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The structure of solvated Li+ has a significant influence on the electrolyte/electrode interphase (EEI) components and desolvation energy barrier, which are two key factors in determining the Li+ diffusion kinetics in lithium metal batteries. Herein, the "solvent activity" concept is proposed to quantitatively describe the correlation between the electrolyte elements and the structure of solvated Li+. Through fitting the correlation of the electrode potential and solvent concentration, we suggest a "low-activity-solvent" electrolyte (LASE) system for deriving a stable inorganic-rich EEI. Nano LiF particles, as a model, were used to capture free solvent molecules for the formation of a LASE system. This advanced LASE not only exhibits outstanding antidendrite growth behavior but also delivers an impressive performance in Li/LiNi0.8Co0.1Mn0.1O2 cells (a capacity of 169 mAh g-1 after 250 cycles at 0.5 C).
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In this paper, a 1 × 2 photonic switch is designed based on a silicon-on-insulator (SOI) platform combined with the phase change material (PCM), Sb2S3, assisted by the direct binary search (DBS) algorithm. The designed photonic switch exhibits an impressive operating bandwidth ranging from 1450 to 1650 nm. The device has an insertion loss (IL) from 0.44 dB to 0.70 dB (of less than 0.7 dB) and cross talk (CT) from -26 dB to -20 dB (of less than -20 dB) over an operating bandwidth of 200 nm, especially an IL of 0.52 dB and CT of -24 dB at 1550 nm. Notably, the device is highly compact, with footprints of merely 3 × 4 µm2. Furthermore, we have extended the device's functionality for multifunctional operation in the C-band that can serve as both a 1 × 2 photonic switch and a 3 dB photonic power splitter. In the photonic switch mode, the device demonstrates an IL of 0.7 dB and a CT of -13.5 dB. In addition, when operating as a 3 dB photonic power splitter, the IL is less than 0.5 dB.
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BACKGROUND: Abnormal activation of FAK is associated with tumor development and metastasis. Through interactions with other intracellular signalling molecules, FAK influences cytoskeletal remodelling, modulation of adhesion signalling, and activation of transcription factors, promoting migration and invasion of tumor cells. However, the exact mechanism that regulates these processes remains unresolved. Herein, our findings indicate that the S-palmitoylation of FAK is crucial for both its membrane localization and activation. METHODS: The palmitoylation of FAK in U251 and T98G cells was assessed by an acyl-PEG exchange (APE) assay and a metabolic incorporation assay. Cellular palmitoylation was inhibited using 2-bromopalmitate, and the palmitoylation status and cellular localization of FAK were determined. A metabolic incorporation assay was used to identify the potential palmitoyl acyltransferase and the palmitoylation site of FAK. Cell Counting Kit-8 (CCK8) assays, colony formation assays, and Transwell assays were conducted to assess the impact of ZDHHC5 in GBM. Additionally, intracranial GBM xenografts were utilized to investigate the effects of genetically silencing ZDHHC5 on tumor growth. RESULTS: Inhibiting FAK palmitoylation leads to its redistribution from the membrane to the cytoplasm and a decrease in its phosphorylation. Moreover, ZDHHC5, a protein-acyl-transferase (PAT), catalyzes this key modification of FAK at C456. Knockdown of ZDHHC5 abrogates the S-palmitoylation and membrane distribution of FAK and impairs cell proliferation, invasion, and epithelial-mesenchymal transition (EMT). Taken together, our research reveals the crucial role of ZDHHC5 as a PAT responsible for FAK S-palmitoylation, membrane localization, and activation. CONCLUSIONS: These results imply that targeting the ZDHHC5/FAK axis has the potential to be a promising strategy for therapeutic interventions for glioblastoma (GBM). Video Abstract.
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Glioblastoma , Glioma , Humanos , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Glioblastoma/metabolismo , Glioma/patologia , Lipoilação , Transdução de SinaisRESUMO
In recent decades, nucleic acid self-assemblies have emerged as popular nanomaterials due to their programmable and robust assembly, prescribed geometry, and versatile functionality. However, it remains a challenge to purify large quantities of DNA nanostructures or DNA-templated nanocomplexes for various applications. Commonly used purification methods are either limited by a small scale or incompatible with functionalized structures. To address this unmet need, we present a robust and scalable method of purifying DNA nanostructures by Sepharose resin-based size exclusion. The resin column can be manually packed in-house with reusability. The separation is driven by a low-pressure gravity flow in which large DNA nanostructures are eluted first followed by smaller impurities of ssDNA and proteins. We demonstrated the efficiency of the method for purifying DNA origami assemblies and protein-immobilized DNA nanostructures. Compared to routine agarose gel electrophoresis that yields 1 µg or less of purified products, this method can purify â¼100-1000 µg of DNA nanostructures in less than 30 min, with the overall collection yield of 50-70% of crude preparation mixture. The purified nanocomplexes showed more precise activity in evaluating enzyme functions and antibody-triggered activation of complement protein reactions.
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Biosensors are currently among the most commonly used devices for analysing biomarkers and play an important role in environmental detection, food safety, and disease diagnosis. Researchers have developed multimodal biosensors instead of single-modal biosensors to meet increasing sensitivity, accuracy, and stability requirements. Metal nanoparticles (MNPs) are beneficial for preparing core probes for multimodal biosensors because of their excellent physical and chemical properties, such as easy regulation and modification, and because they can integrate diverse sensing strategies. This review mainly summarizes the excellent physicochemical properties of MNPs applied as biosensing probes and the principles of commonly used MNP-based multimodal sensing strategies. Recent applications and possible improvements of multimodal biosensors based on MNPs are also described, among which on-site inspection and sensitive detection are particularly important. The current challenges and prospects for multimodal biosensors based on MNPs may provide readers with a new perspective on this field.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , HumanosRESUMO
In this work, the threshold photoionization cross sections from the excited states of lutetium and ytterbium atoms were investigated by the laser pump-probe scheme under the condition of saturated resonant excitation. We obtained the resonance enhanced multiphoton ionization spectra of the lutetium and ytterbium atoms of the lanthanide metals in the range of 307.50-312.50 nm and 265.00-269.00 nm, respectively; the photoionization cross sections of the 5d6s(1D)6p(2D05/2) and 5d6s(3D)6p(2P01/2) states of lutetium and the 4f13(2F0)5d6s2(J = 1) states of ytterbium above threshold regions (0.4-1.6 eV) were measured, and measured values ranged from 2.3 ± 0.2 to 17.7 ± 1.5 Mb.
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In this paper, an age-structured predator-prey system with Beddington-DeAngelis (B-D) type functional response, prey refuge and harvesting is investigated, where the predator fertility function f(a) and the maturation function ß ( a ) are assumed to be piecewise functions related to their maturation period τ . Firstly, we rewrite the original system as a non-densely defined abstract Cauchy problem and show the existence of solutions. In particular, we discuss the existence and uniqueness of a positive equilibrium of the system. Secondly, we consider the maturation period τ as a bifurcation parameter and show the existence of Hopf bifurcation at the positive equilibrium by applying the integrated semigroup theory and Hopf bifurcation theorem. Moreover, the direction of Hopf bifurcation and the stability of bifurcating periodic solutions are studied by applying the center manifold theorem and normal form theory. Finally, some numerical simulations are given to illustrate of the theoretical results and a brief discussion is presented.
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FertilidadeRESUMO
As agents in an emerging technology, Hermetia illucens (Linnaeus, 1758) (Diptera: Stratiomyidae) larvae, black soldier fly, have shown exciting potential for degrading antibiotics in organic solid waste, a process for which gut microorganisms play an important role. This study investigated the characteristics of larval gut bacterial communities effected by typical antibiotics. Initially, antibiotics significantly reduced the diversity of gut bacterial species. After 8 days, diversity recovered to similar to that of the control group in the chlortetracycline, tylosin, and sulfamethoxazole groups. Proteobacteria, Firmicutes, and Actinobacteriota were the dominant phyla at the initial BSFL gut. However, after 4 days treatment, the proportion of Actinobacteriota significantly decreased, but Bacteroidota notably increased. During the conversion process, 18, 18, 17, 21, and 19 core genera were present in the chlortetracycline, sulfamethoxazole, tylosin, norfloxacin, and gentamicin groups, respectively. Pseudomonas, Actinomyces, Morganella, Providencia and Klebsiella might be the important genera with extraordinary resistance and degradation to antibiotics. Statistical analyses of COGs showed that antibiotics changed the microbial community functions of BSFL gut. Compared with the control group, (i) the chlortetracycline, sulfamethoxazole, and tylosin groups showed significant increase in the classification functions of transcription, RNA processing and modificationï¼and so on, (ii) the norfloxacin and gentamicin groups showed significant increase in defense mechanisms and other functions. Note that we categorized the response mechanisms of these classification functions to antibiotics into resistance and degradation. This provides a new perspective to deeply understand the joint biodegradation behavior of antibiotics in environments, and serves as an important reference for further development and utilization of microorganisms-assisted larvae for efficient degradation of antibiotics.
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Clortetraciclina , Dípteros , Microbioma Gastrointestinal , Animais , Dípteros/fisiologia , Larva , Antibacterianos/farmacologia , Norfloxacino , Tilosina , Bactérias , Sulfametoxazol , GentamicinasRESUMO
Digital industrialization represented by big data provides substantial support for the high-quality development of the digital economy, but its impact on urban energy conservation development requires further research. To this end, based on the panel data of Chinese cities from 2010 to 2019 and taking the establishment of the national big data comprehensive pilot zone (NBDCPZ) as a quasi-natural experiment, this paper explores the impact, mechanism, and spatial spillover effect of digital industrialization represented by big data on urban energy conservation development using the Difference-in-Differences (DID) method. The results show that digital industrialization can help achieve urban energy conservation development, which still holds after a series of robustness tests. Mechanism analysis reveals that digital industrialization impacts urban energy conservation development by driving industrial sector output growth, promoting industrial upgrading, stimulating green technology innovation, and alleviating resource misallocation. Heterogeneity analysis indicates that the energy conservation effect of digital industrialization is more significant in the central region, intra-regional demonstration comprehensive pilot zones, large cities, non-resource-based cities, and high-level digital infrastructure cities. Additionally, digital industrialization can promote energy conservation development in neighboring areas through spatial spillover effect. This paper enriches the theoretical framework concerning the relationship between digital industrialization and energy conservation development. The findings have significant implications for achieving the coordinated development of digitalization and conservation.
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Currently, pancreatic cancer (PC) is one of the most lethal malignant tumors. PC is typically diagnosed at a late stage, exhibits a poor response to conventional treatment, and has a bleak prognosis. Unfortunately, PC's survival rate has not significantly improved since the 1960s. Cancer-associated fibroblasts (CAFs) are a key component of the pancreatic tumor microenvironment (TME). They play a vital role in maintaining the extracellular matrix and facilitating the intricate communication between cancer cells and infiltrated immune cells. Exploring therapeutic approaches targeting CAFs may reverse the current landscape of PC therapy. In recent years, nano-drug delivery systems have evolved rapidly and have been able to accurately target and precisely release drugs with little or no toxicity to the whole body. In this review, we will comprehensively discuss the origin, heterogeneity, potential targets, and recent advances in the nano-drug delivery system of CAFs in PC. We will also propose a novel integrated treatment regimen that utilizes a nano-drug delivery system to target CAFs in PC, combined with radiotherapy and immunotherapy. Additionally, we will address the challenges that this regimen currently faces.
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Fibroblastos Associados a Câncer , Neoplasias Pancreáticas , Humanos , Sistemas de Liberação de Fármacos por Nanopartículas , Neoplasias Pancreáticas/tratamento farmacológico , Imunoterapia , Pâncreas , Microambiente TumoralRESUMO
This study proposes a dual-coil magnetorheological torsional vibration damper (MRTVD) and verifies the effectiveness of semi-active damping control to suppress the shaft system's torsional vibration via experimental research. Firstly, the mechanical model of the designed MRTVD and its coupling mechanical model with the rotating shaft system are established. Secondly, the torsional response of the shaft system is obtained via resonance experiments, and the influence of the current on the torsional characteristics of the magnetorheological torsional damper is analyzed. Finally, the MRTVD is controlled using the skyhook control approach. The experimental results demonstrate that when the main shaft passes through the critical speed range at various accelerations, the amplitude of the shaft's torsional vibration decreases by more than 15%, and the amplitude of the shaft's torsional angular acceleration decreases by more than 22%. These conclusions validate the inhibitory effect of MRTVD on the main shaft's torsional vibrations under skyhook control.
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The contamination of microplastics in terrestrial geoenvironment (CMTG) is widespread and severe and has, received considerable attention. However, studies on CMTG are in their initial stages. The literature on CMTG published in the past decade was analyzed through bibliometric analysis, such as the annual publications, countries with the highest contributions, prolific authors, and author keywords. The sources, compositions, migrations and environmental impacts of CMTG are summarized, and possible future directions are proposed. This study analyzed the annual publications, countries with the highest contributions, prolific authors, and author keywords related to microplastics. The results demonstrated that 15,306 articles were published between 2014 and 2023. China is the leading country in terms of the total number of publications. The main sources of CMTG include landfills, agricultural non-point sources, sewage treatment systems and transportation systems. The composition of the CMTG exhibits significantly temporal and spatial variability from different sources. The migration paths of the CMTG were within the soil, groundwater seepage and wind transportation of suspended particles. Microplastics increase soil cohesion, decrease porosity, reduce pore scale, decrease air circulation, and increase water retention capacity, and the exudation of highly water-soluble additives in microplastics can cause secondary contamination of geological entities. Microplastics have an adverse effect on plant growth, animal digestion, microbial activity, energy and lipid metabolism, oxidative stress, and respiratory diseases in humans. It is recommended to develop more efficient and convenient quantitative testing methods for microplastics, formulate globally harmonized testing and evaluation standards, include microplastic testing in testing programs for contaminated soils, and develop efficient methods for the remediation of microplastic contaminated geological bodies.
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Modern Mars is bipolar, cold, and oxidizing, while early Mars was characterized by icy highlands, episodic warmth and reducing atmosphere. The timing and association of the climate and redox transitions remain inadequately understood. Here we examine the spatiotemporal distribution of the low surface iron abundance in the ancient Martian terrains, revealing that iron abundance decreases with elevation in the older Noachian terrains but with latitude in the younger Noachian terrains. These observations suggest: (a) low-temperature conditions contribute to surface iron depletion, likely facilitated by anoxic leaching through freeze-thaw cycles under a reducing atmosphere, and (b) temperature distribution mode shifted from elevation-dominant to latitude-dominant during the Noachian period. Additionally, we find iron leaching intensity decreases from the Early to Late Noachian epoch, suggesting a gradual atmospheric oxidation coupled with temperature mode transition during the Noachian period. We think atmospheric oxidation led to Mars becoming cold and bipolar in its early history.
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Non-thermal atmospheric plasma (NTAP) has been proven to be an effective anti-tumor tool, with various biological effects such as inhibiting tumor proliferation, metastasis, and promoting tumor cell apoptosis. At present, the main conclusion is that ROS and RNS are the main effector components of NTAP, but the mechanisms of which still lack systematic summary. Therefore, in this review, we first summarized the mechanism by which NTAP directly or indirectly causes an increase in intracellular RONS concentration, and the multiple pathways dysregulation (i.e. NRF2, PI3K, MAPK, NF-κB) induced by intracellular RONS. Then, we generalized the relationship between NTAP induced pathways dysregulation and the various biological effects it brought. The summary of the anti-tumor mechanism of NTAP is helpful for its further research and clinical transformation.
Non-thermal atmospheric plasma (NTAP) acts on NADPH oxidase and catalase.The feeding gas and parameters of NTAP affect its impacts on the signaling pathways.The impacts of NTAP and RONS on pathways are not always consistent.NTAP can trigger various anti-tumor biological effects.
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Gases em Plasma , Transdução de Sinais , Humanos , Gases em Plasma/farmacologia , Neoplasias/metabolismo , Neoplasias/patologia , Espécies Reativas de Nitrogênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Animais , Espécies Reativas de Oxigênio/metabolismoRESUMO
Plateau zokor (Eospalax baileyi) is a subterranean rodent and seasonal breeder. During the non-breeding season, the testicles regress, leading to the arrest of spermatogenesis and loss of fertility. The identification of the specific germ cell type at which spermatogenesis is arrested, as well as potential regulatory factors during the non-breeding season, is important for understanding seasonal spermatogenesis in subterranean species. This study analyzed genes in spermatocytes of plateau zokor by referring to single-cell RNA results in mice. We discovered that spermatogenesis is arrested at the spermatocyte during the non-breeding season, which was corroborated via immunofluorescence staining results. The analysis of gene expression during different stages of meiotic prophase I has revealed that germ cell development may be arrested, starting from zygonema, during the non-breeding season. Meanwhile, we discovered that the apoptosis genes were up-regulated, leading to apoptosis in spermatocytes. To confirm that the germ cell differentiation was blocked during the non-breeding season due to a decrease in the androgen level, we used androgen receptor antagonist (flutamide) to intervene in the breeding season and found that the inner diameter of the seminiferous tubules was significantly reduced, spermatogenesis was arrested, and spermatocytes underwent apoptosis. This study revealed that spermatocytes are the terminal of germ cell differentiation in plateau zokor during the non-breeding season and that the arrest of differentiation is attributed to a decline in androgen levels. Our results complement the theoretical basis of seasonal reproduction in plateau zokor.
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This study synthesized five phenolic acid-chitosan copolymers utilizing the carbodiimide-mediated chemical crosslinking reaction. Comprehensive evaluations were conducted on their structural attributes, physicochemical properties, and biological activities. Fourier transform infrared confirmed successful grafting of phenolic acids onto chitosan via amide linkages. Additionally, ultraviolet-visible absorption spectroscopy and proton nuclear magnetic resonance analyses revealed novel absorption peaks between 200 and 400 nm and 6.0-8.0 ppm, respectively, attributable to the incorporated phenolic acids. Notably, the chitosan-gentisate acid copolymer exhibited significantly enhanced biological activity (p < 0.05) compared to pure chitosan and the other four conjugates, attributed to its highest grafting degree of approximately 295.93 mg/g. These modified chitosan derivatives effectively preserved the quality of sea bass (Lateolabrax japonicus) during refrigerated storage, extending its shelf-life by up to 9 days, 7 days, and 4 days relative to control, chitosan, and gentisate acid groups.
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Bass , Quitosana , Animais , Quitosana/química , Gentisatos , Hidroxibenzoatos/química , Polímeros/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The tumor immune microenvironment (TIME) can limit the effectiveness and often leads to significant side effects of conventional cancer therapies. Consequently, there is a growing interest in identifying novel targets to enhance the efficacy of targeted cancer therapy. More research indicates that tumor-associated macrophages (TAMs), originating from peripheral blood monocytes generated from bone marrow myeloid progenitor cells, play a crucial role in the tumor microenvironment (TME) and are closely associated with resistance to traditional cancer therapies. Lipid metabolism alterations have been widely recognized as having a significant impact on tumors and their immune microenvironment. Lipids, lipid derivatives, and key substances in their metabolic pathways can influence the carcinogenesis and progression of cancer cells by modulating the phenotype, function, and activity of TAMs. Therefore, this review focuses on the reprogramming of lipid metabolism in cancer cells and their immune microenvironment, in which the TAMs are especially concentrated. Such changes impact TAMs activation and polarization, thereby affecting the tumor cell response to treatment. Furthermore, the article explores the potential of targeting the lipid metabolism of TAMs as a supplementary approach to conventional cancer therapies. It reviews and evaluates current strategies for enhancing efficacy through TAMs' lipid metabolism and proposes new lipid metabolism targets as potential synergistic options for chemo-radiotherapy and immunotherapy. These efforts aim to stimulate further research in this area.
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Metabolismo dos Lipídeos , Neoplasias , Microambiente Tumoral , Macrófagos Associados a Tumor , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/metabolismo , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Animais , Imunoterapia/métodosRESUMO
BACKGROUND: Systemic and pulmonary coagulopathy and inflammation are important characteristics of transfusion-related acute lung injury (TRALI). Whether microparticles that accumulate in transfused red blood cell concentrates (RBCs) have proinflammatory and procoagulant potential and contribute to adverse reactions of RBC transfusions is unclear. AIM: To investigate the ability of microparticles in stored RBCs to promote thrombin generation and induce human pulmonary microvascular endothelial cell (HMVEC) activation and damage. METHODS: The number and size of microparticles were determined by flow cytometric and nanoparticle tracking analyses, respectively. Thrombin generation and the intrinsic coagulation pathway were assayed by a calibrated automated thrombogram and by measuring activated partial thromboplastin time (aPTT), respectively. The expression of ICAM-1 and the release of cytokines by endothelial cells were detected by flow cytometric analyses. HMVEC damage was assessed by incubating lipopolysaccharide-activated endothelial cells with MP-primed polymorphonuclear neutrophils (PMNs). RESULTS: The size of the microparticles in the RBC supernatant was approximately 100-300 nm. Microparticles promoted thrombin generation in a dose-dependent manner and the aPTT was shortened. Depleting microparticles from the supernatant of RBCs stored for 35 days by either filtration or centrifugation significantly decreased the promotion of thrombin generation. The expression of ICAM-1 on HMVECs was increased significantly by incubation with isolated microparticles. Furthermore, microparticles induced the release of interleukin-6 (IL-6) and interleukin-8 (IL-8) from HMVECs. Microparticles induced lipopolysaccharide-activated HMVEC damage by priming PMNs, but this effect was prevented by inhibiting the PMNs respiratory burst with apocynin. CONCLUSION: Microparticles in stored RBCs promote thrombin generation, HMVEC activation and damage which may be involved in TRALI development.
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Traditional antibiotics are facing a tremendous challenge due to increased antimicrobial resistance; hence, there is an urgent need to find novel antibiotic alternatives. Milk protein-derived antimicrobial peptides (AMPs) are currently attracting substantial attention considering that they showcase an extensive spectrum of antimicrobial activities, with slower development of antimicrobial resistance and safety of raw materials. This review summarizes the molecular properties, and activity mechanisms and highlights the applications and limitations of AMPs derived from milk proteins comprehensively. Also the analytical technologies, especially bioinformatics methodologies, applied in the process of screening, identification, and mechanism illustration of AMPs were underlined. This review will give some ideas for further research and broadening of the applications of milk protein-derived AMPs in the food field.
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Peptídeos Catiônicos Antimicrobianos , Peptídeos Antimicrobianos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Antibacterianos/farmacologia , Proteínas do LeiteRESUMO
INTRODUCTION: Antimicrobial peptides (AMPs) are small-molecule peptides with a unique antimicrobial mechanism. Other notable biological activities of AMPs, including anti-inflammatory, angiogenesis, and bone formation effects, have recently received widespread attention. These remarkable bioactivities, combined with the unique antimicrobial mechanism of action of AMPs, have led to their increasingly important role in bone regeneration. AREAS COVERED: In this review, on the one hand, we aimed to summarize information about the AMPs that are currently used for bone regeneration by reviewing published literature in the PubMed database. On the other hand, we also highlight some AMPs with potential roles in bone regeneration and their possible mechanisms of action. EXPERT OPINION: The translation of AMPs to the clinic still faces many problems, but their unique antimicrobial mechanisms and other conspicuous biological activities suggest great potential. An in-depth understanding of the structure and mechanism of action of AMPs will help us to subsequently combine AMPs with different carrier systems and perform structural modifications to reduce toxicity and achieve stable release, which may be a key strategy for facilitating the translation of AMPs to the clinic.