bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular Vesicular miRNA in Pancreatic Cancer: From Lab to Therapy
Authors: Tiwari Prashant Kumar , Shanmugam Poojhaa , Karn Vamika , Gupta Saurabh , Mishra Richa , Rustagi Sarvesh , Chouhan Mandeep , Verma Devvret , Jha Niraj Kumar , Kumar Sanjay
Published: June 2024

Pancreatic cancer is a prevalent lethal gastrointestinal cancer that generally does not show any symptoms until it reaches advanced stages, resulting in a high mortality rate. People at high risk, such as those with a family history or chronic pancreatitis, do not have a universally accepted screening protocol. Chemotherapy and radiotherapy demonstrate limited effectiveness in the management of pancreatic cancer, emphasizing the urgent need for innovative therapeutic strategies. Recent studies indicated that the complex interaction among pancreatic cancer cells within the dynamic microenvironment, comprising the extracellular matrix, cancer-associated cells, and diverse immune cells, intricately regulates the biological characteristics of the disease. Additionally, mounting evidence suggests that EVs play a crucial role as mediators in intercellular communication by the transportation of different biomolecules, such as miRNA, proteins, DNA, mRNA, and lipids, between heterogeneous cell subpopulations. This communication mediated by EVs significantly impacts multiple aspects of pancreatic cancer pathogenesis, including proliferation, angiogenesis, metastasis, and resistance to therapy. In this review, we delve into the pivotal role of EV-associated miRNAs in the progression, metastasis, and development of drug resistance in pancreatic cancer as well as their therapeutic potential as biomarkers and drug-delivery mechanisms for the management of pancreatic cancer.
Unveiling the RKIP and EGFR Inverse Relationship in Solid Tumors: A Case Study in Cervical Cancer
Authors: Cardoso-Carneiro Diana , Pinheiro Joana , Fontão Patrícia , Nogueira Rosete , Gabriela-Freitas Maria , Raquel-Cunha Ana , Mendes Adriana , Longatto-Filho Adhemar , Marques Fábio , Moreira Marise A. R. , Reis Rui M. , Martinho Olga
Published: June 2024

Raf Kinase Inhibitor Protein (RKIP) is recognized as a bona fide tumor suppressor gene, and its diminished expression or loss is associated with the progression and poor prognosis of various solid tumors. It exerts multifaceted roles in carcinogenesis by modulating diverse intracellular signaling pathways, including those governed by HER receptors such as MAPK. Given the significance of HER receptor overexpression in numerous tumor types, we investigated the potential oncogenic relationship between RKIP and HER receptors in solid tumors. Through a comprehensive in silico analysis of 30 TCGA PanCancer Atlas studies encompassing solid tumors (10,719 samples), we uncovered compelling evidence of an inverse correlation between RKIP and EGFR expression in solid tumors observed in 25 out of 30 studies. Conversely, a predominantly positive association was noted for the other HER receptors (ERBB2, ERBB3, and ERBB4). In particular, cervical cancer (CC) emerged as a tumor type exhibiting a robust inverse association between RKIP and EGFR expression, a finding that was further validated in a cohort of 202 patient samples. Subsequent in vitro experiments involving pharmacological and genetic modulation of EGFR and RKIP showed that RKIP depletion led to significant upregulation of EGFR mRNA levels and induction of EGFR phosphorylation. Conversely, EGFR overactivation decreased RKIP expression in CC cell lines. Additionally, we identified a common molecular signature among patients depicting low RKIP and high EGFR expression and demonstrated the prognostic value of this inverse correlation in CC patients. In conclusion, our findings reveal an inverse association between RKIP and EGFR expression across various solid tumors, shedding new light on the underlying molecular mechanisms contributing to the aggressive phenotype associated with RKIP and EGFR in cervical cancer.
Role of 4-Thiazolidinone–Pyrazoline/Indoline Hybrids Les-4369 and Les-3467 in BJ and A549 Cell Lines
Authors: Kosińska Karolina , Skóra Bartosz , Holota Serhii , Shepeta Yulia , Tabęcka-Łonczyńska Anna , Lesyk Roman , Szychowski Konrad A.
Published: June 2024

Cancer is one of the most important problems of modern societies. Recently, studies have reported the anticancer properties of rosiglitazone related to its ability to bind peroxisome proliferator receptor γ (PPARγ), which has various effects on cancer and can inhibit cell proliferation. In this study, we investigated the effect of new 4-thiazolidinone (4-TZD) hybrids Les-4369 and Les-3467 and their effect on reactive oxygen species (ROS) production, metabolic activity, lactate dehydrogenase (LDH) release, caspase-3 activity, and gene and protein expression in human foreskin fibroblast (BJ) cells and lung adenocarcinoma (A549) cells. The ROS production and caspase-3 activity were mainly increased in the micromolar concentrations of the studied compounds in both cell lines. Les-3467 and Les-4369 increased the mRNA expression of PPARG, P53 (tumor protein P53), and ATM (ATM serine/threonine kinase) in the BJ cells, while the mRNA expression of these genes (except PPARG) was mainly decreased in the A549 cells treated with both of the tested compounds. Our results indicate a decrease in the protein expression of AhR, PPARγ, and PARP-1 in the BJ cells exposed to 1 µM Les-3467 and Les-4369. In the A549 cells, the protein expression of AhR, PPARγ, and PARP-1 increased in the treatment with 1 µM Les-3467 and Les-4369. We have also shown the PPARγ modulatory properties of Les-3467 and Les-4369. However, both compounds prove weak anticancer properties evidenced by their action at high concentrations and non-selective effects against BJ and A549 cells.
Pirfenidone Reverts Global DNA Hypomethylation, Promoting DNMT1/UHRF/PCNA Coupling Complex in Experimental Hepatocarcinoma
Authors: Miranda-Roblero Hipolito Otoniel , Saavedra-Salazar Liliana Faridi , Galicia-Moreno Marina , Arceo-Orozco Scarlet , Caloca-Camarena Fernando , Sandoval-Rodriguez Ana , García-Bañuelos Jesús , Frias-Gonzalez Claudia , Almeida-López Mónica , Martínez-López Erika , Armendariz-Borunda Juan , Monroy-Ramirez Hugo Christian
Published: June 2024

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in the carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-Acetylaminofluorene (2-AAF). The HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.
An Advanced Approach to Object Detection and Tracking in Robotics and Autonomous Vehicles Using YOLOv8 and LiDAR Data Fusion
Authors: Dai Yanyan , Kim Deokgyu , Lee Kidong
Published: June 2024

Accurately and reliably perceiving the environment is a major challenge in autonomous driving and robotics research. Traditional vision-based methods often suffer from varying lighting conditions, occlusions, and complex environments. This paper addresses these challenges by combining a deep learning-based object detection algorithm, YOLOv8, with LiDAR data fusion technology. The principle of this combination is to merge the advantages of these technologies: YOLOv8 excels in real-time object detection and classification through RGB images, while LiDAR provides accurate distance measurement and 3D spatial information, regardless of lighting conditions. The integration aims to apply the high accuracy and robustness of YOLOv8 in identifying and classifying objects, as well as the depth data provided by LiDAR. This combination enhances the overall environmental perception, which is critical for the reliability and safety of autonomous systems. However, this fusion brings some research challenges, including data calibration between different sensors, filtering ground points from LiDAR point clouds, and managing the computational complexity of processing large datasets. This paper presents a comprehensive approach to address these challenges. Firstly, a simple algorithm is introduced to filter out ground points from LiDAR point clouds, which are essential for accurate object detection, by setting different threshold heights based on the terrain. Secondly, YOLOv8, trained on a customized dataset, is utilized for object detection in images, generating 2D bounding boxes around detected objects. Thirdly, a calibration algorithm is developed to transform 3D LiDAR coordinates to image pixel coordinates, which are vital for correlating LiDAR data with image-based object detection results. Fourthly, a method for clustering different objects based on the fused data is proposed, followed by an object tracking algorithm to compute the 3D poses of objects and their relative distances from a robot. The Agilex Scout Mini robot, equipped with Velodyne 16-channel LiDAR and an Intel D435 camera, is employed for data collection and experimentation. Finally, the experimental results validate the effectiveness of the proposed algorithms and methods.
A Road Crack Segmentation Method Based on Transformer and Multi-Scale Feature Fusion
Authors: Xu Yang , Xia Yonghua , Zhao Quai , Yang Kaihua , Li Qiang
Published: June 2024

To ensure the safety of vehicle travel, the maintenance of road infrastructure has become increasingly critical, with efficient and accurate detection techniques for road cracks emerging as a key research focus in the industry. The development of deep learning technologies has shown tremendous potential in improving the efficiency of road crack detection. While convolutional neural networks have proven effective in most semantic segmentation tasks, overcoming their limitations in road crack segmentation remains a challenge. To address this, this paper proposes a novel road crack segmentation network that leverages the powerful spatial feature modeling capabilities of Swin Transformer and the Encoder–Decoder architecture of DeepLabv3+. Additionally, the incorporation of a multi-scale coding module and attention mechanism enhances the network’s ability to densely fuse multi-scale features and expand the receptive field, thereby improving the integration of information from feature maps. Performance comparisons with current mainstream semantic segmentation models on crack datasets demonstrate that the proposed model achieves the best results, with an MIoU of 81.06%, Precision of 79.95%, and F1-score of 77.56%. The experimental results further highlight the model’s superior ability in identifying complex and irregular cracks and extracting contours, providing guidance for future applications in this field.
A Closer Look at the Statistical Behavior of a Chaotic System with Message Inclusion for Cryptographic Applications
Authors: Lupu (Blaj) Adina Elena , Vlad Adriana
Published: June 2024

One technique, especially in chaos-based cryptographic applications, is to include the message in the evolution of the dynamical system. This paper aims to find out if and to what extent the statistical behavior of the chaotic system is affected by the message inclusion in its dynamic evolution. The study is illustrated by the dynamical system described by the logistic map in cryptographic applications based on images. The evaluation of the statistical behavior was performed on an original scheme proposed. The Monte Carlo analysis of the applied Kolmogorov–Smirnov statistical test revealed that the dynamical system in the processing scheme with message inclusion does not modify its proper statistical behavior (revealed by definition relation). This was possible due to the proposed scheme designed. Namely, this scheme contains a decision switch which, supported by an appropriate choice of the magnitude of the scaling factor, ensures that the values of the dynamical system are maintained in the definition domain. The proposed framework for analyzing the statistical properties and for preserving the dynamical system behavior is one main contribution of this research. The message inclusion scheme also provides an enhancement with cryptographic mixing functions applied internally; the statistical behavior of the dynamical system is also analyzed in this case. Thus, the paper contributes to the theoretical complex characterization of the dynamical system considering also the message inclusion case.
Differentiation in Leaf Functional Traits and Driving Factors of the Allopatric Distribution of Tetraploid and Octaploid Buddleja macrostachya in the Sino-Himalayan Region
Authors: Gong Weichang , Li He , Fu Hongbo , Wang Chuanming
Published: June 2024

Leaf functional traits reflect species’ adaptive strategies and habitat requirements. Examining intra-specific variations and their underlying drivers can aid in comprehending species differentiation and adaptation. Here, we investigated the leaf functional traits of Buddleja macrostachya tetraploids and octaploids across 18 sites in the Sino-Himalayan region. The habitat environmental variables were also recorded. In this study, leaf functional traits showed a considerable differentiation in both tetraploid and octaploid B. macrostachya. Redundancy analysis (RDA) revealed that the octaploid cytotypes displayed higher specific leaf area, leaf total nitrogen and phosphorus concentrations, water-use efficiency, and light-use efficiency in contrast to the tetraploid plants. These functional leaf traits exhibited different plasticity levels in both taxa. A positive link was found between habitat altitude and soil total P concentration and the geographic distribution of the B. macrostachya complex, using RDA and Pearson’s correlation. Our findings suggest that both tetraploid and octaploid B. macrostachya exhibited divergent ecological strategies, conservative and acquisitive strategies, respectively. The ecological adaptability of species within the B. macrostachya complex is enhanced by the combination of divergent ecological strategies and high phenotypic plasticity of distinct key ecological traits. Furthermore, abiotic environmental factors influenced the allopatric geographic distribution pattern of the B. macrostachya complex in the Sino-Himalayan region.
Homogenization of the Color of Beech Sapwood and False Heartwood by the Steaming Process
Authors: Dzurenda Ladislav , Dudiak Michal
Published: June 2024

This work presents the results of the homogenization of the color of sapwood and false heartwood Fagus sylvatica L. into a uniform color shade due to the influence of the temperature of saturated moist air and saturated water steam in individual steaming modes. The results of analyses of the influence of temperature within 24 h point out the different changes in the color of the sapwood and the wood of the false heartwood when the uniform color of the beech wood is achieved by the steaming process. By steaming beech wood with a false heartwood saturated with moist air at a temperature of tI = 95 °C during τ = 24 h, the color of the sapwood does not merge with the color of the wood of the false heartwood. The sapwood darkens and, on the other hand, the wood of the false heartwood slightly lightens, while the significant color contrast is removed, but the color homogenization in the individual zones does not occur. The unification of the colors in individual zones occurs during the steaming process at a temperature of saturated water steam tII ≈ 105 °C in 18 h, where the resulting brown color is identified in the color space CIE L*a*b* by the values of the lightness L* = 61.3 ± 2.2 and of the red color a* = 12.4 ± 1.3 and yellow color b* = 19.5 ± 1.4. The most pronounced homogenization of the color occurs through the steaming process at a temperature of saturated water steam tIII ≈ 120 °C, where the wood acquires a uniform dark brown–gray color in a time of τ ≈ 9 h steaming. The coordinates of the color-homogenized steamed beech wood are L* = 55.9 ± 1.9, a* = 12.3 ± 1.2, and b* = 19.6 ± 1.3. The unification of the colors by the steaming process is achieved by darkening both the sapwood and the wood of the false heartwood. In the overall color homogenization, the sapwood and the wood of the false heartwood do not participate equally in the steaming process. While the total color difference between the sapwood and a color homogenized state is quantified by the value ∆EtI* = 8, ∆EtIII* = 22.7, the total color difference in the wood with a false heartwood is only ∆EtI* = 1.9, ∆EtIII* = 11.8.
What Drives the Spatial Variation of Interregional Ancient Trees? A Geoinformatics–Based Approach in Henan, Central China
Authors: Hou Heping , Ren Wanqian , Wang Zexin , He Jing , Liu Binghui , Jing Ying
Published: June 2024

In the context of ecological civilization construction in China, interregional ancient trees are important natural and cultural resources, and it is vital that they are effectively protected and utilized according to their spatial distribution and regional conditions in order to provide a balance between local economic development and the ecological environment. This article analyzes the spatial heterogeneity of 26,842 ancient trees and explores the underlying natural and human factors by using geoinformatics–based techniques (i.e., the nearest neighbor index, kernel density, spatial autocorrelation, and the geographically weighted regression model) in Henan Province, Central China. The research findings conclude that: (1) The interregional ancient trees show positive spatial autocorrelation, and the aggregation effect in Western Henan is the most significant. (2) The growing environment and elevation exert a more obvious influence on the spatial pattern of interregional ancient trees. (3) The main influencing factors per region are different, for example, historical culture in Western Henan, water source and elevation in Southern Henan, and the growing environment in Eastern Henan, while ancient trees in Northern Henan have a weak relationship with each factor. This research facilitates political strategy making for sustainable development and the protection of interregional ancient trees.
Effects of Drought Stress on Abscisic Acid Content and Its Related Transcripts in Allium fistulosum—A. cepa Monosomic Addition Lines
Authors: Nakajima Tetsuya , Yaguchi Shigenori , Hirata Sho , Abdelrahman Mostafa , Wada Tomomi , Mega Ryosuke , Shigyo Masayoshi
Published: June 2024

Climate change has resulted in an increased demand for Japanese bunching onions (Allium fistulosum L., genomes FF) with drought resistance. A complete set of alien monosomic addition lines of A. fistulosum with extra chromosomes from shallot (A. cepa L. Aggregatum group, AA), represented as FF + 1A–FF + 8A, displays a variety of phenotypes that significantly differ from those of the recipient species. In this study, we investigated the impact of drought stress on abscisic acid (ABA) and its precursor, β-carotene, utilizing this complete set. In addition, we analyzed the expression levels of genes related to ABA biosynthesis, catabolism, and drought stress signal transduction in FF + 1A and FF + 6A, which show characteristic variations in ABA accumulation. A number of unigenes related to ABA were selected through a database using Allium TDB. Under drought conditions, FF + 1A exhibited significantly higher ABA and β-carotene content compared with FF. Additionally, the expression levels of all ABA-related genes in FF + 1A were higher than those in FF. These results indicate that the addition of chromosome 1A from shallot caused the high expression of ABA biosynthesis genes, leading to increased levels of ABA accumulation. Therefore, it is expected that the introduction of alien genes from the shallot will upwardly modify ABA content, which is directly related to stomatal closure, leading to drought stress tolerance in FF.
Long Noncoding RNA 6302 Regulates Chicken Preadipocyte Differentiation by Targeting SLC22A16
Authors: Ma Xiangfei , He Yuehua , Liu Cong , Zhu Tingqi , Li Donghua , Li Wenting , Sun Guirong , Kang Xiangtao
Published: June 2024

The excessive deposition of abdominal adipocytes in chickens is detrimental to poultry production. However, the regulatory factors that affect abdominal adipogenesis in chickens are still poorly understood. SLC22A16 is differentially expressed in abdominal preadipocytes and 10-day differentiated adipocytes in chickens, but its role in regulating chicken adipogenesis has not been reported. In this study, the function of SLC22A16 in chicken abdominal preadipocytes was investigated. SLC22A16 is significantly upregulated during abdominal adipocyte differentiation. The overexpression of SLC2A16 upregulated the expression of adipogenic marker genes and proliferation-related genes, and promoted the proliferation of adipocytes and the accumulation of triglycerides. The knockdown of SLC22A16 downregulated the expression of adipogenic marker genes and proliferation-related genes, inhibited the proliferation of adipocytes, and impaired the accumulation of triglycerides in adipocytes. In addition, LNC6302 was differentially expressed in abdominal preadipocytes and mature adipocytes, and was significantly positively correlated with the expression of SLC22A16. Interference with LNC6302 inhibits the expression of adipogenic marker genes and proliferation-related genes. The data supported the notion that LNC6302 promotes the differentiation of chicken abdominal adipocytes by cis-regulating the expression of SLC22A16. This study identified the role of SLC22A16 in the differentiation and proliferation of chicken adipocytes, providing a potential target for improving abdominal adipogenesis in chickens.
A Small Auxin-Up RNA Gene, IbSAUR36, Regulates Adventitious Root Development in Transgenic Sweet Potato
Authors: Zhou Yuanyuan , Li Aixian , Du Taifeng , Qin Zhen , Zhang Liming , Wang Qingmei , Li Zongyun , Hou Fuyun
Published: June 2024

Small auxin-upregulated RNAs (SAURs), as the largest family of early auxin-responsive genes, play important roles in plant growth and development processes, such as auxin signaling and transport, hypocotyl development, and tolerance to environmental stresses. However, the functions of few SAUR genes are known in the root development of sweet potatoes. In this study, an IbSAUR36 gene was cloned and functionally analyzed. The IbSAUR36 protein was localized to the nucleus and plasma membrane. The transcriptional level of this gene was significantly higher in the pencil root and leaf.This gene was strongly induced by indole-3-acetic acid (IAA), but it was downregulated under methyl-jasmonate(MeJA) treatment. The promoter of IbSAUR36 contained the core cis-elements for phytohormone responsiveness. Promoter β-glucuronidase (GUS) analysis in Arabidopsis showed that IbSAUR36 is highly expressed in the young tissues of plants, such as young leaves, roots, and buds. IbSAUR36-overexpressing sweet potato roots were obtained by an efficient Agrobacterium rhizogenes-mediated root transgenic system. We demonstrated that overexpression of IbSAUR36 promoted the accumulation of IAA, upregulated the genes encoding IAA synthesis and its signaling pathways, and downregulated the genes encoding lignin synthesis and JA signaling pathways. Taken together, these results show that IbSAUR36 plays an important role in adventitious root (AR) development by regulating IAA signaling, lignin synthesis, and JA signaling pathways in transgenic sweet potatoes.
Breastfeeding Intention and Breastfeeding Postpartum Outcomes between High-Risk and Low-Risk Pregnant Women: A Greek Prospective Cohort Study
Authors: Brani Panagiota , Mrvoljak-Theodoropoulou Irina , Pechlivani Fani , Iliadou Maria , Antoniou Evangelia , Daskalakis Georgios , Drakakis Peter , Dagla Maria
Published: June 2024

Background: This prospective cohort study, conducted from pregnancy to six months postpartum and grounded in STROBE methodology, quantitatively explores the relationship between antenatal breastfeeding intentions and subsequent breastfeeding outcomes among high-risk pregnant women, compared to a low-risk pregnancy group. Methods: The study was conducted in one of the largest public hospitals in Attica that provides care to pregnant women, enrolling 380 participants divided into high-risk (n = 200) and low-risk (n = 180) cohorts. Data were collected over 20 months (starting from the end of May 2020 until January 2022), spanning from pregnancy to six months postpartum, via comprehensive questionnaires. Results: Statistical analysis revealed a pronounced correlation between prenatal breastfeeding intentions and actual breastfeeding behaviors across both groups. Specifically, 81.1% of women in the high-risk group and 82.5% in the low-risk group expressed intentions of exclusively breastfeeding during pregnancy. By six months postpartum, 54.9% of the high-risk and 64.3% of the low-risk pregnancy group managed to sustain breastfeeding. Extended antenatal hospitalization emerged as a statistically significant factor (p = 0.045) negatively impacting exclusive breastfeeding intentions among high-risk pregnancies. Conclusion: The findings illuminate the critical influence of antenatal intentions on breastfeeding outcomes, particularly among high-risk pregnancies. Moreover, the study identifies the detrimental effect of prolonged hospital stays on breastfeeding aspirations. These insights underscore the necessity for nuanced, supportive interventions aimed at bolstering breastfeeding rates, thereby advancing maternal and neonatal health objectives aligned with World Health Organization recommendations.
Research on the Geographical Pattern, Evolution Model, and Driving Mechanism of Carbon Emission Density from Urban Industrial Land in the Yangtze River Economic Belt of China
Authors: Xie Fei , Zhang Shuaibing , Zhang Qipeng , Zhao Sidong , Lai Min
Published: June 2024

To achieve the goals of “carbon peaking and carbon neutrality”, this paper puts forward the connotation and measurement method for the carbon emission intensity of urban industrial land and conducts an empirical study with the Yangtze River Economic Belt (YREB) as an example. We defined the carbon intensity of urban industrial land as the industrial carbon emissions per unit area of land, which is a spatial mapping of urban industrial economic development and carbon spillover and a key indicator for urban and territorial spatial planning oriented towards the “dual carbon” goal. Findings: The carbon emission density of industrial land in the YREB varied greatly between cities and exhibited significant positive spatial autocorrelation. In addition, the geographical pattern and spatio-temporal evolution model of the urban industrial land carbon emission density had a very complex driving mechanism, and different factors had significant synergistic effects. Therefore, it is suggested that while striving towards the goal of “dual carbon”, the government should incorporate the carbon emission density indicator of urban industrial land into the urban and territorial spatial planning system, and based on the threshold of the medium suitable density, they should design differentiated management policies according to concrete urban policies and encourage cooperation among cities to jointly promote carbon emission management of urban industrial land. In policy design, emphasis should also be placed on highlighting the interactive effects of foreign direct investment, fiscal expenditure, and the number of patent authorizations as well as constructing a combination of policies centered around them to better leverage the impacts of globalization, government intervention, and innovation.
Modulation of Gut Microbial Biomarkers and Metabolites in Cancer Management by Tea Compounds
Authors: Leung Hoi Kit Matthew , Lo Emily Kwun Kwan , Zhang Fangfei , Felicianna  , Ismaiah Marsena Jasiel , Chen Congjia , El-Nezami Hani
Published: June 2024

Cancers are causing millions of deaths and leaving a huge clinical and economic burden. High costs of cancer drugs are limiting their access to the growing number of cancer cases. The development of more affordable alternative therapy could reach more patients. As gut microbiota plays a significant role in the development and treatment of cancer, microbiome-targeted therapy has gained more attention in recent years. Dietary and natural compounds can modulate gut microbiota composition while providing broader and more accessible access to medicine. Tea compounds have been shown to have anti-cancer properties as well as modulate the gut microbiota and their related metabolites. However, there is no comprehensive review that focuses on the gut modulatory effects of tea compounds and their impact on reshaping the metabolic profiles, particularly in cancer models. In this review, the effects of different tea compounds on gut microbiota in cancer settings are discussed. Furthermore, the relationship between these modulated bacteria and their related metabolites, along with the mechanisms of how these changes led to cancer intervention are summarized.
Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies
Authors: Bruserud Øystein , Selheim Frode , Hernandez-Valladares Maria , Reikvam Håkon
Published: June 2024

We review the importance of monocytic differentiation and differentiation induction in non-APL (acute promyelocytic leukemia) variants of acute myeloid leukemia (AML), a malignancy characterized by proliferation of immature myeloid cells. Even though the cellular differentiation block is a fundamental characteristic, the AML cells can show limited signs of differentiation. According to the French–American–British (FAB-M4/M5 subset) and the World Health Organization (WHO) 2016 classifications, monocytic differentiation is characterized by morphological signs and the expression of specific molecular markers involved in cellular communication and adhesion. Furthermore, monocytic FAB-M4/M5 patients are heterogeneous with regards to cytogenetic and molecular genetic abnormalities, and monocytic differentiation does not have any major prognostic impact for these patients when receiving conventional intensive cytotoxic therapy. In contrast, FAB-M4/M5 patients have decreased susceptibility to the Bcl-2 inhibitor venetoclax, and this seems to be due to common molecular characteristics involving mitochondrial regulation of the cellular metabolism and survival, including decreased dependency on Bcl-2 compared to other AML patients. Thus, the susceptibility to Bcl-2 inhibition does not only depend on general resistance/susceptibility mechanisms known from conventional AML therapy but also specific mechanisms involving the molecular target itself or the molecular context of the target. AML cell differentiation status is also associated with susceptibility to other targeted therapies (e.g., CDK2/4/6 and bromodomain inhibition), and differentiation induction seems to be a part of the antileukemic effect for several targeted anti-AML therapies. Differentiation-associated molecular mechanisms may thus become important in the future implementation of targeted therapies in human AML.
Astroglial Dysfunctions in Mood Disorders and Rodent Stress Models: Consequences on Behavior and Potential as Treatment Target
Authors: Bansal Yashika , Codeluppi Sierra A. , Banasr Mounira
Published: June 2024

Astrocyte dysfunctions have been consistently observed in patients affected with depression and other psychiatric illnesses. Although over the years our understanding of these changes, their origin, and their consequences on behavior and neuronal function has deepened, many aspects of the role of astroglial dysfunction in major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) remain unknown. In this review, we summarize the known astroglial dysfunctions associated with MDD and PTSD, highlight the impact of chronic stress on specific astroglial functions, and how astroglial dysfunctions are implicated in the expression of depressive- and anxiety-like behaviors, focusing on behavioral consequences of astroglial manipulation on emotion-related and fear-learning behaviors. We also offer a glance at potential astroglial functions that can be targeted for potential antidepressant treatment.
Prenatal Factors in the Development of Allergic Diseases
Authors: Grijincu Manuela , Buzan Maria-Roxana , Zbîrcea Lauriana-Eunice , Păunescu Virgil , Panaitescu Carmen
Published: June 2024

Allergic diseases are showing increasing prevalence in Western societies. They are characterized by a heightened reactivity towards otherwise harmless environmental stimuli. Allergic diseases showing a wide range of severity of symptoms have a significant impact on the quality of life of affected individuals. This study aims to highlight the mechanisms that induce these reactions, how they progress, and which prenatal factors influence their development. Most frequently, the reaction is mediated by immunoglobulin E (IgE) produced by B cells, which binds to the surface of mast cells and basophils and triggers an inflammatory response. The antibody response is triggered by a shift in T-cell immune response. The symptoms often start in early childhood with eczema or atopic dermatitis and progress to allergic asthma in adolescence. An important determinant of allergic diseases seems to be parental, especially maternal history of allergy. Around 30% of children of allergic mothers develop allergic sensitization in childhood. Genes involved in the regulation of the epithelial barrier function and the T-cell response were found to affect the predisposition to developing allergic disorders. Cord blood IgE was found to be a promising predictor of allergic disease development. Fetal B cells produce IgE starting at the 20th gestation week. These fetal B cells could be sensitized together with mast cells by maternal IgE and IgE–allergen complexes crossing the placental barrier via the low-affinity IgE receptor. Various factors were found to facilitate these sensitizations, including pesticides, drugs, exposure to cigarette smoke and maternal uncontrolled asthma. Prenatal exposure to microbial infections and maternal IgG appeared to play a role in the regulation of T-cell response, indicating a protective effect against allergy development. Additional preventive factors were dietary intake of vitamin D and omega 3 fatty acids as well as decreased maternal IgE levels. The effect of exposure to food allergens during pregnancy was inconclusive, with studies having found both sensitizing and protective effects. In conclusion, prenatal factors including genetics, epigenetics and fetal environmental factors have an important role in the development of allergic disorders in later life. Children with a genetic predisposition are at risk when exposed to cigarette smoke as well as increased maternal IgE in the prenatal period. Maternal diet during pregnancy and immunization against certain allergens could help in the prevention of allergy in predisposed children.
The Formation of D-Allulose 3-Epimerase Hybrid Nanoflowers and Co-Immobilization on Resins for Improved Enzyme Activity, Stability, and Processability
Authors: Ding Wentao , Liu Chensa , Huang Chi , Zhang Xin , Chi Xinyi , Wang Tong , Guo Qingbin , Wang Changlu
Published: June 2024

As a low-calorie sugar, D-allulose is produced from D-fructose catalyzed by D-allulose 3-epimerase (DAE). Here, to improve the catalytic activity, stability, and processability of DAE, we reported a novel method by forming organic–inorganic hybrid nanoflowers (NF-DAEs) and co-immobilizing them on resins to form composites (Re-NF-DAEs). NF-DAEs were prepared by combining DAE with metal ions (Co2+, Cu2+, Zn2+, Ca2+, Ni2+, Fe2+, and Fe3+) in PBS buffer, and were analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and X-ray diffraction. All of the NF-DAEs showed higher catalytic activities than free DAE, and the NF-DAE with Ni2+ (NF-DAE-Ni) reached the highest relative activity of 218%. The NF-DAEs improved the thermal stability of DAE, and the longest half-life reached 228 min for NF-DAE-Co compared with 105 min for the free DAE at 55 °C. To further improve the recycling performance of the NF-DAEs in practical applications, we combined resins and NF-DAEs to form Re-NF-DAEs. Resins and NF-DAEs co-effected the performance of the composites, and ReA (LXTE-606 neutral hydrophobic epoxy-based polypropylene macroreticular resins)-based composites (ReA-NF-DAEs) exhibited outstanding relative activities, thermal stabilities, storage stabilities, and processabilities. The ReA-NF-DAEs were able to be reused to catalyze the conversion from D-fructose to D-allulose, and kept more than 60% of their activities after eight cycles.
Effects of Alkaline Extraction pH on Amino Acid Compositions, Protein Secondary Structures, Thermal Stability, and Functionalities of Brewer’s Spent Grain Proteins
Authors: Hadinoto Kunn , Ling Jordy Kim-Ung , Pu Siyu , Tran The-Thien
Published: June 2024

A high alkaline pH was previously demonstrated to enhance the extraction yield of brewer’s spent grains (BSG) proteins. The effects of extraction pH beyond the extraction yield, however, has not been investigated before. The present work examined the effects of extraction pH (pH 8–12) on BSG proteins’ (1) amino acid compositions, (2) secondary structures, (3) thermal stability, and (4) functionalities (i.e., water/oil holding capacity, emulsifying, and foaming properties). The ideal extraction temperature (60 °C) and BSG-to-solvent ratio (1:20 w/v) for maximizing the extraction yield were first determined to set the conditions for the pH effect study. The results showed that a higher extraction pH led to more balanced compositions between hydrophilic and hydrophobic amino acids and higher proportions of random coils structures indicating increased protein unfolding. This led to superior emulsifying properties of the extracted proteins with more than twofold improvement between pH 8 and a pH larger than 10. The extraction pH, nevertheless, had minimal impact on the water/oil holding capacity, foaming properties, and thermal denaturation propensity of the proteins. The present work demonstrated that a high alkaline pH at pH 11–12 was indeed ideal for both maximizing the extraction yield (37–46 wt.%) and proteins’ functionalities.
Suppression of Ventilation-Induced Diaphragm Fibrosis through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model
Authors: Li Li-Fu , Yu Chung-Chieh , Huang Chih-Yu , Wu Huang-Pin , Chu Chien-Ming , Liu Ping-Chi , Liu Yung-Yang
Published: June 2024

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K-γ pathway. Five days after receiving a single bolus of 0.075 units of bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg of MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-β1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of α-smooth muscle actin, PI3K-γ expression, and myonuclear apoptosis (p < 0.05). Decreased diaphragm contractility and peroxisome proliferator-activated receptor-γ coactivator-1α levels were also observed (p < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K-γ activity (p < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated by PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.
ESMSec: Prediction of Secreted Proteins in Human Body Fluids Using Protein Language Models and Attention
Authors: Wang Yan , Sun Huiting , Sheng Nan , He Kai , Hou Wenjv , Zhao Ziqi , Yang Qixing , Huang Lan
Published: June 2024

The secreted proteins of human body fluid have the potential to be used as biomarkers for diseases. These biomarkers can be used for early diagnosis and risk prediction of diseases, so the study of secreted proteins of human body fluid has great application value. In recent years, the deep-learning-based transformer language model has transferred from the field of natural language processing (NLP) to the field of proteomics, leading to the development of protein language models (PLMs) for protein sequence representation. Here, we propose a deep learning framework called ESM Predict Secreted Proteins (ESMSec) to predict three types of proteins secreted in human body fluid. The ESMSec is based on the ESM2 model and attention architecture. Specifically, the protein sequence data are firstly put into the ESM2 model to extract the feature information from the last hidden layer, and all the input proteins are encoded into a fixed 1000 × 480 matrix. Secondly, multi-head attention with a fully connected neural network is employed as the classifier to perform binary classification according to whether they are secreted into each body fluid. Our experiment utilized three human body fluids that are important and ubiquitous markers. Experimental results show that ESMSec achieved average accuracy of 0.8486, 0.8358, and 0.8325 on the testing datasets for plasma, cerebrospinal fluid (CSF), and seminal fluid, which on average outperform the state-of-the-art (SOTA) methods. The outstanding performance results of ESMSec demonstrate that the ESM can improve the prediction performance of the model and has great potential to screen the secretion information of human body fluid proteins.
Multiplexing LAMP Assays: A Methodological Review and Diagnostic Application
Authors: Crego-Vicente Beatriz , del Olmo Manuel Diego , Muro Antonio , Fernández-Soto Pedro
Published: June 2024

The loop-mediated isothermal amplification (LAMP) technique is a great alternative to PCR-based methods, as it is fast, easy to use and works with high sensitivity and specificity without the need for expensive instruments. However, one of the limitations of LAMP is difficulty in achieving the simultaneous detection of several targets in a single tube, as the methodologies that allow this rely on fluorogenic probes containing specific target sequences, complicating their adaptation and the optimization of assays. Here, we summarize different methods for the development of multiplex LAMP assays based on sequence-specific detection, illustrated with a schematic representation of the technique, and evaluate their practical application based on the real-time detection and quantification of results, the possibility to visualize the results at a glance, the prior stabilization of reaction components, promoting the point-of-care use, the maximum number of specific targets amplified, and the validation of the technique in clinical samples. The various LAMP multiplexing methodologies differ in their operating conditions and mechanism. Each methodology has its advantages and disadvantages, and the choice among them will depend on specific application interests.
Haploidentical HSCT in the Treatment of Pediatric Hematological Disorders
Authors: Marszołek Anna , Leśniak Maria , Sekunda Anna , Siwek Aleksander , Skiba Zuzanna , Lejman Monika , Zawitkowska Joanna
Published: June 2024

Allogeneic hematopoietic stem cell transplantation has become a treatment option for otherwise non-curative conditions, both malignant and benign, affecting children and adults. Nevertheless, the latest research has been focusing extensively on transplantation from related and unrelated haploidentical donors, suitable for patients requiring emergent hematopoietic stem cell transplantation (HSCT) in the absence of an HLA-matched donor. Haploidentical HSCT (haplo-HSCT) can be an effective treatment for non-malignant pediatric disorders, such as primary immunodeficiencies or hemoglobinopathies, by enabling a much quicker selection of the appropriate donor for virtually all patients, low incidence of graft-versus-host disease (GVHD), and transplant-related mortality (TRM). Moreover, the outcomes of haplo-HSCT among children with hematological malignancies have improved radically. The most demanding tasks for clinicians are minimizing T-cell-mediated alloreactivity as well as early GVHD prevention. As a result, several T-cell depletion approaches, such as ex vivo T-cell depletion (TCD), and T-cell replete approaches, such as a combination of anti-thymocyte globulin (ATG), post-transplantation cyclophosphamide (PTCy), cyclosporine/tacrolimus, mycophenolate mofetil, or methotrexate, have been taken up. As more research is needed to establish the most beneficial form of therapy, haplo-HSCT is currently considered an alternative donor strategy for pediatric and adult patients with complications like viral and bacterial infections, invasive fungal disease, and GVHD.
Dexmedetomidine as a Short-Use Analgesia for the Immature Nervous System
Authors: Logashkin Anatoliy , Silaeva Valentina , Mamleev Arsen , Shumkova Viktoria , Sitdikova Violetta , Popova Yaroslavna , Suchkov Dmitrii , Minlebaev Marat
Published: June 2024

Pain management in neonates continues to be a challenge. Diverse therapies are available that cause loss of pain sensitivity. However, because of side effects, the search for better options remains open. Dexmedetomidine is a promising drug; it has shown high efficacy with a good safety profile in sedation and analgesia in the immature nervous system. Though dexmedetomidine is already in use for pain control in neonates (including premature neonates) and infants as an adjunct to other anesthetics, the question remains whether it affects the neuronal activity patterning that is critical for development of the immature nervous system. In this study, using the neonatal rat as a model, the pharmacodynamic effects of dexmedetomidine on the nervous and cardiorespiratory systems were studied. Our results showed that dexmedetomidine has pronounced analgesic effects in the neonatal rat pups, and also weakly modified both the immature network patterns of cortical and hippocampal activity and the physiology of sleep cycles. Though the respiration and heart rates were slightly reduced after dexmedetomidine administration, it might be considered as the preferential independent short-term therapy for pain management in the immature and developing brain.