bluuebunny/crossref_metadata_2025 huggingface dataset:
Vimentin Intermediate Filaments Maintain Membrane Potential of Mitochondria in Growing Neurites
Authors: Dayal Alexander A. , Parfenteva Olga I. , Wang Huiying , Gebreselase Blen Amare , Gyoeva Fatima K. , Alieva Irina B. , Minin Alexander A.
Published: December 2024

Neural precursor cells contain two types of intermediate filaments (IFs): neurofilaments consisting of three IV type proteins and vimentin belonging to the type III IF proteins that disappear at the later stages of differentiation. The involvement of vimentin in neurogenesis was demonstrated earlier; however, the role of its temporary expression in neurons is not clear. We showed that the vimentin IFs that interacted with mitochondria maintained their membrane potential at the appropriate level, and thus, ensured their proper function. We examined the dependence of the mitochondrial membrane potential on the expression of vimentin in a CAD catecholaminergic neuronal cell line that was actively dividing in full culture media but stopped growing and started developing neurites when the serum was removed. Using the CRISPR Cas9 system to knock out the vimentin gene in these cells, we investigated the impact of this on the mitochondrial membrane potential. Our data show that the deletion of the vimentin IFs led to a decrease in the level of the mitochondrial potential. When the vimentin network in these cells was reconstituted by transfection with a plasmid that encoded human protein, the level of the potential was restored. Interestingly, mutated vimentin with a disrupted mitochondria-binding site had no such effect. Our data point to vimentin as a possible target in some neurological pathologies.
YOLOv8s-SNC: An Improved Safety-Helmet-Wearing Detection Algorithm Based on YOLOv8
Authors: Han Daguang , Ying Chunli , Tian Zhenhai , Dong Yanjie , Chen Liyuan , Wu Xuguang , Jiang Zhiwen
Published: December 2024

The use of safety helmets in industrial settings is crucial for preventing head injuries. However, traditional helmet detection methods often struggle with complex and dynamic environments. To address this challenge, we propose YOLOv8s-SNC, an improved YOLOv8 algorithm for robust helmet detection in industrial scenarios. The proposed method introduces the SPD-Conv module to preserve feature details, the SEResNeXt detection head to enhance feature representation, and the C2f-CA module to improve the model’s ability to capture key information, particularly for small and dense targets. Additionally, a dedicated small object detection layer is integrated to improve detection accuracy for small targets. Experimental results demonstrate the effectiveness of YOLOv8s-SNC. When compared to the original YOLOv8, the enhanced algorithm shows a 2.6% improvement in precision (P), a 7.6% increase in recall (R), a 6.5% enhancement in mAP_0.5, and a 4.1% improvement in mean average precision (mAP). This study contributes a novel solution for industrial safety helmet detection, enhancing worker safety and efficiency.
Interfering Nuclear Protein Laminb1 Induces DNA Damage and Reduces Vemurafenib Resistance in Melanoma Cells In Vitro
Authors: Li Yuan , Feng Yuqing , Chen Dan
Published: December 2024

Background/Objectives: Drug resistance poses a substantial clinical challenge in melanoma treatment, yet the underlying mechanism remains elusive. Here, we report the novel role of laminB1, a nuclear structure protein, in regulating the response of BRAF-mutated melanoma cells to vemurafenib. Results: Our analysis of clinical samples and existing databases highlights the tight correlation between the laminB1 expression level and melanoma progression and prognosis. Notably, we observe that laminB1 expression is upregulated when BRAF-mutated melanoma cells develop resistance to vemurafenib. The knockdown of laminB1 substantially increases the sensitivity of melanoma cells to vemurafenib. Furthermore, we found laminB1 suppression increases cell apoptosis via the escalation of DNA damage in a vemurafenib-dose-dependent manner. Conversely, protective cell autophagy is negatively regulated by laminB1 suppression. Interestingly, this distinct regulation pattern of apoptosis and autophagy by laminB1 cooperatively promotes the response of BRAF-mutated melanoma cells to vemurafenib. Conclusions: Our findings unveil the potential of laminB1 as both a diagnosis marker and a therapeutic target of melanoma.
Sustainable Photodegradation of Amoxicillin in Wastewater with a Nickel Aluminate and ZnO Heterosystem Oxides: Experimental and Gaussian Process Regression Modeling Studies
Authors: Kebir Mohammed , Bouallouche Rachida , Nasrallah Noureddine , Tahraoui Hichem , Elboughdiri Noureddine , Ait Merzeg Farid , Dergal Fayçal , Amirouche Saifi , Assadi Aymen Amine , Amrane Abdeltif , Trari Mohamed , Zhang Jie
Published: December 2024

The wastewater generated by the pharmaceutical industry poses a risk to the environment due to undesirable characteristics such as low biodegradability, high levels of contaminants, and the presence of suspended solids, in addition to the high load of organic matter due to the presence of drugs and other emerging products in the effluent. This study aims to reduce the impact of wastewater pollution by removing amoxicillin (AMO) antibiotics as an organic pollutant. In this concept, two synthesized catalysts, NiAl2O4 and ZnO, are sensitive oxides to light energy. The prepared materials were then characterized using X-ray diffraction, UV–vis solid reflectance diffuse, Raman spectroscopy, scanning electron microscopy, BET, and ATR-FTIR spectroscopy. The effects of principal operating parameters under sunlight, namely, the percentage of the mixture of NiAl2O4 and ZnO, the pH of the medium, and the initial concentration of the antibiotic were studied experimentally to determine the optimal conditions for achieving a high degradation rate. The results showed that photodegradation is higher at a pH of 6, with a weight percentage of the mixture of 50% for both catalysts in 1 g/L of the total catalyst dose. Then, the effect of the initial concentration of AMO on the photodegradation reaction showed an important influence on the photodegradation process; as the degradation rate decreases, the initial AMO concentration increases. A high degradation rate of 92% was obtained for an initial AMO concentration of 10 mg/L and a pH of 6. The kinetic study of degradation established that the first-order model and the Langmuir–Hinshelwood (LH) mechanism fit the experimental data perfectly. The study showed the success of using heterosystem photocatalysts and sustainable energy for effective pharmaceutical removal, which can be extended to treat wastewater with other organic emerging pollutants. On the other hand, modeling was introduced using Gaussian process regression (GPR) to predict the degradation rate of AMO under sunlight in the presence of heterogeneous ZnO and NiAl2O4 systems. The model evaluation criteria of GPR in terms of statistical coefficients and errors show very interesting results and the performance of the model used. Where statistical coefficients were close to one (R = 0.9981), statistical errors were very small (RMSE = 0.1943 and MAE = 0.0518). The results suggest that the model has a strong predictive power and can be used to optimize the process of AMO removal from wastewater.
Recent Advances in the Synthesis of Chiral Tetrahydroisoquinolines via Asymmetric Reduction
Authors: Ji Yue , Gao Qiang , Han Weiwei , Fang Baizeng
Published: December 2024

Enantiopure tetrahydroisoquinolines (THIQs), recognized as privileged skeletal structures in natural alkaloids, have attracted considerable attention from chemists due to their biological and pharmacological activities. Synthetic strategies for optically active THIQs have been rapidly and extensively developed in the past decades. In view of simplicity and atom economy, asymmetric reduction of N-heteroaromatics, imines, enamines, and iminium salts containing an isoquinoline (IQ) moiety should be the preferred approaches to obtain chiral THIQs. This review focuses on recent advances in the catalytic asymmetric synthesis of enantiopure THIQs via asymmetric reduction, including asymmetric hydrogenation, transfer hydrogenation, reductive amination, and deracemization. Highly enantioselective synthesis of THIQs was achieved via transition-metal-catalyzed asymmetric reduction and organocatalytic asymmetric reduction utilizing either catalyst activation or substrate activation strategy. Despite much progress in the enantioselective synthesis of THIQs, there still remain considerable opportunities and challenges for progress and developments in this field of research, particularly in the development of asymmetric catalytic systems for the direct reduction of IQs.
Pathophysiology of Angiotensin II-Mediated Hypertension, Cardiac Hypertrophy, and Failure: A Perspective from Macrophages
Authors: Carter Kelly , Shah Eshan , Waite Jessica , Rana Dhruv , Zhao Zhi-Qing
Published: December 2024

Heart failure is a complex syndrome characterized by cardiac hypertrophy, fibrosis, and diastolic/systolic dysfunction. These changes share many pathological features with significant inflammatory responses in the myocardium. Among the various regulatory systems that impact on these heterogeneous pathological processes, angiotensin II (Ang II)-activated macrophages play a pivotal role in the induction of subcellular defects and cardiac adverse remodeling during the progression of heart failure. Ang II stimulates macrophages via its AT1 receptor to release oxygen-free radicals, cytokines, chemokines, and other inflammatory mediators in the myocardium, and upregulates the expression of integrin adhesion molecules on both monocytes and endothelial cells, leading to monocyte-endothelial cell-cell interactions. The transendothelial migration of monocyte-derived macrophages exerts significant biological effects on the proliferation of fibroblasts, deposition of extracellular matrix proteins, induction of perivascular/interstitial fibrosis, and development of hypertension, cardiac hypertrophy and heart failure. Inhibition of macrophage activation using Ang II AT1 receptor antagonist or depletion of macrophages from the peripheral circulation has shown significant inhibitory effects on Ang II-induced vascular and myocardial injury. The purpose of this review is to discuss the current understanding in Ang II-induced maladaptive cardiac remodeling and dysfunction, particularly focusing on molecular signaling pathways involved in macrophages-mediated hypertension, cardiac hypertrophy, fibrosis, and failure. In addition, the challenges remained in translating these findings to the treatment of heart failure patients are also addressed.
Partial Cell Fate Transitions to Promote Cardiac Regeneration
Authors: Yang Jianchang
Published: December 2024

Heart disease, including myocardial infarction (MI), remains a leading cause of morbidity and mortality worldwide, necessitating the development of more effective regenerative therapies. Direct reprogramming of cardiomyocyte-like cells from resident fibroblasts offers a promising avenue for myocardial regeneration, but its efficiency and consistency in generating functional cardiomyocytes remain limited. Alternatively, reprogramming induced cardiac progenitor cells (iCPCs) could generate essential cardiac lineages, but existing methods often involve complex procedures. These limitations underscore the need for advanced mechanistic insights and refined reprogramming strategies to improve reparative outcomes in the heart. Partial cellular fate transitions, while still a relatively less well-defined area and primarily explored in longevity and neurobiology, hold remarkable promise for cardiac repair. It enables the reprogramming or rejuvenation of resident cardiac cells into a stem or progenitor-like state with enhanced cardiogenic potential, generating the reparative lineages necessary for comprehensive myocardial recovery while reducing safety risks. As an emerging strategy, partial cellular fate transitions play a pivotal role in reversing myocardial infarction damage and offer substantial potential for therapeutic innovation. This review will summarize current advances in these areas, including recent findings involving two transcription factors that critically regulate stemness and cardiogenesis. It will also explore considerations for further refining these approaches to enhance their therapeutic potential and safety.
Mobile App Intervention Increases Adherence to Home Exercise Program After Whiplash Injury—A Randomized Controlled Trial (RCT)
Authors: Barun Blaž , Divić Zdravko , Martinović Kaliterna Dušanka , Poljičanin Ana , Benzon Benjamin , Aljinović Jure
Published: December 2024

Objective: Can mobile app intervention via push notifications increase adherence to exercise and reduce disability and pain after a whiplash injury? Methods: A randomized controlled trial was conducted with concealed allocation, blinding of some assessors, and an intention-to-treat analysis. Participants who sustained whiplash injury at most 3 months prior were divided into active and control groups. Both groups completed a two-part physiotherapist-supervised physical therapy program (3-week break in between, ten sessions each, 5x/week). The program included TENS, therapeutic ultrasound, and exercises (breathing, ROM, deep neck flexor activation, and stretching). Both groups were encouraged to exercise at home. The active group additionally received push notifications through the mobile app once a day as a reminder to exercise. Outcomes were adherence to exercise (four-point Likert scale), physical functioning (NDI), pain intensity (VAS), perceived recovery (three-point Likert scale), work information, psychological functioning (PCS), and HRQoL (SF-12) at baseline and 6-month follow-up. Results: At month 6, when comparing the groups, the intervention group showed higher adherence to home exercise (3 [2–4] vs. 2 [2–4]; p = 0.005, median [IQR]) and improved HRQoL (∆SF-12) (20 [6–36] vs. 15 [9–23]; p = 0.038). Unlike the control group, the intervention group showed a significant decrease in pain catastrophizing (31%; p = 0.01). A multivariant analysis showed that mobile app intervention influenced adherence most (≈1 Likert point). The groups did not differ in NDI, pain VAS, perceived recovery, or work limitation. Conclusions: Mobile app intervention increased adherence to home exercise, reduced pain catastrophizing, and increased HRQoL six months after a whiplash injury. Trial registration: ClinicalTrials.gov NCT05704023.
An Intrinsic Characterization of Shannon’s and Rényi’s Entropy
Authors: Schlather Martin , Ditscheid Carmen
Published: December 2024

All characterizations of the Shannon entropy include the so-called chain rule, a formula on a hierarchically structured probability distribution, which is based on at least two elementary distributions. We show that the chain rule can be split into two natural components, the well-known additivity of the entropy in case of cross-products and a variant of the chain rule that involves only a single elementary distribution. The latter is given as a proportionality relation and, hence, allows a vague interpretation as self-similarity, hence intrinsic property of the Shannon entropy. Analogous characterizations are given for the Rényi entropy and its limits, the min-entropy and the Hartley entropy.
Self-Supervised, Multi-View, Semantics-Aware Anchor Clustering
Authors: Wei Kaibin , Li Haifeng , Liu Qing , Zhang Xiongjian
Published: December 2024

Data-driven artificial intelligence systems effectively enhance accuracy and robustness by utilizing multi-view learning to aggregate consistent and complementary information from multi-source data. As one of the most important branches of multi-view learning, multi-view anchor clustering greatly reduces the time complexity via learning similarity graphs between anchors and data instead of data-to-data similarities, which has gained widespread attention in data-driven artificial intelligence domains. However, two issues still exist in current methods: (1) They commonly utilize orthogonal regularization to enhance anchor diversity, which may lead to a distorted anchor distribution, e.g., some clusters might have few or even no corresponding anchors. (2) They only utilize view-sharing anchors to aggregate complementary and consistent information between views, which may fail to ensure anchor robustness due to the heterogeneity gap between views. To this end, self-supervised, multi-view, semantics-aware anchor clustering (SMA2C) is proposed, containing multi-view representation alignment, adaptive anchor selection, and global spectral optimization. Specifically, SMA2C devises dual-level contrastive learning on representations and clustering partitioning between views within a deep encoding–decoding architecture to achieve multi-granularity alignment of views with the heterogeneity gap. Meanwhile, SMA2C introduces adaptive anchor selection via filtering outliers and refining clusters to enhance correlations between clusters and anchors, which ensures the diversity and discriminability of anchors. Finally, extensive evaluations across four real-world datasets confirm that SMA2C establishes a new benchmark for multi-view anchor clustering. In particular, SMA2C achieves a 6.75% improvement in accuracy over the second-best result on the HW dataset.
Susceptibility to Low-Frequency Breakdown in Full-Wave Models of Liquid Crystal-Coaxially-Filled Noise-Shielded Analog Phase Shifters
Authors: Li Jinfeng , Li Haorong
Published: December 2024

Building on the fully encapsulated architecture of liquid crystal (LC) coaxial phase shifters, which leverages noise-shielding advantages for millimeter-wave wideband reconfigurable applications, this study addresses the less-explored issue of low-frequency breakdown (LFB) susceptibility in modern full-wave solvers. Specifically, it identifies the vulnerability nexus between the tuning states (driven by low-frequency bias voltages) and the constitutive elements of LC-filled coaxial phase shifters—namely, the core line, housing grounding, and radially sandwiched tunable dielectrics—operating at millimeter-wave frequencies (60 GHz WiGig), microwave (1 GHz), and far lower frequency regimes (down to 1 MHz, 1 kHz, and 1 Hz) for long-wavelength or quasi-static conditions, with specialized applications in submarine communications and geophysical exploration. For completeness, the study also investigates the device state prior to LC injection, when the cavity is air-filled. Key computational metrics, such as effective permittivity and characteristic impedance, are analyzed. The results show that at 1 kHz, deviations in effective permittivity exceed four orders of magnitude compared to 1 GHz, while characteristic impedance exhibits deviations of three orders of magnitude. More critically, in the LFB regime, theoretical benchmarks from 1 MHz to 1 kHz and 1 Hz demonstrate an exponential increase in prediction error for both effective permittivity, rising from 16.8% to 1.5 × 104% and 1.5 × 107%, and for characteristic impedance, escalating from 8.1% to 1.15 × 103% and 3.9 × 104%, respectively. Consequently, the prediction error of the differential phase shift, minimal at 60 GHz (0.16%), becomes noticeable at 1 MHz (4.39%), increases sharply to 743.88% at 1 kHz, and escalates dramatically to 2.18 × 1010% at 1 Hz. The findings reveal a pronounced frequency asymmetry in LFB susceptibility for the LC coaxial phase shifter biased at extremely low frequencies.
Comparative Study of OLGA and LedaFlow Models for Mechanistic Predictions of Hydrate Transport Dynamics
Authors: Qu Anqi , Dalla Luiz F. R. , Zerpa Luis E. , Palermo Thierry , Mateen Khalid , Fidel-Dufour Annie , Koh Carolyn A.
Published: December 2024

Gas hydrate formation in pipelines transporting multiphase fluids from petroleum reservoirs can lead to the formation of blockages, representing a significant flow assurance challenge. Key issues caused by hydrates include substantial increases in the viscosity of mixed liquid phases and the deposition of hydrates on the pipeline wall. This study compares two existing transient multiphase flow simulators, OLGA and LedaFlow, in terms of their estimation of hydrate formation effects on multiphase flow. Here, we compared in detail the hydrate kinetic models, parameters used, and initial condition setup approaches that influence hydrate formation and affect multiphase flow properties. Based on the comparison between the simulation results, it was found that using both simulators with default setups may not lead to comparable results under certain conditions. Adjusting input parameters, such as the stoichiometric coefficient and hydrate formation enthalpy, is necessary in order to obtain equivalent results. Hydrate modules in both simulators have also been applied to a field case. With appropriate setup, OLGA and LedaFlow produce comparable results during steady-state simulations, which align with field observations. This work provides guidelines for setting up OLGA and LedaFlow simulation models to obtain equivalent results.
Analysis of the Parity-Time Symmetry Model in the Receiver-Based Wireless Power Transfer
Authors: Yan Xiaoxi , Yan Wen
Published: December 2024

Parity-time (PT) symmetry has made encouraging progress in wireless power transmission (WPT), exhibiting significant advantages in terms of system robustness and transmission efficiency. However, there are still challenges that need to be addressed, particularly when classical schemes operate at a fixed frequency in the weak coupling region, where even minor changes in coupling strength can result in excessive current surges. This paper introduced a novel PT-symmetric WPT system featuring negative resistance constructed on the receiver side. We first established a theoretical framework for the classical two-coil PT-symmetric magnetically coupled resonant WPT system and subsequently extended it to incorporate the PT-symmetric WPT system with negative resistance on the receiver. This topological coil configuration facilitated stable power delivery over a broader range, with the capability of self-tuning frequency without requiring additional frequency modulation. This adaptability enabled the system to cater to diverse scenarios and opens up a novel avenue for practical applications of PT symmetry in WPT. Finally, we designed a 10 W prototype to demonstrate the effectiveness of our topology, and the experimental results aligned with our theoretical calculations, validating the feasibility and potential of our PT-symmetric WPT system.
Advancing Heat Pump Adoption in Ukraine’s Low-Carbon Energy Transition
Authors: Trypolska Galyna , Gradziuk Piotr , Semeniuk Andrii , Podolets Roman , Diachuk Oleksandr
Published: December 2024

The European Union established a legislative framework to facilitate the transition to low-carbon energy sources. As Ukraine aspires to join the EU, it is progressively adopting similar legislation. The extensive damage to Ukraine’s fossil fuel-based heat generation infrastructure necessitates the reconstruction of heating and cooling supply systems, with a focus on low-carbon energy sources, particularly heat pumps. Notably, Poland achieved the highest growth in installed heat pump capacities in Europe, offering valuable insights for Ukraine’s energy transition. This study employs the TIMES-Ukraine model to assess the potential proliferation of heat pumps within the country. The findings suggest that, if capital costs for heat pumps decrease, their adoption could accelerate more rapidly than biomass-fired heating systems, particularly in urban single-family homes and buildings lacking central heating systems, over the next decade. While high investment costs may slightly diminish the attractiveness of this technology for space heating, heat pumps consistently outperform biomass heating appliances and potential biomethane-sourced gas boilers.
School Start Times for Solar Alignment: Evaluating the Benefits of Schedule Optimisation for Peak and Cost Reduction
Authors: Michael-Ahile Terhemba , Samuels Jason Avron , Booysen Marthinus Johannes
Published: December 2024

The global push towards sustainable energy usage and the increasing adoption of renewable energy sources, such as solar power, requires innovative approaches to energy management, particularly in energy-intensive sectors such as education. This study proposes a change in school start time from 7 a.m. to 9 a.m. to align operational hours with periods of off-peak electricity demand and maximum solar availability. Four scenarios are compared: baseline (current schedule without solar), shifted schedule without solar, baseline with solar, and shifted schedule with solar integration. The analysis reveals that shifting the school’s operational hours alone leads to a peak demand reduction of 40%, mitigating strain on the grid during high-demand periods. Solar integration without schedule has a less pronounced effect on peak demand (26%). The combination of schedule shifting and solar integration delivers the most significant benefits, with the highest cost reductions (28%) and peak demand reductions (60%). This study demonstrates that synchronised solar energy generation and optimised scheduling can enhance energy efficiency and long-term financial savings, offering a practical solution for reducing operational costs and improving sustainability in schools. This study demonstrates how public institutions can contribute to the energy transition by adapting their operational schedules to align with renewable energy availability, rather than relying on conventional fixed schedules.
A Qualitative Study to Describe the Nature and Scope of Street Medicine Programs in the United States
Authors: Medellin Teresa , Moczygemba Leticia R. , Thurman Whitney
Published: December 2024

Street medicine is a health delivery model designed to provide direct patient care to people experiencing unsheltered homelessness where they are physically located, whether that be on the streets or in encampments. The model has developed in response to the barriers people experiencing homelessness (PEH) encounter when accessing care through traditional points of access such as primary care clinics. Street medicine programs are rapidly emerging across the United States (U.S.) in response to the health needs and challenges associated with care access and coordination for unsheltered homeless individuals. Although street medicine is a rapidly growing field, existing street medicine programs have rarely been studied collectively, limiting our understanding of the nature, scope, and range of street medicine programs in the U.S. This study examined 13 programs from across the U.S. to develop a broad characterization of street medicine programs. Results from interviews with representatives from each of the 13 programs show that there is a high degree of variability among the structure, operations, and scope of care of street medicine programs. However, consistent among street medicine programs is the adoption of a patient-centered approach to care and the use of harm-reduction principles. Street medicine programs are also highly engaged with community partners and affiliate organizations that work in their local and regional areas. Because street medicine programs often serve as a bridge between formal healthcare entities and PEH, street medicine offers a strategy for reconnecting individuals to vital healthcare services.
Investigation of the Interaction Between Angiotensin-Converting Enzyme (ACE) and ACE-Inhibitory Tripeptide from Casein
Authors: Yang Cuicui , Xie Tianzhao , Cai Mengmeng , Xu Xiaoting , Li Muzijun , Liu Pengru , Lan Xiongdiao
Published: December 2024

Angiotensin-converting enzyme (ACE) inhibitory peptides exhibit antihypertensive effects by inhibiting ACE activity, and the study of the interaction between ACEs and inhibitory peptides is important for exploring new therapeutic strategies. In this study, the ACE-inhibitory peptide isolated from casein hydrolysate with the amino acid sequence Leu–Leu–Tyr (LLY) exhibited high ACE-inhibitory activity and stability, which holds significant implications for biochemistry and pharmaceutical applications. Furthermore, systematic investigations were conducted on the interaction between ACE and LLY through various approaches. The Lineweaver–Burk plot indicated the non-competitive inhibition pattern of LLY, suggesting that it binds to the enzyme at the non-active site, and the results were further validated by a molecular docking study. Additionally, multispectral experiments and atomic force microscopy were conducted to further elucidate the underlying mechanism of peptide activity. The findings indicated that LLY could induce a conformational change in ACE, thereby inhibiting its activity. This study contributes to a deeper understanding of the mechanism of action of ACE-inhibitory peptides and bears important significance for drug development in hypertension.
Rapid LC-MS/MS Evaluation of Collagen and Elastin Crosslinks in Human and Mouse Lung Tissue with a Novel Bioanalytical Surrogate Matrix Approach
Authors: Lloyd Sarah M. , Sande Elizabeth J. , Ruterbories Kenneth , O’Brien Stephen P. , Wang Yue-Ting , Phillips Lucy A. , Carr Tracy L. , Clements Meghan , Hazelwood Lisa A. , Tian Yu , He Yupeng , Ji Qin C.
Published: December 2024

Alterations to post-translational crosslinking modifications in the extracellular matrix (ECM) are known to drive the pathogenesis of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Thus, the methodology for measuring crosslinking dynamics is valuable for understanding disease progression. The existing crosslinking analysis sample preparation and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods are typically labor-intensive and time-consuming which limits throughput. We, therefore, developed a rapid approach minimizing specialized equipment and hands-on time. The LC-MS/MS sample analysis time was reduced to two minutes per sample. We then improved the analytical integrity of the method by developing a novel surrogate matrix approach for the dihydroxylysinonorleucine (DHLNL) crosslink. By modifying sample preparation, we prepared a tissue-based surrogate matrix with undetectable levels of endogenous DHLNL, providing a strategy for quantifying this crosslink with a more relevant standard matrix. We then applied this rapid methodology to evaluating crosslinking in lung fibrosis. We showed an increase in DHLNL in human IPF lung relative to healthy donors, as well as in a fibrotic mouse model. Finally, we demonstrated that this increase in DHLNL could be mitigated with an anti-fibrotic compound, suggesting that this assay has potential for evaluating pharmaceutical compound efficacy.
Transgenerational Plasticity Enhances the Tolerance of Duckweed (Lemna minor) to Stress from Exudates of Microcystis aeruginosa
Authors: Li Gengyun , Zheng Tiantian , Wang Gang , Gu Qian , Chang Xuexiu , Qian Yu , Xu Xiao , Wang Yi , Li Bo , Geng Yupeng
Published: December 2024

Transgenerational plasticity (TGP) refers to the influence of ancestral environmental signals on offspring’s traits across generations. While evidence of TGP in plants is growing, its role in plant adaptation over successive generations remains unclear, particularly in floating plants facing fluctuating environments. Duckweed (Lemna minor), a common ecological remediation material, often coexists with the harmful bloom-forming cyanobacterium Microcystis aeruginosa, which releases a highly toxic exudate mixture (MaE) during its growth. In this study, we investigate the TGP of duckweed and its adaptive role under stress from MaE during the bloom-forming process. We found that exposure to MaE induces significant phenotypic plasticity in duckweed, manifested by alterations in morphological, physiological, and transcriptomic profiles. Specifically, MaE exposure significantly affected duckweed, promoting growth at low concentrations but inhibiting it at high concentrations, affecting traits like biomass, frond number, total frond area, and photosynthetic efficiency. Additionally, the activities of antioxidant enzymes, together with the levels of proline, soluble sugars, and proteins, are elevated with increasing MaE concentrations. These plastic changes are largely retained through asexual reproductive cycles, persisting for several generations even under MaE-free conditions. We identified 619 genes that maintain a ‘transcriptional memory’, some of which correlate with the TGP-linked alterations in morphological and physiological traits in response to MaE stress. Notably, progeny from MaE-exposed lineages demonstrate enhanced fitness when re-exposed to MaE. These results enhance our comprehension of the adaptive significance of TGP in plants and suggest feasible approaches for utilizing duckweed’s TGP in the bioremediation of detrimental algal blooms.
Amanita phalloides-Associated Liver Failure: Molecular Mechanisms and Management
Authors: Kayes Tahrima , Ho Vincent
Published: December 2024

Amanita phalloides is well-established as one of the most poisonous mushrooms; toxicity from ingestion was reported as early as the first century. Although native to Europe, this ectomycorrhizal fungus has been widely spread and is responsible for liver toxicity in many parts of the world. Toxicity is characterized by delayed gastrointestinal symptoms mimicking acute gastroenteritis followed by severe hepatotoxicity and liver failure with consequent multi-organ failure. The primary mechanism of liver toxicity is considered to be the inhibition of RNA polymerase II with consequent hepatocyte apoptosis. Treatment measures include supportive measures such as rehydration and correction of electrolytes on initial presentation, activated charcoal and lavage to decrease absorption, extracorporeal purification methods such as plasmapheresis, fractionated plasma separation and adsorption, and molecular adsorbent recirculating system, as well as drug therapies including antibiotics, N-acetylcysteine, and silibinin. Liver transplantation is required in those with acute liver failure and poor prognostic features. Here, we reviewed the basic biology, pathophysiology, and molecular mechanisms of Amanita phalloides liver toxicity, as well as available treatments.
In Vitro Investigation of Biological and Toxic Effects of 4-Octylphenol on Human Cells
Authors: Romanelli Antonio Massimiliano , Montefusco Antonio , Sposito Silvia , Scafuri Bernardina , Caputo Ivana , Paolella Gaetana
Published: December 2024

Alkylphenols are byproducts of anthropogenic activities that widely contaminate waters, soils and air; among them, the most represented are 4-nonylphenol (4-NP) and 4-octylphenol (4-OP). These compounds tend to bioaccumulate in animal and plant tissues and also represent a risk to human health. Indeed, humans are constantly exposed to alkylphenols through ingestion of contaminated water and food, inhalation and dermal absorption. In the present work, we characterized the cytotoxic ability of 4-OP towards several human cell lines, representing the potential main targets in the human body, also comparing its effect with that of 4-NP and of a mixture of both 4-OP and 4-NP in a range of concentrations between 1 and 100 μM. Viability assays demonstrated that each cell type had a peculiar sensitivity to 4-OP and that, in some cases, a combination of the two alkylphenols displayed a higher cytotoxic activity with respect to the single compound. Then, we focused our attention on a liver cell line (HepG2) in which we observed that 4-OP increased cell death and also caused interference with protective physiological cell processes, such as the unfolded protein response, autophagy and the antioxidant response. Finally, our experimental data were compared and correlated with ADMET properties originating from an in silico analysis. Altogether, our findings highlight a possible contribution of this pollutant to deregulation of the normal homeostasis in human liver cells.
Extracellular Vesicles: Biology and Therapeutic Applications
Authors: Visnovitz Tamás
Published: December 2024

Extracellular vesicles (EVs) are phospholipid-bilayer-limited particles in the extracellular space, without self-replicating capabilities [...]
Therapeutic Potential of Prenylated Flavonoids of the Fabaceae Family in Medicinal Chemistry: An Updated Review
Authors: Morante-Carriel Jaime , Nájera Hugo , Samper-Herrero Antonio , Živković Suzana , Martínez-Esteso María José , Martínez-Márquez Ascensión , Sellés-Marchart Susana , Obrebska Anna , Bru-Martínez Roque
Published: December 2024

Much attention has been paid to the potential biological activities of prenylated flavonoids (PFs) in various plant families over the last decade. They have enormous potential for biological activities, such as anti-cancer, anti-diabetic, antimicrobial, anti-inflammatory, anti-Alzheimer’s, and neuroprotective activities. Medicinal chemists have recently shown a strong interest in PFs, as they are critical to the development of new medicines. PFs have been rapidly prepared by isolation and semi- or full synthesis, demonstrating their significant utility in medicinal chemistry research. This study encompasses the research progress on PFs in the last decade, including their pharmacological activities in the Fabaceae family. This information demonstrates the bioactive potential of PF compounds and their role in the control and treatment of various human health problems.
Characterization of the Bone Marrow Lymphoid Microenvironment and Discovery of Prognostic Immune-Related Factors in Acute Myeloid Leukemia
Authors: Kim Yoon-Ju , Kwag Daehun , Kim Bo-Reum , Son Hyunsong , Park Silvia , Kim Hee-Je , Cho Byung-Sik
Published: December 2024

Given the limited comprehensive data on the bone marrow (BM) immune environment in acute myeloid leukemia (AML), we analyzed the distribution and phenotype of T cell subsets, including γδ T cells, and their immune checkpoint (IC) ligands on blasts. We performed multiparametric flow cytometry with BM samples taken from 89 AML patients at the time of diagnosis, remission, and relapse/refractory status after chemotherapy and 13 healthy controls (HCs) to identify immune-related risk factors. Compared to the HCs, the T cells of the AML patients exhibited exhausted features including higher TIGIT levels and similar levels of PD-1 and TIM-3. The γδ T cells were exhausted by the upregulation of TIGIT and/or TIM-3 and downregulation of NKG2D and NKp30, with different patterns in the Vδ1 and Vδ2 subtypes. A successful chemotherapeutic response partially restored the exhausted phenotypes of the T cell subsets. The simultaneous analysis of IC receptors on the T cell subsets and their ligands on blasts showed the prognostic value of a specific IC receptor–ligand pair and the feasibility of risk stratification based on their diverse patterns. Our findings clarified the BM T cell landscape in AML, unveiling the prognostic value of γδ T cells in both diagnosis and remission predictions.
Genetic Determinants of Endurance: A Narrative Review on Elite Athlete Status and Performance
Authors: Bıçakçı Barkın , Cięszczyk Paweł , Humińska-Lisowska Kinga
Published: December 2024

This narrative review explores the relationship between genetics and elite endurance athletes, summarizes the current literature, highlights some novel findings, and provides a physiological basis for understanding the mechanistic effects of genetics in sport. Key genetic markers include ACTN3 R577X (muscle fiber composition), ACE I/D (cardiovascular efficiency), and polymorphisms in PPARA, VEGFA, and ADRB2, influencing energy metabolism, angiogenesis, and cardiovascular function. This review underscores the benefits of a multi-omics approach to better understand the complex interactions between genetic polymorphisms and physiological traits. It also addresses long-standing issues such as small sample sizes in studies and the heterogeneity in heritability estimates influenced by factors like sex. Understanding the mechanistic relationship between genetics and endurance performance can lead to personalized training strategies, injury prevention, and improved health outcomes. Future studies should focus on standardized classification of sports, replication studies involving diverse populations, and establishing solid physiological associations between polymorphisms and endurance traits to advance the field of sports genetics.
Clinicopathological Parameters and Immunohistochemical Profiles in Correlation with MRI Characteristics in Glioblastomas
Authors: Sipos Tamás-Csaba , Attila Kövecsi , Kocsis Lóránd , Bălașa Adrian , Chinezu Rareș , Baróti Beáta Ágota , Pap Zsuzsánna
Published: December 2024

Glioblastoma is considered the most aggressive tumor of the central nervous system. The tumor microenvironment includes several components, such as endothelial cells, immune cells, and extracellular matrix components like matrix metalloproteinase-9 (MMP-9), which facilitates the proliferation of endothelial cells with pro-angiogenic roles. The MRI characteristics of glioblastomas can contribute to determining the prognosis. The aim of this study was to analyze the relationship between tumor angiogenesis in glioblastomas in association with MMP-9 immunoexpression. The results were correlated with the Ki-67 proliferation index, p53 immunoexpression, and the mutational status of IDH1 and ATRX, as well as MRI imaging data. This retrospective study included forty-four patients diagnosed with glioblastoma at the Department of Pathology, Târgu Mureș County Emergency Clinical Hospital. MMP-9 immunoexpression was observed in approximately half of the cases, more frequently in patients over 65 years old. Comparing the imaging data with the immunohistochemical results, we observed that the median tumor volume was higher in glioblastomas with IDH1 and p53 mutations, ATRX wild-type status, negative MMP-9 expression, and high Ki-67 proliferation indexes. The median values of MVD-CD34 and MVD-CD105 were higher in cases with extensive peritumoral edema in the contralateral hemisphere. Additionally, ATRX mutations were frequently associated with a more pronounced deviation of the median structures. To statistically validate the associations between MRI and the histopathological features of glioblastomas, further studies with larger cohorts are required.
Molecular Profiling of Endocrine Resistance in HR+/HER2-Metastatic Breast Cancer: Insights from Extracellular Vesicles-Derived DNA and ctDNA in Liquid Biopsies
Authors: Martínez-Rodríguez Ana , Fuentes-Antrás Jesús , Lorca Víctor , López de Sá Alfonso , Pérez-Segura Pedro , Moreno Fernando , García-Sáenz Jose Angel , García-Barberán Vanesa
Published: December 2024

Standard treatments in hormone receptor-positive (HR+)/HER2-metastatic breast cancer (mBC) typically involve endocrine therapy (ET) combined with CDK4/6 inhibitors, yet resistance to ET remains a persistent challenge in advanced cases. A deeper knowledge of the use of liquid biopsy is crucial for the implementation of precision medicine in mBC with real-time treatment guidance. Our study assesses the prognostic value of PIK3CA and ESR1 mutations in DNA derived from extracellular vesicles (EV-DNA) in longitudinal plasma from 59 HR+/HER2-mBC patients previously exposed to aromatase inhibitors, with a comparative analysis against circulating tumor DNA (ctDNA). Mutations were evaluated by digital PCR. PIK3CA and ESR1 mutations were found in 22 and 25% of patients. Baseline ESR1 mutations in EV-DNA were associated with shorter progression-free survival (PFS) across the cohort, with the Y537S mutation showing a particularly strong impact on the outcome of fulvestrant-treated patients. In contrast, PIK3CA mutations in EV-DNA did not significantly correlate with PFS, whereas in ctDNA, they were linked to poor outcomes. Altogether, this study positions EV-DNA as a valuable biomarker alongside ctDNA, enriching the understanding of different analytes in liquid biopsy and supporting strategies for HR+/HER2-mBC in precision oncology.
Role of Acyl-CoA Thioesterase 7 in Regulating Fatty Acid Metabolism and Its Contribution to the Onset and Progression of Bovine Clinical Mastitis
Authors: Zhou Bin , Zhang Bohao , Han Jiangyuan , Zhang Junjun , Li Jianfu , Dong Weitao , Zhao Xingxu , Zhang Yong , Zhang Quanwei
Published: December 2024

Clinical mastitis (CM) is a prevalent and severe inflammatory disease in dairy cows affecting the mammary glands. Fatty acid (FA) metabolism and associated enzymes are crucial for many physiological and pathological processes in dairy cows. However, the relationships among FA metabolism, FA-associated enzymes, and CM, as well as the mechanisms underlying their interactions, in dairy cows are not fully understood. The aim of this study was to characterize biological process (BP) terms, pathways, and differentially expressed proteins (DEPs) related to FA metabolism from our previous data-independent acquisition proteomic study. Six BPs involving 14 downregulated and 20 upregulated DEPs, and four pathways involving 10 downregulated and 11 upregulated DEPs related to FA synthesis and metabolism were systematically identified. Associated analysis suggested that 12 candidate DEPs obtained from BPs and pathways, especially acyl-CoA thioesterase 7 (ACOT7), regulate long-chain FA (LCFA) elongation and the biosynthesis of unsaturated FAs. Immunohistochemical and immunofluorescence staining results showed that ACOT7 was present mainly in the cytoplasm of mammary epithelial cells. The qRT-PCR and Western blotting results showed that ACOT7 mRNA and protein levels in the mammary glands of the CM group were significantly upregulated compared to those in the healthy group. This evidence indicates that ACOT7 is positively correlated with CM onset and progression in Holstein cows. These findings offer novel insights into the role of FA metabolism and related enzymes in CM and offer potential targets for the development of therapeutic strategies and biomarkers for the prevention and treatment of CM in dairy cows.
Protein Biochips with Three-Dimensional Hydrogel or Polymer Brush Elements for the Detection of Human Serum Immunoglobulin E Specific to Inhalation Allergens
Authors: Miftakhov Rinat A. , Shtylev Georgiy F. , Kachulyak Daria A. , Shishkin Ivan Yu. , Vasiliskov Vadim A. , Butvilovskaya Veronika I. , Kuznetsova Viktoriya E. , Shershov Valeriy E. , Barsky Victor E. , Polyakov Sergey A. , Zasedateleva Olga A. , Chudinov Alexander V.
Published: December 2024

The development of rapid analysis of human serum for the presence of allergen-specific Immunoglobulin E (IgE) is currently important. Consequently, we developed two types of three-dimensional (3D) protein biochips. The first one is a 3D hydrogel biochip containing hydrogel droplets with protein molecules (allergens, immunoglobulins and others). These droplets are disposed on elements consisting of short polymer brushes grafting from a surface of polybutylene terephthalate polymer. The immobilization of proteins was induced by short-wave ultraviolet (UV) radiation. On such a biochip, the kinetics of allergen–sIgE complex formation reached 60% of saturation for 6 h. Also, we developed a 3D brush microchip containing on the surface of a polyethylene terephthalate polymer the brush elements with protein molecules covalently immobilized by opening oxirane cycles by amino and thiol nucleophilic groups contained in proteins. In the case of the 3D brush microchip, the kinetics of allergen–sIgE complex formation reached 100% of saturation for 3 h, and fluorescent signals were 2–3 times higher than those of the 3D hydrogel biochip for some allergens. Thus, the comparative analysis revealed that 3D brush biochips are more useful for further studies of protein–protein interaction than 3D hydrogel ones.