ABSTRACT
Stem cells in vivo can transit between quiescence and activation, two metabolically distinct states. It is increasingly appreciated that cell metabolism assumes profound roles in stem cell maintenance and tissue homeostasis. However, the lack of suitable models greatly hinders our understanding of the metabolic control of stem cell quiescence and activation. In the present study, we have utilized classical signaling pathways and developed a cell culture system to model reversible NSC quiescence and activation. Unlike activated ones, quiescent NSCs manifested distinct morphology characteristics, cell proliferation, and cell cycle properties but retained the same cell proliferation and differentiation potentials once reactivated. Further transcriptomic analysis revealed that extensive metabolic differences existed between quiescent and activated NSCs. Subsequent experimentations confirmed that NSC quiescence and activation transition was accompanied by a dramatic yet coordinated and dynamic shift in RNA metabolism, protein synthesis, and mitochondrial and autophagy activity. The present work not only showcases the broad utilities of this powerful in vitro NSC quiescence and activation culture system but also provides timely insights for the field and warrants further investigations.
Subject(s)
Cell Differentiation , Cell Proliferation , Neural Stem Cells , Neural Stem Cells/metabolism , Neural Stem Cells/cytology , Animals , Mice , Cell Culture Techniques/methods , Cells, Cultured , Cell Cycle/physiology , AutophagyABSTRACT
The pursuit of high energy density in lithium batteries has driven the development of efficient electrodes with low levels of inactive components. Herein, a facile approach involving the use of π-π stacked nigrosine@carbon nanotube nanocomposites as an all-in-one additive for a LiFePO4 cathode has been developed. This design significantly reduces the proportion of inactive substances within the cathode, resulting in a battery that exhibits a high specific capacity of 143 mAh g-1 at a 1 C rate and shows commendable cyclic performance. Furthermore, the elimination of rigid current collectors endows the electrode with flexibility, offering avenues for future wearable energy storage devices.
ABSTRACT
The Cell-Free Protein Synthesis (CFPS) system has been widely employed to facilitate the bottom-up assembly of synthetic cells. It serves as the host for the core machinery of the Central Dogma, standing as an optimal chassis for the integration and assembly of diverse artificial cellular mimicry systems. Despite its frequent use in the fabrication of synthetic cells, establishing a tailored and robust CFPS system for a specific application remains a nontrivial challenge. In this methods paper, we present a comprehensive protocol for the CFPS system, routinely employed in constructing synthetic cells. This protocol encompasses key stages in the preparation of the CFPS system, including the cell extract, template preparation, and routine expression optimization utilizing a fluorescent reporter protein. Additionally, we show representative results by encapsulating the CFPS system within various micro-compartments, such as monolayer droplets, double-emulsion vesicles, and chambers situated atop supported lipid bilayers. Finally, we elucidate the critical steps and conditions necessary for the successful assembly of these CFPS systems in distinct environments. We expect that our approach will facilitate the establishment of good working practices among various laboratories within the continuously expanding synthetic cell community, thereby accelerating progress in the field of synthetic cell development.
Subject(s)
Artificial Cells , Cell-Free System , Protein Biosynthesis , Artificial Cells/chemistry , Artificial Cells/metabolism , Escherichia coli/genetics , Escherichia coli/metabolismABSTRACT
Due to the high expenses involved, 4D-CT data for certain patients may only include five respiratory phases (0%, 20%, 40%, 60%, and 80%). This limitation can affect the subsequent planning of radiotherapy due to the absence of lung tumor information for the remaining five respiratory phases (10%, 30%, 50%, 70%, and 90%). This study aims to develop an interpolation method that can automatically derive tumor boundary contours for the five omitted phases using the available 5-phase 4D-CT data. The dynamic mode decomposition (DMD) method is a data-driven and model-free technique that can extract dynamic information from high-dimensional data. It enables the reconstruction of long-term dynamic patterns using only a limited number of time snapshots. The quasi-periodic motion of a deformable lung tumor caused by respiratory motion makes it suitable for treatment using DMD. The direct application of the DMD method to analyze the respiratory motion of the tumor is impractical because the tumor is three-dimensional and spans multiple CT slices. To predict the respiratory movement of lung tumors, a method called uniform angular interval (UAI) sampling was developed to generate snapshot vectors of equal length, which are suitable for DMD analysis. The effectiveness of this approach was confirmed by applying the UAI-DMD method to the 4D-CT data of ten patients with lung cancer. The results indicate that the UAI-DMD method effectively approximates the lung tumor's deformable boundary surface and nonlinear motion trajectories. The estimated tumor centroid is within 2 mm of the manually delineated centroid, a smaller margin of error compared to the traditional BSpline interpolation method, which has a margin of 3 mm. This methodology has the potential to be extended to reconstruct the 20-phase respiratory movement of a lung tumor based on dynamic features from 10-phase 4D-CT data, thereby enabling more accurate estimation of the planned target volume (PTV).
Subject(s)
Four-Dimensional Computed Tomography , Lung Neoplasms , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/physiopathology , Humans , Four-Dimensional Computed Tomography/methods , Algorithms , Radiographic Image Interpretation, Computer-Assisted/methods , Movement , Sensitivity and Specificity , Reproducibility of Results , Respiratory-Gated Imaging Techniques/methodsABSTRACT
Metallic Zn is considered as a promising anode material because of its abundance, eco-friendliness, and high theoretical capacity. However, the uncontrolled dendrite growth and side reactions restrict its further practical application. Herein, we proposed a ß-cyclodextrin-modified multiwalled carbon nanotube (CD-MWCNT) layer for Zn metal anodes. The obtained CD-MWCNT layer with high affinity to Zn can significantly reduce the transfer barrier of Zn2+ at the electrode/electrolyte interface, facilitating the uniform deposition of Zn2+ and suppressing water-caused side reactions. Consequently, the Zn||Zn symmetric cell assembled with CD-MWCNT shows a significantly enhanced cycling durability, maintaining a cycling life exceeding 1000 h even under a high current density of 5 mA cm-2. Furthermore, the full battery equipped with a V2O5 cathode displays an unparalleled long life. This work unveils a promising avenue toward the achievement of high-performance Zn metal anodes.
ABSTRACT
The challenge of constructing a mechanically robust yet lightweight artificial solid-electrolyte interphase layer on lithium (Li) anodes highlights a trade-off between high battery safety and high energy density. Inspired by the intricate microstructure of the white sea urchin, we first develop a polyvinyl fluoride-hexafluoropropylene (PVDF-HFP) interfacial layer with a triple periodic minimal surface structure (TPMS) that could offer maximal modulus with minimal weight. This design endows high mechanical strength to an ordered porous structure, effectively reduces local current density, polarization, and internal resistance, and stabilizes the anode interface. At a low N/P ratio of ~3, using LiFePO4 as the cathode, Li anodes protected by TPMS-structured PVDF-HFP achieve an extremely low capacity-fading-rate of approximately 0.002 % per cycle over 200 cycles at 1â C, with an average discharge capacity of 142â mAh g-1. Meanwhile, the TPMS porous structure saves 50â wt % of the interfacial layer mass, thereby enhancing the energy density of the battery. The TPMS structure is conducive to large-scale additive manufacturing, which will provide a reference for the future development of lightweight, high-energy-density secondary batteries.
ABSTRACT
Chemotherapy is an effective therapeutic modality; nevertheless, a significant proportion of patients diagnosed with lung adenocarcinoma (LUAD) demonstrate resistance to chemotherapy. Therefore, it is crucial to understand the potential regulatory mechanisms to develop novel treatment strategies. This study aims to understand how increased FAM83B expression impacts mitochondrial activity, cell apoptosis, and chemotherapy effectiveness in LUAD. Multiple assays, such as CCK8, wound healing, EdU, and transwell assays, were employed to confirm the augmented chemotherapy resistance, heightened cell proliferation, migration, and invasion caused by FAM83B overexpression in LUAD cells. Furthermore, MIMP, MTG, and ATP assays were utilized to quantify changes in mitochondrial metabolism. In vitro functional assays were performed to evaluate the influence of FAM83B overexpression on the malignant progression and resistance mechanisms to chemotherapy in LUAD. In the context of this study, it was determined that LUAD patients with increased FAM83B expression had shorter survival times, and tissue samples with FAM83B overexpression were more prone to metastasis compared to primary samples. As a result, FAM83B is identified as an adverse prognostic marker. The mechanistic analysis demonstrated that FAM83B impedes the translocation of calbindin 2 (CALB2) from the cytoplasm to the mitochondria, resulting in the inhibition of apoptosis and the promotion of mitochondrial activity. Consequently, this ultimately confers resistance to chemotherapy in LUAD. Furthermore, the administration of metformin, which blocks mitochondrial oxidative phosphorylation (OXPHOS), can restore sensitivity to drug resistance in LUAD. Taken together, these findings provide substantial evidence supporting the notion that FAM83B enhances chemotherapy resistance in LUAD through the upregulation of mitochondrial metabolism and the inhibition of apoptosis.
Subject(s)
Adenocarcinoma of Lung , Apoptosis , Cell Proliferation , Lung Neoplasms , Mitochondria , Female , Humans , Male , Middle Aged , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Mitochondria/metabolism , Mitochondria/drug effects , Mitochondria/genetics , Mitochondria/pathology , PrognosisABSTRACT
Volatile organic compounds (VOCs) play a major role in O3 formation in urban environments. However, the complexity in the emissions of VOCs and nitrogen oxides (NOx) in industrial cities has made it challenging to identify the key factors influencing O3 formation. This study used observation-based-model (OBM) to analyze O3 sensitivities to VOCs and NOx during summer in a typical industrial city in China. The OBM model results were coupled with a receptor model to analyze the sources of O3. Higher concentrations of O3 precursors were observed during polluted periods indicating that precursor accumulation contributed to the higher maxima of the net ozone formation rate and HOx concentrations. Analyses of ROx· budgets and relative incremental reactivity (RIR) indicated that O3 production is in a chemical transition regime and was sensitive to both VOCs and NOx. Results from Positive Matrix Factorization (PMF) analysis indicated that gasoline vehicle emissions, industrial processes, and coal combustion were major sources of O3 precursors. The sensitivities of O3 production to these sources depend on if both VOC and NOx sensitivities are considered. If only VOCs sensitivity is considered, in contrast, the contribution of anthropogenic sources to O3 production was significantly underestimated. This study highlights the importance of accounting for both VOCs and NOx sensitivities when O3 chemistry is in a transition regime in O3 production attribution studies.
ABSTRACT
In this paper, the effect of three monocarboxylic acids on MIL-125 synthesis was systematically investigated and the results were discussed in detail. X-ray diffractometry (XRD) and nitrogen adsorption-desorption curves indicated that small molecule acids (acetic acid, propionic acid and butyric acid) affected the morphology of MIL-125 and induced lamellar pores and structural defects in the crystals. Thermogravimetric measurements confirmed the presence of acid-regulated defective metal-organic frameworks (MOFs). Electrochemical tests and density function theory calculations indicated that acid modulation could change the forbidden bandwidth of the material. The acid modification strategy effectively promoted the transfer of photogenerated electrons and enhanced the adsorption and activation of O2 and H2O molecules, generating reactive radicals. The modified MOFs also showed excellent performance in the removal of mixed toluene and chlorobenzene. The degradation pathways of the mixture were analyzed by in situ infrared (IR) and gas chromatography-mass spectrometry (GC-MS). The mixture was converted to chlorophenolic intermediates in the presence of reactive oxygen species, further decomposed to form ethers and ethanol, and finally formed small molecules such as carbon dioxide and water. A feasible method was provided for the preparation of photocatalysts for the treatment of mixed VOCs.
ABSTRACT
Irregular Li deposition is the major reason for poor reversibility and cycle instability in Li metal batteries, even leading to safety hazards, the causes of which have been extensively explored. The structural disconnection induced by completely dissolving Li in the traditional testing protocol is a key factor accounting for irregular Li growth during the subsequent deposition process. Herein, the critical role played by the structural connectivity of electrochemical Li reservoir in subsequent Li deposition behaviors is elucidated and a morphology-performance correlation is established. The structural connection and resultant well-distributed morphology of the in situ electrochemical Li reservoir ensure efficient electron transfer and Li+ diffusion pathway, finally leading to homogenized Li nucleation and growth. Tailoring the geometry of Li reservoir can improve the coulombic efficiency and cyclability of anode-free Li metal batteries by optimizing Li deposition behavior.
ABSTRACT
AIMS/INTRODUCTION: Type 2 diabetes triggers an inflammatory response that can damage red blood cells. M2 macrophages have inhibitory effects on inflammation, and play an important role in tissue damage repair and fibrosis. Autologous blood transfusion has the potential to inhibit red blood cell damage by mediating macrophage polarization. MATERIALS AND METHODS: Swiss mice were used to establish a suitable type 2 diabetes model, and autologous blood transfusion was carried out. The mice were killed, the blood of the mice was collected and CD14+ monocytes were sorted. The expression levels of phenotypic molecules CD16, CD32 and CD206 in CD14+ monocytes were analyzed by flow cytometry. The proportion of M1 and M2 macrophages were analyzed by flow cytometry. The Q value, P50 , 2,3-diphosphoglycerate and Na+ -K+ -ATPase of red blood cells were detected. The red blood cell osmotic fragility test analyzed the red blood cell osmotic fragility. Western blot analysis was used to analyze the expression changes of erythrocyte surface membrane proteins or transporters erythrocyte membrane protein band 4.1, sphingosine-1-phosphate, glycolipid transfer protein and signal peptide peptidase-like 2A. RESULTS: Autologous blood transfusion induced a significant increase in the number of macrophages. The state and capacity of blood cells improved with autologous blood transfusion. Reinfusion of fresh autologous blood in type 2 diabetes mice made erythrocytes shrink. The expression of erythrocyte-related proteins proved that the erythrocyte injury in the reinfusion of fresh autologous blood + type 2 diabetes group was significantly reduced. CONCLUSION: The reinfusion of fresh autologous blood into the body of patients with type 2 diabetes can induce macrophage polarization to M2, thereby inhibiting red blood cell damage.
Subject(s)
Diabetes Mellitus, Type 2 , Humans , Mice , Animals , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Diabetes Mellitus, Type 2/metabolism , Monocytes/metabolism , Macrophages/metabolism , Erythrocytes , Inflammation/metabolismABSTRACT
Platelets have long been recognized as key players in hemostasis and thrombosis; however, there is growing evidence that they are also involved in cancer. Preclinical and clinical studies have shown that platelets can promote tumorigenesis and metastasis through various crosstalks between platelets and cancer cells. Platelets play an active role in all stages of tumorigenesis, including tumor growth, tumor cell extravasation, and metastasis. In addition, thrombocytosis in cancer patients is associated with poor patient survival. Platelets are also well-placed to coordinate local and distant tumor-host interactions due to the a- bundance of microparticles and exosomes. Therefore, antitumor drugs targeting platelets have great development and application prospects. The following will review the research progress of anti-tumor drugs targeting platelets.
ABSTRACT
Aflatoxin B1 (AFB1) is an inevitable contaminant in animal feed and agricultural products, which seriously threatens the health of animals. However, there is currently no better diagnostic tool available than depending on clinical symptoms, pathophysiology, biochemical indicators, etc. Here, we profiled the fecal microbiomes of sheep exposed to and not exposed to AFB1 to identify potential non-invasive biomarkers of AFB1 intoxication by 16S rRNA gene sequencing technology, while measuring serum biochemical indexes. The results showed that the sheep exposed to AFB1 had significantly higher levels of the liver function indicators ALT (alanine transaminase) and AST (aspartate aminotransferase), and their microbial profiles were different from those of the CON (Control) group. In detail, the relative abundance of seven phyla and three genera were overrepresented in the AFB1 group from top 10 relative abundance. Importantly, we found that Prevotella and Bifidobacterium were significantly different in the CON and AFB1 groups (p = 0.032 and p = 0.021, respectively) based on linear discriminant analysis effect size (LEfSe) and random forest analysis. Additionally, the area under curve (AUC) of ALT was 1 (95% CI 1.00-1.00; p < 0.001) and that of Bifidobacterium was 0.95 (95% CI 0.81-1.00; p = 0.0275), suggesting that Bifidobacterium correlated with ALT (r = 0.783, p < 0.01) may be a potential biomarker for AFB1 exposure in sheep.
ABSTRACT
Technical advances in biotechnology have greatly accelerated the development of bottom-up synthetic biology. Unlike top-down approaches, bottom-up synthetic biology focuses on the construction of a minimal cell from scratch and the application of these principles to solve challenges. Cell-free protein synthesis (CFPS) systems provide minimal machinery for transcription and translation, from either a fractionated cell lysate or individual purified protein elements, thus speeding up the development of synthetic cell projects. In this review, we trace the history of the cell-free technique back to the first in vitro fermentation experiment using yeast cell lysate. Furthermore, we summarized progresses of individual cell mimicry modules, such as compartmentalization, gene expression regulation, energy regeneration and metabolism, growth and division, communication, and motility. Finally, current challenges and future perspectives on the field are outlined.
Subject(s)
Artificial Cells , Synthetic Biology , Synthetic Biology/methods , Biotechnology/methods , Cell-Free System/metabolism , Artificial Cells/metabolismABSTRACT
Aqueous rechargeable zinc-based batteries (ZBBs) are emerging as desirable energy storage systems because of their high capacity, low cost, and inherent safety. However, the further application of ZBBs still faces many challenges, such as the issues of uncontrolled dendrite growth and severe parasitic reactions occurring at the Zn anode. Herein, an amino-grafted bacterial cellulose (NBC) film is prepared as artificial solid electrolyte interphase (SEI) for the Zn metal anodes, which can significantly reduce zinc nucleation overpotential and lead to the dendrite-free deposition of Zn metal along the (002) crystal plane more easily without any external stimulus. More importantly, the chelation between the modified amino groups and zinc ions can promote the formation of an ultra-even amorphous SEI upon cycling, reducing the activity of hydrate ions, and inhibiting the water-induced side reactions. As a result, the Zn||Zn symmetric cell with NBC film exhibits lower overpotential and higher cyclic stability. When coupled with the V2 O5 cathode, the practical pouch cell achieves superior electrochemical performance over 1000 cycles.
ABSTRACT
BACKGROUND: To study the link between macrophage polarization, PUM1/Cripto-1 pathway and ferroptosis in the allogeneic blood transfusion setting. METHODS: This is an exploratory research. The purpose of this study was to investigate the effect of PUM1/Cripto-1 pathway on ferroptosis by regulating macrophage polarization in allogeneic blood transfused mice. Establish in vitro cell models and in vivo rat models. To find out whether PUM1 and Cripto-1 were expressed, RT-qPCR and Western blot analyses were employed. The macrophage polarization markers iNOS, TNF-, IL-1, IL-6, Arg-1, and IL-10 were utilized to identify M1 and M2 macrophages. JC-1 staining was used to detect ATP membrane potential in peripheral blood macrophages. RESULTS: In animal experiments, expression of Cripto-1 was negatively regulated by PUM1 and promoted M1 type polarization of macrophages. Allogeneic blood transfusion assured good state of macrophage mitochondria. Allogeneic blood transfusion inhibited ferroptosis in macrophages by affecting the PUM1/Cripto-1 pathway. In cell experiments, PUM1 regulated Cripto-1 in mouse macrophage RAW264.7. Polarization of RAW264.7 cells was regulated by the PUM1/Cripto-1 pathway. The effect of PUM1/Cripto-1 pathway on macrophage ferroptosis in cell experiments was consistent with that in animal experiments. CONCLUSIONS: In this study, through in vivo cell experiments and in vitro animal experiments, it was successfully proved that PUM1/Cripto-1 pathway affected ferroptosis by regulating macrophage polarization in allogeneic blood transfused mice.
Subject(s)
Ferroptosis , Hematopoietic Stem Cell Transplantation , Mice , Rats , Animals , Macrophages/metabolism , RAW 264.7 Cells , Intercellular Signaling Peptides and Proteins/metabolism , Blood TransfusionABSTRACT
Despite the physiological significance of effective CO2 diffusion across biological membranes, the underlying mechanism behind this process is not yet resolved. Particularly debatable is the existence of CO2-permeable aquaporins. The lipophilic characteristic of CO2 should, according to Overton's rule, result in a rapid flux across lipid bilayers. However, experimental evidence of limited membrane permeability poses a challenge to this idea of free diffusion. In this review, we summarized recent progress with regard to CO2 diffusion, and discussed the physiological effects of altered aquaporin expression, the molecular mechanisms of CO2 transport via aquaporins, and the function of sterols and other membrane proteins in CO2 permeability. In addition, we highlight the existing limits in measuring CO2 permeability and end up with perspectives on resolving such argument either by determining the atomic resolution structure of CO2 permeable aquaporins or by developing new methods for measuring permeability.
ABSTRACT
The rapid development of synthetic biology has enabled the production of compounds with revolutionary improvements in biotechnology. DNA manipulation tools have expedited the engineering of cellular systems for this purpose. Nonetheless, the inherent constraints of cellular systems persist, imposing an upper limit on mass and energy conversion efficiencies. Cell-free protein synthesis (CFPS) has demonstrated its potential to overcome these inherent constraints and has been instrumental in the further advancement of synthetic biology. Via the removal of the cell membranes and redundant parts of cells, CFPS has provided flexibility in directly dissecting and manipulating the Central Dogma with rapid feedback. This mini-review summarizes recent achievements of the CFPS technique and its application to a wide range of synthetic biology projects, such as minimal cell assembly, metabolic engineering, and recombinant protein production for therapeutics, as well as biosensor development for in vitro diagnostics. In addition, current challenges and future perspectives in developing a generalized cell-free synthetic biology are outlined.
ABSTRACT
Mycotoxin contamination has become one of the biggest hidden dangers of food safety, which seriously threatens human health. Understanding the mechanisms by which mycotoxins exert toxicity is key to detoxification. Ferroptosis is an adjustable cell death characterized by iron overload and lipid reactive oxygen species (ROS) accumulation and glutathione (GSH) depletion. More and more studies have shown that ferroptosis is involved in organ damage from mycotoxins exposure, and natural antioxidants can alleviate mycotoxicosis as well as effectively regulate ferroptosis. In recent years, research on the treatment of diseases by Chinese herbal medicine through ferroptosis has attracted more attention. This article reviews the mechanism of ferroptosis, discusses the role of ferroptosis in mycotoxicosis, and summarizes the current status of the regulation of various mycotoxicosis through ferroptosis by Chinese herbal interventions, providing a potential strategy for better involvement of Chinese herbal medicine in the treatment of mycotoxicosis in the future.
ABSTRACT
Aflatoxin B1 (AFB1) is a common mycotoxin that widely occurs in feed and has severe hepatotoxic effects both in humans and animals. Total flavonoids of Rhizoma Drynaria (TFRD), a traditional Chinese medicinal herb, have multiple biological activities and potential hepatoprotective activity. This study investigated the protective effects and potential mechanisms of TFRD against AFB1-induced liver injury. The results revealed that supplementation with TFRD markedly lessened broiler intestinal permeability by increasing the expression of intestinal tight junction proteins, as well as correcting the changes in gut microbiota and liver damage induced by AFB1. Metabolomics analysis revealed that the alterations in plasma metabolites, especially taurolithocholic acid, were significantly improved by TFRD treatment in AFB1-exposed chickens. In addition, these metabolites were closely associated with [Ruminococcus], ACC, and GPX1, indicating that AFB1 may cause liver injury by inducing bile acid metabolism involving the microbiota-gut-liver axis. We further found that TFRD treatment markedly suppressed oxidative stress and hepatic lipid deposition, increased plasma glutathione (GSH) concentrations, and reversed hepatic ferroptosis gene expression. Collectively, these findings indicate that ferroptosis might contribute to the hepatotoxicity of AFB1-exposed chickens through the microbiota-gut-liver axis interaction mechanisms; furthermore, TFRD was confirmed as an herbal extract that could potentially antagonize mycotoxins detrimental effects.