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Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Here, we report that PTEN deficiency induced Kruppel-like factor 5 (KLF5) acetylation and that interruption of KLF5 acetylation orchestrated intricate interactions between cancer cells and CAFs that enhance FGF receptor 1 (FGFR1) signaling and promote tumor growth. Deacetylated KLF5 promoted tumor cells to secrete TNF-[alpha], which stimulated inflammatory CAFs to release FGF9. CX3CR1 inhibition blocked FGFR1 activation triggered by FGF9 and sensitized PTEN- deficient prostate cancer to the AKT inhibitor capivasertib. This study reveals the role of KLF5 acetylation in reprogramming CAFs and provides a rationale for combined therapies using inhibitors of AKT and CX3CR1., Introduction Prostate cancer is the most common cancer and the second leading cause of cancer-related death in men in the United States (1). Most prostate cancers are localized and androgen [...]

In the context of human active response to exponentially increasing data volumes, memristors have emerged as a focal point in systematic problem‐solving approaches. Particularly, organic memristors, characterized by excellent scalability, flexibility, and 3D stacking capabilities, have shown its tremendous potential in innovative electronic applications. However, the modulation of molecular assembly and interface interaction at the electrode surface poses a challenging task, despite their crucial role in determining the memristive performance. Herein, a collaborative method involving hydrophobic molecular design and interface engineering is proposed to generate high‐quality nanofilms with optimal photoelectric and electrochemical properties. By subjecting the bottom electrode to O2 plasma treatment and chemical modification using a hydrophobic ionic liquid poly(diallyldimethylammonium) bis(trifluoromethanesulfonyl)imide (PTFSI), the hydrophobic compound DN demonstrates exceptional affinity and stronger intermolecular interactions with the electrode surface. Consequently, the two‐terminal device array comprising Al/DN@PTFSI/ITO exhibits robust non‐volatile write‐once‐read‐many times (WORM) memory behavior, resulting in a tripling production yield from 30% to 92% along with a lower threshold voltage of 1.5 V, higher ON/OFF current ratio of 103 and excellent stability. This study presents a versatile approach to optimize the film assembly and material/electrode interface, thereby accelerating the development of organic memristors toward future applications. [ABSTRACT FROM AUTHOR]

The stable combustion of rotating detonation engines is significantly affected by inlet spatial fluctuation, especially during aircraft maneuvering, necessitating extensive research for further engineering enhancements. This study analyzes the effect of the spatial fluctuation of inlet total pressure on the propagation characteristics and evolution mechanisms of rotating detonation waves. The in-house solver, BYRFoam, based on the OpenFOAM platform, is utilized. The velocity deficit of detonation waves is discussed under the different inlet spatial fluctuations of mean total pressure, instability degree, and spatial frequency. The results indicate that the propagation process of detonation waves is divided into wave mode transition and operating mode-locked stages; the latter consists of the self-adjustment stage, low-frequency instability stage, and dynamic equilibrium stage. A dynamic equilibrium mechanism is proposed, which is the self-adjustment process of detonation waves, counter-rotating shock waves, and striped fresh gas, encompassing the stages of strong and weak detonation. Furthermore, the oscillation phenomenon of the peak pressure, frequency, and velocity of detonation waves is seriously related to spatial fluctuation, leading to instability during detonation wave propagation. The instability phenomenon in this study is compared with the experimental data, providing valuable theoretical support for engineering applications involving rotating detonation engines. [ABSTRACT FROM AUTHOR]

The scarcity of freshwater poses a significant threat to sustainable development and human well-being. Exploring and developing state-of-the-art semipermeable materials for seawater desalination could be a potential solution to address this issue. In this study, we unveil the desalination potential of a newly synthesized multilayer covalent organic framework (COF), named ABBPM, showcasing remarkable water permeance reaching 52 L cm−2 day−1 MPa−1 alongside a NaCl rejection rate of 97%. This outstanding performance can be attributed to the advantageous combination of its large pore size (∼3 nm), wide organic skeleton (∼0.94 nm), and the ordered ABC stacking pattern, which creates tortuous yet express water pathways, significantly enhancing filtration efficiency. Free energy analysis reveals that compared to the energy barriers (∼4 kJ mol−1) faced by water molecules, ions encounter higher energy barriers (∼9 kJ mol−1 to ∼11 kJ mol−1) when traversing the 3L ABBPM membrane, which can be primarily attributed to the broad organic skeleton. Moreover, the translocation velocity of water across the multilayer ABBPM membranes surpasses that observed in nanopores on a single-layer graphene or MoS2. Therefore, this study not only presents the multilayer ABBPM COF as a promising candidate for efficient desalination but also proposes a strategic design approach for layered porous structures, with pore sizes exceeding the diameters of hydrated ions, for desalination technology advancement. [ABSTRACT FROM AUTHOR]

Two-dimensional van der Waals materials, with atomic-level thickness and unique electronic structures, have tremendous potential in electronic device applications, making them highly desirable for research in high-performance non-volatile memory. Here, we report a method for the van der Waals epitaxial growth of air-stable and uniformly distributed thin films of a 1T-CrS2 single crystal, based on a simple chemical vapor deposition technique using a binary metal precursor co-reaction growth mechanism controlled by the evaporation rate of the precursor. The corresponding 1T-CrS2 electronic devices can maintain their electrical performance without degradation for up to one month in air. Based on this, we have constructed a floating-gate memory device with a full van der Waals heterostructure, exhibiting a large storage window ratio (approximately 79%), a high on/off ratio (107), and stability for over 1000 cycles. The device demonstrates excellent multi-level data storage stability and can be optically programmed with stable operation using 532 nm laser pulses, showcasing outstanding optoelectronic storage performance. The excellent electrical stability of these two-dimensional materials, the non-volatile nature of the devices, and the stable multi-level storage characteristics present enormous potential for the integration of high-performance non-volatile memory. [ABSTRACT FROM AUTHOR]

Epicardial adipose tissue (EAT) is a fat reservoir close to the myocardium and visceral pericardium. It has special anatomical and physiological characteristics. The volume and deposition site of EAT are closely related to the occurrence and development of atrial fibrillation (AF). This article discusses the connotation of the traditional Chinese medicine theory, " yang transforming qi and yin shaping up the body", and holds that the essence of abnormal accumulation of EAT is " yang transforming qi deficiency and yin constituting form too much". Yin pathogen gradually accumulates, local yin and yang imbalance occurs, and abnormal secretion occurs. With the extension of time, the intrinsic yang heat is accompanied and becomes increasingly exuberant. Finally, yin is difficult to control yang, resulting in EAT infiltrating normal tissues, inducing and promoting the occurrence and progression of AF. Under the guidance of this theory, when distinguishing the amount of yin and yang between the body and EAT, considering the ability of " yang transforming qi" and " yin constituting form" in the whole and part, the method of supporting yang and eliminating yin should be reasonably selected. At the beginning of the disease, it is mainly to restore " yang transforming qi". By avoiding the accumulation of evil from the yin, it dissipates the body of the yin that has become. When the disease progresses, it is necessary to " eliminate pathogenic factor", supplemented by different treatment methods such as eliminating dampness, activating qi, and promoting blood circulation. Furthermore, the whole course of the disease should take care of the patient's deficiency, pay attention to strengthening yang and tonifying the healthy qi, and eliminate yin and evil promptly to improve clinical efficacy. [ABSTRACT FROM AUTHOR]

Continuous rotating detonation engines have been extensively studied due to their high thermal efficiency. The utilization of solid particles as fuel can effectively reduce costs and enhance detonation performance. We have constructed a compressible gas–solid multimedium flow combustion numerical method, employing the double flux model coupled with fifth-order weighted essentially non-oscillatory and third-order total variation diminishing Runge–Kutta schemes to solve the unsteady multi-component chemical reaction Eulerian–Eulerian equations. Finite-rate methods and surface reaction models are used to simulate the combustion of gaseous mixtures and carbon particles. The effects of the inlet total pressure spatial fluctuations and particle diameter on the flow field characteristics of the continuous rotating detonation engine are investigated. The results indicate that changing the fluctuation period significantly affects the number, propagation direction, and intensity of gas–solid two-phase continuous rotating detonation waves (CRDW). The variation of fluctuation amplitude noticeably alters the combustion characteristics of the two-phase continuous rotating detonation wave, and excessively high amplitudes cannot form continuous rotating detonation waves. Introducing solid particles into fuel significantly mitigates the impact of inlet total pressure spatial fluctuation and promotes propagation stability on the detonation waves. Moreover, when solid particle diameters reach or exceed the micrometer scale, they contribute more favorably to generating a stable detonation flow field. However, excessive particle sizes result in a low surface reaction rate and inadequate contribution of heat released from particle combustion to the propagation of detonation waves. [ABSTRACT FROM AUTHOR]

In this study, we successfully synthesized high-quality 2D layered BiOI crystals using a novel space-confined molten salt method. These crystals exhibit a bandgap of 1.9 eV, closely aligning with theoretical expectations. The photodetectors fabricated from these BiOI nanosheets demonstrate exceptional ultraviolet (UV) detection capabilities. Key performance metrics include an ultrahigh photoresponsivity of 1048 mA W−1, an impressive external quantum efficiency of 420%, and a significant detectivity of 4.7 × 1012 Jones, coupled with a fast response time of 420/690 μs at 310 nm. This study not only highlights the potential of BiOI in UV photodetectors but also marks a substantial advancement in the development of high-performance bismuth-based semiconductor optoelectronic devices. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the present work, acute gastric ulcer models were constructed by administering hydrochloric acid/ethanol. The mice ingested white jade snail secretion (WJSS) through gastric infusion. Ulcer areas in gastric tissue were recorded, and malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. Notably, high‐throughput 16S rDNA analysis of intestinal flora and determination of amino acid composition in feces were performed to understand the effect of WJSS on model mice. RESULTS: Compared with the control group, the ulcer area in the WJSS low‐, medium‐ and high‐concentration groups declined by 28.02%, 39.57% and 77.85%, respectively. MDA content decreased by 24.71%, 49.58% and 64.25%, and SOD relative enzyme activity fell by 28.19%, 43.37% and 9.60%, respectively. The amounts of amino acids in the low‐, medium‐ and high‐concentration groups were slightly lower, and probiotic bacteria such as Bacteroidetes and Lactobacillales increased in different‐concentration WJSS groups. Adding WJSS contributes to the establishment of beneficial intestinal flora and the absorption of amino acids. CONCLUSION: Our results showed that WJSS has a beneficial effect on inhibiting hydrochloric acid–ethanolic gastric ulcers, suggesting that WJSS has excellent potential as a novel anti‐ulcer agent. Combined with ulcer area, MDA content, SOD content, gut probiotics and other indicators, a high concentration of WJSS had the best protective effect on acute gastric ulcer. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Cotton (Gossypium hirsutum L.) is one of the main crops in Uzbekistan, which makes a major contribution to the country's economy. The cotton industry has played a pivotal role in the economic landscape of Uzbekistan for decades, generating employment opportunities and supporting the livelihoods of countless individuals across the country. Therefore, having precise and up-to-date data on cotton cultivation areas is crucial for overseeing and effectively managing cotton fields. Nonetheless, there is currently no extensive, high-resolution approach that is appropriate for mapping cotton fields on a large scale, and it is necessary to address the issues related to the absence of ground-truth data, inadequate resolution, and timeliness. In this study, we introduced an effective approach for automatically mapping cotton fields on a large scale. A crop-type mapping method based on phenology was conducted to map cotton fields across the country. This research affirms the significance of phenological metrics in enhancing the mapping of cotton fields during the growing season in Uzbekistan. We used an adaptive feature-fusion network for crop classification using single-temporal Sentinel-2 images and automatically generated samples. The map achieved an overall accuracy (OA) of 0.947 and a kappa coefficient (KC) of 0.795. This model can be integrated with additional datasets to predict yield based on the identified crop type, thereby enhancing decision-making processes related to supply chain logistics and seasonal production forecasts. The early boll opening stage, occurring approximately a little more than a month before harvest, yielded the most precise identification of cotton fields. [ABSTRACT FROM AUTHOR]

Traditionally, rechargeable lithium metal battery systems relied on simple metal cationic species to enable metal nucleation and deposition. However, this mechanism is less applicable to room‐temperature rechargeable aluminum batteries (RABs), which utilize complex ionic species. This work takes advantage of two different MXenes, Mo2Ti2C3Tx and Ti3C2Tx, which have different metal‐termination group bond strengths, interlayer spacings, and surface termination compositions, to amplify and visualize the differences between two promising RAB electrolytes (i.e., urea/AlCl3 and EMImCl/AlCl3). This work allowed us to deduce the following: 1) despite lower coulombic efficiencies, smoother Al deposits are observed when the urea/AlCl3 electrolyte is used; 2) unknown side reactions occur in all the different scenarios, however, they are likely less reversible in the EMImCl/AlCl3 electrolyte; 3) metal‐halogen exchange reactions can occur in all scenarios, forming Al(OF)x and AlFx species; 4) the free urea in urea/AlCl3 electrolyte behaves differently from the urea in aqueous solutions. Overall, due to the characteristics of aluminum, RABs involve vastly different internal mechanisms, resulting in the need for audacious attempts toward system understanding. [ABSTRACT FROM AUTHOR]

Pyroptosis is a form of inflammatory cell death that has been demonstrated to trigger anti-tumor immune responses. Photodynamic therapy (PDT) is an innovative non-invasive treatment for tumors that effectively destroys tumor cells and boosts anti-tumor immune response. The ability of PDT to trigger pyroptosis and its mechanism of action are yet uncertain. In this study, we firstly verified that PDT effectively eliminates tumor cells. TEM and Western blot analysis demonstrated that tumor cells underwent pyroptosis following PDT therapy. Lipo-Ce6 mostly accumulates in the mitochondria of 4 T1 cells, and abundant ROS generated during PDT severely damage cell mitochondria, leading to the release of mitochondrial DNA, triggering the inflammasome caspase-1 signaling cascade, and ultimately causing cell pyroptosis, in addition NAC (a scavenger of ROS) and EB (a scavenger of mitochondrial DNA) can effectively prevent cell pyroptosis by PDT, which indicated the key role of ROS in PDT induced pyroptosis. Moreover, we also found PDT tiggered immunogenic cell death (ICD). Fourthermore, PDT can efficiently suppress tumor growth, trigger ICD and induce cell pyroptosis in mice. The introducing of immune checkpoint inhibitor BMS202 significantly boosts the tumor inhibition rate and promotes the infiltration of immune cells into the tumor. The body weight and HE. staining of normal organs primarily indicated the safety of this combined strategy. Our study demonstrated that PDT induced cell pyroptosis through mitochondrial oxidative damage and PDT induced pyroptosis effectively boost anti-cancer immunity, the combination of PDT and immune checkpoint inhibitor may be a promising clinical tumor treatment approaches., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2024. Published by Elsevier B.V.)

Cancer cell proliferation requires precise control of E2F1 activity; excess activity promotes apoptosis. Here, we developed cell-permeable and bioavailable macrocycles that selectively kill small cell lung cancer (SCLC) cells with inherent high E2F1 activity by blocking RxL-mediated interactions of cyclin A and cyclin B with select substrates. Genome-wide CRISPR/Cas9 knockout and random mutagenesis screens found that cyclin A/B RxL macrocyclic inhibitors (cyclin A/Bi) induced apoptosis paradoxically by cyclin B- and Cdk2-dependent spindle assembly checkpoint activation (SAC). Mechanistically, cyclin A/Bi hyperactivate E2F1 and cyclin B by blocking their RxL-interactions with cyclin A and Myt1, respectively, ultimately leading to SAC activation and mitotic cell death. Base editor screens identified cyclin B variants that confer cyclin A/Bi resistance including several variants that disrupted cyclin B:Cdk interactions. Unexpectedly but consistent with our base editor and knockout screens, cyclin A/Bi induced the formation of neo-morphic Cdk2-cyclin B complexes that promote SAC activation and apoptosis. Finally, orally-bioavailable cyclin A/Bi robustly inhibited tumor growth in chemotherapy-resistant patient-derived xenograft models of SCLC. This work uncovers gain-of-function mechanisms by which cyclin A/Bi induce apoptosis in cancers with high E2F activity, and suggests cyclin A/Bi as a therapeutic strategy for SCLC and other cancers driven by high E2F activity.

Background: The incidence of lung cancer is steadily on the rise, posing a growing threat to human health. The search for therapeutic drugs from natural active substances and elucidating their mechanism have been the focus of anti-tumor research., Objective: Silibinin (SiL) has been shown to be a natural product with a wide range of pharmacological activities, including anti-tumour activity. In our work, SiL was chosen as a possible substance that could inhibit lung cancer. Moreover, its effects on inducing tumor cell death were also studied., Methods: CCK-8 analysis and morphological observation were used to assess the cytotoxic impacts of SiL on lung cancer cells in vitro . The alterations in mitochondrial membrane potential (MMP) and apoptosis rate of cells were detected by flow cytometry. The level of lactate dehydrogenase (LDH) release out of cells was measured. The expression changes of apoptosis or necroptosis-related proteins were detected using western blotting. Protein interactions among RIPK1, RIPK3, and MLKL were analyzed using the co-immunoprecipitation (co-IP) technique. Necrosulfonamide (Nec, an MLKL inhibitor) was used to carry out experiments to assess the changes in apoptosis following the blockade of cell necroptosis. in vitro , SiL was evaluated for its antitumor effects using LLC tumor-bearing mice with mouse lung cancer., Results: With an increased dose of SiL, the proliferation ability of A549 cells was considerably inhibited, and the accompanying cell morphology changed. The results of flow cytometry showed that after SiL treatment, MMP levels decreased, and the proportion of cells undergoing apoptosis increased. There was an increase in cleaved caspase-9, caspase-3, and PARP, with a down-regulation of Bcl-2 and an up-regulation of Bax. In addition, the amount of LDH released from the cells increased following SiL treatment, accompanied by augmented expression and phosphorylation levels of necroptosis-related proteins (MLKL, RIPK1, and RIPK3), and the co-IP assay further confirmed the interactions among these three proteins, indicating the necrosome formation induced by SiL. Furthermore, Nec increased the apoptotic rate of SiL-treated cells and aggravated the cytotoxic effect of SiL, indicating that necroptosis blockade could switch cell death to apoptosis and increase the inhibitory effect of SiL on A549 cells. In LLC-bearing mice, gastric administration of SiL significantly inhibited tumor growth, and H&E staining showed significant damage to the tumour tissue. The results of the IHC showed that the expression of RIPK1, RIPK3, and MLKL was more pronounced in the tumor tissue., Conclusions: This study confirmed the dual effect of SiL, as it can induce both biological processes, apoptosis and necroptosis, in lung cancer. SiL-induced apoptosis involved the mitochondrial pathway, as indicated by changes in caspase-9, Bcl-2, and Bax. Necroptosis may be activated due to the changes in the expression of associated proteins in tumour cells and tissues. It has been observed that blocking necroptosis by SiL increased cell death efficiency. This study helps clarify the anti-tumor mechanism of SiL against lung cancer, elucidating its role in the dual induction of apoptosis and necroptosis. Our work provides an experimental basis for the research on cell death induced by SiL and reveals its possible applications for improving the management of lung cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)