bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing a Community Partnership Addressing Food Security Among Older Adults During COVID-19
Authors: Lee Jenny Jinyoung , Nishita Christy , Braun Kathryn L.
Published: January 2025

For many vulnerable older adults, food access was disrupted during the COVID-19 pandemic. In Hawai‘i, the Kūpuna (the Hawaiian word for elders) Food Security Coalition (KFSC) was formed in March 2020 to address this challenge, leveraging local and federal funding support. This case study presents information on coalition formation and success in addressing this emergency, as well as evaluation data on coalition functioning as assessed by the Collective Impact (CI) framework. Coalition functioning was assessed across the five CI conditions: common agenda, shared measurement, mutually reinforcing activities, continuous communication, and backbone support. Case study data were available from interview and learning circle transcripts, survey findings, and other program documents. Between March and December 2020, the KFSC coordinated efforts of 46 organizations to serve approximately 1.2 million meals to 8300 vulnerable seniors in Honolulu County. Within the first 9 months of existence, the coalition’s measurement system and the common agenda conditions showed advanced maturity, while the other conditions demonstrated moderate maturity levels. Despite challenging leadership transitions, the coalition was successful in helping increase food access and then pivoting in 2021 to promote kūpuna vaccinations, and the coalition continues to meet regularly to address issues of concern to vulnerable older adults. This study provides evidence-based guidance for communities seeking to establish public/non-profit partnerships for emergency food response for older adults, demonstrating how structured coalition approaches can effectively mobilize and coordinate multi-stakeholder efforts during and beyond crises.
The Behaviors and Habits of Young Drivers Living in Small Urban Cities
Authors: Crizzle Alexander M. , McKeown Mackenzie L. , Toxopeus Ryan
Published: January 2025

While studies have typically examined the driving habits of young drivers living in large urban cities, few have examined the habits of young drivers living in smaller cities with large rural surrounding areas. Three surveys were disseminated to 193 young drivers, 65 police officers, and 62 driving instructors to examine the driving habits and challenging driving situations young drivers experience. Almost a fifth (18.1%) reported consuming alcohol prior to driving; alcohol consumption prior to driving was significantly associated with eating food/drinking beverages while driving, cellphone use, and speeding. The most challenging situations young drivers reported were night driving, encountering wild animals on the road, and driving in extreme weather conditions (e.g., ice, snow). Driving instructors reported that young drivers had challenges with lane positioning, speed control, and navigating traffic signs and signals. Additionally, police officers reported issuing tickets to young drivers primarily for failure to stop, distracted driving, impaired driving, and speeding. Young drivers living in smaller cities and rural communities have unique challenges, including interactions with wildlife, driving on gravel roads, and driving in poor weather and road conditions (e.g., ice, snow). Opportunities for young drivers to be exposed to these scenarios during driver training are critical for increasing awareness of these conditions and reducing crash risk.
Long-Term Greenness Effects of Urban Forests to Reduce PM10 Concentration: Does the Impact Benefit the Population Vulnerable to Asthma?
Authors: Jeong Jinsuk , Kim Chaewan , Choi Sumin , Sou Hong-Duck , Park Chan-Ryul
Published: January 2025

This study investigates the effect of urban forests in reducing particulate matter (PM) concentrations and its subsequent impact on the number of asthma care visits. Understanding the mechanisms behind the relationship between the greenness of blocking forests and the reduction in PM is crucial for assessing the associated human health benefits. This study analyzed the influencing factors for reducing long-term PM10 concentrations, utilizing the vegetation index and meteorological variables. Results showed that the reduction in PM10 began in 2011, five years after the establishment of the blocking forest. The annual mean PM10 concentrations decreased significantly, driven primarily by summer wind speed and summer Enhanced Vegetation Index (EVI), explaining approximately 62% of the variation. A decrease in the number of asthma care visits was observed, similar to the trend of PM10 reduction in the residential area and the increase in the greenness of the blocking forest. The influx of PM into the city, primarily driven by prevailing northwesterly winds, may have been mitigated by the growing blocking forest, contributing to a reduction in asthma-related medical visits among urban residents. In particular, since the onset of the COVID-19 pandemic in 2020, the increase in the PM2.5/PM10 ratio in residential areas has become more closely linked to the increase in asthma-related medical visits. It suggests another PM2.5 emission source in the residential area. The number of asthma care visits among children (under 11) and the elderly (over 65) exhibited a strong positive correlation with PM10 levels and a negative correlation with the Normalized Difference Vegetation Index (NDVI). This suggests a link between air quality improvement from the greenness of blocking forests with their capacity to capture PM and respiratory health outcomes, especially for the vulnerable groups to asthma. These findings highlight the need to manage pollutant sources such as transportation and the heating system in residential areas beyond industrial emissions as the point pollution source. The management policies have to focus on protecting vulnerable populations, such as children and the elderly, by implementing small-sized urban forests to adsorb the PM2.5 within the city and establishing blocking forests to prevent PM10 near the industrial complex.
The Societal Cost of Behaviors of Concern Among Individuals with Intellectual and Developmental Disabilities Residing in Small Residential Group Homes
Authors: Johnson Tricia J. , Vondracek Hugh , Moro Teresa , White Cameron D. , Ailey Sarah H.
Published: January 2025

Engagement in behaviors of concern (BoCs) by adults with intellectual and developmental disabilities (IDDs) living in small residential group homes can negatively impact the health, safety, and quality of life of the individuals themselves and others living and working in the home. Little is known about the societal cost of BoCs. The objective of this study was to quantify the cost of BoCs for residents, residential group homes, and public and healthcare services in terms of different behaviors. This descriptive study used incident and monthly behavior-tracking reports collected from small residential group homes for six months prior to implementing a social problem-solving intervention aimed at decreasing BoCs. The mean cost per BoC incident per resident was USD 80 ± 601. Health and safety incidents had the highest cost, followed by begging. BoCs impose costs on small residential group homes, public and healthcare services, and residents themselves.
Out-of-Hospital Cardiac Arrest Ambulance Delay Zones and AED Placement in a Southern Brazilian City
Authors: Bitencourt Marcos Rogério , Bitencourt Mariá Romanio , Silva Lincoln Luís , Santos Amanda Gubert Alves dos , Iora Pedro , Labbado José Anderson , Lemos Mauricio Medeiros , de Paulo Luiz Gustavo , Gabella Júlia Loverde , Lourenço Lopes Costa Juliana , Dolci Hideky Ikeda , Giacomin Vinicius , Pelloso Sandra Marisa , de Barros Carvalho Maria Dalva de Barros , de Andrade Luciano
Published: January 2025

Out-of-hospital cardiac arrests (OHCAs) have high mortality rates, worsened by limited access to automated external defibrillators (AEDs). This study analyzed OHCA response times, identified areas with prolonged ambulance travel times, and proposed optimal AED locations in a medium-sized city in southern Brazil. Data from 278 non-traumatic OHCA cases (2019–2022) in patients over 18 years old, with ambulance response times under 20 min, were included. Spatial survival analysis assessed the probability of exceeding the recommended 5-min (300 s) ambulance response time. The maximal covering location problem identified 100 strategic AED sites within a 150-s reach for bystanders. AED and ambulance travel times were compared using the Wilcoxon test (p < 0.01). Defibrillation occurred in 89 cases (31.01%), and bystander CPR was performed in 149 cases (51.92%). Despite these efforts, 77% of patients died. The median ambulance response time was 11.63 min, exceeding 5 min in most cases, particularly at peak times like 11 a.m. AED placement in selected locations could cover 76% of OHCA occurrences, with a mean AED travel time of 320 s compared to 709 s for ambulances. Strategic AED placement could enhance early defibrillation and improve survival outcomes.
Assessment of Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV) as Complementary Biomarkers to Torquetenovirus (TTV)
Authors: Cinti Lilia , Spezia Pietro Giorgio , Roberto Piergiorgio , Russo Gianluca , Lai Quirino , Carillo Carolina , Frasca Federica , Antonelli Guido , Maggi Fabrizio
Published: January 2025

Recent studies have identified Torquetenovirus (TTV) as a promising biomarker of immune competence, particularly in assessing the vaccine response of solid organ transplant (SOT) recipients. However, given the individual variability of viral load, it is not yet possible to define "normal levels”. Nevertheless, TTV is just one component of the broader Anelloviridae family, which also includes Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV). This study explores whether the viremia of TTMV and TTMDV offers a stronger predictive marker for vaccine efficacy in SOT recipients. A cohort of 168 SOT patients (142 kidney and 26 lung transplant recipients) who received the BNT162B2 mRNA vaccine was examined, with viral loads quantified through virus-specific real-time PCR. While TTV remains a potentially useful biomarker for evaluating immune response, the combined analysis of all anelloviruses viremia provides deeper insights, particularly in cases where TTV is undetectable. Notably, only TTMV exhibited a pattern similar to TTV, suggesting its potential as an alternative biomarker when TTV is absent from the patient’s virome.
Novel RNA-Based Therapies in the Management of Dyslipidemias
Authors: Kosmas Constantine E. , Bousvarou Maria D. , Tsamoulis Donatos , Gianniou Maria , Papakonstantinou Evangelia J. , Rallidis Loukianos S.
Published: January 2025

Pharmaceutical advancements and an improved understanding of pathophysiology have enabled innovative therapies for chronic conditions like dyslipidemia. This condition is marked by abnormalities in lipid homeostasis. Nucleic acid therapeutics, including antisense oligonucleotides and small interfering RNAs, are novel management strategies that silence genes by targeting mRNA. Antisense oligonucleotides modify mRNA to inhibit protein production, whereas small interfering RNAs induce mRNA degradation via the RNA-induced silencing complex (RISC), thus offering promising treatments for dyslipidemia and atherosclerotic cardiovascular disease. Chemical modifications improve their stability and mRNA targeting. RNA-based therapies targeting PCSK9, Lp(a), ApoC-III, and ANGPTL3 hold transformative potential for treating dyslipidemia effectively. This article discusses the latest data from completed and ongoing trials on RNA therapies for dyslipidemia, including inclisiran, pelacarsen, olpasiran, zerlasiran, lepodisiran, volanesorsen, olezarsen, plozasiran, zodasiran, and solbinsiran. Each therapy targets specific molecules while also significantly impacting other lipid parameters. The promising results of these trials indicate potential improvements in lipid therapy and cardiovascular risk reduction, with ongoing studies expected to further refine the role of the novel RNA-based agents in effective lipid management.
Molecular Mechanisms of Vascular Tone in Exercising Pediatric Populations: A Comprehensive Overview on Endothelial, Antioxidative, Metabolic and Lipoprotein Signaling Molecules
Authors: Haferanke Jonas , Baumgartner Lisa , Willinger Laura , Oberhoffer-Fritz Renate , Schulz Thorsten
Published: January 2025

Vasoactive molecules are central regulators of vascular tone, angiogenesis and inflammation. Key molecular agents include nitric oxide (NO), endothelin-1 (ET-1), prostacyclin, free triiodothyronine (fT3), leptin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), superoxide dismutase (SOD), and glutathione peroxidase (GPX). Dysregulation of these compounds can lead to endothelial dysfunction, an early predictor of atherosclerosis and cardiovascular diseases (CVD). Maintaining endothelial health is thus essential for vascular homeostasis and cardiovascular risk prevention. Regular exercise serves as a vital protective measure against CVD and the risk of cardiovascular conditions. However, young athletes often significantly exceed recommended levels of training load, engaging in highly intensive training that leads to substantial physiological adaptations. Despite this, research on the impact of exercise on vasoactive substances in children and adolescents, particularly young athletes, is limited and inconsistent. Most studies focus on those with pre-existing conditions, like obesity or diabetes mellitus. Existing findings suggest exercise may favorably affect vascular biomarkers in youth, but methodological variations hinder consistent conclusions. This literature review examines 68 studies on the effects of exercise on vascular molecules in children and adolescents, young athletes, and children and adolescents with pre-existing conditions, offering deeper insights into how exercise may influence vascular health at the molecular level.
Electrical Stimulation Generates Induced Tumor-Suppressing Cells, Offering a Potential Option for Combatting Breast Cancer and Bone Metastasis
Authors: Cui Changpeng , Xu Yinzhi , Xiong Xue , Aryal Uma K. , Chen Andy , Chien Stanley , You Lidan , Li Baiyan , Yokota Hiroki
Published: January 2025

Treating advanced metastatic cancer, particularly with bone metastasis, remains a significant challenge. In previous studies, induced tumor-suppressing (iTS) cells were successfully generated through genetic, chemical, and mechanical interventions. This study investigates the potential of electrical stimulation to generate iTS cells. Using a custom electrical stimulator with platinum electrodes, mesenchymal stem cells (MSCs) and Jurkat T cells were stimulated under optimized conditions (50 mV/cm, 10–100 Hz, 1 h). Conditioned medium (CM) from electrically stimulated cells demonstrated tumor-suppressing capabilities, inhibiting tumor cell migration, 3D spheroid growth, and cancer tissue fragment viability. Additionally, the CM reduced osteoclast maturation while promoting osteoblast differentiation. Proteomic analysis revealed enrichment of tumor-suppressing proteins, including histone H4, in the CM. Functional studies identified Piezo1 as a key mediator, as its knockdown significantly impaired the tumor-suppressive effects. Mechanistically, the process was distinct from other methods, such as mechanical vibration, with SUN1 inhibition showing no effect on iTS cell generation by electrical stimulation. These findings demonstrate the efficacy of electrical stimulation in enhancing the antitumor capabilities of MSCs and T cells, offering a novel approach to cancer therapy. Further exploration of this strategy could provide valuable insights into developing new treatments for metastatic cancer.
Oxidative Stress Enhances Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts
Authors: Trinh Quang Duy , Takada Kazuhide , Pham Ngan Thi Kim , Takano Chika , Namiki Takahiro , Ito Shun , Takeda Yoshinori , Okitsu Shoko , Ushijima Hiroshi , Hayakawa Satoshi , Komine-Aizawa Shihoko
Published: January 2025

Rubella infection (RuV) during early pregnancy is a known cause of congenital rubella syndrome (CRS). However, the mechanisms by which the virus crosses the placenta and infects the fetus are not fully understood. It has been known that various kinds of cell stresses can occur during the placenta formation. Previously, we demonstrated that low-glucose-induced endoplasmic reticulum stress could drastically enhance RuV infection in immortalized human first-trimester trophoblast cells. In this study, we investigated the roles of oxidative stress in RuV infection in these cells. Oxidative stress was induced in Swan.71 cells by culturing them in medium containing hydrogen peroxide (H2O2) in various concentrations and durations (50 µM or 100 µM for 24 h, or 150 µM for 1 h). RuV infection with a clinical strain was performed 24 h post-treatment, and capsid proteins were visualized at 24 and 48 h post-infection (hpi) using flow cytometry (FCM) and fluorescence microscopy (IF), respectively. The findings demonstrated that oxidative stress significantly enhanced RuV infection, as evidenced by FCM analysis, showing a twofold increase in infection rate, and confirmed by IF assay. Additionally, significantly increased intracellular viral replication was observed at 3 dpi. These findings suggest that oxidative stress during early pregnancy may promote the maternal-to-fetal transmission of rubella, contributing to the development of CRS.
Review of Literature and Recommended Procedures for Management of Unusual Cases of False Positive Troponin Tests
Authors: Salvatici Michela , Sommese Carmen , Corsi Romanelli Massimiliano M. , Drago Lorenzo
Published: January 2025

Heterophile antibodies are immunoglobulins produced by the immune system in response to exposure to animal and bacterial antigens, blood transfusions, autoimmune disorders, hematologic malignancies, dialysis, and pregnancy. Recently, these antibodies have garnered significant attention due to their impact on the accuracy of laboratory test results. Heterophile antibodies can bind not only to specific antigens but also to those from different species, including the antibodies used in laboratory tests. This cross-reactivity with foreign proteins is the basis for their interference in immunological assays, such as those measuring cardiospecific troponins (cTn). This manuscript reviews the literature on cases of heterophile antibody interference in troponin testing and proposes an algorithm for identifying such interference when clinical discrepancies arise. Recognizing and addressing heterophile antibody interference is crucial, particularly for tests like those for troponins, which are key biomarkers in the diagnosis and management of emergency and intensive care patients. The literature emphasizes the need for accurate procedures to distinguish true cardiac damage from false positives, thereby preventing unnecessary additional tests and hospitalizations.
Effect of Temperature on Polyamine Oxidase Genes in Skeletonema dohrnii
Authors: Teng Wei , Sun Jun
Published: January 2025

In our experiments, we investigated the effect of temperature on diatom polyamine metabolism using Skeletonema dohrnii as an experimental algal species. We set three different temperature conditions for incubation and selected Skeletonema dohrnii in the exponential growth period, and analyzed basic physiological parameters, polyamine composition and content, and polyamine oxidase (PAO) gene expression at different temperatures. The results showed that low temperatures led to a decrease in growth rate, an increase in biogenic silica content, an increase in the content of putrescine and spermine, a decrease in the concentration of spermidine, and a down-regulation of PAO gene expression. In addition, high temperature led to an increase in growth rate, a significant change in the concentration of putrescine and spermine, and an increase in spermidine. These findings suggest that changes in temperature affect the growth rate of algae, low temperature increases the biogenic silica content of diatoms, different temperature stresses lead to different kinds of polyamine changes in diatoms, and the PAO gene may play a role in regulating the response of algae to temperature changes. This study lays a foundation for further exploration of the function of the PAO gene in Skeletonema dohrnii.
Persistent Metabolic Changes Are Induced by 24 h Low-Dose Lead (Pb) Exposure in Zebrafish Embryos
Authors: Cooper Gwendolyn , North Ryan , Hunt-Smith Tyler , Larson James , Rennie Madison , Bailey Marguerite L. , Scarlata Suzanne , Merzdorf Christa S. , Bothner Brian
Published: January 2025

Lead (Pb) is a heavy metal associated with a range of toxic effects. Relatively few studies attempt to understand the impact of lead on development from a mechanistic perspective. Danio rerio (zebrafish) embryos are a model organism for studying the developmental consequences of exposure to chemical agents. This study examined the metabolome of developing zebrafish embryos exposed to 5 ppb, 15 ppb, 150 ppb, and 1500 ppb Pb concentrations during the first 24 h post fertilization, followed by 24 h of unexposed development and harvest at 48 h. Untargeted metabolomics and multivariate analysis revealed that various Pb exposures differentially affected the embryonic metabolome. Pathway analyses showed the dysregulation of biopterin, purine, alanine, and aspartate metabolism. Inductively coupled plasma mass spectrometry demonstrated Pb accumulation in embryos. Additionally, decreases in oxidation–reduction ratios were observed in 5–150 ppb groups but not in the 1500 ppb exposure group. This finding, along with several metabolite abundances, suggests a hormetic effect of Pb concentrations on the developing zebrafish metabolome. Together, these data reveal persistent global changes in the embryonic metabolome, pin-point biomarkers for Pb exposure, unveil dose-dependent relationships, and reflect Pb-induced changes in cellular energy. This work highlights aberrant processes and persistent changes underlying low-dose heavy metal exposure during early development.
mRNA Transcript Variants Expressed in Mammalian Cells
Authors: Sharma Yashica , Vo Kevin , Shila Sharmin , Paul Anohita , Dahiya Vinesh , Fields Patrick E. , Rumi M. A. Karim
Published: January 2025

Gene expression or gene regulation studies often assume one gene expresses one mRNA. However, contrary to the conventional idea, a single gene in mammalian cells can express multiple transcript variants translated into several different proteins. The transcript variants are generated through transcription from alternative start sites and alternative post-transcriptional processing of the precursor mRNA (pre-mRNA). In addition, gene mutations and RNA editing further enhance the diversity of the transcript variants. The transcript variants can encode proteins with various domains, expanding the functional repertoire of a single gene. Some transcript variants may not encode proteins but function as non-coding RNAs and regulate gene expression. The expression level of the transcript variants may vary between cell types or within the same cells under different biological conditions. Transcript variants are characteristic of cell differentiation in a particular tissue, and the variants may play a key role in normal development and aging. Studies also reported that some transcript variants may have roles in disease pathogenesis. The biological significances urge studying the complexity of gene expression at the transcript level. This article updates the molecular basis of transcript variants in mammalian cells, including the formation mechanisms and potential roles in host biology. Gaining insight into the transcript variants will not only identify novel mechanisms of gene regulation but also unravel the role of the variants in health and disease.
In Vitro Infection of Human Macrophages with Porphyromonas gingivalis W83
Authors: La Rosa Martina , Spagnolo Alessandra , Gamonal Juan Daniel , Marín Maria Jose , Figuero Elena , Sanz Mariano
Published: January 2025

This study aimed to investigate the innate immune response of human macrophages to Porphyromonas gingivalis W83 using a novel in vitro infection model. The growth kinetics of P. gingivalis W83 were analyzed, revealing an exponential growth phase at 8 h (optical density = 0.70). To establish a reliable macrophage model, the differentiation of THP-1 monocytes into macrophages was optimized using low concentrations of phorbol 12-myristate 13-acetate (PMA). This approach induced enhanced adherence and morphological changes, with full differentiation achieved after 48 h of PMA treatment followed by 24 h of rest. Polarization towards the pro-inflammatory M1 phenotype was successfully induced with interferon-γ (IFN-γ) and lipopolysaccharide (LPS), as confirmed using cytokine profiling. Cytokine analysis using Luminex® technology demonstrated significant increases in interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6, indicating the effective activation of macrophages towards a pro-inflammatory phenotype. Building upon this macrophage model, this study investigated the interactions between macrophages and P. gingivalis W83 during its exponential growth phase. After a one-hour infection period, bacterial DNA quantification in supernatants and lysed macrophages revealed minimal levels of internalized or adherent bacteria, supporting the hypothesis that P. gingivalis effectively evades immune detection. These findings emphasize the utility of this model in uncovering the sophisticated immune evasion strategies employed by P. gingivalis, with significant implications for the development of targeted therapeutic interventions.
Investigating the Inhibitory Effects of Paliperidone on RAGEs: Docking, DFT, MD Simulations, MMPBSA, MTT, Apoptosis, and Immunoblotting Studies
Authors: Singh Akash Pratap , Ahmad Shaban , Roy Ahona , Raza Khalid , Gautam Hemant K.
Published: January 2025

Chronic diseases such as diabetes and cancer are the leading causes of mortality worldwide. Receptors for Advanced Glycation End products (RAGEs) are ubiquitous factors that catalyse Advanced Glycation End products (AGEs), proteins, and lipids that become glycated from sugar ingestion. RAGEs are cell surface receptor proteins and play a broad role in mediating the effects of AGEs on cells, contributing to modifying biological macromolecules like proteins and lipids, which can cause Reactive Oxygen Species (ROS) generation, inflammation, and cancer. We targeted RAGE inhibition analysis and screening of United States Food and Drug Administration (FDA) libraries through molecular docking studies that identified the four most suitable FDA compounds: Zytiga, Paliperidone, Targretin, and Irinotecan. We compared them with the control substrate, Carboxymethyllysine, which showed good binding interaction through hydrogen bonding, hydrophobic interactions, and π-stacking at active site residues of the target protein. Following a 100 ns simulation run, the docked complex revealed that the Root Mean Square Deviation (RMSD) values of two drugs, Irinotecan (1.3 ± 0.2 nm) and Paliperidone (1.2 ± 0.3 nm), were relatively stable. Subsequently, the Molecular Mechanics Poisson–Boltzmann Surface Area (MMPBSA) determined that the Paliperidone molecule had a high negative energy of −13.49 kcal/mol, and the Absorption, Distribution, Metabolism, and Excretion (ADME) properties were in control for use in the mentioned cases. We extended this with many in vitro studies, including an immunoblotting assay, which revealed that RAGEs with High Mobility Group Box 1 (HMGB1) showed higher expression, while RAGEs with Paliperidone showed lower expressions. Furthermore, cell proliferation assay and Apoptosis assay (Annexin-V/PI staining) results revealed that Paliperidone was an effective anti-glycation and anti-apoptotic drug—however, more extensive in vivo studies are needed before its use.
Network Diffusion-Constrained Variational Generative Models for Investigating the Molecular Dynamics of Brain Connectomes Under Neurodegeneration
Authors: Xie Jiajia , Tandon Raghav , Mitchell Cassie S.
Published: January 2025

Alzheimer’s disease (AD) is a complex and progressive neurodegenerative condition with significant societal impact. Understanding the temporal dynamics of its pathology is essential for advancing therapeutic interventions. Empirical and anatomical evidence indicates that network decoupling occurs as a result of gray matter atrophy. However, the scarcity of longitudinal clinical data presents challenges for computer-based simulations. To address this, a first-principles-based, physics-constrained Bayesian framework is proposed to model time-dependent connectome dynamics during neurodegeneration. This temporal diffusion network framework segments pathological progression into discrete time windows and optimizes connectome distributions for biomarker Bayesian regression, conceptualized as a learning problem. The framework employs a variational autoencoder-like architecture with computational enhancements to stabilize and improve training efficiency. Experimental evaluations demonstrate that the proposed temporal meta-models outperform traditional static diffusion models. The models were evaluated using both synthetic and real-world MRI and PET clinical datasets that measure amyloid beta, tau, and glucose metabolism. The framework successfully distinguishes normative aging from AD pathology. Findings provide novel support for the “decoupling” hypothesis and reveal eigenvalue-based evidence of pathological destabilization in AD. Future optimization of the model, integrated with real-world clinical data, is expected to improve applications in personalized medicine for AD and other neurodegenerative diseases.
2-Guanidinobenzimidazole as Ligand in Supramolecular, Coordination and Organometallic Chemistry
Authors: Padilla-Martínez Itzia I. , Cruz Alejandro , García-Báez Efrén V.
Published: January 2025

The benzimidazole core (BI) plays a central role in biologically active molecules. The BI nucleus is widely used as a building block to generate a variety of bioactive heterocyclic compounds to be used as antihelmintics, antiprotozoal, antimalarials, anti-inflammatories, antivirals, antimicrobials, antiparasitics, and antimycobacterials. A versatile BI derivative is the 2-guanidinobenzimidazole (2GBI), which, together with its derivatives, is a very interesting poly-functional planar molecule having a delocalised 10 π electrons system conjugated with the guanidine group. The 2GBI molecule has five nitrogen atoms containing five labile N–H bonds, which interact with the out-ward-facing channel entrance, forming a labile complex with the biological receptor sites. In this work, 2GBI and their derivatives were analyzed as ligands to form host–guest, coordination and organometallic complexes. Synthesis methodology, metal geometries, hydrogen bonding (HB) interactions, and the biological activities of the complexes were discussed.
Tepary Bean (Phaseolus acutifolius) Lectins as Modulators of Intracellular Calcium Mobilization in Breast Cancer and Normal Breast Cells
Authors: Díaz-Betancourt Andrea , Galicia-Castillo María Elizabeth , Morales-Tlalpan Verónica , Chávez-Servín Jorge Luis , Blanco-Labra Alejandro , García-Gasca Teresa , Saldaña Carlos
Published: January 2025

Lectins are proteins that specifically recognize carbohydrates on cell membranes, triggering several cellular events such as apoptosis of cancer-transformed cells; however, the mechanisms of action remain incompletely understood. Our research group has reported that a concentrated fraction of Tepary bean lectins (Phaseolus acutifolius; TBLF) exhibits the concentration-dependent induction of apoptosis in colon cancer cells by caspase activation. It is well established that an increase in cytoplasmic calcium ([Ca2+]i) initiates intracellular signals involved in processes such as exocytosis, gene transcription, apoptosis, cell cycle regulation, and muscle contraction, among others. Furthermore, dysregulated calcium signaling has been implicated in various diseases, including certain neurological disorders and cancer. In this study, we aim to demonstrate the effects of native TBLF lectins and a recombinant lectin (rTBL-1) on calcium mobility in breast cancer cells (MCF-7) and non-cancerous cells (MCF-12F). Both TBLF and rTBL-1 increased intracellular calcium concentrations and mobilized calcium from intracellular stores in a concentration-dependent manner; however, the two cell lines exhibited differential responses. While MCF-12F cells restored cytoplasmic calcium concentration, MCF-7 cells maintained a high intracellular calcium concentration. This strongly suggests that lectins can elicit differential cellular responses in cancer and non-cancer cells due to variations in their intrinsic mechanisms of calcium homeostasis. Finally, we demonstrated that TBLF and rTBL-1 can differentially alter Metabolic Cellular Activity (MCA) as a direct measure of cell viability (CVi) in both cell lines. These findings strengthen the evidence of the therapeutic potential of Tepary bean lectins. Undoubtedly, further studies will be necessary to elucidate the mechanisms underlying their applications.
Optimization of CRISPR/Cas9 Gene Editing System in Sheep (Ovis aries) Oocytes via Microinjection
Authors: Wang Haitao , Yang Hengqian , Li Tingting , Chen Yan , Chen Jieran , Zhang Xiaosheng , Zhang Jinlong , Zhang Yuting , Zhang Na , Ma Runlin , Huang Xun , Liu Qiuyue
Published: January 2025

The CRISPR/Cas9 system has become a powerful tool for molecular design breeding in livestock such as sheep. However, the efficiency of the Cas9 system combined with zygote microinjection remains suboptimal. In this study, mature sheep oocytes were used for microinjection to assess the impact of various factors on Cas9 editing efficiency. We found that the in vitro maturation efficiency of oocytes is related to environmental factors such as air temperature, pressure, and humidity. Our results indicate that high-efficiency gene editing can be achieved when targeting the SOCS2, DYA, and TBXT, using a microinjection mixture with a concentration of 10 ng/μL Cas9 and sgRNA. By optimizing the injection capillary, we significantly reduced the oocyte invalidation rate post-microinjection to 3.1–5.3%. Furthermore, we observed that using either Cas9 protein or mRNA in the microinjection process resulted in different genotypes in the edited oocytes. Importantly, parthenogenetic activation did not appear to affect the editing efficiency. Using this high-efficiency system, we successfully generated SOCS2 or DYA gene-edited sheep, with all lambs confirmed to be genetically modified. This study presents a highly efficient method for producing gene-edited sheep, potentially enabling more precise and effective strategies for livestock breeding.
Hyperbaric Oxygen Therapy for the Treatment of Bone-Related Diseases
Authors: Feng Jie , Zhu Chenyu , Zou Jun , Zhang Lingli
Published: January 2025

Hyperbaric oxygen therapy (HBOT) is a therapeutic modality that enhances tissue oxygenation by delivering 100% oxygen at pressures greater than 1 absolute atmosphere. In recent years, HBOT has shown considerable potential in the treatment of bone diseases. While excess oxygen was once thought to induce oxidative stress, recent studies indicate that when administered within safe limits, HBOT can notably promote bone healing and repair. Extensive basic research has demonstrated that HBOT can stimulate the proliferation and differentiation of osteoblasts and encourage bone angiogenesis. Furthermore, HBOT has been shown to exert a beneficial influence on bone metabolism by modulating the inflammatory response and redox status. These mechanisms are closely related to core issues of bone biology. Specifically, in the context of fracture healing, bone defect repair, and conditions such as osteoporosis, HBOT targets the key bone signaling pathways involved in bone health, thereby exerting a therapeutic effect. Several clinical studies have demonstrated the efficacy of HBOT in improving bone health. However, the optimal HBOT regimen for treating various bone diseases still requires further definition to expand the indications for its clinical application. This paper outlines the mechanisms of HBOT, focusing on its antioxidant stress, promotion of bone vascularization, and anti-inflammatory properties. The paper also describes the application of HBOT in orthopedic diseases, thereby providing a scientific basis for the development of precise and personalized HBOT treatment regimens in clinical orthopedics.
Multi-Omics Analysis Decodes Biosynthesis of Specialized Metabolites Constituting the Therapeutic Terrains of Magnolia obovata
Authors: Rai Megha , Rai Amit , Yokosaka Towa , Mori Tetsuya , Nakabayashi Ryo , Nakamura Michimi , Suzuki Hideyuki , Saito Kazuki , Yamazaki Mami
Published: January 2025

Magnolia obovata is renowned for its unique bioactive constituents with medicinal properties traditionally used to treat digestive disorders, anxiety, and respiratory conditions. This study aimed to establish a comprehensive omics resource through untargeted metabolome and transcriptome profiling to explore biosynthesis of pharmacologically active compounds of M. obovata using seven tissues: young leaf, mature leaf, stem, bark, central cylinder, floral bud, and pistil. Untargeted metabolomic analysis identified 6733 mass features across seven tissues and captured chemo-diversity and its tissue-specificity in M. obovata. Through a combination of cheminformatics and manual screening approach, we confirmed the identities of 105 metabolites, including neolignans, such as honokiol and magnolol, which were found to be spatially accumulated in the bark tissue. RNA sequencing generated a comprehensive transcriptome resource, and expression analysis revealed significant tissue-specific expression patterns. Omics dataset integration identified T12 transcript module from WGCNA being correlated with the biosynthesis of magnolol and honokiol in M. obovata. Notably, phylogenetic analysis using transcripts from T12 module identified two laccase (Mo_LAC1 and Mo_LAC2) and three dirigent proteins from the DIR-b/d subfamily as potential candidate genes involved in neolignan biosynthesis. This research established omics resources of M. obovata and laid the groundwork for future studies aimed at optimizing and further understanding the biosynthesis of metabolites of therapeutic potential.
Genome-Wide Identification of the WD40 Gene Family in Walnut (Juglans regia L.) and Its Expression Profile in Different Colored Varieties
Authors: Xi Ruimin , Ma Jiayu , Qiao Xinyi , Wang Xinhao , Ye Hang , Zhou Huijuan , Yue Ming , Zhao Peng
Published: January 2025

The walnut (Juglans regia) is a woody oilseed crop with high economic and food value as its kernels are edible and its hulls can be widely used in oil extraction and plugging, chemical raw materials, and water purification. Currently, red walnut varieties have emerged, attracting consumer interest due to their high nutritional values as they are rich in anthocyanins. WD40 is a widespread superfamily in eukaryotes that play roles in plant color regulation and resistance to stresses. In order to screen for JrWD40 associated with walnut color, we identified 265 JrWD40s in walnuts by genome-wide identification, which were unevenly distributed on 16 chromosomes. According to the phylogenetic tree, all JrWD40s were classified into six clades. WGD (Whole genome duplication) is the main reason for the expansion of the JrWD40 gene family. JrWD40s were relatively conserved during evolution, but their gene structures were highly varied; lower sequence similarity may be the main reason for the functional diversity of JrWD40s. Some JrWD40s were highly expressed only in red or green walnuts. In addition, we screened 16 unique JrWD40s to walnuts based on collinearity analysis. By qRT-PCR, we found that JrWD40-133, JrWD40-150, JrWD40-155, and JrWD40-206 may regulate anthocyanin synthesis through positive regulation, whereas JrWD40-65, JrWD40-172, JrWD40-191, JrWD40-224, and JrWD40-254 may inhibit anthocyanin synthesis, suggesting that these JrWD40s are key genes affecting walnut color variation.
The RNA Demethyltransferase FTO Regulates Ferroptosis in Major Depressive Disorder
Authors: Meng Kexin , Liu Zijing , Yu Yuesong , Zhang Erning , Yu Xiaolin , Meng Peixin , Xiu Jianbo
Published: January 2025

Major depressive disorder (MDD) is a widespread and severe mental health condition characterized by persistent low mood and loss of interest. Emerging evidence suggests that ferroptosis, an iron-dependent form of cell death, and epigenetic dysregulation contribute to the pathogenesis of MDD. This study investigates the role of RNA demethylase FTO and autophagy regulator BECN1 in ferroptosis and their regulation by the active compound ginsenoside Rb1 (GRb1) as a potential antidepressant strategy. Hippocampal tissues from postmortem MDD patient brains and mice with chronic restraint stress (CRS)-induced depression were analyzed. Ferroptosis was evaluated by analyzing the levels of markers such as glutathione (GSH) and malondialdehyde (MDA). GRb1 was administered to CRS model mice by gavage to explore its effects on ferroptosis-related pathways. The results showed that FTO and BECN1 expression was reduced in the hippocampal tissues of MDD patients and CRS model mice, promoting ferroptosis via disruption of the antioxidant system. Moreover, GRb1 treatment increased FTO and BECN1 expression, modulated m6A methylation, restored the antioxidant balance, and inhibited ferroptosis in CRS model mice. These findings reveal a novel epigenetic mechanism of ferroptosis in MDD and highlight GRb1 as a promising agent for treating depression through the targeting of ferroptosis pathways.
Phenotypic and Gene Expression Alterations in Aquatic Organisms Exposed to Microplastics
Authors: Lee Yun Ju , Kim Woo Ryung , Park Eun Gyung , Lee Du Hyeong , Kim Jung-min , Jeong Hyeon-su , Roh Hyun-Young , Choi Yung Hyun , Srivastava Vaibhav , Mishra Anshuman , Kim Heui-Soo
Published: January 2025

The use of plastics, valued for its affordability, durability, and convenience, has grown significantly with the advancement of industry. Paradoxically, these very properties of plastics have also led to significant environmental challenges. Plastics are highly resistant to decomposition, resulting in their accumulation on land, where they eventually enter aquatic environments, due to natural processes or human activities. Among these plastics, microplastics, which are tiny plastic particles, are particularly concerning when they enter aquatic ecosystems, including rivers and seas. Their small size makes them easily ingestible by aquatic organisms, either by mistake or through natural feeding behaviors, which poses serious risks. Moreover, microplastics readily adsorb other pollutants present in aquatic environments, creating pollutant complexes that can have a synergistic impact, magnifying their harmful effects compared to microplastics or pollutants acting alone. As a result, extensive research has focused on understanding the effects of microplastics on aquatic organisms. Numerous studies have demonstrated that aquatic organisms exposed to microplastics, either alone or in combination with other pollutants, exhibit abnormal hatching, development, and growth. Additionally, many genes, particularly those associated with the antioxidant system, display abnormal expression patterns in these conditions. In this review, we examine these impacts, by discussing specific studies that explore changes in phenotype and gene expression in aquatic organisms exposed to microplastics, both independently and in combination with adsorbed pollutants.
Special Issue “Molecular Mechanisms of Bioactive Nutrients Promoting Health Through Gut Microbiota 2.0”
Authors: Bordiga Matteo , Xu Baojun
Published: January 2025

This Special Issue of the International Journal of Molecular Sciences focuses on the highly relevant and rapidly developing topic of gut microbiota research [...]
Pharmaco-Multiomics: A New Frontier in Precision Psychiatry
Authors: Dhieb Dhoha , Bastaki Kholoud
Published: January 2025

The landscape of psychiatric care is poised for transformation through the integration of pharmaco-multiomics, encompassing genomics, proteomics, metabolomics, transcriptomics, epigenomics, and microbiomics. This review discusses how these approaches can revolutionize personalized treatment strategies in psychiatry by providing a nuanced understanding of the molecular bases of psychiatric disorders and individual pharmacotherapy responses. With nearly one billion affected individuals globally, the shortcomings of traditional treatments, characterized by inconsistent efficacy and frequent adverse effects, are increasingly evident. Advanced computational technologies such as artificial intelligence (AI) and machine learning (ML) play crucial roles in processing and integrating complex omics data, enhancing predictive accuracy, and creating tailored therapeutic strategies. To effectively harness the potential of pharmaco-multiomics approaches in psychiatry, it is crucial to address challenges such as high costs, technological demands, and disparate healthcare systems. Additionally, navigating stringent ethical considerations, including data security, potential discrimination, and ensuring equitable access, is essential for the full realization of this approach. This process requires ongoing validation and comprehensive integration efforts. By analyzing recent advances and elucidating how different omic dimensions contribute to therapeutic customization, this review aims to highlight the promising role of pharmaco-multiomics in enhancing patient outcomes and shifting psychiatric treatments from a one-size-fits-all approach towards a more precise and patient-centered model of care.
G3BP1 Regulates the Cell Cycle by Promoting IFNβ Production to Promote PCV2 Replication and Promotes Nuclear Transfer of Viral Proteins by Direct Binding
Authors: Zhang Xinming , Li Kang , Zhou Shenglan , Zhang Leyi , Wang Lei , Liu Yanling , Wang Shuangyun , Xu Ge , Liang Pengshuai , Xu Zheng , Song Changxu
Published: January 2025

Porcine circovirus type 2 (PCV2) is a significant pathogen responsible for porcine circovirus-associated diseases (PCVAD), and it is widely prevalent in pig farms, leading to huge economic losses for the pig industry. Currently, the ability of PCV2 to enhance its own replication by using the antiviral inflammatory factors IFNα, IFNβ, and IL-2 and its complex immune escape mechanism remain unclear, which has attracted wide attention. Research has indicated that GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1) is involved in the innate immune response to a variety of viruses, primarily by regulating and composing stress granules (SGs) to inhibit viral replication. Our initial studies identified elevated G3BP1 expression during PCV2 infection, paradoxically promoting PCV2 replication. In light of this phenomenon, this study aims to elucidate how PCV2 regulates G3BP1 to enhance its replication. Our findings demonstrate that G3BP1 overexpression further activates PCV2-induced expression of RIG-I, MDA5, cGAS and STING, thereby promoting IFNβ production and affecting cell cycle arrest in the S phase, facilitating PCV2 replication. Moreover, interactions were observed between PCV2 Cap protein and G3BP1’s RGG domain, and between PCV2 Rep protein and G3BP1’s NTF2 and RRM domains, potentially promoting viral protein nuclear transfer. In summary, PCV2 enhances its replication by modulating G3BP1 to induce IFNβ production and directly binds viral proteins to promote viral protein nuclear transfer. This research provides a foundation for further investigation into the immune evasion mechanisms of PCV2.