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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.

Introduction: There have been relatively few attempts to quantitatively assess if, and in which areas, the use of non-animal methods (NAMs) is increasing in biomedical research and importantly, how this compares to the use of live animals. Methods: We conducted a bibliometric analysis of the relative publication of papers reporting the use of NAMs-only compared to those reporting the use of animals, even if they also reported the use of NAMs, over the period 2003 to 2022 across seven research areas (breast cancer, lung disease, blood cancer, heart disease, neurodegenerative diseases, diabetes and toxicology) and five regions (USA, China, France, Germany, United Kingdom). Results: We found that the relative number of publications of research using NAMs-only has been higher than animal-based research for the last 20 years for all research areas and is growing. Research areas differed in their relative publication of NAMs-only based work, with breast cancer and lung disease having consistently the highest ratio of NAMs-only to animal-based publications and heart disease, diabetes and toxicology showing the greatest change over the time period. A key period of change was 2016--18. By 2022 the UK had the highest NAMs-only to animal-based research ratio than any other country for five of the seven research areas and China the lowest for six, accounting for publication rate. Tissue and in silico-based methods were the most common of all NAMs-only publications; lab-on-a-chip and stem cell models are increasing in their use but at much lower levels and rate of increase. Conclusion: We found that proportionately the reliance on animals in these research areas is decreasing, which will be encouraging to those that support the replacement of animal experiments. [ABSTRACT FROM AUTHOR]

Background: Osseointegrated dental implants are widely established as a first-choice treatment for the replacement of missing teeth. Clinical outcomes are however often compromised by short or longer-term biological complications and pathologies. Nanoparticle-coated materials represent a very active research area with the potential to enhance clinical outcomes and reduce complications of implant therapy. This scoping review aimed to summarize current research on various types of nanoparticles (NPs) used as surface modifiers of dental implants and their potential to promote biological and clinical outcomes. Methods: A systematic electronic search was conducted in SCOPUS, PubMed and Google Scholar aiming to identify in vivo, in situ, or in vitro studies published between 2014 and 2024. Inclusion and exclusion criteria were determined and were described in the methods section. Results: A total of 169 articles (44 original papers from Scopus and PubMed, and 125 articles from Google Scholar) were identified by the electronic search. Finally, 30 studies fit the inclusion criteria and were further used in this review. The findings from the selected papers suggest that nanoparticle-coated dental implants show promising results in enhancing bone regeneration and promoting angiogenesis around the implant site. These effects are due to the unique physicochemical properties of nanoparticle-coated implants and the controlled release of bioactive molecules from nanoparticle-modified surfaces. Conclusion: Nanoscale modifications displayed unique properties which could significantly enhance the properties of dental implants and further accelerate revascularization, and osseointegration while facilitating early implant loading. Yet, since many of these findings were based on in-vitro/in-situ systems, further research is required before such technology reaches clinical application. [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]

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]

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]

Background: Dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid isolated from the root of Menispermum dauricum DC, exhibits promising anti-Alzheimer's disease (AD) effects, but its underlying mechanisms remain inadequately investigated. This paper aims to identify potential targets and molecular mechanisms of DAU in AD treatment. Methods: Network pharmacology and molecular docking simulation method were used to screen and focus core targets. Various transgenic Caenorhabditis elegans models were chosen to validate the anti-AD efficacy and mechanism of DAU. Results: There are 66 potential DAU-AD target intersections identified from 100 DAU and 3036 AD-related targets. Subsequent protein-protein interaction (PPI) network analysis identified 16 core targets of DAU for anti-AD. PIK3CA, AKT1 and mTOR were predicted to be the central targets with the best connectivity through the analysis of "compound-target-biological process-pathway network". Molecular docking revealed strong binding affinities between DAU and PIK3CA, AKT1, and mTOR. In vivo experiments demonstrated that DAU effectively reduced paralysis in AD nematodes caused by Aβ aggregation toxicity, downregulated expression of PIK3CA, AKT1, and mTOR homologues (age-1, akt-1, let-363), and upregulated expression of autophagy genes and the marker protein LGG-1. Simultaneously, DAU increased lysosomal content and enhanced degradation of the autophagy-related substrate protein P62. Thioflavin T（Th-T）staining experiment revealed that DAU decreased Aβ accumulation in AD nematodes. Further experiments also confirmed DAU's protein scavenging activity in polyglutamine (polyQ) aggregation nematodes. Conclusion: Collectively, the mechanism of DAU against AD may be related to the activation of the autophagy-lysosomal protein clearance pathway, which contributes to the decrease of Aβ aggregation and the restoration of protein homeostasis. [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]

This document is a correction to a previously published paper titled "All-Natural Immunomodulatory Bioadhesive Hydrogel Promotes Angiogenesis and Diabetic Wound Healing by Regulating Macrophage Heterogeneity." The correction addresses mistakes in Figure 7A, which included the wrong image due to a computer lag during data processing. The incorrect images have been replaced, and errors in the annotations of other figures have also been corrected. The corrections do not impact the results and conclusions of the original article. [Extracted from the article]

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]

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]

Biomaterials with osteoinductivity are widely used for bone defect repair due to their unique structures and functions. Machine learning (ML) is pivotal in analyzing osteoinductivity and accelerating new material design. However, challenges include creating a comprehensive database of osteoinductive materials and dealing with low-quality, disparate data. As a standard for evaluating the osteoinductivity of biomaterials, ectopic ossification has been used. This paper compiles research findings from the past thirty years, resulting in a robust database validated by experts. To tackle issues of limited data samples, missing data, and high-dimensional sparsity, a data enhancement strategy is developed. This approach achieved an area under the curve (AUC) of 0.921, a precision of 0.839, and a recall of 0.833. Model interpretation identified key factors such as porosity, bone morphogenetic protein-2 (BMP-2), and hydroxyapatite (HA) proportion as crucial determinants of outcomes. Optimizing pore structure and material composition through partial dependence plot (PDP) analysis led to a new bone area ratio of 14.7 ± 7 % in animal experiments, surpassing the database average of 10.97 %. This highlights the significant potential of ML in the development and design of osteoinductive materials. This study leverages machine learning to analyze osteoinductive biomaterials, addressing challenges in database creation and data quality. Our data enhancement strategy significantly improved model performance. By optimizing pore structure and material composition, we increased new bone formation rates, showcasing the vast potential of machine learning in biomaterial design. [Display omitted] [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]

This paper presents a novel, cost-effective multisensory system designed for animal monitoring in research settings. The system aims to objectively assess animal welfare and discomfort during experiments, addressing the need for affordable monitoring solutions in research laboratories. Developed and validated in compliance with European regulations on animal experimentation and in accordance with the requirements of the Animal Research Centre at the University of Alcala´ in Madrid. The system integrates Raspberry Pi 4 Model B and Arduino Uno boards with various sensors, including temperature, humidity, ammonia, airborne particles, and an RGB camera. A user-friendly web interface allows remote monitoring and management of the system. This innovation promises to improve the efficiency and feasibility of animal research, enabling more precise and ethical experimentation while advancing scientific knowledge and animal welfare. [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]

There is an ongoing debate about the value of animal experiments to inform medical practice, yet there are limited data on how well therapies developed in animal studies translate to humans. We aimed to assess 2 measures of translation across various biomedical fields: (1) The proportion of therapies which transition from animal studies to human application, including involved timeframes; and (2) the consistency between animal and human study results. Thus, we conducted an umbrella review, including English systematic reviews that evaluated the translation of therapies from animals to humans. Medline, Embase, and Web of Science Core Collection were searched from inception until August 1, 2023. We assessed the proportion of therapeutic interventions advancing to any human study, a randomized controlled trial (RCT), and regulatory approval. We meta-analyzed the concordance between animal and human studies. The risk of bias was probed using a 10-item checklist for systematic reviews. We included 122 articles, describing 54 distinct human diseases and 367 therapeutic interventions. Neurological diseases were the focus of 32% of reviews. The overall proportion of therapies progressing from animal studies was 50% to human studies, 40% to RCTs, and 5% to regulatory approval. Notably, our meta-analysis showed an 86% concordance between positive results in animal and clinical studies. The median transition times from animal studies were 5, 7, and 10 years to reach any human study, an RCT, and regulatory approval, respectively. We conclude that, contrary to widespread assertions, the rate of successful animal-to-human translation may be higher than previously reported. Nonetheless, the low rate of final approval indicates potential deficiencies in the design of both animal studies and early clinical trials. To ameliorate the efficacy of translating therapies from bench to bedside, we advocate for enhanced study design robustness and the reinforcement of generalizability. Based on the analysis of 376 therapies in 54 human diseases, this study shows that, contrary to widespread assertions, the proportion of successful animal-to-human translation may be higher than anticipated; however, the low rate of final regulatory approval indicates potential design flaws of both animal studies and early clinical trials. [ABSTRACT FROM AUTHOR]

INTRODUCTION The aim of the study is the regulatory effect of MicroRNA-210 (MiR-210) on cigarette smoke extract (CSE)-induced mouse lung epithelial type II cells (MLE-12) apoptosis and determine whether the MiR-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via Shh signaling pathway. METHODS Expression of MiR-210 in CSE-induced MLE-12 was assessed by qRT-PCR. The emphysema mouse model and MiR-210 knockdown mice were each established by inhaling cigarette smoke or intratracheal lentiviral vector instillation. The Sonic hedgehog (Shh), Ptch1, Gli1, B-cell lymphoma-2 (Bcl-2), and Caspase 3 protein expressions were detected by Western blotting. mRNA expressions of MiR-210, Shh, Ptch1, and Gli1 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Apoptotic ratios in mice and CSE-induced HPVEC were assessed using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays and flow cytometry. RESULTS Our results showed that MiR-210 mRNA levels were significantly down-regulated in the CSE-induced MLE 12. MLE 12 apoptosis with down-regulated Shh, Ptch1, Gli1, and Bcl-2 expression, increased Caspase 3 expression in the emphysema mouse model and CSE-induced MLE 12. Knockdown MiR-210 can facilitate cell apoptosis and emphysema via the Shh signaling pathway in mice. In vitro, MiR-210 can attenuate the apoptosis of CSE-exposed MLE 12. Moreover, MiR-210 regulated the Shh pathway and promoted its expression. CONCLUSIONS MiRNA-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via the Shh signaling pathway. The present study reveals that MiRNA-210 may be a key regulator of cellular apoptosis and could be explored as a potential therapeutic target in the future. [ABSTRACT FROM AUTHOR]

Xin Li, Hao Xu, Jianfeng Yi, Chunlu Dong, Hui Zhang, Zhengfeng Wang, Long Miao, Wence Zhou. miR‐365 secreted from M2 Macrophage‐derived extracellular vesicles promotes pancreatic ductal adenocarcinoma progression through the BTG2/FAK/AKT axis. J Cell Mol Med. 2021; 25: 4671–4683. https://doi.org/10.1111/jcmm.16405. The above article, published online on 03 April 2021 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor‐in‐Chief, Stefan Constantinescu, The Foundation for Cellular and Molecular Medicine and John Wiley and Sons Ltd. The corresponding author asked to retract the article as they found that the animal experiments did not support all the conclusions of the paper. Subsequently, an investigation into concerns raised by a third party, revealed inappropriate duplications of images between this and other articles that were either previously published or published later in the same year. Thus, the editors consider the conclusions of this manuscript substantially compromised. Although the authors initially asked for the retraction, they did not agree to the retraction wording. [ABSTRACT FROM AUTHOR]

INTRODUCTION This study aimed to investigate the effects of nicotine on the activation of pancreatic stellate cells (PSCs) and pancreatic fibrosis in chronic pancreatitis (CP), along with its underlying molecular mechanisms. METHODS This was an in vivo and in vitro study. In vitro, PSCs were cultured to study the effects of nicotine on their activation and oxidative stress. Transcriptome sequencing was performed to identify potential signaling pathways involved in nicotine action. And the impact of nicotine on mitochondrial Ca2+ levels and Ca2+ transport-related proteins in PSCs was analyzed. The changes in nicotine effects were observed after the knockdown of the mitochondrial calcium uniporter (MCU) in PSCs. In vivo experiments were conducted using a mouse model of CP to assess the effects of nicotine on pancreatic fibrosis and oxidative stress in mice. The alterations in nicotine effects were observed after treatment with the MCU inhibitor Ru360. RESULTS In vitro experiments demonstrated that nicotine promoted PSCs activation, characterized by increased cell proliferation, elevated α-SMA and collagen expression. Nicotine also increased the production of reactive oxygen species (ROS) and cellular malondialdehyde (MDA), exacerbating oxidative stress damage. Transcriptome sequencing revealed that nicotine may exert its effects through the calcium signaling pathway, and it was verified that nicotine elevated mitochondrial Ca2+ levels and upregulated MCU expression. Knockdown of MCU reversed the effects of nicotine on mitochondrial calcium homeostasis, improved mitochondrial oxidative stress damage and structural dysfunction, thereby alleviating the activation of PSCs. In vivo validation experiments showed that nicotine significantly aggravated pancreatic fibrosis in CP mice, promoted PSCs activation, exacerbated pancreatic tissue oxidative stress, and increased MCU expression. However, treatment with Ru360 significantly mitigated these effects. CONCLUSIONS This study confirms that nicotine upregulates the expression of MCU, leading to mitochondrial calcium overload and exacerbating oxidative stress in PSCs, and ultimately promoting PSCs activation and exacerbating pancreatic fibrosis in CP. [ABSTRACT FROM AUTHOR]

INTRODUCTION Apoptosis and chronic inflammation are the main phenotypes in chronic obstructive pulmonary disease (COPD) pathogenesis. Cigarette smoke exposure is the leading risk factor for COPD, which causes aberrant airway epithelial structure and function. As a non-classical calpain, the molecular function of calpain5 (CAPN5) in COPD remains unclear. This study investigated the role of CAPN5 in mediating cigarette smoke extract (CSE)-induced apoptosis and inflammation. METHODS Immunohistochemistry (IHC) and Western blotting (WB) were performed to detect the location and expression of CAPN5. In vitro, BEAS-2B cells were transfected with CAPN5 siRNA or CAPN5 plasmid, followed by phosphatebuffered saline (PBS) or cigarette smoke extract (CSE) treatment. The protein expression levels of CAPN5, NF-κB p65, p-p65, IκBα, p-IκBα and apoptosis proteins (BCL-2, BAX) were measured by WB. Flow cytometry (FCM) was performed to analyze the cell apoptosis index. RESULTS CAPN5 was mainly expressed in the airway epithelium and significantly decreased in the COPD-smoker and emphysema-mouse groups. Silencing CAPN5 significantly decreased the protein expression of BCL-2, IκBα, and increased p-p65 and BAX protein expression. Additionally, an increased apoptosis index was detected after silencing CAPN5. Moreover, overexpression of CAPN5 partly inhibited IκBα degradation and p65 activation, and reduced CSE-induced inflammation and apoptosis. CONCLUSIONS These combined results indicate that CAPN5 could protect against CSEinduced apoptosis and inflammation, which may provide a potential therapeutic target for smoking-related COPD. [ABSTRACT FROM AUTHOR]

INTRODUCTION Macrophages play an important role in chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) impairs autophagy in alveolar macrophages from COPD patients, and autophagic impairment leads to reduced clearance of protein aggregates, dysfunctional mitochondria, and defective bacterial delivery to lysosomes. However, the exact function of lung macrophage autophagy in the pathogenesis of CS-induced COPD remains largely unknown. METHODS Western blot detected the expression of autophagy-related proteins induced by CSE. The model of COPD mice was established by CS exposure combined with CSE intraperitoneal injection. Double immunofluorescence was used to measure the CD206+LC3B+ cells. The morphological changes and effects on lung function were observed. Masson staining detected the changes in collagen fibers in lung tissue. The expression levels of E-cadherinb and N-cadherinb were detected by immunohistochemistry. Western blot detected the expression of ATP6V1E1 in lung tissue. RESULTS At 24 hours of exposure to CSE, the expression levels of LC3B (microtubuleassociated protein 1A/1B-light chain 3B) and P62 (nucleoporin 62) were highest at 1% CSE and AGT5 (nucleoporin 62) at 2.5% CSE; at 48 hours, the expression levels of LC3B, P62 and AGT5 were highest at 2.5% CSE, and as the intervention time increased. CD206+LC3B+ cells were significantly higher in the COPD group. Enhanced macrophage autophagy may promote emphysema formation and aggravate lung function damage. The expression of E-cadherinb in lung tissue of the COPD group was decreased, and N-cadherinb expression was increased; the expression of E-cadherinb was increased, and N-cadherinb expression was decreased in ATG5myeΔ COPD mice. The expression of ATP6V1E1 in the lung tissue was increased in the COPD group; ATP6V1E1 expression was decreased in the lung tissues of ATG5myeΔ COPD mice. CONCLUSIONS CSE enhanced macrophage autophagy, leads to increased lung function impairment and collagenous fiber in lung tissue, as well as promotes epithelialmesenchymal transition, and eventually leads to small airway remodeling, which may be achieved through the ATG5/ATP6V1E1 pathway. [ABSTRACT FROM AUTHOR]

INTRODUCTION The use of e-cigarettes (ECs) has reached unprecedented levels, due to a variety of reasons, including the misconception regarding their safety. Thus, there have been efforts to characterize the effects of EC exposure, including in the context of thirdhand EC (THEC) on a host of disorders, such as cardiovascular disease (CVD). METHODS To address this issue, we sought to characterize the effects of THEC on platelet function and thrombus formation, using a novel mouse exposure protocol that resembles real life scenarios. To assess these effects, a host of related in vivo (i.e. tail bleeding time, and ferric chloride injury induced thrombosis model) assays and in vitro platelet specific (e.g. aggregation, and dense granule secretion) investigative assays were conducted. RESULTS Our in vivo characterization demonstrated that THEC exposed mice exhibited a prothrombotic phenotype reflected by their shortened tail bleeding (THEC: 37 ± 15 seconds, versus clean air: 183 ± 56 s) and occlusion times (THEC: 188 ± 39 s, versus clean air: 519 ± 70 s), relative to those exposed to clean air. Importantly, we found no difference in the platelet counts between the THEC and clean air mice. As for the underlying mechanism, separate experiments revealed significantly enhanced platelet aggregation, dense and alpha granule secretion, as well as integrin/GPIIb-IIIa activation and phosphatidylserine exposure in response to thrombin and ADP agonist stimulation. CONCLUSIONS Taken together, these results provide evidence that THEC does have the capacity to increase the risk of thrombotic disease, which should increase awareness regarding its underappreciated negative health effects. [ABSTRACT FROM AUTHOR]

Aims: Autism is a multifaceted developmental disorder of the nervous system, that necessitates novel therapeutic approaches beyond traditional medications and psychosomatic therapy, such as appropriate sensory integration training. This systematic mapping review aims to synthesize existing knowledge on enriching environmental interventions as an alternative avenue for improving autism, guiding future research and practice. Method: A comprehensive search using the terms ASD and Enriched Environment was conducted across PubMed, EMBASE, ISI, Cochrane, and OVID databases. Most of the literature included in this review was derived from animal model experiments, with a particular focus on assessing the effect of EE on autism-like behavior, along with related pathways and molecular mechanisms. Following extensive group discussion and screening, a total of 19 studies were included for analysis. Results: Enriched environmental interventions exhibited the potential to induce both behavioral and biochemical changes, ameliorating autism-like behaviors in animal models. These improvements were attributed to the targeting of BDNFrelated pathways, enhanced neurogenesis, and the regulation of glial inflammation. Conclusion: This paper underscores the positive impact of enriched environmental interventions on autism through a review of existing literature. The findings contribute to a deeper understanding of the underlying brain mechanisms associated with this intervention. [ABSTRACT FROM AUTHOR]

• Evidence-based analysis of peri‑implant gas accumulation (PIGA). • Postoperative PIGA: common for musculoskeletal Mg implants. • Clinical relevance: potentially associated surgical complications. • Radiological techniques: for quantitative and longitudinal analysis. • Standardized evaluation needed for developing Mg implants. Historically, the rapid degradation and massive gas release from magnesium (Mg) implants resulted in severe emphysema and mechanical failure. With the advent of new alloys and surface treatment methods, optimized Mg implants have re-entered clinics since last decade with reliable performance. However, the optimization aims at slowing down the degradation process, rather than exemption of the gas release. This study involved a systematic evaluation of current preclinical and clinical evidence, regarding the physical signs, symptoms, radiological features, pathological findings and complications potentially associated with peri‑implant gas accumulation (PIGA) after musculoskeletal Mg implantation. The literature search identified 196 potentially relevant publications, and 51 papers were enrolled for further analysis, including 22 preclinical tests and 29 clinical studies published from 2005 to 2023. Various Mg-based materials have been evaluated in animal research, and the application of pure Mg and Mg alloys have been reported in clinical follow-ups involving multiple anatomical sites and musculoskeletal disorders. Soft tissue and intraosseous PIGA are common in both animal tests and clinical follow-ups, and potentially associated with certain adverse events. Radiological examinations especially micro-CT and clinical CT scans provide valuable information for quantitative and longitudinal analysis. While according to simulation tests involving Mg implantation and chemical processing, tissue fixation could lead to an increase in the volume of gas cavity, thus the results obtained from ex vivo imaging or histopathological evaluations should be interpreted with caution. There still lacks standardized procedures or consensus for both preclinical and clinical evaluation of PIGA. However, by providing focused insights into the topic, this evidence-based study will facilitate future animal tests and clinical evaluations, and support developing biocompatible Mg implants for the treatment of musculoskeletal disorders. [ABSTRACT FROM AUTHOR]

INTRODUCTION Endothelial progenitor cells (EPCs) dysfunction is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The transcription factor PU.1 is essential for the maintenance of stem/progenitor cell homeostasis. However, the role of PU.1 in COPD and its effects on EPC function and lunghoming, remain unclear. This study aimed to explore the protective activity of PU.1 and the underlying mechanisms in a cigarette smoke extract (CSE)-induced emphysema mouse model. METHODS C57BL/6 mice were treated with CSE to establish a murine emphysema model and injected with overexpressed PU.1 or negative control adeno-associated virus. Morphometry of lung slides, lung function, and apoptosis of lung tissues were evaluated. Immunofluorescence co-localization was used to analyze EPCs homing into the lung. Flow cytometry was performed to detect EPC count in lung tissues and bone marrow (BM). The angiogenic ability of BM-derived EPCs cultured in vitro was examined by tube formation assay. We determined the expression levels of PU.1, β-catenin, C-X-C motif ligand 12 (CXCL12), C-X-C motif receptor 4 (CXCR4), stem cell antigen-1 (Sca-1), and stemness genes. RESULTS CSE exposure significantly reduced the expression of PU.1 in mouse lung tissues, BM, and BM-derived EPCs. PU.1 overexpression attenuated CSE-induced emphysematous changes, lung function decline, and apoptosis. In emphysematous mice, PU.1 overexpression markedly reversed the decreased proportion of EPCs in BM and promoted the lung-homing of EPCs. The impaired angiogenic ability of BM-derived EPCs induced by CSE could be restored by the overexpression of PU.1. In addition, PU.1 upregulation evidently reversed the decreased expression of β-catenin, CXCL12, CXCR4, Scal-1, and stemness genes in mouse lung tissues, BM, and BM-derived EPCs after CSE exposure. CONCLUSIONS PU.1 alleviates the inhibitory effects of CSE on EPC function and lunghoming via activating the canonical Wnt/β-catenin pathway and CXCL12/CXCR4 axis. While further research is needed, our research may indicate a potential therapeutic target for COPD patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • We propose a decision logic to identify thyroid disruption in aquatic vertebrates. • The decision logic is evidence-based and includes internationally agreed guidelines. • Thyroid-mediated effect patterns must consider consistency and directions of changes. • The weight-of-evidence considers mode-of-action and population relevance assessments. • The decision logic supports regulatory assessments while minimising animal testing. According to the World Health Organisation and European Commission definitions, substances shall be considered as having endocrine disrupting properties if they show adverse effects, have endocrine activity and the adverse effects are a consequence of the endocrine activity (using a weight-of-evidence approach based on biological plausibility), unless the adverse effects are not relevant to humans or non-target organisms at the (sub)population level. To date, there is no decision logic on how to establish endocrine disruption via the thyroid modality in non-mammalian vertebrates. This paper describes an evidence-based decision logic compliant with the integrated approach to testing and assessment (IATA) concept, to identify thyroid-mediated effect patterns in aquatic vertebrates using amphibians as relevant models for thyroid disruption assessment. The decision logic includes existing test guidelines and methods and proposes detailed considerations on how to select relevant assays and interpret the findings. If the mammalian dataset used as the starting point indicates no thyroid concern, the Xenopus Eleutheroembryonic Thyroid Assay allows checking out thyroid-mediated activity in non-mammalian vertebrates, whereas the Amphibian Metamorphosis Assay or its extended, fixed termination stage variant inform on both thyroid-mediated activity and potentially population-relevant adversity. In evaluating findings, the response patterns of all assay endpoints are considered, including the direction of changes. Thyroid-mediated effect patterns identified at the individual level in the amphibian tests are followed by mode-of-action and population relevance assessments. Finally, all data are considered in an overarching weight-of-evidence evaluation. The logic has been designed generically and can be adapted, e.g. to accommodate fish tests once available for thyroid disruption assessments. It also ensures that all scientifically relevant information is considered, and that animal testing is minimised. The proposed decision logic can be included in regulatory assessments to facilitate the conclusion on whether substances meet the endocrine disruptor definition for the thyroid modality in non-mammalian vertebrates. [ABSTRACT FROM AUTHOR]

In this paper, the co-pyrolysis of blends of animal manure (AM) and high-density polyethylene (HDPE) waste was investigated using micro-thermal analysis techniques. Thermogravimetry coupled with Fourier-transform infrared spectroscopy was used to study the process kinetics and potential synergistic effects during co-pyrolysis. Dynamic co-pyrolysis experiments of animal manure (AM) and polyethylene (PE) blends in proportions of (90:10 %) and (80:20 %) were conducted at heating rates of 5, 10, 15, and 20 °C/min under an N 2 atmosphere. The process was analyzed and compared to the results obtained in the pyrolysis of pure components. AM and PE co-pyrolysis exhibited a synergic effect on the pyrolysis process, leading to a favorable change in the CPI pyrolysis initiation index. This was observed in the FTIR, shifting maximum devolatilization peaks by 14 °C towards lower temperatures and a lower activation energy of the main pyrolysis stage, with a decrease from 341.49±4.65 kJ/mol to 273.04±6.93 kJ/mol after the addition of 20 wt% PE to the blend. During co-pyrolysis, the main compounds observed in the FTIR absorption spectra were CO 2 , CO, CH 4 , NH 3 , and aromatic hydrocarbons from AM pyrolysis. Additionally, there was an increase in CH 4 and short-chain hydrocarbons due to the PE pyrolysis. • Co-processing of animal and plastic waste via pyrolysis using TG-FTIR was examined. • Addition of plastics to the animal waste changed CPI over 40 %. • 20 % addition of plastic lower energy activation of main pyrolysis stage by 25 %. • Four independent reaction kinetic models of the AM-PE co-pyrolysis were observed. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine is a severe and common neurological disorder, yet its precise physiological mechanisms remain unclear. The IGF1/IGF1r signaling pathway plays a crucial role in pain modulation. Studies have shown that IGF1, by binding to its receptor IGF1r, activates a series of downstream signaling cascades involved in neuronal survival, proliferation, autophagy and functional regulation. The activation of these pathways can influence nociceptive transmission. Furthermore, alterations in IGF1/IGF1r signaling are closely associated with the development of various chronic pain conditions. Therefore, understanding the specific mechanisms by which this pathway contributes to pain is of significant importance for the development of novel pain treatment strategies. In this study, we investigated the role of IGF1/IGF1r and its potential mechanisms in a mouse model of chronic migraine. Methods: Chronic migraine was induced in mice by repeated intraperitoneal injections of nitroglycerin. Mechanical and thermal hypersensitivity responses were assessed using Von Frey filaments and radiant heat, respectively. To determine the role of IGF1/IGF1r in chronic migraine (CM), we examined the effects of the IGF1 receptor antagonist ppp (Picropodophyllin) on pain behaviors and the expression of calcitonin gene-related peptide (CGRP) and c-Fos. Result: In the nitroglycerin-induced chronic migraine model in mice, neuronal secretion of IGF1 is elevated within the trigeminal nucleus caudalis (TNC). Increased phosphorylation of the IGF1 receptor occurs, predominantly co-localizing with neurons. Treatment with ppp alleviated basal mechanical hypersensitivity and acute mechanical allodynia. Furthermore, ppp ameliorated autophagic dysfunction and reduced the expression of CGRP and c-Fos. Conclusion: Our findings demonstrate that in the chronic migraine (CM) model in mice, there is a significant increase in IGF1 expression in the TNC region. This upregulation of IGF1 leads to enhanced phosphorylation of IGF1 receptors on neurons. Targeting and inhibiting this signaling pathway may offer potential preventive strategies for mitigating the progression of chronic migraine. [ABSTRACT FROM AUTHOR]

Introduction: Propylene glycol (PG) is frequently used as a solvent for various medications. However, there is substantial evidence of Propylene glycol toxicity, such as depression, agitation, and seizures, particularly when used in combination with other drugs. Here, we aimed to study the effect of Propylene glycol administration in combination with amyloid β1-40 injection on hippocampal neurons. Materials & Methods: Thirty-six male Wistar rats were randomly divided into four groups: sham, amyloid β1-40 injection group, Propylene glycol group, and amyloid β1-40+ Propylene glycol group. Alternation behavior, number of neurons in the hippocampus, lipid peroxidation markers, and superoxide dismutase levels were analyzed in all rats. Results: When Propylene glycol was co-administered with amyloid β1-40, a notable reduction in the mean neuronal count was observed in the CA1, CA3, and DG regions compared with the amyloid β1-40 only injected animals (P < 0.05). Furthermore, Propylene glycol induced an increase in lipid peroxidation markers (10.78±0.4) and a decrease in antioxidant content (2.8 ± 0.17) when administered with amyloid β1-40s compared to the animals that received only amyloid β1-40 (P<0.05). A similar pattern was found in alternation behavior compared with the group with amyloid β1-40 injection (P<0.001). Conclusion: Propylene glycol could produce excessive neurotoxicity in regions of the hippocampus when co-administered with amyloid β1-40. It likely increases lipid peroxidation and reduces superoxide dismutase in the rat brain. The use of different agents as a vehicle should be considered, especially in the elderly. [ABSTRACT FROM AUTHOR]

Background: Nanostructured materials used have unique properties and many uses in nanotechnology. The most striking of these is using herbal compounds for the green synthesis of nanoparticles. Among the nanoparticle types used for green synthesis, gold nanoparticles (AuNPs) are used for cancer therapy due to their stable structure and non-cytotoxic. Lung cancer is the most common and most dangerous cancer worldwide in terms of survival and prognosis. In this study, Nasturtium officinale (L.) extract (NO), which contains biomolecules with antioxidant and anticancer effects, was used to biosynthesize AuNPs, and after their characterization, the effect of the green-synthesized AuNPs against lung cancer was evaluated in vitro. Methods: Ultraviolet‒visible (UV‒Vis) spectrophotometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), multiple analysis platform (MAP), and Fourier transform infrared (FT-IR) spectroscopy analyses were performed to characterize the AuNPs prepared from the N. officinale plant extract. Moreover, the antioxidant activity, total phenolic and flavonoid contents and DNA interactions were examined. Additionally, A549 lung cancer cells were treated with 2–48 µg/mL Nasturtium officinale gold nanoparticles (NOAuNPs) for 24 and 48 h to determine the effects on cell viability. The toxicity of the synthesized NOAuNPs to lung cancer cells was determined by the 3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide (MTT) assay, and the anticancer effect of the NOAuNPs was evaluated by apoptosis and cell cycle analyses using flow cytometry. Results: The average size of the NPs was 56.4 nm. The intensities of the Au peaks from EDS analysis indicated that the AuNPs were synthesized successfully. Moreover, the in vitro antioxidant activities of the NO and NOAuNPs were evaluated; these materials gave values of 31.78 ± 1.71% and 31.62 ± 0.46%, respectively, in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay at 200 g/mL and values of 25.89 ± 1.90% and 33.81 ± 0.62%, respectively, in the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. The NO and NOAuNPs gave values of 0.389 ± 0.027 and 0.308 ± 0.005, respectively, in the ferrous ion reducing antioxidant capacity (FRAP) assay and values of 0.078 ± 0.009 and 0.172 ± 0.027, respectively, in the copper ion reducing antioxidant capacity (CUPRAC) assay. When the DNA cleavage activities of NO and the NOAuNPs were evaluated via hydrolysis, both samples cleaved DNA starting at a concentration of 25 g/mL in the cell culture analysis, while the nanoformulation of the NO components gave greater therapeutic and anticancer effects. We determined that the Au nanoparticles were not toxic to A549 cells. Moreover, after treatment with the half-maximal inhibitory concentration (IC50), determined by the MTT assay with A549 cells, we found that at 24 and 48 h, while the necrosis rates were high in cells treated with NO, the rates of apoptosis were greater in cells treated with NOAuNPs. Notably, for anticancer treatment, activating apoptotic pathways that do not cause inflammation is preferred. We believe that these results will pave the way for the use of NOAuNPs in in vitro studies of other types of cancer. Conclusion: In this study, AuNPs were successfully synthesized from N. officinale extract. The biosynthesized AuNPs exhibited toxicity to and apoptotic effects on A549 lung cancer cells. Based on these findings, we suggest that green-synthesized AuNPs are promising new therapeutic agents for lung cancer treatment. However, since this was an in vitro study, further research should be performed in in vivo lung cancer models to support our findings and to explain the mechanism of action at the molecular level. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of Shuanglongjiegu pill (SLJGP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explore its mechanism based on miR-217/RUNX2 axis. Results found that drug-containing serum of SLJGP promoted BMSCs viability with a dose-dependent effect. Under osteogenic differentiation conditions, SLJGP promoted the expression of ALP, OPN, BMP2, RUNX2, and the osteogenic differentiation ability of BMSCs. In addition, SLJGP significantly reduced miR-217 expression, and miR-217 directly targeted RUNX2. After treatment with miR-217 mimic, the promoting effects of SLJGP on proliferation and osteogenic differentiation of BMSCs were significantly inhibited. MiR-217 mimic co-treated with pcDNA-RUNX2 further confirmed that the miR-217/RUNX2 axis was involved in SLJGP to promote osteogenic differentiation of BMSCs. In addition, analysis of Wnt/β-catenin pathway protein expression showed that SLJGP activated the Wnt/β-catenin pathway through miR-217/RUNX2. In conclusion, SLJGP promoted osteogenic differentiation of BMSCs by regulating miR-217/RUNX2 axis and activating Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Objective: Arthritis has been postulated as a prevalent potential risk factor for the emergence of dementia and cognitive impairment. This conjecture prompted an examination of the correlation between arthritis and cognitive impairment using the National Health and Nutrition Examination Survey (NHANES) repository. The analysis was meticulously adjusted for potential confounders such as age and assorted systemic comorbidities, to ensure robustness in the results obtained. Methods: Among 2,398 adults aged 60 years and above, logistic regression and cubic spline models were employed to elucidate the relationship between arthritis and cognitive performance. This was assessed utilizing tests such as Immediate Recall test (IRT), Delayed Recall test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Results: In our investigation, a total of 19931 individuals were analyzed, among which 2,398 patients (12.03%) were identified with arthritis. Subjects with arthritis inflammation had lower DSST and AFT scores compared to the healthy group, indicating cognitive decline. After adjusting for all covariates, arthritis was significantly associated with higher DSST and AFT scores by logistic regression modeling (OR: 0.796, 95% CI: 0.649–0.975; OR: 0.769, 95% CI: 0.611–0.968). Conclusion: Our analysis underscores the potential linkage between arthritis prevalence and cognitive impairment within a nationally representative of US older adults. [ABSTRACT FROM AUTHOR]

Background: Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. Objectives: This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. Methods: The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. Results: Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. Conclusion: By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a devastating malignancy with a high mortality rate, poor prognosis, and limited treatment options. The tumor microenvironment (TME) plays a crucial role in tumor progression and therapy resistance. Multiple subpopulations of cancer-associated fibroblasts (CAFs) within the TME can switch between different states, exhibiting both antitumorigenic and protumorigenic functions in pancreatic cancer. It seems that targeting fibroblast-related proteins and other stromal components is an appealing approach to combat pancreatic cancer. This study employed single-cell transcriptome sequencing to identify MME (Membrane Metalloendopeptidase)-expressing CAFs in pancreatic cancer. Systematic screening was conducted based on tumor differentiation, lymph node metastasis, and T-stage parameters to identify and confirm the existence of a subpopulation of fibroblasts termed MME+CAFs. Subsequent analyses included temporal studies, exploration of intercellular communication patterns focusing on the hypoxia signaling pathway, and investigation of MME+CAF functions in the pancreatic cancer microenvironment. The pathway enrichment analysis and clinical relevance revealed a strong association between high MME expression and glycolysis, hypoxia markers, and pro-cancer inflammatory pathways. The role of MME+CAFs was validated through in vivo and in vitro experiments, including high-throughput drug screening to evaluate potential targeted therapeutic strategies. Single-cell transcriptome sequencing revealed tumor-associated fibroblasts with high MME expression, termed MME+CAF, exhibiting a unique end-stage differentiation function in the TME. MME+CAF involvement in the hypoxia signaling pathway suggested the potential effects on pancreatic cancer progression through intercellular communication. High MME expression was associated with increased glycolysis, hypoxia markers (VEGF), and pro-cancer inflammatory pathways in pancreatic cancer patients, correlating with lower survival rates, advanced disease stage, and higher oncogene mutation rates. Animal experiments confirmed that elevated MME expression in CAFs increases tumor burden, promotes an immunosuppressive microenvironment, and enhances resistance to chemotherapy and immunotherapy. The developed MME+CAF inhibitor IOX2 (a specific prolyl hydroxylase-2 (PHD2) inhibitor), combined with AG (Paclitaxel + Gemcitabine) and anti-PD1 therapy, demonstrated promising antitumor effects, offering a translational strategy for targeting MME in CAFs of pancreatic cancer. The study findings highlighted the significant role of MME+CAF in pancreatic cancer progression by shaping the TME and influencing key pathways. Targeting MME presented a promising strategy to combat the disease, with potential implications for therapeutic interventions aimed at disrupting MME+CAF functions and enhancing the efficacy of pancreatic cancer treatments. [ABSTRACT FROM AUTHOR]

Establishing the context: Intestinal dysbiosis is a significant concern among dog owners, and the gut health of pets is an emerging research field. In this context, the Simulator of the Canine Intestinal Microbial Ecosystem (SCIMETM) was recently developed and validated with in vivo data. Stating the purpose/introducing the study: The current study presents a further application of this model by using amoxicillin and clavulanic acid to induce dysbiosis, aiming to provoke changes in microbial community and metabolite production, which are well-known markers of the disease in vivo. Describing methodology: Following the induction of dysbiosis, prebiotic supplementation was tested to investigate the potential for microbiota recovery under di [ABSTRACT FROM AUTHOR]

Background: Bisphosphonates (BPs) are widely used to inhibit excessive osteoclast activity. However, the potential to compromise bone defect healing has limited their broader application. To better understand the influence of BPs on bone regeneration, we established a bone grafting model with Zoledronate administration, aiming to deepen the understanding of bone remodeling and mineralization processes. Methods: A bone grafting model was established in the distal femurs of male Sprague–Dawley rats. The experimental group received systemic administration of Zoledronate (ZOL, 0.2 mg/kg, administered twice). Histological analysis and immunohistochemistry (IHC) were employed to assess osteoblastic and macrophage activity, tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate osteoclastogenesis. Mineralization was assessed through Micro-CT analysis, Raman spectroscopy, and back-scatter scanning electron microscopy (BSE-SEM). Additionally, the in vitro effects of ZOL on osteoblast and osteoclast activity were investigated to further elucidate its impact on bone regeneration. Results: In vivo, the ZOL group showed increased bone mass, as observed in histological and radiological assessments. However, Micro-CT, Raman spectroscopy, and BSE-SEM detection revealed lower mineralization levels in ZOL group's regenerated bone. Acid-etched SEM analysis showed abnormal osteocyte characteristics in ZOL-group's regenerated bone. Simultaneously, elevated osteopontin (OPN), F4/80 expression along with reduced TRAP expressing was found in the grafting region of ZOL group. In vitro, ZOL did not negatively impact osteogenetic activity (ALP, BMP4, OCN expression) at the tested concentrations (0.02–0.5 g/ml) but significantly impaired mineralization and inhibited osteoclast formation, even at the lowest concentration. Conclusions: This study highlights a less recognized negative effect of ZOL on bone mineralization during bone regeneration. More research is needed to elucidate the underlying mechanism. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), with a high mortality rate of up to 30%. The envelope glycoproteins of SFTSV, glycoprotein N (Gn) and glycoprotein C (Gc), facilitate the recognition of host receptors and the process of membrane fusion, allowing the virus to enter host cells. We previously reported a monoclonal antibody, mAb 40C10, capable of neutralizing different genotypes of SFTSV and SFTSV-related viruses. However, the specific neutralization mechanism is poorly understood. In this study, we elucidated the high-resolution structure of the SFTSV Gn head domain in complex with mAb 40C10, confirming that the binding epitope in the domain I region of SFTSV Gn, and it represented that a novel binding epitope of SFTSV Gn was identified. Through in-depth structural and sequence analyses, we found that the binding sites of mAb 40C10 are relatively conserved among different genotypes of SFTSV and SFTSV-related Heartland virus and Guertu virus, elucidating the molecular mechanism underlying the broad-spectrum neutralizing activity of mAb 40C10. Furthermore, we humanized of mAb 40C10, which is originally of murine origin, to reduce its immunogenicity. The resulting nine humanized antibodies maintained potent affinity and neutralizing activity. One of the humanized antibodies exhibited neutralizing activity at picomolar IC50 values and demonstrated effective therapeutic and protective effects in a mouse infection model. These findings provide a novel target for the future development of SFTSV vaccines or drugs and establish a foundation for the research and development of antibody therapeutics for clinical applications. Author summary: Severe fever with thrombocytopenia syndrome virus (SFTSV) infection has emerged as a global public health issue, and its incidence is increasing annually. Neutralizing antibodies offer rapid and efficient therapeutic potential against viral infections. In this report, we elucidated the crystal structure of a highly effective and broad-spectrum murine neutralizing antibody, mAb 40C10, in complex with the SFTSV glycoprotein N (Gn) head domain. Through structural and sequence analyses, we revealed the molecular mechanism underlying the neutralization activity of mAb 40C10 and unveiled a new, potent, and broad-spectrum neutralizing epitope. Notably, this epitope is conserved across different genotypes of SFTSV and SFTSV-related viruses. The newly identified epitope provides valuable insights for reverse vaccine or drug design. Furthermore, we humanized mAb 40C10 and demonstrated the sustained efficacy of the humanized antibody in animal experiments, potentially advancing the development of clinical antibody therapeutics targeting SFTSV. [ABSTRACT FROM AUTHOR]

In recent years, negative pressure wound dressings have garnered widespread attentions. However, it is challenging to drain the accumulated fluid under negative pressures for hydrogel dressings. To address this issue, this study prepared a chemical/physical duel‐network PEG‐CMCS/AG/MXene hydrogel composed by chemical disulfide crosslinked network of four‐arm polyethylene glycol/carboxymethyl chitosan (4‐Arm‐PEG‐SH/CMCS), and the physical network of hydrogen bond of agar (AG). Under near‐infrared light (NIR) irradiation, the PEG‐CMCS/AG/MXene hydrogel undergoes photothermal heating due to integrate of MXene, which destructs the hydrogen bond network and allows the removal of exudate through a mechanism mimicking the sweat gland‐like effect of skin pores. The photothermal heating effect also enables the antimicrobial activity to prevent wound infections. The excellent electrical conductivity of PEG‐CMCS/AG/MXene can promote cell proliferation under the external electrical stimulation (ES) in vitro. The animal experiments of full‐thickness skin defect model further demonstrate its ability to accelerate wound healing. The conversion between thioester and thiol achieved with L‐cysteine methyl ester hydrochloride (L‐CME) can provides the on‐demand dissolution of the dressing in situ. This study holds promises to provide a novel solution to the issue of fluid accumulations under hydrogel dressings and offers new approaches to alleviating or avoiding the significant secondary injuries caused by frequent dressing changes. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the impact of virtual simulation experiment teaching model and Massive Open Online Course (MOOC) teaching model on the teaching effect in debridement teaching. Methods: The study adopted a quasi-experimental design and used virtual simulation technology to construct a virtual simulation experimental teaching platform for debridement. This study was conducted at the Second Clinical College of Wuhan University. The experimental group was composed of 135 third-year clinical medicine students in the 2020 grade, who received the virtual simulation experimental teaching model; the control group was 122 third-year students in the same major in the 2019 grade, who used the MOOC teaching model. The performance of the two groups of students was evaluated through theoretical tests and animal experiment operation. In addition, the effectiveness of the experimental teaching model and student satisfaction were evaluated through questionnaire surveys. Results: The theoretical test scores and animal experiment report scores of the experimental group were significantly higher than those of the control group, and the debridement animal experiment operation time of the experimental group was shorter than that of the control group, and the difference was statistically significant (P < 0.05). The post-class questionnaire survey of the experimental group showed that most students were satisfied with the virtual simulation experimental teaching model and believed that it represented the future teaching trend. Conclusions: In the teaching of debridement, virtual simulation experiment is an effective t teaching model, which not only helps to improve student performance, but also significantly reduces skill operation time and is recognized by students. [ABSTRACT FROM AUTHOR]

Preclinical studies on pathological pain rely on the von Frey test to examine changes in mechanical thresholds and the acetone spray test to determine alterations in cold sensitivity in rodents. These tests are typically conducted on rodent hindpaws, where animals with pathological pain show reliable nocifensive responses to von Frey filaments and acetone drops applied to the hindpaws. Pathological pain in orofacial regions is also an important clinical problem and has been investigated with rodents. However, performing the von Frey and acetone spray tests in the orofacial region has been challenging, largely due to the high mobility of the head of testing animals. To solve this problem, we implemented a sheltering tube method to assess orofacial nociception in mice. In experiments, mice were sheltered in elevated tubes, where they were well accommodated because the tubes provided safe shelters for mice. Examiners could reliably apply mechanical stimuli with von Frey filament, cold stimuli with acetone spray, and light stimuli with a laser beam to the orofacial regions. We validated this method in Nav1.8-ChR2 mice treated with oxaliplatin that induced peripheral neuropathy. Using the von Frey test, orofacial response frequencies and nociceptive response scores were significantly increased in Nav1.8-ChR2 mice treated with oxaliplatin. In the acetone spray test, the duration of orofacial responses was significantly prolonged in oxaliplatin-treated mice. The response frequencies to laser light stimulation were significantly increased in Nav1.8-ChR2 mice treated with oxaliplatin. Our sheltering tube method allows us to reliably perform the von Frey, acetone spray, and optogenetic tests in orofacial regions to investigate orofacial pain. [ABSTRACT FROM AUTHOR]