bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vivo PET Detection of Lung Micrometastasis in Mice by Targeting Endothelial VCAM-1 Using a Dual-Contrast PET/MRI Probe
Authors: Melemenidis Stavros , Knight James C. , Kersemans Veerle , Perez-Balderas Francisco , Zarghami Niloufar , Soto Manuel Sarmiento , Cornelissen Bart , Muschel Ruth J. , Sibson Nicola R.
Published: July 2024

Current clinical diagnostic imaging methods for lung metastases are sensitive only to large tumours (1–2 mm cross-sectional diameter), and early detection can dramatically improve treatment. We have previously demonstrated that an antibody-targeted MRI contrast agent based on microparticles of iron oxide (MPIO; 1 μm diameter) enables the imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Using a mouse model of lung metastasis, upregulation of endothelial VCAM-1 expression was demonstrated in micrometastasis-associated vessels but not in normal lung tissue, and binding of VCAM-MPIO to these vessels was evident histologically. Owing to the lack of proton MRI signals in the lungs, we modified the VCAM-MPIO to include zirconium-89 (89Zr, t1/2 = 78.4 h) in order to allow the in vivo detection of lung metastases by positron emission tomography (PET). Using this new agent (89Zr-DFO-VCAM-MPIO), it was possible to detect the presence of micrometastases within the lung in vivo from ca. 140 μm in diameter. Histological analysis combined with autoradiography confirmed the specific binding of the agent to the VCAM-1 expressing vasculature at the sites of pulmonary micrometastases. By retaining the original VCAM-MPIO as the basis for this new molecular contrast agent, we have created a dual-modality (PET/MRI) agent for the concurrent detection of lung and brain micrometastases.
Genetic and Epigenetic Association of FOXP3 with Papillary Thyroid Cancer Predisposition
Authors: Achilla Charoula , Chorti Angeliki , Papavramidis Theodosios , Angelis Lefteris , Chatzikyriakidou Anthoula
Published: July 2024

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy with an increased female incidence ratio. The specific traits of X chromosome inheritance may be implicated in gender differences of PTC predisposition. The aim of this study was to investigate the association of two X-linked genes, Forkhead Box P3 (FOXP3) and Protein Phosphatase 1 Regulatory Subunit 3F (PPP1R3F), with PTC predisposition and gender disparity. One hundred thirty-six patients with PTC and an equal number of matched healthy volunteers were enrolled in the study. Genotyping for rs3761548 (FOXP3) and rs5953283 (PPP1R3F) was performed using polymerase chain reaction–restriction fragment length polymorphism assay (PCR-RFLP). The methylation status of FOXP3 was assessed using the combined bisulfite restriction analysis (COBRA) method. The SPSS software was used for statistical analyses. Gender stratification analysis revealed that the CA and AA genotypes and the A allele of FOXP3 rs3761548 variant are associated with PTC predisposition only in females. Moreover, different methylation status was observed up to the promoter locus of FOXP3 between PTC female patients, carrying the CA and CC genotype, and controls. Both revealed associations may explain the higher PTC incidence in females through reducing FOXP3 expression as reported in immune related blood cells.
GPCR-Gα13 Involvement in Mitochondrial Function, Oxidative Stress, and Prostate Cancer
Authors: Wu Di , Casey Patrick J.
Published: July 2024

Gα13 and Gα12, encoded by the GNA13 and GNA12 genes, respectively, are members of the G12 family of Gα proteins that, along with their associated Gβγ subunits, mediate signaling from specific G protein-coupled receptors (GPCRs). Advanced prostate cancers have increased expression of GPCRs such as CXC Motif Chemokine Receptor 4 (CXCR4), lysophosphatidic acid receptor (LPAR), and protease activated receptor 1 (PAR-1). These GPCRs signal through either the G12 family, or through Gα13 exclusively, often in addition to other G proteins. The effect of Gα13 can be distinct from that of Gα12, and the role of Gα13 in prostate cancer initiation and progression is largely unexplored. The oncogenic effect of Gα13 on cell migration and invasion in prostate cancer has been characterized, but little is known about other biological processes such as mitochondrial function and oxidative stress. Current knowledge on the link between Gα13 and oxidative stress is based on animal studies in which GPCR-Gα13 signaling decreased superoxide levels, and the overexpression of constitutively active Gα13 promoted antioxidant gene activation. In human samples, mitochondrial superoxide dismutase 2 (SOD2) correlates with prostate cancer risk and prognostic Gleason grade. However, overexpression of SOD2 in prostate cancer cells yielded conflicting results on cell growth and survival under basal versus oxidative stress conditions. Hence, it is necessary to explore the effect of Gα13 on prostate cancer tumorigenesis, as well as the effect of Gα13 on SOD2 in prostate cancer cell growth under oxidative stress conditions.
Addition of Polyphenols to Drugs: The Potential of Controlling “Inflammaging” and Fibrosis in Human Senescent Lung Fibroblasts In Vitro
Authors: Godoy Maria Carolina Ximenes de , Monteiro Gabriela Arruda , Moraes Bárbara Hakim de , Macedo Juliana Alves , Gonçalves Gisele Mara Silva , Gambero Alessandra
Published: July 2024

The combination of a polyphenol, quercetin, with dasatinib initiated clinical trials to evaluate the safety and efficacy of senolytics in idiopathic pulmonary fibrosis, a lung disease associated with the presence of senescent cells. Another approach to senotherapeutics consists of controlling inflammation related to cellular senescence or “inflammaging”, which participates, among other processes, in establishing pulmonary fibrosis. We evaluate whether polyphenols such as caffeic acid, chlorogenic acid, epicatechin, gallic acid, quercetin, or resveratrol combined with different senotherapeutics such as metformin or rapamycin, and antifibrotic drugs such as nintedanib or pirfenidone, could present beneficial actions in an in vitro model of senescent MRC-5 lung fibroblasts. A senescent-associated secretory phenotype (SASP) was evaluated by the measurement of interleukin (IL)-6, IL-8, and IL-1β. The senescent-associated β-galactosidase (SA-β-gal) activity and cellular proliferation were assessed. Fibrosis was evaluated using a Picrosirius red assay and the gene expression of fibrosis-related genes. Epithelial-mesenchymal transition (EMT) was assayed in the A549 cell line exposed to Transforming Growth Factor (TGF)-β in vitro. The combination that demonstrated the best results was metformin and caffeic acid, by inhibiting IL-6 and IL-8 in senescent MRC-5 cells. Metformin and caffeic acid also restore cellular proliferation and reduce SA-β-gal activity during senescence induction. The collagen production by senescent MRC-5 cells was inhibited by epicatechin alone or combined with drugs. Epicatechin and nintedanib were able to control EMT in A549 cells. In conclusion, caffeic acid and epicatechin can potentially increase the effectiveness of senotherapeutic drugs in controlling lung diseases whose pathophysiological component is the presence of senescent cells and fibrosis.
MyD88 Signaling Accompanied by Microbiota Changes Supports Urinary Bladder Carcinogenesis
Authors: Knezović Dora , Milić Roje Blanka , Vilović Katarina , Franković Lucija , Korac-Prlic Jelena , Terzić Janoš
Published: July 2024

Urinary bladder cancer (BC) inflicts a significant impairment of life quality and poses a high mortality risk. Schistosoma haematobium infection can cause BC, and the urinary microbiota of BC patients differs from healthy controls. Importantly, intravesical instillation of the bacterium Bacillus Calmette-Guerin stands as the foremost therapy for non-muscle invasive BC. Hence, studying the receptors and signaling molecules orchestrating bacterial recognition and the cellular response in the context of BC is of paramount importance. Thus, we challenged Toll-like receptor 4 (Tlr4) and myeloid differentiation factor 88 (Myd88) knock-out (KO) mice with N-butyl-N-(4-hydroxylbutyl)-nitrosamine (BBN), a well-known urinary bladder carcinogen. Gut microbiota, gene expression, and urinary bladder pathology were followed. Acute exposure to BBN did not reveal a difference in bladder pathology despite differences in the animal’s ability to recognize and react to bacteria. However, chronic treatment resulted in reduced cancer invasiveness among Myd88KO mice while the absence of functional Tlr4 did not influence BC development or progression. These differences correlate with a heightened abundance of the Faecalibaculum genus and the lowest microbial diversity observed among Myd88KO mice. The presented data underscore the important role of microbiota composition and MyD88-mediated signaling during bladder carcinogenesis.
Ambient Particulate Matter Induces In Vitro Toxicity to Intestinal Epithelial Cells without Exacerbating Acute Colitis Induced by Dextran Sodium Sulfate or 2,4,6-Trinitrobenzenesulfonic Acid
Authors: Chang Candace , Louie Allen , Zhou Yi , Gupta Rajat , Liang Fengting , Xanthou Georgina , Ereso Jason , Koletic Carolina , Yang Julianne Ching , Sedighian Farzaneh , Lagishetty Venu , Arias-Jayo Nerea , Altuwayjiri Abdulmalik , Tohidi Ramin , Navab Mohamad , Reddy Srinivasa Tadiparthi , Sioutas Constantinos , Hsiai Tzung , Araujo Jesus A. , Jacobs Jonathan P.
Published: July 2024

Inflammatory bowel disease (IBD) is an immunologically complex disorder involving genetic, microbial, and environmental risk factors. Its global burden has continued to rise since industrialization, with epidemiological studies suggesting that ambient particulate matter (PM) in air pollution could be a contributing factor. Prior animal studies have shown that oral PM10 exposure promotes intestinal inflammation in a genetic IBD model and that PM2.5 inhalation exposure can increase intestinal levels of pro-inflammatory cytokines. PM10 and PM2.5 include ultrafine particles (UFP), which have an aerodynamic diameter of <0.10 μm and biophysical and biochemical properties that promote toxicity. UFP inhalation, however, has not been previously studied in the context of murine models of IBD. Here, we demonstrated that ambient PM is toxic to cultured Caco-2 intestinal epithelial cells and examined whether UFP inhalation affected acute colitis induced by dextran sodium sulfate and 2,4,6-trinitrobenzenesulfonic acid. C57BL/6J mice were exposed to filtered air (FA) or various types of ambient PM reaerosolized in the ultrafine size range at ~300 μg/m3, 6 h/day, 3–5 days/week, starting 7–10 days before disease induction. No differences in weight change, clinical disease activity, or histology were observed between the PM and FA-exposed groups. In conclusion, UFP inhalation exposure did not exacerbate intestinal inflammation in acute, chemically-induced colitis models.
Decontamination Effect of Hypochlorous Acid Dry Mist on Selected Bacteria, Viruses, Spores, and Fungi as Well as on Components of Electronic Systems
Authors: Nasiłowska Barbara , Włodarski Maksymilian , Kaliszewski Miron , Bogdanowicz Zdzisław , Krzowski Łukasz , Kopczyński Krzysztof , Witkowski Grzegorz , Czeczott-Urban Agnieszka , Bombalska Aneta , Urbańska Magdalena , Garbat Katarzyna , Sowińska Aleksandra , Kutwin Marta , Koperski Wojciech , Woźniak Ryszard , Mierczyk Zygmunt
Published: July 2024

This publication presents the effect of hypochlorous acid dry mist as a disinfectant on selected bacteria, viruses, spores, and fungi as well as on portable Microlife OXY 300 finger pulse oximeters and electronic systems of Raspberry Pi Zero microcomputers. The impact of hypochlorous acid on microbiological agents was assessed at concentrations of 300, 500, and 2000 ppm of HClO according to PN-EN 17272 (Variant I). Studies of the impact of hypochlorous acid fog on electronic components were carried out in an aerosol chamber at concentrations of 500 ppm and 2000 ppm according to two models consisting of 30 (Variant II) and 90 fogging cycles (Variant III). Each cycle included the process of generating a dry mist of hypochlorous acid (25 mL/m3), decontamination of the test elements, as well as cleaning the chamber of the disinfectant agent. The exposure of the materials examined on hypochlorous acid dry mist in all variants resulted in a decrease in the number of viruses, bacteria, spores, and fungi tested. In addition, the research showed that in the variants of hypochlorous acid fogging cycles analyzed, no changes in performance parameters and no penetration of dry fog of hypochlorous acid into the interior of the tested medical devices and electronic systems were observed.
SnoRNAs: Exploring Their Implication in Human Diseases
Authors: Chauhan Waseem , Sudharshan SJ  , Kafle Sweta , Zennadi Rahima
Published: July 2024

Small nucleolar RNAs (snoRNAs) are earning increasing attention from research communities due to their critical role in the post-transcriptional modification of various RNAs. These snoRNAs, along with their associated proteins, are crucial in regulating the expression of a vast array of genes in different human diseases. Primarily, snoRNAs facilitate modifications such as 2′-O-methylation, N-4-acetylation, and pseudouridylation, which impact not only ribosomal RNA (rRNA) and their synthesis but also different RNAs. Functionally, snoRNAs bind with core proteins to form small nucleolar ribonucleoproteins (snoRNPs). These snoRNAs then direct the protein complex to specific sites on target RNA molecules where modifications are necessary for either standard cellular operations or the regulation of pathological mechanisms. At these targeted sites, the proteins coupled with snoRNPs perform the modification processes that are vital for controlling cellular functions. The unique characteristics of snoRNAs and their involvement in various non-metabolic and metabolic diseases highlight their potential as therapeutic targets. Moreover, the precise targeting capability of snoRNAs might be harnessed as a molecular tool to therapeutically address various disease conditions. This review delves into the role of snoRNAs in health and disease and explores the broad potential of these snoRNAs as therapeutic agents in human pathologies.
Mannan-Binding Lectin Is Associated with Inflammation and Kidney Damage in a Mouse Model of Type 2 Diabetes
Authors: Dørflinger Gry H. , Holt Charlotte B. , Thiel Steffen , Bech Jesper N. , Østergaard Jakob A. , Bjerre Mette
Published: July 2024

Autoreactivity of the complement system may escalate the development of diabetic nephropathy. We used the BTBR OB mouse model of type 2 diabetes to investigate the role of the complement factor mannan-binding lectin (MBL) in diabetic nephropathy. Female BTBR OB mice (n = 30) and BTBR non-diabetic WT mice (n = 30) were included. Plasma samples (weeks 12 and 21) and urine samples (week 19) were analyzed for MBL, C3, C3-fragments, SAA3, and markers for renal function. Renal tissue sections were analyzed for fibrosis, inflammation, and complement deposition. The renal cortex was analyzed for gene expression (complement, inflammation, and fibrosis), and isolated glomerular cells were investigated for MBL protein. Human vascular endothelial cells cultured under normo- and hyperglycemic conditions were analyzed by flow cytometry. We found that the OB mice had elevated plasma and urine concentrations of MBL-C (p < 0.0001 and p < 0.001, respectively) and higher plasma C3 levels (p < 0.001) compared to WT mice. Renal cryosections from OB mice showed increased MBL-C and C4 deposition in the glomeruli and increased macrophage infiltration (p = 0.002). Isolated glomeruli revealed significantly higher MBL protein levels (p < 0.001) compared to the OB and WT mice, and no renal MBL expression was detected. We report that chronic inflammation plays an important role in the development of DN through the binding of MBL to hyperglycemia-exposed renal cells.
A New Method for Growth Factor Enrichment from Dairy Products by Electrodialysis with Filtration Membranes: The Major Impact of Raw Product Pretreatment
Authors: Kadel Sabita , Nichka Vladlen , Thibodeau Jacinthe , Parjikolaei Behnaz Razi , Bazinet Laurent
Published: July 2024

This study is focused on fractionation of insulin-like growth factor I (IGF-I) and transforming growth factor-β2 (TGF-β2) using a new electro-based membrane process calledelectrodialysis with filtration membranes (EDFM). Before EDFM, different pretreatments were tested, and four pH conditions (4.25, 3.85, 3.45, and 3.05) were used during EDFM. It was demonstrated that a 1:1 dilution of defatted colostrum with deionized water to decrease mineral content followed by the preconcentration of GFs by UF is necessary and allow for these compounds to migrate to the recovery compartment during EDFM. MS analyses confirmed the migration, in low quantity, of only α-lactalbumin (α-la) and β-lactoglobulin (β-lg) from serocolostrum to the recovery compartment during EDFM. Consequently, the ratio of GFs to total protein in recovery compartment compared to that of feed serocolostrum solution was 60× higher at pH value 3.05, the optimal pH favoring the migration of IGF-I and TGF-β2. Finally, these optimal conditions were tested on acid whey to also demonstrate the feasibility of the proposed process on one of the main by-products of the cheese industry; the ratio of GFs to total protein was 2.7× higher in recovery compartment than in feed acid whey solution, and only α-la migrated. The technology of GF enrichment for different dairy solutions by combining ultrafiltration and electrodialysis technologies was proposed for the first time.
A Novel Multiplex LAMP Assay for the Detection of Respiratory Human Adenoviruses
Authors: Koryukov Maksim A. , Oscorbin Igor P. , Novikova Lidiya M. , Gordukova Maria A. , Turina Irina E. , Galeeva Elena V. , Kudlay Dmitry A. , Filipenko Maxim L.
Published: July 2024

Human adenoviruses (HAdVs) are common pathogens that are associated with a variety of diseases, including respiratory tract infections (RTIs). Without reliable, fast, and cost-effective detection methods for HAdVs, patients may be misdiagnosed and inappropriately treated. To address this problem, we have developed a multiplex loop-mediated isothermal amplification (LAMP) assay for the detection of the species Human adenovirus B (HAdV-B), Human adenovirus C (HAdV-C) and Human adenovirus E (HAdV-E) that cause RTIs. This multiplexing approach is based on the melting curve analysis of the amplicons with a specific melting temperature for each HAdV species. Without the need for typing of HAdVs, the LAMP results can be visually detected using colorimetric analysis. The assay reliably detects at least 375 copies of HAdV-B and -C and 750 copies of HAdV-E DNA per reaction in less than 35 min at 60 °C. The designed primers have no in silico cross-reactivity with other human respiratory pathogens. Validation on 331 nasal swab samples taken from patients with RTIs showed a 90–94% agreement rate with our in-house multiplex quantitative polymerase chain reaction (qPCR) method. Concordance between the quantitative and visual LAMP was 99%. The novel multiplexed LAMP could be an alternative to PCR for diagnostic purposes, saving personnel and equipment time, or could be used for point-of-care testing.
Pretreatment of Melanoma Cells with Aqueous Ethanol Extract from Madhuca longifolia Bark Strongly Potentiates the Activity of a Low Dose of Dacarbazine
Authors: Środa-Pomianek Kamila , Barycka Anna , Gleńsk Michał , Rajbhandari Meena , Skonieczna Magdalena , Palko-Łabuz Anna , Wesołowska Olga
Published: July 2024

Madhuca longifolia is an evergreen tree distributed in India, Nepal, and Sri Lanka. This tree is commonly known as Mahua and is used in traditional medicine. It was demonstrated that ethanol extract from the bark of M. longifolia possessed potent cytotoxic activity towards two melanoma cell lines, in contrast to aqueous extract that exhibited no activity. Apart from being selectively cytotoxic to cancer cells (with no activity towards non-cancerous fibroblasts), the studied extract induced apoptosis and increased reactive oxygen species generation in melanoma cells. Additionally, the use of the extract together with dacarbazine (both in non-toxic concentrations) resulted in the enhancement of their anticancer activity. Moreover, the pretreatment of melanoma cells with M. longifolia extract potentiated the activity of a low dose of dacarbazine to an even higher extent. It was concluded that ethanol extract of M. longifolia sensitized human melanoma cells to chemotherapeutic drugs. It can therefore be interesting as a promising source of compounds for prospective combination therapy.
Growth Properties and Metabolomic Analysis Provide Insight into Drought Tolerance in Barley (Hordeum vulgare L.)
Authors: Wang Juncheng , Yao Lirong , Hao Jing , Li Chengdao , Li Baochun , Meng Yaxiong , Ma Xiaole , Si Erjing , Yang Ke , Zhang Hong , Shang Xunwu , Wang Huajun
Published: July 2024

Drought stress is a major meteorological threat to crop growth and yield. Barley (Hordeum vulgare L.) is a vital cereal crop with strong drought tolerance worldwide. However, the underlying growth properties and metabolomic regulatory module of drought tolerance remains less known. Here, we investigated the plant height, spike length, effective tiller, biomass, average spikelets, 1000-grain weight, number of seeds per plant, grain weight per plant, ash content, protein content, starch content, cellulose content, and metabolomic regulation mechanisms of drought stress in barley. Our results revealed that the growth properties were different between ZDM5430 and IL-12 under drought stress at different growth stages. We found that a total of 12,235 metabolites were identified in two barley genotype root samples with drought treatment. More than 50% of these metabolites showed significant differences between the ZDM5430 and IL-12 roots. The Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 368 differential metabolites mainly involved in starch and sucrose metabolism, the pentose phosphate pathway, pyrimidine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis in ZDM5430 under drought stress, whereas the different metabolites of IL-12 under drought stress related to starch and sucrose metabolism, the pentose phosphate pathway, 2-oxocarboxylic acid metabolism, cutin, suberine and wax biosynthesis, carbon metabolism, fatty acid biosynthesis, and C5-branched dibasic acid metabolism. These metabolites have application in the tricarboxylic cycle, the urea cycle, the met salvage pathway, amino acid metabolism, unsaturated fatty acid biosynthesis, phenolic metabolism, and glycolysis. On the other hand, the expression patterns of 13 genes related to the abovementioned bioprocesses in different barley genotypes roots were proposed. These findings afford an overview for the understanding of barley roots’ metabolic changes in the drought defense mechanism by revealing the differently accumulated compounds.
The Role of miR-137 in Neurodegenerative Disorders
Authors: Bodai László , Borosta Roberta , Ferencz Ágnes , Kovács Mercédesz , Zsindely Nóra
Published: July 2024

Neurodegenerative diseases affect an increasing part of the population of modern societies, burdening healthcare systems and causing immense suffering at the personal level. The pathogenesis of several of these disorders involves dysregulation of gene expression, which depends on several molecular processes ranging from transcription to protein stability. microRNAs (miRNAs) are short non-coding RNA molecules that modulate gene expression by suppressing the translation of partially complementary mRNAs. miR-137 is a conserved, neuronally enriched miRNA that is implicated in neurodegeneration. Here, we review the current body of knowledge about the role that miR-137 plays in five prominent neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. The presented data indicate that, rather than having a general neuroprotective role, miR-137 modulates the pathology of distinct disorders differently.
The Discovery of Novel α2a Adrenergic Receptor Agonists Only Coupling to Gαi/O Proteins by Virtual Screening
Authors: Zhou Peilan , Lu Fengfeng , Zhu Huili , Shi Beibei , Wang Xiaoxuan , Sun Shiyang , Li Yulei , Su Ruibin
Published: July 2024

Most α2-AR agonists derived from dexmedetomidine have few structural differences between them and have no selectivity for α2A/2B-AR or Gi/Gs, which can lead to side effects in drugs. To obtain novel and potent α2A-AR agonists, we performed virtual screening for human α2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity. Compound P300–2342 and its three analogs significantly decreased the locomotor activity of mice (p < 0.05). Furthermore, P300–2342 and its three analogs inhibited the binding of [3H] Rauwolscine with IC50 values of 7.72 ± 0.76 and 12.23 ± 0.11 μM, respectively, to α2A-AR and α2B-AR. In α2A-AR-HEK293 cells, P300–2342 decreased forskolin-stimulated cAMP production without increasing cAMP production, which indicated that P300–2342 activated α2A-AR with coupling to the Gαi/o pathway but without Gαs coupling. P300–2342 exhibited no agonist but slight antagonist activities in α2B-AR. Similar results were obtained for the analogs of P300–2342. The docking results showed that P300–2342 formed π-hydrogen bonds with Y394, V114 in α2A-AR, and V93 in α2B-AR. Three analogs of P300–2342 formed several π-hydrogen bonds with V114, Y196, F390 in α2A-AR, and V93 in α2B-AR. We believe that these molecules can serve as leads for the further optimization of α2A-AR agonists with potentially few side effects.
Lipid Emulsions Inhibit Labetalol-Induced Vasodilation in the Isolated Rat Aorta
Authors: Lee Soohee , Park Kyeong-Eon , Hwang Yeran , Bae Sungil , Ok Seong-Ho , Ahn Seung-Hyun , Sim Gyujin , Kim Hyun-Jin , Park Seunghyeon , Sohn Ju-Tae
Published: July 2024

Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration.
Genomic and Epigenomic Biomarkers of Immune Checkpoint Immunotherapy Response in Melanoma: Current and Future Perspectives
Authors: Hossain Sultana Mehbuba , Carpenter Carien , Eccles Michael R.
Published: July 2024

Immune checkpoint inhibitors (ICIs) demonstrate durable responses, long-term survival benefits, and improved outcomes in cancer patients compared to chemotherapy. However, the majority of cancer patients do not respond to ICIs, and a high proportion of those patients who do respond to ICI therapy develop innate or acquired resistance to ICIs, limiting their clinical utility. The most studied predictive tissue biomarkers for ICI response are PD-L1 immunohistochemical expression, DNA mismatch repair deficiency, and tumour mutation burden, although these are weak predictors of ICI response. The identification of better predictive biomarkers remains an important goal to improve the identification of patients who would benefit from ICIs. Here, we review established and emerging biomarkers of ICI response, focusing on epigenomic and genomic alterations in cancer patients, which have the potential to help guide single-agent ICI immunotherapy or ICI immunotherapy in combination with other ICI immunotherapies or agents. We briefly review the current status of ICI response biomarkers, including investigational biomarkers, and we present insights into several emerging and promising epigenomic biomarker candidates, including current knowledge gaps in the context of ICI immunotherapy response in melanoma patients.
PIEZO1 Promotes the Migration of Endothelial Cells via Enhancing CXCR4 Expression under Simulated Microgravity
Authors: Wang Yuan , Li Chengfei , Wang Ruonan , Zhao Xingcheng , Pan Yikai , Zhang Qian , Li Shuhan , Fan Jieyi , Wang Yongchun , Sun Xiqing
Published: July 2024

Exposure to microgravity during spaceflight induces the alterations in endothelial cell function associated with post-flight cardiovascular deconditioning. PIEZO1 is a major mechanosensitive ion channel that regulates endothelial cell function. In this study, we used a two-dimensional clinostat to investigate the expression of PIEZO1 and its regulatory mechanism on human umbilical vein endothelial cells (HUVECs) under simulated microgravity. Utilizing quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, we observed that PIEZO1 expression was significantly increased in response to simulated microgravity. Moreover, we found microgravity promoted endothelial cells migration by increasing expression of PIEZO1. Proteomics analysis highlighted the importance of C-X-C chemokine receptor type 4(CXCR4) as a main target molecule of PIEZO1 in HUVECs. CXCR4 protein level was increased with simulated microgravity and decreased with PIEZO1 knock down. The mechanistic study showed that PIEZO1 enhances CXCR4 expression via Ca2+ influx. In addition, CXCR4 could promote endothelial cell migration under simulated microgravity. Taken together, these results suggest that the upregulation of PIEZO1 in response to simulated microgravity regulates endothelial cell migration due to enhancing CXCR4 expression via Ca2+ influx.
Bone Loss in Diabetes Mellitus: Diaporosis
Authors: Kupai Krisztina , Kang Hsu Lin , Pósa Anikó , Csonka Ákos , Várkonyi Tamás , Valkusz Zsuzsanna
Published: July 2024

The objective of this review is to examine the connection between osteoporosis and diabetes, compare the underlying causes of osteoporosis in various forms of diabetes, and suggest optimal methods for diagnosing and assessing fracture risk in diabetic patients. This narrative review discusses the key factors contributing to the heightened risk of fractures in individuals with diabetes, as well as the shared elements impacting the treatment of both diabetes mellitus and osteoporosis. Understanding the close link between diabetes and a heightened risk of fractures is crucial in effectively managing both conditions. There are several review articles of meta-analysis regarding diaporosis. Nevertheless, no review articles showed collected and well-organized medications of antidiabetics and made for inconvenient reading for those who were interested in details of drug mechanisms. In this article, we presented collected and comprehensive charts of every antidiabetic medication which was linked to fracture risk and indicated plausible descriptions according to research articles.
Insight into Mantle Cell Lymphoma Pathobiology, Diagnosis, and Treatment Using Network-Based and Drug-Repurposing Approaches
Authors: Orfanoudaki Georgia , Psatha Konstantina , Aivaliotis Michalis
Published: July 2024

Mantle cell lymphoma (MCL) is a rare, incurable, and aggressive B-cell non-Hodgkin lymphoma (NHL). Early MCL diagnosis and treatment is critical and puzzling due to inter/intra-tumoral heterogeneity and limited understanding of the underlying molecular mechanisms. We developed and applied a multifaceted analysis of selected publicly available transcriptomic data of well-defined MCL stages, integrating network-based methods for pathway enrichment analysis, co-expression module alignment, drug repurposing, and prediction of effective drug combinations. We demonstrate the “butterfly effect” emerging from a small set of initially differentially expressed genes, rapidly expanding into numerous deregulated cellular processes, signaling pathways, and core machineries as MCL becomes aggressive. We explore pathogenicity-related signaling circuits by detecting common co-expression modules in MCL stages, pointing out, among others, the role of VEGFA and SPARC proteins in MCL progression and recommend further study of precise drug combinations. Our findings highlight the benefit that can be leveraged by such an approach for better understanding pathobiology and identifying high-priority novel diagnostic and prognostic biomarkers, drug targets, and efficacious combination therapies against MCL that should be further validated for their clinical impact.
In Vitro Investigation of Pulsed Electromagnetic Field Stimulation (PEMF) with MAGCELL® ARTHRO on the Regulatory Expression of Soluble and Membrane-Bound Complement Factors and Inflammatory Cytokines in Immortalized Synovial Fibroblasts
Authors: Silawal Sandeep , Gesslein Markus , Willauschus Maximilian , Schulze-Tanzil Gundula
Published: July 2024

Pulsed electromagnetic field stimulation (PEMF) is gaining more attention as a non-invasive arthritis treatment. In our study, immortalized synovial fibroblasts (K4IM) derived from a non-arthritic donor were exposed to MAGCELL® ARTHRO, a PEMF device, with 105 mT intensity, 8 Hz frequency, and 2 × 2.5 min sessions conducted thrice with a 1 h interval, to understand the underlying mechanism in regard to the complement system. Additionally, tumor necrosis factor (TNFα, 10 ng/mL) pre-treatment prior to PEMF stimulation, as well as 3-day versus 6-day stimulation, were compared. Gene expression of C4b binding protein-alpha and -beta (C4BPα, C4BPβ), complement factor (CF)-H, CFI, CD55, CD59, Interleukin (IL-6) and TNFα was analyzed. Immunofluorescence staining of CD55, CD59, and Ki67 was conducted. Results showed the absence of C4BPα gene expression, but C4BPβ was present. One and three days of PEMF stimulation caused no significant changes. However, after six days, there was a significant increase in CD55, CFH, and CD59 gene expression, indicating cytoprotective effects. Conversely, IL-6 gene expression increased after six days of stimulation and even after a single session in TNFα pre-stimulated cells, indicating a pro-inflammatory effect. PEMF’s ambivalent, i.e., enhancing complement regulatory proteins and pro-inflammatory cytokines, highlights its complexity at the molecular level.
Microcrack and Porosity Development in Sealed Cement Mortars Measured with Micro-Computed Tomography
Authors: Ševčík Radek , Adámková Irena , Vopálenský Michal , Martauz Pavel , Šmilauer Vít
Published: July 2024

For the first time, this paper explores the role of hydration kinetics on microcrack development in cement mortars using the μ-CT technique with a resolution of 2.2 µm. Three binders were tested: fine-grained ordinary Portland cement (OPC) with Blaine fineness of 391 m2/kg, coarse-grained OPC made from the same clinker with Blaine fineness of 273 m2/kg, and H-cement as a representative of the alkali-activated binder. It was found that most microcracks have a width in the range of 5–10 µm, increasing their occurrence with the progress of sealed hydration. While H-cement and coarse-grained OPC showed a comparable number of microcracks, fine-grained OPC exhibited more than twice the number of microcracks. In this sense, high hydration kinetics induce more microcracks, promoting later coalescence into visible cracks and disintegration of concrete at the end. Therefore, durable concrete with minimum microcracks should be derived from slow hydration kinetics or alkali-activation processes.
Optical Active Meta-Surfaces, -Substrates, and Single Quantum Dots Based on Tuning Organic Composites with Graphene
Authors: Romero Marcelo R. , Bracamonte A. Guillermo
Published: July 2024

In this communication, the design and fabrication of optical active metamaterials were developed by the incorporation of graphene and joining it to different substrates with variable spectroscopical properties. It focuses on how graphene and its derivatives could generate varied optical setups and materials considering modified and enhanced optics within substrates and surfaces. In this manner, it is discussed how light could be tuned and modified along its path from confined nano-patterned surfaces or through a modified micro-lens. In addition to these optical properties generated from the physical interaction of light, it should be added that the non-classical light pathways and quantum phenomena could participate. In this way, graphene and related carbon-based materials with particular properties, such as highly condensed electronics, pseudo-electromagnetic properties, and quantum and luminescent properties, could be incorporated. Therefore, the modified substrates could be switched by photo-stimulation with variable responses depending on the nature of the material constitution. Therefore, the optical properties of graphene and its derivatives are discussed in these types of metasurfaces with targeted optical active properties, such as within the UV, IR, and terahertz wavelength intervals, along with their further properties and respective potential applications.
Resistance Analysis of Crack Propagation in Concrete Subjected to Hydraulic Pressure
Authors: Wang Yang , Sun Jingshan , Wang Gaohui , Li Yongzhen , Xiong Weiqi
Published: July 2024

The KR resistance curve for hydraulic crack propagation in a concrete beam was determined and discussed. A semi-analytical method was introduced to calculate the hydraulic crack propagation in concrete. A series of concrete beams with various hydraulic pressures and initial crack depths were tested, and the hydraulic crack propagation in these beams was calculated. The calculated P-CMOD curves were first verified, and then the calculated KR resistance curve for hydraulic crack propagation was determined. Based on the test results and calculation results, the following conclusions can be drawn: The proposed analysis method can accurately predict the hydraulic crack propagation process in concrete. The KR resistance to hydraulic crack propagation in concrete decreases with the increase in hydraulic pressure but is less influenced by the initial crack depth of the test beams. In addition, the concrete beams collapse immediately under hydraulic fracturing once the KIw curve reaches the KR resistance curve. This indicates that the failure of concrete structures under hydraulic fracturing occurs immediately once the driving force of crack propagation, dominated by the hydraulic pressure in the crack, becomes significant.
Enhancement of Abnormal Grain Growth by Surface Quenching Treatment to Eliminate Cu–Cu Bonding Interfaces Using (111)-Oriented Nanotwinned Copper
Authors: Lu Tsan-Feng , Yen Yu-Ting , Cheng Yuan-Fu , Wang Pei-Wen , Wu YewChung Sermon
Published: July 2024

Cu–Cu joints have been adopted for ultra-high density of packaging for high-end devices. However, the processing temperature must be kept relatively low, preferably below 300 °C. In this study, a novel surface modification technique, quenching treatment, was applied to achieve Cu-to-Cu direct bonding using (111)-oriented nanotwinned Cu. The quenching treatment enabled grain growth across the Cu–Cu bonding interface at 275 °C. During quenching treatment, strain energy was induced in the Cu film, resulting in a wrinkled surface morphology. To analyze the strain energy, we utilized an electron backscattered diffraction system to obtain crystallographic information and confirmed it using kernel average misorientation analysis.
Experimental Dust Absorption Study in Automotive Engine Inlet Air Filter Materials
Authors: Dziubak Tadeusz
Published: July 2024

The purpose of this study was to empirically evaluate the performance of fibrous materials that meet the criteria for inlet air filtration in internal combustion engines. The characteristics of filtration efficiency and accuracy, as well as the characteristics of flow resistance, were determined based on the mass of dust accumulated in the filter bed during the filtration process. Single-layer filter materials tested included cellulose, polyester, and glass microfiber. Multilayer filter media such as cellulose–polyester–nanofibers and cellulose–polyester were also examined. A new composite filter bed—consisting of polyester, glass microfiber, and cellulose—and its filtration characteristics were evaluated. Utilizing specific air filtration quality factors, it was demonstrated that the composite is characterized by high pre-filtration efficiency (99.98%), a short pre-filtration period (qs = 4.21%), high accuracy (dpmax = 1.5–3 µm) for the entire lifespan of the filter, and a 60–250% higher dust absorption coefficient compared to the other tested materials. A filtration composite bed constructed from a group of materials with different filtration parameters can be, due to its high filtration efficiency, accuracy, and dust absorption, an excellent filter material for engine intake air. The composite’s filtration parameters will depend on the type of filter layers and their order relative to the aerosol flow. This paper presents a methodology for the selection and testing of various filter materials.
Effects of Co on Mechanical Properties and Precipitates in a Novel Secondary−Hardening Steel with Duplex Strengthening of M2C and β−NiAl
Authors: Geng Ruming , Han Shun , Pang Xuedong , Yuan Xiaoyuan , Liu Yue , Li Yong , Wang Chunxu
Published: July 2024

Synergistic strengthening of nano−scaled M2C and β−NiAl has become a new route to develop ultra−high secondary−hardening steel. At present, the effect of Co on the synergistic precipitation behavior of duplex phases of M2C and β−NiAl has been rarely reported. This paper revealed the effects of Co on the mechanical properties and duplex precipitates of M2C and β−NiAl in a novel 2.5 GPa ultra−high strength secondary−hardening steel. The tensile tests indicated that a 10% Co−alloy steel achieved a much stronger secondary−hardening effects compared to a Co−free steel during aging process, especially in the early−aging state. Needle−shaped M2C and spherical β−NiAl particles were observed in both Co−alloy and Co−free steels. However, the number density, and volume fraction of M2C were significantly enhanced in the 10% Co−alloy steel. The Mo contents in M2C carbide and α−Fe after aging treatment were both analyzed through experimental determination and thermodynamic calculation, and the results indicated that Co decreased the solubility of Mo in α−Fe, thus promoting the precipitation of Mo−rich carbides.
Characterization of NiCuOxNy Coatings Obtained via RF Sputtering: Structure, Morphology, and Optical Properties
Authors: Velásquez-Méndez Karen Lizzette , Alfonso José Edgar , Bethencourt Manuel , Cifredo Gustavo , Cubillos Gloria Ivonne
Published: July 2024

The rapid advancement of technology necessitates the continual development of versatile materials that can adapt to new electronic devices. Rare earth elements, which are scarce in nature, possess the set of properties required for use as semiconductors. Consequently, this research aims to achieve similar properties using materials that are abundant in nature and have a low commercial cost. To this end, nickel and copper were utilized to synthesize thin films of nickel–copper binary oxynitride via reactive RF sputtering. The influence of nitrogen flow on the structure, morphology, chemical composition, and optical properties of the films was investigated using various characterization techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS), as well as transmittance and absorbance measurements. The crystalline structure of the films shows that they can have preferential growth or be polycrystalline according to the nitrogen flow used during deposition and that both the oxides and oxynitrides of metals are formed. We identified unknown phases specific to this material, termed “NiCuOxNy”. The morphology revealed that the grain size of the coatings was dependent on the nitrogen flow rate, with grain size decreasing as the nitrogen flow rate increased. Notably, the coatings demonstrated transparency for wavelengths exceeding 1000 nm, with an optical band gap ranging from 1.21 to 1.86 eV.
Feasibility Analysis of Bacterial-Treated Coal Gangue for Soil Improvement: Growth-Promoting Effects of Alfalfa
Authors: Wang Yaya , Liu Mingwu , Di Zhiting , Cao Weilong , He Shihua
Published: July 2024

The long-term storage of coal gangue (CG) mountains causes serious environmental problems such as water and air pollution. Thus, sustainable reclamation practices are urgently needed to minimize the environmental impacts brought by CG mountains. Pikovskaya medium was employed to screen microorganisms, which were subsequently utilized to promote the solubilization of CG. XRF, SEM, XRD, and HPLC techniques were employed to characterize the CG before and after bacterial treatment. In this study, we have successfully isolated and purified a bacterial strain, identified as Stenotrophomonas bentonitica BII-R7, which possesses the ability to facilitate the solubilization of nutrient elements from CG. Factors including initial inoculation ratio, incubation time, CG particle size, CG concentration, pH, and temperature were examined to investigate their effects on the biosolubilization of CG. Furthermore, the mechanism underlying the CG solubilization was also probed. Our data demonstrated that low-molecular-weight organic acids, such as acetic acid and formic acid, may harbor a crucial role in promoting the solubilization of CG. Lastly, we found that Stenotrophomonas bentonitica BII-R7, in conjugation with CG, can increase the alfalfa seed germination percentage and promote the growth of alfalfa. Together, these data provide evidence that bacterial-treated CG can be utilized for soil improvement and land reclamation.
Application of Integrated Geological and Geophysical Surveys on the Exploration of Chalcedony Deposits: A Case Study on Nanhong Agate in Liangshan, China
Authors: Gong Shengping , Zhao Keqiang , Wang Mingming , Yan Shengwu , Li Yong , Yang Jianzhou
Published: July 2024

Nanhong agate, esteemed for its vivid color and natural shine, is experiencing a scarcity in supply despite its high demand. The primary deposits of agate, typically found near the surface, have not been extensively explored due to the predominance of traditional manual excavation methods. This research examined the Nanhong agate deposits in the Zhaojue–Meigu region of Liangshan, China, employing the integration of geological and geophysical surveys. Field geological surveys allowed us to outline the general areas where agate is found. Following this, using magnetic surveys, vertical electrical sounding, and controlled-source audio magnetotellurics, agate deposits were located within the conglomerate layer of the second member of the Feixianguan Formation from the Lower Triassic period at depths of less than 100 m. Our results identify mineralized layers, Xuanwei Formation mudstone, and the underlying bedrock, thus supporting the creation of a mineral prediction map. This research provides essential insights and guidance for agate exploration and the development of associated mineral resources.