bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of a Built-in Finned Trombe Wall on the Indoor Thermal Environment in Cold Regions
Authors: Qi Xiaobing , Wang Jialong , Wang Ye
Published: April 2024

This study focuses on energy conservation, reducing the amount of energy consumed to heat a room, and decreasing the intensity of carbon emissions. The research object is a room heated by a floor with a built-in finned Trombe wall (TW) located in Lanzhou, Gansu Province. ANSYS software was employed to conduct a simulation study on parameters such as fin height, transverse spacing, longitudinal spacing, arrangement mode, and fin apex angle. The simulation results were used to determine the fin parameters’ thermal impact on the TW’s thermal performance, including with respect to a room’s thermal environment (TE). The results show that the heat transfer performance of a TW with respect to the thermal environment of a room is the greatest when the height of the heat-absorbing surface is 20 mm, the transverse spacing is 0.20 m, the longitudinal spacing is 0.533 m, and in-line 90° top-angle fins, that is, isosceles right triangle fins, are used. The average Nu number of the fin-type TW is 154.75. Compared with the average Nu number of the finless TW, which is 141.43, the average Nu number increases by 13.32 due to the addition of fins. The optimized fin-type TW has 7.77% higher convective heat supply efficiency than the finless TW. Although the PMV-PPD results of the two TW-type rooms are not very different, the comfort period of the fin-type TW room is longer. At the same time, the LPD3 of the non-finned TW and the finned TW rooms is less than 10%, the wind speed at the head and ankle is less than 0.12 m/s, the air gust sensation is not strong, and the thermal comfort is good, indicating that the addition of fins is beneficial to the improvement of indoor thermal comfort. Compared to standard rooms, finless TW rooms and fin-type TW rooms have energy-saving rates of 36.38% and 44.63%, respectively. Thus, fin-type TW rooms’ energy saving rate is 8.25% higher, resulting in effective savings in heating energy consumption. Therefore, the indoor TE and auxiliary heating conditions are improved, and the integration of solar building technology can be facilitated, which offers significant reference value for energy transformation.
Improving Aeromechanical Performance of Compressor Rotor Blisk with Topology Optimization
Authors: Bandini Alberto , Cascino Alessio , Meli Enrico , Pinelli Lorenzo , Marconcini Michele
Published: April 2024

When it comes to modern design of turbomachinery, one of the most critical objectives is to achieve higher efficiency and performance by reducing weight, fuel consumption, and noise emissions. This implies the need for reducing the mass and number of the components, by designing thinner, lighter, and more loaded blades. These choices may lead to mechanical issues caused by the fluid–structure interaction, such as flutter and forced response. Due to the periodic aerodynamic loading in rotating components, preventing or predicting resonances is essential to avoid or limit the dangerous vibration of the blades; thus, simulation methods are crucial to study such conditions during the machine design. The purpose of this paper is to assess a numerical approach based on a topology optimization method for the innovative design of a compressor rotor. A fluid-structural optimization process has been applied to a rotor blisk which belongs to a one-and-a-half-stage aeronautical compressor including static and dynamic loads coming from blade rotation and fluid flow interaction. The fluid forcing is computed by some CFD TRAF code, and it is processed via time and space discrete Fourier transform to extract the pressure fluctuation components in a cyclic-symmetry environment. Finally, a topological optimization of the disk is performed, and the encouraging results are presented and discussed. The remarkable mass reduction in the component (≈32%), the mode-shape frequency shift from a fluid forcing frequency, and an overall relevant reduction in the dynamic response around Campbell’s crossing confirm the efficacy of the presented methodology.
Elimination of Toxic Solvents from Analytical Methods in Food Analysis: Caffeine Determination in Tea as an Example
Authors: Kalisz Oktawia , Jaworska Aleksandra , Studzińska Sylwia , Bocian Szymon
Published: April 2024

This study presents an innovative method for caffeine determination in tea, employing ethanol as the sole organic solvent for both SPE sample preparation and chromatographic analysis. This approach aligns with green chemistry principles, as confirmed by a comparative study highlighting ethanol’s safety and eco-friendliness compared to traditional solvents. The experiments validate ethanol’s efficacy in caffeine extraction and chromatographic analysis, minimizing environmental impact and eliminating toxicity risks. Utilizing a reduced chromatography column enhances the method’s efficiency and sustainability, resulting in a low limit of quantitation (0.125 μg/mL) and good reproducibility (RSD < 2.5%). Based on tea from the Polish market, the findings reveal the caffeine content (19.29–37.69 mg/g) and endorse ethanol’s role in enhancing sustainable chemical analysis in food science.
Use of Pea Proteins in High-Moisture Meat Analogs: Physicochemical Properties of Raw Formulations and Their Texturization Using Extrusion
Authors: Plattner Blake J. , Hong Shan , Li Yonghui , Talavera Martin J. , Dogan Hulya , Plattner Brian S. , Alavi Sajid
Published: April 2024

A new form of plant-based meat, known as ‘high-moisture meat analogs’ (HMMAs), is captivating the market because of its ability to mimic fresh, animal muscle meat. Utilizing pea protein in the formulation of HMMAs provides unique labeling opportunities, as peas are both “non-GMO” and low allergen. However, many of the commercial pea protein isolate (PPI) types differ in functionality, causing variation in product quality. Additionally, PPI inclusion has a major impact on final product texture. To understand the collective impact of these variables, two studies were completed. The first study compared four PPI types while the second study assessed differences in PPI inclusion amount (30–60%). Both studies were performed on a Wenger TX-52 extruder, equipped with a long-barrel cooling die. Rapid-visco analysis (RVA) and sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) indicated differences in protein solubility among the different PPI types. In general, lower protein solubility led to better product quality, based on visual evaluation. Cutting strength and texture profile analysis showed increasing PPI inclusion from 30–60% led to significantly higher product hardness (14,160–16,885 g) and toughness (36,690–46,195 g. s). PPI4 led to lower product toughness (26,110 and 33,725 g. s), compared to the other PPIs (44,620–60,965 g. s). Heat gelling capacity of PPI4 was also highest among PPI types, by way of least gelation concentration (LGC) and RVA. When compared against animal meat, using more PPI (50–60%) better mimicked the overall texture and firmness of beef steak and pork chops, while less PPI better represented a softer product like chicken breast. In summary, protein content and also functionality such as cold water solubility and heat gelation dictated texturization and final product quality. High cold water solubility and poor heat gelation properties led to excessive protein cross linking and thicker yet less laminated shell or surface layer. This led to lower cutting firmness and toughness, and less than desirable product texture as compared to animal meat benchmarks. On the other hand, pea proteins with less cold water solubility and higher propensity for heat gelation led to products with more laminated surface layer, and higher cutting test and texture profile analysis response. These relationships will be useful for plant-based meat manufacturers to better tailor their products and choice of ingredients.
Relationships among Structure, Physicochemical Properties and In Vitro Digestibility of Starches from Ethiopian Food Barley Varieties
Authors: Gebre Bilatu Agza , Xu Zekun , Ma Mengting , Lakew Berhane , Sui Zhongquan , Corke Harold
Published: April 2024

Studying diversity in local barley varieties can help advance novel uses for the grain. Therefore, starch was isolated from nine Ethiopian food barley varieties to determine starch structural, pasting, thermal, and digestibility characteristics, as well as their inter-relationships. The amylose content in the varieties significantly varied from 24.5 to 30.3%, with a coefficient of variation of 6.1%. The chain length distributions also varied significantly, and fa, fb1, fb2, and fb3 ranged from 26.3 to 29.0, 48.0 to 49.7, 15.0 to 15.9, and 7.5 to 9.5%, respectively. Significant variations were also exhibited in absorbance peak ratios, as well as thermal, pasting, and in vitro digestibility properties, with the latter two parameters showing the greatest diversity. Higher contents of amylose and long amylopectin fractions contributed to higher gelatinization temperatures and viscosities and lower digestibility. Structural characteristics showed strong relationships with viscosity, thermal, and in vitro digestibility properties. Cross 41/98 and Dimtu varieties are more suitable in functional food formulations and for bakery products. These results might inspire further studies to suggest target-based starch modifications and new product development.
Evaluating Intraocular Pressure Alterations during Large Muscle Group Isometric Exercises with Varying Head and Body Positions
Authors: Krobot Cutura Nina , Mrak Maksimilijan , Cutura Dominik-Mate , Petric Vickovic Ivanka , Ruzic Lana
Published: April 2024

Performing physical exercise affects intraocular pressure, and its elevation and fluctuations are the main risk factors for glaucoma development or progression. The aim of this study was to examine the acute alterations in intraocular pressure (IOP) during four unweighted isometric exercises and to determine whether the different head and body positions taken during exercise additionally affect IOP. Twelve healthy volunteers between the ages of 25 and 33 performed four isometric exercises: wall sit in neutral head and body position, elbow plank in prone head and body position, reverse plank in supine head and body position for 1 min, and right-side plank in lateral head and body position for 30 s. Intraocular pressure was measured by applanation portable tonometry, before performing the exercise, immediately after exercise completion, and after five minutes of rest. A significant acute increase in intraocular pressure was found as a response to the performance of the elbow plank (p < 0.01), the reverse plank (p < 0.001), and the right-side plank (p < 0.001). The wall sit exercise did not reveal a statistically significant IOP elevation (p = 0.232). Different head and body positions had no significant additional influence on IOP (F (3,33) = 0.611; p = 0.613), even though the alteration in IOP was found to be greater in exercises with a lower head and body position. Our data revealed that IOP elevation seems to be affected by the performance of the elbow plank, the reverse plank, and the right-side plank; and not by the wall sit exercise. More different isometric exercises should be examined to find ones that are safe to perform for glaucoma patients.
The Social Context of Pregnancy, Respectful Maternity Care, Biomarkers of Weathering, and Postpartum Mental Health Inequities: A Scoping Review
Authors: Basile-Ibrahim Bridget , Combellick Joan , Mead Thomas L. , Sorensen Alee , Batten Janene , Schafer Robyn
Published: April 2024

Background: Mental health disorders are the number one cause of maternal mortality and a significant maternal morbidity. This scoping review sought to understand the associations between social context and experiences during pregnancy and birth, biological indicators of stress and weathering, and perinatal mood and anxiety disorders (PMADs). Methods: A scoping review was performed using PRISMA-ScR guidance and JBI scoping review methodology. The search was conducted in OVID Medline and Embase. Results: This review identified 74 eligible English-language peer-reviewed original research articles. A majority of studies reported significant associations between social context, negative and stressful experiences in the prenatal period, and a higher incidence of diagnosis and symptoms of PMADs. Included studies reported significant associations between postpartum depression and prenatal stressors (n = 17), socioeconomic disadvantage (n = 14), negative birth experiences (n = 9), obstetric violence (n = 3), and mistreatment by maternity care providers (n = 3). Birth-related post-traumatic stress disorder (PTSD) was positively associated with negative birth experiences (n = 11), obstetric violence (n = 1), mistreatment by the maternity care team (n = 1), socioeconomic disadvantage (n = 2), and prenatal stress (n = 1); and inverse association with supportiveness of the maternity care team (n = 5) and presence of a birth companion or doula (n = 4). Postpartum anxiety was significantly associated with negative birth experiences (n = 2) and prenatal stress (n = 3). Findings related to associations between biomarkers of stress and weathering, perinatal exposures, and PMADs (n = 14) had mixed significance. Conclusions: Postpartum mental health outcomes are linked with the prenatal social context and interactions with the maternity care team during pregnancy and birth. Respectful maternity care has the potential to reduce adverse postpartum mental health outcomes, especially for persons affected by systemic oppression.
Perceptions and Experiences of Inequity for Women of Refugee Background Having a Baby during the COVID-19 Pandemic in Melbourne, Australia
Authors: Hearn Fran , Brown Stephanie J. , Szwarc Josef , Toke Shadow , Alqas Alias May , Essa Maryaan , Hydari Shogoufa , Baget Ashay , Riggs Elisha
Published: April 2024

Listening to What Matters is an exploratory descriptive qualitative study that aimed to (1) understand how women of refugee background in Melbourne, Australia experienced access to health information and maternity and/or early parenting care during the COVID-19 pandemic and (2) whether pandemic health directives had an impact on structural inequities for women of refugee background who received maternity and/or early parenting care during the COVID-19 pandemic. Semi-structured interviews were conducted with 41 participants including 17 women of refugee background, who identified as belonging to the Karen, Assyrian Chaldean, Iraqi, Syrian, Afghan, Sudanese, or South Sudanese communities and 24 health and social care professionals who identified as providing pregnancy or early parenting care during the pandemic in the north western suburbs of Melbourne. Interviews with women were conducted in preferred languages by community researchers. Interviews with professionals were conducted in English by researchers. Reflexive thematic data analysis included constructivist positionality and a trauma and violence informed approach. The results reported in this paper include three themes, with four accompanying subthemes, as follows: theme (1), ‘Structural inequities and the toll of the pandemic’; theme (2), ‘Supportive infrastructure’; and theme (3), ‘Cultural safety during the pandemic’. The results demonstrate that cumulative negative impacts such as unequal access to health information, family separation and isolation, inadequate household income, and mental and social health concerns had the potential to amplify pre-existing structural inequities for women of refugee background. Community engagement facilitated by bicultural workers, interpreters, and trusted care providers facilitated fast-paced, two-way communication that built capacity and health literacy for women who were unable to speak English and unfamiliar with the health care system and, improved experiences of care. More research is needed to understand how the intersectional cumulative impacts of structural inequities have affected maternal and neonatal health outcomes for women of refugee background during the pandemic, as well as any differences in maternal and neonatal health outcomes between Australian-born and refugee background women and babies.
Machine Learning-Driven Classification of Urease Inhibitors Leveraging Physicochemical Properties as Effective Filter Criteria
Authors: Morales Natalia , Valdés-Muñoz Elizabeth , González Jaime , Valenzuela-Hormazábal Paulina , Palma Jonathan M. , Galarza Christian , Catagua-González Ángel , Yáñez Osvaldo , Pereira Alfredo , Bustos Daniel
Published: April 2024

Urease, a pivotal enzyme in nitrogen metabolism, plays a crucial role in various microorganisms, including the pathogenic Helicobacter pylori. Inhibiting urease activity offers a promising approach to combating infections and associated ailments, such as chronic kidney diseases and gastric cancer. However, identifying potent urease inhibitors remains challenging due to resistance issues that hinder traditional approaches. Recently, machine learning (ML)-based models have demonstrated the ability to predict the bioactivity of molecules rapidly and effectively. In this study, we present ML models designed to predict urease inhibitors by leveraging essential physicochemical properties. The methodological approach involved constructing a dataset of urease inhibitors through an extensive literature search. Subsequently, these inhibitors were characterized based on physicochemical properties calculations. An exploratory data analysis was then conducted to identify and analyze critical features. Ultimately, 252 classification models were trained, utilizing a combination of seven ML algorithms, three attribute selection methods, and six different strategies for categorizing inhibitory activity. The investigation unveiled discernible trends distinguishing urease inhibitors from non-inhibitors. This differentiation enabled the identification of essential features that are crucial for precise classification. Through a comprehensive comparison of ML algorithms, tree-based methods like random forest, decision tree, and XGBoost exhibited superior performance. Additionally, incorporating the “chemical family type” attribute significantly enhanced model accuracy. Strategies involving a gray-zone categorization demonstrated marked improvements in predictive precision. This research underscores the transformative potential of ML in predicting urease inhibitors. The meticulous methodology outlined herein offers actionable insights for developing robust predictive models within biochemical systems.
The Effect of Enteric-Derived Lipopolysaccharides on Obesity
Authors: Wang Kai , Lai Weiwen , Min Tianqi , Wei Jintao , Bai Yan , Cao Hua , Guo Jiao , Su Zhengquan
Published: April 2024

Endotoxin is a general term for toxic substances in Gram-negative bacteria, whose damaging effects are mainly derived from the lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, and is a strong pyrogen. Obesity is a chronic, low-grade inflammatory condition, and LPS are thought to trigger and exacerbate it. The gut flora is the largest source of LPS in the body, and it is increasingly believed that altered intestinal microorganisms can play an essential role in the pathology of different diseases. Today, the complex axis linking gut flora to inflammatory states and adiposity has not been well elucidated. This review summarises the evidence for an interconnection between LPS, obesity, and gut flora, further expanding our understanding of LPS as a mediator of low-grade inflammatory disease and contributing to lessening the effects of obesity and related metabolic disorders. As well as providing targets associated with LPS, obesity, and gut flora, it is hoped that interventions that combine targets with gut flora address the individual differences in gut flora treatment.
Higher Seasonal Variation of Systemic Inflammation in Bipolar Disorder
Authors: Dallaspezia Sara , Cardaci Vincenzo , Mazza Mario Gennaro , De Lorenzo Rebecca , Rovere Querini Patrizia , Colombo Cristina , Benedetti Francesco
Published: April 2024

Seasonal rhythms affect the immune system. Evidence supports the involvement of immuno-inflammatory mechanisms in bipolar disorder (BD), with the neutrophil to lymphocyte ratio (NLR), and the systemic immune-inflammatory index (SII; platelets × neutrophils/lymphocytes) consistently reported to be higher in patients with BD than in HC, but seasonal rhythms of innate and adaptive immunity have never been studied. We retrospectively studied NLR and SII in 824 participants divided into three groups: 321 consecutively admitted inpatients affected by a major depressive episode in course of BD, and 255 consecutively admitted inpatients affected by obsessive–compulsive disorder (OCD; positive psychiatric control), and 248 healthy controls (HC). Patients with BD showed markedly higher markers of systemic inflammation in autumn and winter, but not in spring and summer, in respect to both HC and patients with OCD, thus suggesting a specific effect of season on inflammatory markers in BD, independent of a shared hospital setting and drug treatment. Given that systemic inflammation is emerging as a new marker and as target for treatment in depressive disorders, we suggest that seasonal rhythms should be considered for tailoring antidepressant immuno-modulatory treatments in a precision medicine approach.
Lectin-like Transcript-1 (LLT1) Expression in Oral Squamous Cell Carcinomas: Prognostic Significance and Relationship with the Tumor Immune Microenvironment
Authors: de Vicente Juan C. , Lequerica-Fernández Paloma , Rodrigo Juan P. , Rodríguez-Santamarta Tania , Blanco-Lorenzo Verónica , Prieto-Fernández Llara , Corte-Torres Daniela , Vallina Aitana , Domínguez-Iglesias Francisco , Álvarez-Teijeiro Saúl , García-Pedrero Juana M.
Published: April 2024

Lectin-like transcript-1 (LLT1) expression is detected in different cancer types and is involved in immune evasion. The present study investigates the clinical relevance of tumoral and stromal LLT1 expression in oral squamous cell carcinoma (OSCC), and relationships with the immune infiltrate into the tumor immune microenvironment (TIME). Immunohistochemical analysis of LLT1 expression was performed in 124 OSCC specimens, together with PD-L1 expression and the infiltration of CD20+, CD4+, and CD8+ lymphocytes and CD68+ and CD163+-macrophages. Associations with clinicopathological variables, prognosis, and immune cell densities were further assessed. A total of 41 (33%) OSCC samples showed positive LLT1 staining in tumor cells and 55 (44%) positive LLT1 in tumor-infiltrating lymphocytes (TILs). Patients harboring tumor-intrinsic LLT1 expression exhibited poorer survival, suggesting an immunosuppressive role. Conversely, positive LLT1 expression in TILs was significantly associated with better disease-specific survival, and also an immune-active tumor microenvironment highly infiltrated by CD8+ T cells and M1/M2 macrophages. Furthermore, the combination of tumoral and stromal LLT1 was found to distinguish three prognostic categories (favorable, intermediate, and adverse; p = 0.029, Log-rank test). Together, these data demonstrate the prognostic relevance of tumoral and stromal LLT1 expression in OSCC, and its potential application to improve prognosis prediction and patient stratification.
Therapeutic Potential of 4-Hexylresorcinol in Preserving Testicular Function in Streptozotocin-Induced Diabetic Rats
Authors: Oh Ji-Hyeon , Choi Je-Yong , Kim Dae-Won , Kim Seong-Gon , Garagiola Umberto
Published: April 2024

It is known that many diabetic patients experience testicular atrophy. This study sought to investigate the effect of 4-hexylresorcinol (4HR) on testicular function in rats with streptozotocin (STZ)-induced diabetes, focusing on testicular weight, sperm motility, histological alterations, and serum testosterone levels to understand the efficacy of 4HR on testes. Our findings reveal that 4HR treatment significantly improves testicular health in diabetic rats. Notably, the STZ group exhibited a testicular weight of 1.22 ± 0.48 g, whereas the STZ/4HR group showed a significantly enhanced weight of 1.91 ± 0.26 g (p < 0.001), aligning closely with the control group’s weight of 1.99 ± 0.17 g and the 4HR group’s weight of 2.05 ± 0.24 g, indicating no significant difference between control and 4HR groups (p > 0.05). Furthermore, the STZ/4HR group demonstrated significantly improved sperm motility compared to the STZ group, with apoptotic indicators notably reduced in the STZ/4HR group relative to the STZ group (p < 0.05). These results underscore the therapeutic potential of 4HR for maintaining testicular function under diabetic conditions.
Discovery of Strong 3-Nitro-2-Phenyl-2H-Chromene Analogues as Antitrypanosomal Agents and Inhibitors of Trypanosoma cruzi Glucokinase
Authors: Carey Shane M. , O’Neill Destiny M. , Conner Garrett B. , Sherman Julian , Rodriguez Ana , D’Antonio Edward L.
Published: April 2024

Chagas disease is one of the world’s neglected tropical diseases, caused by the human pathogenic protozoan parasite Trypanosoma cruzi. There is currently a lack of effective and tolerable clinically available therapeutics to treat this life-threatening illness and the discovery of modern alternative options is an urgent matter. T. cruzi glucokinase (TcGlcK) is a potential drug target because its product, d-glucose-6-phosphate, serves as a key metabolite in the pentose phosphate pathway, glycolysis, and gluconeogenesis. In 2019, we identified a novel cluster of TcGlcK inhibitors that also exhibited anti-T. cruzi efficacy called the 3-nitro-2-phenyl-2H-chromene analogues. This was achieved by performing a target-based high-throughput screening (HTS) campaign of 13,040 compounds. The selection criteria were based on first determining which compounds strongly inhibited TcGlcK in a primary screen, followed by establishing on-target confirmed hits from a confirmatory assay. Compounds that exhibited notable in vitro trypanocidal activity over the T. cruzi infective form (trypomastigotes and intracellular amastigotes) co-cultured in NIH-3T3 mammalian host cells, as well as having revealed low NIH-3T3 cytotoxicity, were further considered. Compounds GLK2-003 and GLK2-004 were determined to inhibit TcGlcK quite well with IC50 values of 6.1 µM and 4.8 µM, respectively. Illuminated by these findings, we herein screened a small compound library consisting of thirteen commercially available 3-nitro-2-phenyl-2H-chromene analogues, two of which were GLK2-003 and GLK2-004 (compounds 1 and 9, respectively). Twelve of these compounds had a one-point change from the chemical structure of GLK2-003. The analogues were run through a similar primary screening and confirmatory assay protocol to our previous HTS campaign. Subsequently, three in vitro biological assays were performed where compounds were screened against (a) T. cruzi (Tulahuen strain) infective form co-cultured within NIH-3T3 cells, (b) T. brucei brucei (427 strain) bloodstream form, and (c) NIH-3T3 host cells alone. We report on the TcGlcK inhibitor constant determinations, mode of enzyme inhibition, in vitro antitrypanosomal IC50 determinations, and an assessment of structure–activity relationships. Our results reveal that the 3-nitro-2-phenyl-2H-chromene scaffold holds promise and can be further optimized for both Chagas disease and human African trypanosomiasis early-stage drug discovery research.
A Multifunctionalized Potyvirus-Derived Nanoparticle That Targets and Internalizes into Cancer Cells
Authors: Truchado Daniel A. , Juárez-Molina María , Rincón Sara , Zurita Lucía , Tomé-Amat Jaime , Lorz Corina , Ponz Fernando
Published: April 2024

Plant viral nanoparticles (VNPs) are attractive to nanomedicine researchers because of their safety, ease of production, resistance, and straightforward functionalization. In this paper, we developed and successfully purified a VNP derived from turnip mosaic virus (TuMV), a well-known plant pathogen, that exhibits a high affinity for immunoglobulins G (IgG) thanks to its functionalization with the Z domain of staphylococcal Protein A via gene fusion. We selected cetuximab as a model IgG to demonstrate the versatility of this novel TuMV VNP by developing a fluorescent nanoplatform to mark tumoral cells from the Cal33 line of a tongue squamous cell carcinoma. Using confocal microscopy, we observed that fluorescent VNP–cetuximab bound selectively to Cal33 and was internalized, revealing the potential of this nanotool in cancer research.
D-Loop Mutations as Prognostic Markers in Glioblastoma—A Pilot Study
Authors: Szmyd Bartosz , Stanisławska Patrycja , Podstawka Małgorzata , Zaczkowski Karol , Izbiński Patryk M. , Kulczycka-Wojdala Dominika , Stawski Robert , Wiśniewski Karol , Janczar Karolina , Braun Marcin , Białasiewicz Piotr , Jaskólski Dariusz J. , Bobeff Ernest J.
Published: April 2024

Glioblastoma, a highly aggressive brain tumor, poses significant treatment challenges. A deeper investigation into its molecular complexity is essential for the identification of novel prognostic biomarkers and therapeutic strategies, potentially improving patient outcomes in terms of survival and quality of life. While nuclear DNA mutations have been extensively studied, the role of mitochondrial DNA (mtDNA) mutations, specifically in the D-loop region, remains poorly understood. This prospective case-control study aimed to assess the prognostic significance of the mtDNA D-loop m.16126T>C variant in glioblastoma patients. Immunohistochemistry and droplet digital PCR (ddPCR) were employed for mutation analysis, complemented by statistical analyses and a literature review. The study cohort comprised 22 glioblastoma patients (mean age 59.36 ± 14.17, 12 (54.55%) females), and 25 controls (59.48 ± 13.22, 12 (80%) females). The D-loop m.16126T>C variant was observed in four (18%) of the glioblastoma samples and was associated with shorter median survival (9.5 vs. 18 months; p = 0.016, log-rank test). This study underscores the importance of investigating mtDNA, especially D-loop variants, in glioblastoma, suggesting its potential as a prognostic biomarker and, therefore, its possible therapeutic targets, warranting further exploration.
Hydrogen Sulfide Exerted a Pro-Angiogenic Role by Promoting the Phosphorylation of VEGFR2 at Tyr797 and Ser799 Sites in Hypoxia–Reoxygenation Injury
Authors: Zhang Sen , Cheng Yongfeng , Guan Yining , Wen Jiyue , Chen Zhiwu
Published: April 2024

The protective effects of hydrogen sulfide (H2S) against ischemic brain injury and its role in promoting angiogenesis have been established. However, the specific mechanism underlying these effects remains unclear. This study is designed to investigate the regulatory impact and mechanism of H2S on VEGFR2 phosphorylation. Following expression and purification, the recombinant His-VEGFR2 protein was subjected to LC-PRM/MS analysis to identify the phosphorylation sites of VEGFR2 upon NaHS treatment. Adenovirus infection was used to transfect primary rat brain artery endothelial cells (BAECs) with the Ad-VEGFR2WT, Ad-VEGFR2Y797F, and Ad-VEGFR2S799A plasmids. The expression of VEGFR2 and recombinant Flag-VEGFR2, along with Akt phosphorylation, cell proliferation, and LDH levels, was assessed. The migratory capacity and tube-forming potential of BAECs were assessed using wound healing, transwell, and tube formation assays. NaHS notably enhanced the phosphorylation of VEGFR2 at Tyr797 and Ser799 sites. These phosphorylation sites were identified as crucial for mediating the protective effects of NaHS against hypoxia–reoxygenation (H/R) injury. NaHS significantly enhanced the Akt phosphorylation, migratory capacity, and tube formation of BAECs and upregulated the expression of VEGFR2 and recombinant proteins. These findings suggest that Tyr797 and Ser799 sites of VEGFR2 serve as crucial mediators of H2S-induced pro-angiogenic effects and protection against H/R injury.
Evolutionary Changes in Primate Glutamate Dehydrogenases 1 and 2 Influence the Protein Regulation by Ligands, Targeting and Posttranslational Modifications
Authors: Aleshina Yulia A. , Aleshin Vasily A.
Published: April 2024

There are two paralogs of glutamate dehydrogenase (GDH) in humans encoded by the GLUD1 and GLUD2 genes as a result of a recent retroposition during the evolution of primates. The two human GDHs possess significantly different regulation by allosteric ligands, which is not fully characterized at the structural level. Recent advances in identification of the GDH ligand binding sites provide a deeper perspective on the significance of the accumulated substitutions within the two GDH paralogs. In this review, we describe the evolution of GLUD1 and GLUD2 after the duplication event in primates using the accumulated sequencing and structural data. A new gibbon GLUD2 sequence questions the indispensability of ancestral R496S and G509A mutations for GLUD2 irresponsiveness to GTP, providing an alternative with potentially similar regulatory features. The data of both GLUD1 and GLUD2 evolution not only confirm substitutions enhancing GLUD2 mitochondrial targeting, but also reveal a conserved mutation in ape GLUD1 mitochondrial targeting sequence that likely reduces its transport to mitochondria. Moreover, the information of GDH interactors, posttranslational modification and subcellular localization are provided for better understanding of the GDH mutations. Medically significant point mutations causing deregulation of GDH are considered from the structural and regulatory point of view.
A Complex-Type N-Glycan-Specific Lectin Isolated from Green Alga Halimeda borneensis Exhibits Potent Anti-Influenza Virus Activity
Authors: Mu Jinmin , Hirayama Makoto , Morimoto Kinjiro , Hori Kanji
Published: April 2024

Marine algal lectins specific for high-mannose N-glycans have attracted attention because they strongly inhibit the entry of enveloped viruses, including influenza viruses and SARS-CoV-2, into host cells by binding to high-mannose-type N-glycans on viral surfaces. Here, we report a novel anti-influenza virus lectin (named HBL40), specific for complex-type N-glycans, which was isolated from a marine green alga, Halimeda borneensis. The hemagglutination activity of HBL40 was inhibited with both complex-type N-glycan and O-glycan-linked glycoproteins but not with high-mannose-type N-glycan-linked glycoproteins or any of the monosaccharides examined. In the oligosaccharide-binding experiment using 26 pyridylaminated oligosaccharides, HBL40 only bound to complex-type N-glycans with bi- and triantennary-branched sugar chains. The sialylation, core fucosylation, and the increased number of branched antennae of the N-glycans lowered the binding activity with HBL40. Interestingly, the lectin potently inhibited the infection of influenza virus (A/H3N2/Udorn/72) into NCI-H292 cells at IC50 of 8.02 nM by binding to glycosylated viral hemagglutinin (KD of 1.21 × 10−6 M). HBL40 consisted of two isolectins with slightly different molecular masses to each other that could be separated by reverse-phase HPLC. Both isolectins shared the same 16 N-terminal amino acid sequences. Thus, HBL40 could be useful as an antivirus lectin specific for complex-type N-glycans.
Manganese- and Platinum-Driven Oxidative and Nitrosative Stress in Oxaliplatin-Associated CIPN with Special Reference to Ca4Mn(DPDP)5, MnDPDP and DPDP
Authors: Karlsson Jan Olof G. , Jynge Per
Published: April 2024

Platinum-containing chemotherapeutic drugs are efficacious in many forms of cancer but are dose-restricted by serious side effects, of which peripheral neuropathy induced by oxidative–nitrosative-stress-mediated chain reactions is most disturbing. Recently, hope has been raised regarding the catalytic antioxidants mangafodipir (MnDPDP) and calmangafodipir [Ca4Mn(DPDP)5; PledOx®], which by mimicking mitochondrial manganese superoxide dismutase (MnSOD) may be expected to overcome oxaliplatin-associated chemotherapy-induced peripheral neuropathy (CIPN). Unfortunately, two recent phase III studies (POLAR A and M trials) applying Ca4Mn(DPDP)5 in colorectal cancer (CRC) patients receiving multiple cycles of FOLFOX6 (5-FU + oxaliplatin) failed to demonstrate efficacy. Instead of an anticipated 50% reduction in the incidence of CIPN in patients co-treated with Ca4Mn(DPDP)5, a statistically significant increase of about 50% was seen. The current article deals with confusing differences between early and positive findings with MnDPDP in comparison to the recent findings with Ca4Mn(DPDP)5. The POLAR failure may also reveal important mechanisms behind oxaliplatin-associated CIPN itself. Thus, exacerbated neurotoxicity in patients receiving Ca4Mn(DPDP)5 may be explained by redox interactions between Pt2+ and Mn2+ and subtle oxidative–nitrosative chain reactions. In peripheral sensory nerves, Pt2+ presumably leads to oxidation of the Mn2+ from Ca4Mn(DPDP)5 as well as from Mn2+ in MnSOD and other endogenous sources. Thereafter, Mn3+ may be oxidized by peroxynitrite (ONOO−) into Mn4+, which drives site-specific nitration of tyrosine (Tyr) 34 in the MnSOD enzyme. Conformational changes of MnSOD then lead to the closure of the superoxide (O2•−) access channel. A similar metal-driven nitration of Tyr74 in cytochrome c will cause an irreversible disruption of electron transport. Altogether, these events may uncover important steps in the mechanism behind Pt2+-associated CIPN. There is little doubt that the efficacy of MnDPDP and its therapeutic improved counterpart Ca4Mn(DPDP)5 mainly depends on their MnSOD-mimetic activity when it comes to their potential use as rescue medicines during, e.g., acute myocardial infarction. However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron paramagnetic resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ in binding to fodipir (DPDP), hence suggesting that the previously reported protective efficacy of MnDPDP against CIPN is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.
Genome-Wide Identification of Calmodulin-Binding Protein 60 Gene Family and the Function of GhCBP60B in Cotton Growth and Development and Abiotic Stress Response
Authors: Luo Kun , Sha Long , Li Tengyu , Wang Chenlei , Zhao Xuan , Pan Jingwen , Zhu Shouhong , Li Yan , Chen Wei , Yao Jinbo , Rong Junkang , Zhang Yongshan
Published: April 2024

The calmodulin-binding protein 60 (CBP60) family is a gene family unique to plants, and its members play a crucial role in plant defense responses to pathogens and growth and development. Considering that cotton is the primary source of natural cotton textile fiber, the functional study of its CBP60 gene family members is critical. In this research, we successfully identified 162 CBP60 members from the genomes of 21 species. Of these, 72 members were found in four cotton species, divided into four clades. To understand the function of GhCBP60B in cotton in depth, we conducted a detailed analysis of its sequence, structure, cis-acting elements, and expression patterns. Research results show that GhCBP60B is located in the nucleus and plays a crucial role in cotton growth and development and response to salt and drought stress. After using VIGS (virus-induced gene silencing) technology to conduct gene silencing experiments, we found that the plants silenced by GhCBP60B showed dwarf plants and shortened stem nodes, and the expression of related immune genes also changed. In further abiotic stress treatment experiments, we found that GhCBP60B-silenced plants were more sensitive to drought and salt stress, and their POD (peroxidase) activity was also significantly reduced. These results imply the vital role of GhCBP60B in cotton, especially in regulating plant responses to drought and salt stress. This study systematically analyzed CBP60 gene family members through bioinformatics methods and explored in depth the biological function of GhCBP60B in cotton. These research results lay a solid foundation for the future use of the GhCBP60B gene to improve cotton plant type and its drought and salt resistance.
Targeting Macrophages: Therapeutic Approaches in Diabetic Kidney Disease
Authors: Lin Da-Wei , Yang Tsung-Ming , Ho Cheng , Shih Ya-Hsueh , Lin Chun-Liang , Hsu Yung-Chien
Published: April 2024

Diabetes is not solely a metabolic disorder but also involves inflammatory processes. The immune response it incites is a primary contributor to damage in target organs. Research indicates that during the initial phases of diabetic nephropathy, macrophages infiltrate the kidneys alongside lymphocytes, initiating a cascade of inflammatory reactions. The interplay between macrophages and other renal cells is pivotal in the advancement of kidney disease within a hyperglycemic milieu. While M1 macrophages react to the inflammatory stimuli induced by elevated glucose levels early in the disease progression, their subsequent transition to M2 macrophages, which possess anti-inflammatory and tissue repair properties, also contributes to fibrosis in the later stages of nephropathy by transforming into myofibroblasts. Comprehending the diverse functions of macrophages in diabetic kidney disease and regulating their activity could offer therapeutic benefits for managing this condition.
Molecular Pathways of Vulnerable Carotid Plaques at Risk of Ischemic Stroke: A Narrative Review
Authors: Miceli Giuseppe , Basso Maria Grazia , Pintus Chiara , Pennacchio Andrea Roberta , Cocciola Elena , Cuffaro Mariagiovanna , Profita Martina , Rizzo Giuliana , Tuttolomondo Antonino
Published: April 2024

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of ischemic stroke secondary to large-artery atherosclerosis. In macroscopic evaluation, vulnerable plaques are characterized by one or more of the following features: microcalcification; neovascularization; lipid-rich necrotic cores (LRNCs); intraplaque hemorrhage (IPH); thin fibrous caps; plaque surface ulceration; huge dimensions, suggesting stenosis; and plaque rupture. Recognizing these macroscopic characteristics is crucial for estimating the risk of cerebrovascular events, also in the case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that are scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talk governing plaque inflammation, rupture potential, and thrombogenicity. The current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehensive analysis of the current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional attributes that characterize vulnerable plaques.
Serum Levels of miR-122-5p and miR-125a-5p Predict Hepatotoxicity Occurrence in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation
Authors: Mikulski Damian , Kościelny Kacper , Dróżdż Izabela , Mirocha Grzegorz , Nowicki Mateusz , Misiewicz Małgorzata , Perdas Ewelina , Strzałka Piotr , Wierzbowska Agnieszka , Fendler Wojciech
Published: April 2024

Hepatic complications are an acknowledged cause of mortality and morbidity among patients undergoing hematopoietic stem cell transplantation. In this study, we aimed to evaluate the potential role in the prediction of liver injury of five selected microRNAs (miRNAs)—miR-122-5p, miR-122-3p, miR-15b-5p, miR-99b-5p, and miR-125a-5p—in the setting of autologous hematopoietic stem cell transplantation (ASCT). A total of 66 patients were included in the study: 50 patients (75.8%) with multiple myeloma (MM) and 16 (24.2%) with lymphoma. Blood samples were collected after the administration of the conditioning regimen, on the day of transplant (day 0). The expression levels of selected miRNAs were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using the miRCURY LNA miRNA Custom PCR Panels (QIAGEN). In a multivariate logistic regression analysis adjusted for age, sex, and the administered conditioning regimen, two miRNAs, hsa-miR-122-5p (odds ratio, OR 2.10, 95% confidence interval, CI: 1.29–3.42, p = 0.0029) and hsa-miR-125a-5p (OR 0.27, 95% CI: 0.11–0.71, p = 0.0079), were independent for hepatic toxicity occurrence during the 14 days after transplant. Our model in 10-fold cross-validation preserved its diagnostic potential with a receiver operating characteristics area under the curve (ROC AUC) of 0.75, 95% CI: 0.63–0.88 and at optimal cut-off reached 72.0% sensitivity and 74.4% specificity. An elevated serum level of miR-122-5p and decreased level of miR-125a-5p on day 0 are independent risk factors for hepatotoxicity in ASCT recipients, showing promise in accurately predicting post-ASCT complications. Identifying patients susceptible to complications has the potential to reduce procedure costs and optimize the selection of inpatient or outpatient procedures.
In Vitro and In Silico Studies on Cytotoxic Properties of Oxythiamine and 2′-Methylthiamine
Authors: Malinowska Marta , Czerniecka Magdalena , Jastrzebska Izabella , Ratkiewicz Artur , Tylicki Adam , Wawrusiewicz-Kurylonek Natalia
Published: April 2024

It is important to search for cytostatic compounds in order to fight cancer. One of them could be 2′-methylthiamine, which is a thiamine antimetabolite with an additional methyl group at the C-2 carbon of thiazole. So far, the cytostatic potential of 2′-methylthiamine has not been studied. We have come forward with a simplified method of synthesis using commercially available substrates and presented a comparison of its effects, as boosted by oxythiamine, on normal skin fibroblasts and HeLa cancer cells, having adopted in vitro culture techniques. Oxythiamine has been found to inhibit the growth and metabolism of cancer cells significantly better than 2′-methylthiamine (GI50 36 and 107 µM, respectively), while 2′-methylthiamine is more selective for cancer cells than oxythiamine (SI = 180 and 153, respectively). Docking analyses have revealed that 2′-methylthiamine (ΔG −8.2 kcal/mol) demonstrates a better affinity with thiamine pyrophosphokinase than thiamine (ΔG −7.5 kcal/mol ) and oxythiamine (ΔG −7.0 kcal/mol), which includes 2′-methylthiamine as a potential cytostatic. Our results suggest that the limited effect of 2′-methylthiamine on HeLa arises from the related arduous transport as compared to oxythiamine. Given that 2′-methylthiamine may possibly inhibit thiamine pyrophosphokinase, it could once again be considered a potential cytostatic. Thus, research should be carried out in order to find the best way to improve the transport of 2′-methylthiamine into cells, which may trigger its cytostatic properties.