CRISPR-array-mediated imaging of non-repetitive and multiplex genomic loci in living cells.

Dynamic imaging of genomic loci is key for understanding gene regulation, but methods for imaging genomes, in particular non-repetitive DNAs, are limited. We developed CRISPRdelight, a DNA-labeling system based on endonuclease-deficient CRISPR-Cas12a (dCas12a), with an engineered CRISPR array to track DNA location and motion. CRISPRdelight enables robust imaging of all examined 12 non-repetitive genomic loci in different cell lines. We revealed the confined movement of the CCAT1 locus (chr8q24) at the nuclear periphery for repressed expression and active motion in the interior nucleus for transcription. We uncovered the selective repositioning of HSP gene loci to nuclear speckles, including a remarkable relocation of HSPH1 (chr13q12) for elevated transcription during stresses. Combining CRISPR-dCas12a and RNA aptamers allowed multiplex imaging of four types of satellite DNA loci with a single array, revealing their spatial proximity to the nucleolus-associated domain. CRISPRdelight is a user-friendly and robust system for imaging and tracking genomic dynamics and regulation.

CDKL3 is a targetable regulator of cell cycle progression in cancers.

Cell cycle regulation is largely abnormal in cancers. Molecular understanding and therapeutic targeting of the aberrant cell cycle are essentially meaningful. Here, we identified an under-appreciated Serine/Threonine kinase, CDKL3 (Cyclin-dependent kinase like 3), crucially drives the rapid cell cycle progression and cell growth in cancers. Mechanism-wise, CDKL3 localizes in the nucleus and associates with specific cyclin to directly phosphorylate Retinoblastoma (Rb) for quiescence exit. In parallel, CDKL3 prevents the ubiquitin-proteasomal degradation of CDK4 by direct phosphorylation on T172 to sustain G1 phase advancement. The crucial function of CDKL3 in cancers was demonstrated both in vitro and in vivo. We also designed, synthesized and characterized a first-in-class CDKL3-specific inhibitor, HZ1. HZ1 exhibits greater potency than CDK4/6 (Cyclin-dependent kinase 4/6) inhibitor in pan-cancer treatment by causing cell cycle arrest and overcomes the acquired resistance of the latter. In particular, CDKL3 has significant clinical relevance in colon cancer, and the effectiveness of HZ1 was demonstrated by murine and patient-derived cancer models. Collectively, this work presented an integrated paradigm of cancer cell cycle regulation and suggested CDKL3-targeting as a feasible approach in cancer treatment.

A novel selenium analog of HDACi-based twin drug induces apoptosis and cell cycle arrest via CDC25A to improve prostate cancer therapy.

Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer chemicals has produced exciting progress in cancer treatment. Herein, we developed a novel prodrug via the ligation of dichloroacetate to selenium-containing potent HDAC inhibitors. The effect and mechanism of this compound in the treatment of prostate cancer were also studied. Methods: The concerned prodrug SeSA-DCA was designed and synthesized under mild conditions. This compound's preclinical studies, including the pharmacokinetics, cell toxicity, and anti-tumor effect on prostate cancer cell lines, were thoroughly investigated, and its possible synergistic mechanism was also explored and discussed. Results: SeSA-DCA showed good stability in physiological conditions and could be rapidly decomposed into DCA and selenium analog of SAHA (SeSAHA) in the tumor microenvironment. CCK-8 experiments identified that SeSA-DCA could effectively inhibit the proliferation of a variety of tumor cell lines, especially in prostate cancer. In further studies, we found that SeSA-DCA could also inhibit the metastasis of prostate cancer cell lines and promote cell apoptosis. At the animal level, oral administration of SeSA-DCA led to significant tumor regression without obvious toxicity. Moreover, as a bimolecular coupling compound, SeSA-DCA exhibited vastly superior efficacy than the mixture with equimolar SeSAHA and DCA both in vitro and in vivo. Our findings provide an important theoretical basis for clinical prostate cancer treatment. Conclusions: Our in vivo and in vitro results showed that SeSA-DCA is a highly effective anti-tumor compound for PCa. It can effectively induce cell cycle arrest and growth suppression and inhibit the migration and metastasis of PCa cell lines compared with monotherapy. SeSA-DCA's ability to decrease the growth of xenografts is a little better than that of docetaxel without any apparent signs of toxicity. Our findings provide an important theoretical basis for clinical prostate cancer treatment.

Phase division and recognition of crystal HRTEM images based on machine learning and deep learning.

The High Resolution Transmission Electron Microscope (HRTEM) images provide valuable insights into the atomic microstructure, dislocation patterns, defects, and phase characteristics of materials. However, the current analysis and research of HRTEM images of crystal materials heavily rely on manual expertise, which is labor-intensive and susceptible to subjective errors. This study proposes a combined machine learning and deep learning approach to automatically partition the same phase regions in crystal HRTEM images. The entire image is traversed by a sliding window to compute the amplitude spectrum of the Fast Fourier Transform (FFT) in each window. The generated data is transformed into a 4-dimensional (4D) format. Principal component analysis (PCA) on this 4D data estimates the number of feature regions. Non-negative matrix factorization (NMF) then decomposes the data into a coefficient matrix representing feature region distribution, and a feature matrix corresponding to the FFT magnitude spectra. Phase recognition based on deep learning enables identifying the phase of each feature region, thereby achieving automatic segmentation and recognition of phase regions in HRTEM images of crystals. Experiments on zirconium and oxide nanoparticle HRTEM images demonstrate the proposed method achieve the consistency of manual analysis. Code and supplementary material are available at https://github.com/rememberBr/HRTEM2.

Ramelteon protects against social defeat stress-associated abnormal behaviors.

Psychological stress affects the neuroendocrine regulation, which modulates mental status and behaviors. Melatonin, a hormone synthesized primarily by the pineal gland, regulates many brain functions, including circadian rhythms, pain, sleep, and mood. Selective pharmacological melatonin agonist ramelteon has been clinically used to treat mood and sleep disorders. Posttraumatic stress disorder (PTSD) is a psychiatric condition associated with severe trauma; it is generally triggered by traumatic events, which lead to severe anxiety and uncontrollable trauma recall. We recently reported that repeated social defeat stress (RSDS) may induce robust anxiety-like behaviors and social avoidance in mice. In the present study, we investigated whether melatonin receptor activation by melatonin and ramelteon regulates RSDS-induced behavioral changes. Melatonin treatment improved social avoidance and anxiety-like behaviors in RSDS mice. Moreover, treatment of the non-selective MT1/MT2 receptor agonist, ramelteon, markedly ameliorated RSDS-induced social avoidance and anxiety-like behaviors. Moreover, activating melatonin receptors also balanced the expression of monoamine oxidases, glucocorticoid receptors, and endogenous antioxidants in the hippocampus. Taken together, our findings indicate that the activation of both melatonin and ramelteon regulates RSDS-induced anxiety-like behaviors and PTSD symptoms. The current study also showed that the regulatory effects of neuroendocrine mechanisms and cognitive behaviors on melatonin receptor activation in repeated social defeat stress.

New vision of HookEfficientNet deep neural network: Intelligent histopathological recognition system of non-small cell lung cancer.

BACKGROUND: Efficient and precise diagnosis of non-small cell lung cancer (NSCLC) is quite critical for subsequent targeted therapy and immunotherapy. Since the advent of whole slide images (WSIs), the transition from traditional histopathology to digital pathology has aroused the application of convolutional neural networks (CNNs) in histopathological recognition and diagnosis. HookNet can make full use of macroscopic and microscopic information for pathological diagnosis, but it cannot integrate other excellent CNN structures. The new version of HookEfficientNet is based on a combination of HookNet structure and EfficientNet that performs well in the recognition of general objects. Here, a high-precision artificial intelligence-guided histopathological recognition system was established by HookEfficientNet to provide a basis for the intelligent differential diagnosis of NSCLC. METHODS: A total of 216 WSIs of lung adenocarcinoma (LUAD) and 192 WSIs of lung squamous cell carcinoma (LUSC) were recruited from the First Affiliated Hospital of Zhengzhou University. Deep learning methods based on HookEfficientNet, HookNet and EfficientNet B4-B6 were developed and compared with each other using area under the curve (AUC) and the Youden index. Temperature scaling was used to calibrate the heatmap and highlight the cancer region of interest. Four pathologists of different levels blindly reviewed 108 WSIs of LUAD and LUSC, and the diagnostic results were compared with the various deep learning models. RESULTS: The HookEfficientNet model outperformed HookNet and EfficientNet B4-B6. After temperature scaling, the HookEfficientNet model achieved AUCs of 0.973, 0.980, and 0.989 and Youden index values of 0.863, 0.899, and 0.922 for LUAD, LUSC and normal lung tissue, respectively, in the testing set. The accuracy of the model was better than the average accuracy from experienced pathologists, and the model was superior to pathologists in the diagnosis of LUSC. CONCLUSIONS: HookEfficientNet can effectively recognize LUAD and LUSC with performance superior to that of senior pathologists, especially for LUSC. The model has great potential to facilitate the application of deep learning-assisted histopathological diagnosis for LUAD and LUSC in the future.

Synergistic action and mechanism of scoparone, a key bioactive component of Artemisia capillaris, and spirodiclofen against spider mites.

BACKGROUND: Plants have numerous defensive secondary metabolites to withstand insect attacks. Scoparone, which is extracted from the medicinal plant Artemisia capillaris, has potent acaricidal effects on Tetranychus cinnabarinus. Spirodiclofen, derived from a tetronic acid derivative, is a potent commercial acaricide that is extensively used globally. However, whether scoparone has synergistic effects when used in conjunction with spirodiclofen and the underlying synergistic mechanism remains unclear. RESULTS: Scoparone exhibited a potent synergistic effect when it was combined with spirodiclofen at a 1:9 ratio. Subsequently, cytochrome P450 monooxygenase (P450) activity, RNA-Seq and qPCR assays indicated that the enzyme activity of P450 and the expression of one P450 gene from T. cinnabarinus, TcCYP388A1, were significantly inhibited by scoparone and spirodiclofen + scoparone; conversely, P450 was activated in spirodiclofen-exposed mites. Importantly, RNAi-mediated silencing of the TcCYP388A1 gene markedly increased the susceptibility of spider mites to spirodiclofen, scoparone and spirodiclofen + scoparone, and in vitro, the recombinant TcCYP388A1 protein could metabolize spirodiclofen. Molecular docking and functional analyses further indicated that R117, which is highly conserved in Arachnoidea species, may be a vital specific binding site for scoparone in the mite TcCYP388A1 protein. This binding site was subsequently confirmed using mutagenesis data, which revealed that this binding site was the sole site selected by scoparone in spider mites over mammalian or fly CYP388A1. CONCLUSIONS: These results indicate that the synergistic effects of scoparone and spirodiclofen on mites occurs through the inhibition of P450 activity, thus reducing spirodiclofen metabolism. The synergistic effect of this potent natural product on the detoxification enzyme-targeted activity of commercial acaricides may offer a sustainable strategy for pest mite resistance management. © 2024 Society of Chemical Industry.

Extracellular Matrix Remodeling Alleviates Memory Deficits in Alzheimer's Disease by Enhancing the Astrocytic Autophagy-Lysosome Pathway.

Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short-term memory loss and reduced amyloid-beta (Aß) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aß plaques, and enhanced astrocyte recruitment to surrounding plaques. Importantly, ECM remodeling enhanced the autophagy-lysosome pathway in astrocytes, thereby mediating Aß clearance and alleviating AD pathology. ECM remodeling also promoted Aß plaque phagocytosis by astrocytes by activating the astrocytic phagocytosis receptor MERTK and promoting astrocytic vesicle circulation. The study identified a cellular mechanism in which ECM remodeling activates the astrocytic autophagy-lysosomal pathway and alleviates AD pathology. Targeting ECM remodeling may represent a potential therapeutic strategy for AD and serve as a reference for the treatment of this disease.

Multidimensional water level and water quality response to severe drought in Xingyun Lake.

Drought stress has a significant impact on the quality and quantity of lake water. Understanding this impact is crucial for preventing water security risks and pollution recovery. However, there is a lack of systemic understanding of how drought affects water quality and quantity, and how they change in multiple dimensions. This manuscript established a synthesized methodology with the principles to judge the applicability and three steps of application to detect the change in water quality and water level under severe drought in Xingyun Lake, China. Results show that (1) The water level and water quality of Xingyun Lake have a synchronous and evident response to drought during 2009-2014. The rainfall during 2008-2015 declined by 22.9 % to normal, and the inundated area and lake water depth in 2012 decreased by 10.50 % from 2002 to 1.38 m to the average depth, respectively. The pollution index climbed above 1.21 after 2008, fluctuating around 1.42. (2) Under drought, the water quality indicators significantly changed in the terms of the overall feature, trend, eigenvalue, and morphological characteristics. The water quality indicators of Set2008-2015 are significantly different from set2000-2007 and not in the groups of set1994-2000. The morphological characteristics of water quality indicators in set2008-2015 differs significantly from that in set2000-2007 shown by the minimum, maximum, median, quartiles, and extreme values. (3) Although NH3-N showed no significant change, the water quality deteriorated in the physical, chemical, and biological aspects. The TP, IMN, and BOD5 changed more evidently than DO and NH3-N. (4) Water quality grade and indicator concentration deteriorated significantly and sharply under severe drought and are threatened deeply by TP and TN. The synthesized methodology is scientifically constructed and canbe employed in the characteristics cognition of water quality and water level to severe drought in and out of this research. And the intervention time and various regulating measures for pollution degradation and water quality recovery canbe constructed based on the multi-dimensional analysis of water quality change under drought evolution.

Bacmethy: A novel and convenient tool for investigating bacterial DNA methylation pattern and their transcriptional regulation effects.

DNA methylation serves as the primary mode of epigenetic regulation in prokaryotes, particularly through transcriptional regulation. With the rapid implementation of third-generation sequencing technology, we are currently experiencing a golden age of bacterial epigenomics. However, there has been a lack of comprehensive research exploring the versatility and consequential impact of bacterial DNA methylome on cellular and physiological functions. There is a critical need for a user-friendly bioinformatics tool that can effectively characterize DNA methylation modification features and predict the regulation patterns. To address this gap, the current study introduces Bacmethy, an innovative tool that utilizes SMRT-seq data and offers a range of analytical modules. First, the tool classifies methylation sites in the genome, highlighting the distinct regulations present under varying modification fractions and location enrichment. Furthermore, this tool enables us to identify regulatory region methylation and potential cis and trans interactions between methylation sites and regulatory effectors. Using benchmark data sets and our data, we show that our tool facilitates the understanding of the distinctive traits of DNA methylation modifications and predicts transcriptional regulation effects on important physiological and pathological functions. Bacmethy code is freely available, and the Docker image is downloadable. Bacmethy has been made available as a user-friendly web server interface at https://bacmethy.med.sustech.edu.cn.

Cu(II) complex that synergistically potentiates cytotoxicity and an antitumor immune response by targeting cellular redox homeostasis.

Developing anticancer drugs with low side effects is an ongoing challenge. Immunogenic cell death (ICD) has received extensive attention as a potential synergistic modality for cancer immunotherapy. However, only a limited set of drugs or treatment modalities can trigger an ICD response and none of them have cytotoxic selectivity. This provides an incentive to explore strategies that might provide more effective ICD inducers free of adverse side effects. Here, we report a metal-based complex (Cu-1) that disrupts cellular redox homeostasis and effectively stimulates an antitumor immune response with high cytotoxic specificity. Upon entering tumor cells, this Cu(II) complex enhances the production of intracellular radical oxidative species while concurrently depleting glutathione (GSH). As the result of heightening cellular oxidative stress, Cu-1 gives rise to a relatively high cytotoxicity to cancer cells, whereas normal cells with low levels of GSH are relatively unaffected. The present Cu(II) complex initiates a potent ferroptosis-dependent ICD response and effectively inhibits in vivo tumor growth in an animal model (c57BL/6 mice challenged with colorectal cancer). This study presents a strategy to develop metal-based drugs that could synergistically potentiate cytotoxic selectivity and promote apoptosis-independent ICD responses through perturbations in redox homeostasis.

Preparation and Wettability Analysis of Metal Biofunctional Surfaces Based on the Microquadrangular Structure.

Improving the hydrophobic properties of aluminum alloys is crucial for industry. In previous reports, researchers prepared superhydrophobic surfaces by fabricating micro-nanostructures on the metal surface with a nanosecond laser. However, no researchers have formed microquadrangular groove structures on the metal surface. In this article, inspired by the bamboo leaf, a microquadrangular structure is designed and processed using nanosecond laser technology to form a superhydrophobic functional surface. The effects of laser processing parameters, such as laser power, scanning speed, scanning time, defocus and fill spacing on the size, surface morphology features, and wettability of the microquadrangular structure, are investigated by a single-factor experimental method. The experimental results show the optimal size of the processed microquadrangular structure obtained from the experiment with an error of 1.28% from the design size, where the fill spacing has the greatest effect on the size and the scanning time, defocus, and fill spacing have great influence on the surface morphology. The contact angle of water drops on the surface can reach 154.7°, and the power has the greatest influence on the wettability. Laser parameters have distinct effects on the properties of the materials. Therefore, by regulation of the laser parameters, the formation of the microstructure can be availably controlled and the result of hydrophobicity can be achieved.

Cocaine and amphetamine-regulated transcript improves myocardial ischemia-reperfusion injury through PI3K/AKT signalling pathway.

Myocardial ischemia-reperfusion injury (MIRI) is a common clinic scenario that occurs in the context of reperfusion therapy for acute myocardial infarction. It has been shown that cocaine and amphetamine-regulated transcript (CART) can ameliorate cerebral ischemia-reperfusion (I/R) injury, but the effect of CART on MIRI has not been studied yet. Here, we revealed that CART protected the heart during I/R process by inhibiting apoptosis and excessive autophagy, indicating that CART would be a potential drug candidate for the treatment of MIRI. Further analysis showed that CART upregulated the activation of phospho-AKT, leading to downregulation of lactate dehydrogenase (LDH) release, apoptosis, oxidative stress and excessive autophagy after I/R, which was inhibited by PI3K inhibitor, LY294002. Collectively, CART attenuated MIRI through inhibition of cardiomyocytes apoptosis and excessive autophagy, and the protective effect was dependent on PI3K/AKT signalling pathway.

Critical roles of the miR-17∼92 family in thymocyte development, leukemogenesis, and autoimmunity.

Thymocyte development requires precise control of PI3K-Akt signaling to promote proliferation and prevent leukemia and autoimmune disorders. Here, we show that ablating individual clusters of the miR-17∼92 family has a negligible effect on thymocyte development, while deleting the entire family severely impairs thymocyte proliferation and reduces thymic cellularity, phenocopying genetic deletion of Dicer. Mechanistically, miR-17∼92 expression is induced by Myc-mediated pre-T cell receptor (TCR) signaling, and miR-17∼92 promotes thymocyte proliferation by suppressing the translation of Pten. Retroviral expression of miR-17∼92 restores the proliferation and differentiation of Myc-deficient thymocytes. Conversely, partial deletion of the miR-17∼92 family significantly delays Myc-driven leukemogenesis. Intriguingly, thymocyte-specific transgenic miR-17∼92 expression does not cause leukemia or lymphoma but instead aggravates skin inflammation, while ablation of the miR-17∼92 family ameliorates skin inflammation. This study reveals intricate roles of the miR-17∼92 family in balancing thymocyte development, leukemogenesis, and autoimmunity and identifies those microRNAs (miRNAs) as potential therapeutic targets for leukemia and autoimmune diseases.

A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development.

The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females' fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.

Revisiting the advances and challenges in the clinical applications of extracellular vesicles in cancer.

Extracellular vesicles (EVs) have been the subject of an exponentially growing number of studies covering their biogenesis mechanisms, isolation and analysis techniques, physiological and pathological roles, and clinical applications, such as biomarker and therapeutic uses. Nevertheless, the heterogeneity of EVs both challenges our understanding of them and presents new opportunities for their potential application. Recently, the EV field experienced a wide range of advances. However, the challenges also remain huge. This review focuses on the recent progress and difficulties encountered in the practical use of EVs in clinical settings. In addition, we also explored the concept of EV heterogeneity to acquire a more thorough understanding of EVs and their involvement in cancer, specifically focusing on the fundamental nature of EVs.

Transcriptome dynamics of the BHK21 cell line in response to human coronavirus OC43 infection.

The progress of viral infection involves numerous transcriptional regulatory events. The identification of the newly synthesized transcripts helps us to understand the replication mechanisms and pathogenesis of the virus. Here, we utilized a time-resolved technique called metabolic RNA labeling approach called thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq) to differentially elucidate the levels of steady-state and newly synthesized RNAs of BHK21 cell line in response to human coronavirus OC43 (HCoV-OC43) infection. Our results showed that the Wnt/ß-catenin signaling pathway was significantly enriched with the newly synthesized transcripts of BHK21 cell line in response to HCoV-OC43 infection. Moreover, inhibition of the Wnt pathway promoted viral replication in the early stage of infection, but inhibited it in the later stage of infection. Furthermore, remdesivir inhibits the upregulation of the Wnt/ß-catenin signaling pathway induced by early infection with HCoV-OC43. Collectively, our study showed the diverse roles of Wnt/ß-catenin pathway at different stages of HCoV-OC43 infection, suggesting a potential target for the antiviral treatment. In addition, although infection with HCoV-OC43 induces cytopathic effects in BHK21 cells, inhibiting apoptosis does not affect the intracellular replication of the virus. Monitoring newly synthesized RNA based on such time-resolved approach is a highly promising method for studying the mechanism of viral infections.

A novel histone deacetylase inhibitor Se-SAHA attenuates isoproterenol-induced heart failure via antioxidative stress and autophagy inhibition.

Heart failure is associated with histone deacetylase (HDAC) regulation of gene expression, the inhibition of which is thought to be beneficial for heart failure therapy. Here, we explored the cardioprotective effects and underlying mechanism of a novel selenium-containing HDAC inhibitor, Se-SAHA, on isoproterenol (ISO)-induced heart failure. We found that pretreatment with Se-SAHA attenuated ISO-induced cardiac hypertrophy and fibrosis in neonatal rat ventricular myocytes (NRVMs). Se-SAHA significantly attenuated the generation of ISO-induced reactive oxygen species (ROS) and restored the expression levels of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) in vitro. Furthermore, Se-SAHA pretreatment prevented the accumulation of autophagosomes. Se-SAHA reversed the high expression of HDAC1 and HDAC6 induced by ISO incubation. However, after the addition of the HDAC agonist, the effect of Se-SAHA on blocking autophagy was inhibited. Using ISO-induced mouse models, cardiac ventricular contractile dysfunction, hypertrophy, and fibrosis was reduced treated by Se-SAHA. In addition, Se-SAHA inhibited HDAC1 and HDAC6 overexpression in ISO-treated mice. Se-SAHA treatment significantly increased the activity of SOD2 and improved the ability to eliminate free radicals. Se-SAHA hindered the excessive levels of the microtubule-associated protein 1 light chain 3 (LC3)-II and Beclin-1 in heart failure mice. Collectively, our results indicate that Se-SAHA exerts cardio-protection against ISO-induced heart failure via antioxidative stress and autophagy inhibition.

Konjac glucomannan-fibrin composite hydrogel as a model for ideal scaffolds for cell-culture meat.

In this study, composite gel was prepared from konjac glucomannan (KGM) and fibrin (FN). Composite gels with different concentration ratios were compared in terms of their mechanical properties, rheological properties, water retention, degradation rate, microstructure and biocompatibility. The results showed that the composite gels had better gel strength and other properties than non-composite gels. In particular, composite hydrogels with low Young's modulus formed when the KGM concentration was 0.8% and the FN concentration was 1.2%. The two components were cross linked through hydrogen-bond interaction, which formed a more stable gel structure with excellent water retention and in-vitro degradation rates, which were conducive to myogenic differentiation of ectomesenchymal stem cells (EMSCs). KGM-FN composite gel was applied to the preparation of cell-culture meat, which had similar texture properties and main nutrients to animal meat as well as higher content of dry base protein and dry base carbohydrate.