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Objectives: To analyze Australia's high-cited papers (HCPs) receiving ≥100 citations in pharmacology during 2002–2021 and examine the research characteristics, study performance of the top 30 leading participating organizations and authors, and identification of top 30 journals publishing in this area and sub-fields of their research. Materials and Methods: Australia's HCPs on pharmacology research from the top 30 most productive organizations were identified and extracted from the Scopus database from 2002 to 2021 on 21 September 2022 using a search strategy. Select bibliometric measures were utilized to evaluate the publication productivity of important players in this area. The network analysis was performed to evaluate the collaborative interactions amongst the countries, organizations, authors, and keywords. Results: Of the 19,418 Australia's publications (articles) in pharmacology from the top 30 most productive organizations during 2002–2022, only 685 (3.53%) were HCPs, which together received 1,14,623 citations, averaging 164.4 citations per paper (CPP) and the citations ranged from 100 to 1,230. Two papers had more than 1,000 citations and 16 papers had 500 citations. Of the 685 HCPs, 40.58% (278) and 11.39% (78) received external funding support and were international collaboratives. The most productive organizations were Monash University (n = 155), the University of Queensland (n = 111) and the University of Melbourne (n = 97). The most impactful organizations in terms of CPP and relative citation index (RCI) were James Cook University (203.22 and 1.21), Australian National University (196.67 and 1.18) and Queensland University of Technology (193.45 and 1.16). The most productive authors were J. Li (n = 24), C. J. H. Porter (n = 24) and R. L. Nation (n = 23) (Monash University, Melbourne); and the most impactful authors in terms of CPP were A. Christopoulos (Monash Institute of Pharmaceutical Sciences, Melbourne) (288.21), C.W. Pouton (Monash University, Melbourne) (241.50), and D.L. Peterson (University of Queensland, Brisbane) (225.58). The most productive journals were Antimicrobial Agents and Chemotherapy (n = 59), Environmental Pollution (n = 43) and Journal of Medicinal Chemistry (n = 42). The most impactful journals in terms of CPP were Nature Reviews Drug Discovery (371.8), Antiviral Research (286.86) and European Journal of Pharmaceutical Sciences (253.0). The most important keywords with their frequency of appearances were Animal Experiments (108), Metabolism (76), Drug Effects (67), Animal Models (65), Protein Expression (64), Anti-Bacterial Agents (62), Drug Delivery Systems (54), Drug Formulation (44), Signal Transduction (42), and so on. Conclusion: There is an urgent need to increase national funding and expand international collaboration in priority areas, which will help to increase and diversify research output and improve research impact. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to elucidate the connection between osteoclastic forkhead transcription factor O1 (FoxO1) and periodontitis and explore the underlying mechanism by which FoxO1 knockdown regulates osteoclast formation. Materials and Methods: A conventional ligature‐induced periodontitis model was constructed to reveal the alterations in the proportion of osteoclastic FoxO1 in periodontitis via immunofluorescence staining. Additionally, RNA sequencing (RNA‐seq) was performed to explore the underlying mechanisms of FoxO1 knockdown‐mediated osteoclastogenesis, followed by western blotting, quantitative polymerase chain reaction, and enzyme‐linked immunosorbent assay. Results: FoxO1+ osteoclasts were enriched in the alveolar bone in experimental periodontitis. Moreover, FoxO1 knockdown led to impaired osteoclastogenesis with low expression of osteoclast differentiation‐related genes, accompanied by an insufficient osteoclast maturation phenotype. Mechanistically, RNA‐seq revealed that the nuclear factor kappa B (NF‐κB) and nucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were inhibited in FoxO1‐knockdown osteoclasts. Consistent with this, MCC950, an effective inhibitor of the NLRP3 inflammasome, substantially attenuated osteoclast formation. Conclusions: FoxO1 knockdown contributed to the inhibition of osteoclastogenesis by effectively suppressing NF‐κB signaling and NLRP3 inflammasome activation. This prospective study reveals the role of FoxO1 in mediating osteoclastogenesis and provides a viable therapeutic target for periodontitis treatment. [ABSTRACT FROM AUTHOR]

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]

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]

Background: Multi-nozzle nebulisers for pressurised intraperitoneal aerosol chemotherapy (PIPAC) are implemented in clinical practice to improve the homogeneity of tissue drug delivery. Nonetheless, the advantages of such devices over one-nozzle nebulisers have not been demonstrated thus far. In this study, we compared the performance of multi- and one-nozzle nebulisers by conducting physical and ex vivo pharmacological experiments. Methods: The one-nozzle nebuliser Capnopen® and the multi-nozzle nebuliser were the subjects of this study. In physical experiments, the aerosol droplet size was measured by laser diffraction spectroscopy. Spatial spray patterns were depicted on blotting paper. Pharmacological experiments were performed on the enhanced inverted bovine urinary bladder model, demonstrating real-time tissue drug delivery, aerosol sedimentation and homogeneity of doxorubicin and cisplatin tissue distribution. Results: The multi-nozzle nebuliser had a sixfold greater aerosolisation flow and a threefold greater angle of aerosolisation than Capnopen®. The aerosol particle size and distribution range were higher than that of Capnopen®. Spray patterns on blotting paper were more extensive with the multi-nozzle nebuliser. Real-time tissue drug delivery with the multi-nozzle nebuliser was over 100 ml within 1 min, and the aerosol sedimentation was 48.9% ± 21.2%, which was not significantly different from that of Capnopen®. The doxorubicin and cisplatin tissue concentrations were greater with Capnopen®. Although there was no significant difference in the homogeneity of doxorubicin distribution between the two devices, the homogeneity of cisplatin distribution was significantly higher with Capnopen®. Conclusion: The multi-nozzle PIPAC nebuliser did not fulfil expectations. Even though the surface spray patterns were broader with the multi-nozzle nebuliser, the tissue drug homogeneity and concentration were greater with Capnopen®. [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]

[Objectives] To explore the difference of purgative effect of Mongolian medicine Euphorbia pekinensis and Pharbitidis Semen(black) by animal experiment, taking Euphorbia pekinensis and Pharbitidis Semen(black) as the research object. [Methods] Sixty Kunming mice were randomly divided into blank group(n=20), Euphorbia pekinensis group(n=20) and Pharbitidis Semen(black) group(n=20). After fasted but provided with free acess to drinking water for 3 d, the mice were intragastrically administered with drinking water, Euphorbia pekinensis test solution and Pharbitidis Semen(black) test solution, respectively. The mice were then placed separately in a mouse cage covered with filter paper for purgation test and intestinal propulsion test. [Results] The time of the first purgation in the Euphorbia pekinensis group and the Pharbitidis Semen(black) group was longer than that in the blank group(P<0.05). The total times of purgation and defecation within 5 h in the Euphorbia pekinensis group and the Pharbitidis Semen(black) group were higher than those in the blank group(P<0.05); the purgation index and intestinal propulsion rate in the Euphorbia pekinensis group and the Pharbitidis Semen(black) group were higher than those in the blank group(P<0.05). [Conclusions] The Mongolian medicine Euphorbia pekinensis was similar to Pharbitidis Semen(black) in purgation test and intestinal propulsion test, and could play a substitute role. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to study in vitro atomization properties of the self-developed sodium sivelestat for inhalation, evaluate the feasibility of this preparation as an aerosol inhalation, and provide the guidance for the following animal administration experiment. Firstly, in order to ensure accurate, uniform and stable doses of the self-developed product after administration, its atomization performance was analyzed through the testing of fine particle mass and the total emitted dose, and the results of its atomization parameters meet the requirement of inhalation. Next, Atomization characteristics of two commonly used nebulizers, air compressed nebulizer and mesh nebulizer, were studied and compared. The results showed that mesh atomizers have a smaller and more uniform particle size distribution. And then, the experiment of acute lung injury induced by aerosol inhalation of lipopolysaccharide in mice was used to test the therapeutic effect of our self-developed formulation, and compared with the positive control (sodium sivelestat for injection). The results showed that inhalation had a lower concentration and was equally effective than injection of sodium sivelestat. All the results support that the self-developed sodium sivelestat can be used as an aerosol inhaled drug. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) encompasses a spectrum of manifestations from simple steatosis to steatohepatitis, progressive fibrosis, cirrhosis and liver cancer. Emerging research has spotlighted flavonoids as promising candidates for interfering the initiation, promotion and progression of ALD. Thus this paper provides a comprehensive exposition on the effects of flavonoids on ALD and elucidates the underlying mechanisms. The results show that luteolin, soyasaponin, and isoliquiritigenin have demonstrated the ability to reduce liver fat synthesis, regulate lipid metabolism, and mitigate the undesirable accumulation of fat in hepatocytes. Quercetin and genistein exhibit excellent antioxidant properties, inhibiting lipid peroxidation and oxidative stress, thereby alleviating cellular inflammation and reducing the damage caused by alcohol to hepatocytes. Naringin, cyanidin, and butein also show promise in resisting liver fibrosis. The therapeutic effects of flavonoids on ALD have been validated through cell and animal experiments. However, the application development of flavonoids in functional foods still faces challenges due to insufficient research and industrialization hurdles. [ABSTRACT FROM AUTHOR]

Brody disease (BD) is an "ultra-rare" human genetic disorder of skeletal muscle function due to defects in the atp2a1 gene causing deficiency of the SERCA protein, isoform1. The main clinical signs are exercise-induced stiffness and delayed muscular relaxation after physical exercises, even mild ones. No mouse model nor specific therapies exist for Brody myopathy, which is therefore considered an orphan disease. Bovine congenital pseudomyotonia (PMT) is a muscular disorder characterized by an impairment of muscle relaxation and is the only mammalian model of human BD. The pathogenetic mechanism underlying bovine PMT has been recently clarified. These findings prompted us to purpose a potential pharmacological approach addressing a specific population of BD patients who exhibit reduced expression but still exhibit activity of the SERCA1 pump. Preclinical research involving in vivo studies is essential and necessary before clinical trials can be pursued and SERCA protein shows a high degree of conservation among species. So far, the only animal models available to study BD in vivo are a group of zebrafish mutant lines known as accordion zebrafish (acc). In this paper, we focused on a comprehensive characterization of the "acctq206" zebrafish variant. Our aim was to use this mutant line as an experimental animal model for testing the novel therapeutic approach for BD. [ABSTRACT FROM AUTHOR]

Purpose: Over the last decade or so, ethical and societal aspects of radiological protection have received increasing attention. This is also reflected in the publications of the International Commission on Radiological Protection (ICRP). The current paper aims at identifying relevant ethical and societal topics which should receive attention in the context of radiological protection for offspring and next generations. Materials and Methods: We present a non-comprehensive review of the subject, based on presentation made at an ICRP workshop in Budapest in 2022. We first discuss the ethical values promoted by ICRP, and the application of these values in cases of (potential) pre-conceptual and prenatal radiation exposures. We then consider experience gained after the Fukushima accident indicating particular societal concerns about the health effects of such exposures. Results and Conclusions: Beneficence/non-maleficence, prudence, justice and dignity, the "core values" of the system of radiological protection have special roles to play when heritable and/or in utero effects are to be considered. Prudence, in particular, must be taken account of in view of the fact that solid scientific data in humans are largely lacking in this area, and it is necessary to rely on insights from animal experiments as well as theoretical considerations. As regards societal considerations, the perception of risk among (potentially) affected populations needs to be taken seriously. Accountability, transparency, and inclusivity, the "procedural values" promoted by ICRP for the practical implementation of the system of radiological protection play a central role in overcoming skepticism and creating trust. Stakeholder involvement should emphasize cooperation and dialogue, which allows for the joint evaluation of an exposure situation by experts and affected people. [ABSTRACT FROM AUTHOR]

The number of genome assemblies has rapidly increased in recent history, with NCBI databases reaching over 41,000 eukaryotic genome assemblies across about 2,300 species. Increases in read length and improvements in assembly algorithms have led to increased contiguity and larger genome assemblies. While this number of assemblies is impressive, only about a third of these assemblies have corresponding genome size estimations for their respective species on publicly available databases. In this paper, genome assemblies are assessed regarding their total size compared to their respective publicly available genome size estimations. These deviations in size are assessed related to genome size, kingdom, sequencing platform, and standard assembly metrics, such as N50 and BUSCO values. A large proportion of assemblies deviate from their estimated genome size by more than 10%, with increasing deviations in size with increased genome size, suggesting nonprotein coding and structural DNA may be to blame. Modest differences in performance of sequencing platforms are noted as well. While standard metrics of genome assessment are more likely to indicate an assembly approaching the estimated genome size, much of the variation in this deviation in size is not explained with these raw metrics. A new, proportional N50 metric is proposed, in which N50 values are made relative to the average chromosome size of each species. This new metric has a stronger relationship with complete genome assemblies and, due to its proportional nature, allows for a more direct comparison across assemblies for genomes with variation in sizes and architectures. [ABSTRACT FROM AUTHOR]

Purpose: Studies have recently shown a correlation between the elemental components of coal dusts, including potassium aluminosilicates, and the lung response as a potential driver for lung diseases associated with inhalation of coal dust. Here we aimed to systematically review the evidence for the association between exposure to potassium bearing dusts and lung outcomes in human studies as well as adverse cellular response in animal/cell culture studies. Methods: A systematic search of the National Library of Medicine (PubMed), Embase and Web of Science was conducted in May 2024. Studies regarding exposure to potassium bearing dusts and aluminosilicates and respiratory consequence were included in the search. Articles were screened, with a secondary assessment for relevance and extraction of key information using a systematic review process. Results: We identified 64 studies, of which 35 were human studies, 22 involved animal experiments and 12 were in vitro studies with 5 papers having both in vivo and in vitro studies. Our review found some evidence that a range of potassium rich dusts increased incidence of respiratory symptoms and lung diseases, although the effect on radiological changes in the lung and pulmonary function loss was not consistent. The in vivo animal and in vitro studies consistently demonstrated an inflammatory response and cytotoxic effect after exposure to these dusts. Conclusion: Given complexity in the dust compositions and lack of direct evidence attributing these specific responses to potassium, we are not able to conclude the effect of potassium minerals in coal on development of respiratory diseases, warranting further research. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid. This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research. PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI. Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality. In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days (p < 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females (p = 0.008). Quercetin was also associated with improved inclined plane test score (p = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA (p < 0.0001) and MPO (p = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased (p = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI. Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI. [ABSTRACT FROM AUTHOR]

Color discrimination in jumping spiders Hasarius adansoni was examined by heat-avoidance learning in association with colored papers. The arena for the experiment was divided into two halves by a pair of colored papers. The colored papers used in this study were blue, green, yellow, red, white, gray and black. In training sessions, one half of the arena was heated from the bottom by a hot plate, and freely walking spiders were individually trained to avoid the heated half. In subsequent memory tests without heat, they consistently avoided the heat-associated colored papers. We found that jumping spiders could learn blue-green, blue-yellow, blue-red, blue-gray, green-yellow, green-red, green-gray, yellow-red, yellow-gray and red-gray patterns. Moreover, spiders trained with a blue-white pattern, a green-white pattern, a yellow-white pattern or a red-white pattern could discriminate the blue, green, yellow or red from black. It seems that jumping spiders can discriminate the blue, green, yellow and red papers by their hue, although brightness may also be used together with the color cue to discriminate colored papers. [ABSTRACT FROM AUTHOR]

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]

Purpose: Recently, there has been rapid development in model-informed drug development, which has the potential to reduce animal experiments and accelerate drug discovery. Physiologically based pharmacokinetic (PBPK) and machine learning (ML) models are commonly used in early drug discovery to predict drug properties. However, basic PBPK models require a large number of molecule-specific inputs from in vitro experiments, which hinders the efficiency and accuracy of these models. To address this issue, this paper introduces a new computational platform that combines ML and PBPK models. The platform predicts molecule PK profiles with high accuracy and without the need for experimental data. Methods: This study developed a whole-body PBPK model and ML models of plasma protein fraction unbound ( f up ), Caco-2 cell permeability, and total plasma clearance to predict the PK of small molecules after intravenous administration. Pharmacokinetic profiles were simulated using a "bottom-up" PBPK modeling approach with ML inputs. Additionally, 40 compounds were used to evaluate the platform's accuracy. Results: Results showed that the ML-PBPK model predicted the area under the concentration-time curve (AUC) with 65.0 % accuracy within a 2-fold range, which was higher than using in vitro inputs with 47.5 % accuracy. Conclusion: The ML-PBPK model platform provides high accuracy in prediction and reduces the number of experiments and time required compared to traditional PBPK approaches. The platform successfully predicts human PK parameters without in vitro and in vivo experiments and can potentially guide early drug discovery and development. [ABSTRACT FROM AUTHOR]

Spinal cord compression is a source of pathology routinely seen in clinical practice. However, there remain unanswered questions surrounding both the understanding of pathogenesis and the best method of treatment. This arises from limited real-life testing of the mechanical properties of the spinal cord, either through cadaveric human specimens or animal testing, both of which suffer from methodological, as well as ethical, issues. To conduct a review of the literature on the mechanical properties of the spinal cord. A systematic review of the literature on the mechanical properties of the spinal cord is undertaken. All literature reporting the testing of the mechanical properties of the spinal cord. Reported physiological mechanical properties of the spinal cord. The methodological quality of the studies has been assessed within the ARRIVE guidelines using the CAMARADES framework and SYRCLE's risk of bias tool. This paper details the methodologies and results of the reported testing. We show that (1) the research quality of previous work does not follow published guidelines on animal treatment or risk of bias, (2) no standard protocol has been employed for sample preparation or mechanical testing, (3) this leads to a wide distribution of results for the tested mechanical properties, not applicable to the living human or animal, and (4) animal testing is not a good proxy for human application. The findings summarize the sum of current knowledge inherent to the mechanical properties of the spinal cord and may contribute to the development of a physical model which is applicable to the living human 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 spinal cord compression. [ABSTRACT FROM AUTHOR]

Advanced general visual object tracking models have been drastically developed with the access of large annotated datasets and progressive network architectures. However, a general tracker always suffers domain shift when directly adopting to specific testing scenarios. In this paper, we dedicate to addressing the animal tracking problem by proposing a spatio-temporal inference module and a coarse-to-fine tracking strategy. In terms of tracking animals, non-rigid deformation is a typical challenge. Therefore, we particularly design a novel transformer-based inference structure where the changing animal state is transmitted across continuous frames. By explicitly transmitting the appearance variations, this spatio-temporal module enables adaptive target learning, boosting the animal tracking performance compared to the fixed template matching approaches. Besides, considering the altered contours of animals in different frames, we propose to perform coarse-to-fine tracking to obtain a fine-grained animal bounding box with a dedicated distribution-aware regression module. The coarse tracking phase focuses on distinguishing the target against potential distractors in the background. While the fine-grained tracking phase aims at accurately regressing the final animal bounding box. To facilitate animal tracking evaluation, we captured and annotated 145 video sequences with 20 categories from the zoo, forming a new test set for animal tracking, coined ZOO145. We also collected a dataset, AnimalSOT, with 162 video sequences from existing tracking test benchmarks. The experimental performance on animal tracking datasets, MoCA, ZOO145, and AnimalSOT, demonstrate the merit of the proposed approach against advanced general tracking approaches, providing a baseline for future animal tracking studies. [ABSTRACT FROM AUTHOR]

Postoperative adhesions complicate the majority of surgical procedures, imposing an excess medical burden. The segregation of injured tissue from healthy tissue is considered the optimal therapeutic strategy. However, achieving hemostasis while preventing adhesions in the immediate postoperative setting continues to pose a significant challenge. This paper presents the in situ formation of an asymmetrically adhesive hydrogel barrier via a sprayable dry powder (SDP) that enables interfacial water‐induced, ultra‐rapid gelation. Owing to SDP hydrophilicity and the interstitial spaces between particles, it can rapidly and efficiently absorb interfacial water, thereby facilitating smooth cross‐linking between material functional groups and tissue functional groups. In addition, SDP becomes less adhesive after gelation as a layer of interfacial water forms on the surface of the SDP hydrogel, enhancing its anti‐adhesion properties. Animal experiment outcomes demonstrate that SDP exhibits significant asymmetric adhesive properties before and after gelation, successfully preventing postoperative adhesions. As a result, SDP heralds a novel approach to the development of adhesives that can simultaneously mitigate adhesions and promptly arrest bleeding. [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]

Neuronal optogenetics is a technique to control the activity of neurons with light. This is achieved by artificial expression of light-sensitive ion channels in the target cells. By optogenetic methods, cells that are naturally light-insensitive can be made photosensitive and addressable by illumination and precisely controllable in time and space. So far, optogenetics has primarily been a basic research tool to better understand the brain. However, initial studies are already investigating the possibility of using optogenetics in humans for future therapeutic approaches for neuronal based diseases such as Parkinson's disease, epilepsy, or to promote stroke recovery. In addition, optogenetic methods have already been successfully applied to a human in an experimental setting. Neuronal optogenetics also raises ethical and legal issues, e.g., in relation to, animal experiments, and its application in humans. Additional ethical and legal questions may arise when optogenetic methods are investigated on cerebral organoids. Thus, for the successful translation of optogenetics from basic research to medical practice, the ethical and legal questions of this technology must also be answered, because open ethical and legal questions can hamper the translation. The paper provides an overview of the ethical and legal issues raised by neuronal optogenetics. In addition, considering the technical prerequisites for translation, the paper shows consistent approaches to address these open questions. The paper also aims to support the interdisciplinary dialogue between scientists and physicians on the one hand, and ethicists and lawyers on the other, to enable an interdisciplinary coordinated realization of neuronal optogenetics. [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]

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]

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]

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]

Background: Stroke is a major contributor to disability and death worldwide. Studies have demonstrated that inflammasome/pyroptosis and its mediated inflammatory response are important factors aggravating brain injury after stroke. We aimed to investigate and map the knowledge structure and global trends on inflammasome/pyroptosis in stroke. Methods: All relevant documents were obtained from the Web of Science on 5 June 2023. Bibliometric visualization diagrams were created using VOSviewer and CiteSpace. Excel was used for statistical analysis and drawing graphs. Results: A total of 1106 publications were included, with more articles published each year, especially since 2014. China (740 papers), Zhejiang University (57 papers), Wang J (25 papers), and the Journal of Neuroinflammation (45 papers) were the most productive countries, institutions, authors, and journals, respectively. The United States was the country with highest centrality (0.56) and total link strength (171), and all of the top 10 institutions were in China. China and the U.S. cooperated closely. The centralities of the top 10 authors were all lower than 0.01; no leader has yet emerged in this field. "NLRP3 inflammasome" ranked first with 447 occurrences among 2136 keywords, of which 56 terms appeared more than 10 times when categorized into four clusters: cluster 1 (inflammation), cluster 2 (pyroptosis), cluster 3 (NLRP3 inflammasome), and cluster 4 (neuroinflammation). The studies focused on the mechanisms of inflammasome/pyroptosis in stroke were mainly limited to cell and animal experiments. Conclusion: Interest in inflammasome/pyroptosis in stroke is progressively increasing. The NLRP3 inflammasome is the most extensively studied and has been a research hotspot. The mechanisms of cell death in stroke are complex and future studies are needed to strengthen the clinical research on the relationship between pyroptosis-related processes and stroke, determine at which stage NLRP3 inflammasome activation, and clarify the detailed mechanism of NLRP3 in stroke. [ABSTRACT FROM AUTHOR]

Ghee, a clarified butter commonly used in Indian cuisine for centuries. Both beneficial and harmful effects of ghee on health are found in many research works, and it creates more confusion about the intake of ghee and its effect on health. To overcome this confusion, it was decided to conduct a systematic review of experimental studies (In vivo) to synthesize available information on the oral intake of Ghee and its effect on lipid profile and other parameters. Twenty in vivo studies were identified, conducted in animals, and published between 1960 and 2020. The published research quality was assessed using ARRIVE guidelines and SYRCLE’s risk of Bias tool. Three of the 20 experiments were not included in the present study as they don't have abstracts, full papers, or free access to full papers. Source of milk fat (cow/ buffalo), method of preparation (cream/curd starter or traditional/modern) and form of usage (plain/fried - oxidized) alters the composition of ghee, which affects its effect on Lipid profile (TC, TG, HDL, LDL) and other parameters. The use of ghee, along with other fatty substances, may reduce the unhealthy effects of other plain or fried oils. Quantity (5, 10, and 20% of total calories) and duration (28, 60, 90, 120, and 270 days) of ghee affect lipid profile and other parameters differently. [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]

Society's compassion towards nonhuman animals used in experimentation has grown exponentially. This paper adopts critical discourse analysis to examine how the animal experimentation industry negotiates this societal moral response. To this end, the discourse of the largest animal experimentation interest group in Spain has been studied. Our findings show that the industry, as represented by this interest group, does not negotiate compassion with authenticity but rather creates an illusion of it through opportunistic lexical choices and suppressions, including contradictions and incongruities. We conclude by defining such a discourse as illusory authenticity, a discourse with which the industry conveniently frames itself as altruistic and concerned about animal suffering while at the same time discouraging the public's cultivation of compassion towards nonhuman animal suffering. This is done by means of perpetuating a logic that frames nonhuman animals as inferior beings whose existence is at the service of humanity. [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]

[Display omitted] • We reviewed the literature on isolation of Toxoplasma gondii directly in cell culture. • Four experiments were reported to isolate T. gondii from different animals in Vero and HFF cell cultures. • We recommend an in vitro protocol to isolate T. gondii. • This method is simpler, more cost-effective, ethically more acceptable, and less time-sensitive. Toxoplasma gondii is an apicomplexan protozoan parasite that can infect mammals and birds. The infection can cause acute toxoplasmosis and death in susceptible hosts. Bioassay using cats and mice has been the standard for the isolation of T. gondii from infected hosts for the past several decades. However, bioassay is labor-intensive, expensive, and involves using laboratory animals. To search alternative approaches and o work towards replacement of animal experiments, we summarized the key literature and conducted four experiments to isolate T. gondii in vitro by cell culture. A few heart tissue samples from animals with the highest antibody titers in a given collection were used for T. gondii isolation. These experiments included samples from five out of 51 wild ducks, four of 46 wild turkeys, six of 24 white-tailed deer, as well as from six kangaroos that had died with acute toxoplasmosis in a zoo. These experiments resulted in three isolates from five chronically infected wild ducks (60%), four isolates from four chronically infected wild turkeys (100%), one isolate from six chronically infected white-tailed deer (17%), and four isolates from six kangaroos with acute toxoplasmosis (67%). In addition, five isolates from the five chronically infected wild ducks were obtained by bioassay in mice, showing a 100% success rate, which is higher than the 60% rate by direct cell culture. These T. gondii isolates were successfully propagated in human foreskin fibroblast (HFF) or Vero cells, and genotyped by multilocus PCR-RFLP markers. The results showed that it is practical to isolate T. gondii directly in cell culture. Although the cell culture approach may not be as sensitive as the bioassay, it does provide an alternative that is simple, cost-effective, ethically more acceptable, and less time-sensitive to isolate T. gondii. In this paper we propose a procedure that may be applied and further optimized for isolation of T. gondii. [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]

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]

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]

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]

The development of cation electrokinetic concentrators (CECs) has been hindered by the lack of commercial anion-exchange membranes (AEMs). This paper introduces a γ-cyclodextrin-modified quaternized chitosan/polyvinyl alcohol (γ-CD/QCS/PVA) composite as an AEM, which is combined with a microchip to fabricate a CEC. Remarkably, the CEC only concentrates cationic species, thereby overcoming the interference of the highly abundant, negatively charged serum albumin in the blood sample. P-Glycoprotein (P-gp) is recognized as an efflux transporter protein that influences the pharmacokinetics (PK) of various compounds. The CEC was used to evaluate the activity of P-gp by detecting the positively charged rhodamine 123 (Rho123 is a classical substrate of P-gp) with no interference from serum albumin in the serum sample. Using the CEC, the enrichment factor (EF) of Rho123 exceeded 105-fold under DC voltage application. The minimal sample consumption of the CEC (<10 μL) enables reduction of animal sacrifice in animal experiments. Here, the CEC has been applied to evaluate the transport activity of P-gp in in vitro and in vivo experiments by detecting Rho123 in the presence of P-gp inhibitors or agonists. The results are in good agreement with those reported in previous reports. Therefore, the CEC presents a promising application potential, owing to its simple fabrication process, high sensitivity, minimal sample consumption, lack of interference from serum albumin and low cost. [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 first "R" from animal research ethics prescribes the replacement of animal experiments with animal-free alternatives. However, the question of when an animal-free method qualifies as an alternative to animal experiments remains unresolved. Drawing lessons from another debate in which the word "alternative" is central, the ethical debate on alternatives to germline genome editing, this paper develops a general account of when something qualifies as an alternative to something. It proposes three ethically significant conditions that technique, method, or approach X must meet to qualify as an alternative to Y: (1) X must address the same problem as Y, under an appropriate description of that problem; (2) X must have a reasonable chance of success, compared to Y, in solving the problem; and (3) X must not be ethically unacceptable as a solution. If X meets all these conditions, its relative advantages and disadvantages determine whether it is preferable, indifferent, or dispreferable as an alternative to Y. This account is then applied to the question of whether animal-free research methods qualify as alternatives to animal research. Doing so breaks down the debate around this question into more focused (ethical and other) issues and illustrates the potential of the account. [ABSTRACT FROM AUTHOR]

Background: Lewis serologic reagents frequently give inaccurate phenotyping results. Furthermore these serologic reagents are often used in nonserologic assays such as inhibition and immunohistochemistry. In both scenarios knowledge of the fine specificity and cross-reactivity of these reagents will improve the quality of results obtained.Study Design and Methods: A range of contemporary and historical workshop and developmental Lewis reagents including mouse monoclonal (MoAb) and human and goat polyclonal (PoAb) reagents were evaluated. All were evaluated both against Lewis kodecytes expressing only single Le(a) , Le(b) , ALe(b) , BLe(b) , Le(x) , Le(y) , ALe(y) , or BLe(y) antigens and against the same antigens inkjet printed on a paper-based microplate and analyzed by enzyme immunoassay. Nine clinical samples were also evaluated. A kodecyte antigen dilution sensitivity assay was used to establish the ratio of Le(b) antigen between group A1 /A2 and O RBCs.Results: A continuum of cross-reactivity from Le(x) through to H was observed with MoAbs. All PoAb and few MoAb anti-Le(a) samples and reagents cross-reacted to some degree with Le(b) antigen. Some PoAb and MoAb anti-Le(b) did not cross-react with Le(a) . All polyclonal goat anti-Le(b) reagents showed substantial activity against ALe(b) and BLe(b) , while no MoAb reagent had this activity. A1 RBCs had less than half the Le(b) antigen of A2 /O RBCs.Conclusions: Substantial cross-reactivity of both MoAbs and PoAbs with related antigens highlights the risks of using serologic reagents in nonserologic assays or against synthetic antigens. The lack of ALe(b) activity in anti-Le(b) MoAbs explains their poor performance against blood group A1 Le(a-b+) phenotypes. [ABSTRACT FROM AUTHOR]

This paper investigates the 'cynical scientist' as a figure in British animal science discourse that developed in relation to the nineteenth-century emergence of the 'sceptical scientist'. Here, efforts by scientists to demarcate their profession's territory led to religious backlash against an alleged 'divorce' of British science from Christian morality. Animal experimentation became embroiled in this controversy through antivivisectionists' conviction that animal research was symptomatic of scientific scepticism and Continental atheism's malign influence. Accusations of cynicism ultimately forced British scientists to accept legal regulation following the 1875 Royal Commission on Vivisection. British scientists were, however, able to utilise their political leverage and credibility as experts to favourably influence licensing and inspection. We suggest that efforts to silence public claims of scientific cynicism may have enabled 'cynical scientists' to remain invisible and that this was marked by privilege and power, not marginality. Nevertheless, we argue that regulation and reforms have also worked to internalise within British animal science the notion that scientific cynicism must be combatted through proper governance and internal discipline. [ABSTRACT FROM AUTHOR]

For the diagnosis of pediatric osteomyelitis, the sensitivity, specificity, and predictive value of erythrocyte sedimentation rate (ESR) were evaluated in this study.Methods: A systematic computer-based search was performed for relevant articles focusing on the ESR diagnosis of pediatric osteomyelitis in PubMed, Embase, and the Cochrane Library with an inclusion criteria: 1) the diagnostic utility of ESR for diagnosing osteomyelitis patients under the age of 18;2) two-by-two contingency tables can be obtained. Case reports, review papers, and animal experiments were excluded.Results: The diagnostic meta-analysis included 8 studies involving 348 children with osteomyelitis, all of whom were tested for ESR. Diagnostic meta-analysis revealed a sensitivity and specificity of 0.90, 95% confidence interval (CI) (0.86– 0.93), and 0.50 (95% CI,0.47– 0.54) for ESR in pediatric osteomyelitis diagnosis, respectively. The positive likelihood ratio (LR), negative LR, and diagnostic odds ratio were 1.38,(95% CI,1.08– 1.78), 0.46, (95% CI,0.26– 0.73), and 3.20, (95% CI,1.33– 7.69), respectively. The area under the curve (AUC) was determined to be 0.80 based on the summary receiver operating characteristic curve (SROC).Conclusion: The literature on the use of ESR in pediatric osteomyelitis diagnosis was thoroughly reviewed in this study. It was also found that ESR may be useful as a biomarker for pediatric osteomyelitis diagnosis. Due to its low specificity, it should be used in combination with other markers such as C-reactive protein, neutrophil percentage, and white blood cell count. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM) generally recurs locally with a dismal median survival of <18 months. Combining thermal therapy with radiation therapy enhances radiation response and improves clinical outcomes. This study evaluates a thermobrachytherapy balloon implant intended for the simultaneous heat and radiation treatment of tumor resection cavities. The data demonstrate that our prototype implant produces spherically symmetric heat and radiation dose distributions around the balloon, while the in vivo experiments confirm our ability to heat ≥40 °C at a 5 mm distance from the balloon surface in highly perfused pig brain tissue. The device is now ready for the finalization of regulatory approvals in anticipation of early-stage clinical investigation. Previous work has reported the design of a novel thermobrachytherapy (TBT) balloon implant to deliver magnetic nanoparticle (MNP) hyperthermia and high-dose-rate (HDR) brachytherapy simultaneously after brain tumor resection, thereby maximizing their synergistic effect. This paper presents an evaluation of the robustness of the balloon device, compatibility of its heat and radiation delivery components, as well as thermal and radiation dosimetry of the TBT balloon. TBT balloon devices with 1 and 3 cm diameter were evaluated when placed in an external magnetic field with a maximal strength of 8.1 kA/m at 133 kHz. The MNP solution (nanofluid) in the balloon absorbs energy, thereby generating heat, while an HDR source travels to the center of the balloon via a catheter to deliver the radiation dose. A 3D-printed human skull model was filled with brain-tissue-equivalent gel for in-phantom heating and radiation measurements around four 3 cm balloons. For the in vivo experiments, a 1 cm diameter balloon was surgically implanted in the brains of three living pigs (40–50 kg). The durability and robustness of TBT balloon implants, as well as the compatibility of their heat and radiation delivery components, were demonstrated in laboratory studies. The presence of the nanofluid, magnetic field, and heating up to 77 °C did not affect the radiation dose significantly. Thermal mapping and 2D infrared images demonstrated spherically symmetric heating in phantom as well as in brain tissue. In vivo pig experiments showed the ability to heat well-perfused brain tissue to hyperthermic levels (≥40 °C) at a 5 mm distance from the 60 °C balloon surface. [ABSTRACT FROM AUTHOR]

This review outlines the function of oxidative stress in DR and discusses therapeutic strategies to treat DR with antioxidants. Published papers on oxidative stress in DR and therapeutic strategies to treat DR with antioxidants were collected and reviewed via database searching on PubMed. The abnormal development of DR is a complicated process. The pathogenesis of DR has been reported to involve oxidative stress, despite the fact that the mechanisms underlying this are still not fully understood. Excessive reactive oxygen species (ROS) accumulation can damage retina, eventually leading to DR. Increasing evidence have demonstrated that antioxidant therapy can alleviate the degeneration of retinal capillaries in DR. Oxidative stress can play an important contributor in the pathogenesis of DR. Furthermore, animal experiments have shown that antioxidants are a beneficial therapy for treating DR, but more clinical trial data is needed. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA), characterized by inflammation and articular cartilage degradation, is a prevalent arthritis among geriatric population. This paper was to scrutinize the novel mechanism of long noncoding RNA (lncRNA) NEAT1 in OA etiology. Methods: A total of 10 OA patients and 10 normal individuals was included in this study. Cell model of OA was built in human normal chondrocytes induced by lipopolysaccharide (LPS). An OA Wistar rat model was established through intra-articular injection of L-cysteine and papain mixtures (proportion at 1:2) into the right knee. Quantitative reverse transcription-polymerase chain reaction was employed to ascertain the expression levels of NEAT1, microRNA (miR)-374b-5p and post-GPI attachment to protein 1 (PGAP1), while dual-luciferase reporter experiments were used for the validation of target relationship among them. Cell cycle and apoptosis were calculated by flow cytometry analysis. CCK-8 assay was done to evaluate the proliferative potentials of chondrocytes. The levels of cell cycle-related proteins (Cyclin A1, Cyclin B1 and Cyclin D2) and pro-apoptotic proteins (Caspase3 and Caspase9) were measured by western blotting. Tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 levels were determined via ELISA. Hematoxylin & eosin (HE) Staining was used for pathological examination in OA rats. Results: Pronounced downregulation of NEAT1 and PGAP1 and high amounts of miR-374b-5p were identified in OA patients, LPS-induced chondrocytes and OA rats. NEAT1 targeted miR-374b-5p to control PGAP1 expression. Loss of NEAT1 or upregulation of miR-374b-5p dramatically accelerated apoptosis, led to the G1/S arrest and promoted the secretion of inflammatory cytokines in LPS-induced chondrocytes, while ectopic expression of PGAP1 exhibited the opposite influences on chondrocytes. Additionally, we further indicated that upregulation of miR-374b-5p attenuated the effects of PGAP1 overexpression on LPS-induced chondrocytes. Conclusions: Reduced NEAT1 induces the development of OA via miR-374b-5p/PGAP1 pathway. This suggests that the regulatory axis NEAT1/miR-374b-5p/PGAP1 is a novel and prospective target for OA treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic tumours present significant treatment challenges due to their resistance to chemotherapy and complex tumour microenvironment. Choosing the appropriate preclinical models and understanding how their characteristics affect drug delivery to the tumours is essential for designing clinically relevant experiments. This study investigates pancreatic tumours growing orthotopically or subcutaneously and presents the properties of their tumour microenvironments and their impacts on drug delivery. Pancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy, mainly due to its resistance to chemotherapy and its complex tumour microenvironment characterised by stromal desmoplasia. There is a need for new strategies to improve the delivery of drugs and therapeutic response. Relevant preclinical tumour models are needed to test potential treatments. This paper compared orthotopic and subcutaneous PDAC tumour models and their suitability for drug delivery studies. A novel aspect was the broad range of tumour properties that were studied, including tumour growth, histopathology, functional vasculature, perfusion, immune cell infiltration, biomechanical characteristics, and especially the extensive analysis of the structure and the orientation of the collagen fibres in the two tumour models. The study unveiled new insights into how these factors impact the uptake of a fluorescent model drug, the macromolecule called 800CW. While the orthotopic model offered a more clinically relevant microenvironment, the subcutaneous model offered advantages for drug delivery studies, primarily due to its reproducibility, and it was characterised by a more efficient drug uptake facilitated by its collagen organisation and well-perfused vasculature. The tumour uptake seemed to be influenced mainly by the structural organisation and the alignment of the collagen fibres and perfusion. Recognising the diverse characteristics of these models and their multifaceted impacts on drug delivery is crucial for designing clinically relevant experiments and improving our understanding of pancreatic cancer biology. [ABSTRACT FROM AUTHOR]

This paper takes up Axel Honneth's suggestion that we, in the 21st century Western world, should revisit the Marxian idea of reification; unlike Honneth, however, this paper applies reification to the ways in which humans relate to non-human animals, particularly in the context of scientific experiments. Thinking about these practices through the lens of reification, the paper argues, yields a more helpful understanding of what is regarded as problematic in those practices than the standard animal rights approaches. The second part of the paper offers ways of overcoming reification that go beyond Honneth's idea of recognition by introducing Iris Murdoch's idea of attention. This proposed strategy makes the ethical relevance of reification more salient and makes it possible to counter reification through a practice such as attention which, unlike recognition, can be consciously established. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper presents an experimental study on a brachytherapy multi-needle insertion device, manipulated using a collaborative robot, to assess a set of characteristics: accuracy, needle deflection due to resistance forces, instrument and needle wear and the influence of insertion speed and rotation during needle manipulation inside the liver parenchyma. This paper presents a study regarding the design and the experimental setup of a medical robotic system for brachytherapy using tribology analysis. The robotic system is composed of a collaborative robotic arm and a multi-needle brachytherapy instrument controlled using a unified control system embedding a haptic device and force-feedback. This work is oriented towards identifying the technical characteristics of the system components to determine the accuracy of the procedure, as well as using different scenarios for needle insertion in ex vivo porcine liver tissue in order to determine the forces required for insertion and extraction of the needle and the friction coefficient that accompanies the previously mentioned forces. Subsequent to the computation of the friction forces, the normal forces and the wear during the needle insertion are determined with the scope of predicting the lifecycle of some components of the medical device. [ABSTRACT FROM AUTHOR]

The effects of neodymium:yttrium-aluminium-garnet (Nd:YAG) laser and silicon carbide (SiC) paper on the surface micro-topography of titanium-6 aluminium-4 vanadium (Ti6Al4V) alloy were examined in relation to the response of bone cells. The study was performed in three distinct stages: (1) after surface treatment of samples by laser and SiC paper, the surface hardness, surface roughness, corrosion resistance and surface tension were evaluated; (2) the growth of mouse connective tissue fibroblast cells (L-929) on untreated and treated samples was assessed in vitro; (3) the response of goat osteoblast cells to untreated and treated implanted samples was assessed in vivo. The surface roughness varied between 7 +/- 0.02 for laser-treated samples (LTSs) at 140 J cm(-2) and 21.8 +/- 0.05 for mechanically treated samples (MTSs). The surface hardness was found to vary from 377 Vickers hardness number (VHN) for MTSs to 850 VHN for LTSs. A corrosion potential of -0.21V was achieved for the LTSs compared with -0.51V for the MTSs. The LTSs exhibited a more hydrophilic behaviour (i.e. wettability) than did the MTSs. No cytotoxicity effect, unlike for the MTSs, was observed for the LTSs. The results of in vivo tests indicated longitudinal growth of osteoblast cells along the grooves on the samples formed by the SiC paper, and multidirectional spreading of the cells on the LTSs. [ABSTRACT FROM AUTHOR]