Long-term mesoscale imaging of 3D intercellular dynamics across a mammalian organ.

A comprehensive understanding of physio-pathological processes necessitates non-invasive intravital three-dimensional (3D) imaging over varying spatial and temporal scales. However, huge data throughput, optical heterogeneity, surface irregularity, and phototoxicity pose great challenges, leading to an inevitable trade-off between volume size, resolution, speed, sample health, and system complexity. Here, we introduce a compact real-time, ultra-large-scale, high-resolution 3D mesoscope (RUSH3D), achieving uniform resolutions of 2.6 × 2.6 × 6 µm3 across a volume of 8,000 × 6,000 × 400 µm3 at 20 Hz with low phototoxicity. Through the integration of multiple computational imaging techniques, RUSH3D facilitates a 13-fold improvement in data throughput and an orders-of-magnitude reduction in system size and cost. With these advantages, we observed premovement neural activity and cross-day visual representational drift across the mouse cortex, the formation and progression of multiple germinal centers in mouse inguinal lymph nodes, and heterogeneous immune responses following traumatic brain injury-all at single-cell resolution, opening up a horizon for intravital mesoscale study of large-scale intercellular interactions at the organ level.

Identifying PE2 and PE5 Proteins from Existing Mass Spectrometry Data Using pFind.

The Chromosome-Centric Human Proteome Project (C-HPP) aims to identify all proteins encoded by the human genome. Currently, the human proteome still contains approximately 2000 PE2-PE5 proteins, referring to annotated coding genes that lack sufficient protein-level evidence. During the past 10 years, it has been increasingly difficult to identify PE2-PE5 proteins in C-HPP approaches due to the limited occurrence. Therefore, we proposed that reanalyzing massive MS data sets in repository with newly developed algorithms may increase the occurrence of the peptides of these proteins. In this study, we downloaded 1000 MS data sets via the ProteomeXchange database. Using pFind software, we identified peptides referring to 1788 PE2-PE5 proteins. Among them, 11 PE2 and 16 PE5 proteins were identified with at least 2 peptides, and 12 of them were identified using 2 peptides in a single data set, following the criteria of the HPP guidelines. We found translation evidence for 16 of the 11 PE2 and 16 PE5 proteins in our RNC-seq data, supporting their existence. The properties of the PE2 and PE5 proteins were similar to those of the PE1 proteins. Our approach demonstrated that mining PE2 and PE5 proteins in massive data repository is still worthy, and multidata set peptide identifications may support the presence of PE2 and PE5 proteins or at least prompt additional studies for validation. Extremely high throughput could be a solution to finding more PE2 and PE5 proteins.

Improving NiFe Electrocatalysts through Fluorination-Driven Rearrangements for Neutral Water Electrolysis.

Neutral electrolysis to produce hydrogen is prime challenging owing to the sluggish kinetics of water dissociation for the electrochemical reduction of water to molecular hydrogen. An ion-enriched electrode/electrolyte interface for electrocatalytic reactions can efficiently obtain a stable electrolysis system. Herein, we found that interfacial accumulated fluoride ions and the anchored Pt single atoms/nanoparticles in catalysts can improve hydrogen evolution reaction (HER) activity of NiFe-based hydroxide catalysts, prolonging the operating stability at high current density in neutral conditions. NiFe hydroxide electrode obtains an outstanding performance of 1000 mA cm-2 at low overpotential of 218 mV with 1000 h operation at 100 mA cm-2. Electrochemical experiments and theoretical calculations have demonstrated that the interfacial fluoride contributes to promote the adsorption of Pt to proton for sustaining a large current density at low potential, while the Pt single atoms/nanoparticles provide H adsorption sites. The synergy effect of F and Pt species promotes the formation of Pt─H and F─H bonds, which accelerate the adsorption and dissociation process of H2O and promote the HER reaction with a long-term durability in neutral conditions.

Innovative Zinc Anodes: Advancing Metallurgy Methods to Battery Applications.

Aqueous zinc metal batteries (AZMBs) are emerging as a powerful contender in the realm of large-scale intermittent energy storage systems, presenting a compelling alternative to existing ion battery technologies. They harness the benefits of metal zinc's high safety, natural abundance, and favorable electrochemical potential (-0.762 V vs Standard hydrogen electrode, SHE), alongside an impressive theoretical capacity (820 mAh g-1 and 5655 mAh cm-3). However, the electrochemical performance of ZMBs is impeded by several challenges, including poor compatibility with high-loading cathodes and persistent side reactions. These issues are intricately linked to the inherent physicochemical properties of the zinc metal anodes (ZMAs). Here, this review delves into the traditional methods of ZMAs production, encompassing extraction, electrodeposition, and rolling processes. The discussion then progresses to an exploration of cutting-edge methodologies designed to enhance the electrochemical performance of ZMAs. These methods are categorized into alloying, pre-treatment of substrate, advanced electrodeposition techniques, and the development of composite anodes utilizing zinc powder. The review offers a comparative analysis of the merits and drawbacks of various optimization strategies, highlighting the beneficial outcomes achieved. It aspires to inspire novel concepts for the advancement and innovation of next-generation zinc-based energy storage solutions.

FMO2 ameliorates nonalcoholic fatty liver disease by suppressing ER-to-Golgi transport of SREBP1.

BACKGROUND AND AIMS: NAFLD comprises a spectrum of liver disorders with the initial abnormal accumulation of lipids in hepatocytes called NAFL, progressing to the more serious NASH in a subset of individuals. Our previous study revealed that global flavin-containing monooxygenase 2 (FMO2) knockout causes higher liver weight in rats. However, the role of FMO2 in NAFLD remains unclear. Herein, we aimed to determine the function and mechanism of FMO2 in liver steatosis and steatohepatitis. APPROACH AND RESULTS: The expression of FMO2 was significantly downregulated in patients with NAFL/NASH and mouse models. Both global and hepatocyte-specific knockout of FMO2 resulted in increased lipogenesis and severe hepatic steatosis, inflammation, and fibrosis, whereas FMO2 overexpression in mice improved NAFL/NASH. RNA sequencing showed that hepatic FMO2 deficiency is associated with impaired lipogenesis in response to metabolic challenges. Mechanistically, FMO2 directly interacts with SREBP1 at amino acids 217-296 competitively with SREBP cleavage-activating protein (SCAP) and inhibits SREBP1 translocation from the endoplasmic reticulum (ER) to the Golgi apparatus and its subsequent activation, thus suppressing de novo lipogenesis (DNL) and improving NAFL/NASH. CONCLUSIONS: In hepatocytes, FMO2 is a novel molecule that protects against the progression of NAFL/NASH independent of enzyme activity. FMO2 impairs lipogenesis in high-fat diet-induced or choline-deficient, methionine-deficient, amino acid-defined high-fat diet-induced steatosis, inflammation, and fibrosis by directly binding to SREBP1 and preventing its organelle translocation and subsequent activation. FMO2 thus is a promising molecule for targeting the activation of SREBP1 and for the treatment of NAFL/NASH.

Photon-level single-pixel 3D tomography with masked attention network.

Tomography plays an important role in characterizing the three-dimensional structure of samples within specialized scenarios. In the paper, a masked attention network is presented to eliminate interference from different layers of the sample, substantially enhancing the resolution for photon-level single-pixel tomographic imaging. The simulation and experimental results have demonstrated that the axial resolution and lateral resolution of the imaging system can be improved by about 3 and 2 times respectively, with a sampling rate of 3.0 %. The scheme is expected to be seamlessly integrated into various tomography systems, which is conducive to promoting the tomographic imaging for biology, medicine, and materials science.

Understanding the probiotic potential of Lactobacillus plantarum: Antioxidant capacity, non-specific immunity and intestinal microbiota improvement effects on Manila clam Ruditapes philippinarum.

Lactic acid bacteria (LAB) have beneficial effects on aquatic animals, improving their immune system and intestinal microbiota. Nevertheless, the probiotic effects of LAB on the Manila clam Ruditapes philippinarum remain poorly understood. Herein, the effects of administering Lactobacillus plantarum at final doses of 1 × 105 CFU/L (T5 group), 1 × 107 CFU/L (T7 group), and 1 × 109 CFU/L (T9 group) in the rearing water for eight weeks were evaluated for the antioxidant capacity, non-specific immunity, resistance to Vibrio parahaemolyticus infection, and intestinal microbiota of R. philippinarum. The rearing water without the addition of L. plantarum served as a control. The results showed that the T7 and T9 groups demonstrated a significant elevation in the disease resistance of clams against V. parahaemolyticus, in the activities of alkaline phosphatase and lysozyme in the hepatopancreas, and in the expression of antioxidant- and immune-related genes, including SOD, GPx, and GST. Meanwhile, the T7 group showed a significant enhancement in superoxide dismutase and catalase activities and CAT expression, while the T9 group experienced a remarkable elevation in reduced glutathione content. Only catalase activity was markedly elevated in the T5 group. The expression of SOD, CAT, GPx, and GST was significantly elevated in three treatment groups following the V. parahaemolyticus challenge. The T7 group exhibited a significant increase in intestinal microbiota richness. Significant increases were noted in Firmicutes abundance across all three treatment groups and in Actinobacteriota in the T5 and T7 groups. Additionally, the opportunistic pathogen Escherichia-Shigella abundance significantly decreased in three treatment groups. Furthermore, administration of 1 × 107 CFU/L L. plantarum enhanced the stability of the intestinal microecosystem, whereas a dose of 1 × 109 CFU/L might have a negative effect. The application of three doses of L. plantarum significantly enhanced intestinal microbiota functions related to the immune response and oxidative stress regulation, while a higher dose (1 × 109 CFU/L) might inhibit several functions. In conclusion, the application of L. plantarum in the rearing water exerted beneficial effects on the antioxidant capacity, non-specific immunity, resistance to V. parahaemolyticus, and the intestinal microbiota stability and functions of R. philippinarum. The beneficial effects of L. plantarum on R. philippinarum were dose-dependent, and the final dose of 1 × 107 CFU/L exhibited the optimal effects.

Attentional bias for rejection and sad words in Chinese left-behind children with depression.

BACKGROUND: This study aimed to examine attentional bias (AB) for sad and social rejection words in Chinese left-behind children (LBC) with depression. METHOD: We investigated both stimulus specificity and components of AB in different groups using a cross-sectional design. Data were drawn from a school assessment of depression and anxiety, from which we selected LBC with depression (n = 40), LBC without depression (n = 33), a control group with depression (n = 31), and a control group without depression (n = 37). AB was measured with a dot-probe task covering two stimulus types (sad and rejection). RESULTS: The analysis of AB scores revealed a significant three-way interaction (LBC × depression × word type), F(1, 137) = 4.00, p = 0.047, η2 = 0.028, with depressed non-LBC exhibiting a significant depression × word type interaction, F(1, 66) = 4.67, p = 0.034, η2 = 0.066, while the depression × word type interaction was not significant in LBC, F(1, 71) = 0.18, p = 0.675, η2 = 0.002. Depressed children living with their parents showed AB towards sad words but not rejection words, while depressed LBC showed greater AB towards both rejection and sad words. CONCLUSIONS: The findings provide evidence that an AB towards sad information is critically involved in the depressed LBC. Compared with non-LBC depressed individuals, an AB for rejection may be involved as a risk factor in the LBC. It sheds light on the effective intervention programmes for LBC's depression and have important practical significance for reducing depression and improving the mental health of LBC.

The practice and facilitators of, and barriers to, implementing individualized repositioning frequency: A national cross-sectional survey of critical care nurses.

AIMS: To understand the clinical status of implementing individualized repositioning frequency-and its barriers and facilitators-among critical care nurses in China, in view of developing targeted intervention strategies and improving guideline implementation. DESIGN: A cross-sectional survey. METHODS: A self-report questionnaire was developed with reference to the Theoretical Domains Framework and administered to critical care nurses in 15 hospitals across eastern, southern, western, northern, and central geographical areas of China from 20 February 2023 to 16 March 2023. Data were collected for personal demographics, clinical practice status, and from Likert-type responses about barriers to and facilitators of implementing individualized repositioning frequency. RESULTS: In total, 574 effective questionnaires were collected. Only 3.8 % of respondents reported that their hospital/ward uses an individualized repositioning frequency rule. Six facilitator domains identified were: social/professional role and identity; beliefs about capabilities; optimism; beliefs about consequences; reinforcement; and intentions. Seven barrier domains were: knowledge; skills; goals; memory, attention and decision processes; environmental context and resources; social influences; and behavioral regulation. Inferential analysis showed that critical care nurses who had higher degrees, more years of work, more environmental support, and more nursing experience were prone to being more positive in response to the implementation of individualized repositioning frequency. CONCLUSION: The clinical practice status of implementing individualized repositioning frequency among critical care nurses in China is unsatisfactory. Implementation is essential but complex and is influenced by several factors. Theory-based suggestions for improving this situation are provided on the basis of identified barriers.

The Protective Role of Interleukin 17A in Acinetobacter baumannii Pneumonia Is Associated with Candida albicans in the Airway.

Recent studies have found that the coexistence of fungi and bacteria in the airway may increase the risk of infection, contribute to the development of pneumonia, and increase the severity of disease. Interleukin 17A (IL-17A) plays important roles in host resistance to bacterial and fungal infections. The objective of this study was to determine the effects of IL-17A on Acinetobacter baumannii-infected rats with a previous Candida albicans airway inoculation. The incidence of A. baumannii pneumonia was higher in rats with C. albicans in the airway than in noninoculated rats, and it decreased when amphotericin B was used to clear C. albicans, which influenced IL-17A levels. IL-17A had a protective effect in A. baumannii pneumonia associated with C. albicans in the airway. Compared with A. baumannii-infected rats with C. albicans in the airway that did not receive IL-17A, recombinant IL-17A (rIL-17A) supplementation decreased the incidence of A. baumannii pneumonia (10/15 versus 5/17; P = 0.013) and the proportion of neutrophils in the lung (84 ± 3.5 versus 74 ± 4.3%; P = 0.033), reduced tissue destruction and inflammation, and decreased levels of myeloperoxidase (MPO) (1.267 ± 0.15 versus 0.233 ± 0.06 U/g; P = 0.0004), reactive oxygen species (ROS) (132,333 ± 7,505 versus 64,667 ± 10,115 AU; P = 0.0007) and lactate dehydrogenase (LDH) (2.736 ± 0.05 versus 2.1816 ± 0.29 U/g; P = 0.0313). In vitro experiments revealed that IL-17A had no significant effect on the direct migration ability and bactericidal capability of neutrophils. However, IL-17A restrained lysis cell death and increased apoptosis of neutrophils (2.9 ± 1.14 versus 7 ± 0.5%; P = 0.0048). Taken together, our results suggest that C. albicans can depress IL-17A levels, which when supplemented may have a regulatory function that limits the accumulation of neutrophils in inflammatory areas, providing inflammatory response homeostasis.

The application of quantitative telomerase activity measurement as an important indicator to monitor the cardiomyocyte differentiation process of human induced pluripotent stem cells under defined conditions.

The construction of an in vitro differentiation system for human induced pluripotent stem cells (hiPSCs) has made exciting progress, but it is still of great significance to clarify the differentiation process. The use of conventional genetic and protein-labeled microscopes to observe or detect different stages of hiPSC differentiation is not specific enough and is cumbersome and time-consuming. In this study, in addition to analyzing the expression of gene/protein-related markers, we used a previously reported simple and excellent quantitative method of cellular telomerase activity based on a quartz crystal microbalance (TREAQ) device to monitor the dynamic changes in cellular telomerase activity in hiPSCs during myocardial differentiation under chemically defined conditions. Finally, by integrating these results, we analyzed the relationship between telomerase activity and the expression of marker genes/proteins as well as the cell type at each study time point. This dynamic quantitative measurement of cellular telomerase activity should be a promising indicator for monitoring dynamic changes in a stage of hiPSC differentiation and inducing cell types. This study provided a quantitative, dynamic and simple monitoring index for the in vitro differentiation process of hiPSC-CMs, which was a certain reference value for the optimization and improvement of the induction system.

Visible-Light-Mediated Annulation/Thiolation of 2-Isocyanobiaryls with Disulfides to Organoylthiophenanthridines Derivatives.

A visible-light-induced annulation/thiolation of 2-isocyanobiaryls with dialkyl(aryl)disulfides has been established, delivering a sustainable and atom-economic route to 6-organoylthiophenanthridines with wild functional group tolerance and good to excellent yields under oxidant-, base-, and transition-metal-free conditions.

Dietary l-carnitine regulates liver lipid metabolism via simultaneously activating fatty acid ß-oxidation and suppressing endoplasmic reticulum stress in large yellow croaker fed with high-fat diets.

Dietary l-carnitine (LC) is a nutritional factor that reduces liver lipid content. However, whether dietary LC can improve lipid metabolism via simultaneous activation of mitochondrial fatty acid (FA) ß-oxidation and suppression of endoplasmic reticulum (ER) stress is still unknown. Large yellow croaker were fed with a high-fat diet (HFD) supplemented with dietary LC at 0, 1·2 or 2·4 ‰ for 10 weeks. The results indicated that a HFD supplemented with LC reduced the liver total lipid and TAG content and improved serum lipid profiles. LC supplementation administered to this fish increased the liver antioxidant capacity by decreasing serum and liver malondialdehyde levels and enhancing the liver antioxidant capacity, which then relieved the liver damage. Dietary LC increased the ATP dynamic process and mitochondrial number, decreased mitochondrial DNA damage and enhanced the protein expression of mitochondrial ß-oxidation, biogenesis and mitophagy. Furthermore, dietary LC supplementation increased the expression of genes and proteins related to peroxisomal ß-oxidation and biogenesis. Interestingly, feeding fish with LC-enriched diets decreased the protein levels indicative of ER stress, such as glucose-regulated protein 78, p-eukaryotic translational initiation factor 2a and activating transcription factor 6. Dietary LC supplementation downregulated mRNA expression relative to FA synthesis, reduced liver lipid and relieved liver damage through regulating ß-oxidation and biogenesis of mitochondria and peroxisomes, as well as the ER stress pathway in fish fed with HFD. The present study provides the first evidence that dietary LC can improve lipid metabolism via simultaneously promoting FA ß-oxidation capability and suppressing the ER stress pathway in fish.

A Simple and Low-cost Preliminary Quantification of Target Membrane Protein in Single Cells.

To study the heterogeneity of target membrane proteins in single cells with cellular integrity, we proposed a simple and low-cost method to obtain the copy number of the membrane proteins. HeLa cells were labeled by FITC affinity bodies specifically targeting HER2 membrane proteins. The immunolabeled HeLa cells were quantified by a laboratory-built laser induced fluorescence detector. A series of fluorescent microspheres with known number of FITC molecules on the surface were used to establish the calibration curve, instead of the standard fluorescent solutions, because the morphology of the microspheres was similar to the cells, and the distribution of FITC on the spheres were similar to the distribution of HER2 on the HeLa. The fluorescence intensity of the cells was converted to the molecule number of HER2 by the calibration curve. A capillary electrophoresis system was used to drive the microspheres and cells through the detection window. The copy number of HER2 in HeLa cells ranged from 4,036 to 1,224,920 ± 100 (2.5-97.5%), and the median of copy numbers were 104,438 ± 100 per cell. This method for measuring low-abundance membrane proteins can be utilized for the initial exploration of proteomics in ordinary laboratories.

Regulated cell death pathways in cardiomyopathy.

Heart disease is a worldwide health menace. Both intractable primary and secondary cardiomyopathies contribute to malignant cardiac dysfunction and mortality. One of the key cellular processes associated with cardiomyopathy is cardiomyocyte death. Cardiomyocytes are terminally differentiated cells with very limited regenerative capacity. Various insults can lead to irreversible damage of cardiomyocytes, contributing to progression of cardiac dysfunction. Accumulating evidence indicates that majority of cardiomyocyte death is executed by regulating molecular pathways, including apoptosis, ferroptosis, autophagy, pyroptosis, and necroptosis. Importantly, these forms of regulated cell death (RCD) are cardinal features in the pathogenesis of various cardiomyopathies, including dilated cardiomyopathy, diabetic cardiomyopathy, sepsis-induced cardiomyopathy, and drug-induced cardiomyopathy. The relevance between abnormity of RCD with adverse outcome of cardiomyopathy has been unequivocally evident. Therefore, there is an urgent need to uncover the molecular and cellular mechanisms for RCD in order to better understand the pathogenesis of cardiomyopathies. In this review, we summarize the latest progress from studies on RCD pathways in cardiomyocytes in context of the pathogenesis of cardiomyopathies, with particular emphasis on apoptosis, necroptosis, ferroptosis, autophagy, and pyroptosis. We also elaborate the crosstalk among various forms of RCD in pathologically stressed myocardium and the prospects of therapeutic applications targeted to various cell death pathways.

Diagnostic value of multiple b-value diffusion-weighted imaging in discriminating the malignant from benign breast lesions.

OBJECTIVE: The conventional breast Diffusion-weighted imaging (DWI) was subtly influenced by microcirculation owing to the insufficient selection of the b values. However, the multiparameter derived from multiple b-value exhibits more reliable image quality and maximize the diagnostic accuracy. We aim to evaluate the diagnostic performance of stand-alone parameter or in combination with multiparameter derived from multiple b-value DWI in differentiating malignant from benign breast lesions. METHODS: A total of forty-one patients diagnosed with benign breast tumor and thirty-eight patients with malignant breast tumor underwent DWI using thirteen b values and other MRI functional sequence at 3.0 T magnetic resonance. Data were accepted mono-exponential, bi-exponential, stretched-exponential, aquaporins (AQP) model analysis. A receiver operating characteristic curve (ROC) was used to evaluate the diagnostic performance of quantitative parameter or multiparametric combination. The Youden index, sensitivity and specificity were used to assess the optimal diagnostic model. T-test, logistic regression analysis, and Z-test were used. P value < 0.05 was considered statistically significant. RESULT: The ADCavg, ADCmax, f, and α value of the malignant group were lower than the benign group, while the ADCfast value was higher instead. The ADCmin, ADCslow, DDC and ADCAQP showed no statistical significance. The combination (ADCavg-ADCfast) yielded the largest area under curve (AUC = 0.807) with sensitivity (68.42%), specificity (87.8%) and highest Youden index, indicating that multiparametric combination (ADCavg-ADCfast) was validated to be a useful model in differentiating the benign from breast malignant lesion. CONCLUSION: The current study based on the multiple b-value diffusion model demonstrated quantitatively multiparametric combination (ADCavg-ADCfast) exhibited the optimal diagnostic efficacy to differentiate malignant from benign breast lesions, suggesting that multiparameter would be a promising non-invasiveness to diagnose breast lesions.

Online micro solid phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry for trace analysis of endogenous plant hormones in Ulva linza.

OBJECTIVE: Ulva linza (L.) is a species of green algae widely distributed in China. We aimed to establish a sensitive online analytical method for quantification of endogenous phytohormones in fresh minute seaweed samples. METHOD: The method for quantification of endogenous plant hormones in fresh minute samples was developed based on a homemade online micro solid phase extraction (m-SPE) system coupled with an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) platform. The online m-SPE instrument injected the eluent of m-SPE directly onto the LC separation column, improving the utilization of samples and saving time. The m-SPE column, of which the effective size was 9.6 × 2 mm i.d., was filled with 19 mg of C18 (10 µm). RESULTS: Under optimized conditions, the limits of detection were 0.002-0.060 ng ml-1 for five plant hormones. The actual sample recoveries of phytohormones were 76.4-103.4% and the coefficients of variance were below 14.1%. The temporal distribution of these endogenous plant hormones of U. linza during different growth periods is described. CONCLUSION: The proposed online m-SPE method was successfully applied to quantification of endogenous acidic and alkaline plant hormones in U. linza. It provides important information for the further study of the physiological and ecological effects of plant hormones in lower algal species.

Uncovering the Novel Role of NR1D1 in Regulating BNIP3-Mediated Mitophagy in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic, incurable condition characterized by mucosal inflammation and intestinal epithelial cell (IEC) damage. The circadian clock gene NR1D1, implicated in UC and the critical mitophagy process for epithelial repair, needs further exploration regarding its role in mitophagy regulation in UC. METHODS: We created a jet lag mouse model and induced colitis with dextran sulfate sodium (DSS), investigating NR1D1's role. Intestinal-specific Nr1d1 knockout mice were also generated. RNA sequencing, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays helped ascertain NR1D1's regulatory effect on BNIP3 expression. The mitochondrial state in IECs was assessed through transmission electron microscopy, while confocal microscopy evaluated mitophagy-associated protein expression in colon tissue and CCD841 cells. Cell apoptosis and reactive oxygen species (ROS) were measured via flow cytometry. RESULTS: We observed reduced NR1D1 expression in the IECs of UC patients, accentuated under jet lag and DSS exposure in mice. NR1D1 ablation led to disrupted immune homeostasis and declined mitophagy in IECs. NR1D1, usually a transcriptional repressor, was a positive regulator of BNIP3 expression, leading to impaired mitophagy, cellular inflammation, and apoptosis. Administering the NR1D1 agonist SR9009 ameliorated colitis symptoms, primarily by rectifying defective mitophagy. CONCLUSIONS: Our results suggest that NR1D1 bridges the circadian clock and UC, controlling BNIP3-mediated mitophagy and representing a potential therapeutic target. Its agonist, SR9009, shows promise in UC symptom alleviation.

BIRC5 Inhibition Is Associated with Pyroptotic Cell Death via Caspase3-GSDME Pathway in Lung Adenocarcinoma Cells.

Lung adenocarcinoma (LUAD) is a prevalent type of thoracic cancer with a poor prognosis and high mortality rate. However, the exact pathogenesis of this cancer is still not fully understood. One potential factor that can contribute to the development of lung adenocarcinoma is DNA methylation, which can cause changes in chromosome structure and potentially lead to the formation of tumors. The baculoviral IAP repeat containing the 5 (BIRC5) gene encodes the Survivin protein, which is a multifunctional gene involved in cell proliferation, migration, and invasion of tumor cells. This gene is elevated in various solid tumors, but its specific role and mechanism in lung adenocarcinoma are not well-known. To identify the potential biomarkers associated with lung adenocarcinoma, we screened the methylation-regulated differentially expressed genes (MeDEGs) of LUAD via bioinformatics analysis. Gene ontology (GO) process and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to investigate the biological function and pathway of MeDEGs. A protein-protein interaction (PPI) network was employed to explore the key module and screen hub genes. We screened out eight hub genes whose products are aberrantly expressed, and whose DNA methylation modification level is significantly changed in lung adenocarcinoma. BIRC5 is a bona fide marker which was remarkably up-regulated in tumor tissues. Flow cytometry analysis, lactate dehydrogenase release (LDH) assay and Micro-PET imaging were performed in A549 cells and a mouse xenograft tumor to explore the function of BIRC5 in cell death of lung adenocarcinoma. We found that BIRC5 was up-regulated and related to a high mortality rate in lung adenocarcinoma patients. Mechanically, the knockdown of BIRC5 inhibited the proliferation of A549 cells and induced pyroptosis via caspase3/GSDME signaling. Our findings have unraveled that BIRC5 holds promise as a novel biomarker and therapeutic target for lung adenocarcinoma. Additionally, we have discovered a novel pathway in which BIRC5 inhibition can induce pyroptosis through the caspase3-GSDME pathway in lung adenocarcinoma cells.

Effects of Dietary Bile Acids on Growth Performance, Lipid Deposition, and Intestinal Health of Rice Field Eel (Monopterus albus) Fed with High-Lipid Diets.

The purpose of this trial was to study the positive effects of bile acids (BAs) on growth performance and intestinal health of rice field eel fed with high-lipid diets (HLDs). Rice field eels (initial weight 17.00 ± 0.10 g) were divided into four groups, each group containing four repetitions and feeding with different isonitrogenous diet: control diet containing 7% lipid content, HLDs containing the lipid content increased to 13%, HLDs supplementing with 0.025% BAs and 0.05% BAs, respectively. After 8 weeks, compared control group, the fish fed HLDs had no significant effect on weight gain rate and specific growth rate (P > 0.05), but increased the lipid deposition in tissues and intestinal lipase activity, and damaged to intestinal oxidative stress, inflammatory response, physical barrier, and structural integrity (P < 0.05). Dietary BAs significantly increased weight gain rate and specific growth rate in fish fed with HL diets (P < 0.05) and reduced feed conversation rate (P < 0.05). Further, the eels fed with BAs reduced the total lipid content in liver, muscle, and whole body (P < 0.05). Dietary BAs decreased the activity of intestinal lipase (P < 0.05). Meanwhile, BAs supplemented in HLDs improved intestinal antioxidant capacity through increasing the activities of T-SOD (total superoxide dismutase), GSH-PX (glutathione peroxidase), CAT (catalase), T-AOC (total antioxidant capacity), whereas reducing MDA (malondialdehyde) content (P < 0.05). Moreover, dietary BAs regulated the mRNA expression related to inflammatory response, oxidative stress, and physical barrier in intestine, such as tnf-α, il-8, tlr-8, il-10, nrf2, keap1, claudin12, and claudin15 (P < 0.05). Dietary BAs supplementation also enhanced the intestinal structural integrity characterized by increased fold height and lamina propria width (P < 0.05). This study showed that dietary BAs supplemented in HLDs (13% lipid) could increase the growth performance of rice field eel, reduce lipid deposition in tissues and whole body, and enhance intestinal health.