bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal Pattern and Convergence Test of Energy Eco-Efficiency in the Yellow River Basin
Authors: Feng Shan , Kong Yawen , Liu Shuguang , Zhou Hongwei
Published: January 2023

Examining the convergence characteristics of energy eco-efficiency in the Yellow River Basin (YRB) is of great significance for the sustainable development of China. It fulfills the international commitment to carbon peak and carbon neutrality. Based on the Super-EBM model and ML index, this paper measures the energy eco-efficiency of 60 cities in the YRB during 2006–2018, and then spatial and temporal patterns are both analyzed before the final investigation of the convergence in the YRB. The results show the following: (1) From 2006 to 2018, the energy eco-efficiency of the YRB showed a significant upward trend, but there was still a 25.61% improvement compared with the production frontier. (2) The spatial differentiation of the energy eco-efficiency in the YRB was significant, and the inter-regional differences were the main reason for this. (3) There was no σ-convergence in energy eco-efficiency in the YRB during 2006–2018, but absolute and conditional β-convergence did occur. (4) Although the significant factors in the convergences were different, the levels of energy eco-efficiency in the different reaches all developed towards stable levels, and the catch-up effects in the less-developed regions were significant.
Automatic Production of Deep Learning Benchmark Dataset for Affine-Invariant Feature Matching
Authors: Yao Guobiao , Zhang Jin , Gong Jianya , Jin Fengxiang
Published: January 2023

To promote the development of deep learning for feature matching, image registration, and three-dimensional reconstruction, we propose a method of constructing a deep learning benchmark dataset for affine-invariant feature matching. Existing images often have large viewpoint differences and areas with weak texture, which may cause difficulties for image matching, with respect to few matches, uneven distribution, and single matching texture. To solve this problem, we designed an algorithm for the automatic production of a benchmark dataset for affine-invariant feature matching. It combined two complementary algorithms, ASIFT (Affine-SIFT) and LoFTR (Local Feature Transformer), to significantly increase the types of matching patches and the number of matching features and generate quasi-dense matches. Optimized matches with uniform spatial distribution were obtained by the hybrid constraints of the neighborhood distance threshold and maximum information entropy. We applied this algorithm to the automatic construction of a dataset containing 20,000 images: 10,000 ground-based close-range images, 6000 satellite images, and 4000 aerial images. Each image had a resolution of 1024 × 1024 pixels and was composed of 128 pairs of corresponding patches, each with 64 × 64 pixels. Finally, we trained and tested the affine-invariant deep learning model, AffNet, separately on our dataset and the Brown dataset. The experimental results showed that the AffNet trained on our dataset had advantages, with respect to the number of matching points, match correct rate, and matching spatial distribution on stereo images with large viewpoint differences and weak texture. The results verified the effectiveness of the proposed algorithm and the superiority of our dataset. In the future, our dataset will continue to expand, and it is intended to become the most widely used benchmark dataset internationally for the deep learning of wide-baseline image matching.
Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer’s Disease Progression
Authors: Andronie-Cioara Felicia Liana , Ardelean Adriana Ioana , Nistor-Cseppento Carmen Delia , Jurcau Anamaria , Jurcau Maria Carolina , Pascalau Nicoleta , Marcu Florin
Published: January 2023

Aging is the most prominent risk factor for late-onset Alzheimer’s disease. Aging associates with a chronic inflammatory state both in the periphery and in the central nervous system, the evidence thereof and the mechanisms leading to chronic neuroinflammation being discussed. Nonetheless, neuroinflammation is significantly enhanced by the accumulation of amyloid beta and accelerates the progression of Alzheimer’s disease through various pathways discussed in the present review. Decades of clinical trials targeting the 2 abnormal proteins in Alzheimer’s disease, amyloid beta and tau, led to many failures. As such, targeting neuroinflammation via different strategies could prove a valuable therapeutic strategy, although much research is still needed to identify the appropriate time window. Active research focusing on identifying early biomarkers could help translating these novel strategies from bench to bedside.
Fli1 and Tissue Fibrosis in Various Diseases
Authors: Mikhailova Elena V. , Romanova Irina V. , Bagrov Alexei Y. , Agalakova Natalia I.
Published: January 2023

Being initially described as a factor of virally-induced leukemias, Fli1 (Friend leukemia integration 1) has attracted considerable interest lately due to its role in both healthy physiology and a variety of pathological conditions. Over the past few years, Fli1 has been found to be one of the crucial regulators of normal hematopoiesis, vasculogenesis, and immune response. However, abnormal expression of Fli1 due to genetic predisposition, epigenetic reprogramming (modifications), or environmental factors is associated with a few diseases of different etiology. Fli1 hyperexpression leads to malignant transformation of cells and progression of cancers such as Ewing’s sarcoma. Deficiency in Fli1 is implicated in the development of systemic sclerosis and hypertensive disorders, which are often accompanied by pronounced fibrosis in different organs. This review summarizes the initial findings and the most recent advances in defining the role of Fli1 in diseases of different origin with emphasis on its pro-fibrotic potential.
Organogermanium THGP Induces Differentiation into M1 Macrophages and Suppresses the Proliferation of Melanoma Cells via Phagocytosis
Authors: Azumi Junya , Takeda Tomoya , Shimada Yasuhiro , Zhuang Tao , Tokuji Yoshihiko , Sakamoto Naoya , Aso Hisashi , Nakamura Takashi
Published: January 2023

M1 macrophages are an important cell type related to tumor immunology and are known to phagocytose cancer cells. In previous studies, the organogermanium compound poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132) and its hydrolysate, 3-(trihydroxygermyl) propanoic acid (THGP), have been reported to exert antitumor effects by activating NK cells and macrophages through the induction of IFN-γ activity in vivo. However, the detailed molecular mechanism has not been clarified. In this study, we found that macrophages differentiate into the M1 phenotype via NF-κB activation under long-term culture in the presence of THGP in vitro and in vivo. Furthermore, long-term culture with THGP increases the ability of RAW 264.7 cells to suppress B16 4A5 melanoma cell proliferation. These mechanisms indicate that THGP promotes the M1 polarization of macrophages and suppresses the expression of signal-regulatory protein alpha (SIRP-α) in macrophages and CD47 in cancers. Based on these results, THGP may be considered a new regulatory reagent that suppresses tumor immunity.
Optimization and Technical Considerations for the Dye-Exclusion Protocol Used to Assess Blood–Brain Barrier Integrity in Adult Drosophila melanogaster
Authors: Bhasiin Kesshni , Heintz Olivia , Colodner Kenneth J.
Published: January 2023

The blood–brain barrier (BBB) is a multicellular construct that regulates the diffusion and transport of metabolites, ions, toxins, and inflammatory mediators into and out of the central nervous system (CNS). Its integrity is essential for proper brain physiology, and its breakdown has been shown to contribute to neurological dysfunction. The BBB in vertebrates exists primarily through the coordination between endothelial cells, pericytes, and astrocytes, while invertebrates, which lack a vascularized circulatory system, typically have a barrier composed of glial cells that separate the CNS from humoral fluids. Notably, the invertebrate barrier is molecularly and functionally analogous to the vertebrate BBB, and the fruit fly, Drosophila melanogaster, is increasingly recognized as a useful model system in which to investigate barrier function. The most widely used technique to assess barrier function in the fly is the dye-exclusion assay, which involves monitoring the infiltration of a fluorescent-coupled dextran into the brain. In this study, we explore analytical and technical considerations of this procedure that yield a more reliable assessment of barrier function, and we validate our findings using a traumatic injury model. Together, we have identified parameters that optimize the dye-exclusion assay and provide an alternative framework for future studies examining barrier function in Drosophila.
The Problem of Host and Pathogen Genetic Variability for Developing Strategies of Universally Efficacious Vaccination against and Personalised Immunotherapy of Tuberculosis: Potential Solutions?
Authors: Bretscher Peter A.
Published: January 2023

Rational vaccination against and immunotherapy of any infectious disease requires knowledge of how protective and non-protective immune responses differ, and how immune responses are regulated, so their nature can be controlled. Strong Th1 responses are likely protective against M tuberculosis. Understanding how immune class regulation is achieved is pertinent to both vaccination and treatment. I argue that variables of infection, other than PAMPs, primarily determine the class of immunity generated. The alternative, non-PAMP framework I favour, allows me to propose strategies to achieve efficacious vaccination, transcending host and pathogen genetic variability, to prevent tuberculosis, and personalised protocols to treat disease.
Oligorecurrent Non-Small-Cell Lung Cancer Treated by Chemo-Radiation Followed by Immunotherapy and Intracranial Radiosurgery: A Case Report and Mini Review of Literature
Authors: Bruni Alessio , Bertolini Federica , D’Angelo Elisa , Guaitoli Giorgia , Imbrescia Jessica , Cappelli Anna , Guidi Gabriele , Stefani Alessandro , Dominici Massimo , Lohr Frank
Published: January 2023

Locally advanced non-small-cell lung cancer still represents a “grey zone” in terms of the best treatment choice and optimal clinical outcomes. Indeed, most patients may be suitable to receive different treatments with similar outcomes such as chemo-radiotherapy (CHT-RT) followed by immunotherapy (IO) or surgery followed by adjuvant local/systemic therapies. We report a clinical case of a patient submitted to primary thoracic surgery who developed a mediastinal nodal recurrence successfully treated by CHT-RT-IO. Subsequently, a single brain lesion was found to have been successfully treated by single fraction stereotactic ablative radiotherapy. The patient is still on follow-up and she is free from disease having a good quality of life. In this report, we also perform a mini review about the role of CHT-RT followed by IO in treating loco-regional relapse after surgery. The role of SABR after IO is also evaluated, finding that it is safe and well tolerated. More robust and larger clinical data are needed in this particular setting to better define the role of the combination of systemic and local treatments in the management of intrathoracic and intracranial relapse for patients already submitted to CHT-RT followed by immunotherapy.
Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model
Authors: Lee Eun-Ji , Yang Ju-Hye , Yang Hye Jin , Cho Chong-Kwan , Choi Jang-Gi , Chung Hwan-Suck
Published: January 2023

Blocking immune checkpoints, programmed death-1 (PD-1) and its ligand PD-L1, has proven a promising anticancer strategy for enhancing cytotoxic T cell activity. Although we previously demonstrated that ginsenoside Rg3, Rh2, and compound K block the interaction of PD-1 and PD-L1, the antitumor effect through blockade of this interaction by Korean Red Ginseng alone is unknown. Therefore, we determined the effects of Korean Red Ginseng extract (RGE) on the PD-1/PD-L1 interaction and its antitumor effects using a humanized PD-1/PD-L1-expressing colorectal cancer (CRC) mouse model. RGE significantly blocked the interaction between human PD-1 and PD-L1 in a competitive ELISA. The CD8+ T cell-mediated tumor cell killing effect of RGE was evaluated using murine hPD-L1-expressing MC38 cells and tumor-infiltrating hPD-1-expressing CD8+ T cells isolated from hPD-L1 MC38 tumor-bearing hPD-1 mice. RGE also reduced the survival of hPD-L1 MC38 cells in a cell co-culture system using tumor-infiltrating CD8+ T cells as effector cells combined with hPD-L1 MC38 target cells. RGE or Keytruda (positive control) treatment markedly suppressed the growth of hPD-L1 MC38 allograft tumors, increased CD8+ T cell infiltration into tumors, and enhanced the production of Granzyme B. RGE exhibits anticancer effects through the PD-1/PD-L1 blockade, which warrants its further development as an immunotherapy.
Photodynamic Therapy of Aluminum Phthalocyanine Tetra Sodium 2-Mercaptoacetate Linked to PEGylated Copper–Gold Bimetallic Nanoparticles on Colon Cancer Cells
Authors: Simelane Nokuphila Winifred Nompumelelo , Matlou Gauta Gold , Abrahamse Heidi
Published: January 2023

This work reports for the first time on the synthesis, characterization, and photodynamic therapy efficacy of the novel aluminium (III) chloride 2(3), 9(10), 16(17), 23(24)-tetrakis-(sodium 2-mercaptoacetate) phthalocyanine (AlClPcTS41) when alone and when conjugated to PEGylated copper–gold bimetallic nanoparticles (PEG-CuAuNPs) as photosensitizers on colon cancer cells (Caco-2). The novel AlClPcTS41 was covalently linked to the PEG-CuAuNPs via an amide bond to form AlClPcTS41-PEG-CuAuNPs. The amide bond was successfully confirmed using FTIR while the crystal structures were studied using XRD. The morphological and size variations of the PEG-CuAuNPs and AlClPcTS41-PEG-CuAuNPs were studied using TEM, while the hydrodynamic sizes and polydispersity of the particles were confirmed using DLS. The ground state electron absorption spectra were also studied and confirmed the typical absorption of metallated phthalocyanines and their nanoparticle conjugates. Subsequently, the subcellular uptake, cellular proliferation, and PDT anti-tumor effect of AlClPcTS41, PEG-CuAuNPs, and AlClPcTS41-PEG-CuAuNPs were investigated within in vitro Caco-2 cells. The designed AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs demonstrated significant ROS generation abilities that led to the PDT effect with a significantly decreased viable cell population after PDT treatment. These results demonstrate that the novel AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs had remarkable PDT effects against Caco-2 cells and may trigger apoptosis cell death pathway, indicating the potential of the AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs in enhancing the cytotoxic effect of PDT treatment.
Protective Effects of Arbutus unedo L. Honey in the Alleviation of Irinotecan-Induced Cytogenetic Damage in Human Lymphocytes—An In Vitro Study
Authors: Jurič Andreja , Brčić Karačonji Irena , Gašić Uroš , Milojković Opsenica Dušanka , Prđun Saša , Bubalo Dragan , Lušić Dražen , Vahčić Nada , Kopjar Nevenka
Published: January 2023

Strawberry tree (Arbutus unedo L.) honey (STH) has been used since ancient times as a folk medicine remedy, especially in certain Mediterranean countries. This honey, rich in phenolic content, is well recognized for its antioxidant, anti-inflammatory, and antimicrobial activities, and is used for the treatment of skin lesions as well as gastrointestinal and respiratory disorders. This study investigated whether STH alleviates genome damage in human peripheral blood lymphocytes produced by the cytotoxic drug irinotecan. The phenolic profile of STH was previously estimated by ultra-high-performance liquid chromatography coupled to a linear ion trap–Orbitrap hybrid mass spectrometer. The effects of STH were evaluated at three concentrations (1×, 5×, and 10×), based on the daily consumption of the honey by an adult person. After 2 h of in vitro exposure, standard lymphocyte cultures for the analysis of chromosome aberrations and the cytokinesis-block micronucleus cytome assay were established. Our results demonstrate that STH offered remarkable geno- and cytoprotection when administered with irinotecan. These findings are relevant for drawing preliminary conclusions regarding the in vitro safety of the tested honey. However, further studies are needed with the application of more complex experimental models.
The Antidepressant Paroxetine Reduces the Cardiac Sodium Current
Authors: Plijter Ingmar S. , Verkerk Arie O. , Wilders Ronald
Published: January 2023

A considerable amount of literature has been published on antidepressants and cardiac ion channel dysfunction. The antidepressant paroxetine has been associated with Brugada syndrome and long QT syndrome, albeit on the basis of conflicting findings. The cardiac voltage-gated sodium channel (NaV1.5) is related to both of these syndromes, suggesting that paroxetine may have an effect on this channel. In the present study, we therefore carried out patch clamp experiments to examine the effect of paroxetine on human NaV1.5 channels stably expressed in human embryonic kidney 293 (HEK-293) cells as well as on action potentials of isolated rabbit left ventricular cardiomyocytes. Additionally, computer simulations were conducted to test the functional effects of the experimentally observed paroxetine-induced changes in the NaV1.5 current. We found that paroxetine led to a decrease in peak NaV1.5 current in a concentration-dependent manner with an IC50 of 6.8 ± 1.1 µM. In addition, paroxetine caused a significant hyperpolarizing shift in the steady-state inactivation of the NaV1.5 current as well as a significant increase in its rate of inactivation. Paroxetine (3 µM) affected the action potential of the left ventricular cardiomyocytes, significantly decreasing its maximum upstroke velocity and amplitude, both of which are mainly regulated by the NaV1.5 current. Our computer simulations demonstrated that paroxetine substantially reduces the fast sodium current of human left ventricular cardiomyocytes, thereby slowing conduction and reducing excitability in strands of cells, in particular if conduction and excitability are already inhibited by a loss-of-function mutation in the NaV1.5 encoding SCN5A gene. In conclusion, paroxetine acts as an inhibitor of NaV1.5 channels, which may enhance the effects of loss-of-function mutations in SCN5A.
Advancing PHBV Biomedical Potential with the Incorporation of Bacterial Biopigment Prodigiosin
Authors: Ponjavic Marijana , Malagurski Ivana , Lazic Jelena , Jeremic Sanja , Pavlovic Vladimir , Prlainovic Nevena , Maksimovic Vesna , Cosovic Vladan , Atanase Leonard Ionut , Freitas Filomena , Matos Mariana , Nikodinovic-Runic Jasmina
Published: January 2023

The quest for sustainable biomaterials with excellent biocompatibility and tailorable properties has put polyhydroxyalkanoates (PHAs) into the research spotlight. However, high production costs and the lack of bioactivity limit their market penetration. To address this, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was combined with a bacterial pigment with strong anticancer activity, prodigiosin (PG), to obtain functionally enhanced PHBV-based biomaterials. The samples were produced in the form of films 115.6–118.8 µm in thickness using the solvent casting method. The effects of PG incorporation on the physical properties (morphology, biopolymer crystallinity and thermal stability) and functionality of the obtained biomaterials were investigated. PG has acted as a nucleating agent, in turn affecting the degree of crystallinity, thermal stability and morphology of the films. All samples with PG had a more organized internal structure and higher melting and degradation temperatures. The calculated degree of crystallinity of the PHBV copolymer was 53%, while the PG1, PG3 and PG3 films had values of 64.0%, 63.9% and 69.2%, respectively. Cytotoxicity studies have shown the excellent anticancer activity of films against HCT116 (colon cancer) cells, thus advancing PHBV biomedical application potential.
Involvement of TRPM7 in Alcohol-Induced Damage of the Blood–Brain Barrier in the Presence of HIV Viral Proteins
Authors: Mack Michelle L. , Huang Wenfei , Chang Sulie L.
Published: January 2023

Ethanol (EtOH) exerts its effects through various protein targets, including transient receptor potential melastatin 7 (TRPM7) channels, which play an essential role in cellular homeostasis. We demonstrated that TRPM7 is expressed in rat brain microvascular endothelial cells (rBMVECs), the major cellular component of the blood–brain barrier (BBB). Heavy alcohol drinking is often associated with HIV infection, however mechanisms underlying alcohol-induced BBB damage and HIV proteins, are not fully understood. We utilized the HIV-1 transgenic (HIV-1Tg) rat to mimic HIV-1 patients on combination anti-retroviral therapy (cART) and demonstrated TRPM7 expression in rBMVECs wass lower in adolescent HIV-1Tg rats compared to control animals, however control and HIV-1Tg rats expressed similar levels at 9 weeks, indicating persistent presence of HIV-1 proteins delayed TRPM7 expression. Binge exposure to EtOH (binge EtOH) decreased TRPM7 expression in control rBMVECs in a concentration-dependent manner, and abolished TRPM7 expression in HIV-1Tg rats. In human BMVECs (hBMVECs), TRPM7 expression was downregulated after treatment with EtOH, HIV-1 proteins, and in combination. Next, we constructed in vitro BBB models using BMVECs and found TRPM7 antagonists enhanced EtOH-mediated BBB integrity changes. Our study demonstrated alcohol decreased TRPM7 expression, whereby TRPM7 could be involved in the mechanisms underlying BBB alcohol-induced damage in HIV-1 patients on cART.
Diffusion Tensor Imaging in Amyotrophic Lateral Sclerosis: Machine Learning for Biomarker Development
Authors: Behler Anna , Müller Hans-Peter , Ludolph Albert C. , Kassubek Jan
Published: January 2023

Diffusion tensor imaging (DTI) allows the in vivo imaging of pathological white matter alterations, either with unbiased voxel-wise or hypothesis-guided tract-based analysis. Alterations of diffusion metrics are indicative of the cerebral status of patients with amyotrophic lateral sclerosis (ALS) at the individual level. Using machine learning (ML) models to analyze complex and high-dimensional neuroimaging data sets, new opportunities for DTI-based biomarkers in ALS arise. This review aims to summarize how different ML models based on DTI parameters can be used for supervised diagnostic classifications and to provide individualized patient stratification with unsupervised approaches in ALS. To capture the whole spectrum of neuropathological signatures, DTI might be combined with additional modalities, such as structural T1w 3-D MRI in ML models. To further improve the power of ML in ALS and enable the application of deep learning models, standardized DTI protocols and multi-center collaborations are needed to validate multimodal DTI biomarkers. The application of ML models to multiparametric MRI/multimodal DTI-based data sets will enable a detailed assessment of neuropathological signatures in patients with ALS and the development of novel neuroimaging biomarkers that could be used in the clinical workup.
Fabrication and Characterization Techniques of In Vitro 3D Tissue Models
Authors: Shyam Rohin , Reddy L. Vinod Kumar , Palaniappan Arunkumar
Published: January 2023

The culturing of cells in the laboratory under controlled conditions has always been crucial for the advancement of scientific research. Cell-based assays have played an important role in providing simple, fast, accurate, and cost-effective methods in drug discovery, disease modeling, and tissue engineering while mitigating reliance on cost-intensive and ethically challenging animal studies. The techniques involved in culturing cells are critical as results are based on cellular response to drugs, cellular cues, external stimuli, and human physiology. In order to establish in vitro cultures, cells are either isolated from normal or diseased tissue and allowed to grow in two or three dimensions. Two-dimensional (2D) cell culture methods involve the proliferation of cells on flat rigid surfaces resulting in a monolayer culture, while in three-dimensional (3D) cell cultures, the additional dimension provides a more accurate representation of the tissue milieu. In this review, we discuss the various methods involved in the development of 3D cell culture systems emphasizing the differences between 2D and 3D systems and methods involved in the recapitulation of the organ-specific 3D microenvironment. In addition, we discuss the latest developments in 3D tissue model fabrication techniques, microfluidics-based organ-on-a-chip, and imaging as a characterization technique for 3D tissue models.
Opposite Modulation of the NMDA Receptor by Glycine and S-Ketamine and the Effects on Resting State EEG Gamma Activity: New Insights into the Glutamate Hypothesis of Schizophrenia
Authors: Haaf Moritz , Curic Stjepan , Rauh Jonas , Steinmann Saskia , Mulert Christoph , Leicht Gregor
Published: January 2023

NMDA-receptor hypofunction is increasingly considered to be an important pathomechanism in schizophrenia. However, to date, it has not been possible to identify patients with relevant NMDA-receptor hypofunction who would respond to glutamatergic treatments. Preclinical models, such as the ketamine model, could help identify biomarkers related to NMDA-receptor function that respond to glutamatergic modulation, for example, via activation of the glycine-binding site. We, therefore, aimed to investigate the effects of opposing modulation of the NMDA receptor on gamma activity (30–100 Hz) at rest, the genesis of which appears to be highly dependent on NMDA receptors. The effects of subanesthetic doses of S-ketamine and pretreatment with glycine on gamma activity at rest were examined in twenty-five healthy male participants using 64-channel electroencephalography. Psychometric scores were assessed using the PANSS and the 5D-ASC. While S-ketamine significantly increased psychometric scores and gamma activity at the scalp and in the source space, pretreatment with glycine did not significantly attenuate any of these effects when controlled for multiple comparisons. Our results question whether increased gamma activity at rest constitutes a suitable biomarker for the target engagement of glutamatergic drugs in the preclinical ketamine model. They might further point to a differential role of NMDA receptors in gamma activity generation.
Transcriptome Analysis Revealed the Dynamic and Rapid Transcriptional Reprogramming Involved in Cold Stress and Related Core Genes in the Rice Seedling Stage
Authors: Wu Bian , Chen Siyuan , Cheng Shiyuan , Li Changyan , Li Sanhe , Chen Junxiao , Zha Wenjun , Liu Kai , Xu Huashan , Li Peide , Shi Shaojie , Yang Guocai , Chen Zhijun , Liu Kai , You Aiqing , Zhou Lei
Published: January 2023

Cold damage is one of the most important environmental factors influencing crop growth, development, and production. In this study, we generated a pair of near-isogenic lines (NILs), Towada and ZL31, and Towada showed more cold sensitivity than ZL31 in the rice seedling stage. To explore the transcriptional regulation mechanism and the reason for phenotypic divergence of the two lines in response to cold stress, an in-depth comparative transcriptome study under cold stress was carried out. Our analysis uncovered that rapid and high-amplitude transcriptional reprogramming occurred in the early stage of cold treatment. GO enrichment and KEGG pathway analysis indicated that genes of the response to stress, environmental adaptation, signal transduction, metabolism, photosynthesis, and the MAPK signaling pathway might form the main part of the engine for transcriptional reprogramming in response to cold stress. Furthermore, we identified four core genes, OsWRKY24, OsCAT2, OsJAZ9, and OsRR6, that were potential candidates affecting the cold sensitivity of Towada and ZL31. Genome re-sequencing analysis between the two lines revealed that only OsWRKY24 contained sequence variations which may change its transcript abundance. Our study not only provides novel insights into the cold-related transcriptional reprogramming process, but also highlights the potential candidates involved in cold stress.
Current Trends in Molecular Imprinting: Strategies, Applications and Determination of Target Molecules in Spain
Authors: Urriza-Arsuaga Idoia , Guadaño-Sánchez Miriam , Urraca Javier Lucas
Published: January 2023

Over the last decades, an increasing demand for new specific molecular recognition elements has emerged in order to improve analytical methods that have already been developed in order to reach the detection/quantification limits of target molecules. Molecularly imprinted polymers (MIPs) have molecular recognition abilities provided by the presence of a template molecule during their synthesis, and they are excellent materials with high selectivity for sample preparation. These synthetic polymers are relatively easy to prepare, and they can also be an excellent choice in the substitution of antibodies or enzymes in different kinds of assays. They have been properly applied to the development of chromatographic or solid-phase extraction methods and have also been successfully applied as electrochemical, piezoelectrical, and optical sensors, as well as in the catalysis process. Nevertheless, new formats of polymerization can also provide new applications for these materials. This paper provides a comprehensive comparison of the new challenges in molecular imprinting as materials of the future in Spain.
Microcalcification and 99mTc-Pyrophosphate Uptake without Increased Bone Metabolism in Cardiac Tissue from Patients with Transthyretin Cardiac Amyloidosis
Authors: Mori Atsushi , Saito Yukihiro , Nakamura Kazufumi , Iida Toshihiro , Akagi Satoshi , Yoshida Masashi , Taniyama Makiko , Miyoshi Toru , Ito Hiroshi
Published: January 2023

Transthyretin cardiac amyloidosis (ATTR-CA) is characterized by high 99mTc-labeled bone tracer uptake in the heart. However, the mechanism of bone tracer uptake into the heart remains controversial. Since bone tracer uptake into metastatic bone tumors is thought to be associated with increased bone metabolism, we examined 99mTc-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in the EMB tissues in patients with ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) in this study. The uptake of 99mTc-PYP in the heart was significantly higher in the ATTR-CA patients than in the AL-CA and non-CA patients. A higher percentage of ATTR-CA EMB tissue showed von Kossa-positive microparticles: ATTR-CA, 62%; AL-CA, 33%; and non-CA, 0%. Calcified microparticles were identified using transmission electron microscopy. However, none of the osteogenic marker genes, osteoclastic marker genes, or phosphate/pyrophosphate-related genes were upregulated in the EMB samples from ATTR-CA patients compared to those from AL-CA and non-CA patients. These results suggest that active calcification-promoting mechanisms are not involved in the microcalcification observed in the heart in ATTR-CA. The mechanisms explaining bone tracer uptake in the heart, which is stronger than that in the ribs, require further investigation.
Are Non-Invasive Modalities for the Assessment of Atherosclerosis Useful for Heart Failure Predictions?
Authors: Osawa Kazuhiro , Miyoshi Toru
Published: January 2023

Heart failure (HF) is becoming an increasingly common issue worldwide and is associated with significant morbidity and mortality, making its prevention an important clinical goal. The criteria evaluated using non-invasive modalities such as coronary artery calcification, the ankle-brachial index, and carotid intima-media thickness have been proven to be effective in determining the relative risk of atherosclerotic cardiovascular disease. Notably, risk assessments using these modalities have been proven to be superior to the traditional risk predictors of cardiovascular disease. However, the ability to assess HF risk has not yet been well-established. In this review, we describe the clinical significance of such non-invasive modalities of atherosclerosis assessments and examine their ability to assess HF risk. The predictive value could be influenced by the left ventricular ejection fraction. Specifically, when the ejection fraction is reduced, its predictive value increases because this condition is potentially a result of coronary artery disease. In contrast, using these measures to predict HF with a preserved ejection fraction may be difficult because it is a heterogeneous condition. To overcome this issue, further research, especially on HF with a preserved ejection fraction, is required.
Autophagy Is Required to Sustain Increased Intestinal Cell Proliferation during Phenotypic Plasticity Changes in Honey Bee (Apis mellifera)
Authors: Guo Yueqin , Hu Ruoyang , Li Naikang , Li Nannan , Wu Jiangli , Yu Huimin , Tan Jing , Li Zhouhua , Xu Shufa
Published: January 2023

Tissue phenotypic plasticity facilitates rapid adaptation of organisms to biotic and/or abiotic pressure. The reproductive capacity of honey bee workers (Apis mellifera) is plastic and responsive to pheromones produced by broods and the queen. Egg laying workers (ELWs), which could reactivate their ovaries and lay haploid eggs upon queen lost, have been commonly discussed from many aspects. However, it remains unclear whether midgut homeostasis in ELWs is affected during plastic changes. Here, we found that the expression of nutrition- and autophagy-related genes was up-regulated in the midguts of ELWs, compared with that in nurse workers (NWs) by RNA-sequencing. Furthermore, the area and number of autophagosomes were increased, along with significantly increased cell death in the midguts of ELWs. Moreover, cell cycle progression in the midguts of ELWs was increased compared with that in NWs. Consistent with the up-regulation of nutrition-related genes, the body and midgut sizes, and the number of intestinal proliferation cells of larvae reared with royal jelly (RJ) obviously increased more than those reared without RJ in vitro. Finally, cell proliferation was dramatically suppressed in the midguts of ELWs when autophagy was inhibited. Altogether, our data suggested that autophagy was induced and required to sustain cell proliferation in ELWs’ midguts, thereby revealing the critical role of autophagy played in the intestines during phenotypic plasticity changes.
Molecular Determinants of Chronic Venous Disease: A Comprehensive Review
Authors: Costa Davide , Andreucci Michele , Ielapi Nicola , Serraino Giuseppe Filiberto , Mastroroberto Pasquale , Bracale Umberto Marcello , Serra Raffaele
Published: January 2023

Chronic Venous Disease (CVD) refers to several pathological and hemodynamic alterations of the veins of lower limbs causing a wide range of symptoms and signs with a high prevalence in the general population and with disabling consequences in the most severe forms. The etiology and pathophysiology of CVD is complex and multifactorial, involving genetic, proteomic, and cellular mechanisms that result in changes to the venous structure and functions. Expressions of several genes associated with angiogenesis, vascular development, and the regulation of veins are responsible for the susceptibility to CVD. Current evidence shows that several extracellular matrix alterations (ECM) could be identified and in some cases pharmacologically targeted. This review shows the most up to date information on molecular determinants of CVD in order to provide a complete overview of the current knowledge on this topic. In particular, the article explores the genetic influence, the hormonal influence, ECM imbalance, and histopathology of CVD and the role of endothelial dysfunction in CVD.
T-Cell Immunity in COVID-19-Recovered Individuals and Individuals Vaccinated with the Combined Vector Vaccine Gam-COVID-Vac
Authors: Krechetov Sergey Petrovich , Vtorushina Valentina Valentinovna , Inviyaeva Evgenia Vladimirovna , Gorodnova Elena Aleksandrovna , Kolesnik Svetlana Vladimirovna , Kudlay Dmitry Anatolievich , Borovikov Pavel Igorevich , Krechetova Liubov Valentinovna , Dolgushina Nataliya Vitalievna , Sukhikh Gennady Tikhonovich
Published: January 2023

The COVID-19 pandemic has required extensive research on the new coronavirus SARS-CoV-2 and the creation of new highly effective vaccines. The presence of T-cells in the body that respond to virus antigens suggests adequate antiviral immunity. We investigated T-cell immunity in individuals who recovered from mild and moderate COVID-19 and in individuals vaccinated with the Gam-COVID-Vac combined vector vaccine. The ELISPOT method was used to determine the number of T-cells responding with IFN-γ synthesis to stimulation by peptides containing epitopes of the S-protein or N-, M-, ORF3, and ORF7 proteins, using peripheral blood mononuclear cells (PBMCs). At the same time, the multiplex method was used to determine the accumulation of IFN-γ and other cytokines in the culture medium. According to the data obtained, the proportion of positive conclusions about the T-cell immune response to SARS-CoV-2 antigens in control, recovered, and vaccinated individuals was 12%, 70%, and 52%, respectively. At the same time, more than half of the vaccinated individuals with a T-cell response were sensitized to the antigens of N-, M-, ORF3, and ORF7 proteins not produced by Gam-COVID-Vac, indicating a high likelihood of asymptomatic SARS-CoV-2 infection. Increased IFN-γ release by single sensitized T-cells in response to specific stimulation in recovered and vaccinated individuals did not result in the accumulation of this and other cytokines in the culture medium. These findings suggest a balance between cytokine production and utilization by immunocompetent cells as a prerequisite for providing a controlled cytokine signal and avoiding a “cytokine storm”.
Superiority of [11C]methionine over [18F]deoxyglucose for PET Imaging of Multiple Cancer Types Due to the Methionine Addiction of Cancer
Authors: Kubota Yutaro , Sato Toshihiko , Hozumi Chihiro , Han Qinghong , Aoki Yusuke , Masaki Noriyuki , Obara Koya , Tsunoda Takuya , Hoffman Robert M.
Published: January 2023

Positron emission tomography (PET) is widely used to detect cancers. The usual isotope for PET imaging of cancer is [18F]deoxyglucose. The premise of using [18F]deoxyglucose is that cancers are addicted to glucose (The Warburg effect). However, cancers are more severely addicted to methionine (The Hoffman effect). [11C]methionine PET (MET-PET) has been effectively used for the detection of glioblastoma and other cancers in the brain, and in comparison, MET-PET has been shown to be more sensitive and accurate than [18F]deoxyglucose PET (FDG-PET). However, MET-PET has been limited to cancers in the brain. The present report describes the first applications of MET-PET to cancers of multiple organs, including rectal, bladder, lung, and kidney. The results in each case show that MET-PET is superior to FDG-PET due to the methionine addiction of cancer and suggest that the broad application of MET-PET should be undertaken for cancer detection.
The RSPH4A Gene in Primary Ciliary Dyskinesia
Authors: De Jesús-Rojas Wilfredo , Meléndez-Montañez Jesús , Muñiz-Hernández José , Marra-Nazario André , Alvarado-Huerta Francisco , Santos-López Arnaldo , Ramos-Benitez Marcos J. , Mosquera Ricardo A.
Published: January 2023

The radial spoke head protein 4 homolog A (RSPH4A) gene is one of more than 50 genes that cause Primary ciliary dyskinesia (PCD), a rare genetic ciliopathy. Genetic mutations in the RSPH4A gene alter an important protein structure involved in ciliary pathogenesis. Radial spoke proteins, such as RSPH4A, have been conserved across multiple species. In humans, ciliary function deficiency caused by RSPH4A pathogenic variants results in a clinical phenotype characterized by recurrent oto-sino-pulmonary infections. More than 30 pathogenic RSPH4A genetic variants have been associated with PCD. In Puerto Rican Hispanics, a founder mutation (RSPH4A (c.921+3_921+6delAAGT (intronic)) has been described. The spectrum of the RSPH4A PCD phenotype does not include laterality defects, which results in a challenging diagnosis. PCD diagnostic tools can combine transmission electron microscopy (TEM), nasal nitric oxide (nNO), High-Speed Video microscopy Analysis (HSVA), and immunofluorescence. The purpose of this review article is to provide a comprehensive overview of current knowledge about the RSPH4A gene in PCD, ranging from basic science to human clinical phenotype.
The Remodeling of Dermal Collagen Fibrous Structures in Mice under Zero Gravity: The Role of Mast Cells
Authors: Shishkina Viktoriya , Kostin Andrey , Volodkin Artem , Samoilova Vera , Buchwalow Igor , Tiemann Markus , Atiakshin Dmitri
Published: January 2023

Mechanisms of adaptive rearrangements of the fibrous extracellular matrix of connective tissues under microgravity practically remain unexplored, despite the most essential functions of the stroma existing to ensure the physiological activity of internal organs. Here we analyzed the biomaterial (the skin dermis) of C57BL/6J mice from the Rodent Research-4 experiment after a long stay in space flight. The biomaterial was fixed onboard the International Space Station. It was found that weightlessness resulted in a relative increase in type III collagen-rich fibers compared to other fibrous collagens in the skin. The number of mast cells in the skin did not change, but their secretory activity increased. At the same time, co-localization of mast cells with fibroblasts, as well as impregnated fibers, was reduced. Potential molecular–cellular causes of changes in the activity of fibrillogenesis under zero-gravity conditions and the slowdown of the polymerization of tropocollagen molecules into supramolecular fibrous structures, as well as a relative decrease in the number of fibrous structures with a predominant content of type-I collagen, are discussed. The data obtained evidence of the different sensitivity levels of the fibrous and cellular components of a specific tissue microenvironment of the skin to zero-gravity conditions. The obtained data should be taken into account in the systematic planning of long-term space missions in order to improve the prevention of undesirable effects of weightlessness.
c-Abl Tyrosine Kinase Is Required for BDNF-Induced Dendritic Branching and Growth
Authors: Chandía-Cristi América , Stuardo Nicolás , Trejos Cristian , Leal Nancy , Urrutia Daniela , Bronfman Francisca C. , Álvarez Rojas Alejandra
Published: January 2023

Brain-derived neurotrophic factor (BDNF) induces activation of the TrkB receptor and several downstream pathways (MAPK, PI3K, PLC-γ), leading to neuronal survival, growth, and plasticity. It has been well established that TrkB signaling regulation is required for neurite formation and dendritic arborization, but the specific mechanism is not fully understood. The non-receptor tyrosine kinase c-Abl is a possible candidate regulator of this process, as it has been implicated in tyrosine kinase receptors’ signaling and trafficking, as well as regulation of neuronal morphogenesis. To assess the role of c-Abl in BDNF-induced dendritic arborization, wild-type and c-Abl-KO neurons were stimulated with BDNF, and diverse strategies were employed to probe the function of c-Abl, including the use of pharmacological inhibitors, an allosteric c-Abl activator, and shRNA to downregulates c-Abl expression. Surprisingly, BDNF promoted c-Abl activation and interaction with TrkB receptors. Furthermore, pharmacological c-Abl inhibition and genetic ablation abolished BDNF-induced dendritic arborization and increased the availability of TrkB in the cell membrane. Interestingly, inhibition or genetic ablation of c-Abl had no effect on the classic TrkB downstream pathways. Together, our results suggest that BDNF/TrkB-dependent c-Abl activation is a novel and essential mechanism in TrkB signaling.
Molecular and Translational Research on Bone Tumors
Authors: Rossi Michela , Del Fattore Andrea
Published: January 2023

Primary bone tumors (PBTs) represent a huge variety of rare malignancies that originate in the skeletal system [...]
Synthesis of Bimetallic BiPO4/ZnO Nanocomposite: Enhanced Photocatalytic Dye Degradation and Antibacterial Applications
Authors: Krishnan Muthukumar , Subramanian Harinee , Ramachandran Sathish Kumar , Muthukumarasamy Arulmozhi , Ramadoss Dineshram , Mahalingam Ashok , Rathinam Arthur James , Dahms Hans-Uwe , Hwang Jiang-Shiou
Published: January 2023

Multidrug-resistant strains (MDRs) are becoming a major concern in a variety of settings, including water treatment and the medical industry. Well-dispersed catalysts such as BiPO4, ZnO nanoparticles (NPs), and different ratios of BiPO4/ZnO nanocomposites (NCs) were synthesized through hydrothermal treatments. The morphological behavior of the prepared catalysts was characterized using XRD, Raman spectra, PL, UV–Vis diffuse reflectance spectroscopy (UV-DRS), SEM, EDX, and Fe-SEM. MDRs were isolated and identified by the 16s rDNA technique as belonging to B. flexus, B. filamentosus, P. stutzeri, and A. baumannii. The antibacterial activity against MDRs and the photocatalytic methylene blue (MB) dye degradation activity of the synthesized NPs and NCs were studied. The results demonstrate that the prepared BiPO4/ZnO-NCs (B1Z4-75:300; NCs-4) caused a maximum growth inhibition of 20 mm against A. baumannii and a minimum growth inhibition of 12 mm against B. filamentosus at 80 μg mL−1 concentrations of the NPs and NCs. Thus, NCs-4 might be a suitable alternative to further explore and develop as an antibacterial agent. The obtained results statistically justified the data (p ≤ 0.05) via one-way analysis of variance (ANOVA). According to the results of the antibacterial and photocatalytic study, we selected the best bimetallic NCs-4 for the photoexcited antibacterial effect of MDRs, including Gram ve+ and Gram ve− strains, via UV light irradiation. The flower-like NCs-4 composites showed more effectiveness than those of BiPO4, ZnO, and other ratios of NCs. The results encourage the development of flower-like NCs-4 to enhance the photocatalytic antibacterial technique for water purification.
Prediction of Bone Healing around Dental Implants in Various Boundary Conditions by Deep Learning Network
Authors: Kung Pei-Ching , Hsu Chia-Wei , Yang An-Cheng , Chen Nan-Yow , Tsou Nien-Ti
Published: January 2023

Tissue differentiation varies based on patients’ conditions, such as occlusal force and bone properties. Thus, the design of the implants needs to take these conditions into account to improve osseointegration. However, the efficiency of the design procedure is typically not satisfactory and needs to be significantly improved. Thus, a deep learning network (DLN) is proposed in this study. A data-driven DLN consisting of U-net, ANN, and random forest models was implemented. It serves as a surrogate for finite element analysis and the mechano-regulation algorithm. The datasets include the history of tissue differentiation throughout 35 days with various levels of occlusal force and bone properties. The accuracy of day-by-day tissue differentiation prediction in the testing dataset was 82%, and the AUC value of the five tissue phenotypes (fibrous tissue, cartilage, immature bone, mature bone, and resorption) was above 0.86, showing a high prediction accuracy. The proposed DLN model showed the robustness for surrogating the complex, time-dependent calculations. The results can serve as a design guideline for dental implants.