bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineralogical Method as an Effective Way to Predict Gold Ore Types of Deposits in Platform Areas (East of the Siberian Platform)
Authors: Nikiforova Zinaida
Published: June 2024

The study of the mineralogical and geochemical features of placer gold and the mechanisms of its distribution in the territory east of the Siberian platform, overlain by a thick cover of Mesozoic–Cenozoic deposits, where traditional methods of searching for gold fields are not effective, allowed researchers, for the first time, to establish the stages of ore formation and to predict the types of gold deposits and their location. The identified indicators of placer gold (morphology, granulometry, chemical composition, micro-inclusions, and internal structures) indicate that ore occurrences in both the Precambrian and Mesozoic stages of ore formation were primary sources of placer gold. The identification of characteristic indicators in placer gold for certain types of gold deposits allowed researchers to prove the formation of gold ore sources east of the Siberian platform for the first time: low-sulfide quartz gold, gold–ferruginous quartzite, gold–copper–porphyry, and gold–platinoid formations are found in the Precambrian stage of ore formation and gold–silver, gold–sulfide–quartz, and gold–rare metal formations are found in the Mesozoic stages of ore formation. Thus, for the first time, based on a huge amount of factual material, it is proved that the mineralogical and geochemical features of placer gold carry enormous information about both the endogenous origin of gold (stages of ore formation—Precambrian and Mesozoic) and the expected type of formation of the predicted deposits. It is established that the predicted type of ore sources corresponds to a certain geological and structural position; this contributes to a more correct selection of methods for searching for ore and placer gold deposits in closed territories and assessing their prospects. In general, the application of the mineralogical method for the first time makes it possible to develop criteria for predicting resources and types of gold deposits, and to assess the prospects of gold mining potential in platform areas at a new level of knowledge.
The Effect of an Anionic Polyacrylamide on the Flotation of Chalcopyrite, Enargite, and Bornite
Authors: Jimenez Ginna , Cabrera Pablo , Rodriguez Angie , Cuervo Camilo , Gutierrez Leopoldo
Published: June 2024

Water recycling in mining is essential to decrease water usage, which results in the accumulation of high concentrations of inorganic and organic substances in the process water. Consequently, adverse impacts on the flotation process of copper sulfides may arise. High-molecular-weight polymers based on anionic polyacrylamides (PAMs) are used as tailing flocculants in mineral processing plants. The recirculation of water recovered from the tailing thickeners to the flotation process introduces residual PAMs, which can impact the flotation of important copper sulfides like chalcopyrite, bornite, and enargite. This issue has been rarely studied. In this work, results on the effect of an anionic polyacrylamide (PAM) of medium–low anionicity on the flotation of chalcopyrite, enargite, and bornite are reported and analyzed. The results show that PAM molecules depress the flotation of chalcopyrite, enargite, and bornite under a wide range of pH values. The experimental data indicate that the depressing effect of PAMs on copper sulfides increases with pH. The zeta potential results reveal that this parameter becomes less negative with the addition of PAMs, indicating interactions between PAM molecules and the surfaces of the copper sulfides. PAM adsorption on copper sulfides increases with pH, which correlates with the flotation and zeta potential data. It is proposed that the interactions between PAM molecules and copper sulfides are explained by the presence of surface iron and copper hydroxides that create chemically active adsorption sites.
Paleo-Sedimentary Environment and Formation Mechanism of the Organic-Rich Shale of the Permian Lucaogou Formation, Jimsar Sag, Junggar Basin, China
Authors: Zhao Zhongying , Lin Senhu , Luo Xia , Zhang Lijun
Published: June 2024

The Jimsar Sag is an important shale oil exploration target area in the Junggar Basin, northwestern China. The Permian Lucaogou Formation, with a thickness of 200–300 m, is the primary exploration target. High-frequency variation in lithology is a typical feature of the Lucaogou Formation, reflecting the fluctuation of the depositional environment and organic matter enrichment. The evolution of the depositional environment and accumulation mechanism of organic matter still need to be elucidated for the Lucaogou Formation. High-resolution sampling of the entire Lucaogou Formation was applied to a 248 m long core from Well JX in the Jimsar Sag to examine the depositional environment and organic matter enrichment. The findings unveiled that the Lucaogou Formation was deposited under a hot and arid climate, within the confines of a closed saline paleo-lake, where sediments endured an extended period of anoxic conditions, displayed periodic oscillations in paleo-temperature and paleo-salinity values over time, alongside a continuous rise in paleo-water depth. The predominant source lithology of the Lucaogou Formation is felsic igneous rock. Small-scale transgression and hydrothermal sedimentation occurred during the deposition of the Lucaogou Formation. The prevailing hot climate and enduring reducing environment fostered ideal circumstances for the enrichment of organic matter in the Lucaogou Formation. Due to different sedimentary environments and enrichment mechanisms, organic matter is enriched in two modes in the Lucaogou Formation.
Optimization of Flotation Conditions for Long-Flame Coal Mud by Response Surface Method
Authors: Ao Linfang , Zhang Hongbo , Zhang Jingkun , Li Guoping
Published: June 2024

With the application of modern coal mining technology and the fact that there are fewer and fewer high-quality coal seams, the quality enhancement and utilization of low-rank coal are gaining more and more attention. To solve the problems of high consumption of chemicals and low recovery of refined coal in the flotation separation process of low-rank coal, the long-flame coal from the Inner Mongolia Autonomous Region of China was selected as the research object, and the factors affecting the flotation process were analyzed and optimized by adopting the response surface method and establishing a regression model with high precision and reliability. The test results showed that the primary and secondary relationships of the factors on the fine coal yield were as follows: slurry concentration > frother dosage > collector dosage; and the primary and secondary relationships of the factors on the flotation refinement index were as follows: slurry concentration > collector dosage > frother dosage. The optimal conditions for flotation were 2453.09 g/t of collector, 795.84 g/t of frother, and 50.04 g/L of slurry concentration. Under these conditions, the fine coal yield was 51.51%, and the relative error of 53.71% was 4.27%. The flotation refinement index was 21.34%, and the relative error with the predicted value of 21.58% was 1.12%. The relative error of the experimental results was within a reasonable range, which indicated that the regression model obtained by the response surface method was highly reliable. The research results are of great significance to strengthen the comprehensive utilization of long-flame coal in full particle size and improve the economic benefits of coal enterprises.
Petrogenetic Implications of the Lithium-Rich Tongtianmiao Granite Pluton, South China: Evidence from Geochemistry and Geochronology
Authors: Yu Xinhui , Zhou Yongzhang , Cao Wei , Wang Hanyu , Zhang Can , Zhong Lifeng , Wei Wu , Wang Zhiqiang , Yao Jianying , Chen Zhiqiang , Xu Qinghe
Published: June 2024

The South China Block, a region renowned for its extensive granite distribution and rich metal deposits, serves as a natural laboratory for the study of granite-related mineralization. This research focuses on the Tongtianmiao granite pluton, which is located at the intersection of the Qin-Hang and Nanling metallogenic belts and has been confirmed as a significant lithium mineral resource. Despite its discovery and ongoing development, the lithium-rich Tongtianmiao pluton has been understudied, particularly concerning its petrogenesis, which has only recently come to the forefront of scientific inquiry. By integrating an array of petrogeochemical data with geochronological studies derived from zircon and monazite dating, this study provides insights into the magmatic processes related to lithium enrichment in the Tongtianmiao granites. The Tongtianmiao granites are classified as A-type granites characterized by high SiO2 contents (69.18–78.20 wt.%, average = 74.08 wt.%), K2O + Na2O contents (4.59–8.34 wt.%, average = 6.86 wt.%), A/CNK > 1.2, and low concentrations of Ca, Mg, and Fe. These granites are enriched in alkali metals such as Li, Rb, and Cs but are significantly depleted in Ba, Sr, and Eu. They show no significant fractionation of light or heavy rare-earth elements but present characteristic tetrad effects. A finding of this study is the identification of multiple ages from in situ zircon U–Pb dating, which implies a prolonged history of magmatic activity. However, given the high uranium content in zircons, which could render U–Pb ages unreliable, emphasis is placed on the monazite U–Pb ages. These ages cluster at approximately 172.1 ± 1.1 Ma and 167.9 ± 1.6 Ma, indicating a Middle Jurassic period of granite formation. This timing correlates with the retreat of the Pacific subduction plate and the associated NE-trending extensional fault activity, which likely provided favorable conditions for lithium enrichment. The study concluded that the Tongtianmiao granites were formed through partial melting of crustal materials and subsequent underplating by mantle-derived materials, and were contaminated by strata materials. This process resulted in the formation of highly differentiated granite through magmatic differentiation and external forces. These findings have significant implications for understanding the petrogenesis of lithium-rich granites and are expected to inform future exploration endeavors in the Tongtianmiao pluton.
Micromechanical Estimates Compared to FE-Based Methods for Modelling the Behaviour of Micro-Cracked Viscoelastic Materials
Authors: Abou Chakra Sarah , Bary Benoît , Lemarchand Eric , Bourcier Christophe , Granet Sylvie , Talandier Jean
Published: June 2024

The purpose of this study is to investigate the effective behaviour of a micro-cracked material whose matrix bulk and shear moduli are ruled by a linear viscoelastic Burgers model. The analysis includes a detailed study of randomly oriented and distributed cracks displaying an overall isotropic behaviour, as well as aligned cracks resulting in a transversely isotropic medium. Effective material properties are approximated with the assumption that the homogenized equivalent medium exhibits the characteristics of a Burgers model, leading to the identification of short-term and long-term homogenized modules in the Laplace–Carson space through simplified formulations. The crucial advantage of this analytical technique consists in avoiding calculations of the inverse Laplace–Carson transform. The micromechanical estimates are validated through comparisons with FE numerical simulations on 3D microstructures generated with zero-thickness void cracks of disc shape. Intersections between randomly oriented cracks are accounted for, thereby highlighting a potential percolation phenomenon. The effects of micro-cracks on the material’s behaviour are then studied with the aim of providing high-performance creep models for macrostructure calculations at a moderate computation cost through the application of analytical homogenization techniques.
Cell-Free Protein Expression by a Reconstituted Transcription–Translation System Energized by Sugar Catabolism
Authors: Sato Gaku , Miyazawa Shintaro , Doi Nobuhide , Fujiwara Kei
Published: June 2024

Cooperation between catabolism and anabolism is crucial for maintaining homeostasis in living cells. The most fundamental systems for catabolism and anabolism are the glycolysis of sugars and the transcription–translation (TX-TL) of DNA, respectively. Despite their importance in living cells, the in vitro reconstitution of their cooperation through purified factors has not been achieved, which hinders the elucidation of the design principle in living cells. Here, we reconstituted glycolysis using sugars and integrated it with the PURE system, a commercial in vitro TX-TL kit composed of purified factors. By optimizing key parameters, such as glucokinase and initial phosphate concentrations, we determined suitable conditions for their cooperation. The optimized system showed protein synthesis at up to 33% of that of the original PURE system. We observed that ATP consumption in upstream glycolysis inhibits TX-TL and that this inhibition can be alleviated by the co-addition of glycolytic intermediates, such as glyceraldehyde 3-phosphate, with glucose. Moreover, the system developed here simultaneously synthesizes a subset of its own enzymes, that is, glycolytic enzymes, in a single test tube, which is a necessary step toward self-replication. As glycolysis and TX-TL provide building blocks for constructing cells, the integrated system can be a fundamental material for reconstituting living cells from purified factors.
Analyzing Respiratory Sinus Arrhythmia: A Markov Chain Approach with Hypertensive Patients and Arachnophobic Individuals
Authors: Rodriguez-Torres Erika Elizabeth , Azpeitia-Cruz María Fernanda , Escamilla-Muñoz Jaqueline , Vázquez-Mendoza Isaac
Published: June 2024

Respiratory Sinus Arrhythmia (RSA) manifests as cyclic fluctuations in heart rate in synchrony with breathing. Gaining insights into the dynamics of RSA within the cardiac muscle functioning is crucial for comprehending its physiological and clinical significance. This study presents an analytical framework employing Markov chains to probe RSA patterns, with a specific emphasis on individuals with hypertension and arachnophobia. We delve into the concept of RSA and its potential cardiovascular implications, particularly among populations characterized by hypertension or normotension and fear of spiders. This study utilizes Markov chain modeling, an innovative method used to scrutinize RSA dynamics across diverse cohorts, with the aim of unveiling underlying patterns and mechanisms. This research contributes to the advancement of our understanding of RSA and its correlation with cardiac function across varied demographics, potentially guiding tailored diagnostic and therapeutic interventions. Our findings highlight significant disparities between hypertensive and normotensive participants, as well as spider-fearful individuals employing techniques to confront their fear compared with those without such strategies.
Transition Metal Oxide Nanomaterials: New Weapons to Boost Anti-Tumor Immunity Cycle
Authors: Liu Wanyi , Song Xueru , Jiang Qiong , Guo Wenqi , Liu Jiaqi , Chu Xiaoyuan , Lei Zengjie
Published: June 2024

Semiconductor nanomaterials have emerged as a significant factor in the advancement of tumor immunotherapy. This review discusses the potential of transition metal oxide (TMO) nanomaterials in the realm of anti-tumor immune modulation. These binary inorganic semiconductor compounds possess high electron mobility, extended ductility, and strong stability. Apart from being primary thermistor materials, they also serve as potent agents in enhancing the anti-tumor immunity cycle. The diverse metal oxidation states of TMOs result in a range of electronic properties, from metallicity to wide-bandgap insulating behavior. Notably, titanium oxide, manganese oxide, iron oxide, zinc oxide, and copper oxide have garnered interest due to their presence in tumor tissues and potential therapeutic implications. These nanoparticles (NPs) kickstart the tumor immunity cycle by inducing immunogenic cell death (ICD), prompting the release of ICD and tumor-associated antigens (TAAs) and working in conjunction with various therapies to trigger dendritic cell (DC) maturation, T cell response, and infiltration. Furthermore, they can alter the tumor microenvironment (TME) by reprogramming immunosuppressive tumor-associated macrophages into an inflammatory state, thereby impeding tumor growth. This review aims to bring attention to the research community regarding the diversity and significance of TMOs in the tumor immunity cycle, while also underscoring the potential and challenges associated with using TMOs in tumor immunotherapy.
Hybrid Organic–Si C-MOSFET Image Sensor Designed with Blue-, Green-, and Red-Sensitive Organic Photodiodes on Si C-MOSFET-Based Photo Signal Sensor Circuit
Authors: Jeong Ui-Hyun , Park Joo-Hyeong , Choi Ji-Ho , Lee Woo-Guk , Park Jea-Gun
Published: June 2024

The resolution of Si complementary metal–oxide–semiconductor field-effect transistor (C-MOSFET) image sensors (CISs) has been intensively enhanced to follow the technological revolution of smartphones, AI devices, autonomous cars, robots, and drones, approaching the physical and material limits of a resolution increase in conventional Si CISs because of the low quantum efficiency (i.e., ~40%) and aperture ratio (i.e., ~60%). As a novel solution, a hybrid organic–Si image sensor was developed by implementing B, G, and R organic photodiodes on four n-MOSFETs for photocurrent sensing. Photosensitive organic donor and acceptor materials were designed with cost-effective small molecules, i.e., the B, G, and R donor and acceptor small molecules were Coumarin6 and C_60, DMQA and MePTC, and ZnPc and TiOPc, respectively. The output voltage sensing margins (i.e., photocurrent signal difference) of the hybrid organic–Si B, G, and R image sensor pixels presented results 17, 11, and 37% higher than those of conventional Si CISs. In addition, the hybrid organic–Si B, G, and R image sensor pixels could achieve an ideal aperture ratio (i.e., ~100%) compared with a Si CIS pixel using the backside illumination process (i.e., ~60%). Moreover, they may display a lower fabrication cost than image sensors because of the simple image sensor structure (i.e., hybrid organic–Si photodiode with four n-MOSFETs).
Assessment of Special Rubberized Concrete Types Utilizing Portable Non-Destructive Tests
Authors: El-Nemr Amr , Shaaban Ibrahim G.
Published: June 2024

Concrete is the second most common material demanded over the world. Recently, a trending issue is the vast tracking in constructing infrastructure to ensure traffic movement and life quality. Concrete types such as self and rolled compacted concrete offer magical solutions ensuring vast infrastructure and life quality. However, these structures must be assessed using non-destructive testing methods to observe the difference between the concrete types. Several studies have used recycled waste, specifically the crumb rubber extracted from old tires, as a potential replacement for natural aggregate in concrete manufacturing. However, limited research has been devoted to nondestructive testing of produced concrete to further evaluate existing concrete elements containing crumb rubber. This study investigates the self and rolled compacted concrete in comparison with normal ones, in addition to using chopped rubber as recycled materials. This study examines the concrete manufactured destructively by evaluating its compressive, tensile, and flexural strength, in addition to impact resistance, and correlates those results with the non-destructive such as Schmit hammer and Ultrasonic Pulse (UPV) for extended utilization of the concrete produced and data publication. The results showed unique performance and a high potential for data contribution to the extensive utilization of self-compacted rubberized concrete and rolled compacted concrete.
Telmisartan Reduces LPS-Mediated Inflammation and Induces Autophagy of Microglia
Authors: Affram Kwame O. , Janatpour Zachary C. , Shanbhag Nagesh , Villapol Sonia , Symes Aviva J.
Published: June 2024

Background: Chronic neuroinflammation mediated by persistent microglial activation is strongly linked to neurodegeneration. Therefore, targeting microglial activation could be beneficial in treating neurodegenerative disorders. Angiotensin receptor blockers (ARBs), commonly prescribed for high blood pressure, exhibit prominent anti-inflammatory effects in the brain and are considered potential therapies for neurodegenerative diseases and neurotrauma. Although all ARBs are angiotensin II receptor type I antagonists, some ARBs act through other signaling pathways, allowing for multiple mechanisms of action. The anti-inflammatory mechanisms of ARBs are not well understood. Methods: In this study, we compared eight different FDA-approved ARBs for their ability to reduce the LPS stimulation of primary microglia or BV2 cells through analyses of nitric oxide production, reactive oxygen species generation, and the mRNA of proinflammatory cytokines. Finding specific and unique effects of telmisartan, we interrogated signaling pathways and other downstream effectors of telmisartan activity on microglia. Results: Our findings indicate that telmisartan showed the greatest efficacy in reducing the LPS induction of reactive oxygen species (ROS) and nitric oxide production in microglia. Uniquely amongst ARBs, telmisartan activated AMPK phosphorylation and inhibited mTOR phosphorylation. Telmisartan’s anti-inflammatory activity was partially inhibited by the AMPK inhibitor compound C. Furthermore, telmisartan uniquely induced markers of autophagy in microglia through an AMPK–mTOR–autophagy pathway. Telmisartan also reduced microglial viability. Telmisartan’s cytotoxicity was partially ameliorated by an autophagy inhibitor and a pan-caspase inhibitor, indicating a link between microglial autophagy and apoptosis. Conclusions: We conclude that telmisartan has unique properties relative to other ARBs, including potent anti-inflammatory actions and an induction of microglial autophagy, which may enable specific therapeutic uses.
Placebo and Nocebo Effects on Sports and Exercise Performance: A Systematic Literature Review Update
Authors: Chhabra Bhavya , Szabo Attila
Published: June 2024

Sports performance could be affected by placebo and nocebo effects. The last literature review on placebo and nocebo effects on sports and exercise performance was published in 2019. In the past five years, several new studies have been published. This review aimed to update the previous synthesis and evaluate the results of new studies focusing on placebo or nocebo interventions in sports and exercise by determining the form and magnitude of their effect. Hence, we searched for empirical studies published from 2019 until the end of May 2024 indexed in PubMed, Medline, Web of Science, EBSCO, and Google Scholar databases. The search yielded 20 eligible studies with control or baseline-control conditions, focusing on nutritional, mechanical, and other mixed ergogenic aids. They yielded small to large placebo effects (Cohen’s d) for nutritional (d = 0.86), mechanical (d = 0.38), cream and gel (d = 0.05), and open-label placebo (d = 0.16) interventions. The pooled effect size for placebo effects was moderate to large (d = 0.67), larger than in the earlier review, suggesting that placebo effects can improve motor performance even more than previously reported. However, based on five measures from three studies, the nocebo effects were almost twice as large (d = 1.20). Accordingly, the current findings support and expand the last review in the field by yielding additional support for placebo and nocebo effects in sports and exercise.
New Findings Regarding the Effects of Selected Blue Food Colorants (Genipin, Patent Blue V, and Brilliant Blue FCF) on the Hemostatic Properties of Blood Components In Vitro
Authors: Olas Beata , Kontek Bogdan , Sławińska Natalia , Białecki Jacek
Published: June 2024

Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants—genipin, patent blue V, and brilliant blue FCF—on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1–200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.
Exploring the Influence of Acid-Base Status on Athletic Performance during Simulated Three-Day 400 m Race
Authors: Chiron François , Erblang Mégane , Gulören Bora , Bredariol Federica , Hamri Imad , Leger Damien , Hanon Christine , Tiollier Eve , Thomas Claire
Published: June 2024

This study aimed to investigate the ability of highly trained athletes to consistently perform at their highest level during a simulated three-day 400 m race and to examine the impact of an alkaline diet associated with chronic consumption of bicarbonate-rich water or placebo on their blood metabolic responses before and after the three races. Twenty-two highly trained athletes, divided into two groups—one with an alkalizing diet and placebo water (PLA) and the other with an alkalizing diet and bicarbonate-rich water (BIC)—performed a 400 m race for three consecutive days. Performance metrics, urine and blood samples assessing acid-base balance, and indirect markers of neuro-muscular fatigue were measured before and after each 400 m race. The evolution of the Potential Renal Acid Load (PRAL) index and urinary pH highlights the combination of an alkalizing diet and bicarbonate-rich hydration, modifying the acid-base state (p < 0.05). Athletes in the PLA group replicated the same level of performance during three consecutive daily races without an increase in fatigue-associated markers. Athletes experienced similar levels of metabolic perturbations during the three 400 m races, with improved lactate clearance 20 min after the third race compared to the first two (p < 0.05). This optimization of the buffering capacity through ecological alkaline nutrition and hydration allowed athletes in the BIC group to improve their performance during the third 400 m race (p < 0.01). This study highlights athletes’ ability to replicate high-level performances over three consecutive days with the same extreme level of metabolic disturbances, and an alkaline diet combined with bicarbonate-rich water consumption appears to enhance performance in a 400 m race.
Modulation of Gut Microbiome and Autism Symptoms of ASD Children Supplemented with Biological Response Modifier: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study
Authors: Hrnciarova Jela , Kubelkova Klara , Bostik Vanda , Rychlik Ivan , Karasova Daniela , Babak Vladimir , Datkova Magdalena , Simackova Katerina , Macela Ales
Published: June 2024

The etiology and mechanisms of autism and autism spectrum disorder (ASD) are not yet fully understood. There is currently no treatment for ASD for providing significant improvement in core symptoms. Recent studies suggest, however, that ASD is associated with gut dysbiosis, indicating that modulation of gut microbiota in children with ASD may thus reduce the manifestation of ASD symptoms. The aim of this pilot study (prospective randomized, double-blinded, placebo-controlled) was to evaluate efficacy of the biological response modifier Juvenil in modulating the microbiome of children with ASD and, in particular, whether Juvenil is able to alleviate the symptoms of ASD. In total, 20 children with ASD and 12 neurotypical children were included in our study. Supplementation of ASD children lasted for three months. To confirm Juvenil’s impact on the gut microbiome, stool samples were collected from all children and the microbiome’s composition was analyzed. This pilot study demonstrated that the gut microbiome of ASD children differed significantly from that of healthy controls and was converted by Juvenil supplementation toward a more neurotypical microbiome that positively modulated children’s autism symptoms.
Single-Cell Assessment of Human Stem Cell-Derived Mesolimbic Models and Their Responses to Substances of Abuse
Authors: Rudibaugh Thomas P. , Tam Ryan W. , Estridge R. Chris , Stuppy Samantha R. , Keung Albert J.
Published: June 2024

The mesolimbic pathway connects ventral tegmental area dopaminergic neurons and striatal medium spiny neurons, playing a critical role in reward and stress behaviors. Exposure to substances of abuse during development and adulthood has been linked to adverse outcomes and molecular changes. The rise of human cell repositories and whole-genome sequences enables human functional genomics ‘in a dish’, offering insights into human-specific responses to substances of abuse. Continued development of new models is needed, and the characterization of in vitro models is also necessary to ensure appropriate experimental designs and the accurate interpretation of results. This study introduces new culture conditions for generating medium spiny neurons and dopaminergic neurons with an early common media, allowing for coculture and assembloid generation. It then provides a comprehensive characterization of these and prior models and their responses to substances of abuse. Single-cell analysis reveals cell-type-specific transcriptomic responses to dopamine, cocaine, and morphine, including compound and cell-type-specific transcriptomic signatures related to neuroinflammation and alterations in signaling pathways. These findings offer a resource for future genomics studies leveraging human stem cell-derived models.
MultiTEP-Based Vaccines Targeting SARS-CoV-2 Spike Protein IgG Epitopes Elicit Robust Binding Antibody Titers with Limited Virus-Neutralizing Activity
Authors: Antonyan Tatevik , Chilingaryan Garri , Zagorski Karen , Ghazaryan Manush , Hovakimyan Armine , Davtyan Hayk , Petrushina Irina , King Olga , Kniazev Roman , Petrovsky Nikolai , Ghochikyan Anahit
Published: June 2024

Within the last two decades, SARS-CoV-2 was the third zoonotic severe acute respiratory betacoronavirus (sarbecovirus) to infect humans, following SARS and MERS. The disruptions caused by the pandemic underscore the need for a universal vaccine against respiratory betacoronaviruses. Our group previously developed the universal platform for vaccine development, MultiTEP, which has been utilized in this study to generate a range of SARS-CoV-2 epitope vaccine candidates. We prepared and characterized 18 vaccines incorporating small peptide fragments from SARS-CoV-2 Spike protein fused with the MultiTEP sequence using overlapping PCR. Wild-type mice were immunized intramuscularly with the immunogen formulated in AdvaxCpG adjuvant. Serum antibodies were detected by ELISA, surrogate neutralization, and pseudovirus neutralization assays. Finally, the most promising vaccine candidate was administered to three non-human primates. All vaccines generated high titers of spike-binding IgG antibodies. However, only three vaccines generated antibodies that blocked RBD binding to the ACE2 receptor in a surrogate virus neutralization assay. However, none of the vaccines induced antibodies able to neutralize pseudotype viruses, including after the administration of the lead vaccine to NHPs. MultiTEP-based COVID-19 vaccines elicited robust, IgG-binding responses against the Spike protein in mice and non-human primates, but these antibodies were not neutralizing, underscoring the need to refine this approach further.
Epidemiological Characterization and Genetic Variation of the SARS-CoV-2 Delta Variant in Palestine
Authors: Ereqat Suheir , Alikhan Nabil-Fareed , Al-Jawabreh Amer , Matthews Michaela , Al-Jawabreh Ahmed , de Oliveira Martins Leonardo , Trotter Alexander J. , Al-Kaila Mai , Page Andrew J. , Pallen Mark J. , Nasereddin Abedelmajeed
Published: June 2024

The emergence of new SARS-CoV-2 variants in Palestine highlights the need for continuous genetic surveillance and accurate screening strategies. This case series study aimed to investigate the geographic distribution and genetic variation of the SARS-CoV-2 Delta Variant in Palestine in August 2021. Samples were collected at random in August 2021 (n = 571) from eight districts in the West Bank, Palestine. All samples were confirmed as positive for COVID-19 by RT-PCR. The samples passed the quality control test and were successfully sequenced using the ARTIC protocol. The Delta Variant was revealed to have four dominant lineages: B.1.617 (19%), AY.122 (18%), AY.106 (17%), and AY.121 (13%). The study revealed eight significant purely spatial clusters (p < 0.005) distributed in the northern and southern parts of Palestine. Phylogenetic analysis of SARS-CoV-2 genomes (n = 552) showed no geographically specific clades. The haplotype network revealed three haplogroups without any geographic distribution. Chronologically, the Delta Variant peak in Palestine was shortly preceded by the one in the neighboring Israeli community and shortly followed by the peak in Jordan. In addition, the study revealed an extremely intense transmission network of the Delta Variant circulating between the Palestinian districts as hubs (SHR ≈ 0.5), with Al-Khalil, the district with the highest prevalence of COVID-19, witnessing the highest frequency of transitions. Genetic diversity analysis indicated closely related haplogroups, as haplotype diversity (Hd) is high but has low nucleotide diversity (π). However, nucleotide diversity (π) in Palestine is still higher than the global figures. Neutrality tests were significantly (p < 0.05) low, including Tajima’s D, Fu-Li’s F, and Fu-Li’s D, suggesting one or more of the following: population expansion, selective sweep, and natural negative selection. Wright’s F-statistic (Fst) showed genetic differentiation (Fst > 0.25) with low to medium gene flow (Nm). Recombination events were minimal between clusters (Rm) and between adjacent sites (Rs). The study confirms the utility of the whole genome sequence as a surveillance system to track the emergence of new SARS-CoV-2 variants for any possible geographical association and the use of genetic variation analysis and haplotype networking to delineate any minimal change or slight deviation in the viral genome from a reference strain.
Humoral Immune Response in Immunized Sheep with Bovine Coronavirus Glycoproteins Delivered via an Adenoviral Vector
Authors: Pratelli Annamaria , Capozza Paolo , Minesso Sergio , Lucente Maria Stella , Pellegrini Francesco , Tempesta Maria , Franceschi Valentina , Buonavoglia Canio , Donofrio Gaetano
Published: June 2024

Bovine coronavirus (BCoV) is distributed globally and mainly causes different clinical manifestations: enteric diarrhea in calves, winter dysentery in adults, and respiratory symptoms in cattle of all ages. Low mortality and high morbidity are the hallmarks of BCoV infection, usually associated with substantial economic losses for the livestock industry. Vaccination, combined with the implementation of biosecurity measures, is the key strategy for the prevention of infections. This pilot study evaluates the immunogenicity of a recombinant vaccine containing two BCoV antigens (S and M) in sheep, compared to vaccines containing only the M or S protein. Three groups of sheep were inoculated intramuscularly at day 0 and day 21 with recombinant adenoviruses expressing BCoV S protein (AdV-BCoV-S), BCoV M protein (AdV-BCoV-M), or both proteins (AdV-BCoV-S + M). Serum antibodies were evaluated using immunofluorescence (IF) and serum neutralization (SN) tests. Moderate seroconversion was observed by day 21, but serum antibodies detected via SN increased from 1:27.5 (day 21) to 1:90 (day 28) in sheep inoculated with the recombinant AdV expressing both the S- and M-BCoV proteins. Based on the SN results, a repeated-measures ANOVA test indicated a more significant difference in immune response between the three groups (F = 20.47; p < 0.001). The experimental investigation produced satisfactory results, highlighting that the S + M recombinant vaccine was immunogenic, stimulating a valid immune response. Despite some inherent limitations, including a small sample size and the absence of challenge tests, the study demonstrated the efficacy of the immune response induced via the recombinant vaccine containing both S and M proteins compared to that induced via the individual proteins S or M.
Evaluation of Three Different Selective Media for Enumeration of Clostridium perfringens in Untreated and Treated Wastewater
Authors: Karon A. J. , Bailey Emily S. , Sobsey Mark D.
Published: June 2024

Current and emerging legislation in North Carolina and other regions calls for the enumeration of Clostridium perfringens as a surrogate indicator for protozoan parasites in various types of waters. Past studies that have evaluated selective media for the detection of this bacterium have provided limited, conflicting, and inconclusive results. In this study, membrane filtration was used to enumerate C. perfringens as culturable spores or total culturable cells in 19 samples of untreated and 25 samples of partially treated wastewaters on 3 candidate media, Tryptose Sulfite Cycloserine Agar (TSC), CP ChromoSelect Agar (CPCS), and membrane Clostridium perfringens Agar (m-CP) in parallel, and the results were compared. Presumptive isolates from each agar were further subjected to phenotypic confirmation tests for acid phosphatase production and stormy fermentation to further determine the performance of each agar. The CPCS agar was determined to have the highest enumerative capacity of total C. perfringens cells when compared to both TSC agar and m-CP agar (p-value < 0.05), but there was no significant difference in its ability to detect spores when compared to TSC agar (p-value > 0.05). The overall specificity of CPCS agar as determined by agreement of results from both confirmation tests was 0.81, while the specificity of TSC agar was only 0.28. Based on its performance, ease of preparation and use and consistency of colony characteristics, CPCS agar is recommended as the preferred medium for C. perfringens enumeration in wastewater.
Pharmacological Activation of SIRT3 Modulates the Response of Cancer Cells to Acidic pH
Authors: Aventaggiato Michele , Arcangeli Tania , Vernucci Enza , Barreca Federica , Sansone Luigi , Pellegrini Laura , Pontemezzo Elena , Valente Sergio , Fioravanti Rossella , Russo Matteo Antonio , Mai Antonello , Tafani Marco
Published: June 2024

Cancer cells modulate their metabolism, creating an acidic microenvironment that, in turn, can favor tumor progression and chemotherapy resistance. Tumor cells adopt strategies to survive a drop in extracellular pH (pHe). In the present manuscript, we investigated the contribution of mitochondrial sirtuin 3 (SIRT3) to the adaptation and survival of cancer cells to a low pHe. SIRT3-overexpressing and silenced breast cancer cells MDA-MB-231 and human embryonic kidney HEK293 cells were grown in buffered and unbuffered media at pH 7.4 and 6.8 for different times. mRNA expression of SIRT3 and CAVB, was measured by RT-PCR. Protein expression of SIRT3, CAVB and autophagy proteins was estimated by western blot. SIRT3-CAVB interaction was determined by immunoprecipitation and proximity ligation assays (PLA). Induction of autophagy was studied by western blot and TEM. SIRT3 overexpression increases the survival of both cell lines. Moreover, we demonstrated that SIRT3 controls intracellular pH (pHi) through the regulation of mitochondrial carbonic anhydrase VB (CAVB). Interestingly, we obtained similar results by using MC2791, a new SIRT3 activator. Our results point to the possibility of modulating SIRT3 to decrease the response and resistance of tumor cells to the acidic microenvironment and ameliorate the effectiveness of anticancer therapy.
Efficacy and Safety of Pharmacological Treatment in Patients with Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis
Authors: Zhu He , Wen Bei , Xu Jijun , Zhang Yuelun , Xu Li , Huang Yuguang
Published: June 2024

Complex regional pain syndrome (CRPS) is a disabling condition that usually affects the extremities after trauma or surgery. At present, there is no FDA-approved pharmacological treatment for patients with CRPS. We performed this systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological therapies and determine the best strategy for CRPS. We searched the databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov, for published eligible randomized controlled trials (RCTs) comparing pharmacological treatment with placebo in CRPS patients. Target patients were diagnosed with CRPS according to Budapest Criteria in 2012 or the 1994 consensus-based IASP CRPS criteria. Finally, 23 RCTs comprising 1029 patients were included. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty (confidence in evidence and quality of evidence). Direct meta-analysis showed that using bisphosphonates (BPs) (mean difference [MD] −2.21, 95% CI −4.36–−0.06, p = 0.04, moderate certainty) or ketamine (mean difference [MD] −0.78, 95% CI −1.51–−0.05, p = 0.04, low certainty) could provide long-term (beyond one month) pain relief. However, there was no statistically significant difference in the efficacy of short-term pain relief. Ketamine (rank p = 0.55) and BPs (rank p = 0.61) appeared to be the best strategies for CRPS pain relief. Additionally, BPs (risk ratio [RR] = 1.86, 95% CI 1.34–2.57, p < 0.01, moderate certainty) and ketamine (risk ratio [RR] = 3.45, 95% CI 1.79–6.65, p < 0.01, moderate certainty) caused more adverse events, which were mild, and no special intervention was required. In summary, among pharmacological interventions, ketamine and bisphosphonate injection seemed to be the best treatment for CRPS without severe adverse events.
The Antimicrobial Effect of Cornus mas L. and Sorbus aucuparia L. Fruit Extracts against Resistant Uropathogens in Correlation with the Prevalence of Urinary Tract Infections in Companion Animals
Authors: Aurori Mara , Novac Cristiana Ștefania , Nadăș George Cosmin , Crăciun Smaranda , Fiţ Nicodim , Andrei Sanda
Published: June 2024

Urinary tract infections (UTIs) are a widespread condition in pets, with many antibiotics being prescribed, contributing to the rise in antimicrobial resistance, which is a worldwide threat. This study’s main objective was to analyze the in vitro antimicrobial activity of Cornus mas and Sorbus aucuparia fruit hydro-ethanolic extracts towards bacteria identified in the urine of companion animals experiencing UTIs. Urine samples were collected from dogs and cats (n = 83; 47 negative, 36 positive); several bacterial strains were identified (n = 49) belonging to the Escherichia, Enterococcus, Staphylococcus, Proteus, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter, Leclercia, and Kocuria genera. Bacterial susceptibility was tested using the disk diffusion method, with the majority being resistant to several beta-lactams, quinolones, trimethoprim/sulfamethoxazole, and nitrofurantoin. Subsequently, 13 resistant isolates were selected to evaluate the fruits extracts’ antimicrobial potential using the agar well diffusion and broth microdilution methods. Cornus mas exhibited the greatest activity against Gram-negatives (primarily Pseudomonas luteola), while Sorbus aucuparia showed maximum effects towards Gram-positives (particularly Enterococcus faecalis). The MIC was 0.01 μg/μL for both extracts; the MBC was 0.08 μg/μL for Cornus mas and 0.05 μg/μL for Sorbus aucuparia. However, Cornus mas showed a stronger bactericidal effect. This is the first study to investigate these fruit extracts in UTI isolates of companion animals, and these extracts might be used as substitutes or adjuvants for antibiotics, thus contributing to a reduction in antimicrobial resistance.
Descriptive Analysis of Adverse Events Reported for New Multiple Myeloma Medications Using FDA Adverse Event Reporting System (FAERS) Databases from 2015 to 2022
Authors: Alrasheed Marwan A. , Alamer Khalid A. , Albishi Mashael , Alsuhibani Abdulrahman A. , Almohammed Omar A. , Alwhaibi Abdulrahman , Almajed Abdullah N. , Guo Jeff J.
Published: June 2024

Background: New multiple myeloma (MM) medications have revolutionized the treatment landscape, but they are also associated with a range of adverse events (AEs). This study aims to provide a comprehensive overview of AEs reported for four new MM medications: daratumumab, ixazomib, elotuzumab, and panobinostat. Methods: This study uses a descriptive retrospective approach to analyze the FDA Adverse Event Reporting System (FAERS) from 2015 to 2022. It includes variables like medication names, report details, patient demographics, adverse events, and reporter types. The initial dataset consists of over 3700 adverse events, which are categorized into 21 groups for clarity and comparison. Results: The FAERS database revealed 367,756 adverse events (AEs) associated with novel multiple myeloma drugs from 2015–2022. Ixazomib had the highest number of reported AEs with 206,243 reports, followed by daratumumab with 98,872 reports, then elotuzumab with 26,193 AEs. Ixazomib’s AE reports increased dramatically over the study period, rising approximately 51-fold from 1183 in 2015 to 60,835 in 2022. Of the medications studied, ixazomib also recorded the highest number of deaths (24,206), followed by daratumumab (11,624), panobinostat (7227), and elotuzumab (3349). The majority of AEs occurred in patients aged 55–64 and 65–74 years. Conclusions: Ixazomib, a new MM medication, had the highest number of AEs reported. Also, it has the highest rate of reported deaths compared to other new MM medications. Clinicians should be aware of the potential AEs associated with this medication and further research is needed to understand the reasons for the high number of AEs and to develop mitigation strategies. More attention should also be paid to the safety of new multiple myeloma medications in younger patients.