bluuebunny/crossref_metadata_2025 huggingface dataset:
Unintended Consequences of Urban Expansion and Gold Mining: Elevated Indoor Radon Levels in Gauteng Communities’ Neighboring Gold Mine Tailings
Authors: Mphaga Khathutshelo Vincent , Utembe Wells , Shezi Busisiwe , Mbonane Thokozani P. , Rathebe Phoka C.
Published: July 2024

The province of Gauteng in South Africa has a rich history of gold mining, which has driven economic growth and urbanization. Gold mining has also created over 270 gold mine tailings (GMT), now surrounded by human settlements due to a housing shortage. These GMT pose a health risk as they harbor elevated uranium, which over time undergoes radioactive decay to produce radon, a known lung carcinogen. This study aimed to investigate the potential correlation between the proximity to gold mine tailings (GMT) and indoor radon concentrations in Gauteng’s residential dwellings. Volume activity of radon (VAR) inside 330 residential dwellings was measured in residential dwellings located proximally (<2 km) and distally (>2 km) to gold mine tailings using AlphaE radon monitors during winter. An interviewer-administered questionnaire was utilized to obtain data on factors that may influence indoor radon activities. Descriptive statistics and bivariate logistic regression analyzed the influence of proximity to gold mine tailings and dwelling characteristics on VAR. Furthermore, VAR was compared to the World Health Organization (WHO) radon reference level of 100 Bq/m3. Residential dwellings near gold mine tailings had significantly higher average indoor radon concentrations (103.30 Bq/m3) compared to the control group (65.19 Bq/m3). Residential dwellings proximal to gold mine tailings were three times more likely to have VAR beyond the WHO reference level of 100 Bq/m3. Furthermore, they had estimated annual effective doses of 2.60 mSv/y compared to 1.64 mSv/y for the control group. This study highlighted a concerning association between proximity to gold mine tailings and elevated indoor radon levels. Public health interventions prioritizing residential dwellings near gold mine tailings are crucial. Educational campaigns and financial assistance for radon mitigation systems in high-risk dwellings are recommended. Residents near gold mine tailings are encouraged to ensure continuous natural ventilation through frequent opening of windows and doors.
Network Topology of Wing Veins in Hawaiian Flies Mitigates Allometric Dilemma
Authors: Sugiyama Kazuki , Kubota Yoshihiro , Mochizuki Osamu
Published: July 2024

Specific Hawaiian fruit flies have an extra crossvein (ECV) in the wing vein network which connects contiguously with another crossvein and forms a unique cruciform topology. These flies are distinguished by their large wings and their allometrically small vein diameters compared to those of typical fruit flies. Small vein diameters may increase frictional energy loss during internal blood transport, although they lead to an improvement in the wing’s moment of inertia. Our hypothesis was that the ECV’s presence would reduce the hydraulic resistance of the entire vein network. To investigate the hemodynamic effects of its presence, the flow rate of blood and frictional pressure loss within the vein networks was simulated by modeling them as hydraulic circuits. The results showed a 3.1% reduction in pressure loss owing to the network topology created by the presence of the ECV. This vein and its contiguous crossvein diverted part of the blood from the wing veins topologically parallel to them, reducing the pressure loss in these bypassed veins. The contiguity of the ECV to the other crossvein provided the shortest blood transfer route and lowest pressure drop between these crossveins. The results suggest that the presence of the ECV may counterbalance the heightened resistance caused by constricted veins.
Long Term Follow-Up Observation in Small Choroidal Melanocytic Tumors
Authors: Prieto-Domínguez Laura , García-Álvarez Ciro , Muñoz-Moreno Maria F. , Diezhandino Patricia , Miguel-Perez David , Saornil María A.
Published: July 2024

Background: The purpose of this study is to analyze the long-term evolution of patients with small choroidal melanocytic tumors (SCMTs) undergoing observation, and to assess their rate of transformation into melanomas and survival. Methods: A retrospective single-cohort study of patients with SCMTs (1–3 mm in height and 5–10 mm in base) diagnosed from January 1992 to February 2023 was carried out, with observation as the initial treatment. The main criterion for a transformation into melanoma is considered to be an increase in size of more than 1 mm in height and/or more than 1 mm in base measured on an ultrasound/retinography, recorded in two consecutive visits separated by one to three months. Results: 243 patients were included with a mean age of 65.3 years and a mean follow-up of 7.9 years (6 months–27.9 years); 27 patients showed tumor growth. The probabilities of growth at 5, 10, and 15 years are 10%, 14%, and 17%, respectively. Regarding survival, 22 patients died and only 3 deaths were due to melanoma metastasis. Survival rates at 5 and 10 years are 99% and 97%. Conclusions: Observation is a viable therapeutic option for SCMTs, avoiding the side effects of treatment, considering the majority of these tumors do not progress to melanoma. With close monitoring, patients can be treated promptly upon detecting a transformation. Additionally, the findings confirm that small melanocytic tumors can lead to metastatic disease, albeit at a low rate.
VISTA Emerges as a Promising Target against Immune Evasion Mechanisms in Medulloblastoma
Authors: Muñoz Perez Natalia , Pensabene Juliana M. , Galbo Phillip M. , Sadeghipour Negar , Xiu Joanne , Moziak Kirsten , Yazejian Rita M. , Welch Rachel L. , Bell W. Robert , Sengupta Soma , Aulakh Sonikpreet , Eberhart Charles G. , Loeb David M. , Eskandar Emad , Zheng Deyou , Zang Xingxing , Martin Allison M.
Published: July 2024

Background: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration is crucial for developing more effective immunotherapies. Methods: We utilize a syngeneic mouse model to investigate the tumor immune microenvironment of MB and compare our findings to transcriptomic and proteomic data from human MB. Results: Flow cytometry reveals a notable presence of CD45hi/CD11bhi macrophage-like and CD45int/CD11bint microglia-like tumor-associated macrophages (TAMs), alongside regulatory T-cells (Tregs), expressing high levels of the inhibitory checkpoint molecule VISTA. Compared to sham control mice, the CD45hi/CD11bhi compartment significantly expands in tumor-bearing mice and exhibits a myeloid-specific signature composed of VISTA, CD80, PD-L1, CTLA-4, MHCII, CD40, and CD68. These findings are corroborated by proteomic and transcriptomic analyses of human MB samples. Immunohistochemistry highlights an abundance of VISTA-expressing myeloid cells clustering at the tumor–cerebellar border, while T-cells are scarce and express FOXP3. Additionally, tumor cells exhibit immunosuppressive properties, inhibiting CD4 T-cell proliferation in vitro. Identification of VISTA’s binding partner, VSIG8, on tumor cells, and its correlation with increased VISTA expression in human transcriptomic analyses suggests a potential therapeutic target. Conclusions: This study underscores the multifaceted mechanisms of immune evasion in MB and highlights the therapeutic potential of targeting the VISTA–VSIG axis to enhance anti-tumor responses.
High Mobility Group AT-hook 2: A Biomarker Associated with Resistance to Enzalutamide in Prostate Cancer Cells
Authors: Liadi Yusuf Mansur , Campbell Taaliah , Hwang Bor-Jang , Elliott Bethtrice , Odero-Marah Valerie
Published: July 2024

Metastatic prostate cancer (mPCa) is a leading cause of mortality, partly due to its resistance to anti-androgens like enzalutamide. Snail can promote this resistance by increasing full-length AR and AR-V7. High Mobility Group AT-hook 2 (HMGA2), a DNA-binding protein upstream of Snail, is crucial in proliferation and epithelial–mesenchymal transition (EMT). This study examines HMGA2’s role in enzalutamide resistance. LNCaP and 22Rv1 cells overexpressing wild-type HMGA2, but not truncated HMGA2, showed EMT. Both variants led to a decreased sensitivity to enzalutamide but not alisertib compared to Neo control cells. The overexpression of HMGA2 did not alter AR expression. Enzalutamide-resistant C4-2B cells (C4-2B MDVR) had higher HMGA2 and AR/AR variant expression than enzalutamide-sensitive C4-2B cells but remained sensitive to alisertib. The HMGA2 knockdown in C4-2B MDVR cells increased sensitivity to both enzalutamide and alisertib without changing AR expression. A clinical analysis via cBioPortal revealed HMGA2 alterations in 3% and AR alterations in 59% of patients. The HMGA2 changes were linked to treatments like enzalutamide, abiraterone, or alisertib, with amplifications more prevalent in bone, lymph node, and liver metastases. Conclusively, HMGA2 is a potential biomarker for enzalutamide resistance in mPCa, independent of Snail and AR signaling, and alisertib may be an effective treatment for mPCa that expresses HMGA2.
How to Implement Pressurized Intraperitoneal Aerosol Chemotherapy into a National Health System Scenario: A Single-Center Retrospective Analysis of Costs and Economic Sustainability at a High-Volume Italian Hospital
Authors: Aulicino Matteo , Orsini Cecilia , D’Annibale Giorgio , Barberis Lorenzo , Catania Paolo , Abatini Carlo , Attalla El Halabieh Miriam , Ferracci Federica , Lodoli Claudio , Santullo Francesco , Pacelli Fabio , Di Giorgio Andrea
Published: July 2024

PIPAC is a new surgical procedure and a viable treatment option for PSM patients, due to promising therapeutic outcomes, minimal invasiveness, limited surgical morbidity, and systemic toxicity side effects. However, its implementation throughout hospitals is hard to obtain due to its fragile economical sustainability. A retrospective health economic analysis was conducted in order to evaluate the cost of hospitalization for patients undergoing PIPAC treatment at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, in Rome. The average cost of a PIPAC procedure was defined based on the cost of surgery (cost of surgical material, operating room, intraperitoneal chemotherapy), hospital stay, diagnostic examinations, and drugs used during the stay. A total of 493 PIPAC procedures were performed on 222 patients with peritoneal metastases or primary peritoneal cancer from 2017 to 2023. Since the mean remuneration for each PIPAC hospitalization is €5916 and the mean expenditure per hospitalization is €6538, this results in an operating profit per PIPAC hospitalization of −€622. The reimbursement of PIPAC treatment by the Italian National Health System currently only partially covers the hospital’s costs. Development of specific codes and adequate reimbursement for PIPAC by recognizing this procedure as a proper treatment for peritoneal carcinomatosis is essential.
Sex Differences Affect the NRF2 Signaling Pathway in the Early Phase of Liver Steatosis: A High-Fat-Diet-Fed Rat Model Supplemented with Liquid Fructose
Authors: Di Veroli Benedetta , Bentanachs Roger , Roglans Núria , Alegret Marta , Giona Letizia , Profumo Elisabetta , Berry Alessandra , Saso Luciano , Laguna Juan Carlos , Buttari Brigitta
Published: July 2024

Sex differences may play a role in the etiopathogenesis and severity of metabolic dysfunction-associated steatotic liver disease (MASLD), a disorder characterized by excessive fat accumulation associated with increased inflammation and oxidative stress. We previously observed the development of steatosis specifically in female rats fed a high-fat diet enriched with liquid fructose (HFHFr) for 12 weeks. The aim of this study was to better characterize the observed sex differences by focusing on the antioxidant and cytoprotective pathways related to the KEAP1/NRF2 axis. The KEAP1/NRF2 signaling pathway, autophagy process (LC3B and LAMP2), and endoplasmic reticulum stress response (XBP1) were analyzed in liver homogenates in male and female rats that were fed a 12-week HFHFr diet. In females, the HFHFr diet resulted in the initial activation of the KEAP1/NRF2 pathway, which was not followed by the modulation of downstream molecular targets; this was possibly due to the increase in KEAP1 levels preventing the nuclear translocation of NRF2 despite its cytosolic increase. Interestingly, while in both sexes the HFHFr diet resulted in an increase in the levels of LC3BII/LC3BI, a marker of autophagosome formation, only males showed a significant upregulation of LAMP2 and XBP1s; this did not occur in females, suggesting impaired autophagic flux in this sex. Overall, our results suggest that males are characterized by a greater ability to cope with an HFHFr metabolic stimulus mainly through an autophagic-mediated proteostatic process while in females, this is impaired. This might depend at least in part upon the fine modulation of the cytoprotective and antioxidant KEAP1/NRF2 pathway resulting in sex differences in the occurrence and severity of MASLD. These results should be considered to design effective therapeutics for MASLD.
Synthesis and Characterization of Titania-Coated Hollow Mesoporous Hydroxyapatite Composites for Photocatalytic Degradation of Methyl Red Dye in Water
Authors: Shafiq Farishta , Yu Simiao , Pan Yongxin , Qiao Weihong
Published: July 2024

Hollow mesoporous hydroxyapatite (HM-HAP) composites coated with titania are prepared to increase the stability and catalytic performance of titania for azo dyes present in the wastewater system. In this work, HM-HAP particles were first synthesized by a hydrothermal method utilizing the CaCO3 core as a template and then coated with titania to form TiO2/HM-HAP composites. Utilizing SEM, XRD, XPS, BET, FTIR, EDS, UV–vis DRS spectroscopy, and point of zero charge (PZC) analysis, the coating morphological and physicochemical parameters of the produced samples were analyzed. The photocatalytic efficiency of the synthesized coated composites was assessed by the degradation of methyl red (MR) dye in water. The results indicated that TiO2/HM-HAP particles could efficiently photodegrade MR dye in water under UV irradiation. The 20% TiO2/HM-HAP coating exhibited high catalytic performance, and the degradation process was followed by the pseudo-first-order (PFO) kinetic model with a rate constant of 0.033. The effect of pH on the degradation process was also evaluated, and the maximum degradation was observed at pH 6. The analysis of degraded MR dye products was investigated using LC-MS and FTIR analysis. Finally, a good support material, HM-HAP for TiO2 coatings, which provides a large number of active adsorption sites and has catalytic degradation performance for MR dye, was revealed.
A Light-Driven Carbon Nanocoil Microrobot
Authors: Liu Yuli , Sun Rui , Sun Yanming , Shen Jian , Wu Xizhuo , Xi Xin , Pan Lujun
Published: July 2024

Mobile microrobots are of great scientific significance. However, external actuation and control methods are still challenging to conduct. We present a single carbon nanocoil (CNC) microrobot induced by an NIR laser beam, capable of light-driven locomotion and photothermal actuation. This research demonstrates that CNC-based microrobots roll away from the focal spot when the laser beam is focused near the CNC. The maximum translational distance of a CNC microrobot increases with an increase in laser power, and the direction of motion is guided by controlling the focusing position of NIR. CNC-based microrobots can load and transport multiple cells under NIR light irradiation, resulting from the temperature gradient generated by photothermal conversion, which causes thermophoresis. The hydrophobic surface and unique helical structure of CNCs are beneficial to the underwater drag reduction in CNC microrobots’ motion and the adhesion of cells on CNC microrobots. Therefore, CNC microrobots, as cell vectors driven by a laser beam, may find applications in a wide range of biomedical applications. In addition, the rotation of a CNC powered by a laser beam provides promising prospects for the future of nanomechanical devices using a carbon nanocoil as a micro/nanomotor.
CMAS Corrosion Resistance of Plasma-Sprayed YSZ and Yb2O3-Y2O3-Co-Stabilized ZrO2 Coatings under 39–40 KW Spraying Power
Authors: Zhang Wenkang , Liu Wei , Liu Yangguang , Wang Weize , Yang Ting , Li Kaibin , Wang Junhao , Zhang Xiaoqin , Yang Shilong , Liu Pengpeng , Zhang Chengcheng
Published: July 2024

This study uses atmospheric plasma spraying (APS) technology to prepare thermal barrier coatings (TBCs) with yttrium-stabilized zirconia (YSZ) and Yb2O3-Y2O3-co-stabilized ZrO2 (YbYSZ) materials at different spraying powers. It analyzes the differences and changes in the microstructure, thermodynamic properties, and mechanical properties of the TBCs. The CaO-MgO-Al2O3-SiO2 (CMAS) resistance of coatings was tested using thermal cycling-CMAS experiments and isothermal corrosion experiments. Compared to YSZ coatings, YbYSZ coatings have lower thermal conductivity, a higher hardness and elastic modulus, a longer lifetime under thermal cycling-CMAS conditions, and lower penetration and degradation depths. Under thermal cycling-CMAS coupling conditions, the optimal power range for the longest thermal cycling lifetime for both coatings is 39–40 kW. Overall, compared to the YSZ material, the YbYSZ material exhibits superior properties.
Diatoms’ Diversity in the Assessment of the Impact of Diamond and Oil and Gas Mining on Aquatic Ecosystems of the Central Yakut Plain (Eastern Siberia, Yakutia) Using Bioindication and Statistical Mapping Methods
Authors: Barinova Sophia , Gabyshev Viktor , Genkal Sergey , Gabysheva Olga
Published: July 2024

Diamond and oil and gas production carries risks to the aquatic ecosystem. In Eastern Siberia, on the territory of the Central Yakut Plain, mining development of the Yakut diamond-bearing province and Tas-Yuryakh oil and gas condensate field has been underway for several decades. But the problem of studying negative consequences in the region is covered only from the point of view of the impact on terrestrial ecosystems. The purpose of this study was to assess the impact of diamond and oil and gas production on the aquatic ecosystems of the region using the bioindicative properties of diatoms. The work used previously widely tested methods of ecological mapping, JASP, and species–environments relationship analysis. The results of chemical analysis of water showed that in oil and gas production areas, there is no pollution with petroleum products, but the concentration of silicon and zinc is increased. The study identified key pollutants in the Central Yakut Plain and demonstrated the effectiveness of diatoms as bioindicators. Elevated chloride levels were found in diamond mining areas, and increased copper levels were noted in oil production regions. In the diatom flora of the region, 144 species were identified, of which 137 are indicator species. Natural and anthropogenic clusters of environmental factors are identified, characterized by a specific effect on the species composition and taxonomic structure of diatom communities. The results obtained are suitable for assessing the level of anthropogenic impact on aquatic communities of photosynthetic microorganisms in permafrost conditions.
Elementary Observations: Building Blocks of Physical Information Gain
Authors: Müller J. Gerhard
Published: July 2024

In this paper, we are concerned with the process of experimental information gain. Building on previous work, we show that this is a discontinuous process in which the initiating quantum-mechanical matter–instrument interactions are being turned into macroscopically observable events (EOs). In the course of time, such EOs evolve into spatio-temporal patterns of EOs, which allow conceivable alternatives of physical explanation to be distinguished. Focusing on the specific case of photon detection, we show that during their lifetimes, EOs proceed through the four phases of initiation, detection, erasure and reset. Once generated, the observational value of EOs can be measured in units of the Planck quantum of physical action h=4.136×10−15eVs. Once terminated, each unit of entropy of size kB=8.617×10−5eV/K, which had been created in the instrument during the observational phase, needs to be removed from the instrument to ready it for a new round of photon detection. This withdrawal of entropy takes place at an energetic cost of at least two units of the Landauer minimum energy bound of ELa=ln⁡2kBTD for each unit of entropy of size kB.
Biogas-to-Power Systems Based on Solid Oxide Fuel Cells: Thermodynamic Analysis of Stack Integration Strategies
Authors: Baldinelli Arianna , Desideri Umberto , Fantozzi Francesco , Cinti Giovanni
Published: July 2024

Biogas presents a renewable fuel source with substantial potential for reducing carbon emissions in the energy sector. Exploring this potential in the farming sector is crucial for fostering the development of small-scale distributed biogas facilities, leveraging indigenous resources while enhancing energy efficiency. The establishment of distributed biogas plants bolsters the proportion of renewable energy in the energy matrix, necessitating efficient power generation technologies. Given their proximity to bio-waste production sites like farms and digesters, optimising combined heat and power generation systems is imperative for energy self-sufficiency. Small-scale biogas facilities demand specific power generation technologies capable of achieving notable efficiencies, ranging from 40% to 55%. This study focuses on employing Solid Oxide Fuel Cells (SOFCs) in biogas-to-power systems and investigates the theoretical operation of SOFCs with fuel mixtures resulting from different biogas lean upgrading pathways. Therefore, starting from ten mixtures including CH4, CO2, H2, H2O, N2, and O2, the study proposes a method to assess their impact on the electrochemical performance, degradation, and energy equilibrium of SOFC units. The model embeds thermodynamic equilibrium, the Nernst potential, and energy balance, enabling a comprehensive comparison across these three analytical domains. The findings underscore the unsuitability of dry biogas and dry biomethane due to the potential risk of carbon deposition. Moreover, mixtures incorporating CO2, with or without H2, present significant thermal balance challenges.
Investigation on Cryogenic Cavitation Characteristics of an Inducer Considering Thermodynamic Effects
Authors: Guo Xiaomei , Yang Mingyu , Li Fengqin , Zhu Zuchao , Cui Baoling
Published: July 2024

An inducer is a key component in a cryogenic pump to improve its cavitation performance. The thermodynamic effects of the cryogenic medium make the cryogenic cavitation flow extremely complicated. For this reason, it is crucial to investigate the cryogenic cavitation flow of the inducer which is equipped upstream of the cryogenic pump. In this paper, the isothermal cavitation model is modified based on the law of heat conduction, and the cryogenic cavitation model of the inducer is developed by considering thermodynamic effects. The turbulence model is also modified to account for the compressibility of cryogenic cavitation flow. The methods of numerical calculations are performed to investigate the influence of thermodynamic effects on cryogenic cavitation of the inducer. The law of the spatio-temporal evolution of cryogen cavitation in the inducer is clarified. The initial position, development and collapse phenomenon of cavitation are obtained. The relationship between the generation and collapse of the cavitation and the work capacity of the inducer’s blade, the relationship between thermodynamic effects and the influence of the inducer’s blade tip leakage vortex and thermodynamic on cryogenic cavitation of the inducer are revealed.
Consecutive Year-by-Year Planning of Grid-Side Energy Storage System Considering Demand-Side Response Resources
Authors: Xu Haidong , Ding Yifan , Sun Feifei , Wang Renshun , Geng Guangchao , Jiang Quanyuan
Published: July 2024

Demand-side response (DR) and energy storage system (ESS) are both important means of providing operational flexibility to the power system. Thus, DR has a certain substitution role for ESS, but unlike DR, ESS planning has a coupling relationship between years, which makes it difficult to guarantee the reasonableness of the ESS planning results by considering only a single year. To achieve the optimal construction timing of ESS, this paper develops a consecutive year-by-year framework integrating DR and ESS to analyse and quantify the substitution effect of DR on energy storage while realizing year-by-year ESS planning. Our methods are as follows: (1) A consecutive year-by-year DR model and an ESS model are proposed; (2) These two models are combined together to achieve the purpose of considering DR in the ESS planning stage. Here, system reserve, renewable energy consumption, and preservation of power supply are given consideration to optimise the reliability and economy of the system; (3) The method is validated using a provincial real-world power grid in the eastern part of China. The optimal results of five consecutive years of planning show that DR substitutes 19.7% of the ESS capacity.
Study on the Mechanical Properties of Roots and Friction Characteristics of the Root–Soil Interface of Two Tree Species in the Coastal Region of Southeastern China
Authors: Lin Yunzhao , Jian Wenbin , Zhu Zuteng , Wu Yilong , Wang Hao , Fan Xiufeng
Published: July 2024

The tensile strength of roots and the friction characteristics of the root–soil interface of tree species are the indicators that play a crucial role in understanding the mechanism of soil reinforcement by roots. To calculate the effectiveness of the reinforcement of soil by tree roots based on essential influencing parameters, typical trees in the coastal region of southeastern China selected for this study were subjected to tests of the tensile mechanical properties of their roots, as well as studies on the friction characteristics of the root–soil interface and the microscopic interfaces. The results indicated that in the 1–7 diameter classes, the root tensile strength of both Pinus massoniana and Cunninghamia lanceolata was negatively correlated with the root diameter in accordance with the power function. The root tensile strength of these two trees, however, was positively correlated with the lignin content but negatively correlated with cellulose and hemicellulose contents. The shear strength at the root–soil interface and the vertical load exhibited a constitutive relationship, which followed the Mohr–Coulomb criterion. As the root diameter increased, both the cohesion and the friction coefficients at the root–soil interface gradually increased, but the growth rate stood at around 15%. The cohesion value of the root–soil interface of the two trees decreased linearly with the increase in soil moisture content within the range of 25 to 45%. At the microinterface, the root surface of C. lanceolata exhibited concave grooves and convex ridges that extended along the axial direction of roots, with their height differences increasing with the enlargement of the root diameter. The rough surface of P. massoniana roots had areas composed of polygonal meshes, with an increase observed in the mesh density with increasing root diameter.
Exonic Short Interspersed Nuclear Element Insertion in FAM161A Is Associated with Autosomal Recessive Progressive Retinal Atrophy in the English Shepherd
Authors: Stanbury Katherine , Schofield Ellen , McLaughlin Bryan , Forman Oliver , Mellersh Cathryn
Published: July 2024

Progressive retinal atrophies (PRAs) are a genetically heterogeneous group of inherited eye diseases that affect over 100 breeds of dog. The initial clinical sign is visual impairment in scotopic conditions, as a consequence of rod photoreceptor cell degeneration. Photopic vision degeneration then follows, due to progression of the disease to the cone photoreceptors, and ultimately results in complete blindness. Two full-sibling English Shepherds were diagnosed with PRA at approximately 5 years old and tested clear of all published PRA genetic variants. This study sought to identify the novel PRA-associated variant segregating in the breed. We utilised a combined approach of whole genome sequencing of the probands and homozygosity mapping of four cases and 22 controls and identified a short interspersed nuclear element within an alternatively spliced exon in FAM161A. The XP_005626197.1 c.17929_ins210 variant was homozygous in six PRA cases and heterozygous or absent in control dogs, consistent with a recessive mode of inheritance. The insertion is predicted to extend exon 4 by 39 aberrant amino acids followed by an early termination stop codon. PRA is intractable to treatment, so the development of a genetic screening test, based on the associated variant, is significant, because it provides dog breeders/owners with a means of reducing the frequency of the disease variant within this breed as well as minimising the risk of breeding puppies that will develop this blinding disease.
Transcriptomic Analysis of Arachidonic Acid Pathway Genes Provides Mechanistic Insight into Multi-Organ Inflammatory and Vascular Diseases
Authors: Aradhyula Vaishnavi , Breidenbach Joshua D. , Khatib-Shahidi Bella Z. , Slogar Julia N. , Eyong Sonia A. , Faleel Dhilhani , Dube Prabhatchandra , Gupta Rajesh , Khouri Samer J. , Haller Steven T. , Kennedy David J.
Published: July 2024

Arachidonic acid (AA) metabolites have been associated with several diseases across various organ systems, including the cardiovascular, pulmonary, and renal systems. Lipid mediators generated from AA oxidation have been studied to control macrophages, T-cells, cytokines, and fibroblasts, and regulate inflammatory mediators that induce vascular remodeling and dysfunction. AA is metabolized by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) to generate anti-inflammatory, pro-inflammatory, and pro-resolutory oxidized lipids. As comorbid states such as diabetes, hypertension, and obesity become more prevalent in cardiovascular disease, studying the expression of AA pathway genes and their association with these diseases can provide unique pathophysiological insights. In addition, the AA pathway of oxidized lipids exhibits diverse functions across different organ systems, where a lipid can be both anti-inflammatory and pro-inflammatory depending on the location of metabolic activity. Therefore, we aimed to characterize the gene expression of these lipid enzymes and receptors throughout multi-organ diseases via a transcriptomic meta-analysis using the Gene Expression Omnibus (GEO) Database. In our study, we found that distinct AA pathways were expressed in various comorbid conditions, especially those with prominent inflammatory risk factors. Comorbidities, such as hypertension, diabetes, and obesity appeared to contribute to elevated expression of pro-inflammatory lipid mediator genes. Our results demonstrate that expression of inflammatory AA pathway genes may potentiate and attenuate disease; therefore, we suggest further exploration of these pathways as therapeutic targets to improve outcomes.
Divergence of Phyllosphere Microbial Community Assemblies and Components of Volatile Organic Compounds between the Invasive Sphagneticola trilobata, the Native Sphagneticola calendulacea and Their Hybrids, and Its Implications for Invasiveness
Authors: Zhang Hui , Li Shanshan , Zhou Sheng , Guo Wei , Chen Ping , Li Yongquan , Wu Wei
Published: July 2024

Closely-related plant groups with distinct microbiomes, chemistries and ecological characteristics represent tractable models to explore mechanisms shaping species spread, competitive dynamics and community assembly at the interface of native and introduced ranges. We investigated phyllosphere microbial communities, volatile organic compound (VOC) compositions, and potential interactions among introduced S. trilobata, native S. calendulacea and their hybrid in South China. S. trilobata exhibited higher α diversity but significantly different community composition compared to the native and hybrid groups. However, S. calendulacea and the hybrid shared certain microbial taxa, suggesting potential gene flow or co-existence. The potent antimicrobial VOC profile of S. trilobata, including unique compounds like p-cymene (13.33%), likely contributes to its invasion success. The hybrid’s intermediate microbial and VOC profiles suggest possible consequences for species distribution, genetic exchange, and community assembly in heterogeneous environments. This hybrid deserves further study as both an opportunity for and threat to diversity maintenance. These differentiating yet connected plant groups provide insight into ecological and evolutionary dynamics shaping microbiome structure, species co-occurrence and competitive outcomes during biological exchange and habitat transformation. An interdisciplinary approach combining chemical and microbial ecology may reveal mechanisms underlying community stability and change, informing management of species spread in a globalized world.
Advances in CircRNAs in the Past Decade: Review of CircRNAs Biogenesis, Regulatory Mechanisms, and Functions in Plants
Authors: Zhang Dongqin , Ma Yue , Naz Misbah , Ahmed Nazeer , Zhang Libo , Zhou Jing-Jiang , Yang Ding , Chen Zhuo
Published: July 2024

Circular RNA (circRNA) is a type of non-coding RNA with multiple biological functions. Whole circRNA genomes in plants have been identified, and circRNAs have been demonstrated to be widely present and highly expressed in various plant tissues and organs. CircRNAs are highly stable and conserved in plants, and exhibit tissue specificity and developmental stage specificity. CircRNAs often interact with other biomolecules, such as miRNAs and proteins, thereby regulating gene expression, interfering with gene function, and affecting plant growth and development or response to environmental stress. CircRNAs are less studied in plants than in animals, and their regulatory mechanisms of biogenesis and molecular functions are not fully understood. A variety of circRNAs in plants are involved in regulating growth and development and responding to environmental stress. This review focuses on the biogenesis and regulatory mechanisms of circRNAs, as well as their biological functions during growth, development, and stress responses in plants, including a discussion of plant circRNA research prospects. Understanding the generation and regulatory mechanisms of circRNAs is a challenging but important topic in the field of circRNAs in plants, as it can provide insights into plant life activities and their response mechanisms to biotic or abiotic stresses as well as new strategies for plant molecular breeding and pest control.
A Systematic Review and Meta-Analysis of Noise Annoyance as a Determinant of Physiological Changes Linked to Disease Promotion
Authors: Senerth Emily , Pasumarthi Tejanth , Tangri Neha , Abbi Bhavya , Bickett Skye , McNamee James P. , Michaud David S. , Morgan Rebecca L.
Published: July 2024

This systematic review investigates the certainty of evidence (CoE) regarding noise annoyance as a determinant of biological changes known to contribute to disease development. We searched PubMed MEDLINE, EMBASE, Cochrane Central, and CINAHL for English-language comparative studies conducted on humans of any age from 1 January 1940, to 28 August 2023. Further, studies that provided quantitative data on the relationship between noise annoyance and biomarkers of interest were included. Where possible, random-effects meta-analyses were used to calculate the odds ratios of noise annoyance on biomarkers and biological conditions considered to be risk factors for developing health effects. The risk of bias of individual studies was assessed using the Risk of Bias of Non-randomized Studies of Exposures (ROBINS-E) instrument. The CoE for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The search identified 23 primary studies reporting on relevant biomarkers. Although some studies and pooled estimates suggest a possible association between noise annoyance and biological measures, the CoE overall is very low due to concerns with the risk of bias, inconsistency, and imprecision in the estimates of effects. In the context of environmental impact assessment, where guidelines aim to mitigate the prevalence of populations experiencing a high level of noise annoyance, our results suggest that such practices should be grounded in the understanding that annoyance is health-relevant because it reflects an undesirable reaction to noise, rather than a precursor to chronic physical health conditions.
Vitamin B12 Metabolism: A Network of Multi-Protein Mediated Processes
Authors: Mucha Patryk , Kus Filip , Cysewski Dominik , Smolenski Ryszard T. , Tomczyk Marta
Published: July 2024

The water-soluble vitamin, vitamin B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its deficiency can lead to hematological and neurological disorders; however, the manifestation of these clinical outcomes is relatively late. It leads to difficulties in the early diagnosis of vitamin B12 deficiency. A prolonged lack of vitamin B12 may have severe consequences including increased morbidity to neurological and cardiovascular diseases. Beyond inadequate dietary intake, vitamin B12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabolism. Despite nearly 70 years of knowledge since the isolation and characterization of this vitamin, there are still gaps in understanding its metabolic pathways. Thus, this review aims to compile current knowledge about the crucial proteins necessary to efficiently accumulate and process vitamin B12 in humans, presenting these systems as a multi-protein network. The epidemiological consequences, diagnosis, and treatment of vitamin B12 deficiency are also highlighted. We also discuss clinical warnings of vitamin B12 deficiency based on the ongoing test of specific moonlighting proteins engaged in vitamin B12 metabolic pathways.
Alginate Oligosaccharides Enhance Antioxidant Status and Intestinal Health by Modulating the Gut Microbiota in Weaned Piglets
Authors: Liu Ming , Deng Xiong , Zhao Yong , Everaert Nadia , Zhang Hongfu , Xia Bing , Schroyen Martine
Published: July 2024

Alginate oligosaccharides (AOSs), which are an attractive feed additive for animal production, exhibit pleiotropic bioactivities. In the present study, we investigated graded doses of AOS-mediated alterations in the physiological responses of piglets by determining the intestinal architecture, barrier function, and microbiota. A total of 144 weaned piglets were allocated into four dietary treatments in a completely random design, which included a control diet (CON) and three treated diets formulated with 250 mg/kg (AOS250), 500 mg/kg (AOS500), and 1000 mg/kg AOS (AOS1000), respectively. The trial was carried out for 28 days. Our results showed that AOS treatment reinforced the intestinal barrier function by increasing the ileal villus height, density, and fold, as well as the expression of tight junction proteins, especially at the dose of 500 mg/kg AOS. Meanwhile, supplementations with AOSs showed positive effects on enhancing antioxidant capacity and alleviating intestinal inflammation by elevating the levels of antioxidant enzymes and inhibiting excessive inflammatory cytokines. The DESeq2 analysis showed that AOS supplementation inhibited the growth of harmful bacteria Helicobacter and Escherichia_Shigella and enhanced the relative abundance of Faecalibacterium and Veillonella. Collectively, these findings suggested that AOSs have beneficial effects on growth performance, antioxidant capacity, and gut health in piglets.
Screen-Printed Electrodes—A Promising Tool for Antineoplastic Drug Detection (Cisplatin and Bleomycin) in Biological Samples
Authors: Mirica (Ion) Andreea-Cristina , Stan Dana , Zaharia Dragos-Cosmin , Iovu Horia , Mocanu Sorin , Avram Marioara , Bocancia-Mateescu Lorena-Andreea
Published: July 2024

Cancer remains one of the leading causes for death worldwide. Palliative chemotherapy is vital for certain cancer patients, highlighting the critical need for treatment monitoring tools to prevent drug accumulation and mitigate the risk of high toxicity. Therefore, our aim was to evaluate the potential of screen-printed electrodes for the development of sensitive and accurate biosensors for the detection/quantification of antineoplastic drugs. To this purpose, we developed a cisplatin sensor. By functionalizing the gold electrode with human serum albumin and by collecting the electrochemical signal obtained in a H2O2 solution, through voltammetry measurements, we were able to correlate the current measured at 430 mV with the concentration of cisplatin present in human serum samples, with a correlation coefficient of R2 = 0.99. Also, a bleomycin biosensor was developed and proven functional, but further optimization steps were employed in order to improve the accuracy. The developed biosensors have a detection range of 0.0006–43.2 mg/mL for cisplatin and 0.23–7.56 μg/mL for bleomycin in the serum samples. Our preliminary results show that these biosensors can facilitate the real-time monitoring of cisplatin and bleomycin serum levels, allowing healthcare professionals to tailor treatment strategies based on individual patient responses.
Systematic Review of Naturally Derived Substances That Act as Inhibitors of the Nicotine Metabolizing Enzyme Cytochrome P450 2A6
Authors: Tzoupis Haralampos , Papavasileiou Konstantinos D. , Papatzelos Stavros , Mavrogiorgis Angelos , Zacharia Lefteris C. , Melagraki Georgia , Afantitis Antreas
Published: July 2024

Tobacco smoking has been highlighted as a major health challenge in modern societies. Despite not causing death directly, smoking has been associated with several health issues, such as cardiovascular diseases, respiratory disorders, and several cancer types. Moreover, exposure to nicotine during pregnancy has been associated with adverse neurological disorders in babies. Nicotine Replacement Therapy (NRT) is the most common strategy employed for smoking cessation, but despite its widespread use, NRT presents with low success and adherence rates. This is attributed partially to the rate of nicotine metabolism by cytochrome P450 2A6 (CYP2A6) in each individual. Nicotine addiction is correlated with the high rate of its metabolism, and thus, novel strategies need to be implemented in NRT protocols. Naturally derived products are a cost-efficient and rich source for potential inhibitors, with the main advantages being their abundance and ease of isolation. This systematic review aims to summarize the natural products that have been identified as CYP2A6 inhibitors, validated through in vitro and/or in vivo assays, and could be implemented as nicotine metabolism inhibitors. The scope is to present the different compounds and highlight their possible implementation in NRT strategies. Additionally, this information would provide valuable insight regarding CYP2A6 inhibitors, that can be utilized in drug development via the use of in silico methodologies and machine-learning models to identify new potential lead compounds for optimization and implementation in NRT regimes.
Effects of Modulating BMP9, BMPR2, and AQP1 on BMP Signaling in Human Pulmonary Microvascular Endothelial Cells
Authors: Lotsios Nikolaos S. , Keskinidou Chrysi , Dimopoulou Ioanna , Kotanidou Anastasia , Langleben David , Orfanos Stylianos E. , Vassiliou Alice G.
Published: July 2024

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive increase in mean pulmonary arterial pressure. Mutations in the BMPR2 and AQP1 genes have been described in familial PAH. The bone morphogenetic proteins BMP9 and BMP10 bind with high affinity to BMPR2. Administration of BMP9 has been proposed as a potential therapeutic strategy against PAH, although recent conflicting evidence dispute the effect of such a practice. Considering the involvement of the above molecules in PAH onset, progression, and therapeutic value, we examined the effects of modulation of BMP9, BMPR2, and AQP1 on BMP9, BMP10, BMPR2, AQP1, and TGFB1 expression in human pulmonary microvascular endothelial cells in vitro. Our results demonstrated that silencing the BMPR2 gene resulted in increased expression of its two main ligands, namely BMP9 and BMP10. Exogenous administration of BMP9 caused the return of BMP10 to basal levels, while it restored the decreased AQP1 protein levels and the decreased TGFB1 mRNA and protein expression levels caused by BMPR2 silencing. Moreover, AQP1 gene silencing also resulted in increased expression of BMP9 and BMP10. Our results might possibly imply that the effect of exogenously administered BMP9 on molecules participating in the BMP signaling pathway could depend on the expression levels of BMPR2. Taken together, these results may provide insight into the highly complex interactions of the BMP signaling pathway.
A Novel Affordable and Reliable Framework for Accurate Detection and Comprehensive Analysis of Somatic Mutations in Cancer
Authors: Atzeni Rossano , Massidda Matteo , Pieroni Enrico , Rallo Vincenzo , Pisu Massimo , Angius Andrea
Published: July 2024

Accurate detection and analysis of somatic variants in cancer involve multiple third-party tools with complex dependencies and configurations, leading to laborious, error-prone, and time-consuming data conversions. This approach lacks accuracy, reproducibility, and portability, limiting clinical application. Musta was developed to address these issues as an end-to-end pipeline for detecting, classifying, and interpreting cancer mutations. Musta is based on a Python command-line tool designed to manage tumor-normal samples for precise somatic mutation analysis. The core is a Snakemake-based workflow that covers all key cancer genomics steps, including variant calling, mutational signature deconvolution, variant annotation, driver gene detection, pathway analysis, and tumor heterogeneity estimation. Musta is easy to install on any system via Docker, with a Makefile handling installation, configuration, and execution, allowing for full or partial pipeline runs. Musta has been validated at the CRS4-NGS Core facility and tested on large datasets from The Cancer Genome Atlas and the Beijing Institute of Genomics. Musta has proven robust and flexible for somatic variant analysis in cancer. It is user-friendly, requiring no specialized programming skills, and enables data processing with a single command line. Its reproducibility ensures consistent results across users following the same protocol.
Identification of Ribonuclease Inhibitors for the Control of Pathogenic Bacteria
Authors: Matos Rute G. , Simmons Katie J. , Fishwick Colin W. G. , McDowall Kenneth J. , Arraiano Cecília M.
Published: July 2024

Bacteria are known to be constantly adapting to become resistant to antibiotics. Currently, efficient antibacterial compounds are still available; however, it is only a matter of time until these compounds also become inefficient. Ribonucleases are the enzymes responsible for the maturation and degradation of RNA molecules, and many of them are essential for microbial survival. Members of the PNPase and RNase II families of exoribonucleases have been implicated in virulence in many pathogens and, as such, are valid targets for the development of new antibacterials. In this paper, we describe the use of virtual high-throughput screening (vHTS) to identify chemical compounds predicted to bind to the active sites within the known structures of RNase II and PNPase from Escherichia coli. The subsequent in vitro screening identified compounds that inhibited the activity of these exoribonucleases, with some also affecting cell viability, thereby providing proof of principle for utilizing the known structures of these enzymes in the pursuit of new antibacterials.