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The aim of this study is to explore the perceptions of Chinese registered nurses on toxic leadership behaviours of nurse managers and to determine its type, cause and response measures.The nurse manager is the front-line leader of the nurses who provide services directly to patients. Previous evidence suggests that toxic leadership behaviours of nurse managers do exist and it is necessary to understand the specifics of it.We used phenomenological research methods to conduct semi-structured in-depth interviews among 12 nurses at a tertiary hospital in Wuhan over the period from January to March 2022. And the data were analysed using Colaizzi seven-step analysis method.Four themes were discovered: (a) nurses' perceptions of toxic leadership behaviours; (b) toxic leadership behaviours of nurse managers; (c) reasons for toxic leadership behaviours of nurse managers and (d) measures for toxic leadership behaviours of nurse managers.Chinese nurses are exposed to the toxic leadership of nurse managers for multiple reasons and respond differently.This study helps nursing managers identify which behaviours are harmful to the nurse that require special attention in developing strategies to buffer against nurse managers' toxic leadership.

Many factors such as trauma and COVID-19 cause acute kidney injury (AKI). Late AKI have a very high incidence and mortality rate. Early diagnosis of AKI provides a critical therapeutic time window for AKI treatment to prevent progression to chronic renal failure. However, the current clinical detection based on creatinine and urine output isn't effective in diagnosing early AKI. In recent years, the early diagnosis of AKI has made great progress with the advancement of information technology, nanotechnology, and biomedicine. These emerging methods are mainly divided into two aspects: First, predicting AKI through models construct by machine learning; Second, early diagnosis of AKI through detection of newly-discovered early biomarkers. Currently, these methods have shown great potential and become an attractive tool for the early diagnosis of AKI. Therefore, it is very important to discuss and summarize these methods for the early diagnosis of AKI. In this review, we first systematically summarize the application of machine learning in AKI prediction algorithms and specific scenarios. In addition, we introduce the key role of early biomarkers in the progress of AKI, and then comprehensively summarize the application of emerging detection technologies for early AKI. Finally, we discuss current challenges and prospects of machine learning and biomarker detection. The review is expected to provide new insights for early diagnosis of AKI, and provided important inspiration for the design of early diagnosis of other major diseases.

Liver models are vital for the liver diseases and drug research as many novel drugs. However, traditional liver models cannot meet this need, mainly because they cannot replicate the complex physiological structure and microenvironment of the liver, especially the O

Facile, efficient, and inexpensive biosensing systems are in high demand for biomedical test. In recent years, numerous smartphone-based biosensing systems have been developed to match demand for biomedical test in source-limited environment. However, application of these smartphone-based biosensing systems was limited because of performance gap between the smartphone-based systems and commercial plate readers. In this study, we have developed a smart tablet-phone-based colorimetric plate reader (STPCPR) with intelligent and dynamic light modulation for broad-range colorimetric assays. The STPCPR allows controllable modulation of exciting light in three different color channels that is lack in conventional smartphone-based system. Using optimized exciting modulation, the STPCPR shows higher sensitivities, lower detection limits, and broader detection ranges in test of pigments, proteins, and cells when compared to conventional plate readers and smartphone-based system. Therefore, the developed STPCPR can serve as an ideal next-generation smartphone-based biosensing system for point-of-care colorimetric test in diverse biomedical applications in source-limited environment.

Gut microbiota dysbiosis is critical in the etiology of polycystic ovary syndrome (PCOS). However, the mechanisms of gut microbiota in PCOS pathogenesis have not been fully elucidated. We aimed to explore the role of gut microbiota-derived macrophage pyroptosis in PCOS. This study conducted dehydroepiandrosterone (DHEA) induced PCOS mice model, 16S rDNA sequencing, western blot, genetic knocking out, transcriptome and translatome profiling, et al. to evaluate the underlying mechanisms. 16S rDNA sequencing showed reduced gut Akkermansia and elevated gram-negative bacteria (Desulfovibrio and Burkholderia) abundances in DHEA induced PCOS mice, which was accompanied by increased serum lipopolysaccharide (LPS). LPS could induce macrophage pyroptosis in mice ovaries, also activated in PCOS. Gasdermin D (GSDMD) is the final executor of macrophage pyroptosis. We demonstrated that Gsdmd knockout in mice could dramatically ameliorate PCOS. Mechanistically, transcriptome and translatome profiling revealed that macrophage pyroptosis disrupted estrogen production and promoted apoptosis of granulosa cells. Interferon (IFN)-γ, which was elevated in PCOS mice serum and ovaries, enhanced macrophage pyroptosis and exacerbated its effect on estrogen receptor in granulosa cells. Inspiringly, we identified that disulfiram and metformin could augment gut Akkermansia abundance, reduce serum IFN-γ level, inhibit macrophage pyroptosis in ovaries, therefore ameliorating PCOS. Collectively, this study emphasizes that macrophage pyroptosis, which was induced by gut microbiota dysbiosis and enhanced by IFN-γ, plays a key role in PCOS pathogenesis through estrogen synthesis dysfunction and apoptosis of granulosa cells. Disulfiram and metformin, which enhanced gut Akkermansia abundance and suppressed macrophage pyroptosis, may be considered as potential therapeutic strategies for PCOS.

Paralytic shellfish toxins (e.g., saxitoxin, STX; gonyautoxin-2, GTX-2) and tetrodotoxin (TTX) are highly toxic and widely distributed ion channel marine toxins which specifically block the voltage-dependent sodium channels (VDSCs), causing great harm to human health. It is urgent to exploit new detection methods with high specificity and high efficiency. Here, a portable high-throughput cardiomyocyte-based potential biosensor was established with cardiomyocytes, a 16-well microelectrodes (MEs) sensor and a robust 32-channel recording system, which presented high-quality and high-consistency extracellular field potential (EFP) signals in each well with a long duration of 80 h. The feature parameters, including firing rate (FR), spike amplitude (SA), spike slope (SS), spike duration (SD) and field potential duration (FPD), were extracted from EFP to quantitatively assess the toxic effects of these ion channel toxins. Importantly, the biosensor showed temporal specificity and parametric selectivity under toxin treatments, and FR, SS and SD were the optimal parameters to STX, TTX and GTX-2, respectively. This biosensor can rapidly detect 0.29 ng/mL STX, 0.30 ng/mL TTX and 0.16 ng/mL GTX-2 within 5 min, 10 min and 15 min, respectively. Thus, our novel multi-well cardiomyocyte-based biosensor will be a promising tool for high-effective detection of ion channel toxins.

Study question Does NAT10-mediated N4-acetylcytidine (ac4C) in RNA, a newly identified mRNA epigenetic modification, participate in modulating in vitro maturation(IVM) of oocytes? Summary answer NAT10-mediated ac4C modification is an important regulatory factor during oocyte maturation in vitro, by regulating genes associated with translation, mitochondrial functions and protein destabilization. What is known already Unlike somatic cells, transcription and translation are uncoupled during oocyte maturation and gene expression is mainly regulated by post-transcriptional modulation, including mRNA degradation, translation and posttranslational modification, which are complex and have not been fully investigated. RNA ac4C is a newly identified mRNA modification and a key determinant of post-transcriptional regulation, which has been shown to promote mRNA stability and translation, and NAT10 is the only known RNA acetyltransferase. Therefore, NAT10-mediated ac4C represents a possible epigenetic regulator in oocyte maturation. Study design, size, duration Oocytes at different stages from mice were collected to detect the changing levels of ac4C and NAT10 during maturation. NAT10 in GV-stage oocytes was knocked down before IVM, to confirm the regulatory role of NAT10-mediated ac4C in meiotic process, followed by further exploration of cellular mechanisms. Each experiment was repeated at least three times, and data were analyzed by chi-square test, one-way ANOVA or unpaired-sample t-test. Participants/materials, setting, methods The expression of ac4C and NAT10 was detected by immunohistochemistry. NAT10 was knocked down in GV-stage oocytes by RNA interference through electroporation. The efficacy of knockdown was confirmed by qPCR and immunohistochemistry targeting ac4C and NAT10, and the percentages of oocytes maturated in vitro were compared among groups. High-throughput sequencing and RNA immunoprecipitation were performed to reveal the modulated genes. Proteins specifically binding to ac4C sites were identified by RNA pulldown and mass spectrometry. Main results and the role of chance We first retrieved publicly available data from GEO and found that transcripts with potential ac4C sites were enriched in genes downregulated during IVM (P Limitations, reasons for caution This study was performed in vitro. The role of NAT10-mediated ac4C in vivo remains to be elucidated. Also, limited by current techniques, ac4C modification in oocytes cannot be detected. Our exploration of regulated genes and ac4C binding proteins were performed in somatic cell lines. Wider implications of the findings: Post-transcriptional modulation is crucial in oocyte maturation. Our study using in-vitro systems for mouse oocyte identified NAT10-mediated ac4C as an important regulator in IVM. It provided a new insight into the epigenetic mechanisms of IVM, which may lead to improvement of clinical IVM systems. Trial registration number Not applicable

Study question Does NAT10-mediated N4-acetylcytidine (ac4C) in RNA, a newly identified mRNA epigenetic modification, participate in modulating in vitro maturation(IVM) of oocytes? Summary answer NAT10-mediated ac4C modification is an important regulatory factor during oocyte maturation in vitro, by regulating genes associated with translation, mitochondrial functions and protein destabilization. What is known already Unlike somatic cells, transcription and translation are uncoupled during oocyte maturation and gene expression is mainly regulated by post-transcriptional modulation, including mRNA degradation, translation and posttranslational modification, which are complex and have not been fully investigated. RNA ac4C is a newly identified mRNA modification and a key determinant of post-transcriptional regulation, which has been shown to promote mRNA stability and translation, and NAT10 is the only known RNA acetyltransferase. Therefore, NAT10-mediated ac4C represents a possible epigenetic regulator in oocyte maturation. Study design, size, duration Oocytes at different stages from mice were collected to detect the changing levels of ac4C and NAT10 during maturation. NAT10 in GV-stage oocytes was knocked down before IVM, to confirm the regulatory role of NAT10-mediated ac4C in meiotic process, followed by further exploration of cellular mechanisms. Each experiment was repeated at least three times, and data were analyzed by chi-square test, one-way ANOVA or unpaired-sample t-test. Participants/materials, setting, methods The expression of ac4C and NAT10 was detected by immunohistochemistry. NAT10 was knocked down in GV-stage oocytes by RNA interference through electroporation. The efficacy of knockdown was confirmed by qPCR and immunohistochemistry targeting ac4C and NAT10, and the percentages of oocytes maturated in vitro were compared among groups. High-throughput sequencing and RNA immunoprecipitation were performed to reveal the modulated genes. Proteins specifically binding to ac4C sites were identified by RNA pulldown and mass spectrometry. Main results and the role of chance We first retrieved publicly available data from GEO and found that transcripts with potential ac4C sites were enriched in genes downregulated during IVM (P Limitations, reasons for caution This study was performed in vitro. The role of NAT10-mediated ac4C in vivo remains to be elucidated. Also, limited by current techniques, ac4C modification in oocytes cannot be detected. Our exploration of regulated genes and ac4C binding proteins were performed in somatic cell lines. Wider implications of the findings Post-transcriptional modulation is crucial in oocyte maturation. Our study using in-vitro systems for mouse oocyte identified NAT10-mediated ac4C as an important regulator in IVM. It provided a new insight into the epigenetic mechanisms of IVM, which may lead to improvement of clinical IVM systems. Trial registration number not applicable

The development of new drugs is a lengthy process, while the observation of serious side effects, such as cardiotoxicity, can result in the drug to be withdrawn even after development, leading to heavy burden on human health and social economy. To assess the drug cardiotoxicity, the electrical and mechanical properties of cardiomyocytes are increasingly being used to investigate the mechanisms and potential toxicity of drugs. Conventional non-invasive and label-free recording strategies are not well suited to record the integrated electromechanical signals from the single cell in a high-throughput manner, whereas label-based recordings strategies suffer from phototoxicity and drug side effects, precluding their long-time detection. In this study, we established a new multimodal microelectrode biosensing system to achieve the simultaneous and dynamic interrogation of electromechanical signals from multisite single cardiomyocytes. This multimodal device can detect subtle changes in the electromechanical signals induced by ion channel drugs during the excitation-contraction coupling of cardiomyocytes. The use of electromechanical integrated single cell signals for drug assessment was compared with commercial drug assays, and our multimodal microelectrode biosensing system can afford record electromechanical integrated signals as well as efficiently identify the effects of ion channel-blocking drugs on the electrical and mechanical properties of cardiomyocytes. Our multimodal microelectrode biosensing system is a potential valuable platform in the fields of cardiology and pharmacology.

N4-acetylcytidine (ac4C), a newly identified epigenetic modification within mRNA, has been characterized as a crucial regulator of mRNA stability and translation efficiency. However, the role of ac4C during oocyte maturation, the process mainly controlled via post-transcriptional mechanisms, has not been explored. N-acetyltransferase 10 (NAT10) is the only known enzyme responsible for ac4C production in mammals and ac4C-binding proteins have not been reported yet. In this study, we have documented decreasing trends of both ac4C and NAT10 expression from immature to mature mouse oocytes. With NAT10 knockdown mediated by small interfering RNA (siRNA) in germinal vesicle (GV)-stage oocytes, ac4C modification was reduced and meiotic maturation in vitro was significantly retarded. Specifically, the rate of first polar body extrusion was significantly decreased with NAT10 knockdown (34.6%) compared to control oocytes without transfection (74.6%) and oocytes transfected with negative control siRNA (72.6%) (p < 0.001), while rates of germinal vesicle breakdown (GVBD) were not significantly different (p = 0.6531). RNA immunoprecipitation and high-throughput sequencing using HEK293T cells revealed that the modulated genes were enriched in biological processes associated with nucleosome assembly, chromatin silencing, chromatin modification and cytoskeletal anchoring. In addition, we identified TBL3 as a potential ac4C-binding protein by a bioinformatics algorithm and RNA pulldown with HEK293T cells, which may mediate downstream cellular activities. Taken together, our results suggest that NAT10-mediated ac4C modification is an important regulatory factor during oocyte maturation in vitro and TBL3 is a potential ac4C-binding protein.

This paper deals with a fully parabolic singular chemotaxis-(growth) system with indirect signal production or consumption $$\begin{aligned} \left\{ \begin{aligned}&u_t=\Delta u-\chi \nabla \cdot \left( \frac{u}{v}\nabla v\right) +f(u),&(x,t)\in \Omega \times (0,\infty ), \\&v_t=\Delta v+h(v,w),&(x,t)\in \Omega \times (0,\infty ), \\&w_t=\Delta w- w+u,&(x,t)\in \Omega \times (0,\infty ), \end{aligned} \right. \end{aligned}$$ under homogeneous Neumann boundary conditions in a smooth convex bounded domain $$\Omega \subset {\mathbb {R}}^{2}$$ , where $$\chi >0$$ . When $$f(u)=0$$ , $$h(v,w)=-v+w$$ , we prove that the solution (u, v, w) of this model is globally uniformly bounded in time and exponentially converges to the steady state $$(\overline{u_{0}},\overline{u_{0}},\overline{u_{0}})$$ in the norm of $$L^{\infty }(\Omega )$$ provided that $$\chi 0$$ , where $$\overline{u_{0}}:=\frac{1}{|\Omega |}\int _{\Omega }u_{0}(x)\mathrm{d}x$$ . Moreover, in the case of $$f(u)=ru-\mu u^{2}$$ , $$h(v,w)=-v+w$$ , where $$r\in {\mathbb {R}}$$ , and $$\mu >0$$ , we obtain the global existence of solutions for this system. Furthermore, under the conditions of $$f(u)=ru-\mu u^{2}$$ , $$h(v,w)=-vw$$ and $$\mu >0$$ , $$r>0$$ , the solution (u, v, w) is also global in time.

Cardiovascular disease (CVD) is the number one cause of death in humans. Arrhythmia induced by gene mutations, heart disease, or hERG K+ channel inhibitors is a serious CVD that can lead to sudden death or heart failure. Conventional cardiomyocyte-based biosensors can record extracellular potentials and mechanical beating signals. However, parameter extraction and examination by the naked eye are the traditional methods for analyzing arrhythmic beats, and it is difficult to achieve automated and efficient arrhythmic recognition with these methods. In this work, we developed a unique automated template matching (ATM) cardiomyocyte beating model to achieve arrhythmic recognition at the single beat level with an interdigitated electrode impedance detection system. The ATM model was established based on a rhythmic template with a data length that was dynamically adjusted to match the data length of the target beat by spline interpolation. The performance of the ATM model under long-term astemizole, droperidol, and sertindole treatment at different doses was determined. The results indicated that the ATM model based on a random rhythmic template of a signal segment obtained after astemizole treatment presented a higher recognition accuracy (100% for astemizole treatment and 99.14% for droperidol and sertindole treatment) than the ATM model based on arrhythmic multitemplates. We believe this highly specific ATM method based on a cardiomyocyte beating model has the potential to be used for arrhythmia screening in the fields of cardiology and pharmacology.

The biosynthesis of flavones has drawn considerable attention. However, the presence of flavones and their biosynthesis in tomato (Solanum lycopersicum) remain unclear. Here, we confirmed that flavones are present in MicroTom tomato and unexpectedly found that a tomato polyphenol oxidase (SlPPO F) possesses a flavone synthase-like activity and catalyzes the conversion of eriodictyol to luteolin without the need for any cofactor. SlPPO F showed a similar K

Electroporation serves as a powerful technique to introduce the exogenous nucleotides, DNA, RNA, proteins, dyes, and virus particles into cells. Through the effect of high intensity of electric field, the permeability of the cell membrane is instantaneously improved to absorb the exogenous molecules in surrounding medium. To protect the cell viability, ultralow-voltage electroporation techniques are well developed by versatile devices, and delivery efficiency is commonly assessed by label-based analysis by microscope-ImageJ or flow cytometry. However, accuracy and complexity of these analytical strategies still hinder efficient and precise biomedical studies in situ. Here we developed an intracellular delivery biosensing system by nanostrawed electroporation array (NEA) that can efficiently assess the universal electroporation performance by cell viability, delivery efficiency, and cell mortality. The intracellular delivery biosensing system consists of NEA, fluorescent microscope, and automated analysis software. Intracellular delivery biosensing system of electroporation quality is based on the enhanced fluorescent watershed segmentation (enhanced FWS) algorithm, which possessed low deviation (~5%) and significantly shortened the operation time (~8 s/10 images) in contrast to high deviation (~13%) and long operation time (~10 min/10 images) of conventional inaccurate, labor-intensive and time-consuming methods. It is believed that the intracellular delivery biosensing system will be a promising universal platform to assess nanodevice electroporation in the fields of cell biology, biotechnology, and medicine.

Uterine fibroids are common benign tumors in the female reproductive system. A hysterectomy is the most effective treatment for symptomatic fibroids. For patients desiring pregnancy, laparoscopic intracapsular myomectomy (LM) is an alternative surgery option. Although LM is widely accepted to treat fibroids, it is technically demanding with risk of excessive bleeding and difficult suturing, especially in cases with large fibroids or tumors in unusual locations. Therefore, we developed an intracapsular rotary-cut procedure (IRCP) as a modification of laparoscopic intracapsular myomectomy, with the intention to minimize risks of LM and help uterine healing. A summary of the improvements to the IRCP is described: 1) making an incision at the site of the fibroid with a length of one-third to one-half of the fibroid's diameter at a depth reaching the fibroid's surface; 2) holding the fibroid stably and making rotary cuts on the fibroid at a depth of 0.5-1 cm within its pseudo-capsule while pulling it outward slightly, making sure not to cut off any pieces of the fibroid; and 3) repeating the cutting-and-pulling until the longest dimension of the fibroid is outside the incision. The multiple cuts are to minimize the diameter and extend the length of the fibroid. When the multiple cuts cause half of the fibroid body to "shrink", the fibroid is squeezed out by contraction of the surrounding myometrium. Evaluation of the outcomes of IRCP showed that the time of enucleation and suturing, intraoperative bleeding, and decline of hemoglobin were significantly lower in the IRCP group than the LM group. As for reproductive outcomes, the full-term live birth rate of the IRCP group was significantly higher than that of LM group. However, there was no difference in delivery modes between the two groups. In conclusion, IRCP significantly benefits fertility preservation by minimizing damage to the uterus, protecting myofibers of the pseudo-capsule, and resulting in a shallower residual cavity, which eases stitching and causes less bleeding. It is worthwhile to adopt IRCP in younger patients who desire preservation of their fertility.

Cardiac arrhythmia and drug-induced cardiotoxicity seriously threaten the human life. To develop antiarrhythmic agents and prevent the drug-induced cardiotoxicity, it is demanded to explore the high-specificity and high-efficiency drug screening platforms for preclinical investigations. Here, a specific electromechanical integrated correlation (EMIC) model was established based on the synchronized signal recording of cardiomyocyte-based biosensing system. The cardiomyocyte-based biosensing system consists of an integrated electromechanical device and a synchronized recording instrument. By extracting the feature points and correlation information of both electrical and mechanical signals, the multi-parameters of EMIC are applied for the drug recognition, showing the good specificity to analyze the typical Na+, K+, Ca2+ channel blockers. Further, visualized analysis of EMIC parameters was performed using the extracted parameters of synchronized recording signals to present the drug specific recognition functions. By heat map, radar map, and principal component analysis (PCA), the specific features and patterns were intuitively displayed to achieve the drug recognition. We believe this high-content and high-specific drug recognition strategy will be a promising and alternative method for the preclinical screening of cardiac safety and drug development in biomedical fields.

14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is enriched in the brain cortex and exerts protective effect against neuronal apoptosis induced by ischemia/reperfusion. Although apoptosis has been well recognized to be closely associated with mitochondrial biogenesis and function, it is still unclear whether the neuroprotective effect of 14,15-EET is mediated by promotion of mitochondrial biogenesis and function in cortical neurons under the condition of oxygen-glucose deprivation (OGD). In this study, we found that 14,15-EET improved cell viability and inhibited apoptosis of cortical neurons. 14,15-EET significantly increased the mitochondrial mass and the ratio of mitochondrial DNA to nuclear DNA. Key makers of mitochondrial biogenesis, peroxisome proliferator activator receptor gamma-coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), were elevated at both mRNA and protein levels in the cortical neurons treated with 14,15-EET. Moreover, 14,15-EET markedly attenuated the decline of mitochondrial membrane potential, reduced ROS, while increased ATP synthesis. Knockdown of cAMP-response element binding protein (CREB) by siRNA blunted the up-regulation of PGC-1α and NRF-1 stimulated by 14,15-EET, and consequently abolished the neuroprotective effect of 14,15-EET. Our results indicate that 14,15-EET protects neurons from OGD-induced apoptosis by promoting mitochondrial biogenesis and function through CREB mediated activation of PGC-1α and NRF-1.