Pyroptosis inhibitors MCC950 and VX-765 mitigate myocardial injury by alleviating oxidative stress, inflammation, and apoptosis in acute myocardial hypoxia.

Acute myocardial infarction (AMI) is a prevalent cardiovascular disease with high morbidity and mortality rates worldwide. Pyroptosis is an inflammatory form of programmed cell death that has been linked to various pathological conditions. However, its exact contribution to the onset and progression of heart injury in AMI has not yet fully elucidated. Herein, we established mouse AMI model by ligating the left anterior descending artery and performed transcriptome analysis during the early phase of AMI. Mouse HL-1 and human AC-16 cardiomyocytes were subjected to hypoxia to simulate ischemic injury in vitro. Our results revealed a significant activation of the inflammatory response at 3 h post-ligation, as confirmed by RNA sequencing. We identified the occurrence of NLRP3 inflammasome-mediated pyroptosis in the cardiac tissues of human cases with AMI, as well as in mouse models of AMI and hypoxia-induced cardiomyocytes, using immunohistochemistry staining and Western blotting assays. Concurrently, pharmacological inhibition of NLRP3 inflammasome-mediated pyroptosis with MCC950 and VX-765 effectively decreased hypoxia-induced cardiomyocytes injury, while mitigating myocardial oxidative stress, apoptosis and inflammation caused by hypoxia. Moreover, the circulating levels of gasdermin D (GSDMD), the pyroptosis executor, were remarkably elevated in the plasma of mice with early AMI and in the supernatant of hypoxia-exposed cardiomyocytes in a time-dependent manner using ELISA and Western blotting. Furthermore, the change in circulating GSDMD positively correlated with Creatine Kinase-MB (CK-MB) in the plasma of early-stage AMI mouse. In summary, these findings indicated a critical role for NLRP3 inflammasome-mediated pyroptosis in the progression of AMI, the administration of MCC950 and VX-765 may be attractive candidate therapeutic approaches for cardiac injury caused by acute hypoxia or even AMI. Additionally, the circulating GSDMD exhibits potential as a newly diagnostic biomarker for AMI.

Development of the pediatric family-based dignity therapy protocol for terminally ill children (ages 7-18) and their families: A mixed-methods study.

OBJECTIVES: Dignity therapy (DT) is well-established in adults, and it might potentially benefit the younger population. This study aims to develop a pediatric family-based dignity therapy (P-FBDT) protocol for terminally ill children and their families. METHODS: A parallel mixed-methods design was used. The P-FBDT protocol was developed based on the adult DT, and meanwhile by taking children-specific dignity characteristics and Chinese family-oriented culture into consideration. The protocol was then evaluated and modified based on the quantitative and qualitative feedback from 2-round surveys of 14 pediatric oncology or pediatric palliative care experts. RESULTS: The P-FBDT involves terminally ill children and their families in meaningful interactions including a series of conversations and creative activities, which will be recorded and then edited into a document-based generativity entity. The P-FBDT protocol was recognized as highly reasonable and the P-FBDT interview guide was endorsed as important, acceptable, clear, comprehensive, and suitable to be used in pediatric palliative care practice in Chinese culture (>90%). Potential benefits, possible challenges, and practical considerations of the P-FBDT were also proposed. SIGNIFICANCE OF RESULTS: The P-FBDT was perceived to be potentially beneficial to terminally ill children and their families by engaging in a series of meaningful family interactions and creating a lasting memento to be preserved. The protocol needs to be pilot tested among terminally ill children and families for feasibility and potential efficacy in practice.

Biomarkers Screening and Mechanisms Analysis of the Restraint Stress-Induced Myocardial Injury in Hyperlipidemia ApoE-/- Mice.

OBJECTIVES: To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/- mice. METHODS: The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/- mice. Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers. RESULTS: Proteomic analysis showed that there were 43 significantly up-regulated and 58 significantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group. Among them, GBP2, TAOK3, TFR1 and UCP1 were biomarkers with great diagnostic potential. KEGG pathway enrichment analysis indicated that ferroptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model. The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model. CONCLUSIONS: Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferroptosis. Four potential biomarkers are selected for myocardial injury diagnosis, providing a new direction for sudden cardiac death (SCD) caused by hyperlipidemia combined with the restraint stress.

The dignity of terminally ill children in pediatric palliative care: perspectives of parents and healthcare providers.

BACKGROUND: The Chochinov Dignity Model was developed based on a cohort of adult patients with advanced cancer, but its role among dying children is not clear. This study aims to develop a model of dignity for children receiving pediatric palliative care based on the Chochinov Dignity Model. METHODS: This is a descriptive qualitative study. Participants included a total of 11 parents and 14 healthcare providers who were recruited from a tertiary children's hospital in Beijing and the Pediatric Palliative Care Subspecialty Group of the Pediatrics Society of the Chinese Medical Association using purposive sampling. Thematic framework analysis was used to analyze data. RESULTS: The themes of the empirical Dignity Model were broadly supported in this study, but some themes were interpreted differently in the child population. Compared with the original model, some child-specific themes were identified including acknowledging regret, a sense of security, the company of important loved ones, realizing unfinished wishes, decent and dignified death, resolving family disputes, and fairness. CONCLUSIONS: This is the first study on Dignity Model for terminal children. Knowledge of children's dignity can promote reflection of healthcare providers and caregivers regarding the values underlying their performance in pediatric palliative care, and develop certain practical interventions to strengthen children and their families' sense of dignity at end of life.

An Improved Projector Calibration Method by Phase Mapping Based on Fringe Projection Profilometry.

Aiming at the problem of the low accuracy of projector calibration in a structured light system, an improved projector calibration method is proposed in this paper. One of the key ideas is to estimate the sub-pixel coordinates in the projector image plane using local random sample consensus (RANSAC). A bundle adjustment (BA) algorithm is adopted to optimize the calibration parameters to further improve the accuracy and robustness of the projector calibration. After system calibration and epipolar rectification, the mapping relationship between the pixel coordinates and the absolute phase in the projector image plane is established by using cubic polynomial fitting, and the disparity is rapidly solved by using the mapping relationship, which not only ensures the measurement accuracy, but also improves the measurement efficiency. The experimental results demonstrated that the average re-projection error after optimization is reduced to 0.03 pixels, and the proposed method is suitable for high-speed 3D reconstruction without the time-consuming homogenous point searching.

Global research trends and foci of artificial intelligence-based tumor pathology: a scientometric study.

BACKGROUND: With the development of digital pathology and the renewal of deep learning algorithm, artificial intelligence (AI) is widely applied in tumor pathology. Previous researches have demonstrated that AI-based tumor pathology may help to solve the challenges faced by traditional pathology. This technology has attracted the attention of scholars in many fields and a large amount of articles have been published. This study mainly summarizes the knowledge structure of AI-based tumor pathology through bibliometric analysis, and discusses the potential research trends and foci. METHODS: Publications related to AI-based tumor pathology from 1999 to 2021 were selected from Web of Science Core Collection. VOSviewer and Citespace were mainly used to perform and visualize co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references and keywords in this field. RESULTS: A total of 2753 papers were included. The papers on AI-based tumor pathology research had been continuously increased since 1999. The United States made the largest contribution in this field, in terms of publications (1138, 41.34%), H-index (85) and total citations (35,539 times). We identified the most productive institution and author were Harvard Medical School and Madabhushi Anant, while Jemal Ahmedin was the most co-cited author. Scientific Reports was the most prominent journal and after analysis, Lecture Notes in Computer Science was the journal with highest total link strength. According to the result of references and keywords analysis, "breast cancer histopathology" "convolutional neural network" and "histopathological image" were identified as the major future research foci. CONCLUSIONS: AI-based tumor pathology is in the stage of vigorous development and has a bright prospect. International transboundary cooperation among countries and institutions should be strengthened in the future. It is foreseeable that more research foci will be lied in the interpretability of deep learning-based model and the development of multi-modal fusion model.

Dignity therapists' experience of conducting dignity therapy with terminal cancer patients in mainland China: A descriptive qualitative study.

OBJECTIVE: This study investigated the experience of conducting dignity therapy with terminal cancer patients from the perspective of dignity therapists in mainland China. METHODS: Semistructured interviews were conducted with 15 trained dignity therapists from across mainland China who have performed at least one time dignity therapy for terminal cancer patients. Data were analysed using content analysis. RESULTS: Four main themes emerged. Firstly, therapists reported that they had many culture-specific experiences of conducting dignity therapy with Chinese patients. Secondly, they encountered various challenges while recruiting and delivering dignity therapy to patients. Thirdly, through conducting dignity therapy, therapists gained personal development although sometimes they empathised with patients' negative emotions. Lastly, they perceived great benefits of conducting dignity therapy to the culture of caring in clinical practice and healthcare provider-patient relationship. CONCLUSION: Chinese culture influenced dignity therapists' experience of conducting dignity therapy in mainland China. A series of challenges and benefits of conducting dignity therapy to therapists' personal growth and clinical work were perceived. It is suggested that cultural impacts on dignity therapy implementation and the therapists' ability to deal with practical and emotional challenges need to be addressed in dignity therapy training. A more resource-saving dignity therapy protocol would be significant for dignity therapy implementation.

Life meaning constructed from dignity therapy in traditional Chinese culture: A qualitative analysis of dignity therapy generativity documents.

OBJECTIVES: To examine the thematic features of dignity therapy generativity documents of advanced cancer patients receiving chemotherapy in mainland China from the perspective of meaning-making during dignity therapy. METHODS: This is a qualitative descriptive study. Content analysis was used to analyze 24 dignity therapy generativity documents derived from a quasi-experimental trial of dignity therapy for advanced cancer patients receiving chemotherapy in a daycare center at a cancer hospital in northern China. RESULTS: Among the 24 advanced cancer patients whose generativity documents were analyzed, 14 were male and ranged in age from 26 to 78 years (average = 50.3). Two dimensions emerged from the data: (1) the sources of meaning in life, which consisted of social relationships, things and circumstances providing meaning in life, and (2) the ultimate meaning in life, referring to finding one's real self and realizing the purpose in life, including personal life goals, dignity and autonomy, and morality of patients. SIGNIFICANCE OF RESULTS: The multidimensional constructs of meaning in life with distinctive traditional Chinese cultural characteristics could provide insights into dignity-conserving care for advanced cancer patients with Chinese culture and provide evidence for refining the implementation protocol of DT through intentionally addressing the ultimate meaning of patients in the therapeutic session.

Cardiac Nestin+ Mesenchymal Stromal Cells Enhance Healing of Ischemic Heart through Periostin-Mediated M2 Macrophage Polarization.

Mesenchymal stromal cells (MSCs) show potential for treating cardiovascular diseases, but their therapeutic efficacy exhibits significant heterogeneity depending on the tissue of origin. This study sought to identify an optimal source of MSCs for cardiovascular disease therapy. We demonstrated that Nestin was a suitable marker for cardiac MSCs (Nes+cMSCs), which were identified by their self-renewal ability, tri-lineage differentiation potential, and expression of MSC markers. Furthermore, compared with bone marrow-derived MSCs (Nes+bmMSCs) or saline-treated myocardial infarction (MI) controls, intramyocardial injection of Nes+cMSCs significantly improved cardiac function and decreased infarct size after acute MI (AMI) through paracrine actions, rather than transdifferentiation into cardiac cells in infarcted heart. We further revealed that Nes+cMSC treatment notably reduced pan-macrophage infiltration while inducing macrophages toward an anti-inflammatory M2 phenotype in ischemic myocardium. Interestingly, Periostin, which was highly expressed in Nes+cMSCs, could promote the polarization of M2-subtype macrophages, and knockdown or neutralization of Periostin remarkably reduced the therapeutic effects of Nes+cMSCs by decreasing M2 macrophages at lesion sites. Thus, the present work systemically shows that Nes+cMSCs have greater efficacy than do Nes+bmMSCs for cardiac healing after AMI, and that this occurs at least partly through Periostin-mediated M2 macrophage polarization.

Low Distortion of Noise Filter Realization with 6.34 V/µs Fast Slew Rate and 120 mVp-p Output Noise Signal.

In order to reduce Gaussian noise, this paper proposes a method via taking the average of the upper and lower envelopes generated by capturing the high and low peaks of the input signal. The designed fast response filter has no cut-off frequency, so the high order harmonics of the actual signal remain unchanged. Therefore, it can immediately respond to the changes of input signal and retain the integrity of the actual signal. In addition, it has only a small phase delay. The slew rate, phase delay and frequency response can be confirmed from the simulation results of Multisim 13.0. The filter outlined in this article can retain the high order harmonics of the original signal, achieving a slew rate of 6.34 V/µs and an almost zero phase difference. When using our filter to physically test the input signal with a noise level of 3 Vp-p Gaussian noise, a reduced noise signal of 120 mVp-p is obtained. The noise can be suppressed by up to 4% of the raw signal.

Pharmacokinetics of N-ethylpentylone and its effect on increasing levels of dopamine and serotonin in the nucleus accumbens of conscious rats.

N-Ethylpentylone (NEP) is one of the most confiscated synthetic cathinones in the world. However, its pharmacology and pharmacokinetics remain largely unknown. In this study, the pharmacokentics of NEP in rat nucleus accumbens (NAc) was assessed via brain microdialysis after the intraperitoneal (ip) administration of NEP (20 or 50 mg/kg). The concentrations of dopamine (DA) and serotonin (5-HT) and their metabolites, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and 5-hydroxyindoleacetic acid (5-HIAA), were simultaneously monitored to elucidate the pharmacological effect of NEP. In addition, the plasma levels of NEP were also assessed. The pharmacokinetics of NEP showed a dose-related pattern, with NEP rapidly passing through the blood-brain barrier and reaching a maximum concentration (Cmax ) at approximately 40-minutes postdose. Approximately 4% of plasma NEP was distributed to the NAc, and considering a homogeneous brain distribution, over 90% of plasma NEP was potentially distributed to the brain. High values of area under curve (AUC) and mean residence time (MRT) of NEP were observed in both the NAc and plasma, indicating large and long-lasting effects. NEP elicited dose-related increases in microdialysate DA and 5-HT and increased the concentration of 3-MT in a dose-related manner. However, the rate of DA converted into 3-MT was unaffected. NEP had a negative effect on the rates of which DA and 5-HT were transformed into DOPAC and 5-HIAA, respectively. In summary, NEP rapidly entered the NAc and showed a long-lasting effect. In addition, DA increased more significantly than 5-HT, indicating a large potential for NEP abuse.

Aberrant endoplasmic reticulum stress mediates coronary artery spasm through regulating MLCK/MLC2 pathway.

Coronary artery spasm (CAS) is a pathophysiological phenomenon that may cause myocardial infarction and lead to circulatory collapse and death. Aberrant endoplasmic reticulum (ER) stress causes accumulation of misfolding proteins and has been reported to be involved in a variety of vascular diseases. The present study investigated the role of ER stress in the development of CAS and explored the possible molecular mechanisms. Initially, it was found that ER stress markers were elevated in response to drug-induced vascular smooth muscle cells (VSMCs) contraction. Pharmacologic activation of ER stress using Tunicamycin (Tm) persistently induced CAS and significantly promoted Pituitrin-induced CAS in mice as well as in a collagen gel contraction assay. On the contrary, pharmacologic inhibition of ER stress using 4-phenylacetic acid (4-PBA) completely blunted Pituitrin-induced CAS development in mice. Moreover, during the drug-induced VSMCs contraction, expression of ER stress markers were increased in parallel to those of myosin light chain kinase (MLCK) and phosphor-MLC2 (p-MLC2, at Ser19). After inhibiting MLCK activity by using its specific inhibitor ML-7, the ER stress activator Tm failed to activate the MLCK/MLC2 pathway and could neither trigger CAS in mice nor induce VSMCs contraction in vitro. Our results suggested that aberrant ER stress mediated CAS via regulating the MLCK/MLC2 pathway. ER stress activators might be more robust than the common drugs (Pituitrin or acetylcholine) as to induce vasocontraction and thus may serve as potential therapeutics against chronic bleeding, while its inhibitor might be useful for treatment of severe CAS caused by other medication.

Simultaneous determination of N-ethylpentylone, dopamine, 5-hydroxytryptamine and their metabolites in rat brain microdialysis by liquid chromatography tandem mass spectrometry.

N-Ethylpentylone (NEP) is a popular synthetic cathinone abused worldwide. To obtain more information about its pharmacokinetics and pharmacodynamics, a rapid, simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the determination of NEP, two important neurotransmitters, dopamine and serotonin, and their metabolites, including 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and 5-hydroxyindole-3-acetic acid, in rat brain microdialysate. The analytes were separated on a Phnomenex Polar C18 column, with a mobile phase of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) under gradient elution to shorten the total chromatographic run time. A triple quadruple mass spectrometer coupled with an electrospray ionization source in both positive and negative ion mode was used to detect the analytes. This method showed excellent accuracy (87.4-113.5%) and precision (relative standard deviation <15%) at three quality control levels. The limits of detection were 0.2 ng/mL for NEP and 0.2-50 nm for the others and good linearity was obtained. This study pioneered a method to integrate exogenous drugs and endogenous neurotransmitters as the drugs act on the same determination system, which means that this innovation can provide support for further study of the addictive effects of NEP or other synthetic cathinones on extracellular levels of dopamine and 5-hydroxytryptamine.

Axin1 up-regulated 1 accelerates stress-induced cardiomyocytes apoptosis through activating Wnt/ß-catenin signaling.

Stress-induced cardiomyocyte apoptosis contributes to the pathogenesis of a variety of cardiovascular diseases, but how stress induces cardiomyocyte apoptosis remains largely unclear. The present study aims to investigate the effects of Axin1 up-regulated 1 (Axud1), a novel pro-apoptotic protein, on the cardiomyocyte survival and the underlying mechanisms. To this end, a rat model under restraint stress (RS) was established and in vitro stress-induced cardiomyocytes culture was achieved. Our data showed that Axud1 was upregulated in the rat myocardia after exposure to RS. Anti-apoptotic Bcl-2 was decreased, whereas pro-apoptotic Bax and Cleaved caspase-3 (Cc3) were increased in a time-dependent manner. The Wnt/ß-catenin signaling was observed to be interestingly activated in heart undergoing RS. In addition, the treatment of norepinephrine (NE) to in vitro cardiomyocytes increased Axud1 level and induced cell apoptosis. Wnt/ß-catenin signaling was consistently activated. Knockdown of Axud1 using specific siRNA blunted NE-induced cardiomyocytes apoptosis and also inactivated the Wnt/ß-catenin signaling. XAV-939, an inhibitor of Wnt/ß-catenin signaling, partially reversed the pro-apoptotic effect of NE. In conclusion, Axud1 accelerated stress-induced cardiomyocytes apoptosis through activation of Wnt/ß-catenin signaling pathway. Our data provided novel evidence that therapeutic strategies against Axud1 or Wnt/ß-catenin signaling might be promising in relation to RS-induced myocardial injury.

MicroRNA-20b suppresses the expression of ZFP-148 in viral myocarditis.

Viral myocarditis is a common cardiovascular disease, which seriously endangers the health of people and even leads to sudden unexpected death. MicroRNAs play very important roles in various physical and pathological processes including cardiogenesis and heart diseases. In recent years, miR-20b has been implicated in various diseases such as breast cancer, gastric cancer, hepatocellular carcinoma, cardiovascular diseases. However, the function of miR-20b in the pathological progress of viral myocarditis has not been reported. In this study, we found that miR-20b was up-regulated in mouse heart tissues post Coxsackievirus B3 (CVB3) infection. Bioinformatics analysis identified ZFP-148, a transcription factor that plays essential roles in the regulation of virus replication, is one of the predicted targets of miR-20b. MiR-20b expression was found to be up-regulated and ZFP-148 protein level was markedly repressed during viral myocarditis. Further studies demonstrated that miR-20b directly binds to the 3'-UTR of ZFP-148 and suppresses its translation. Moreover, aberrant expression of miR-20b promoted the expression of anti-apoptosis proteins Bcl-2 and Bcl-xL, suggesting that altered gene expression might promote cardiomyocytes survival in viral myocarditis. Our findings indicated that miR-20b might be a potential therapeutic target for CVB3-induced viral myocarditis and a useful marker for the diagnosis of viral myocarditis.

Phosphorylated Myosin Light Chain 2 (p-MLC2) as a Molecular Marker of Antemortem Coronary Artery Spasm.

BACKGROUND It is not uncommon that only mild coronary artery stenosis is grossly revealed after a system autopsy. While coronary artery spasm (CAS) is the suspected mechanism of these deaths, no specific biomarker has been identified to suggest antemortem CAS. MATERIAL AND METHODS To evaluate the potential of using phosphorylated myosin light chain 2 (p-MLC2) as a diagnostic marker of antemortem CAS, human vascular smooth muscle cells (VSMCs) were cultured and treated with common vasoconstrictors, including prostaglandins F2α (PGF2α), acetylcholine (ACh), and 5-hydroxy tryptamine (5-HT). The p-MLC2 level was examined in the cultured cells using Western blot analysis and in a rat model of spasm provocation tests using immunohistochemistry (IHC). Effects of increased p-MLC2 level on VSMCs contractile activities were assessed in vitro using confocal immunofluorescence assay. Four fatal cases with known antemortem CAS were collected and subject to p-MLC2 detection. RESULTS The p-MLC2 was significantly increased in VSMCs after treatments with vasoconstrictors and in the spasm provocation tests. Myofilament was well-organized and densely stained in VSMCs with high p-MLC2 level, but disarrayed in VSMCs with low p-MLC2 level. Three of the 4 autopsied cases showed strongly positive staining of p-MLC2 at the stenosed coronary segment and the adjacent interstitial small arteries. The fourth case was autopsied at the 6th day after death and showed negative-to-mild positive staining of p-MLC2. CONCLUSIONS p-MLC2 might be a useful marker for diagnosis of antemortem CAS. Autopsy should be performed as soon as possible to collect coronary arteries for detection of p-MLC2.

MicroRNA-19b Downregulates Gap Junction Protein Alpha1 and Synergizes with MicroRNA-1 in Viral Myocarditis.

Viral myocarditis (VMC) is a life-threatening disease that leads to heart failure or cardiac arrhythmia. A large number of researches have revealed that mircroRNAs (miRNAs) participate in the pathological processes of VMC. We previously reported that miR-1 repressed the expression of gap junction protein α1 (GJA1) in VMC. In this study, miR-19b was found to be significantly upregulated using the microarray analysis in a mouse model of VMC, and overexpression of miR-19b led to irregular beating pattern in human cardiomyocytes derived from the induced pluripotent stem cells (hiPSCs-CMs). The upregulation of miR-19b was associated with decreased GJA1 in vivo. Furthermore, a miR-19b inhibitor increased, while its mimics suppressed the expression of GJA1 in HL-1 cells. When GJA1 was overexpressed, the miR-19b mimics-mediated irregular beating was reversed in hiPSCs-CMs. In addition, the effect of miR-19b on GJA1 was enhanced by miR-1 in a dose-dependent manner. These data suggest miR-19b contributes to irregular beating through regulation of GJA1 by cooperating with miR-1. Based on the present and our previous studies, it could be indicated that miR-19b and miR-1 might be critically involved in cardiac arrhythmia associated with VMC.

Generation of a human induced pluripotent stem cell line (SHUPLi002-A) from PBMCs of a healthy female donor.

Human induced pluripotent stem cells (iPSCs) have good multi-lineage differentiation potential, which is an ideal model for studying the pathogenesis of diseases and drug screening.Here, we generated an iPSC line, SHUPLi002-A, from peripheral blood mononuclear cells (PBMCs) of a healthy 28-year-old female individual using episomal vectors. SHUPLi002-A is characterized by expression of classical pluripotent stem cell markers as well as teratoma formation assays to evaluate their differentiation capacity in vivo.

Influence of Fibre Orientation on the Slotting Quality of CFRP Composites Using the Multi-Tooth Mill.

Carbon fibre-reinforced plastic (CFRP) composites, prized for their exceptional properties, often encounter surface quality issues during slotting due to their inherent heterogeneity. This paper tackles CFRP slotting challenges by employing multi-tooth mills in experiments with various fibre orientations and tool feed rates. In-plane scratching tests are performed under linearly varying loads; then, slotting experiments are conducted at different parameters. The scratching test results indicate that the fibre orientation and cutting angles have significant influences on forces and fracture process. The slotting experiments demonstrate that cutting forces and surface roughness Sa of the bottom slotting surface are notably affected by the fibre orientation, with disparities between up-milling and down-milling sides. Reorganising Sa data by local fibre cutting angle θ highlights consistent Sa variations between up-milling and down-milling sides for 0° ≤ θ ≤ 90°, with lower Sa on the up-milling side. However, for 90° < θ ≤ 150°, Sa variations diverge, with lower Sa on the down-milling side. Unexpectedly, Sa on the down-milling side decreases with increasing θ in this range. Additionally, the tool feed rate exerts a more pronounced influence on Sa on the up-milling side.