bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of direct-fed microbials supplementation on in vitro and ex vivo ruminal fermentation and nutrient degradability in lactating Holstein dairy cows
Authors: Oyebade Adeoye O , Arriola Kathy , Queiroz Oscar , Cappellozza Bruno I , Vyas Diwakar 
Published: December 2024

Abstract
We conducted two experiments to evaluate the effect of direct-fed microbials (DFM) on fermentation parameters and nutrient degradability with two different approaches using rumen fluid from lactating Holstein dairy cows. In Exp. 1, three doses of a DFM containing Lactobacillus animalis and Propionibacterium freudenreichii (PRO-A) at doses of 3.9 × 106, 7.8 × 106, and 11.7 × 106 CFU or a DFM containing PRO-A, Bacillus subtilis, and B. licheniformis (PRO-B) at doses of 15.2 × 106, 30.4 × 106, and 45.6 × 106 CFU were incubated using corn silage as substrate and pooled rumen fluid from three-rumen fistulated lactating Holstein cows. Dry matter and NDF degradability, gas production, and rumen pH were measured over a 24-h period. In Exp. 2, three ruminally cannulated multiparous cows (165 ± 63 DIM) were used in a 3 × 3 Latin square design. Each experimental period was of 28 d. All cows received a corn silage-based TMR (basal diet), and were assigned to: 1) Control (CON), 2) PRO-A: Basal diet top-dressed with PRO-A at 3 × 109 CFU/day, and 3) PRO-B: Basal diet top-dressed with PRO-B at 11.8 × 109 CFU/day. An ex vivo study (Exp. 2) was conducted using rumen fluid collected during wk 4 of each experimental period from experimental animals. Treatments included: CON, PRO-A, PRO-B, each of which utilized rumen fluid from donor cows given respective treatments. Another set of rumen fluid from PRO-A and PRO-B cows were dosed with additional dose of respective DFM, resulting in two more treatments (PRO-A+ and PRO-B+). In Exp. 1, linear effects (P = 0.03) were observed on in vitro NDF degradability following DFM incubation. In Exp. 2, no treatment effects were observed on DM and NDF digestibility. In summary, DFM increased DM and NDF degradability in vitro using rumen fluid from cows not exposed to DFM; however, no effects were observed under ex vivo experimental conditions when rumen fluid was collected from cows consuming DFM.
Nanoliposomal system for augmented antibacterial and antiproliferative efficacy of Melissa officinalis L. extract
Authors: Nizam Nagihan , Taner Gokce , Cagal Munevver Muge 
Published: December 2024

Abstract

Objective
This study focused on the nanoliposomal encapsulation of bioactive compounds extracted from Melissa officinalis L. (ME) using ethanol as a strategy to improve the antibacterial activity, anticytotoxic, and antiproliferative properties.

Methods
Nanoliposomes loaded with ME (MEL) were characterized for total phenolic content, particle size, polydispersity, and encapsulation efficiency. The minimum inhibitory concentration (MIC) values for MEL and ME were determined to evaluate antibacterial activity. To examine the toxicity profiles of ME and MEL, tests were conducted on the A549 and BEAS-2B cell lines using the MTT assay. Furthermore, an in vitro sctrach assay was conducted to evaluate the antiproliferative effects of ME and MEL on A549 cells.

Results
Nanoliposomes presented entrapment efficiency higher than 80%, nanometric particle size, and narrow polydispersity. The MIC values for MEL and ME were observed as 93.75 μg/μL against E. coli. MIC values for MEL and ME were achieved as 4.68 μg/μL and 9.375 μg/mL against S. aureus, respectively. The IC50 values for ME were determined to be 1.13 mg/mL and 0.806 mg/mL, while the IC50 values for MEL were found to be 3.5 mg/mL and 0.868 mg/mL on A549 and BEAS-2B cell lines, respectively. Additionally, The MEL showed an antiproliferative effect against A549 cells at 500 μg/mL concentration.

Conclusion
All experimental findings unequivocally demonstrate that the novel nanoliposomal system has effectively augmented the antibacterial activities and antiproliferative effects of ME. The initial findings indicate that nanoliposomes could effectively serve as carriers for ME in pharmaceutical applications.
Impact of micro-nano plastics in daily life on human health: toxicological evaluation from the perspective of normal tissue cells and organoids
Authors: Wang Jie , Xie Lan-Gui , Wu Xian-Fu , Zhao Zong-Ge , Lu Yong , Sun Hui-Min 
Published: December 2024

Abstract
Plastics are the most frequently used materials in people’s daily life, and the primary and secondary microplastics generated from them may harm the health of adults. This paper focuses on the summary of the existence of microplastics in many objects most closely related to people in daily life, the toxicological influences it causes in cultured human normal cells and organoids, and the prospects for future research directions. Micro- and nano-plastics (MNPs) are found in almost all of our everyday products, such as food, drink, and daily necessities, etc. It can enter the digestive tract, respiratory system, and body fluids of the human body, and at lower or equal environment concentrations exhibits obvious cytotoxicity and genotoxicity toward cells and organoids, probably becoming a kind of toxin affecting human health. In addition, due to MNPs can be transferred from the placenta to the embryo, long-term growth-tracking studies of newborns should be done vitally. Besides, due to their wide usability in daily products and the ability to penetrate cytomembranes, the toxicological effects of polyethylene and polypropylene nanoplastic particles equal to or lower than environmental (normal exposure to human body) concentrations are recommended to be studied on human health in the future. Finally, for those individuals who carry MNPs, long-term health evaluation must be performed.
Predicting the molecular mechanisms of cardiovascular toxicity induced by per- and polyfluoroalkyl substances: an In Silico network toxicology perspective
Authors: Karakuş Fuat , Kuzu Burak 
Published: December 2024

Abstract
Background: Per- and polyfluoroalkyl substances (PFAS) are human-made chemicals that accumulate in the human body and the environment over time. Humans are primarily exposed to PFAS through drinking water, food, consumer products, and dust. These exposures can have many adverse health effects, including cardiovascular diseases (CVDs) and factors contributing to CVDs. This study identified the molecular mechanisms of CVDs caused by PFAS. Methods: For this purpose, various computational tools, such as the Comparative Toxicogenomic Database, ShinyGO, ChEA3, MIENTURNET, GeneMANIA, STRING, and Cytoscape, were used to conduct in silico analyses. Results: The results showed that 10 genes were common between PFAS and CVDs, and among these common genes, the PPAR signaling pathway, fatty acid metabolic processes, and lipid binding were the most significantly associated gene ontology terms. Among the top 10 transcription factors (TFs) related to these common genes, peroxisome proliferator-activated receptor gamma and androgen receptor were the most prominent. Additionally, hsa-miR-130b-3p, hsa-miR-130a-3p, and hsa-miR-129-5p were featured microRNAs involved in PFAS-induced CVDs. Finally, PPARA and PPARG were identified as core genes involved in PFAS-induced CVDs. Conclusion: These findings may contribute to a better understanding of the molecular mechanisms and reveal new potential targets in PFAS-induced CVDs.
Outcomes of HIV-infected children on antiretroviral therapy for at least 10 years at the Essos Hospital Centre, Cameroon: contributing to the elimination of paediatric AIDS in tropical settings
Authors: Njom Nlend Anne Esther , Fokam Joseph , Mekoui Suzanne , Epée Ngoué Jeannette , Nga Motaze Annie Carole , Colizzi Vittorio , Perno Carlo-Federico , Ndjolo Alexis , Halle-Ekane Gregory-Edie , Sandie Arsene 
Published: December 2024

Abstract
Evidence on long-term outcomes of children receiving antiretroviral therapy (ART) in low- and middle-income countries (LMICs) is of utmost importance to optimize current and future therapeutic strategies for HIV. We sought to ascertain the long-term responses among ART-experienced children and their potential implications. A retrospective, observational, facility-based cohort study was conducted among 136 ART-experienced children monitored for 10 years (2007–2017) at the Essos Hospital Centre in Yaoundé, Cameroon. Primary outcomes were good clinical response defined as the World Health Organization (WHO) clinical stage 1/2, immune restoration as CD4 &gt;500 cells/mm3, viral suppression (VS) as viral load (VL) &lt;1000, or viral undetectability as VL &lt;40 copies/ml at the last follow-up and their predictors (P &lt; .05). At ART initiation among the 90 eligible children, median (interquartile range) age was 29.5 (11–60) months, 53.3% were males, 34.5% were at WHO clinical stage 1/2, median-CD4 was 497 cells/mm3, and initial ART-regimens were mainly zidovudine-lamivudine-nevirapine (85.5%) and zidovudine-lamivudine-efavirenz (12.2%). After 10 years of follow-up, 36.7% were switched to protease-based ART regimens, those at WHO clinical stage 1/2 improved to 75.5%; median-CD4 increased to 854 cells/mm3; 83.3% achieved VS, while only 10% achieved viral undetectability. Following multivariate analysis, no predictor of VS or immune recovery was identified (P &gt; .05). In this LMIC, long-term outcomes of children on ART appear encouraging, characterized by moderate VS rate and immune recovery. However, challenges in achieving viral undetectability indicate continuous viral replication and risks of drug resistance emergence that may jeopardize effectiveness of future paediatric ART strategies.
Rosthornin B alleviates inflammatory diseases via directly targeting NLRP3
Authors: Yang Yanqing , Liu Didi , Cao Hairuo , Lu Li , Zhang Wei , Liu Chenfei , Zeng Yao , Shang Feifei , Tao Ye , Zhao Bao , Wang Fengchao , Tang Tiantian , Deng Mengmeng 
Published: December 2024

AbstractAberrant activation of the NLRP3 inflammasome contributes to the evolution of diverse inflammatory diseases. Inhibition of the NLRP3 inflammasome has been proven to be an effective treatment strategy for NLRP3‐driven diseases. This study revealed that multiple natural diterpenes from Isodon plants can inhibit the NLRP3 inflammasome, among which Rosthornin B (Ros B) exhibited the best inhibitory effect, with an IC50 of 0.39 μM. Further study revealed that Ros B directly interacts with NLRP3, thereby restraining NEK7‐NLRP3 interaction and inhibiting NLRP3 inflammasome assembly and activation. Remarkably, Ros B had a significant therapeutic benefit in mouse models of NLRP3‐driven septic shock, peritonitis, and colitis. Our study has identified a series of natural diterpenes that target the NLRP3 inflammasome. These natural diterpenes, especially those with low IC50 values, may lead to the development of new drugs and potential clinical therapies for diseases driven by NLRP3 inflammasome activation.
Exploring combination therapy centered on targeted immunotherapy for advanced hepatocellular carcinoma: a beacon of hope
Authors: Wang Yanbin , Wu Yuqi , Zhang Hong , Wang Jing , Song Anping , Qiu Hong , Yuan Xianglin , Xiong Hua , Zou Yanmei 
Published: December 2024

Abstract
Hepatocellular carcinoma (HCC) is an aggressive malignancy that is highly prevalent worldwide. It is often diagnosed at an advanced stage, which poses challenges for curative treatment and leads to an unfavorable prognosis. The introduction of targeted therapy drugs, such as tyrosine kinase inhibitors, and immunotherapeutic drugs, including immune checkpoint inhibitors, has substantially improved the therapeutic effectiveness for advanced HCC. However, their efficacy remains suboptimal, owing to challenges related to patient responsiveness and drug resistance. To address these challenges, researchers have investigated combination therapies, including targeted immunotherapy, and triple therapies based on targeted immunotherapy, such as a combination of radiotherapy and targeted immunotherapy. In addition, they conducted a comprehensive investigation of potential new targets and drugs, yielding a series of significant findings. This review presents an outline of the treatment mechanisms and associated clinical research findings on mainstream targeted therapies, immunotherapies, and combination therapies. It also summarizes the current status of combination therapies for advanced HCC and anticipates future developments and trends in this field.
Survival time and prognostic factors in dogs diagnosed with haemangiosarcoma in UK first opinion practice
Authors: Taylor C. , Barry G.J. , O’Neill D.G. , Guillén A. , Pickard P. , Labadie J. , Brodbelt D.C. 
Published: December 2024

AbstractVisceral haemangiosarcoma is considered clinically aggressive in dogs, with perceived poor prognosis often leading to euthanasia at presentation. This study aimed to determine survival times and prognostic factors in dogs with haemangiosarcoma under first-opinion care.Dogs diagnosed with haemangiosarcoma in first-opinion practice in 2019 were identified in VetCompass electronic health records (EHRs) and manually examined to capture variables potentially associated with survival. Median survival time (MST) from diagnosis was calculated for the whole population and based on the primary tumour location. Binary logistic regression was used to explore differences between dogs that died on the day of diagnosis and those that survived ≥1 day. Cox proportional hazards modelling explored factors associated with time to death in dogs that survived ≥1 day.Across all haemangiosarcoma cases (n=788), overall MST was 9.0 days (95%CI:5.0-15.0, range: 0-1789) and proportional 1-year survival was 12.0% (95%CI:9.7-15.0%). Dogs with splenic (MST=4.0 days, 95%CI 0.0-9.0) and cutaneous haemangiosarcoma (MST=119.0 days,95%CI:85.0-248.0) had MST greater than 0 days. Male sex and increasing tumour size were associated with increased hazard of death while cutaneous location and surgery were associated with reduced hazard of death.A very short survival time was identified for haemangiosarcoma under first-opinion care. Although survival time was longest for cutaneous cases, the actualised prognosis was poor overall for haemangiosarcoma. This study provides valuable information for contextualised care and dialogues with clients in first-opinion practice.
Data-driven discovery of cell-type-directed network-correcting combination therapy for Alzheimer’s disease
Authors: Li Yaqiao , Serras Carlota Pereda , Blumenfeld Jessica , Xie Min , Hao Yanxia , Deng Elise , Chun You Young , Holtzman Julia , An Alice , Yoon Seo Yeon , Tang Xinyu , Rao Antara , Woldemariam Sarah , Tang Alice , Zhang Alex , Simms Jeffrey , Lo Iris , Oskotsky Tomiko , Keiser Michael J , Huang Yadong , Sirota Marina 
Published: December 2024

AbstractAlzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by heterogeneous molecular changes across diverse cell types, posing significant challenges for treatment development. To address this, we introduced a cell-type-specific, multi-target drug discovery strategy grounded in human data and real-world evidence. This approach integrates single-cell transcriptomics, drug perturbation databases, and clinical records. Using this framework, letrozole and irinotecan were identified as a potential combination therapy, each targeting AD-related gene expression changes in neurons and glial cells, respectively. In an AD mouse model, this combination therapy significantly improved memory function and reduced AD-related pathologies compared to vehicle and single-drug treatments. Single-nuclei transcriptomic analysis confirmed that the therapy reversed disease-associated gene networks in a cell-type-specific manner. These results highlight the promise of cell-type-directed combination therapies in addressing multifactorial diseases like AD and lay the groundwork for precision medicine tailored to patient-specific transcriptomic and clinical profiles.Graphic Abstract
Tissue-Specific Cell Type Annotation with Supervised Representation Learning using Split Vector Quantization and Its Comparisons with Single-cell Foundation Models
Authors: Heryanto Yusri Dwi , Zhang Yao-zhong , Imoto Seiya 
Published: December 2024

AbstractCell-type annotation in single-cell data involves identifying and labeling the cell types based on their gene expression profiles or molecular features. Recently, with advances in single-cell foundation models (FMs), unsupervised annotation and transfer learning with FMs have been explored for cell-type annotation tasks. However, because FMs are usually pre-trained in an unsupervised manner on data spanning a wide variety of tissues and cell types, their representations for specific tissues may lack specificity and become overly generalized. In this work, we propose a novel supervised representation learning method using split-vector-quantization, single-cell Vector-Quantization Classifier (scVQC). We evaluated scVQC against both supervised and unsupervised representation learning approaches, with a focus on foundation models pretrained on large-scale single-cell datasets, such as scBERT and scGPT. The experimental results highlight the importance of label supervision in cell-type annotation tasks and demonstrate that the learned codebook effectively profiles and distinguishes different cell types.
Occurrence of the Humboldt Penguin (Spheniscus humboldti, Meyen, 1834) in El Ferrol Bay, Chimbote, Peru, and strategies for its conservation
Authors: Loayza-Aguilar Rómulo E. , Medina-Quezada Heillyn , Merino Fernando , Saldaña-Rojas Guillermo B. , Mendoza Sorayda , Olivos-Ramirez Gustavo E. 
Published: December 2024

ABSTRACTThe Humboldt penguin is an emblematic species of the Humboldt ecosystem of Peru and Chile, declared as vulnerable in The IUCN Red List of Threatened Species in 2020. By 2023, its population was estimated around 9,900 pairs, which means a decrease of 93% of its population in 70 years. In response to a warning of its occurrence on the Guaneras Islands located in El Ferrol Bay (Chimbote, Peru), the objective of this study was to verify its presencein situ. Between October and November 2024, four expeditions were carried out on the leeward side of the Islote Peña Blanca (White Rock Islet), Isla Blanca (White Island), Isla Ferrol del Norte (Northern Ferrol Island), Isla Ferrol del Centro (Central Ferrol Island), and Isla Ferrol del Sur (Southern Ferrol Island). The presence of 149 individuals, 5 of them juveniles, and one chick accompanied by its parent, was verified on Northern Ferrol Island, Central Ferrol Island, and Southern Ferrol Island. It is estimated that the presence of these organisms is explained by the improvement of oceanographic conditions in this bay. Considering the high vulnerability of the species, the local community must articulate efforts to guarantee the establishment of its population in this particular habitat.
A gut-microbiota-muscle axis that protects against age-related motor decline by regulating mitochondrial fission inC. elegans
Authors: Dennis Nathan , Vazquez-Prada Mireya , Xue Feng , Freeman Laura M. , Karamalegos Antonis , Kudzminkaite Brigita , Brown Ian , Ezcurra Marina 
Published: December 2024

AbstractAcross diverse taxa, the composition of the microbiota is associated with lifelong host health. A mechanistic understanding of how microbial communities influence host physiology could lead to microbiota-based interventions for lifelong health. Here, we have developed a new host-microbiota model system utilising the model organismC. eleganscombined with a defined natural microbiota (DefNatMta) consisting of 11 bacteria isolated from wildC. elegans, to study host-microbiota interactions in a more natural setting. We show that DefNatMta colonises theC. elegansgut, forming a stable and distinct gut microbiota. Using DefNatMta, we find a gut microbiota-muscle axis by which the microbiota affects age-related motility and muscular strength and protects against age-related decline in motor function. The gut microbiota-muscle axis acts by altering metabolism and mitochondrial network dynamics in muscle, and requires dynamin-related protein 1 DRP-1, a regulator of mitochondrial fission to protect against age-related motility decline. Our study demonstrates a gut microbiota-muscle axis and microbiota-mitochondria communication affecting age-related muscle function.
Short- and long-term reconfiguration of rat prefrontal cortical networks following single doses of psilocybin
Authors: Purple Ross J. , Gupta Rahul , Thomas Christopher W. , Golden Caroline T. , Froudist-Walsh Seán , Jones Matthew W. 
Published: December 2024

SUMMARYWe quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybin. Using chronically implanted Neuropixels probes, we recorded local field potentials (LFP) alongside action potentials from hundreds of neurons spanning infralimbic, prelimbic and cingulate subregions of the medial prefrontal cortex of freely-behaving adult rats. Psilocybin (0.3mg/kg or 1mg/kg i.p.) unmasked 100Hz high frequency oscillations that were most pronounced within the infralimbic cortex, persisted for approximately 1h post-injection and were accompanied by decreased net pyramidal cell firing rates and reduced signal complexity. These acute effects were more prominent during resting behaviour than during a sustained attention task. LFP 1-, 2- and 6-days post-psilocybin showed gradually-emerging increases in beta and low-gamma (20-60Hz) power, specific to the infralimbic cortex. These findings reveal features of psychedelic action not readily detectable in human brain imaging, implicating infralimbic network oscillations as potential biomarkers of psychedelic-induced network plasticity over multi-day timescales.
PEX1G843Dremains functional in peroxisome biogenesis but is rapidly degraded by the proteasome
Authors: Sheedy Connor J. , Chowdhury Soham P. , Ali Bashir A. , Miyamoto Julia , Pang Eric Z. , Bacal Julien , Tavasoli Katherine U. , Richardson Chris D. , Gardner Brooke M. 
Published: December 2024

AbstractThe PEX1/PEX6 AAA-ATPase is required for the biogenesis and maintenance of peroxisomes. Mutations inHsPEX1andHsPEX6disrupt peroxisomal matrix protein import and are the leading cause of Peroxisome Biogenesis Disorders (PBDs). The most common disease-causing mutation in PEX1 is theHsPEX1G843Dallele, which results in a reduction of peroxisomal protein import. Here we demonstrate thatin vitrothe homologous yeast mutant,ScPex1G700D, reduces the stability of Pex1’s active D2 ATPase domain and impairs assembly with Pex6, but can still form an active AAA-ATPase motor.In vivo,ScPex1G700Dexhibits only a slight defect in peroxisome import. We generated model humanHsPEX1G843Dcell lines and show that PEX1G843Dis rapidly degraded by the proteasome, but that induced overexpression of PEX1G843Dcan restore peroxisome import. Additionally, we found that the G843D mutation reduces PEX1’s affinity for PEX6, and that impaired assembly is sufficient to induce degradation of PEX1WT. Lastly, we found that fusing a deubiquitinase to PEX1G843Dsignificantly hinders its degradation in mammalian cells. Altogether, our findings suggest a novel regulatory mechanism for PEX1/PEX6 hexamer assembly and highlight the potential of protein stabilization as a therapeutic strategy for PBDs arising from the G843D mutation and other PEX1 hypomorphs.