S. , Graham Stuart L. , Gupta Vivek
Published: September 2023

Purpose: To investigate the relationship between the apolipoprotein E (APOE) ε4 allele and retinal structural and vascular characteristics in older adult participants from several research studies. We also studied the relationship between these structural and vascular characteristics with multifocal visual evoked potential (mfVEP) indices, neuropsychological parameters and MRI brain volumes in these participants. Methods: In this study, 109 participants with a mean (SD) age of 67.1 (9.0) years were recruited. Participants were classified as APOE ε4 carriers or non-carriers based on the presence or absence of the ε4 allele. Baseline measurements included peripapillary retinal nerve fibre layer optical coherence tomography (RNFL OCT), and OCT–angiography (OCT-A) for evaluation of the retinal layer thickness and vessel density (VD) parameters. A multifocal visual evoked potential (mfVEP) test, including amplitude and latency, was used to assess the visual pathway function. Finally, cognitive function was evaluated using a battery of neuropsychological tests. OCT-A images were analysed in ImageJ to quantify VD in the superficial and deep vascular plexus and the size of the foveal avascular zone (FAZ). The relationship between carriers of APOE ε4 allele and these ocular parameters was analysed using generalised estimating equation (GEE) models and data adjusted for age, sex and inter-eye differences as within-subject variables (p < 0.05). Results: Twenty-four participants were APOE ε4 carriers. Temporal RNFL thickness was decreased in APOE ε4 carriers (p < 0.01). Vessel density between carriers and non-carriers was not significantly different at either the superficial or deep level. The FAZ area was significantly smaller in ε4 carriers in both superficial (p < 0.01) and deep layers (p < 0.003). Conclusions: Retinal abnormalities were present in participants with increased genetic risk of dementia due to presence of the ε4 allele. These findings provide preliminary evidence for their potential role in the diagnosis of dementia.