bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Composition of Natural, Agricultural, and Technogenic Soils of Both Forest and Forest-Tundra of the Russian North
Authors: Abakumov Evgeny , Zverev Aleksei , Andronov Evgeny , Nizamutdinov Timur
Published: August 2023

Technogenic processes and agrodevelopment of the soil cover lead to significant transformations of soil chemical and biological properties. New methods of soil microbiology, including next-generation sequencing, allows us to investigate soil microbial composition in detail, including the taxonomy and ecological functions of soil bacteria. This study presents data on the taxonomic diversity of mature and anthropogenically disturbed soils in various ecosystems of Russia. Natural soils in the southern taiga (Leningrad region and Novgorod region), northern taiga (Komi republic), forest-tundra, and tundra (Nadym city and Salekhard city) were investigated using next-generation sequencing (16S rDNA amplicon sequencing). In each natural bioclimatic zone, anthropogenically disturbed quarry soils or agriculturally transformed soils were also investigated. It was found that Proteobacteria, Actinobateriota, Acidobateriota, Bacteroidota, Chroloflexi, Planctomycetota, Verrucomicrobiota and Firmicutes phyla were dominant in natural soils, with minor differences between agrosoils and mature soils. In the soils of quarries, there were revealed processes of declining diversity of microbiome communities and the replacement of them by bacterial communities, different from natural and agrogenic soils. Thus, the microbial community is the most sensitive indicator of anthropogenic soil amendments and can serve to assess the success of soil self-restoration after human intervention.
Development of High-Power Ultrasonic System Dedicated to Metal Powder Atomization
Authors: Kustron Pawel , Korzeniowski Marcin , Sajbura Adam , Piwowarczyk Tomasz , Kaczynski Pawel , Sokolowski Pawel
Published: August 2023

The article presents the results of the development works and research on the atomization process carried out using two prototype high-power ultrasonic systems. Ultrasonic systems have been designed to develop a new metal powder production process; these materials are increasingly used in modern manufacturing processes such as additive technologies or spraying and surfacing processes. The preliminary studies presented in the article were conducted for water to assess the effectiveness of both systems and to verify the theoretical and structural assumptions. In ultrasonic atomization, the ultrasonic wave causes the phenomenon of cavitation, which leads to the overcoming of the surface tension forces of the liquid and its disintegration into fine droplets. The important parameters that affect the properties of the produced droplets include, among others, the frequency of the sonotrode vibrations and the amplitude of the vibrations of the working plate. As part of the research, the paper presents the process of selecting the sonotrode geometry for two different values of the transducer’s natural frequencies (20 kHz and 70 kHz). In the design process, the finite element method was used to perform a harmonic analysis and develop the geometry of the sonotrode and the working plate. The design assumptions and the design process were presented. The modeled and then ultrasonic waveguides were verified experimentally by measuring the deflection distribution on the working plate surface using a high-precision laser displacement sensor. Then, the work ultimately resulted in conducting atomization tests of water. The obtained aerosols and the mechanism of their formation were studied using a high-speed camera. Finally, using Matlab R2020a software and image analysis scripts, it was possible to analyze the droplet size distribution generated by both systems. It was observed that 50% of the produced droplets were in the range of 35–55 μm for a 20 kHz system, while for a 70 kHz system it was 10–25 μm, which is a very satisfying distribution in terms of metal powder atomization.
Nondestructive Evaluation of Thermal Barrier Coatings’ Porosity Based on Terahertz Multi-Feature Fusion and a Machine Learning Approach
Authors: Li Rui , Ye Dongdong , Zhang Qiukun , Xu Jianfei , Pan Jiabao
Published: August 2023

Thermal barrier coatings (TBCs) play a crucial role in safeguarding aero-engine blades from high-temperature environments and enhancing their performance and durability. Accurate evaluation of TBCs’ porosity is of paramount importance for aerospace material research. However, existing evaluation methods often involve destructive testing or lack precision. In this study, we proposed a novel nondestructive evaluation method for TBCs’ porosity, utilizing terahertz time-domain spectroscopy (THz-TDS) and a machine learning approach. The primary objective was to achieve reliable and precise porosity evaluation without causing damage to the coatings. Multiple feature parameters were extracted from THz-TDS data to characterize porosity variations. Additionally, correlation analysis and p-value testing were employed to assess the significance and correlations among the feature parameters. Subsequently, the dung-beetle-optimizer-algorithm-optimized random forest (DBO-RF) regression model was applied to accurately predict the porosity. Model performance was evaluated using K-fold cross-validation. Experimental results demonstrated the effectiveness of our proposed method, with the DBO-RF model achieving high precision and robustness in porosity prediction. The model evaluation revealed a root-mean-square error of 1.802, mean absolute error of 1.549, mean absolute percentage error of 8.362, and average regression coefficient of 0.912. This study introduces a novel technique that presents a dependable nondestructive testing solution for the evaluation and prediction of TBCs’ porosity, effectively monitoring the service life of TBCs and determining their effectiveness. With its practical applicability in the aerospace industry, this method plays a vital role in the assessment and analysis of TBCs’ performance, driving progress in aerospace material research.
Application of Interpretable Machine Learning for Production Feasibility Prediction of Gold Mine Project
Authors: Kang Kun , Chen Qishen , Wang Kun , Zhang Yanfei , Zhang Dehui , Zheng Guodong , Xing Jiayun , Long Tao , Ren Xin , Shang Chenghong , Cui Bojing
Published: August 2023

In the context of globalization in the mining industry, assessing the production feasibility of mining projects by smart technology is crucial for the improvement of mining development efficiency. However, evaluating the feasibility of such projects faces significant challenges due to incomplete data and complex variables. In recent years, the development of big data technology has offered new possibilities for rapidly evaluating mining projects. This study conducts an intelligent evaluation of gold mines based on global mineral resources data to estimate whether a gold mine project can be put into production. A technical workflow is constructed, including data filling, evaluation model construction, and production feasibility evaluation. Based on the workflow, the missing data is filled in by the Miceforest imputation algorithm first. The evaluation model is established based on the Random Forest model to quantitatively predict the feasibility of the mining project being put into production, and important features of the model are extracted using Shapley Additive explanation(SHAP). This workflow may enhance the efficiency and accuracy of quantitative production feasibility evaluation for mining projects, with an accuracy rate increased from 93.80% to 95.99%. Results suggest that the features of estimated mine life and gold ore grade have the most significant impact on production feasibility.
Evaluation of Drug Release Profiles of Titanium Plates Coated with PLGA or Chitosan with Meropenem Using UPLC: An In Vitro Study
Authors: Al-Qubaisey Mohammad I. , Khounganian Rita M. , Syed Saeed A. , Saif Sameh A.
Published: August 2023

In some cases, titanium plates could be a reservoir for harboring bacteria resulting in challenging cases of infection. Current estimates indicate that 10–12% of plates require removal due to infection, exposure, pain, and discomfort. The present investigation was conducted to evaluate the potential sustained meropenem-coated plates amalgamated with “PLGA” polylactic co-glycolic acid and chitosan polymers with the concurrent sterilization effect of gamma irradiation. After coating the plates with either M “meropenem”, MP “meropenem-PLGA, or MC “meropenem-chitosan”, they were divided into two groups of sterile and non-sterile coated plates. The drug release was studied over three-time intervals of 1, 3, and 7 days using ultrahigh-performance liquid chromatography. Overall, the three materials had similar drug release on day one, both in sterile and non-sterile groups, while on days 3 and 7, a noticeable increase in the drug release was perceived in favor of MP. At the same time, no statistically significant difference was observed between sterile and non-sterile groups. A statistically significant increase in drug release was observed between and within the materials over time, with no overall difference between sterile and non-sterile groups.
Research Hotspots and Trends of Bone Xenograft in Clinical Procedures: A Bibliometric and Visual Analysis of the Past Decade
Authors: Li Jiayue , Zhao Yujue , Chen Shili , Wang Simin , Zhong Wen , Zhang Qing
Published: August 2023

Background: Bone defect therapy is a common clinical challenge for orthopedic and clinical physicians worldwide, and the therapeutic effect affects the physiological function and healthy life quality of millions of patients. Compared with traditional autogenous bone transplants, bone xenografts are attracting attention due to their advantages of unlimited availability and avoidance of secondary damage. However, there is currently a lack of bibliometric analysis on bone xenograft. This study aimed to use bibliometric methods to analyze the literature on bone xenograft from 2013 to 2023, to explore the current status, hotspots, and future trends of research in this field, and to promote its development and progress. Methods: Using the Web of Science Core Collection database, we retrieved and collected publication data related to xenogeneic bone grafting materials worldwide from January 2013 to March 2023. Origin (2021), CiteSpace (6.2.R2 standard), and an online bibliometric platform were used for bibliometric analysis and data visualization. Results: A total of 3395 documents were retrieved, and 686 eligible papers were selected. The country and institutions with the highest number of publications and centrality were the United States (125 papers, centrality = 0.44) and the University of Zurich (29 papers, centrality = 0.28), respectively. The most cited author was Araujo MG (163 times), and the author with the most significant centrality was Froum SJ (centrality = 0.09). The main keyword clusters were “tissue engineering”, “sinus floor elevation”, “dental implants”, “tooth extraction”, and “bone substitutes”. The most significant bursting keywords in the last three years were “platelet rich fibrin”. Conclusions: Research on bone xenograft is steadily growing and will continue to rise. Currently, research hotspots and directions are mainly focused on dental implants related to bone-augmentation techniques and bone tissue engineering. In the future, research hotspots and directions may focus on decellularization technology and investigations involving platelet-rich fibrin.
Hypoactive Visual Cortex, Prefrontal Cortex and Insula during Self-Face Recognition in Adults with First-Episode Major Depressive Disorder
Authors: Fan Zebin , Liu Zhening , Yang Jie , Yang Jun , Sun Fuping , Tang Shixiong , Wu Guowei , Guo Shuixia , Ouyang Xuan , Tao Haojuan
Published: August 2023

Self-face recognition is a vital aspect of self-referential processing, which is closely related to affective states. However, neuroimaging research on self-face recognition in adults with major depressive disorder is lacking. This study aims to investigate the alteration of brain activation during self-face recognition in adults with first-episode major depressive disorder (FEMDD) via functional magnetic resonance imaging (fMRI); FEMDD (n = 59) and healthy controls (HC, n = 36) who performed a self-face-recognition task during the fMRI scan. The differences in brain activation signal values between the two groups were analyzed, and Pearson correlation analysis was used to evaluate the relationship between the brain activation of significant group differences and the severity of depressive symptoms and negative self-evaluation; FEMDD showed significantly decreased brain activation in the bilateral occipital cortex, bilateral fusiform gyrus, right inferior frontal gyrus, and right insula during the task compared with HC. No significant correlation was detected between brain activation with significant group differences and the severity of depression and negative self-evaluation in FEMDD or HC. The results suggest the involvement of the malfunctioning visual cortex, prefrontal cortex, and insula in the pathophysiology of self-face recognition in FEMDD, which may provide a novel therapeutic target for adults with FEMDD.
Drug-Delivery Silver Nanoparticles: A New Perspective for Phenindione as an Anticoagulant
Authors: Nikolova Stoyanka , Milusheva Miglena , Gledacheva Vera , Feizi-Dehnayebi Mehran , Kaynarova Lidia , Georgieva Deyana , Delchev Vassil , Stefanova Iliyana , Tumbarski Yulian , Mihaylova Rositsa , Cherneva Emiliya , Stoencheva Snezhana , Todorova Mina
Published: August 2023

Anticoagulants prevent the blood from developing the coagulation process, which is the primary cause of death in thromboembolic illnesses. Phenindione (PID) is a well-known anticoagulant that is rarely employed because it totally prevents coagulation, which can be a life-threatening complication. The goal of the current study is to synthesize drug-loaded Ag NPs to slow down the coagulation process. Methods: A rapid synthesis and stabilization of silver nanoparticles as drug-delivery systems for phenindione (PID) were applied for the first time. Results: Several methods are used to determine the size of the resulting Ag NPs. Additionally, the drug-release capabilities of Ag NPs were established. Density functional theory (DFT) calculations were performed for the first time to indicate the nature of the interaction between PID and nanostructures. DFT findings supported that galactose-loaded nanostructure could be a proper delivery system for phenindione. The drug-loaded Ag NPs were characterized in vitro for their antimicrobial, cytotoxic, and anticoagulant activities, and ex vivo for spasmolytic activity. The obtained data confirmed the drug-release experiments. Drug-loaded Ag NPs showed that prothrombin time (PT, sec) and activated partial thromboplastin time (APTT, sec) are approximately 1.5 times longer than the normal values, while PID itself stopped coagulation at all. This can make the PID-loaded Ag NPs better therapeutic anticoagulants. PID was compared to PID-loaded Ag NPs in antimicrobial, spasmolytic activity, and cytotoxicity. All the experiments confirmed the drug-release results.
Porcine Models of Spinal Cord Injury
Authors: Wathen Connor A. , Ghenbot Yohannes G. , Ozturk Ali K. , Cullen D. Kacy , O’Donnell John C. , Petrov Dmitriy
Published: August 2023

Large animal models of spinal cord injury may be useful tools in facilitating the development of translational therapies for spinal cord injury (SCI). Porcine models of SCI are of particular interest due to significant anatomic and physiologic similarities to humans. The similar size and functional organization of the porcine spinal cord, for instance, may facilitate more accurate evaluation of axonal regeneration across long distances that more closely resemble the realities of clinical SCI. Furthermore, the porcine cardiovascular system closely resembles that of humans, including at the level of the spinal cord vascular supply. These anatomic and physiologic similarities to humans not only enable more representative SCI models with the ability to accurately evaluate the translational potential of novel therapies, especially biologics, they also facilitate the collection of physiologic data to assess response to therapy in a setting similar to those used in the clinical management of SCI. This review summarizes the current landscape of porcine spinal cord injury research, including the available models, outcome measures, and the strengths, limitations, and alternatives to porcine models. As the number of investigational SCI therapies grow, porcine SCI models provide an attractive platform for the evaluation of promising treatments prior to clinical translation.
Management of Obesity-Related Inflammatory and Cardiovascular Diseases by Medicinal Plants: From Traditional Uses to Therapeutic Targets
Authors: Saad Bashar
Published: August 2023

Inflammation is a crucial factor in the development and progression of cardiovascular diseases (CVD). Cardiac remodeling in the presence of persistent inflammation leads to myocardial fibrosis and extracellular matrix changes, which reduce cardiac function, induce arrhythmias, and finally, cause heart failure. The majority of current CVD treatment plans concentrate on reducing risk factors such as hyperlipidemia, type 2 diabetes, and hypertension. One such strategy could be inflammation reduction. Numerous in vitro, animal, and clinical studies indicate that obesity is associated with low-grade inflammation. Recent studies have demonstrated the potential of medicinal plants and phytochemicals to cure and prevent obesity and inflammation. In comparison to conventional therapies, the synergistic effects of several phytochemicals boost their bioavailability and impact numerous cellular and molecular targets. Focusing on appetite, pancreatic lipase activity, thermogenesis, lipid metabolism, lipolysis and adipogenesis, apoptosis in adipocytes, and adipocyte life cycle by medicinal plants and phytochemicals represent an important goal in the development of new anti-obesity drugs. We conducted an extensive review of the literature and electronic databases, including Google Scholar, PubMed, Science Direct, and MedlinePlus, for collecting data on the therapeutic effects of medicinal plants/phytochemicals in curing obesity and its related inflammation and CVD diseases, including cellular and molecular mechanisms, cytokines, signal transduction cascades, and clinical trials.
In Vitro Study of the Multimodal Effect of Na+/K+ ATPase Blocker Ouabain on the Tumor Microenvironment and Malignant Cells
Authors: Harich Octavia-Oana , Gavriliuc Oana-Isabella , Ordodi Valentin-Laurentiu , Tirziu Alexandru , Paunescu Virgil , Panaitescu Carmen , Bojin Maria-Florina
Published: August 2023

Na+/K+ ATPase is a protein involved in the active transport of ions across the cellular membrane. Ouabain is a cardiotonic glycoside that, by inhibiting the Na+/K+ pump, interferes with cell processes mediated directly by the pump, but also indirectly influences other cellular processes such as cell cycle and proliferation, growth, cell differentiation, angiogenesis, migration, adhesion, and invasion. We used the SK-BR-3 breast cancer cell line, mesenchymal stem cells (MSCs), and tumor-associated fibroblasts (TAFs) in vitro to determine the effects of ouabain exposure on these cellular types. The results showed a multi-level effect of ouabain mainly on tumor cells, in a dose-dependent manner, while the TAFs and their normal counterparts were not significantly influenced. Following exposure to ouabain, the SK-BR-3 cells changed their morphologic appearance, decreased the expression of immunophenotypic markers (CD29, Her2, VEGF), the proliferation rate was significantly decreased (Ki67 index), the cells were blocked in the G0 phase of the cell cycle and suffered necrosis. These data were correlated with the variable expression of α and β Na+/K+ pump subunits in tumor cells, resulting in decreased ability to adhere to the VCAM-1 substrate in functional flow chamber studies. Being indicative of the pro-apoptotic and inhibitory effect of ouabain on tumor invasion and metastasis, the results support the addition of ouabain to the oncological therapeutic arsenal, trailing the “repurposing drugs” approach.
Utilizing an Oxidized Biopolymer to Enhance the Bonding of Glass Ionomer Luting Cement Particles for Improved Physical and Mechanical Properties
Authors: Alsunbul Hanan , Khan Aftab Ahmed , De Vera Merry Angelyn Tan , Bautista Leonel S. J. , Javed Ravish
Published: August 2023

This study aimed to determine the reinforcing effect of two weight ratios of Gum Arabic (GA) natural biopolymer, i.e., 0.5% and 1.0% in the powdered composition of glass ionomer luting cement. GA powder was oxidized and GA-reinforced GIC in 0.5 and 1.0 wt.% formulations were prepared in rectangular bars using two commercially available GIC luting materials (Medicem and Ketac Cem Radiopaque). The control groups of both materials were prepared as such. The effect of reinforcement was evaluated in terms of microhardness, flexural strength (FS), fracture toughness (FT), and tensile strength (TS). The internal porosity and water contact angle formation on the study samples were also evaluated. Film thickness was measured to gauge the effect of micron-sized GA powder in GA–GIC composite. Paired sample t-tests were conducted to analyze data for statistical significance (p < 0.05). The experimental groups of both materials containing 0.5 wt.% GA–GIC significantly improved FS, FT, and TS compared to their respective control groups. However, the microhardness significantly decreased in experimental groups of both cements compared to their respective control groups. The addition of GA powder did not cause a significant increase in film thickness and the water contact angle of both 0.5 and 1.0 wt.% GA–GIC formulations were less than 90o. Interestingly, the internal porosity of 0.5 wt.% GA–GIC formulations in both materials were observed less compared to their respective control groups. The significantly higher mechanical properties and low porosity in 0.5 wt.% GA–GIC formulations compared to their respective control group indicate that reinforcing GA powder with 0.5 wt.% in GIC might be promising in enhancing the mechanical properties of GIC luting materials.
Lipid Metabolism Disorder in Cerebrospinal Fluid Related to Parkinson’s Disease
Authors: Qiu Jiewen , Wei Lijian , Su Yilin , Tang Yuting , Peng Guoyou , Wu Yimin , He Yan , Liu Hanqun , Guo Wenyuan , Wu Zhuohu , Xu Pingyi , Mo Mingshu
Published: August 2023

Background: Abnormal accumulation of lipids is found in dopamine neurons and resident microglia in the substantia nigra of patients with Parkinson’s disease (PD). The accumulation of lipids is an important risk factor for PD. Previous studies have mainly focussed on lipid metabolism in peripheral blood, but little attention has been given to cerebrospinal fluid (CSF). We drew the lipidomic signature in CSF from PD patients and evaluated the role of lipids in CSF as biomarkers for PD diagnosis. Methods: Based on lipidomic approaches, we investigated and compared lipid metabolism in CSF from PD patients and healthy controls without dyslipidaemia in peripheral blood and explored the relationship of lipids between CSF and serum by Pearson correlation analysis. Results: A total of 231 lipid species were detected and classified into 13 families in the CSF. The lipid families, including phosphatidylcholine (PC), sphingomyelin (SM) and cholesterol ester (CE), had significantly increased expression compared with the control. Hierarchical clustering was performed to distinguish PD patients based on the significantly changed expression of 34 lipid species. Unsupervised and supervised methods were used to refine this classification. A total of 12 lipid species, including 3-hydroxy-dodecanoyl-carnitine, Cer(d18:1/24:1), CE(20:4), CE(22:6), PC(14:0/18:2), PC(O-18:3/20:2), PC(O-20:2/24:3), SM(d18:0/16:0), SM(d18:2/14:0), SM(d18:2/24:1), SM(d18:1/20:1) and SM(d18:1/12:0), were selected to draw the lipidomic signature of PD. Correlation analysis was performed and showed that the CE family and CE (22:6) in CSF had a positive association with total cholesterol in the peripheral blood from PD patients but not from healthy controls. Conclusions: Our results revealed that the lipidomic signature in CSF may be considered a potential biomarker for PD diagnosis, and increased CE, PC and SM in CSF may reveal pathological changes in PD patients, such as blood–brain barrier leakage.
Problematic Substance Use among Sexual Minority and Heterosexual Young Adults during COVID-19
Authors: Haik Amanda K. , Hussong Andrea M.
Published: August 2023

Sexual minority young adults (SMYAs), compared to heterosexual young adults (HYAs), are a uniquely high-risk population for problematic substance use, a disparity perhaps exacerbated by the COVID-19 pandemic. This study tested whether SMYAs had more problematic substance use than HYAs during the pandemic due to isolation and loneliness as well as lower family closeness. Participants (N = 141) aged 23–29 completed self-report surveys in 2014–2015 as college students and in the summer of 2021 as young adults (59% White, 26% Black/African American, 9% Asian/Middle Eastern, 6% Hispanic/Latino, and <1% American Indian/Alaska Native). Results of multivariate regression and multiple group path analyses did not support hypothesized effects—SMYAs did not have greater increases in problematic substance use compared to HYAs, isolation and loneliness were not significant mediators, and family closeness was not a significant moderator. However, SMYAs experienced a lack of social safety—increased loneliness and decreased family closeness—compared to HYAs. Further research is needed to investigate both the impact and underlying processes of this decreased social safety on SMYA well-being beyond the pandemic to better inform tailored supports and interventions.
How Service Employees’ Mindfulness Links to Task Performance through Psychological Resilience, Deep Acting, and Customer-Oriented Behavior
Authors: Kim Jeong Sik , Park Hyun Jung
Published: August 2023

This study investigates the specific pathways through which mindfulness influences task performance, focusing on the sequential mediating roles of psychological resilience, customer-oriented behavior, and deep acting. Structural equation modeling is used to analyze data collected from 359 employees in the service industry in Korea. The results confirm that mindfulness has a significant direct and indirect relationship with task performance. Improved resilience through mindfulness can be the basis for fostering customer-oriented behavior and deep acting, which sequentially enhance task performance. This study provides a comprehensive understanding of how mindfulness leads to improvements in task performance and highlights the significance of mindfulness for both customers and service employees. It also expands the existing knowledge of mindfulness by empirically integrating resilience, customer-oriented behavior, and deep acting, which have not been extensively studied in mindfulness research. The findings have practical implications from a managerial perspective, emphasizing the importance of mindfulness resources in the workplace.
A Review of Studies on Heat Transfer in Buildings with Radiant Cooling Systems
Authors: Hu Rong , Sun Shilin , Liang Jincan , Zhou Zhiping , Yin Yingde
Published: August 2023

Due to their benefits in interior thermal comfort, energy saving, and noise reduction, radiant cooling systems have received wide attention. Radiant cooling systems can be viewed as a part of buildings’ maintenance structure and a component of cooling systems, depending on their construction. This article reviews studies on heat exchange in rooms utilizing radiant cooling systems, including research on conduction in radiant system structures, system cooling loads, cooling capacity, heat transfer coefficients of cooling surfaces, buildings’ thermal performance, and radiant system control strategy, with the goal of maximizing the benefits of energy conservation. Few studies have examined how radiant cooling systems interact with the indoor environment; instead, earlier research has focused on the thermal performance of radiant cooling systems themselves. Although several investigations have noted variations between the operating dynamics of radiant systems and conventional air conditioning systems, the cause has not yet been identified and quantified. According to heat transfer theory, the authors suggest that additional research on the performance of radiant systems should consider the thermal properties of inactive surfaces and that buildings’ thermal inertia should be used to coordinate radiant system operation.
L-Pampo™, a Novel TLR2/3 Agonist, Acts as a Potent Cancer Vaccine Adjuvant by Activating Draining Lymph Node Dendritic Cells
Authors: Heo Yoonki , Ko Eunbyeol , Park Sejung , Park Si-On , Ahn Byung-Cheol , Yum Jung-Sun , Chun Eunyoung
Published: August 2023

TLR agonists have emerged as an efficient cancer vaccine adjuvant system that induces robust immune responses. L-pampo™, a proprietary vaccine adjuvant of TLR2 and TLR3 agonists, promotes strong humoral and cellular immune responses against infectious diseases. In this study, we demonstrate that vaccines formulated with L-pampo™ affect the recruitment and activation of dendritic cells (DCs) in draining lymph nodes (dLNs) and leading to antigen-specific T-cell responses and anti-tumor efficacy. We analyzed DC maturation and T-cell proliferation using flow cytometry and ELISA. We determined the effect of L-pampo™ on DCs in dLNs and antigen-specific T-cell responses using flow cytometric analysis and the ELISPOT assay. We employed murine tumor models and analyzed the anti-tumor effect of L-pampo™. We found that L-pampo™ directly enhanced the maturation and cytokine production of DCs and, consequently, T-cell proliferation. OVA or OVA peptide formulated with L-pampo™ promoted DC migration into dLNs and increased activation markers and specific DC subsets within dLNs. In addition, vaccines admixed with L-pampo™ promoted antigen-specific T-cell responses and anti-tumor efficacy. Moreover, the combination of L-pampo™ with an immune checkpoint inhibitor synergistically improved the anti-tumor effect. This study suggests that L-pampo™ can be a potent cancer vaccine adjuvant and a suitable candidate for combination immunotherapy.
Influence of the Hypersensitivity to Low Dose Phenomenon on the Tumor Response to Hypofractionated Stereotactic Body Radiation Therapy
Authors: Le Reun Eymeric , Granzotto Adeline , Pêtre Adeline , Bodgi Larry , Beldjoudi Guillaume , Lacornerie Thomas , Vallet Véronique , Bouchet Audrey , Al-Choboq Joëlle , Bourguignon Michel , Thariat Juliette , Bourhis Jean , Lartigau Eric , Foray Nicolas
Published: August 2023

Stereotactic body radiation therapy (SBRT) has made the hypofractionation of high doses delivered in a few sessions more acceptable. While the benefits of hypofractionated SBRT have been attributed to additional vascular, immune effects, or specific cell deaths, a radiobiological and mechanistic model is still needed. By considering each session of SBRT, the dose is divided into hundreds of minibeams delivering some fractions of Gy. In such a dose range, the hypersensitivity to low dose (HRS) phenomenon can occur. HRS produces a biological effect equivalent to that produced by a dose 5-to-10 times higher. To examine whether HRS could contribute to enhancing radiation effects under SBRT conditions, we exposed tumor cells of different HRS statuses to SBRT. Four human HRS-positive and two HRS-negative tumor cell lines were exposed to different dose delivery modes: a single dose of 0.2 Gy, 2 Gy, 10 × 0.2 Gy, and a single dose of 2 Gy using a non-coplanar isocentric minibeams irradiation mode were delivered. Anti-γH2AX immunofluorescence, assessing DNA double-strand breaks (DSB), was applied. In the HRS-positive cells, the DSB produced by 10 × 0.2 Gy and 2 Gy, delivered by tens of minibeams, appeared to be more severe, and they provided more highly damaged cells than in the HRS-negative cells, suggesting that more severe DSB are induced in the “SBRT modes” conditions when HRS occurs in tumor. Each SBRT session can be viewed as hyperfractionated dose delivery by means of hundreds of low dose minibeams. Under current SBRT conditions (i.e., low dose per minibeam and not using ultra-high dose-rate), the response of HRS-positive tumors to SBRT may be enhanced significantly. Interestingly, similar conclusions were reached with HRS-positive and HRS-negative untransformed fibroblast cell lines, suggesting that the HRS phenomenon may also impact the risk of post-RT tissue overreactions.
Optimisation of Sample Preparation from Primary Mouse Tissue to Maintain RNA Integrity for Methods Examining Translational Control
Authors: Munro June , Gillen Sarah L. , Mitchell Louise , Laing Sarah , Karim Saadia A. , Rink Curtis J. , Waldron Joseph A. , Bushell Martin
Published: August 2023

The protein output of different mRNAs can vary by two orders of magnitude; therefore, it is critical to understand the processes that control gene expression operating at the level of translation. Translatome-wide techniques, such as polysome profiling and ribosome profiling, are key methods for determining the translation rates occurring on specific mRNAs. These techniques are now widely used in cell lines; however, they are underutilised in tissues and cancer models. Ribonuclease (RNase) expression is often found to be higher in complex primary tissues in comparison to cell lines. Methods used to preserve RNA during lysis often use denaturing conditions, which need to be avoided when maintaining the interaction and position of the ribosome with the mRNA is required. Here, we detail the cell lysis conditions that produce high-quality RNA from several different tissues covering a range of endogenous RNase expression levels. We highlight the importance of RNA integrity for accurate determination of the global translation status of the cell as determined by polysome gradients and discuss key aspects to optimise for accurate assessment of the translatome from primary mouse tissue.
Plasma Exosome Proteins ILK1 and CD14 Correlated with Organ-Specific Metastasis in Advanced Gastric Cancer Patients
Authors: Zhou Chenfei , Qiao Changting , Ji Jun , Xi Wenqi , Jiang Jinling , Guo Liting , Wu Junwei , Qi Feng , Cai Qu , Damink Steven W. M. Olde , Zhang Jun
Published: August 2023

The exosome plays important roles in driving tumor metastasis, while the role of exosome proteins during organ-specific metastasis in gastric cancer has not been fully understood. To address this question, peripheral blood samples from 12 AGC patients with organ-specific metastasis, including distant lymphatic, hepatic and peritoneal metastasis, were collected to purify exosomes and to detect exosome proteins by Nano-HPLC–MS/MS. Gastric cancer cell lines were used for in vitro experiments. Peripheral blood sample and ascites sample from one patient were further analyzed by single-cell RNA sequencing. GO and KEGG enrichment analysis showed different expression proteins of hepatic metastasis were correlated with lipid metabolism. For peritoneal metastasis, actin cytoskeleton regulation and glycolysis/gluconeogenesis could be enriched. ILK1 and CD14 were correlated with hepatic and peritoneal metastasis, respectively. Overexpression of CD14 and ILK1 impacted the colony formation ability of gastric cancer and increased expression of Vimentin. CD14 derived from immune cells in malignant ascites correlated with high activation of chemokine- and cytokine-mediated signaling pathways. In summary, biological functions of plasma exosome proteins among AGC patients with different metastatic modes were distinct, in which ILK1 and CD14 were correlated with organ-specific metastasis.
Cannabidiol Enhances Cabozantinib-Induced Apoptotic Cell Death via Phosphorylation of p53 Regulated by ER Stress in Hepatocellular Carcinoma
Authors: Jeon Youngsic , Kim Taejung , Kwon Hyukjoon , Kim Jeong-Kook , Park Young-Tae , Ham Jungyeob , Kim Young-Joo
Published: August 2023

Cannabidiol (CBD), a primary constituent in hemp and cannabis, exerts broad pharmacological effects against various diseases, including cancer. Additionally, cabozantinib, a potent multi-kinase inhibitor, has been approved for treating patients with advanced hepatocellular carcinoma (HCC). Recently, there has been an increase in research on combination therapy using cabozantinib to improve efficacy and safety when treating patients. Here, we investigated the effect of a combination treatment of cabozantinib and CBD on HCC cells. CBD treatment enhanced the sensitivity of HCC cells to cabozantinib-mediated anti-cancer activity by increasing cytotoxicity and apoptosis. Phospho-kinase array analysis demonstrated that the apoptotic effect of the combination treatment was mainly related to p53 phosphorylation regulated by endoplasmic reticulum (ER) stress when compared to other kinases. The inhibition of p53 expression and ER stress suppressed the apoptotic effect of the combination treatment, revealing no changes in the expression of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-8, or cleaved caspase-9. Notably, the effect of the combination treatment was not associated with cannabinoid receptor 1 (CNR1) and the CNR2 signaling pathways. Our findings suggest that the combination therapy of cabozantinib and CBD provides therapeutic efficacy against HCC.
Synthesis of g-C3N4@ZnIn2S4 Heterostructures with Extremely High Photocatalytic Hydrogen Production and Reusability
Authors: Chang Yu-Cheng , Chiao Yung-Chang , Chang Chi-Jung
Published: August 2023

The g-C3N4@ZnIn2S4 heterostructures were successfully synthesized through a combination of thermal annealing and hydrothermal methods. To enhance the photocatalytic hydrogen production performance and explore the interface between charge carriers, heterostructures of g-C3N4@ZnIn2S4 were fabricated using varying weights of g-C3N4 nanostructures under visible light irradiation. Remarkably, the photocatalytic hydrogen production efficiency of g-C3N4@ZnIn2S4 heterostructures with 0.01 g g-C3N4 nanostructures was significantly improved, showing approximately 228.6 and 2.58 times higher than that of g-C3N4 nanostructures and ZnIn2S4 nanostructures, respectively. This enhancement in photocatalytic performance is attributed to the effective utilization of visible light and the efficient separation of photogenerated electron-hole pairs facilitated by the heterojunction structures. Moreover, the reusability test validated the outstanding performance of g-C3N4@ZnIn2S4 heterostructures, as they maintained high photocatalytic hydrogen production even after undergoing eight cycles without any noticeable decrease in efficiency. This study offers a promising strategy for designing and synthesizing an environmentally friendly g-C3N4@ZnIn2S4 heterojunction with potential applications in photocatalytic hydrogen evolution.
Primary and hTERT-Transduced Mesothelioma-Associated Fibroblasts but Not Primary or hTERT-Transduced Mesothelial Cells Stimulate Growth of Human Mesothelioma Cells
Authors: Ries Alexander , Slany Astrid , Pirker Christine , Mader Johanna C. , Mejri Doris , Mohr Thomas , Schelch Karin , Flehberger Daniela , Maach Nadine , Hashim Muhammad , Hoda Mir Alireza , Dome Balazs , Krupitza Georg , Berger Walter , Gerner Christopher , Holzmann Klaus , Grusch Michael
Published: August 2023

Pleural mesothelioma (PM) is an aggressive malignancy that develops in a unique tumor microenvironment (TME). However, cell models for studying the TME in PM are still limited. Here, we have generated and characterized novel human telomerase reverse transcriptase (hTERT)-transduced mesothelial cell and mesothelioma-associated fibroblast (Meso-CAF) models and investigated their impact on PM cell growth. Pleural mesothelial cells and Meso-CAFs were isolated from tissue of pneumothorax and PM patients, respectively. Stable expression of hTERT was induced by retroviral transduction. Primary and hTERT-transduced cells were compared with respect to doubling times, hTERT expression and activity levels, telomere lengths, proteomes, and the impact of conditioned media (CM) on PM cell growth. All transduced derivatives exhibited elevated hTERT expression and activity, and increased mean telomere lengths. Cell morphology remained unchanged, and the proteomes were similar to the corresponding primary cells. Of note, the CM of primary and hTERT-transduced Meso-CAFs stimulated PM cell growth to the same extent, while CM derived from mesothelial cells had no stimulating effect, irrespective of hTERT expression. In conclusion, all new hTERT-transduced cell models closely resemble their primary counterparts and, hence, represent valuable tools to investigate cellular interactions within the TME of PM.
PAI-1 Regulation of p53 Expression and Senescence in Type II Alveolar Epithelial Cells
Authors: Rana Tapasi , Jiang Chunsun , Banerjee Sami , Yi Nengjun , Zmijewski Jaroslaw W. , Liu Gang , Liu Rui-Ming
Published: August 2023

Cellular senescence contributes importantly to aging and aging-related diseases, including idiopathic pulmonary fibrosis (IPF). Alveolar epithelial type II (ATII) cells are progenitors of alveolar epithelium, and ATII cell senescence is evident in IPF. Previous studies from this lab have shown that increased expression of plasminogen activator inhibitor 1 (PAI-1), a serine protease inhibitor, promotes ATII cell senescence through inducing p53, a master cell cycle repressor, and activating p53-p21-pRb cell cycle repression pathway. In this study, we further show that PAI-1 binds to proteasome components and inhibits proteasome activity and p53 degradation in human lung epithelial A549 cells and primary mouse ATII cells. This is associated with a senescence phenotype of these cells, manifested as increased p53 and p21 expression, decreased phosphorylated retinoblastoma protein (pRb), and increased senescence-associated beta-galactose (SA-β-gal) activity. Moreover, we find that, although overexpression of wild-type PAI-1 (wtPAI-1) or a secretion-deficient, mature form of PAI-1 (sdPAI-1) alone induces ATII cell senescence (increases SA-β-gal activity), only wtPAI-1 induces p53, suggesting that the premature form of PAI-1 is required for the interaction with the proteasome. In summary, our data indicate that PAI-1 can bind to proteasome components and thus inhibit proteasome activity and p53 degradation in ATII cells. As p53 is a master cell cycle repressor and PAI-1 expression is increased in many senescent cells, the results from this study will have a significant impact not only on ATII cell senescence/lung fibrosis but also on the senescence of other types of cells in different diseases.
Hepatocyte Sirtuin 6 Protects against Atherosclerosis and Steatohepatitis by Regulating Lipid Homeostasis
Authors: Zhu Yingdong , Hu Shuwei , Pan Xiaoli , Gopoju Raja , Cassim Bawa Fathima N. , Yin Liya , Xu Yanyong , Zhang Yanqiao
Published: August 2023

Histone deacetylase Sirtuin 6 (SIRT6) regulates many biological processes. SIRT6 is known to regulate hepatic lipid metabolism and inhibit the development of nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the role of hepatocyte SIRT6 in the development of atherosclerosis and further characterize the mechanism underlying SIRT6’s effect on NAFLD. Ldlr−/− mice overexpressing or lacking hepatocyte SIRT6 were fed a Western diet for 16 weeks. The role of hepatic SIRT6 in the development of nonalcoholic steatohepatitis (NASH), atherosclerosis, and obesity was investigated. We also investigated whether p53 participates in the pathogenesis of NAFLD in mice overexpressing hepatic SIRT6. Our data show that loss of hepatocyte SIRT6 aggravated the development of NAFLD, atherosclerosis, and obesity in Ldlr−/− mice, whereas adeno-associated virus (AAV)-mediated overexpression of human SIRT6 in the liver had opposite effects. Mechanistically, hepatocyte SIRT6 likely inhibited the development of NAFLD by inhibiting lipogenesis, lipid droplet formation, and p53 signaling. Hepatocyte SIRT6 also likely inhibited the development of atherosclerosis by inhibiting intestinal lipid absorption and hepatic VLDL secretion. Hepatic SIRT6 also increased energy expenditure. In conclusion, our data indicate that hepatocyte SIRT6 protects against atherosclerosis, NAFLD, and obesity by regulating lipid metabolism in the liver and intestine.
Investigating the Mental Health Impacts of Climate Change in Youth: Design and Implementation of the International Changing Worlds Study
Authors: Vercammen Ans , Yatirajula Sandhya Kanaka , Daniel Mercian , Maharaj Sandeep , Campbell Michael H. , Greaves Natalie , Guinto Renzo , Aruta John Jamir Benzon , Peñamante Criselle Angeline , Wray Britt , Lawrance Emma L.
Published: August 2023

As climate change continues unabated, research is increasingly focused on capturing and quantifying the lesser-known psychological responses and mental health implications of this humanitarian and environmental crisis. There has been a particular interest in the experiences of young people, who are more vulnerable for a range of reasons, including their developmental stage, the high rates of mental health conditions among this population, and their relative lack of agency to address climate threats. The different geographic and sociocultural settings in which people are coming of age afford certain opportunities and present distinct challenges and exposures to climate hazards. Understanding the diversity of lived experiences is vitally important for informing evidence-based, locally led psychosocial support and social and climate policies. In this Project Report we describe the design and implementation of the “Changing Worlds” study, focusing on our experiences and personal reflections as a transdisciplinary collaboration representing the UK, India, Trinidad and Tobago, Guyana, Barbados, the Philippines, and the USA. The project was conceived within the planetary health paradigm, aimed at characterizing and quantifying the impacts of human-mediated environmental systems changes on youth mental health and wellbeing. With input from local youth representatives, we designed and delivered a series of locally adapted surveys asking young people about their mental health and wellbeing, as well as their thoughts, emotions, and perceived agency in relation to the climate crisis and the global COVID-19 pandemic. This project report outlines the principles that guided the study design and describes the conceptual and practical hurdles we navigated as a distributed and interdisciplinary research collaboration working in different institutional, social, and research governance settings. Finally, we highlight lessons learned, specify our recommendations for other collaborative research projects in this space, and touch upon the next steps for our work. This project explicitly balances context sensitivity and the need for quantitative, globally comparable data on how youth are responding to and coping with environmental change, inspiring a new vision for a global community of practice on mental health in climate change.
Peptide-Based Vectors for Gene Delivery
Authors: Yang Juan , Luo Guo-Feng
Published: August 2023

Gene therapy is the ultimate therapeutic technology for diseases related to gene abnormality. However, the use of DNA alone has serious problems, such as poor stability and difficulty in entering target cells. The development of a safe and efficient gene delivery system is the cornerstone of gene therapy. Of particular interest, multifunctional peptides are rationally designed as non-viral vectors for efficient gene delivery. As components of gene delivery vectors, these peptides play critically important roles in skeleton construction, the implementation of targeting strategies, cell membrane penetration, endosome rupture, and nuclear transport. In recent years, the research of functional peptide-based gene delivery vectors has made important progress in improving transfection efficiency. The latest research progress and future development direction of peptide-based gene delivery vectors are reviewed in this paper.