Mitigating animal methods bias to reduce animal use and improve biomedical translation.

Nonanimal biomedical research methods have advanced rapidly over the last decade making them the first-choice model for many researchers due to improved translatability and avoidance of ethical concerns. Yet confidence in novel nonanimal methods is still being established and they remain a small portion of nonclinical biomedical research, which can lead peer reviewers to evaluate animal-free studies or grant proposals in a biased manner. This "animal methods bias" is the preference for animal-based research methods where they are not necessary or where nonanimal-based methods are suitable. It affects the fair consideration of animal-free biomedical research, hampering the uptake and dissemination of these approaches by putting pressure on researchers to conduct animal experiments and potentially perpetuating the use of poorly translatable model systems. An international team of researchers and advocates called the Coalition to Illuminate and Address Animal Methods Bias (COLAAB) aims to provide concrete evidence of the existence and consequences of this bias and to develop and implement solutions towards overcoming it. The COLAAB recently developed the first of several mitigation tools: the Author Guide for Addressing Animal Methods Bias in Publishing, which is described herein along with broader implications and future directions of this work.

Professional quality of life in animal research personnel is linked to retention & job satisfaction: A mixed-methods cross-sectional survey on compassion fatigue in the USA.

BACKGROUND: Working with research animals can be both rewarding and challenging. The rewarding part of the work is associated with understanding the necessity for animal research to improve the health of humans and animals and the knowledge that one can provide care and compassion for the animals. Challenges with animal research include witnessing stress/pain in animals necessitated by scientific requirements, end of study euthanasia, and societal stigmatization about animal research. These challenges could be compounded with more general workplace stresses, in turn, impacting job retention and satisfaction. However, these factors have yet to be formally evaluated. Therefore, the purpose of this survey was to comprehensively evaluate professional quality of life's correlation with key workplace metrics. METHODS: Six institutions were recruited to participate in a longitudinal intervention trial on compassion fatigue resiliency. This manuscript reports key baseline metrics from this survey. A cross-sectional mixed methods survey was developed to evaluate professional quality of life, job satisfaction, retention, and factors influencing compassion fatigue resiliency. Quantitative data were analyzed via general linear models and qualitative data were analyzed by theme. RESULTS: Baseline data was collected from 198 participants. Personnel who reported higher compassion satisfaction also reported higher retention and job satisfaction. Conversely, personnel who reported higher burnout also reported lower job satisfaction. In response to open-ended questions, participants said their compassion fatigue was impacted by institutional culture (70% of participants), animal research (58%), general mental health (41%), and specific compassion fatigue support (24%). CONCLUSIONS: In conclusion, these results show that professional quality of life is related to important operational metrics of job satisfaction and retention. Furthermore, compassion fatigue is impacted by factors beyond working with research animals, including institutional culture and general mental health support. Overall, this project provides rationale and insight for institutional support of compassion fatigue resiliency.

Protective effect of quercetin on lipopolysaccharide­induced miscarriage based on animal experiments and network pharmacology.

Spontaneous abortion (SA) occurs in woman of child­bearing age, jeopardizing their physical and mental health. Quercetin is a natural flavonoid, which exhibits a variety of pharmacological activities. However, the role and mechanisms of quercetin in SA still need to be further explored. Animal experiments were performed to examine the effect of quercetin in treating SA. Institute of Cancer Research mice were injected with lipopolysaccharide into the tail vein on the 7th day of gestation to establish a SA model. Gavage was performed during days 3­8 of gestation with high­, medium­ and low­dose of quercetin. Then the effect of quercetin on embryos was evaluated. Animal experiment showed that quercetin could remarkably reduce the embryo loss rate and increase the mean weight of surviving embryos to some degree. Furthermore, network pharmacology was employed to explore the underlying mechanisms of quercetin in the treatment of SA. Several databases were used to collect the targets of SA and quercetin. Protein­protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to elucidate the interactions between SA and quercetin. The relative mRNA expressions of several targets in uterine were detected by quantitative reverse transcriptase polymerase chain reaction (RT­qPCR). Network pharmacology indicated that the effects of quercetin in treating SA were mainly related to hormone response and the modulation of defense response and inflammatory response, involving signaling pathways such as PI3K­Akt, VEGF, MAPK and core targets such as AKT1, albumin, caspase­3. RT­qPCR showed that quercetin could up­regulate AKT1, MAPK1, PGR, SGK1 and down­regulate ESR1, MAPK3. The results showed that quercetin may modulate multiple signaling pathways by targeting core targets to prevent and treat SA.

Effects of Saikosaponin-A on Insulin Resistance in Obesity: Computational and Animal Experimental Study.

Obesity is known to be associated with increased inflammation and dysregulated autophagy, both of which contribute to insulin resistance. Saikosaponin-A (SSA) has been reported to exhibit anti-inflammatory and lipid-lowering properties. In this research, we employed a combination of computational modeling and animal experiments to explore the effects of SSA. Male C57BL/6 mice were categorized into four groups: normal diet, high-fat diet (HFD), HFD + atorvastatin 10 mg/kg, and HFD + SSA 10 mg/kg. We conducted oral glucose and fat tolerance tests to assess metabolic parameters and histological changes. Furthermore, we evaluated the population of Kupffer cells (KCs) and examined gene expressions related to inflammation and autophagy. Computational analysis revealed that SSA displayed high binding affinity to tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, fibroblast growth factor 21 (FGF21), and autophagy-related 7 (ATG7). Animal study demonstrated that SSA administration improved fasting and postprandial glucose levels, homeostatic model assessment of insulin resistance (HOMA-IR) index, as well as triglyceride, free fatty acid, total cholesterol, low-density lipoprotein cholesterol (LDL-C)-cholesterol, and high-density lipoprotein cholesterol (HDL-C)-cholesterol levels in HFD-fed mice. Moreover, SSA significantly reduced liver weight and fat accumulation, while inhibiting the infiltration and M1 activation of KCs. At the mRNA level, SSA downregulated TNF-α and NF-κB expression, while upregulating FGF21 and ATG7 expression. In conclusion, our study suggests that SSA may serve as a therapeutic agent for addressing the metabolic complications associated with obesity. This potential therapeutic effect is attributed to the suppression of inflammatory cytokines and the upregulation of FGF21 and ATG7.

[Current regulations in the Animal Welfare Act and the significance for animal research]. / Aktuelle Regelungen im Tierschutzgesetz und Bedeutung für die tierexperimentelle Forschung.

Due to the legal implantation of the 3R principle, the number of laboratory animals decreased significantly over the past 10 years. In this article, the historical development of animal experiments over the last decade will be presented in the context of the current regulations of the Animal Welfare Act. It points out bureaucratic obstacles to the approval of animal experiments, which jeopardize Germany as a research location for both academia and industry. The article presents constructive proposals for solutions. This should be done in accordance with the DFG recommendation to ensure efficient biomedical research while maintaining the highest animal welfare standards.

60 Years of the 3Rs symposium: Lessons learned and the road ahead.

When The Principles of Humane Experimental Technique was published in 1959, authors William Russell and Rex Burch had a modest goal: to make researchers think about what they were doing in the laboratory - and to do it more humanely. Sixty years later, their groundbreaking book was celebrated for inspiring a revolution in science and launching a new field: The 3Rs of alternatives to animal experimentation. On November 22, 2019, some pioneering and leading scientists and researchers in the field gathered at the Johns Hopkins Bloomberg School of Public Health in Bal-timore for the 60 Years of the 3Rs Symposium: Lessons Learned and the Road Ahead. The event was sponsored by the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), the Foundation for Chemistry Research and Initiatives, the Alternative Research & Development Foundation (ARDF), the American Cleaning Institute (ACI), the International Fragrance Association (IFRA), the Institute for In Vitro Sciences (IIVS), John "Jack" R. Fowle III, and the Society of Toxicology (SoT). Fourteen pres-entations shared the history behind the groundbreaking publication, international efforts to achieve its aims, stumbling blocks to progress, as well as remarkable achievements. The day was a tribute to Russell and Burch, and a testament to what is possible when people from many walks of life - science, government, and industry - work toward a common goal.

William Russell and Rex Burch published their book The Principles of Humane Experimental Technique in 1959. The book encouraged researchers to replace animal experiments where it was possible, to refine experiments with animals in order to reduce their suffering, and to reduce the number of animals that had to be used for experiments to the minimum. Sixty years later, a group of pioneering and leading scientists and researchers in the field gathered to share how the publi­cation came about and how the vision inspired international collaborations and successes on many different levels including new laws. The paper includes an overview of important milestones in the history of alternatives to animal experimentation.

Course on Breeding, Handling, and Experimental Procedures of Zebrafish (Danio rerio): Training, Refinement, Paradigm Shift, and Dissemination of Knowledge from Brazil to the World.

Currently, in Brazil, all researchers involved in animal experimentation must undergo training in laboratory animal science to stay updated on biology, methodology, ethics, and legal considerations related to the use of animals. The training program presented in this study not only aims to fulfill a legal obligation but also intends to train students and professionals to effectively care for their biomodels. It seeks to help them understand the importance of this care, both for the welfare of the animals and for the results of their projects. In total, 58 participants were present at the event (pre-event and full-time course). These participants consisted students and professionals from 11 institutions and 5 different countries. These numbers demonstrate the successful attainment of the desired capillarity in the scientific community and the posterior dissemination of knowledge. Through this course, it was possible to train the participants and raise their awareness about the importance of applying scientific knowledge in their daily practices to maintain the animals, ensuring the welfare of the models and refining the research. Finally, the program presented in this study, as well as the strategies adopted, can serve as a model for other institutions aiming to achieve similar results.

[Mechanism of Fushen Granules treat peritoneal dialysis-related peritonitis by regulating TLR4/NF-κB pathway:based on network pharmacology and animal experiments].

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets. The obtained 276 common targets were imported into DAVID for GO function enrichment and KEGG pathway enrichment. The main signaling pathway of Fushen Granules in the treatment of PDRP was predicted as Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB. The rat model of uremia was induced by 5/6 nephrectomy. From two weeks after operation, the rat model of peritoneal dialysis(PD) was established by intraperitoneal injection of 20 mL dialysate with 1.25% glucose every day. The sham operation group and model group received 2 mL normal saline by gavage every day. The rats in Fushen Gra-nules groups were administrated with 2 mL solutions of low-(0.54 g·kg~(-1)), medium-(1.08 g·kg~(-1)) and high-dose(2.16 g·kg~(-1)) Fushen Granules every day. The bifico group received 2 mL(113.4 mg·kg~(-1)) of bifico solution every day. At the end of the 8th week, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in each group were measured. The serum levels of hypersensitive C reactive protein(hs-CRP), tumor necrosis factor(TNF)-α, and interleukin(IL)-6 were measured, and the pathological changes in the colon tissue were observed by hematoxylin-eosin(HE) staining. The serum levels of lipopolysaccharide(LPS) and lipopolysaccharide-binding protein(LBP) of rats were measured, and the expression levels of LBP, TLR4, NF-κB p65, inhibitor of κB kinase α(IκBα), TNF-α, and IL-1ß in the colon tissue were determined. Compared with sham operation group, the model group had abnormal structure of all layers of colon tissue, sparse and shorter intestinal villi, visible edema in mucosal layer, wider gap, obvious local inflammatory cell infiltration, significantly decreased body weight(P<0.01), and significantly increased kidney function index(Scr, BUN) content(P<0.01). Serum levels of inflammatory cytokines(hs-CRP, TNF-α, IL-6), LPS and LBP were significantly increased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß were significantly increased(P<0.01), and protein expressions of IκBα were significantly decreased(P<0.01). Compared with model group, intestinal villi damage in colonic tissue of rats in low-, medium-and high-dose Fushen Granules groups and bifico group were alleviated to different degrees, edema in submucosa was alleviated, space was narrowed, and inflammatory cell infiltration in lamina propria was reduced. The contents of renal function index(Scr, BUN) and serum inflammatory factors(hs-CRP, TNF-α, IL-6) were significantly decreased(P<0.05 or P<0.01) in medium-and high-dose Fushen Granules groups and bifico group(P<0.05 or P<0.01). Serum LPS and LBP contents in Fushen Granules group and bifico group were significantly decreased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß in Fushen Granules group were significantly decreased(P<0.05 or P<0.01), and protein expressions of IκBα were significantly increased(P<0.01). The expression of LBP protein in bifico group was significantly decreased(P<0.01). The results suggest that Fushen Granules can protect the residual renal function of PD rats, reduce the inflammatory response, and protect the colon tissue. Based on network pharmacology, TLR4/NF-κB pathway may be the main signaling pathway of Fushen granule in the treatment of PDRP. The results showed that Fushen Granules could improve intestinal inflammation and protect intestinal barrier to prevent PDRP by regulating the expression of key factors in TLR4/NF-κB pathway in colon of PD rats.

[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

Recommendations for measuring and standardizing light for laboratory mammals to improve welfare and reproducibility in animal research.

Light enables vision and exerts widespread effects on physiology and behavior, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter experiments in an appropriate physiological and behavioral state. Furthermore, proper consideration of light during experimentation is important both when it is explicitly employed as an independent variable and as a general feature of the environment. This Consensus View discusses metrics to use for the quantification of light appropriate for nonhuman mammals and their application to improve animal welfare and the quality of animal research. It provides methods for measuring these metrics, practical guidance for their implementation in husbandry and experimentation, and quantitative guidance on appropriate light exposure for laboratory mammals. The guidance provided has the potential to improve data quality and contribute to reduction and refinement, helping to ensure more ethical animal use.

Rodent tests for psychiatric drugs get a rethink.

Under pressure to ditch a controversial swim test for depression, scientists look for more precise measures.

Phase-out planning for animal experimentation.

Since the late 2010s, the idea of phase-out planning for animal experimentation (PPAE) has come to the foreground of political debates, but central notions and arguments are understood differently by different participants and stand in need of clarification. This article draws on public communications on ten political projects related to PPAE to propose a philosophical explication of PPAE and to articulate proponents' central moral argument. According to the argument, the phase-out of animal experimentation is morally desirable and planned interventions are both necessary and sufficient to achieve it. The normative and descriptive premises of the argument are stated and discussed, flagging questions that need answering for a more thorough assessment of the argument. This results in a series of seven action points for researchers and stakeholders of phase-out planning for animal experimentation. The overall goal is to enable an open and productive discussion about PPAE in public, political, and academic settings.

In recent years, a new demand has entered the political arena: that the phase-out of animal experimentation should be planned. But it is important to understand exactly what this means. This article draws on ten documents from governments, parliaments, and NGOs to tease out what they mean by "planning the phase-out of animal experimentation." It also discusses the main argument that is advanced in favor of phase-out planning and highlights seven gaps in our knowledge that we should try to fill in order to move the discussion forward. In sum, the article is the first to explicitly define phase-out planning for animal experimentation and to directly discuss its pros and cons from a philosophical point of view. This is helpful in avoiding misunderstandings and talking past each other, enabling an open and productive debate.

Resveratrol ameliorates ulcerative colitis by upregulating Nrf2/HO­1 pathway activity: Integrating animal experiments and network pharmacology.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory condition affecting the rectum and colon. Inflammation and compromisation of the intestinal mucosal barrier are key in UC pathogenesis. Resveratrol (Res) is a naturally occurring polyphenol that exhibits anti­inflammatory and antioxidant properties. Nuclear factor erythroid­2­related factor 2/heme oxygenase 1 (Nrf2/HO­1) pathway regulates occurrence and development of numerous types of diseases through anti­inflammatory and antioxidant activity. However, it is not clear whether Nrf2/HO­1 pathway is involved in the treatment of Res in UC. Therefore, the present study aimed to investigate whether Res modulates the Nrf2/HO­1 signaling pathway to attenuate UC in mice. Dextran sulfate sodium (DSS) was used to induce experimental UC in male C57BL/6J mice. Disease activity index (DAI) and hematoxylin eosin (H&E) staning was used to assessed the magnitude of colonic lesions in UC mice. ELISA) was utilized to quantify inflammatory cytokines (IL­6, IL­1ß, TNF­α and IL­10) in serum and colon tissues. Immunohistochemistry and Western blot were used to evaluate the expression levels of tight junction (TJ) proteins [zonula occludens (ZO)­1 and Occludin] in colon tissues. Pharmacokinetic (PK) parameters of Res were derived from TCMSP database. Networkpharmacology was employed to identify the biological function and pharmacological mechanism of Res in the process of relieving UC, and the key target was screened. The binding ability of Res and key target was verified by molecular docking. Finally, the effectiveness of key target was substantiated by Western blot. Res decreased DAI, ameliorated histopathological changes such as crypt loss, disappeatance of the mucosal epithelium, and inflammatory infiltration in mice. Additionally, Res decreased expression of pro­inflammatory cytokines IL­6, IL­1ß and TNF­α and increased anti­inflammatory factor IL­10 expression. Res also restored the decreased protein expression of ZO­1 and occludin after DSS treatment, increasing the integrity of the intestinal mucosal barrier. The PK properties of Res suggested that Res possesses the therapeutic potential for oral administration. Network pharmacology revealed that Res alleviated UC through anti­inflammatory and antioxidant pathways, and confirmed that Nrf2 has a high binding affinity with Res and is a key target of Res against UC. Western blotting demonstrated that Res treatment increased the protein levels of Nrf2 and HO­1. In conclusion, Res treatment activated the Nrf2/HO­1 pathway to decrease clinical symptoms, inflammatory responses, and intestinal mucosal barrier damage in experimental UC mice.

Associations of Bisphenols Exposure and Hyperuricemia Based on Human Investigation and Animal Experiments.

Hyperuricemia is characterized by elevated blood uric acid (UA) levels, which can lead to certain diseases. Epidemiological studies have explored the association between environmental contaminant exposure and hyperuricemia. However, few studies have investigated the role of chemical exposure in the development of hyperuricemia. Here, we sought to investigate the effects of bisphenol exposure on the occurrence of hyperuricemia. Fifteen bisphenol chemicals (BPs) were detected in human serum and urine samples collected from an area with a high incidence of hyperuricemia in China. Serum UA levels positively correlated with urinary bisphenol S (BPS), urinary bisphenol P (BPP), and serum bisphenol F (BPF). The effects of these three chemicals on UA levels in mice were explored at various exposure concentrations. An increase in serum UA levels was observed in BPS- and BPP-exposed mice. The results showed that BPS exposure increased serum UA levels by damaging the structure of the kidneys, whereas BPP exposure increased serum UA levels by disturbing purine metabolism in the liver. Moreover, BPF did not induce an increase in serum UA levels owing to the inhibition of guanine conversion to UA. In summary, we provide evidence of the mechanisms whereby exposure to three BPs disturbs UA homeostasis. These findings provide new insights into the risks of exposure to bisphenol chemicals.

The role of cellular senescence-related genes in Asthma: Insights from bioinformatics and animal experiments.

BACKGROUND: Asthma is a heterogeneous chronic respiratory disease, affecting about 10% of the global population. Cellular senescence is a multifaceted phenomenon defined as the irreversible halt of the cell cycle, commonly referred to as the senescence-associated secretory phenotype. Recent studies suggest that cellular senescence may play a role in asthma. This study aims to dissect the role and biological mechanisms of CSRGs in asthma, enhancing our understanding of the progression of asthma. METHODS: The study utilized the GSE147878 dataset, employing methods like WGCNA, Differential analysis, Cibersort, GO, KEGG, unsupervised clustering, and GSVA to explore CSRGs functions and immune cell patterns in asthma. Machine learning identified key diagnostic genes, validated externally with the GSE165934 dataset and through qRT-PCR and WB experiments in animal models. RESULT: From the GSE147878 dataset, 24 CSRGs were identified, highlighting their role in immune and inflammatory processes in asthma. Differences in CD4 naive T cells and activated dendritic cells between asthma and control groups underscored CSRGs' role in immune regulation. Cluster analysis revealed two distinct asthma patient groups with unique immune microenvironments. Machine learning identified five genes, leading to a TF-miRNA-mRNA network and singling out RHOA and RBM39 as key diagnostic genes, which were experimentally validated. Finally, a nomogram was created based on these genes. CONCLUSION: This study, utilizing bioinformatics and animal experiments, identified RHOA and RBM39 as key diagnostic genes for asthma, providing new insights into the potential role and biological mechanisms of CSRGs in asthma.

Join the discussion on animal welfare, ethics and rights.

A panel of experts will lead a conversation on the concepts of animal welfare, ethics and rights at this year's Animal Welfare Foundation Discussion Forum.

Perceptions of 3R implementation in European animal research: A systematic review, meta-analysis, and meta-synthesis of barriers and facilitators.

OBJECTIVES: The purpose of this systematic review was to examine how the scientific community in Europe that is involved with research with animals perceives and experiences the implementation of 3R (Replace, Reduce, Refine). METHODS: A systematic search of the literature published in the past ten years was performed in PubMed, Web of Science and Scopus. Publications were screened for eligibility using a priori inclusion criteria, and only empirical evidence (quantitative, qualitative, or mixed methodologies) was retained. Quantitative survey items were investigated by conducting a meta-analysis, and the qualitative data was summarized using an inductive meta-synthetic approach. Included publications were assessed using the Quality Assessment for Diverse Studies tool. RESULTS: 17 publications were included (eight quantitative, seven qualitative, two mixed-methods). The meta-analysis revealed that scientists are skeptical about achieving replacement, even if they believe that 3R improve the quality of experimental results. They are optimistic concerning the impact of 3R on research costs and innovation, and see education as highly valuable for the implementation of 3R. The meta-synthesis revealed four barriers (systemic dynamics, reification process, practical issues, insufficient knowledge) and four facilitators (efficient use of animals, caring for animals, regulatory uptake, supportive workplace environment). CONCLUSION: These findings show actionable levers at the local and systemic levels, and may inform regulators and institutions in their 3R policies. TRIAL REGISTRATION: The protocol was registered into the PROSPERO database under the number CRD42023395769.

Giant monkey facility could ease U.S. shortage.

Breeder would be the country's largest; locals and animal welfare advocates are concerned.