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Poor research reporting is a major contributing factor to low study reproducibility, financial and animal waste. The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines were developed to improve reporting quality and many journals support these guidelines. The influence of this support is unknown. We hypothesized that papers published in journals supporting the ARRIVE guidelines would show improved reporting compared with those in non-supporting journals. In a retrospective, observational cohort study, papers from 5 ARRIVE supporting (SUPP) and 2 non-supporting (nonSUPP) journals, published before (2009) and 5 years after (2015) the ARRIVE guidelines, were selected. Adherence to the ARRIVE checklist of 20 items was independently evaluated by two reviewers and items assessed as fully, partially or not reported. Mean percentages of items reported were compared between journal types and years with an unequal variance t-test. Individual items and sub-items were compared with a chi-square test. From an initial cohort of 956, 236 papers were included: 120 from 2009 (SUPP; n = 52, nonSUPP; n = 68), 116 from 2015 (SUPP; n = 61, nonSUPP; n = 55). The percentage of fully reported items was similar between journal types in 2009 (SUPP: 55.3 ± 11.5% [SD]; nonSUPP: 51.8 ± 9.0%; p = 0.07, 95% CI of mean difference -0.3-7.3%) and 2015 (SUPP: 60.5 ± 11.2%; nonSUPP; 60.2 ± 10.0%; p = 0.89, 95%CI -3.6-4.2%). The small increase in fully reported items between years was similar for both journal types (p = 0.09, 95% CI -0.5-4.3%). No paper fully reported 100% of items on the ARRIVE checklist and measures associated with bias were poorly reported. These results suggest that journal support for the ARRIVE guidelines has not resulted in a meaningful improvement in reporting quality, contributing to ongoing waste in animal research., Competing Interests: The authors have declared that no competing interests exist.

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 Bal­timore 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 pres­entations 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.

The paper mulberry (Broussonetia papyrifera) leaf is rich in alkaloids and flavonoids, which has high medicinal and feeding value. We aimed to analyze the effects of B. papyrifera leaf extract on growth performance, antioxidant capacity, immune functions, and fecal microflora of weaned piglets. Thirty healthy, 28-day-old piglets were randomly assigned to three groups and fed with a basal diet supplemented with 0, 150, and 300 g/t B. papyrifera leaf extract for 42 days (control group, group I, and group II) separately. The result revealed that the final weight of piglets in group II was higher than the other groups, and the diarrhea rate in this group was 62.9% lower than in the control group. The feed conversion ratio in group I was significantly lower than the other two groups. Higher blood urine nitrogen concentration was noted in group II, higher glutathione peroxidase and catalase in group II, higher superoxide dismutase in the control group, and higher immune globulins (Ig) IgG, IgA, and IgM in group II. There was no significant difference in community richness and community diversity among the three groups of fecal samples. The relative level of Roseburia was higher in groups I and II, while Lactobacillus was higher in the control group. In conclusion, supplementation with B. papyrifera leaf extract at a certain dosage can increase growth performance and antioxidant capacity of weaned piglets, reduce the occurrence of diarrhea, enhance immune functions and disease resistance, and affect the composition of fecal microflora. [ABSTRACT FROM AUTHOR]

Aging is associated with substantial physiological changes and constitutes a major risk factor for neurological disorders including dementia. Alterations in gene expression upon aging have been extensively studied; however, an in-depth characterization of post-transcriptional regulatory events remains elusive. Here, we profiled the age-related changes of the transcriptome and translatome in the female mouse hippocampus by RNA sequencing of total RNA and polysome preparations at four ages (3-, 6-, 12-, 20-month-old); and we implemented a variety of bioinformatics approaches to unravel alterations in transcript abundance, alternative splicing, and polyadenylation site selection. We observed mostly wellcoordinated transcriptome and translatome expression signatures across age including upregulation of transcripts related to immune system processes and neuroinflammation, though transcripts encoding ribonucleoproteins or associated with mitochondrial functions, calcium signaling and the cell-cycle displayed substantial discordant profiles, suggesting translational control associated with age-related deficits in hippocampal-dependent behavior. By contrast, alternative splicing was less preserved, increased with age and was associated with distinct functionally-related transcripts encoding proteins acting at synapses/dendrites, RNA-binding proteins; thereby predicting regulatory roles for RBM3 and CIRBP. Only minor changes in polyadenylation site selection were identified, indicating pivotal 3'-end selection in young adults compared to older groups. Overall, our study provides a comprehensive resource of age-associated post-transcriptional regulatory events in the mouse hippocampus, enabling further examination of the molecular features underlying age-associated neurological diseases. [ABSTRACT FROM AUTHOR]

Abstract: The ARRIVE (Animals in Research: Reporting In Vivo Experiments) guidelines were endorsed by the Shock Society in 2012, but to date there has been no systematic evaluation of research reporting quality for Shock. We systematically assessed 100 randomly selected animal-based research articles published between 2014 and 2018 for reporting quality and statistical practice, compared with 40 pre-ARRIVE studies. More than half of surveyed papers omitted verifiable ethical oversight information and basic animal descriptive information. Few papers reported best-practice methods, such as sample size justification (10%), randomization (43%), randomization method (7%), blinding (23%). Only one paper reported effect sizes to interpret study results. Most troubling was inadequate reporting of welfare-related information (anesthesia, analgesia, humane endpoints, euthanasia). Almost a decade after ARRIVE endorsement, our findings show that reporting deficiencies have persisted with little sign of correction. There is a clear need for investigators to increase transparency of research methods reporting, and drastically improve skills in experimental design. Improvement in standards and greater attention paid to reporting will lead to improvement in reproducibility, replicability, and research quality. It is incumbent upon the research community to improve reporting practices; accurate and transparent reporting is integral to producing rigorous and ethical science., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Background: Schizophrenia is a complex neuropsychiatric disorder of unclear etiology. The strongest known genetic risk factor is the 22q11.2 microdeletion. Research has yet to confirm which genes within the deletion region are implicated in schizophrenia. The minimal 1.5 megabase deletion contains MIR185, which encodes microRNA 185. Methods: We determined miR-185 expression in embryonic and adult mouse brains. Common and rare variants at this locus were then investigated using a human genetics approach. First, we performed gene-based analyses for MIR185 common variants and target genes using Psychiatric Genomics Consortium genome-wide association data. Second, MIR185 was resequenced in German patients (n = 1000) and controls (n = 500). We followed up promising variants by genotyping an additional European sample (patients, n = 3598; controls, n = 4082). Results: In situ hybridization in mice revealed miR-185 expression in brain regions implicated in schizophrenia. Gene-based tests revealed association between common variants in 3 MIR185 target genes (ATAT1, SH3PXD2A, NTRK3) and schizophrenia. Further analyses in mice revealed overlapping expression patterns for these target genes and miR185. Resequencing identified 2 rare patient-specific novel variants flanking MIR185. However, follow-up genotyping provided no further evidence of their involvement in schizophrenia. Limitations: Power to detect rare variant associations was limited. Conclusion: Human genetic analyses generated no evidence of the involvement of MIR185 in schizophrenia. However, the expression patterns of miR-185 and its target genes in mice, and the genetic association results for the 3 target genes, suggest that further research into the involvement of miR-185 and its downstream pathways in schizophrenia is warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Schizophrenia is a highly heritable neurodevelopmental disorder. A genetic variant of microRNA-137 (miR-137) has yielded significant genome-wide association with schizophrenia, suggesting that this miRNA plays a key role in its etiology. Therefore, a molecular network of interacting miR-137 targets may provide insights into the biological processes underlying schizophrenia. METHODS: We first used bioinformatics tools to obtain and analyze predicted human and mouse miR-137 targets. We then determined miR-137 levels in rat barrel cortex after environmental enrichment (EE), a neuronal plasticity model that induces upregulation of several predicted miR-137 targets. Subsequently, expression changes of these predicted targets were examined through loss of miR-137 function experiments in rat cortical neurons. Finally, we conducted bioinformatics and literature analyses to examine the targets that were upregulated upon miR-137 downregulation. RESULTS: Predicted human and mouse miR-137 targets were enriched in neuronal processes, such as axon guidance, neuritogenesis and neurotransmission. The miR-137 levels were significantly downregulated after EE, and we identified 5 novel miR-137 targets through loss of miR-137 function experiments. These targets fit into a glucocorticoid receptor-dependent signalling network that also includes 3 known miR-137 targets with genome-wide significant association with schizophrenia. LIMITATIONS: The bioinformatics analyses involved predicted human and mouse miR-137 targets owing to lack of information on predicted rat miR-137 targets, whereas follow-up experiments were performed with rats. Furthermore, indirect effects in the loss of miR-137 function experiments cannot be excluded. CONCLUSION: We have identified a miR-137-regulated protein network that contributes to our understanding of the molecular basis of schizophrenia and provides clues for future research into psychopharmacological treatments for schizophrenia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although previous study has demonstrated that brain-derived neurotrophic factor (BDNF) is involved in the antidepressant-like effect of oleanolic acid, there is little information regarding the details of the molecular mechanism involved in this effect. METHODS: We used a chronic unpredictable mild stress (CUMS) model to test the antidepressant-like effect of oleanolic acid on depressant-like behaviour, miR-132 expression and synaptic protein expression in the male mouse hippocampus. Furthermore, we explored the possible signalling pathways associated with miR-132 expression that mediate the effect of oleanolic acid on neuronal proliferation. RESULTS: The results demonstrated that a 3-week treatment with oleanolic acid ameliorated CUMS-induced anhedonic and anxiogenic behaviours. Furthermore, we found that oleanolic acid led to the BDNF-related phosphorylation and activation of extracellular signal-regulated kinases (ERK) and cyclic adenosine monophosphate response element binding protein (CREB), which was associated with the upregulation of miR-132 and hippocampal neuronal proliferation. Moreover, experiments with an miR-132 antagomir revealed that targeting miR-132 led to inhibition of neuronal proliferation and the postsynaptic density protein 95, but did not affect presynaptic protein synapsin I. LIMITATIONS: Several other stimuli can also induce CREB phosphorylation in the hippocampus. Thus, regulation of miR-132 may not be restricted to neurotrophic signalling. CONCLUSION: Our results show that oleanolic acid induces the upregulation of miR-132, which serves as an important regulator of neurotrophic actions, mainly through the activation of the hippocampal BDNF-ERK-CREB signalling pathways. [ABSTRACT FROM AUTHOR]

Most Human African Trypanosomiasis (HAT) control programmes in areas endemic for Trypanosoma brucei gambiense rely on a strategy of active mass screening with the Card Agglutination Test for Trypanosomiasis (CATT)/T. b. gambiense. We evaluated the performance, stability and reproducibility of the CATT/T. b. gambiense on blood-impregnated filter papers (CATT-FP) in Kajo-Keji County, South-Sudan, where some areas are inaccessible to mobile teams. The CATT-FP was performed with a group of 100 people with a positive CATT on whole blood including 17 confirmed HAT patients and the results were compared with the CATT on plasma (CATT-P). The CATT-FP was repeated on impregnated filter papers stored at ambient and refrigerated temperature for 1, 3, 7 and 14 days. Another 82 patients with HAT, including 78 with a positive parasitology, were tested with the CATT-FP and duplicate filter paper samples were sent to a reference laboratory to assess reproducibility. The CATT-FP was positive in 90 of 99 patients with HAT (sensitivity: 91%). It was less sensitive than the CATT-P (mean dilution difference: -2.5). There was no significant loss of sensitivity after storage for up to 14 days both at ambient and cool temperature. Reproducibility of the CATT-FP was found to be excellent (kappa: 0.84). The CATT-FP can therefore be recommended as a screening test for HAT in areas where the use of CATT-P is not possible. Further studies on larger population samples in different endemic foci are still needed before the CATT-FP can be recommended for universal use. [ABSTRACT FROM AUTHOR]

Reported analgesic use following experimental surgery is low in rodents and there has been little published information on the frequency of analgesic use in other laboratory species. A structured literature review was conducted to examine analgesic administration in larger laboratory animals. The Scirus search engine was used to identify studies published in peer-reviewed journals that reported carrying out experimental surgery on 'large' laboratory animals, specifically rabbits, pigs, sheep, dogs and non-human primates. Seventy-four studies between 2000 and 2001 and 75 studies between 2005 and 2006 were included in the review. There was an increase in the reported administration of systemic analgesics to these species from 50% in 2000-2001 to 63% in 2005-2006. When all agents with analgesic properties were considered (systemic analgesics, local anaesthetics and anaesthetics with analgesic components), the proportion of papers that reported some form of analgesic administration to 'large' laboratory animals increased from 86% in 2000-2001 to 89% in 2005-2006. Overall rabbits, pigs, sheep, dogs and non-human primates were more likely to receive analgesics following potentially painful experimental procedures than has been reported in laboratory rodents but analgesic administration to 'large' laboratory species is still not optimal. [ABSTRACT FROM AUTHOR]

Open science in its broadest sense can make better science and provide benefits to researchers. When applied to animal experimentation, it can prevent unnecessary use of animals, because knowledge and experiences about past animal experimentation are shared openly to be consulted and used by other researchers. By extension, open science can accelerate the much anticipated transition towards animal-free innovations or New Approach Methodologies (NAMs). The purpose of this paper is to bring together and further share the preparations and findings of a symposium held at Utrecht University on aspects of open science that researchers doing animal experiments can and should take into account to improve their research and benefit themselves. The paper offers a onefigure guideline for that purpose. [ABSTRACT FROM AUTHOR]

Background: Spinal cord compression is a pathology seen in routine clinical practice. However, there remain a number of unanswered questions around both the understanding of the pathogenesis and the best method of treatment of the condition. This is partly due to the issues of the real-life testing of the physical properties of the spinal cord, either through the use of cadaveric human specimens or through animal testing, both of which have methodological, as well as ethical, issues. Design and methods: This paper details a protocol for a systematic review of the literature on the mechanical properties of the spinal cord. We will conduct a literature search of a number of electronic databases, along with the grey literature, as a single-stage search. All literature will be screened for appropriate studies which will then be reviewed fully to extract relevant information on the methodology and mechanics of the reported testing along with the results. Two reviewers will separately screen and extract the data, with a comparison of results to ensure concordance. Conflicts will be resolved through discussion and independent arbitration as required. The methodological quality of the studies will be assessed within the ARRIVE guidelines using the CAMARADES framework and SYRCLE risk of bias tool. A narrative synthesis will be created with the appropriate tables to describe the demographics and findings of the included studies. Discussion: The systematic review described here will form the basis of an understanding of the current literature around the physical properties of the spinal cord. This will allow future work to develop a physical model of the spinal cord, which is translatable to patients for analysis and testing in a controlled and repeatable fashion. Such a model would be the basis for further clinical research to improve outcomes from this condition. Trial registration: Prospero registration number: CRD42022361933. [ABSTRACT FROM AUTHOR]

Background: Excessive inflammation is a major cause of implant failure. The surface morphology, hydrophilicity, and loading of biomaterials are major properties modulating anti-inflammatory macrophage activation. This paper investigates the regulatory effects of modifying the surface of Titanium dioxide nanotubes (TNTs) with graphene oxide (GO) on the polarization of mouse monocyte macrophages (RAW264.7). Methods: TNT was produced by the anodic oxidation of titanium. GO was subsequently electrodeposited on the TNT to obtain a TNT–GO composite. The samples were characterised through scanning electron microscopy (SEM), Raman spectroscopy, and X-ray diffraction. RAW264.7 cells were separately seeded onto the surface of three groups of samples: pure Ti, TNT, and TNT–GO. Under the condition of lipopolysaccharide stimulation, the influence of the sample surfaces on the gene expression profiles was investigated through RNA sequence analysis. In addition, cell spreading was observed through SEM, cell adhesion and proliferation were analysed using the CCK8 assay, and the expression of inflammation-related factors was investigated by ELISA and cellular immunofluorescence staining. The production of reactive oxygen species (ROS) in the RAW264.7 cells on the surface of the three groups was detected via immunofluorescence staining. Results: The CCK8 results indicated that the adhesion and proliferation of the RAW264.7 cells were reduced on the TNT and TNT–GO surfaces. ELISA results revealed significant differences in the pro-inflammatory factors tumour necrosis factor-α and interleukin-6 secretion among the three groups at 24 h (p < 0.05). The secretion of pro-inflammatory factors significantly reduced and the expression of anti-inflammatory factor IL-10 increased on the TNT and TNT–GO surfaces. The RNA sequencing, ELISA, and cell immunofluorescence staining test results suggested that the inflammatory response of M1 polarization was reduced and the M2 polarization of macrophages was induced on the TNT–GO surface, which may be attributed to the reduction in ROS production. Conclusions: Under lipopolysaccharide stimulation, the inflammatory response of the RAW264.7 cells was reduced and the M2 polarization of macrophages was promoted on the TNT–GO surface, which may be caused by the reduced ROS production. Consequently, the designed TNT–GO material is promising for implants owing to its excellent inflammation regulation ability. [ABSTRACT FROM AUTHOR]

UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). Photodamage and other bulky lesions occurring in nuclear genomes can be repaired through nucleotide excision repair (NER), where incisions on both sides of a damaged site precede the removal of a single-stranded oligonucleotide containing the damage. Mitochondrial genomes (mtDNAs) are also susceptible to damage from UV light, but current evidence suggests that the only way to eliminate bulky mtDNA damage is through mtDNA degradation. Damage-containing oligonucleotides excised during NER can be captured with antidamage antibodies and sequenced (XR-seq) to produce high-resolution maps of active repair locations following UV exposure. We analyzed previously published datasets from Arabidopsis thaliana, Saccharomyces cerevisiae , and Drosophila melanogaster to identify reads originating from the mtDNA (and plastid genome in A. thaliana). In A. thaliana and S. cerevisiae , the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt in S. cerevisiae and 28 nt in A. thaliana with distinct secondary peaks occurring in regular intervals. These reads also show a nonrandom distribution of di-pyrimidines (the substrate for CPD formation) with TT enrichment at positions 7–8 of the reads. Therefore, UV damage to mtDNA appears to result in production of DNA fragments of characteristic lengths and positions relative to the damaged location. The mechanisms producing these fragments are unclear, but we hypothesize that they result from a previously uncharacterized DNA degradation pathway or repair mechanism in mitochondria. [ABSTRACT FROM AUTHOR]

Environmental electromagnetic interference (EMI) has always been a major interference source for multiple-channel neural recording systems, and little theoretical work has been attempted to address it. In this paper, equivalent circuit models are proposed to model both electromagnetic interference sources and neural signals in such systems, and analysis has been performed to generate the design guidelines for neural probes and the subsequent recording circuit towards higher common-mode interference (CMI) rejection performance while maintaining the recorded neural action potential (AP) signal quality. In vivo animal experiments with a configurable 32-channel neural recording system are carried out to validate the proposed models and design guidelines. The results show the power spectral density (PSD) of environmental 50 Hz EMI interference is reduced by three orders from 4.43 × 10−3 V2/Hz to 4.04 × 10−6 V2/Hz without affecting the recorded AP signal quality in an unshielded experiment environment. [ABSTRACT FROM AUTHOR]

Background: Fermentation is a widely used method of natural food preservation that has consequences on the nutritional value of the transformed food. Fermented dairy products are increasingly investigated in view of their ability to exert health benefits beyond their nutritional qualities.Objective: To explore the mechanisms underpinning the health benefits of fermented dairy intake, the present study followed the effects of milk fermentation, from changes in the product metabolome to consequences on the human serum metabolome after its ingestion.Methods: A randomized crossover study design was conducted in 14 healthy men [mean age: 24.6 y; mean body mass index (in kg/m2): 21.8]. At the beginning of each test phase, serum samples were taken 6 h postprandially after the ingestion of 800 g of a nonfermented milk or a probiotic yogurt. During the 2-wk test phases, subjects consumed 400 g of the assigned test product daily (200 g, 2 times/d). Serum samples were taken from fasting participants at the end of each test phase. The serum metabolome was assessed through the use of LC-MS-based untargeted metabolomics.Results: Postprandial serum metabolomes after milk or yogurt intake could be differentiated [orthogonal projections to latent structures discriminant analysis (OPLS-DA) Q2 = 0.74]. Yogurt intake was characterized by higher concentrations of 7 free amino acids (including proline, P = 0.03), reduced concentrations of 5 bile acids (including glycocholic acid, P = 0.04), and modulation of 4 indole derivative compounds (including indole lactic acid, P = 0.01). Fasting serum samples after 2 wk of daily intake of milk or yogurt could also be differentiated based on their metabolic profiles (OPLS-DA Q2 = 0.56) and were discussed in light of the postprandial results.Conclusion: Metabolic pathways related to amino acids, indole derivatives, and bile acids were modulated in healthy men by the intake of yogurt. Further investigation to explore novel health effects of fermented dairy products is warranted.This trial was registered at clinicaltrials.gov as NCT02230345. [ABSTRACT FROM AUTHOR]

Simple Summary: Animals are frequently used to determine whether new compounds have the potential to be used as drugs against the parasitic disease leishmaniasis. There is, however, no consensus on the best animal model, and many different ones are used. This review explored the many different models and identified their strengths and weaknesses. The work showed that many papers on animal models for leishmaniasis lack a thorough description of the experimental procedures used, are deficient in appropriate ethical review (to safeguard the welfare of the animals), and measures to reduce, refine or replace animal studies are hardly addressed. Mice and hamsters are most frequently used, but there are many differences in how the animal experiment is set up. We propose a more generalized animal model, in particular to ensure that different experiments can be better compared. Furthermore, we make a plea to report all animal experiments in the same way, and all experiments must be scrutinized by appropriate ethical review committees. Many different animal models are in use for drug development for leishmaniasis, but a universal model does not exist. There is a plethora of models, and this review assesses their design, quality, and limitations, including the attention paid to animal welfare in the study design and execution. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines of available literature after the year 2000 describing animal models for leishmaniasis. The risk of bias was determined using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias assessment tool. A total of 10,980 records were initially identified after searching the databases PubMed, EMBASE, LILACS, and SciELO. Based on the application of predetermined exclusion and inclusion criteria, a total of 203 papers describing 216 animal experiments were available for full analysis. Major reasons for exclusion were a lack of essential study information or appropriate ethical review and approval. Mice (82.8%; an average of 35.9 animals per study) and hamsters (17.1%; an average of 7.4 animals per study) were the most frequently used animals, mostly commercially sourced, in the included studies. All studies lacked a formal sample size analysis. The promastigote stages of L. amazonensis or L. major were most frequently used to establish experimental infections (single inoculum). Animal welfare was poorly addressed in all included studies, as the definition of a human end-point or consideration of the 3Rs (Replacement, Reduction, Refinement) was hardly addressed. Most animals were euthanized at the termination of the experiment. The majority of the studies had an unknown or high risk of bias. Animal experiments for drug development for leishmaniasis mainly poorly designed and of low quality, lack appropriate ethical review, and are deficient in essential information needed to replicate and interpret the study. Importantly, aspects of animal welfare are hardly considered. This underpins the need to better consider and record the details of the study design and animal welfare. [ABSTRACT FROM AUTHOR]

Simple Summary: Canadian universities and the quasi-regulatory body overseeing animal research (Canadian Council on Animal Care) increasingly use the language of "transparency" to assert that their practices have sufficient public oversight and legitimacy in the eyes of the Canadian public. This paper analyses how this new "transparency" in fact operates to conceal the realities of these animals' lives and inhibit genuine public oversight and ethical engagement. For many years, the lives of animals used for research in Canadian universities have been hidden from public view due both to physical concealment (e.g., security procedures and impenetrable labs) and administrative concealment (non-disclosure of information). Their lives unfold out of sight both physically and discursively, unavailable to the Canadian public for ethical consideration and democratic oversight. Recently, in response to calls by the public to end this secrecy, Canadian universities and the Canadian Council on Animal Care have embraced the language of "transparency" and have begun releasing documentation about animal research practices and procedures. This paper argues that this new "transparency" acts as its own kind of concealment practice, obscuring and displacing meaningful information while constructing highly selective ways of seeing animals in science, and manufacturing acquiescence/consent on the part of the public. [ABSTRACT FROM AUTHOR]

Human induced pluripotent stem cell (hiPSC)-derived brain spheroids can recapitulate the complex cytoarchitecture of the brain, as well as the genetic/epigenetic footprint of human brain development. However, hiPSC-derived 3D models such as spheroid and organoids does not have a perfusable microvascular network, which plays a vital role in maintaining homeostasis in vivo. With the critical balance of positive and negative angiogenic modulators, 3D microvascular network can be achieved by angiogenesis. This paper reports on a microfluidic-based three-dimensional, cortical spheroid grafted on the vascular-network. Vascular network was formed by inducing angiogenic sprouting using concentration gradient-driven angiogenic factors in the microfluidic device. We investigate critical factors for angiogenic vascular network formation with spheroid placement, including 1) a PKCα activator, phorbol-12-myristate-13-acetate (PMA); 2) orientation of endothelial cells under perfusion and permeability of vascular network; 3) effect of extracellular matrix (ECM) types and their densities on angiogenesis; and 4) integration with cortical spheroid on vascular network. This paper demonstrates proof of concept for the potential utility of a membrane-free in vitro cortical spheroid tissue construct with perfusable microvascular network that can be scaled up to a high throughput platform. It can provide a cost-effective alternative platform to animal testing by modeling brain diseases and disorders, and screening drugs. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the influence of different dentin pretreatment procedures on the resulting abrasive dentin wear. Methods: Two groups (A, B) of 60 dentin samples each were prepared. Group A was brushed with an abrasive slurry (RDA = 85) and group B with a different abrasive slurry (RDA = 174). Four subgroups in each group (n = 15) were created (A1–A4) and (B1–B4). The subgroups were pretreated as follows: A1 + B1 with 1200-grit grinding paper, A2 + B2 with 1200- and 2000-grit papers, A3 + B3 with 1200-, 2000-, and 4000-grit papers, A4 + B4 with 1200-, 2000-, 4000-grit papers and with 1000 brushing strokes with a slurry of Elmex toothpaste. All samples were brushed for 25 min at 120 strokes/min. Abrasive dentin wear was measured for each sample profilometrically and the subgroups were compared with each other within the same group. Repeated measures one-way ANOVA was conducted to compare the subgroups and pairwise contrasts were estimated for multiple testing according to Tukey (α = 0.05). Results: The resulting abrasive dentin wear in group A ranged between 15.3 ± 3.4 µm and 17.3 ± 5.5 µm and between 20.3 ± 6.8 µm and 22.5 ± 2.6 µm in group B. No statistically significant difference was noticed between any subgroups within the same group (p ˃ 0.05). Conclusions: Different dentin pretreatment procedures do not affect the resulting abrasive dentin wear independent of the RDA value of the employed abrasive slurry. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis imposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae. The existence of serologically distinct serovars of C. trachomatis suggests that a vaccine will need to provide protection against multiple serovars. Chlamydia spp. use a highly conserved type III secretion system (T3SS) composed of structural and effector proteins which is an essential virulence factor. In this study, we expressed the T3SS needle protein of Chlamydia muridarum, TC_0037, an ortholog of C. trachomatis CdsF, in a replication-defective adenoviral vector (AdTC_0037) and evaluated its protective efficacy in an intravaginal Chlamydia muridarum model. For better immune responses, we employed a heterologous prime-boost immunization protocol in which mice were intranasally primed with AdTC_0037 and subcutaneously boosted with recombinant TC_0037 and Toll-like receptor 4 agonist monophosphoryl lipid A mixed in a squalene nanoscale emulsion. We found that immunization with TC_0037 antigen induced specific humoral and T cell responses, decreased Chlamydia loads in the genital tract, and abrogated pathology of upper genital organs. Together, our results suggest that TC_0037, a highly conserved chlamydial T3SS protein, is a good candidate for inclusion in a Chlamydia vaccine. [ABSTRACT FROM AUTHOR]

Background: Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in cognitive dysfunction. The disturbance of cognitive processes associated with depression, especially the impairment of learning and memory, exacerbates illness and increases recurrence of depression. XingPiJieYu (XPJY) is one of the most widely clinical formulas of traditional Chinese medicine (TCM) and can improve the symptoms of depression, including learning and memory. However, its regulatory effects haven't been comprehensively studied so far. Recently, some animal tests have indicated that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway in hippocampus is closely related to depression and the pathogenesis of cognitive function impairments. The present study was performed to investigate the effect and mechanism of XPJY on depression and learning and memory in animal model. Materials: The rat model of depression was established by chronic unpredictable stress (CUS) for 21 days. The rats were randomly divided into six groups: control group, CUS group, CUS + XPJY (1.4 g/kg, 0.7 g/kg and 0.35 g/kg) groups, and CUS + sertraline (10 mg/kg) group. The sucrose preference, open field exploration and Morris water maze (MWM) were tested. The expression of cAMP, CREB, PKA and BDNF protein in hippocampus was examined with Elisa and Western Blot. The mRNA level of CREB and BDNF in hippocampus was measured with PCR. Results: The results demonstrated that rats subjected to CUS exhibited decreases in sucrose preference, total ambulation, percentage of central ambulation, rearing in the open field test and spatial performance in the MWM. CUS reduced the expression of cAMP, PKA, CREB and BDNF in hippocampus of model rats. These effects could be reversed by XPJY. Conclusion: The results indicated that XPJY can improve depression and related learning and memory and the effect of XPJY is partly exerted through the cAMP-PKA-CREB-BDNF signaling pathway. [ABSTRACT FROM AUTHOR]

Temporal accuracy is a fundamental characteristic of logging technology and is needed to correlate data streams. Single biologgers sensing animal movement (accelerometers, gyroscope, magnetometers, collectively inertial measurement unit; IMU) have been extensively used to study the ecology of animals. To better capture whole body movement and increase the accuracy of behavior classification, there is a need to deploy multiple loggers on a single individual to capture the movement of multiple body parts. Yet due to temporal drift, accurately aligning multiple IMU datasets can be problematic, especially as deployment duration increases. In this paper we quantify temporal drift and errors in commercially available IMU data loggers using a combination of robotic and animal borne experiments. The variance in drift rate within a tag is over an order of magnitude lower (σ = 0.001 s h−1) than the variance between tags (σ = 0.015 s·h−1), showing that recording frequency is a characteristic of each tag and not a random variable. Furthermore, we observed a large offset (0.54 ± 0.016 s·h−1) between two groups of tags that had differing recording frequencies, and we observed three instances of instantaneous temporal jumps within datasets introducing errors into the data streams. Finally, we show that relative drift rates can be estimated even when deployed on animals displaying various behaviors without the tags needing to be simultaneously moved. For the tags used in this study, drift rates can vary significantly between tags, are repeatable, and can be accurately measured in the field. The temporal alignment of multiple tag datasets allows researchers to deploy multiple tags on an individual animal which will greatly increase our knowledge of movement kinematics and expand the range of movement characteristics that can be used for behavioral classification. [ABSTRACT FROM AUTHOR]

Paradoxically, tumor development and progression can be inhibited and promoted by the immune system. After three stages of immune editing, namely, elimination, homeostasis and escape, tumor cells are no longer restricted by immune surveillance and thus develop into clinical tumors. The mechanisms of immune escape include abnormalities in antitumor-associated immune cells, selection for immune resistance to tumor cells, impaired transport of T cells, and the formation of an immunosuppressive tumor microenvironment. A population of distinct immature myeloid cells, myeloid-derived suppressor cells (MDSCs), mediate immune escape primarily by exerting immunosuppressive effects and participating in the constitution of an immunosuppressive microtumor environment. Clinical trials have found that the levels of MDSCs in the peripheral blood of cancer patients are strongly correlated with tumor stage, metastasis and prognosis. Moreover, animal experiments have confirmed that elimination of MDSCs inhibits tumor growth and metastasis to some extent. Therefore, MDSCs may become the target of immunotherapy for many cancers, and eliminating MDSCs can help improve the response rate to cancer treatment and patient survival. However, a clear definition of MDSCs and the specific mechanism involved in immune escape are lacking. In this paper, we review the role of the MDSCs population in tumor development and the mechanisms involved in immune escape in different tumor contexts. In addition, we discuss the use of these cells as targets for tumor immunotherapy. This review not only contributes to a systematic and comprehensive understanding of the essential role of MDSCs in immune system reactions against tumors but also provides information to guide the development of cancer therapies targeting MDSCs. [ABSTRACT FROM AUTHOR]

This study explored the development of polyvinylpyrrolidone (PVP)–honey-gel (PHG) through 3D printing, aiming to develop a multifunctional bio-tape with adhesive and degradable properties. Based on the potential of honey to promote wound healing due to its antibacterial and anti-inflammatory properties, a PVP–honey-based 3D printing ink was developed by combining honey and PVP to create PHG through 3D printing technology that can form a film with strong adhesion and flexibility. First, the chemical–physical properties of PHG and its 3D printing performance were characterized. The line width achievable in 3D printing for the PHG line can extend to ∼100 µm. In addition, the adhesive properties of the PHG film were evaluated by using a 180° peeling test on various materials (glass, copper, wood, and pig skin), highlighting its potential for diverse applications. Finally, the application of the PHG film as a bio-tape was demonstrated through a successful animal experiment on a rabbit's skin wound. Due to its adhesive and degradable properties, the bio-tape exhibited 3D conformability and ease of removal without residue. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The aims of this study were to label the versatile amino acid l-lysine with 99mTc using 2,3-dimercapto-succinic acid (DMSA) as a chelator, and to assess its tumor imaging feasibility under in vivo and in vitro conditions, and finally to determine the subcellular biodistribution of this radiopharmaceutical. Materials and Methods: DMSA-l-lysine was chemically synthesized and labeled with sodium pertechnetate. Nuclear magnetic resonance (NMR) and mass spectral analysis of DMSA-l-lysine were conducted. Radiochemical purity was determined by thin-layer chromatography (TLC) and paper chromatography. Cellular uptake, competition and subcellular localization studies were performed in rat breast cancer cells (13762). In vivo studies of planar imaging and biodistribution studies were performed on female Fischer 344 rats. Medical Internal Radiation Dose (MIRD) dosimetry estimates were calculated. Results: Radiochemical purity (determined by radio-TLC and high-performance liquid chromatography) of these compounds was >95%. 99mTc-DMSA-l-lysine showed good uptake in in vitro cell culture assays and uptake was reduced in competition studies. 99mTc-DMSA-l-lysine accumulates in the nucleus as much as in the cytoplasm and it was also shown that accumulation of the 99mTc-DMSA-l-lysine in the nucleus increases as a function of a time. There was an increase in tumor-to-blood and tumor-to-muscle count density ratios. Tumor/background ratios were 5.75 at 1 hour and 6.87 at 2 hours. In vivo tissue distribution studies revealed that radiation dosimetry of blood-forming organs were within radiation dose limits. Conclusion: DMSA-l-lysine kits can be labeled with 99mTc easily and efficiently, with high radiochemical purity and cost-effectiveness. In vitro cellular uptake and scintigraphic imaging studies demonstrated the pharmacokinetic distribution and feasibility of using 99mTc-DMSA-l-lysine for tumor imaging. [Copyright &y& Elsevier]

The article discusses the laws governing the scientific procedures on animal experimentation and testing in Great Britain. Conventional wisdom asserts that law does not generally mix well with science, at least not if its role is to define and permit only what society considers to be acceptable scientific experiments. Laws have been in effective to regulate the nature and circumstances of experiments using animals and to control and limit any associated pain.

Background: Myocardial infarction (MI) is a major cause of heart failure. The carboxypeptidase cathepsin A is a novel target in the treatment of cardiac failure. We aim to show that recently developed inhibitors of the protease cathepsin A attenuate post-MI heart failure.Methods: Mice were subjected to permanent left anterior descending artery (LAD) ligation or sham operation. 24 h post-surgery, LAD-ligated animals were treated with daily doses of the cathepsin A inhibitor SAR1 or placebo. After 4 weeks, the three groups (sham, MI-placebo, MI-SAR1) were evaluated.Results: Compared to sham-operated animals, placebo-treated mice showed significantly impaired cardiac function and increased plasma BNP levels. Cathepsin A inhibition prevented the increase of plasma BNP levels and displayed a trend towards improved cardiac functionality. Proteomic profiling was performed for the three groups (sham, MI-placebo, MI-SAR1). More than 100 proteins were significantly altered in placebo-treated LAD ligation compared to the sham operation, including known markers of cardiac failure as well as extracellular/matricellular proteins. This ensemble constitutes a proteome fingerprint of myocardial infarction induced by LAD ligation in mice. Cathepsin A inhibitor treatment normalized the marked increase of the muscle stress marker CA3 as well as of Igγ 2b and fatty acid synthase. For numerous further proteins, cathepsin A inhibition partially dampened the LAD ligation-induced proteome alterations.Conclusions: Our proteomic and functional data suggest that cathepsin A inhibition has cardioprotective properties and support a beneficial effect of cathepsin A inhibition in the treatment of heart failure after myocardial infarction. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper explores why it is ethical to rehome all healthy laboratory animals after the experiments have finished. We describe our own rehoming experience from the joint Ani-mal Welfare Body of Utrecht University and the University Medical Centre Utrecht, the Nether-lands. During a pilot period, over 350 animals were successfully rehomed. Now, rehoming in our lab is a standard policy and common practice. We discuss several challenges and our responses to those through the continuous evaluation of this adoption program. This paper explores the ethical imperative of rehoming all healthy animals of sentient species after experiments have finished or when they have become otherwise redundant. We take into account disparate perspectives in animal ethics and see how they point in the same direction. We illustrate our case with our own rehoming experience from the joint Animal Welfare Body of Utrecht University and the University Medical Centre Utrecht, the Netherlands. The primary pilot proved successful, after which the principle of rehoming became standing policy and common practice. We discuss several challenges and our responses to those through continuous evaluation of the adoption program. [ABSTRACT FROM AUTHOR]

In order to better demonstrate the relationship between agricultural economic structure growth and environmental pollution, an autoregressive model based on time-varying parameter vector was proposed. In the process of developing the research, this paper introduces the LDMI method, based on the time-varying parameter vector autoregression model, with the help of sampling formula calculation and other methods. Efforts were made to obtain credible conclusions. The experiment result shows that in this study, a total of 10,000 samples were taken. According to this value, 10000/116.15 = 86, which means that at least 86 unrelated samples can be obtained. Therefore, we can determine that each indicator mentioned in this paper has valid samples when it is introduced into the time-varying parameter vector autoregression (TVP-VAR) model for parameter estimation. After sampling detection image analysis and data calculation, the effect of energy structure, energy intensity industrial structure, and scale effect on the emission scale of environmental pollutants was obtained. It is proved that through the research of this paper, two main conclusions are finally obtained, and the influence of the five factors mentioned above is summarized. [ABSTRACT FROM AUTHOR]

Simple Summary: Oncolytic herpes simplex viruses (oHSVs) employ as natural entry receptors nectin1 or HVEM. In contrast, retargeted oHSVs (ReHVs) employ as an entry receptor a tumor-associated antigen that no longer interacts with nectin1/HVEM and, thus, spares normal cells. Prior to entry, both oHSVs and ReHVs attach to cells by interaction of gC and gB glycoproteins with heparan sulphates and chondroitin sulphates (glycosaminoglycans–GAGs). The systemic delivery of oncolytic viruses would be the ideal route for hard-to-reach or metastatic cancers that constitute unmet clinical needs. In an accompanying paper, we reported that the blood complement and the antiviral neutralizing antibodies represent the major blood factors that inactivate systemically administered ReHVs. Here, we asked whether ReHV adsorption to GAGs acts as a sink and subtracts the virus from circulation. We report that a genetic modification in gC, which reduced its interaction with GAGs, resulted in a longer half-life of circulating ReHV and a higher anticancer efficacy of systemically (but not intratumorally) administered ReHV. The role of the interaction with cell-surface glycosaminoglycans (GAGs) during in vivo HSV infection is currently unknown. The rationale of the current investigation was to improve the anticancer efficacy of systemically administered retargeted oHSVs (ReHVs) by decreasing their binding to GAGs, including those of endothelial cells, blood cells, and off-tumor tissues. As a proof-of-principle approach, we deleted seven amino acids critical for interacting with GAGs from the glycoprotein C (gC) of R-337 ReHV. The modification in the resulting R-399 recombinant prolonged the half-life in the blood of systemically administered R-399 and enhanced its biodistribution to tumor-positive lungs and to the tumor-negative liver. Ultimately, it greatly increased the R-399 efficacy against metastatic-like lung tumors upon IV administration but not against subcutaneous tumors upon IT administration. These results provide evidence that the increased efficacy seen upon R-399 systemic administration correlated with the slower clearance from the circulation. To our knowledge, this is the first in vivo evidence that the partial impairment of the gC interaction with GAGs resulted in a prolonged half-life of circulating ReHV, an increase in the amount of ReHV taken up by tissues and tumors, and, ultimately, an enhanced anticancer efficacy of systemically administered ReHV. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmunity illness, mainly featured with synovitis of the joint. The specificity of ferroptosis is disparate in different diseases, and the mechanism of ferroptosis in RA has some uncertainty yet. Therefore, the mechanism of ferroptosis was deeply observed in RA patients and animal models. In this paper, plasma of RA patients, the tumor necrosis factor-alpha-induced human synovial fibroblasts, and an animal model of arthritis induced by collagen were applied to initially inquire about the therapeutic effect of ferroptosis. For the RA patients, ELISA detected protein expression of glutathione (GSH), GPX4, Nrf2, Keap-1, and ferritin. In cell experiments, erastin or fer-1 regulated the invasion of human synovial fibroblast cells, mitochondrial membrane potential, reactive oxygen species (ROS) expression, marker protein, and so on. For the animal experiments, 32 Sprague–Dawley male rats were randomly separated into four groups with a collagen-induced RA model for 14 days and administered with erastin or fer-1 for 35 days. The expressions of GSH, GPX4, Nrf2, and Keap-1 were lower, and the ferritin was higher in RA patients, and the expressions of these proteins varied significantly after disease remission. In addition, ferroptosis inactivation also reduced the proliferation and migration ability, mitochondrial membrane potential, and ROS in cells. We discovered unexpectedly that activation of ferroptosis meaningfully forbore the foot swelling in animals with CIA, reduced arthritis scores, destruction of bone, and articular synovitis, and also decreased the high expression of inflammatory factors in plasma. There is a nonlinear relationship between human disease manifestations and animal model pathology. Ferroptosis regulating in RA for humans or animals may produce different effects. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. Patient concerns: Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. Diagnosis: Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). Interventions: The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. Outcomes: A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. Conclusion: The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation. [ABSTRACT FROM AUTHOR]

Viral diseases affecting both humans and animals are a serious public problem. Chemical modifications of the structure of compounds of natural origin, e.g., betulin, seem to be a promising model in the search for new antiviral agents. The subject of our work was to conduct preliminary tests on the antiviral activity of phosphonic derivatives of betulin and betulinic acid and to assess the pharmacokinetic profile of target compounds. Human (HHV-1, HAdV-5) and animal viruses (BEV, VSV) were used in the in vitro tests. Additionally, this paper presents the results of research using in silico methods (ADMET and molecular docking). Two compounds (betulin 29-phosphonate 3 and 3-(3′,3′-dimethylsuccinyl)betulin acid 29-phosphonate 8a) showed antiviral activity against BEV, and compound 3 was also active against HAdV-5. For compound 3, which showed advantageous pharmacokinetic parameters, molecular docking was performed to determine possible interactions with the cellular target HAdV-5 endopeptidase, which plays an important role in various functions of the virus. Selecting the most active derivatives makes it possible to plan tests on an animal model. [ABSTRACT FROM AUTHOR]

Simple Summary: TP is a widely utilized anticancer medication, particularly effective in treating HCC. Thorough investigation into TP's molecular mechanism in HCC treatment is crucial for precise and combination therapy. In this paper, we have unveiled a novel mechanism of TP in HCC treatment, where it inhibits tumor growth by reducing lipid accumulation. While the inhibition of P53 gene activity is commonly thought to be the reason for TP's effectiveness in treating HCC, this new mechanism serves as a significant complement to the current understanding, paving the way for innovative approaches to HCC treatment. Hepatocellular carcinoma (HCC), which is the third leading cause of cancer-related mortality in the world, presents a significant medical challenge. Triptolide (TP) has been identified as an effective therapeutic drug for HCC. However, its precise therapeutic mechanism is still unknown. Understanding the mechanism of action of TP against HCC is crucial for its implementation in the field of HCC treatment. We hypothesize that the anti-HCC actions of TP might be related to its modulation of HCC lipid metabolism given the crucial role that lipid metabolism plays in promoting the progression of HCC. In this work, we first demonstrate that, both in vitro and in vivo, TP significantly reduces lipid accumulation in HCC cells. Additionally, we notice that lipoprotein lipase (LPL) expression is markedly upregulated in HCC, and that its levels are positively connected with the disease's progression. It is interesting to note that TP dramatically reduces LPL activity, which in turn prevents HCC growth and reduces lipid accumulation. Additionally, the effect of TP on LPL is a direct correlation. These results definitely demonstrate that TP protects hepatocytes against abnormal accumulation of lipids by transcriptionally suppressing LPL, which reduces the development of HCC. This newly identified pathway provides insight into the process through which TP exerts its anti-HCC actions. [ABSTRACT FROM AUTHOR]

The crucial issue in electrical impedance (EI) measurements lies in the galvanic interaction between the electrodes and the investigated material. This paper brings together the basic and applied research experience and combines their results with excellent properties. Consequently, innovative precise methodologies have emerged, enabling the direct modeling of EI measurements, free from the inaccuracies often associated with numerical approaches. As an outcome of the efficiency and robustness of the applied method, the conductivity of the material and the electrodes are represented by a common piecewise function, which is used to solve the differential equation modeling of the EI measurement. Moreover, this allows the possibility for modeling the conductivity of electrodes with continuous functions, providing an important generalization of the Complete Electrode Model (CEM), which has been widely used so far. The effectiveness of the novel approach was showcased through two distinct case studies. In the first case study, potential functions within both the material and the electrodes were computed using the CEM. In the second case study, calculations were performed utilizing the newly introduced continuous electrode model. The simulation results suggest that the new method is a powerful tool for biological research, from in vitro experiments to animal studies and human applications. [ABSTRACT FROM AUTHOR]

For patients who had testicular tissue cryopreserved before receiving gonadotoxic therapies, transplantation of testicular tissues and cells has been recommended as a potential therapeutic option. There are no studies that indicate the generation of sperm after human immature testicular tissue (ITT) or spermatogonial stem cells (SSCs) transplantation. The use of releasing scaffolds and localized drug delivery systems as well as the optimizing transplantation site can play an effective role in increasing the efficiency and improving the quality of testicular tissue and cell transplantation in animal models. Current research is focused on optimizing ITT and cell transplantation, the use of releasing scaffolds, and the selection of the right transplantation site that might restore sperm production or male infertility treatment. By searching the PubMed and Google Scholar databases, original and review papers were collected. Search terms were relevant for SSCs and tissue transplantation. In this review, we'll focus on the potential advantages of using scaffolds and choosing the right transplantation site to improve transplantation outcomes. [ABSTRACT FROM AUTHOR]

The American Association for Laboratory Animal Science endorses the United States Government "Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training" and requires that all papers published in Comparative Medicine report research conducted in conformance with these principles. Research for papers submitted from outside the United States must be in conformance with the guidelines of that country's government. The Editor reserves the right to reject papers reporting results of research not adhering to these principles.

The American Association for Laboratory Animal Science endorses the United States Government "Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training" and requires that all papers published in Comparative Medicine report research conducted in conformance with these principles. Research for papers submitted from outside the United States must be in conformance with the guidelines of that country's government. The Editor reserves the right to reject papers reporting results of research not adhering to these principles.

The article discusses the implications of developmental dyslexia, which is also called the congenital word-blindness, as well as recent speculations which have yet to be confirmed. These are derived from experiments conducted on normal humans and monkeys, as well as humans suffering from the experiments of nature. The notion that linguistic competence depends upon associations between vision and hearing implies that the mechanism employed in reading may not be unique to the reading-process.

Functional foods can be considered to be those whole, fortified, enriched or enhanced foods that provide health benefits beyond the provision of essential nutrients (e.g., vitamins and minerals), when they are consumed at efficacious levels as part of a varied diet on a regular basis. Linking the consumption of functional foods or food ingredients with health claims should be based on sound scientific evidence, with the "gold standard" being replicated, randomized, placebo-controlled, intervention trials in human subjects. However, not all foods on the market today that are claimed to be functional foods are supported by enough solid data to merit such claims. This review categorizes a variety of functional foods according to the type of evidence supporting their functionality, the strength of that evidence and the recommended intakes. Functional foods represent one of the most intensively investigated and widely promoted areas in the food and nutrition sciences today. However, it must be emphasized that these foods and ingredients are not magic bullets or panaceas for poor health habits. Diet is only one aspect of a comprehensive approach to good health. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphatase (G6Pase) is a multicomponent system located in the endoplasmic reticulum comprising a catalytic subunit and transporters for glucose-6-phosphate, inorganic phosphate, and glucose. We have recently cloned a novel gene that encodes an islet-specific G6Pase catalytic subunit-related protein (IGRP) (Ebert et al., Diabetes 48:543-551, 1999). To begin to investigate the molecular basis for the islet-specific expression of the IGRP gene, a series of truncated IGRP-chloramphenicol acetyltransferase (CAT) fusion genes were transiently transfected into the islet-derived mouse betaTC-3 and hamster insulinoma tumor cell lines. In both cell lines, basal fusion gene expression decreased upon progressive deletion of the IGRP promoter sequence between -306 and -66, indicating that multiple promoter regions are required for maximal IGRP-CAT expression. The ligation-mediated polymerase chain reaction footprinting technique was then used to compare trans-acting factor binding to the IGRP promoter in situ in betaTC-3 cells, which express the endogenous IGRP gene, and adrenocortical Y1 cells, which do not. Multiple trans-acting factor binding sites were selectively identified in betaTC-3 cells that correlate with regions of the IGRP promoter identified as being required for basal IGRP-CAT fusion gene expression. The data suggest that hepatocyte nuclear factor 3 may be important for basal IGRP gene expression, as it is for glucagon, GLUT2, and Pdx-1 gene expression. In addition, binding sites for several trans-acting factors not previously associated with islet gene expression, as well as binding sites for potentially novel proteins, were identified. [ABSTRACT FROM AUTHOR]

D-allulose, D-sorbose and D-tagatose are D-fructose isomers that are called rare sugars. These rare sugars have been studied intensively in terms of biological production and food application as well as physiological effects. There are limited papers with regard to the transporters mediating the intestinal absorption of these rare sugars. We examined whether these rare sugars are absorbed via sodium-dependent glucose cotransporter 1 (SGLT1) as well as via GLUT type 5 (GLUT5) using rats. High-fructose diet fed rats, which express more intestinal GLUT5, exhibited significantly higher peripheral concentrations, Cmax and AUC0–180 min when D-allulose, D-sorbose and D-tagatose were orally administrated. KGA-2727, a selective SGLT1 inhibitor, did not affect the peripheral and portal vein concentrations and pharmacokinetic parameters of these rare sugars. The results suggest that D-allulose, D-sorbose and D-tagatose are likely transported via GLUT5 but not SGLT1 in rat small intestine. [ABSTRACT FROM AUTHOR]