bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Nuclear-Centric Scenarios for Ukraine’s Low-Carbon Energy Transition Using Diffusion and Regression Techniques
Authors: Denysov Viktor , Kulyk Mykhailo , Babak Vitalii , Zaporozhets Artur , Kostenko Ganna
Published: October 2024

This study presents a mathematical model for forecasting the development of Ukraine’s Integrated Power System (IPS) until 2040, with a specific focus on the expansion of nuclear energy as a cornerstone of the nation’s low-carbon transition. The model is an extension of Frank Bass’s mixed influence diffusion model, incorporating both economic and technological factors. These factors are treated as stochastic variables essential for accurately predicting the evolution of an integrated energy system, particularly in the context of rapid renewable energy sources (RES) growth. The model employs regression techniques using generalized logistic curves, improving forecasting efficiency by aligning modeling parameters with experimental data. The study’s results indicate the potential for optimizing IPS components, including nuclear and thermal power generation, through the model’s application. The model is distinguished by its inclusion of economic and technological impacts, such as state matrices, control actions, and external influence matrices, which enhance the accuracy of simulations and predictions. The validation of the model, based on scenarios of electricity consumption and generation, shows significant alignment with observed trends, confirming the model’s reliability. The findings suggest that this model is an effective tool for developing and refining energy system scenarios, with nuclear energy playing a pivotal role in Ukraine’s sustainable energy future.
An Experimental Study of Boiling Heat Transfer and Quench Front Propagation Velocity During Quenching of a Cylinder Rod in Subcooled Water
Authors: Sun Yuanyang , Jian Huanyan , Xiong Ping , Zhou Linglan
Published: October 2024

In this study, a quenching experiment was conducted at atmospheric pressure to investigate the flow and heat-transfer characteristics of cylindrical rods made from SS, FeCrAl, and Zr-4 under various subcooling degrees (ΔTsub). The inverse heat-conduction problem (IHCP) method and image-processing technique were utilized to determine the surface temperature and heat flux, vapor film thickness, and quench front propagation. The results show that smaller solid kρcp and larger ΔTsub result in relatively more efficient quenching boiling heat transfer, thinner vapor film thickness, and greater quench front propagation velocity. The quench front originates at the bottom of the test specimen and becomes progressively larger in velocity with time. It eventually converges with the downward-propagating quench front in the upper middle of the test specimen. Moreover, at the beginning of quench front propagation, the SS and FeCrAl test specimens have a constant velocity region. However, because the Zr-4 test specimen has a small kρcp, the velocities gradually increase from the onset of quench front generation. Furthermore, the measured average quench front velocities are consistent with the experimental datum from the literature. However, the predicted model proposed by Duffey underestimates the propagation velocity due to ignoring the cooling effect of film boiling.
Rubber-Based Agroforestry Ecosystems Enhance Soil Enzyme Activity but Exacerbate Microbial Nutrient Limitations
Authors: Xu Wenxian , Zhang Yingying , Tahir Ashar , Cao Yumiao , Kuang Changgeng , Guo Xinwei , Sun Rui , Liu Wenjie , Wu Zhixiang , Yang Qiu
Published: October 2024

Agroforestry ecosystems are an efficient strategy for enhancing soil nutrient conditions and sustainable agricultural development. Soil extracellular enzymes (EEAs) are important drivers of biogeochemical processes. However, changes in EEAs and chemometrics in rubber-based agroforestry systems and their mechanisms of action are still not fully understood. Distribution of EEAs, enzymatic stoichiometry, and microbial nutrient limitation characteristics of rubber plantations under seven planting patterns (RM, rubber monoculture system; AOM, Hevea brasiliensis-Alpinia oxyphylla Miq; PAR, Hevea brasiliensis-Pandanus amaryllifolius Roxb; AKH, Hevea brasiliensis-Alpinia katsumadai Hayata; CAA, Hevea brasiliensis-Coffea Arabica; CCA, Hevea brasiliensis-Cinnamomum cassia (L.) D. Don, and TCA, Hevea brasiliensis-Theobroma Cacao) were analyzed to investigate the metabolic limitations of microorganisms and to identify the primary determinants that restrict nutrient limitation. Compared with rubber monoculture systems, agroforestry ecosystems show increased carbon (C)-acquiring enzyme (EEAC), nitrogen (N)-acquiring enzyme (EEAN), and phosphorus (P)-acquiring enzyme (EEAP) activities. The ecoenzymatic stoichiometry model demonstrated that all seven plantation patterns experienced C and N limitation. Compared to the rubber monoculture system, all agroforestry systems exacerbated the microbial limitations of C and N by reducing the vector angle and increasing vector length. P limitation was not detected in any plantation pattern. In agroforestry systems, progression from herbs to shrubs to trees through intercropping results in a reduction in soil microbial nutrient constraints. This is primarily because of the accumulation of litter and root biomass in tree-based systems, which enhances the soil nutrient content (e.g., soil organic carbon, total nitrogen, total phosphorus, and ammonium nitrogen) and accessibility. Conversely, as soil depth increased, microbial nutrient limitations tended to become more pronounced. Partial least squares path modelling (PLS-PM) indicated that nutrient ratios and soil total nutrient content were the most important factors influencing microbial C limitation (−0.46 and 0.40) and N limitation (−0.30 and −0.42). This study presented novel evidence regarding the constraints and drivers of soil microbial metabolism in rubber agroforestry systems. Considering the constraints of soil nutrients and microbial metabolism, intercropping of rubber trees with arboreal species is recommended over that of herbaceous species to better suit the soil environment of rubber plantation areas on Hainan Island.
Carbon Stock Estimation of Poplar Plantations Based on Additive Biomass Models
Authors: Yin Minglong , Gao Ting , Zhao Yuhao , Ni Ruiqiang , Zheng Peijin , Zhao Yuyao , Zhang Jinshan , Li Kun , Li Chuanrong
Published: October 2024

Accurate estimation of biomass and carbon stocks in forest ecosystems is critical for understanding their roles in carbon sequestration and climate change mitigation. Currently, the development of stand biomass models and carbon stock estimation at the regional scale has emerged as a prominent research priority. In this study, 225 Populus spp. (poplar) trees in Shandong Province, China, were destructively sampled to obtain the biomass of their components. Two models (MS1 and MS2) were developed using allometric equations and the seemingly unrelated regression (SUR) method to ensure additive properties across tree components. The model evaluation employed the leave-one-out jackknife (LOO) method, considering statistics such as adjusted R-squared (Ra2), root mean square error (RMSE), mean absolute percent error (MAPE), and mean absolute error (MAE). The results from our models demonstrated high accuracy, with MS2 slightly outperforming MS1 after incorporating tree height as an independent variable. The models reliably estimated component-specific biomass and carbon stocks, with distinct variations observed in the carbon content among foliage (47.14 ± 2.07%), branches (47.26 ± 2.48%), stems (47.67 ± 2.21%), and roots (46.37 ± 2.78%). Carbon stocks in poplar plantations increased with the diameter class, ranging from 5 to 35 cm and correspondingly from 3.670 to 172.491 Mg C ha−1. As the diameter class increases, the carbon allocation strategy of poplars aligns with the CSR strategy, transitioning from prioritizing growth competition to emphasizing self-stabilization. Our research proposes a robust framework for assessing biomass and carbon stocks in poplar plantations, which is essential for evidence-based forest management strategies.
Menthol-Based Extraction of Fragile Wooden Coffin Lid (7–10th Centuries CE) in Laboratory Archaeology Excavation
Authors: Liu Yong , Chen Jiake , Li Cunxin , Han Xiangna , Wang Hao , Bai Jinsong , Liu Xiaohua
Published: October 2024

Block lifting is a key step in stabilizing and removing fragile remains at archaeological excavation sites. Due to its favorable working properties and adhesive effect, menthol has recently been proposed as a volatile binding medium for temporary consolidation in archaeological conservation. This paper presents a case study on the use of menthol in the extraction and restoration of a large wooden coffin lid, approximately 1.9 m long and 0.9 m wide, from tomb 11 (M11) at Xie’ertala, located east of a Xie’ertala town in Hailar City, Inner Mongolia, dating to the 7th to 10th centuries CE. This coffin lid had fragmented into numerous wooden pieces, and was preserved in a relatively arid steppe environment, necessitating the extraction of the lid as a consolidated block. The use of menthol for consolidating and lifting the highly fragmented wooden coffin lid was intended to preserve critical archaeological information while avoiding damage to the underlying objects. An analysis of the physicochemical properties of these wooden remains suggests that the timber used for the coffin lid belongs to a common pine species from the Hulunbuir region. The degradation of the coffin lid was relatively mild, as shown by Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscope (SEM) results. Dynamic Vapor Sorption (DVS) tests indicated that the hygroscopicity of the archaeological wood was 23.4%, compared to 21.1% for the reference sample, demonstrating good environmental stability. The safety of menthol as a treatment for fragile wooden remains was evaluated by comparing changes in the morphological and porosity characteristics of the coffin lid before and after menthol treatment. After treatment, the widths of the fissures remained largely unchanged, with all relative variations being less than 1%, and the porosity as well as pore size distribution of the wood showed negligible changes. Gas Chromatography–Mass Spectrometry (GC-MS) results showed that only 0.6% of menthol residue remained after 8 days of sublimation. This pilot study demonstrates that menthol is a safe temporary consolidant for block lifting and offers a promising alternative to the widely used cyclododecane. In conclusion, this research provided a new approach for conservators to safely lift similarly large and fragile wood remains during archaeological excavations.
Magneto-eklinostrophic Flow, Electromagnetic Columns, and von Kármán Vortices in Magneto-Fluid Dynamics
Authors: Vadasz Peter
Published: October 2024

An analogy between magneto-fluid dynamics (MFD/MHD) and geostrophic flow in a rotating frame of reference, including the existence of electromagnetic columns identical to Taylor–Proudman columns, is identified and demonstrated theoretically here. The latter occurs within the limit of large values of a dimensionless group representing the magnetic field number. Such conditions are shown to be easily satisfied in reality. Consequently, the electromagnetic fluid flow subject to these conditions is two dimensional and the streamlines are shown to be identical to the pressure lines, in complete analogy to rotating geostrophic flows. These results suggest that von Kármán vortices are anticipated in the wake of virtual electromagnetic columns. An experimental setup is suggested to confirm the theoretical results experimentally.
First Derivative Approximations and Applications
Authors: Dimitrov Yuri , Georgiev Slavi , Todorov Venelin
Published: October 2024

In this paper, we consider constructions of first derivative approximations using the generating function. The weights of the approximations contain the powers of a parameter whose modulus is less than one. The values of the initial weights are determined, and the convergence and order of the approximations are proved. The paper discusses applications of approximations of the first derivative for the numerical solution of ordinary and partial differential equations and proposes an algorithm for fast computation of the numerical solution. Proofs of the convergence and accuracy of the numerical solutions are presented and the performance of the numerical methods considered is compared with the Euler method. The main goal of constructing approximations for integer-order derivatives of this type is their application in deriving high-order approximations for fractional derivatives, whose weights have specific properties. The paper proposes the construction of an approximation for the fractional derivative and its application for numerically solving fractional differential equations. The theoretical results for the accuracy and order of the numerical methods are confirmed by the experimental results presented in the paper.
Adaptive Fault-Tolerant Control of Mobile Robots with Fractional-Order Exponential Super-Twisting Sliding Mode
Authors: Wu Hao , Wang Shuting , Xie Yuanlong , Li Hu
Published: October 2024

Industrial mobile robots easily experience actuator loss of some effectiveness and additive bias faults due to the working scenarios, resulting in unexpected performance degradation. This article proposes a novel adaptive fault-tolerant control (FTC) strategy for nonholonomic mobile robot systems subject to simultaneous actuator lock-in-place (LIP) and partial loss-of-effectiveness (LOE) faults. First, a nominal fractional-order sliding mode controller based on the designed exponential super-twisting reaching law is investigated to reduce the reaching phase time and eliminate the chattering. To address the time-varying LIP faults and uncertainties, a novel barrier function (BF)-based gain is explored to assist the super-twisting law. An estimator is designed to estimate the lower bound of the time-varying partial LOE fault coefficients, thus without requiring the boundary information of faults that is commonly requested in traditional FTC schemes. Combined with the nominal controller clubbed with BF and estimator-based LOE fault compensation term, the fault-tolerant controller is finally constructed. The proposed FTC scheme achieves fast convergence and the sliding variables can be confined in a predetermined neighborhood of the sliding manifold under actuator faults. The results show that the proposed controller has superior tracking performance under faulty conditions compared with other state-of-the-art adaptive FTC approaches.
Recent Progress of Antisense Oligonucleotide Therapy for Superoxide-Dismutase-1-Mutated Amyotrophic Lateral Sclerosis: Focus on Tofersen
Authors: Moriyama Hidenori , Yokota Toshifumi
Published: October 2024

Amyotrophic lateral sclerosis (ALS) is a refractory neurodegenerative disease characterized by the degeneration and loss of motor neurons, typically resulting in death within five years of onset. There have been few effective treatments, making the development of robust therapies an urgent challenge. Genetic mutations have been identified as contributors to ALS, with mutations in superoxide dismutase 1 (SOD1), which neutralizes the harmful reactive oxygen species superoxide, accounting for approximately 2% of all ALS cases. To counteract the toxic gain of function caused by SOD1 mutations, therapeutic strategies aimed at suppressing SOD1 gene expression have shown promise. Antisense oligonucleotide (ASO) is an artificially synthesized, short, single-stranded DNA/RNA molecule that binds to target RNA to alter gene expression, representing a next-generation therapeutic approach. In 2023, tofersen became the first ASO drug approved by the FDA for ALS. Administered intrathecally, tofersen specifically binds to SOD1 mRNA, inhibiting the production of toxic SOD1 protein, thereby improving biomarkers of ALS. The long-term efficacy and safety of tofersen require further validation, and the development of more optimized treatment protocols is essential. A series of studies and therapeutic developments related to SOD1 mutations have advanced the understanding of ALS pathophysiology and significantly contributed to treatment strategies for central nervous system disorders. This review focuses on an overview of SOD1 mutations and the development process of tofersen, aiming to deepen the understanding of advancements in ALS research and discuss future challenges and directions for ASO therapy.
Neuromodulators in Acute and Chronic Cough in Children: An Update from the Literature
Authors: Foti Randazzese Simone , Toscano Fabio , Gambadauro Antonella , La Rocca Mariarosaria , Altavilla Giulia , Carlino Mariagrazia , Caminiti Lucia , Ruggeri Paolo , Manti Sara
Published: October 2024

Cough is one of the most common reasons leading to pediatric consultations, negatively impacting the quality of life of patients and caregivers. It is defined as a sudden and forceful expulsion of air from the lungs through the mouth, typically triggered by irritation or the stimulation of sensory nerves in the respiratory tract. This reflex is controlled by a neural pathway that includes sensory receptors, afferent nerves, the brainstem’s cough center, efferent nerves, and the muscles involved in coughing. Based on its duration, cough in children may be classified as acute, lasting less than four weeks, and chronic, persisting for more than four weeks. Neuromodulators have shown promise in reducing the frequency and severity of cough by modulating the neural pathways involved in the cough reflex, although they require careful monitoring and patient selection to optimize the outcomes. This review aims to examine the rationale for using neuromodulators in the management of cough in children.
Disruption of Erythritol Catabolism via the Deletion of Fructose-Bisphosphate Aldolase (Fba) and Transaldolase (Tal) as a Strategy to Improve the Brucella Rev1 Vaccine
Authors: Elizalde-Bielsa Aitor , Lázaro-Antón Leticia , de Miguel María Jesús , Muñoz Pilar M. , Conde-Álvarez Raquel , Zúñiga-Ripa Amaia
Published: October 2024

Brucellosis is a bacterial zoonosis caused by the genus Brucella, which mainly affects domestic animals. In these natural hosts, brucellae display a tropism towards the reproductive organs, such as the placenta, replicating in high numbers and leading to placentitis and abortion, an ability also exerted by the B. melitensis live-attenuated Rev1 strain, the only vaccine available for ovine brucellosis. It is broadly accepted that this tropism is mediated, at least in part, by the presence of certain preferred nutrients in the placenta, particularly erythritol, a polyol that is ultimately incorporated into the Brucella central carbon metabolism via two reactions dependent on transaldolase (Tal) or fructose-bisphosphate aldolase (Fba). In the light of these remarks, we propose that blocking the incorporation of erythritol into the central carbon metabolism of Rev1 by deleting the genes encoding Tal and Fba may impair the ability of the vaccine to proliferate massively in the placenta. Therefore, a Rev1ΔfbaΔtal double mutant was generated and confirmed to be unable to use erythritol. This mutant exhibited a reduced intracellular fitness both in BeWo trophoblasts and THP-1 macrophages. In the murine model, Rev1ΔfbaΔtal provided comparable protection to the Rev1 reference vaccine while inducing fewer adverse reproductive events in pregnant animals. Altogether, these results postulate the Rev1ΔfbaΔtal mutant as a reproductively safer Rev1-derived vaccine candidate to be studied in the natural host.
Emerging Nanomedicine Approaches in Targeted Lung Cancer Treatment
Authors: Alexandru Isaic , Davidescu Lavinia , Motofelea Alexandru Cătălin , Ciocarlie Tudor , Motofelea Nadica , Costachescu Dan , Marc Monica Steluta , Suppini Noemi , Șovrea Alina Simona , Coșeriu Răzvan-Lucian , Bondor Daniela-Andreea , Bobeică Laura-Gabriela , Crintea Andreea
Published: October 2024

Lung cancer, the leading cause of cancer-related deaths worldwide, is characterized by its aggressive nature and poor prognosis. As traditional chemotherapy has the disadvantage of non-specificity, nanomedicine offers innovative approaches for targeted therapy, particularly through the development of nanoparticles that can deliver therapeutic agents directly to cancer cells, minimizing systemic toxicity and enhancing treatment efficacy. VEGF and VEGFR are shown to be responsible for activating different signaling cascades, which will ultimately enhance tumor development, angiogenesis, and metastasis. By inhibiting VEGF and VEGFR signaling pathways, these nanotherapeutics can effectively disrupt tumor angiogenesis and proliferation. This review highlights recent advancements in nanoparticle design, including lipid-based, polymeric, and inorganic nanoparticles, and their clinical implications in improving lung cancer outcomes, exploring the role of nanomedicine in lung cancer diagnoses and treatment.
Phylogenomic Analysis and Functional Characterization of the APETALA2/Ethylene-Responsive Factor Transcription Factor Across Solanaceae
Authors: Yang Fan , Han Songxue , Zhang Yangxin , Chen Xiangxiang , Gai Wenxian , Zhao Tao
Published: October 2024

The AP2/ERF family constitutes one of the largest groups of transcription factors in the Solanaceae. AP2/ERF contributes to various plant biological processes, including growth, development, and responses to various stresses. The origins and functional diversification of AP2/ERF within the Solanaceae family remain poorly understood, primarily because of the complex interactions between whole-genome duplications (WGDs) and tandem duplications. In this study, a total of 1282 AP2/ERF proteins are identified from 7 Solanaceae genomes. The amplification of AP2/ERF genes was driven not only by WGDs but also by the presence of clusters of tandem duplicated genes. The conservation of synteny across different chromosomes provides compelling evidence for the impact of the WGD event on the distribution pattern of AP2/ERF genes. Distinct expression patterns suggest that the multiple copies of AP2/ERF genes evolved in different functional directions, catalyzing the diversification of roles among the duplicated genes, which was of great significance for the adaptability of Solanaceae. Gene silencing and overexpression assays suggest that ERF-1 members’ role in regulating the timing of floral initiation in C. annuum. Our findings provide insights into the genomic origins, duplication events, and function divergence of the Solanaceae AP2/ERF.
Bovine Lactoferrin Promotes Neurite Outgrowth in PC12 Cells via the TrkA Receptor
Authors: Nagashima Daichi , Mizukami Noa , Ogawa Nana , Suzuki Sayaka , Ohno Megumi , Aoki Ryoken , Furukawa Megumi , Izumo Nobuo
Published: October 2024

Lactoferrin (LF) is a multifunctional protein abundant in breast milk that modulates the functions of neural stem cells. Recent studies have demonstrated the efficacy of bovine LF (bLF) in mitigating behavioral changes; however, the molecular mechanisms on the nervous system have not yet been elucidated. The presented study aimed to characterize the molecular mechanisms of bLF on nerve extension in PC12 cells. PC12 cells were treated with 0.01–1000 µg/mL of bLF, and cell viability was determined using the cell counting kit-8 assay after treatment for 24 h. Morphometric evaluation was performed after 24 or 72 h of treatment with 50 ng/mL nerve growth factor (NGF) or 100–500 µg/mL bLF. The molecular mechanisms were investigated using Western blotting and real-time quantitative PCR. Cell viability was significantly decreased after treatment with 600–1000 µg/mL bLF for 24 h compared with the control group. Morphometric evaluation revealed neurite outgrowth after 72 h of NGF treatment, with a significant increase in neurite outgrowth after treatment with 250 µg/mL bLF. The phosphorylated p44/42 expression ratio peaked at 5 min and persisted for up to 10 min. Quantitative real-time PCR revealed a significant decrease in MAP2 expression. Our findings suggested that bLF enhanced PC12 cell neurite outgrowth to a similar extent as NGF. These effects are thought to be mediated via the TrkA receptor and activated by the phosphorylated ERK signaling pathway. Therefore, this study demonstrates that bLF promotes neurite outgrowth via a pathway similar to that of NGF.
Rectal Epithelial Stem Cell Kinetics in Acute Radiation Proctitis
Authors: Ghosh Sharmila , Morita Akinori , Nishiyama Yuichi , Sakaue Masahiro , Fujiwara Ken , Morita Daiki , Sonoyama Yuichiro , Higashi Yuichi , Sasatani Megumi
Published: October 2024

The intestinal tract is a typical radiosensitive tissue, and radiation rectal injury is a severe side effect that limits the prescribed dose in radiotherapy of the abdominal and pelvic region. Understanding the post-irradiation kinetics of Lgr5-positive stem cells is crucial in comprehending this adverse process. In this study, we utilized Lgr5-EGFP knock-in mice expressing EGFP and LGR5 antibody fluorescence staining of wild-type mice. At the state of radiation injury, the qPCR analysis showed a significant decrease in the expression level of Lgr5 in the rectal epithelial tissue. The dose-response relationship analysis showed that at low to moderate doses up to 10 gray (Gy), Lgr5-clustered populations were observed at the base of the crypt, whereas at sublethal doses (20 Gy and 29 Gy), the cells exhibited a dot-like scatter pattern, termed Lgr5-dotted populations. During recovery, 30 days post-irradiation, Lgr5-clustered populations gradually re-emerged while Lgr5-dotted populations declined, implying that some of the Lgr5-dotted stem cell populations re-clustered, aiding regenerations. Based on statistical analysis of the dose-response relationship using wild-type mice, the threshold dose for destroying these stem cell structures is 18 Gy. These findings may help set doses in mouse abdominal irradiation experiments for radiation intestinal injury and for understanding the histological process of injury development.
Special Issue: Cotton Molecular Genomics and Genetics 2.0
Authors: Cheng Shuaishuai , Zhu Qian-Hao , Sun Jie
Published: October 2024

Cotton is a multiuse economic crop cultivated worldwide [...]
The Gut Microbiome Advances Precision Medicine and Diagnostics for Inflammatory Bowel Diseases
Authors: Mousa Walaa K. , Al Ali Aya
Published: October 2024

The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.
Immunity and Coagulation in COVID-19
Authors: Avdonin Piotr P. , Blinova Maria S. , Serkova Anastasia A. , Komleva Lidia A. , Avdonin Pavel V.
Published: October 2024

Discovered in late 2019, the SARS-CoV-2 coronavirus has caused the largest pandemic of the 21st century, claiming more than seven million lives. In most cases, the COVID-19 disease caused by the SARS-CoV-2 virus is relatively mild and affects only the upper respiratory tract; it most often manifests itself with fever, chills, cough, and sore throat, but also has less-common mild symptoms. In most cases, patients do not require hospitalization, and fully recover. However, in some cases, infection with the SARS-CoV-2 virus leads to the development of a severe form of COVID-19, which is characterized by the development of life-threatening complications affecting not only the lungs, but also other organs and systems. In particular, various forms of thrombotic complications are common among patients with a severe form of COVID-19. The mechanisms for the development of thrombotic complications in COVID-19 remain unclear. Accumulated data indicate that the pathogenesis of severe COVID-19 is based on disruptions in the functioning of various innate immune systems. The key role in the primary response to a viral infection is assigned to two systems. These are the pattern recognition receptors, primarily members of the toll-like receptor (TLR) family, and the complement system. Both systems are the first to engage in the fight against the virus and launch a whole range of mechanisms aimed at its rapid elimination. Normally, their joint activity leads to the destruction of the pathogen and recovery. However, disruptions in the functioning of these innate immune systems in COVID-19 can cause the development of an excessive inflammatory response that is dangerous for the body. In turn, excessive inflammation entails activation of and damage to the vascular endothelium, as well as the development of the hypercoagulable state observed in patients seriously ill with COVID-19. Activation of the endothelium and hypercoagulation lead to the development of thrombosis and, as a result, damage to organs and tissues. Immune-mediated thrombotic complications are termed “immunothrombosis”. In this review, we discuss in detail the features of immunothrombosis associated with SARS-CoV-2 infection and its potential underlying mechanisms.
Genetics of Exertional Heat Illness: Revealing New Associations and Expanding Heterogeneity
Authors: Sambuughin Nyamkhishig , Mungunsukh Ognoon , Klein Michael G. , Ren Mingqiang , Bedocs Peter , Kazman Josh B. , Cofer Kristen , Friel Liam P. , McNally Beth , Kwon Kyung , Haigney Mark C. , Leggit Jeffrey C. , Pazgier Marzena , Deuster Patricia A. , O’Connor Francis G.
Published: October 2024

Environmental heat stress represents a pervasive threat to warfighters, athletes, and occupational workers, impacting performance and increasing the risk of injury. Exertional heat illness (EHI) is a spectrum of clinical disorders of increasing severity. While frequently predictable, EHI can occur unexpectedly and may be followed by long-term comorbidities, including cardiovascular dysfunction and exercise intolerance. The objective of this study was to assess genetic factors contributing to EHI. Whole-exome sequencing was performed in a cohort of 53 cases diagnosed with EHI. Rare variants in prioritized gene sets were analyzed and classified per published guidelines. Clinically significant pathogenic and potentially pathogenic variants were identified in 30.2% of the study cohort. Variants were found in 14 genes, including the previously known RYR1 and ACADVL genes and 12 other genes (CAPN3, MYH7, PFKM, RYR2, TRPM4, and genes for mitochondrial disorders) reported here for the first time in EHI. Supporting structural and functional studies of the TRPM4 p.Arg905Trp variant show that it impairs the thermal sensitivity of the TRPM4 channel, revealing a potentially new molecular mechanism contributing to EHI susceptibility. Our study demonstrates associations between EHI and genes implicated in muscle disorders, cardiomyopathies, thermoregulation, and oxidative phosphorylation deficiencies. These results expand the genetic heterogeneity of EHI and shed light on its molecular pathogenesis.
Exploring Border Conditions for Spontaneous Emergence of Chirality in Allylboration of 1,2,3-Triazolic Aldehydes
Authors: Mikhailov Oleg A. , Gurskii Mikhail E. , Kurbangalieva Almira R. , Gridnev Ilya D.
Published: October 2024

A case of spontaneous chirality generation was observed during a synthetic project studying the allylboration of 1,2,3-triazolic aldehydes. Here, we present computational studies supported by experimental findings targeting the elucidation of border conditions required for the observation of spontaneous chirality generation in the reaction of 1-Ar-1H-1,2,3-triazole-4-carbaldehydes 1a,b with triallylborane. Three possible sources of symmetry breaking were found computationally. Thus, dimerization of the initial reaction products, alcoholates 4a,b, gives dimers 5a,b (homochiral) and 6a,b (heterochiral). The latter were computed to be more stable thermodynamically, which can lead to amplification of the initial stochastic imbalance of the enantiomers of 4a,b via the reservoir mechanism. Furthermore, enantiomeric excess can be increased during the transfer of the second allylic group in the reaction of optically active boronates 4a,b with 1a,b, which was computed to be enantioselective due to the strong activating and stereoregulating properties of the 1,2,3-triazole group. In addition, reactions of borinic esters 8a,b, products of the previous reaction with triallylborane, recovered in each case two molecules of 4a,b of the same handedness, which can lead to additional chirality amplification. Experimentally, reactions of optically active alcohols (+)-R-2a,b with triallylborane provided chiral alcoholates 4a,b, which were reacted with equivalent amounts of corresponding aldehydes 1a,b. Unexpectedly, in two series of 10 experiments each, preferential formation of both enantiomers of the newly formed product was observed: seven times S and three times R in the case of 1a and six times S and four times R in the case of 1b.
Special Issue: “Molecular Signatures of Gynecological Cancers—Breast Cancer, Ovarian Cancer, Cervical Cancer, and Endometrial Cancer 2.0”
Authors: Gulyaeva Lyudmila
Published: October 2024

Cancer of women’s reproductive organs (gynecological cancers) and breast cancer affect women all over the world [...]
Beneficial Effects of Selenium and Its Supplementation on Carcinogenesis and the Use of Nanoselenium in the Treatment of Malignant Tumors
Authors: Maleczek Monika , Reszeć-Giełażyn Joanna , Szymulewska-Konopko Katarzyna
Published: October 2024

Selenium was recognized as a non-toxic element in the second half of the 20th century. Since then, the positive impact of selenium on the functioning of the human body has been noticed. It has been shown that low levels of selenium in the body are significantly associated with a higher risk of developing cancer. Selenium acts as an antioxidant and inhibits the proliferation of cancer cells. It has been shown that selenium supplementation may contribute to reducing the risk of DNA mutations and carcinogenesis. Nanomedicine has become very helpful in both the diagnosis and treatment of cancer. Due to its anticancer properties, selenium is used in nanotechnology as selenium nanoparticles.
Flower-Shaped PCR Scaffold-Based Lateral Flow Bioassay for Bacillus cereus Endospores Detection
Authors: Tian Jingjing , Zhang Zhuyi , Shi Yaning , Wu Zichao , Shao Yuting , Wang Limin , Xu Xinglian , Xin Zhihong
Published: October 2024

Bacillus cereus, a foodborne pathogen, produces resilient endospores that are challenging to detect with conventional methods. This study presents a novel Flower-Shaped PCR Scaffold-based Lateral Flow Biosensor (FSPCRS-LFB), which employs an aptamer-integrated PCR scaffold as capture probes, replacing the traditional streptavidin-biotin (SA-Bio) approach. The FSPCRS-LFB demonstrates high sensitivity and cost-efficiency in detecting B. cereus endospores, with a limit of detection (LOD) of 4.57 endospores/mL a visual LOD of 102 endospores/mL, and a LOD of 6.78 CFU/mL for endospore-cell mixtures. In chicken and tea samples, the platform achieved LODs of 74.5 and 52.8 endospores/mL, respectively, with recovery rates of 82.19% to 97.88%. Compared to existing methods, the FSPCRS-LFB offers a 3.7-fold increase in sensitivity while reducing costs by 26% over the SA-Bio strategy and 87.5% over rolling circle amplification (RCA). This biosensor provides a rapid, sensitive and cost-effective solution for point-of-care testing (POCT) of B. cereus endospores, expanding detection capabilities and offering novel approaches for pathogen detection.
Curcumin and Methotrexate: A Promising Combination for Osteosarcoma Treatment via Hedgehog Pathway Inhibition
Authors: Giliberti Giulia , Marrapodi Maria Maddalena , Di Feo Giuseppe , Pota Elvira , Di Martino Martina , Di Pinto Daniela , Rossi Francesca , Di Paola Alessandra
Published: October 2024

Osteosarcoma (OS) is the most severe bone tumor in children. A chemotherapy regimen includes a combination of high-dose Methotrexate (MTX), doxorubicin, and cisplatin. These drugs cause acute and chronic side effects, such as infections, thrombocytopenia, neutropenia, DNA damage, and inflammation. Therefore, to identify new therapeutic strategies, effective and with a safety profile, is necessary. The Hedgehog (Hh) signaling pathway involved in tumorigenesis is active in OS. Hh components Patched receptor 1 (PTCH1), Smoothened (SMO), and glioma-associated oncogene homolog transcription factors (GLI1 and GLI2) are overexpressed in OS cell lines and patient samples. Curcumin (CUR)—with antioxidant and anti-cancer properties—downregulates Hh components in cancer, inhibiting progression. This study investigates CUR effects on the MG-63 OS cell line, alone and combined with MTX, to propose a novel therapeutic approach. Our study suggests CUR as a novel therapeutic agent in OS, particularly when combined with MTX. Targeting the Hh signaling pathway, CUR and MTX showed significant pro-apoptotic effects, increasing the BAX/Bcl-2 ratio and total apoptotic cell percentage. They reduced the expression of Hh pathway components (PTCH1, SMO, GLI1, and GLI2), inhibiting OS cell proliferation, survival, and invasion. CUR and MTX combined determined a β-Catenin decrease and a trend toward reducing NF-kB and matrix metalloproteinases (MMP-2 and MMP-9). Our findings suggest CUR as a support to OS treatment, improving outcomes and reducing the adverse effects of current therapies.
Genetic Variability in the CPA1 Gene and Its Impact on Acute Pancreatitis Risk: New Insights from a Large-Scale Study
Authors: Głuszek Stanisław , Adamus-Białek Wioletta , Chrapek Magdalena , Dziuba Anna , Dulębska Julia , Kozieł Dorota , Matykiewicz Jarosław , Wawszczak-Kasza Monika
Published: October 2024

Acute pancreatitis (AP) is a common and potentially lethal disease. Over the last 10 years, AP has become one of the most important healthcare problems. On a global scale, the incidence has increased by 63% over the last 20 years. AP is usually caused by gallstones and excessive alcohol consumption and genetic factors play an important role in the development of inflammation. Recent studies involving the CPA1 mutations are ambiguous and dependent on the population studied. In this study, the variability of the CPA1 gene in patients with AP was analyzed. Genetic material was isolated from the blood of 301 patients with AP and 184 healthy individuals. Identification of the variants in exons 5, 6, 8, and 9 with introns was performed using molecular biology methods. Mutations were identified by comparison to the reference sequence (NM_001868.4). Statistical analysis included the identification of mutations correlating with the risk of AP, the etiology of inflammation, and family history. Several novel mutations in the CPA1 gene have been identified, along with a high degree of variability within the coding region of the carboxypeptidase gene. A correlation between mutations CPA1:c.1072 + 84del; c.987 + 57G>A and increased risk of developing AP was found. Two protective mutations, CPA1:c.625A>T, c.1072 + 94del, were identified. The CPA1 gene is characterized by high sequence variability and regions in which mutations lead to an increased risk of developing AP. Single or co-occurring mutations of the CPA1 gene can significantly affect the risk of developing AP.
Genome-Wide Association Study for Seed Yield of Tepary Bean Using Whole-Genome Resequencing
Authors: Ravelombola Waltram , Manley Aurora , Pham Hanh , Brown Madeline , Ruhl Caroline , Ghosh Protik
Published: October 2024

Tepary bean (Phaseolus acutifolius A. Gray) is a diploid legume species (2n = 2x = 22). It is the most drought- and heat-tolerant crop of the genus Phaseolus. Tepary bean is native to the northern part of Mexico and the south-western part of the U.S. The lack of molecular markers associated with agronomic traits such as 100-seed weight and seed yield limit the development of elite tepary bean cultivars. Therefore, the objectives of this study were to evaluate tepary bean for 100-seed weight and yield, and identify single-nucleotide polymorphism (SNP) markers associated with these traits. A total of 230,000 high-quality SNPs obtained from the whole-genome resequencing of 153 tepary bean accessions were used for this study. For 100-seed weight, a total of 5 and 20 SNPs were found using a mixed linear model (MLM) and compressed mixed linear model (cMLM), respectively. A candidate gene, Phacu.CVR.002G320800.13, encoding the squamosa promoter-binding protein-like (SBP domain) transcription factor family protein was found to be associated with 100-seed weight. For seed yield, a total of one and eight SNPs were identified using an MLM and cMLM, respectively. Phacu.CVR.009G294200.1, encoding for peroxidase family protein, was identified as a candidate gene for seed yield. Both Phacu.CVR.002G320800.13 and Phacu.CVR.009G294200.1 are likely to be involved in seed development of tepary bean. This is one of the few studies investigating the genetics of 100-seed weight and seed yield in tepary bean.
Profiling Bioactive Components of Natural Eggshell Membrane (NEM) for Cartilage Protection and Its Protective Effect on Oxidative Stress in Human Chondrocytes
Authors: Kim Jin-Woo , Lee Dong-Ho , Lee Kang-Woo , Na In-Su , Lee Na-Yeon , Kim Jong-Kyu , Chun Yoon-Seok , Yoon Nam-Kyu , Kim Byung-Kwon , Yang Sung-Keun , Shim Soon-Mi
Published: October 2024

The current study aimed to investigate the physicochemical properties of the natural eggshell membrane (NEM) and its protective effects against H2O2-induced oxidative stress in human chondrocytes (SW-1353). Bioactive components from NEM related to cartilage were profiled, consisting of 1.1 ± 0.07% hyaluronic acid, 1.2 ± 0.25% total sulfated glycosaminoglycans as chondroitin sulfate, 3.1 ± 0.33% collagen, and 54.4 ± 2.40% total protein. Protein was hydrolyzed up to 43.72 ± 0.76% using in vitro gastro–intestinal digestive enzymes. Peptides eluted at 9.58, 12.46, and 14.58 min using nano-LC-ESI-MS were identified as TEW, SWVE, and VYL peptides with an M/Z value of 435.1874, 520.2402, and 394.2336, respectively. Radical scavenging activity of NEM at 10 mg/mL using the ABTS assay was revealed to be 2.1 times higher than that of the positive control. NEM treatment significantly enhanced cellular SOD expression (p < 0.05). Pre-treatment with NEM (0.1, 1, and 10 mg/mL) dose-dependently reduced H2O2-induced ROS levels in SW-1353. Cell live imaging confirmed that NEM pre-treatment led to a significant reduction in apoptosis expression compared to control. Results from the present study suggest that NEM rich in cartilage protective components including hyaluronic acid, collagen, and chondroitin antioxidative peptides could be a potential therapeutic agent for osteoarthritis (OA) by scavenging oxidative stress.
Exploring the Blood Biomarkers and Potential Therapeutic Agents for Human Acute Mountain Sickness Based on Transcriptomic Analysis, Inflammatory Infiltrates and Molecular Docking
Authors: Yan Jiayi , Zhang Zhuo , Ge Yunxuan , Chen Junru , Gao Yue , Zhang Boli
Published: October 2024

A high-altitude, low-pressure hypoxic environment has severe effects on the health and work efficiency of its residents, and inadequate preventive measures and adaptive training may lead to the occurrence of AMS. Acute exposure to hypoxia conditions can have a less-favorable physiological effect on the human immune system. However, the regulation of the immune system in high-altitude environments is extremely complex and remains elusive. This study integrated system bioinformatics methods to screen for changes in immune cell subtypes and their associated targets. It also sought potential therapeutically effective natural compound candidates. The present study observed that monocytes, M1 macrophages and NK cells play a crucial role in the inflammatory response in AMS. IL15RA, CD5, TNFSF13B, IL21R, JAK2 and CXCR3 were identified as hub genes, and JAK2 was positively correlated with monocytes; TNFSF13B was positively correlated with NK cells. The natural compound monomers of jasminoidin and isoliquiritigenin exhibited good binding affinity with JAK2, while dicumarol and artemotil exhibited good binding affinity with TNFSF13B, and all are expected to become a potential therapeutic agents.
Dinochromosome Heterotermini with Telosomal Anchorages
Authors: Kwok Alvin Chun Man , Yan Kosmo Ting Hin , Wen Shaoping , Sun Shiyong , Li Chongping , Wong Joseph Tin Yum
Published: October 2024

Dinoflagellate birefringent chromosomes (BfCs) contain some of the largest known genomes, yet they lack typical nucleosomal micrococcal-nuclease protection patterns despite containing variant core histones. One BfC end interacts with extranuclear mitotic microtubules at the nuclear envelope (NE), which remains intact throughout the cell cycle. Ultrastructural studies, polarized light and fluorescence microscopy, and micrococcal nuclease-resistant profiles (MNRPs) revealed that NE-associated chromosome ends persisted post-mitosis. Histone H3K9me3 inhibition caused S-G2 delay in synchronous cells, without any effects at G1. Differential labeling and nuclear envelope swelling upon decompaction indicate an extension of the inner compartment into telosomal anchorages (TAs). Additionally, limited effects of low-concentration sirtinol on bulk BfCs, coupled with distinct mobility patterns in MNase-digested and psoralen-crosslinked nuclei observed on 2D gels, suggest that telomeric nucleosomes (TNs) are the primary histone structures. The absence of a nucleosomal ladder with cDNA probes, the presence of histone H2A and telomere-enriched H3.3 variants, along with the immuno-localization of H3 variants mainly at the NE further reinforce telomeric regions as the main nucleosomal domains. Cumulative biochemical and molecular analyses suggest that telomeric repeats constitute the major octameric MNRPs that provision chromosomal anchorage at the NE.