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Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.

Nitrogen pollution poses a substantial threat to water bodies, making the exploration of effective treatment technologies imperative. Among these, biological denitrification stands out as one of the most efficient methods. Various materials, including biochar, graphene, carbon nanotubes, and nanoparticles, have gained widespread use across different industries due to their unique properties. Numerous studies have investigated the impact of these materials on microbial denitrification individually, focusing on their influence on key enzymatic processes, functional genes, electron transport, functional proteins, and microbial metabolic activities. This manuscript aims to contribute a comprehensive and holistic perspective by presenting consolidated data on the collective impact of biochar, graphene, carbon nanotubes, and nanoparticles on microbial denitrification. The combination of biochar and microorganisms improves denitrification performance by 415%. Graphene increases enzyme activity (100–175.4%). The coupling of carbon nanotubes and microorganisms reduced denitrification performance by 57.42%. Nanoparticles reduce denitrification performance (73.4%), enzyme activity (63%), and electron transfer rate (52.4%) by entering the cell membrane. Moreover, these materials have been observed to induce alterations in the community structure of microorganisms involved in denitrification. The manuscript delves into the intricate details of how these materials influence the conformational changes of denitrifying enzymes, emphasizing the relationship between enzyme activity and structural modifications. Overall, this manuscript not only provides a thorough analysis of the effects of biochar, graphene, carbon nanotubes, and nanoparticles on microbial denitrification but also explores their implications for the conformational dynamics of denitrifying enzymes. Furthermore, it outlines avenues for future research, offering a roadmap to guide upcoming studies in this critical field. [ABSTRACT FROM AUTHOR]

The biological denitrification process is crucial for removing nitrogen and reducing nitrous oxide (N2O) emissions. To investigate the mechanism of action of key enzymes in the denitrification process, it is necessary to analyze the protein structure, active site, and conformational changes of denitrifying enzymes. X-ray crystallography, nuclear magnetic resonance (NMR), and cryogenic electron microscopy (Cryo-EM), as well as spectroscopic analyses such as Raman resonance and UV-vis, have been used to study the structure of denitrifying enzymes. However, practical application is limited by protein folding and assembly, as well as issues of purity, concentration, and homogeneity. This review summarizes the biochemical properties of the four denitrifying enzymes and typical purification methods. Additionally, this review emphasizes important factors to consider during protein expression, crude extract, and chromatographic purification. It also provides insight into the future development of protein purification methods for denitrifying enzymes. This review aims to bridge the gap between the complex biochemical process of denitrifying enzymes and the technical intricacies of protein purification, with the ultimate goal of reducing N2O emissions in ecosystems. [ABSTRACT FROM AUTHOR]

Nitrous oxide (N2O) is a potent greenhouse gas that accumulates in the atmosphere due to anthropogenic N2O emissions, disrupting the nitrogen balance. N2O reductase (N2OR) in denitrifying bacteria contributes to the nitrogen cycle by converting N2O to molecular nitrogen as a last step. For the reduction of N2O during denitrification, electron donors must supply two electrons. This review discusses the in vivo physiological electron donors involved in the reduction reaction of N2OR: cytochrome c55X and pseudoazurin, as well as the non-physiological electron donors commonly used in N2OR studies: reduced MV/BV, dithionite, and ascorbate. The kinetic parameters of the connection between N2OR and the electron donors are also included. This aim of this review to gain further insight into the reduction mechanism of N2OR, presenting the electron transfer center, CuA, and the catalytic center, CuZ, of N2OR. The state changes of Cu site have a significant impact on electron transfer and N2O binding. Moreover, the review focuses on potential electron transfer pathways and binding sites in the electron donor → CuA → CuZ process, along with the steady-state turnover in the CuZ site. Additionally, the review explains the commonly used methods in mechanistic studies of N2OR. Modulating the electron transfer pathways of N2OR holds promise as an approach to decreasing N2O emissions. [ABSTRACT FROM AUTHOR]

The imbalance between energy intake and energy expenditure leads to the prevalence of obesity worldwide. A strategy to simultaneously limit energy intake and promote energy expenditure would be an important new obesity treatment. Here, we identified rhamnose as a nonnutritive sweetener to promote adipose thermogenesis and energy expenditure. Rhamnose promotes cAMP production and PKA activation through dopamine receptor D1 in adipose tissue. As a result, rhamnose administration promotes UCP1-dependent thermogenesis and ameliorates obesity in mice. Thus, we have demonstrated a rhamnose–dopamine receptor D1–PKA axis critical for thermogenesis, and that rhamnose may have a role in therapeutic molecular diets against obesity. [ABSTRACT FROM AUTHOR]

Perfluorinated compounds (PFCs) are a novel type of environmental pollutant with a specific structure. PFCs have become a global concern due to their environmental persistence and biotoxicity properties. In this paper, we review the hazardous effects, detection technologies, and treatment methods of PFCs. We present the current status of PFCs pollution in water, the atmosphere, soil, and organisms. Moreover, we show that PFCs have toxic effects, such as hepatotoxicity, neurotoxicity, immunotoxicity, endocrine disruption, and reproductive and developmental toxicity. Six sample pretreatment techniques and four assays for PFCs are listed in this paper. This review focuses on the analysis of the treatment methods for PFCs, such as physical adsorption, microbial degradation, photochemical oxidation, electrochemical oxidation, acoustic oxidation, Fenton oxidation, and so on. We systematically analyze the treatment effects, removal mechanisms, and future directions of various technologies to provide support and suggestions for PFCs pollution control technologies. [ABSTRACT FROM AUTHOR]

Background: Astrocytes are extensively utilized as starting cells for neuronal conversion. Our previous study discovered that a portion of primary cultured mouse neonatal cortical astrocytes can be directly converted into neurons after exposure to a neurogenic induction condition. Recent in vivo studies have demonstrated astrocyte heterogeneity in terms of their developmental origin, molecular profile, physiology, and functional outputs. We hypothesized that the heterogeneity of primary astrocytes in our study could influence their conversion potential., Methods and Results: We performed single-cell RNA sequencing on cells harvested at key time points during in vitro astrocyte-to-neuron conversion, specifically on Day 1 and Day 9. Through single-cell RNA sequencing analysis, we identified several subpopulations of astrocytes, labeled as Astrocyte 1 to Astrocyte 3, based on distinct gene expression patterns. Pseudotime trajectory analysis predicted the existence of three distinct cell states throughout the conversion process. Astrocyte 3 exhibited a higher propensity for neuronal conversion, with proliferation genes like Mki67 being highly expressed. Additionally, several candidate genes were identified as potentially crucial in the conversion process. Astrocyte 3 is considered a unique subtype population of astrocytes., Conclusions: Our investigation underscores the diversity of primary neonatal cortical astrocytes and provides critical insights into the potential for astrocyte-to-neuron conversion, which may be harnessed to enhance the efficiency of this astrocyte-neuron conversion process., Competing Interests: Declarations. Ethical approval: All experimental protocols involving live animals in this study followed the guidelines of the by-laws on experimentation on animals, and were approved by the Ethics Committee for the Use of Animal Subjects of the Tongji University (Approval Code: TJAB04121102). Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)