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Objective: The current study aimed to explore the relationships between urinary metals and vital capacity index (VCI) in 380 children and adolescents in Northeast China using a variety of statistical methods. Methods: A cross-sectional survey was conducted among 380 children and adolescents in Liaoning Province, China. To assess the relationships between urinary metals and VCI, Elastic-net (ENET) regression, multivariate linear regression, weighted quantile sum (WQS), bayesian kernel machine regression (BKMR) and quantile-based g computation (qgcomp) were adopted. Results: The ENET model selected magnesium (Mg), vanadium (V), manganese (Mn), arsenic (As), tin (Sn) and lead (Pb) as crucial elements. In multiple linear regression, we observed urinary Pb, Mn was negatively correlated with VCI individually in both total study population and adolescents (all p values < 0.05) in the adjustment model. The WQS indices were negatively related with VCI in total study population (β=-3.19, 95%CI: -6.07, -0.30) and adolescents (β=-3.46, 95%CI: -6.58, -0.35). The highest weight in total study population was Pb (38.80%), in adolescents was Mn (35.10%). In the qgcomp, Pb (31.90%), Mn (27.20%) were the major negative contributors to the association in the total population (β=-3.51, 95%CI: -6.29, -0.74). As (42.50%), Mn (39.90%) were the main negative contributors (β=-3.95, 95% CI: -6.68, -1.22) among adolescents. The results of BKMR were basically consistent with WQS and qgcomp analyses. Conclusions: Our results indicated that Pb and Mn were priority toxic materials on VCI. The cumulative effect of metals was negatively related to VCI, and this relationship was more pronounced in adolescents. [ABSTRACT FROM AUTHOR]

Almost all cancer treatments are significantly limited by the strong tumor microenvironment (TME) fortress formed by abnormal vasculature, dense extracellular matrix (ECM), multidrug resistance (MDR) system, and immune "cold" environment. In the huge efforts of dismantling the TME fortress, nitric oxide (NO)‐based nanomedicines are increasingly occupying a central position and have already been identified as super "strong polygonal warriors" to dismantle TME fortress for efficient cancer treatment, benefiting from NO's unique physicochemical properties and extremely fascinating biological effects. However, there is a paucity of systematic review to elaborate on the progress and fundamental mechanism of NO‐based nanomedicines in oncology from this aspect. Herein, the key characteristics of TME fortress and the potential of NO in reprogramming TME are delineated and highlighted. The evolution of NO donors and the advantages of NO‐based nanomedicines are discussed subsequently. Moreover, the latest progress of NO‐based nanomedicines for solid tumors is comprehensively reviewed, including normalizing tumor vasculature, overcoming ECM barrier, reversing MDR, and reactivating the immunosuppression TME. Lastly, the prospects, limitations, and future directions on NO‐based nanomedicines for TME manipulation are discussed to provide new insights into the construction of more applicable anticancer nanomedicines. [ABSTRACT FROM AUTHOR]

Highlights: The factors affecting electrophysiological recordings from active micro-nano-collaborative bioelectronic devices were discussed in terms of principle and fabrication. An overview of the applications of active micro-nano-collaborative bioelectronic devices in cardiomyocytes and neurons was further presented. The challenges faced by active micro-nano-collaborative bioelectronic devices in intracellular electrophysiological studies and their prospective biomedical applications are discussed. The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience. In recent years, active micro/nano-bioelectronic devices have undergone significant advancements, thereby facilitating the study of electrophysiology. The distinctive configuration and exceptional functionality of these active micro-nano-collaborative bioelectronic devices offer the potential for the recording of high-fidelity action potential signals on a large scale. In this paper, we review three-dimensional active nano-transistors and planar active micro-transistors in terms of their applications in electro-excitable cells, focusing on the evaluation of the effects of active micro/nano-bioelectronic devices on electrophysiological signals. Looking forward to the possibilities, challenges, and wide prospects of active micro-nano-devices, we expect to advance their progress to satisfy the demands of theoretical investigations and medical implementations within the domains of cardiology and neuroscience research. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare retrospectively the extent of blastulation timing (Day 5 or later) and expansion grade to predict the ability of blastocysts to give rise to a pregnancy. Blastocysts frozen on day 5 with a lower expansion grade (group D5) or day 6 with a higher expansion grade (group D6) were included. A single embryo was thawed and transferred on day 5 after ovulation or progesterone supplementation. Differences in patient baseline characteristics, endometrial preparation and pregnancy outcomes between groups were stratified by patient age and anti-Müllerian hormone (AMH) levels. Logistic regression was used to analyse the results. A total of 617 blastocysts in group D5 and 1134 blastocysts in group D6 were assessed. Stratified analyses showed higher biochemical pregnancy, clinical pregnancy and live birth rates for patients aged less than 30 years old, and higher ongoing pregnancy rate for patients with AMH ≥ 1.1 ng/ml. For patients aged less than 30 years old, the biochemical pregnancy, clinical pregnancy and live birth rates in group D5 were higher than those in group D6. [ABSTRACT FROM AUTHOR]

This paper deals with a two-competing-species chemotaxis system with indirect signal production u t = d 1 Δ u − χ 1 ∇ ⋅ (u ∇ w) + f 1 (u , v) , (x , t) ∈ Ω × (0 , ∞) , v t = d 2 Δ v − χ 2 ∇ ⋅ (v ∇ w) + f 2 (u , v) , (x , t) ∈ Ω × (0 , ∞) , w t = Δ w − w + z , (x , t) ∈ Ω × (0 , ∞) , z t = Δ z − z + u + v , (x , t) ∈ Ω × (0 , ∞) , under homogeneous Neumann boundary conditions in a smoothly bounded domain Ω ⊂ ℝ n (n ≥ 1) , with the nonnegative initial data (u 0 , v 0 , w 0 , z 0) , where d i > 0 and χ i > 0 , i = 1 , 2. When f 1 (u , v) = μ 1 u (1 − u − a 1 v) , f 2 (u , v) = μ 2 v (1 − v − a 2 u) , we study the global existence and boundedness of classical solutions to the above system in a three-dimensional bounded domain under some suitable conditions of parameters. When f 1 (u , v) = u (a 0 − a 1 u − a 2 v − a 3 ∫ Ω u − a 4 ∫ Ω v) , f 2 (u , v) = v (b 0 − b 1 u − b 2 v − b 3 ∫ Ω u − b 4 ∫ Ω v) , we discuss the existence of globally bounded solution for all n ≤ 3 provided that the parameters satisfy some suitable assumptions. Furthermore, we consider the asymptotic stabilization of globally bounded solutions to the above system under weak competition and strongly asymmetric competition cases, respectively. [ABSTRACT FROM AUTHOR]

This paper deals with a two-competing-species chemotaxis system with indirect signal consumption u t = d 1 Δ u - χ 1 ∇ · (u ∇ w) + μ 1 u (1 - u - a 1 v) , (x , t) ∈ Ω × (0 , ∞) , v t = d 2 Δ v - χ 2 ∇ · (v ∇ w) + μ 2 v (1 - v - a 2 u) , (x , t) ∈ Ω × (0 , ∞) , w t = Δ w - w z , (x , t) ∈ Ω × (0 , ∞) , z t = Δ z - z + u + v , (x , t) ∈ Ω × (0 , ∞) , ∂ u ∂ ν = ∂ v ∂ ν = ∂ w ∂ ν = ∂ z ∂ ν = 0 , (x , t) ∈ ∂ Ω × (0 , ∞) , u , v , w , z x , 0 = u 0 x , v 0 x , w 0 x , z 0 x , x ∈ Ω , under homogeneous Neumann boundary conditions in a smooth bounded domain Ω ⊂ R n (n ≤ 2) , with the nonnegative initial data u 0 , v 0 , w 0 , z 0 ∈ C 0 Ω ¯ × C 0 Ω ¯ × W 1 , ∞ Ω × W 1 , ∞ Ω , where χ i > 0 , d i > 0 , a i > 0 and μ i > 0 ( i = 1 , 2 ). It is shown that the system has a global bounded classical solution for arbitrary size of μ 1 , μ 2 > 0 . Additionally, we consider the asymptotic stabilization of solutions to the above system as follows: When a 1 , a 2 ∈ (0 , 1) , the global bounded classical solution (u, v, w, z) exponentially converges to ( 1 - a 1 1 - a 1 a 2 , 1 - a 2 1 - a 1 a 2 , 0 , 2 - a 1 - a 2 1 - a 1 a 2 ) in the L ∞ -norm as t → ∞ ; When a 1 > 1 > a 2 > 0 and a 1 a 2 < 1 , the global bounded classical solution (u, v, w, z) exponentially converges to (0, 1, 0, 1) in the L ∞ -norm as t → ∞ ; When a 1 = 1 > a 2 > 0 , the global bounded classical solution (u, v, w, z) polynomially converges to (0, 1, 0, 1) in the L ∞ -norm as t → ∞ . [ABSTRACT FROM AUTHOR]

Lipase plays a pivotal role in the rancidity pathway of lipids and it hinders the industrial development of oat products. The existing methods to inactivate lipase are energy intensive and cause nutrient loss. Understanding the structure and characteristics of oat lipase could lead to better inactivation methods. Oat Lipase was extracted, partially purified, and its characteristics and structure were studied. The partially purified protein matched the Os06g0157000 protein with 36.5 kDa and belonged to the 'GDSL' lipolytic enzyme family. Oat lipase showed highest catalytic activity at 40 °C, pH 7.5 and held stability below 50 °C and at pH 7.0–8.0. Cu2+, Fe3+, Ba2+, K+ and Mg2+ all inhibited oat lipase activity, with Fe3+ having the strongest effect. The oat lipase showed high specificity for hydrolysis of oat oil. The results of molecular docking and molecular dynamics analysis showed that avenanthramides (AVAS), rutin, and ferulic acid were potential lipase inhibitors, with ferulic acid having the greatest effect. In storage experiments of pearled oats, ferulic acid delayed lipid hydrolysis and lipid oxidation degradation. In the present study, we found a natural lipase inhibition that is safe and nutritional. [Display omitted] • Extraction and purification of oat lipase from naked oat. • Enzymatic properties of oat lipase (temperature, pH, metal ions, substrate specificity) were investigated. • Molecular docking and molecular dynamics analysis proved that ferulic acid was a potential inhibitor. • Ferulic acid delayed lipid hydrolysis and lipid oxidation degradation to prolong the shelf life of pearled oats. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 2 and nutrient gradients. Liver-on-a-chip (LOC), based on microfluidic technology, can not only closely simulate the physiological structure and microenvironment of the liver through the design of suitable microchannels, but can also incorporate advanced biosensors with high sensitivity and potential for rapid responses to microenvironmental signals and liver function indicators. Nevertheless, LOCs have not been widely exploited for liver disease research or the screening of drugs for hepatotoxicity because of considerable professional barriers. In this review, we comprehensively summarize recent progress in LOC development and the embedding of biosensors into LOCs. We first introduce the physiological characteristics and microenvironment of the liver and then summarize the fabrication process and advantages of LOCs. We subsequently focus on recent advances relating to three-dimensional (3D) hepatocyte organization and the simulation of hepatic sinusoids and lobules in LOCs and further systematically summarize the research progress in biosensor-integrated LOCs. Finally, we discuss the potential value of LOCs and the challenges facing their exploitation. In conclusion, this review provides insights into the design and development of biosensor-integrated LOCs aiming to promote further research into this promising platform. • The integration of various biosensors into LOC is highlighted. • Application of well-designed LOCs and integrated biosensors are systematically reviewed. • The challenges underlying LOC and integrated biosensor are deeply discussed. [ABSTRACT FROM AUTHOR]

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. • Multimodal microelectrode biosensing system perform the electromechanical integrated recording of signal cardiomyocytes. • The multimodal device was designed to simultaneously record electromechanical integrated signals in situ. • The biosensing system can sensitively identify the ion channel-blocking drug effect on excitation-contraction coupling. [ABSTRACT FROM AUTHOR]

[Display omitted] • MicroTom tomato contained flavones including luteolin and apigenin. • Tomato shows flavone synthase-like activity catalyzed eriodictyol to luteolin. • A polyphenol oxidase, SlPPO F, showed this flavone synthase-like activity. • SlPPO F flavone synthase-like activity depended on oxidase properties. • SlPPO F showed high catalytic efficiency and thermostability. 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 m value to that of other polyphenol oxidases, and could be inhibited by ascorbic acid. The flavone synthase-like activity of SlPPO F exhibited strict substrate specificity and only accepted flavanones with two hydroxyl groups (3′ and 4′) on the B ring as substrates. SlPPO F showed higher catalytic efficiency and better thermostability than type I flavone synthase from Apium graveolens, suggesting its possible application in enzyme engineering. In summary, we identified flavones in tomato and unraveled a polyphenol oxidase exhibiting flavone synthase-like activity. [ABSTRACT FROM AUTHOR]

Known as a bioactive compound with various biological functions for plants and humans, chicoric acid is the major secondary metabolite presented in the whole plant of purple coneflower (Echinacea purpurea (L.) Moench). It is synthesized from caftaric acid and chlorogenic acid (5-caffeoyl quinic acid) by a special acyltransferase. Interestingly, the relative contents of chicoric acid and its two substrates in seeds were different from those of other tissues. The diversity mechanism of these chemicals and the underlying physiological significance remain unknown. Here, through a non-target metabolomic analysis, significant metabolic shifts, especially the dynamics of the contents of chicoric acid and its two substrates, were observed during the seed germination process. The contents of caftaric acid and chicoric acid kept on increasing after sprout, while chlorogenic acid decreased and converted to chicoric acid. Accordingly, the structural genes responsible for the biosynthesis of caftaric acid and chicoric acid were upregulated since sprout, just a little head of accumulation of chemicals. The upstream biosynthetic genes providing essential precursor caffeoyl CoA was also induced since sprout explain the increase of the sum of these compounds. Interestingly, during the seed germination process, chicoric acid was secreted into the culture medium and showed a more substantial growth inhibition effect on A. thaliana than its two substrates, indicating the significance of its biosynthesis. In summary, these results demonstrate the metabolic change and its biological meaning during the germination process of purple coneflower seeds. [Display omitted] • Purple coneflower is the worldwide popular medicinal plant. • Metabolic shifts occur during purple coneflower seed germination. • Upregulated biosynthetic genes result in the metabolic shifts. • Chicoric acid is a better allelochemical compared to its substrates. • The biosynthesis of chicoric acid shows important physiological significance. [ABSTRACT FROM AUTHOR]

Simple Summary: Calretinin (CALB2), which is a Ca2+-binding protein, plays a known pivotal role in the neural system in vertebrates. The role of CALB2 in mammalian gonads has been gradually recognized; however, little information on the function of CALB2 in fish gonads has been reported. Therefore, we firstly identified the calb2 gene in Paralichthys olivaceus (P. olivaceus), and then investigated its tissue distribution and localization in the gonads by real-time PCR, western blotting, and immunohistochemistry. The P. olivaceus calb2 mRNA was relatively highly expressed in both the testis and ovary. The CALB2 protein is located in Leydig cells of the testis and ovarian germ epithelial cells in P. olivaceus. This study provides a basis for further explorations on the function and regulation mechanism of calb2 in fish gonads. Although its function in mammalian gonads has been gradually recognized, the expression and function of calretinin (CALB2)—a Ca2+-binding protein—in the testis and ovary of fish are still unclear. Here, we identified the cDNA sequences of calb2 in Paralichthys olivaceus (P. olivaceus); analyzed its gene structure and phylogenetic and syntenic relationship by bioinformatics; and investigated its tissue distribution and localization in the gonads by real-time PCR, western blotting, and immunohistochemistry. The P. olivaceuscalb2 gene has 11 exons and 10 introns, and the full-length cDNA is 1457 bp, including an open reading frame (ORF) of 816 bp encoding 271 amino acids. The CALB2 of P. olivaceus has a higher homology with Lates calcarifer (99%) compared with other species. The conserved synteny of calb2 neighboring gene loci was also detected in fish. Real-time PCR showed that the expression of calb2 mRNA is abundant not only in the brain, but also in the gonads, and exhibits a higher expression in the testis than in the ovary. Western blotting indicated that the CALB2 protein has a higher expression in the testis compared with the ovary. Immunohistochemistry demonstrated that the CALB2 protein appears in Leydig cells and the ovarian germ epithelium. These results reveal that calb2 plays an important role in the gonads of P. olivaceus. [ABSTRACT FROM AUTHOR]

Summary: The metabolism of massively accumulated chlorogenic acid is crucial for the successful germination of purple coneflower (Echinacea purpurea (L.) Menoch). A serine carboxypeptidase‐like (SCPL) acyltransferase (chicoric acid synthase, CAS) utilizes chlorogenic acid to produce chicoric acid during germination. However, it seems that the generation of chicoric acid lags behind the decrease in chlorogenic acid, suggesting an earlier route of chlorogenic acid metabolism.We discovered another chlorogenic acid metabolic product, 3,5‐dicaffeoylquinic acid, which is produced before chicoric acid, filling the lag phase. Then, we identified two additional typical clade IA SCPL acyltransferases, named chlorogenic acid condensing enzymes (CCEs), that catalyze the biosynthesis of 3,5‐dicaffeoylquinic acid from chlorogenic acid with different kinetic characteristics.Chlorogenic acid inhibits radicle elongation in a dose‐dependent manner, explaining the potential biological role of SCPL acyltransferases‐mediated continuous chlorogenic acid metabolism during germination. Both CCE1 and CCE2 are highly conserved among Echinacea species, supporting the observed metabolism of chlorogenic acid to 3,5‐dicaffeoylquinic acid in two Echinacea species without chicoric acid accumulation.The discovery of SCPL acyltransferase involved in the biosynthesis of 3,5‐dicaffeoylquinic acid suggests convergent evolution. Our research clarifies the metabolism strategy of chlorogenic acid in Echinacea species and provides more insight into plant metabolism. [ABSTRACT FROM AUTHOR]

This paper deals with a fully parabolic singular chemotaxis-(growth) system with indirect signal production or consumption u t = Δ u - χ ∇ · u v ∇ v + f (u) , (x , t) ∈ Ω × (0 , ∞) , v t = Δ v + h (v , w) , (x , t) ∈ Ω × (0 , ∞) , w t = Δ w - w + u , (x , t) ∈ Ω × (0 , ∞) , under homogeneous Neumann boundary conditions in a smooth convex bounded domain Ω ⊂ R 2 , where χ > 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 (u 0 ¯ , u 0 ¯ , u 0 ¯) in the norm of L ∞ (Ω) provided that χ < χ 0 with χ 0 > 0 , where u 0 ¯ : = 1 | Ω | ∫ Ω u 0 (x) d x . Moreover, in the case of f (u) = r u - μ u 2 , h (v , w) = - v + w , where r ∈ R , and μ > 0 , we obtain the global existence of solutions for this system. Furthermore, under the conditions of f (u) = r u - μ u 2 , h (v , w) = - v w and μ > 0 , r > 0 , the solution (u, v, w) is also global in time. [ABSTRACT FROM AUTHOR]

The purpose of the study is to investigate the metabolic characteristics of placental tissue in patients diagnosed with gestational diabetes mellitus (GDM). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was employed to qualitatively and quantitatively analyze the metabolites in placental tissues obtained from 25 healthy pregnant women and 25 pregnant women diagnosed with GDM. Multilevel statistical methods are applied to process intricate metabolomics data. Meanwhile, we applied machine learning techniques to identify biomarkers that could potentially predict the risk of long-term complications in patients with GDM as well as their offspring. We identified 1902 annotated metabolites, out of which 212 metabolites exhibited significant differences in GDM placentas. In addition, the study identifies a set of risk biomarkers that effectively predict the likelihood of long-term complications in both pregnant women with GDM and their offspring. The accuracy of this panel was measured by the area under the receiver operating characteristic curve (ROC), which was found to be 0.992 and 0.960 in the training and validation sets, respectively. This study enhances our understanding of GDM pathogenesis through metabolomics. Furthermore, the panel of risk markers identified could prove to be a valuable tool in predicting potential long-term complications for both GDM patients and their offspring. [ABSTRACT FROM AUTHOR]

Female fecundity declines in a nonlinear manner with age during the reproductive years, even as ovulatory cycles continue, which reduces female fertility, disrupts metabolic homeostasis, and eventually induces various chronic diseases. Despite this, the aging‐related cellular and molecular changes in human ovaries that occur during these reproductive years have not been elucidated. Here, single‐cell RNA sequencing (scRNA‐seq) of human ovaries is performed from different childbearing ages and reveals that the activation of the pyroptosis pathway increased with age, mainly in macrophages. The enrichment of pyroptotic macrophages leads to a switch from a tissue‐resident macrophage (TRM)‐involve immunoregulatory microenvironment in young ovaries to a pyroptotic monocyte‐derived macrophage (MDM)‐involved proinflammatory microenvironment in middle‐aged ovaries. This remolded ovarian immuno‐microenvironment further promotes stromal cell senescence and accelerated reproductive decline. This hypothesis is validated in a series of cell and animal experiments using GSDMD‐KO mice. In conclusion, the work expands the current understanding of the ovarian aging process by illustrating a pyroptotic macrophage‐involved immune mechanism, which has important implications for the development of novel strategies to delay senescence and promote reproductive health. [ABSTRACT FROM AUTHOR]

Aim. The aim of this study is to analyse the toxic leadership behavior of nurse managers perceived by nurses and its related factors. Background. Toxic leadership is becoming more common as a risk factor in nursing. However, there is a scarcity of research on the elements that influence toxic leadership practices from the perspective of nurses' perceptions. Methods. A cross-sectional study was conducted with 455 nurses from August to October 2022. A demographic information questionnaire and a negative behavior scale for nurse managers were used. Descriptive statistics, Kruskal–Wallis H test or Mann–Whitney U test, and multiple linear regression were used to explore the relevant factors of nurses' perceived toxic leadership behaviors of nurse managers. Results. The population was dominated by 423 (92.97%) females, 318 (69.89%) married, and 420 (92.31%) with a bachelor's degree. The toxic leadership behavior scale score for nurse managers was 109 (87, 123) and the score for each entry was (2.94 ± 0.92). Gender, educational level, department, number of night shifts, and nature of employment were the influencing factors of the negative leadership behavior of nurse leaders as perceived by nurses (P < 0.05), explaining a total of 43.1% of the total variance. Conclusion. In general, nurses' perceived toxic leadership behaviors of nurse managers were at a moderate level. More toxic leadership behaviors were observed by nurses who were female, less educated, on busy units, with unstable nature of appointments, and with frequent night shift rotation. Implications for Nursing Management. Focus on the psychological condition of nurses who are female, less educated, work in busy units, have an unstable nature of employment, and rotate night shifts frequently. The negative impacts of toxic leadership behaviors might be lessened as a result. [ABSTRACT FROM AUTHOR]

• Pyroptosis is a distinctive feature of endometriosis. • Pyroptosis triggers the secretion of chemokines and drives immune cell infiltration, lead to immune disorders in endometriosis. • Molecular typing based on pyroptosis offered valuable insights into accurate diagnosis and precise therapy in endometriosis. Endometriosis is a refractory and recurrent gynecological condition which affects about 10 % of reproductive-age women. The dysfunctional immune system is a well-established element in disease pathogenesis. Pyroptosis, a novel form of inflammatory cell death, has been revealed to be strongly connected with immune responses in tumors. Nevertheless, its relationship with microenvironment characteristics and clinical features in endometriosis is unclear. Here, we performed bioinformatics analysis on published data in humans and revealed a significant but neglected role of pyroptosis in endometriosis. Samples with higher PyrScores were generally accompanied with more aggressive disease features, such as EMT, angiogenesis and immune disorders. We further confirmed in animal models that pyroptosis exacerbated immune dysfunction by recruiting activated immune cell including macrophages, DC, neutrophils, CD8+ Tcm and Tregs with unregulated CCL2, CCL3, CXCL2 and CXCL3. Collectively, pyroptosis is a distinctive feature of endometriosis. Our work provides insights into further studies targeting pyroptosis for molecular typing and individualized precise therapy. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • A smart tablet–phone-based colorimetric plate reader (STPCPR) is developed. • STPCPR modulates intensity of exciting light for colorimetric assays. • STPCPR have quantitative measurements of pigments, proteins, and cells. • STPCPR shows improvements on sensitivity, detection limit, and detection range. • STPCPR is an ideal next-generation smartphone-based biosensing system. [ABSTRACT FROM AUTHOR]

Particulate matter pollution (PMP) has been identified as a substantial contributor to cancer. However, accurately delineating the evolving trends in cancer burden attributable to PMP remains an ongoing challenge. The 1990–2019 disability-adjusted life years (DALYs) were used for cancers attributable to PMP from the Global Burden and Disease Study (GBD) 2019, including ambient particulate matter pollution (APMP) and household air pollution from solid fuels (HAP). The joinpoint regression and the Bayesian age-period-cohort (BAPC) model were employed to assess the corresponding trends over the periods 1990–2019 and 2020–2050, respectively. Additionally, statistical models such as frontier analysis and health inequality analysis were also utilized. During the 30-year period, cancer DALYs attributable to APMP increased globally, while those attributable to HAP and PMP decreased. Cancer DALYs attributable to APMP were positively correlated with socio-demographic index (SDI), while those attributable to PMP and HAP were negatively correlated with SDI. Frontier analysis identified the countries and regions requiring urgent action to mitigate PMP-attributable cancer. Finally, it was anticipated that the cancer burden attributable to APMP would increase during 2020 to 2050, while the burden attributable to HAP and PMP would decrease. This study conducted an epidemiological investigation of the burden of cancer attributable to APMP, HAP and PMP in various regions and populations worldwide, providing epidemiological insights into the global burden of cancer attributable to PMP and guiding policy and research directions. [Display omitted] • From 1990 to 2019, global cancer burden attributable to APMP increased, while which attributable to PMP and HAP decreased. • Cancer burden attributable to PMP is negatively correlated with SDI. • Cancer burden attributable to PMP is disproportionately higher among elderly and male populations. • By 2050, cancer burden attributable to APMP is likely to rise, while which attributable to PMP and HAP is likely to fall. [ABSTRACT FROM AUTHOR]

Aim: 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. Background: 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. Methods: 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. Results: 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. Conclusion: Chinese nurses are exposed to the toxic leadership of nurse managers for multiple reasons and respond differently. Implications for Nursing Management: 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. [ABSTRACT FROM AUTHOR]

Immunotherapy has revolutionized cancer treatment, dramatically improving survival rates of melanoma and lung cancer patients. Nevertheless, immunotherapy is almost ineffective against ovarian cancer (OC) due to its cold tumor immune microenvironment (TIM). Many traditional medications aimed at remodeling TIM are often associated with severe systemic toxicity, require frequent dosing, and show only modest clinical efficacy. In recent years, emerging nanomedicines have demonstrated extraordinary immunotherapeutic effects for OC by reversing the TIM because the physical and biochemical features of nanomedicines can all be harnessed to obtain optimal and expected tissue distribution and cellular uptake. However, nanomedicines are far from being widely explored in the field of OC immunotherapy due to the lack of appreciation for the professional barriers of nanomedicine and pathology, limiting the horizons of biomedical researchers and materials scientists. Herein, a typical cold tumor‐OC is adopted as a paradigm to introduce the classification of TIM, the TIM characteristics of OC, and the advantages of nanomedicines for immunotherapy. Subsequently, current nanomedicines are comprehensively summarized through five general strategies to substantially enhance the efficacy of immunotherapy by heating the cold OC. Finally, the challenges and perspectives of this expanding field for improved development of clinical applications are also discussed. [ABSTRACT FROM AUTHOR]

• Gut microbiota dysbiosis related LPS activates macrophage pyroptosis in PCOS ovary. • Genetic knockout and medical inhibition of macrophage pyroptosis alleviate PCOS. • Macrophage pyroptosis induces granulosa cells dysfunction and apoptosis. • IFN-γ elevated in PCOS enhances macrophage pyroptosis and its effects. • Disulfiram/ metformin modulates gut microbiota, reduces serum IFN-γ, inhibits pyroptosis and ameliorates PCOS. 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. [ABSTRACT FROM AUTHOR]

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. • Intracellular delivery biosensing system by nanostrawed electroporation array was established. • Electroporation quality analysis was based on the enhanced fluorescent watershed segmentation (enhanced FWS) algorithm. • Biosensing system can efficiently assess the electroporation performance by viability, delivery efficiency and mortality. • Intracellular delivery biosensing system possessed accurate and efficient performance in intracellular delivery analysis. [ABSTRACT FROM AUTHOR]

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. Image 1 • Cardiomyocyte-based biosensing system records synchronized electromechanical signals. • Electromechanical integrated correlation (EMIC) model was established. • EMIC model was optimized by long-term stability and solvent stability test. • Visualized recognition of EMIC model was developed for ion channel blockers. [ABSTRACT FROM AUTHOR]