Construction of Dual-Active Sites by Interfacing with Polyhydroxy Fullerene on Nickel Hydroxide Surfaces to Promote CO2 Deep Photoreduction to CH4.

Due to the complex series of elementary steps involved, achieving deep photoreduction of CO2 to multielectron products such as CH4 remains a challenging task. Therefore, it is crucial to strategically design catalysts that facilitate the controlled formation of the crucial intermediates and provide precise control over the reaction pathway. Herein, we present a pioneering approach by employing polyhydroxy fullerene (PHF) molecules to modify the surface of Ni(OH)2, creating stable and effective synergistic sites to enhance the formation of CH4 from CO2 under light irradiation. As a result, the optimized PHF-modified Ni(OH)2 cocatalyst achieves a CH4 production rate of 455 µmol g-1 h-1, with an electron-based selectivity of approximately 60%. The combination of in situ characterizations and theoretical calculations reveals that the hydroxyl species on the surface of PHF can participate in stabilizing crucial intermediates and facilitating water activation, thereby altering the reaction pathway to form CH4 instead of CO. This study provides a novel approach to regulating the selectivity of photocatalytic CO2 reduction by exploring molecular surface modification through interfacing with functionalized carbon clusters.

Research Progress on Benzimidazole Fungicides: A Review.

Benzimidazole fungicides are a class of highly effective, low-toxicity, systemic broad-spectrum fungicides developed in the 1960s and 1970s, based on the fungicidal activity of the benzimidazole ring structure. They exhibit biological activities including anticancer, antibacterial, and antiparasitic effects. Due to their particularly outstanding antibacterial properties, they are widely used in agriculture to prevent and control various plant diseases caused by fungi. The main products of benzimidazole fungicides include benomyl, carbendazim, thiabendazole, albendazole, thiophanate, thiophanate-methyl, fuberidazole, methyl (1-{[(5-cyanopentyl)amino]carbonyl}-1H-benzimidazol-2-yl) carbamate, and carbendazim salicylate. This article mainly reviews the physicochemical properties, toxicological properties, disease control efficacy, and pesticide residue and detection technologies of the aforementioned nine benzimidazole fungicides and their main metabolite (2-aminobenzimidazole). On this basis, a brief outlook on the future research directions of benzimidazole fungicides is presented.

Organo-Photoredox Catalyzed gem-Difluoroallylation of Glycine and Glycine Residue in Peptides.

An organo-photoredox catalyzed gem-difluoroallylation of glycine with α-trifluoromethyl alkenes via direct C(sp3)-H functionalization of glycine and C-F bond activation of α-trifluoromethyl alkenes has been described. As a consequence, a broad range of gem-difluoroalkene-containing unnatural amino acids are afforded in moderate to excellent yields. This reaction exhibits multiple merits such as readily available starting materials, broad substrate scope, and mild reaction conditions. The feasibility of this reaction has been highlighted by the late-stage modification of several peptides as well as the improved in vitro antifungal activity of compound 3v toward Valsa mali compared to that with commercial azoxystrobin.

Expression of overall survival-EMT-immune cell infiltration genes predict the prognosis of glioma.

This study investigates the crucial role of immune- and epithelial-mesenchymal transition (EMT)-associated genes and non-coding RNAs in glioma development and diagnosis, given the challenging 5-year survival rates associated with this prevalent CNS malignant tumor. Clinical and RNA data from glioma patients were meticulously gathered from CGGA databases, and EMT-related genes were sourced from dbEMT2.0, while immune-related genes were obtained from MSigDB. Employing consensus clustering, novel molecular subgroups were identified. Subsequent analyses, including ESTIMATE, TIMER, and MCP counter, provided insights into the tumor microenvironment (TIME) and immune status. Functional studies, embracing GO, KEGG, GSVA, and GSEA analyses, unraveled the underlying mechanisms governing these molecular subgroups. Utilizing the LASSO algorithm and multivariate Cox regression, a prognostic risk model was crafted. The study unveiled two distinct molecular subgroups with significantly disparate survival outcomes. A more favorable prognosis was linked to low immune scores, high tumor purity, and an abundance of immune infiltrating cells with differential expression of non-coding RNAs, including miRNAs. Functional analyses illuminated enrichment of immune- and EMT-associated pathways in differentially expressed genes and non-coding RNAs between these subgroups. GSVA and GSEA analyses hinted at abnormal EMT status potentially contributing to glioma-associated immune disorders. The risk model, centered on OS-EMT-ICI genes, exhibited promise in accurately predicting survival in glioma. Additionally, a nomogram integrating the risk model with clinical characteristics demonstrated notable accuracy in prognostic predictions for glioma patients. In conclusion, OS-EMT-ICI gene and non-coding RNA expression emerges as a valuable indicator intricately linked to immune microenvironment dysregulation, offering a robust tool for precise prognosis prediction in glioma patients within the OBMRC framework.

Overcoming colloidal nanoparticle aggregation in biological milieu for cancer therapeutic delivery: Perspectives of materials and particle design.

Nanoparticles as cancer therapeutic carrier fail in clinical translation due to complex biological environments in vivo consisting of electrolytes and proteins which render nanoparticle aggregation and unable to reach action site. This review identifies the desirable characteristics of nanoparticles and their constituent materials that prevent aggregation from site of administration (oral, lung, injection) to target site. Oral nanoparticles should ideally be 75-100 nm whereas the size of pulmonary nanoparticles minimally affects their aggregation. Nanoparticles generally should carry excess negative surface charges particularly in fasting state and exert steric hindrance through surface decoration with citrate, anionic surfactants and large polymeric chains (polyethylene glycol and polyvinylpyrrolidone) to prevent aggregation. Anionic as well as cationic nanoparticles are both predisposed to protein corona formation as a function of biological protein isoelectric points. Their nanoparticulate surface composition as such should confer hydrophilicity or steric hindrance to evade protein corona formation or its formation should translate into steric hindrance or surface negative charges to prevent further aggregation. Unexpectedly, smaller and cationic nanoparticles are less prone to aggregation at cancer cell interface favoring endocytosis whereas aggregation is essential to enable nanoparticles retention and subsequent cancer cell uptake in tumor microenvironment. Present studies are largely conducted in vitro with simplified simulated biological media. Future aggregation assessment of nanoparticles in biological fluids that mimic that of patients is imperative to address conflicting materials and designs required as a function of body sites in order to realize the future clinical benefits.

Hydrogen Nanobubbles Generated In Situ from Nanoscale Zerovalent Iron with Water to Further Enhance Selenite Sequestration.

Gas nanobubbles used for water treatment and recovery give rise to great concern for their unique advantages of less byproducts, higher efficiency, and environmental friendliness. Nanoscale zerovalent iron (nZVI), which has also been widely explored in the field of environmental remediation, can generate gas hydrogen by direct reaction with water. Whether nanoscale hydrogen bubbles can be produced to enhance the pollution removal of the nZVI system is one significant concern involved. Herein, we report direct observations of in situ generation of hydrogen nanobubbles (HNBs) from nZVI in water. More importantly, the formed HNBs can enhance indeed the reduction of Se(IV) beyond the chemical reduction ascribed to Fe(0), especially in the anaerobic environment. The possible mechanism is that HNBs enhance the reducibility of the system and promote electron transport in the solution. This study demonstrates a unique function of HNBs combined with nZVI for the pollutant removal and a new approach for in situ HNB generation for potential applications in the fields of in situ remediation agriculture, biotechnology, medical treatment, health, etc.

Identification of cuproptosis-related gene SLC31A1 and upstream LncRNA-miRNA regulatory axis in breast cancer.

Mounting evidence indicate that cuproptosis, a novel form of programmed cell death, contributes to cancer development and progression. However, a comprehensive analysis regarding the expressions, functions, and regulatory network of cuproptosis-related genes is still lacking. In the present work, cuproptosis-related genes, upstream miRNAs and lncRNAs, and clinical data of breast cancer from TCGA database were analyzed by R language including Cox regression analysis, correlation calculation, ROC curve construction, and survival evaluation, and were further verified by public-available databases. Chemosensitivity and immune infiltration were also evaluated by online tools. SLC31A1 was significantly increased in breast cancer samples than those in normal tissues. SLC31A1 was negatively related to a favorable outcome in breast cancer, and the AUC value increased with the prolongation of follow-up time. LINC01614 and miR-204-5p were potential upstream regulators of SLC31A1. Moreover, SLC31A1 was significantly positively correlated with different immune cells infiltration, immune cell biomarkers, and immune checkpoints in breast cancer. SLC31A1 was a potential cuproptosis-related gene in breast cancer, which was significantly upregulated and was able to predict diagnosis, prognosis, chemosensitivity, and immune infiltration. LINC01640/miR-204-5p/SLC31A1 might be a significant and promising axis during cuproptosis in breast cancer.

Customization of Soft Tissue Expanders: Improving Safety, Accuracy, and Efficiency for Treatment of Large and Complicated Skin Lesions.

BACKGROUND: Soft tissue expansion is a common technique for restoring large skin defects. Fixed-type expanders may be inappropriate for the following reasons: (1) the shapes and sizes of the defects vary in different patients; and (2) the bulged base of the fixed-type expander does not fit the curve of the human body, which may induce complications such as concave deformities or nerve palsy from continuous mechanical compression. The customized expander adjusts better to the shape and the topography of the expansion site compared with the fixed-type expander. It improves expansion efficiency and reduces complications caused by compression. METHODS: Between 2016 and 2022, customized soft tissue expansion was performed in 38 patients with skin lesions, including giant congenital melanocytic nevi and postburn scars. This series of patients included patients with a specific donor site shape that is unsuitable for fixed-type expanders. An expander was customized according to the shape of the donor site and then implanted in the subcutaneous pocket. After the expander reached a sufficient volume, the expander was removed, and the extra expanded skin flap was transferred to resurface the skin lesion. In the follow-up, the outcome and the complications were recorded. RESULTS: All the customized expanders fit not only the dimension but also the topography of the donor site. During expansion, 2 patients experienced leakage of the expander, and 3 patients suffered a skin rupture. In the remaining 33 patients, the expansion was successfully completed, and the expanded flaps restored the skin lesions as designed. The color and texture of the skin flaps remained satisfactory after long-term follow-up. CONCLUSIONS: Unlike fixed-type expanders, our customized expanders make it possible for "accurate" expansion, irrespective of the dimension and topography of the donor area. Customization of the expander helps increase efficiency and reduce complications caused by undue compression.

TEMPO oxidized cellulose nanocrystal (TOCNC) scaffolded nanoscale zero-valent iron (nZVI) for enhanced chromium removal.

The conventional carboxymethyl cellulose (CMC) stabilization hampered available active sites of adsorption and reduction, due to irregular shape of nanoscale zero-valent iron (nZVI) particles with augmented average size and passivated surface, leading to insufficient removal and poor resistance against complex environmental conditions. Herein, we presented (2,2,6,6-Tetramethylpiperidine-1-oxyl)-mediated (TEMPO-mediated) oxidation of cellulose nanocrystal (TOCNC) scaffolded nZVI (nZVI@TOCNC) with enhanced efficiency for chromium removal in comparison with CMC stabilized nZVI (nZVI@CMC). The anchoring of nZVI at the functional sites of TOCNC was initiated by liquid-phase chemical reduction method. The nZVI@TOCNC showed improved nZVI distribution with uniform particle size and thinner shell (∼1 nm). Characterizations using FT-IR, XPS and XRD demonstrated that bindings between TOCNC and nZVI were through hydrogen bonds, electrostatic attractions, coordination-covalent bonds and bidentate chelation. TOCNC with shorter branch-chain (-COC-) surrounding the nZVI could potentially form a porous and compact "mesh" to rigidly encapsulate nZVI, while CMC wrapped around nZVI in the way of traditional polymeric stabilizers. Thus, 0.5 g/L nZVI@TOCNC achieved 99.96% Cr (Ⅵ) removal efficiency (20 mg/L) at pH = 7 and the removal capacity were up to 55.86 mg/g. The nZVI@TOCNC consistently presented higher removal efficiency than nZVI@CMC under wide pH range (3-7). Cr (Ⅵ) was reduced to Cr (Ⅲ) by nZVI@TOCNC with deposition of CrxFe1-x (OH)3 and Cr2O3. The predominant mechanisms of removal probably consisted of electrostatic attractions, reduction, co-precipitation and surface complexation. The pseudo-second-order kinetic model well-fitted the sorption kinetic, indicating TOCNC scaffold stabilized nZVI for efficient reduction of Cr (Ⅵ) through multi-layer adsorption. As a template and delivery carrier, TOCNC shows promising potential to further improve the capability and practice of nZVI for in situ treatment of industrial waste water with heavy metal pollution.

Identification of a novel five ferroptosis-related gene signature as a promising prognostic model for breast cancer.

BACKGROUND: Breast cancer (BCa) is a major challenge for women's health worldwide. Ferroptosis is closely related to tumorigenesis and cancer progression. However, the prognostic value of ferroptosis-related genes in BCa remains unclear, and more accurate prognostic models are urgently needed. METHODS: Gene expression profiles and clinical information of BCa patients were collected from public databases. LASSO and multivariate Cox regression analysis were utilized to construct the prognostic gene signature. Kaplan-Meier plotter, receiver operating characteristic (ROC) curves, and nomogram were used to validate the prognostic value of the gene signature. Gene set enrichment analysis was performed to explore the molecular functions and signaling pathways. RESULTS: Differentially expressed ferroptosis-related genes between BCa samples and normal tissues were obtained. A novel five-gene signature including BCL2, SLC40A1, TFF1, APOOL, and PRAME was established for prognosis prediction. Patients stratified into high-risk or low-risk group displayed significantly different survival. Kaplan-Meier and ROC curves showed a good performance for survival prediction in different cohorts. Biological function analysis revealed that the five-gene signature was associated with cancer progression, immune infiltration, immune response, and drug resistance. Nomogram including the five-gene signature was established. CONCLUSION: A novel five ferroptosis-related gene signature and nomogram could be used for prognostic prediction in BCa.

Lysine butyrylation of HSP90 regulated by KAT8 and HDAC11 confers chemoresistance.

Posttranslational modification dramatically enhances protein complexity, but the function and precise mechanism of novel lysine acylation modifications remain unknown. Chemoresistance remains a daunting challenge to successful treatment. We found that lysine butyrylation (Kbu) is specifically upregulated in chemoresistant tumor cells and tissues. By integrating butyrylome profiling and gain/loss-of-function experiments, lysine 754 in HSP90 (HSP90 K754) was identified as a substrate for Kbu. Kbu modification leads to overexpression of HSP90 in esophageal squamous cell carcinoma (ESCC) and its further increase in relapse samples. Upregulation of HSP90 contributes to 5-FU resistance and can predict poor prognosis in cancer patients. Mechanistically, HSP90 K754 is regulated by the cooperation of KAT8 and HDAC11 as the writer and eraser, respectively; SDCBP increases the Kbu level and stability of HSP90 by binding competitively to HDAC11. Furthermore, SDCBP blockade with the lead compound V020-9974 can target HSP90 K754 to overcome 5-FU resistance, constituting a potential therapeutic strategy.

Distribution of Metallic Elements in Four Group Components of High-Temperature Coal Tar Pitch.

The metallic elements in high-temperature coal tar pitch (HCTP) will affect the properties of carbon materials produced from the HCTP. The study on the metallic elements in HCTP is essential for the quality improvement of its derived carbon materials. In this paper, the content of 15 metallic elements in HCTP and its four group components, including n-heptane-soluble substance (HS), n-heptane-insoluble-toluene-soluble substance (HI-TS), toluene-insoluble-quinoline-soluble substance (TI-QS), and quinoline-insoluble substance (QI), was determined. The results show that the content of Na, Ca, Fe, Mg, Zn, K, Pb, and Al is more than 100 ppm and is much higher than that of other metallic elements. The content of Ni, V, Cr, Mo, Sb, Cu, and Mn ranges from 0 to 50 ppm. By mass calculation of the contents of four group components in HCTP, it can be concluded that Na and Fe are randomly distributed in the group components. Al, Zn, Pb, V, and Mn are mainly distributed in the inorganic form in the QI component. Ca, Mg, K, Ni, Cr, Mo, Sb, and Cu are mainly distributed in the small molecular group components such as HS and HI-TS.

Circular RNA EPHA3 suppresses progression and metastasis in prostate cancer through the miR-513a-3p/BMP2 axis.

BACKGROUND: Circular RNAs (circRNAs) may regulate the onset and progression of human malignancies by competitively binding to microRNA (miRNA) sponges, thus regulating the downstream genes. However, aberrant circRNA expression patterns and their biological functions in prostate cancer (PCa) warrant further studies. Our research sought to shed further light on the possible role and molecular mechanism of circEPHA3 action in controlling the growth and metastasis of PCa cells. MATERIALS AND METHODS: circEPHA3 (has_circ_0066596) was initially screened from a previous circRNA microarray and identified following Actinomycin D and RNase R assays. Fluorescence in situ hybridization, biotin-coupled probe RNA pulldown, and dual-luciferase reporter gene assays were performed to examine the relationship between circEPHA3 and miR-513a-3p. The biological role of circEPHA3 in PCa was assessed by CCK8, wound healing, Transwell assays, and animal experiments. RESULTS: We identified a novel circular RNA, circEPHA3 (has_circ_0066596), which was down-regulated in high-grade PCa tissues and cell lines. The outcomes of CCK8, wound healing, Transwell assays, and animal experiments revealed that circEPHA3 prohibited the progression and metastasis of PCa in vivo and in vitro. Mechanistically, circEPHA3 was directly bound to miR-513a-3p and regulated the downstream gene, BMP2, thereby serving as a tumor suppressor in PCa. CONCLUSIONS: As a tumor suppressor, circEPHA3 inhibited the proliferation and metastasis of PCa cells through the miR-513a-3p/BMP2 axis, suggesting that circEPHA3 might be a potential therapeutic target for PCa.

Lysine 2-hydroxyisobutyrylation of NAT10 promotes cancer metastasis in an ac4C-dependent manner.

Posttranslational modifications add tremendous complexity to proteomes; however, gaps remain in knowledge regarding the function and regulatory mechanism of newly discovered lysine acylation modifications. Here, we compared a panel of non-histone lysine acylation patterns in metastasis models and clinical samples, and focused on 2-hydroxyisobutyrylation (Khib) due to its significant upregulation in cancer metastases. By the integration of systemic Khib proteome profiling in 20 paired primary esophageal tumor and metastatic tumor tissues with CRISPR/Cas9 functional screening, we identified N-acetyltransferase 10 (NAT10) as a substrate for Khib modification. We further showed that Khib modification at lysine 823 in NAT10 functionally contribute to metastasis. Mechanistically, NAT10 Khib modification enhances its interaction with deubiquitinase USP39, resulting in increased NAT10 protein stability. NAT10 in turn promotes metastasis by increasing NOTCH3 mRNA stability in an N4-acetylcytidine-dependent manner. Furthermore, we discovered a lead compound #7586-3507 that inhibited NAT10 Khib modification and showed efficacy in tumor models in vivo at a low concentration. Together, our findings bridge newly identified lysine acylation modifications with RNA modifications, thus providing novel insights into epigenetic regulation in human cancer. We propose that pharmacological inhibition of NAT10 K823 Khib modification constitutes a potential anti-metastasis strategy.

[Electroacupuncture inhibits neuron injury of SAMP8 mice by reducing inflammatory response].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Baihui"(GV20) and "Shenshu" (BL23) on the pathological injury of neurons in SAMP8 mice and the anti-inflammatory effect on neuron repair, providing a new experimental basis for EA prevention and treatment of Alzheimer's disease. METHODS: Twelve 7-month-old SAMP8 mice were randomly divided into model and EA groups, and 6 SAMR1 mice of the same age and genetic background were used as normal group. Mice in the EA group were needled at GV20 and bilateral BL23, and EA (1 mA, 2 Hz) was applied to bilateral BL23 for 15 min, once daily, 10 d as a course for a total of 4 courses, with an interval of 1 d. Mice in the normal and model groups were captured and fixed in the same way as the EA group. The spatial learning and memory ability was detected by Morris water maze test. Neuronal nuclear antigen (NeuN) positive expression and the number of NeuN-positive cells in dentate gyrus (DG) were detected by immunofluorescence staining. The protein expression levels of ionized calcium binding adapter molecule 1(Iba-1), tumor necrosis factor-α(TNF-α), interleukin (IL)-6 and IL-1ß in hippocampus were detected by Western blot. The ultrastructure of nerve cells in DG was observed by transmission electron microscopy. RESULTS: Compared with the normal group, the average escape latency was prolonged(P<0.01), the number of platform crossing was significantly reduced (P<0.01), the average fluorescence intensity of NeuN and the number of NeuN-positive cells in hippocampus DG region decreased (P<0.05), the expression levels of Iba-1, TNF-α, IL-6 and IL-1ß in hippocampus were increased (P<0.05) in the model group.Compared with the model group, the ave-rage escape latency was shortened (P<0.01), the number of platform crossing times was significantly increased (P<0.01), the average fluorescence intensity of NeuN and the number of NeuN-positive cells in hippocampus DG region increased (P<0.05), the expression levels of Iba-1, TNF-α, IL-6 and IL-1ß in hippocampus were decreased (P<0.05) in the EA group. The morphology of nerve cells in the hippocampus DG region was normal， and the organelles in the cytoplasm were clear, complete and regularly distributed in the normal group. However, the morphology of nerve cells in the model group was seriously irregular, which was also irregular in EA group but somewhat relieved compared with model group. CONCLUSION: EA at GV20 and BL23 can improve the learning and memory ability of SAMP8 mice, which may be related to inhibiting the neuroinflammatory response, increasing the number of neurons and improving the ultrastructure of the DG region of the hippocampus to play the role of neuron protection.

Separation and Analysis of Oxygen-Containing Compounds in a Shaanxi Middle/Low-Temperature Coal Tar.

A middle/low-temperature coal tar (M/LTCT) was obtained from a low-temperature carbonization plant in Shaanxi, China. The M/LTCT was separated into light components and coal tar pitch through extraction. A series of alkanes, aromatic hydrocarbons, oxygen-containing arenes (OCAs), and nitrogen-containing arenes were fractionated from light components by medium-pressure preparative chromatography with gradient elution using petroleum ether and ethyl acetate. They were analyzed using a gas chromatography-mass spectrometer (GC-MS) and a Fourier transform infrared spectrometer. The OCAs were analyzed by a Fourier transform Orbitrap MS (quadrupole exactive Orbitrap mass spectrometer), and the molecular distribution of the O 1-O 6 species was studied. OCAs are mainly oxygen-containing aromatic compounds, including aromatic phenols, furans, alkoxy aromatic hydrocarbons, aromatic ethers, aromatic aldehydes, aromatic ketones, and aromatic acids. The position of the oxygen atom on the aromatic ring and the condensation form of the aromatic ring are studied.

N4-acetylcytidine modification of lncRNA CTC-490G23.2 promotes cancer metastasis through interacting with PTBP1 to increase CD44 alternative splicing.

Although N4-acetylcytidine (ac4C) modification affects the stability and translation of mRNA, it is unknown whether it exists in noncoding RNAs, and its biological function is unclear. Here, nucleotide-resolution method for profiling CTC-490G23.2 ac4C sites and gain- and loss-of-function experiments revealed that N-acetyltransferase 10 (NAT10) is responsible for ac4C modification of long noncoding RNAs (lncRNAs). NAT10-mediated ac4C modification leads to the stabilization and overexpression of lncRNA CTC-490G23.2 in primary esophageal squamous cell carcinoma (ESCC) and its further upregulation in metastatic tissues. CTC-490G23.2 significantly promotes cancer invasion and metastasis in vitro and in vivo. Mechanistically, CTC-490G23.2 acts as a scaffold to increase the binding of CD44 pre-mRNA to polypyrimidine tract-binding protein 1 (PTBP1), resulting in a oncogenic splicing switch from the standard isoform CD44s to the variant isoform CD44v(8-10). CD44v(8-10), but not CD44s, binds to and increases the protein stability of vimentin. Expression levels of CTC-490G23.2 and CD44v(8-10) can predict poor prognosis in cancer patients. Furthermore, the antisense oligonucleotide (ASO)/SV40-LAH4-L1 peptide self-assembled nanocomplexes targeting CTC490G23.2 exerts a significantly suppressive effect on cancer metastasis. The outcome of this study will provide new mechanistic insight into the ac4C modification of lncRNAs and useful clues for the development of novel systemic therapies and prognostic biomarkers.

Insights into the Selective Transformation of Ceria Sulfation and Iron/Manganese Mineralization for Enhancing the Selective Recovery of Rare Earth Elements.

To cope with the urgent and unprecedented demands for rare earth elements (REEs) in sophisticated industries, increased attention has been paid to REE recovery from recycled streams. However, the similar geochemical behaviors of REEs and transition metals often result in poor separation performance due to nonselectivity. Here, a unique approach based on the selective transformation between ceria sulfation and iron/manganese mineralization was proposed, leading to the enhancement of the selective separation of REEs. The mechanism of the selective transformation of minerals could be ascribed to the distinct geochemical and metallurgical properties of ions, resulting in different combinations of cations and anions. According to hard-soft acid-base (HSAB) theory, the strong Lewis acid of Ce(III) was inclined to combine with the hard base of sulfates (SO42-), while the borderline acid of Fe(II)/Mn(II) prefers to interact with oxygen ions (O2-). Both in situ characterization and density functional theory (DFT) calculation further revealed that such selective transformation might trigger by the generation of an oxygen vacancy on the surface of CeO2, leading to the formation of Ce2(SO4)3 and Fe/Mn spinel. Although the electron density difference of the configurations (CeO2-x-SO4, Fe2O3-x-SO4, and MnO2-x-SO4) shared a similar direction of the electron transfer from the metals to the sulfate-based oxygen, the higher electron depletion of Ce (QCe = -1.91 e) than Fe (QFe = -1.66 e) and Mn (QMn = -1.64 e) indicated the higher stability in the Ce-O-S complex, resulting in the larger adsorption energy of CeO2-x-SO4 (-6.88 eV) compared with Fe2O3-x-SO4 (-3.10 eV) and MnO2-x-SO4 (-2.49 eV). This research provided new insights into the selective transformation of REEs and transition metals in pyrometallurgy and thus offered a new approach for the selective recovery of REEs from secondary resources.

Downregulation of CAMK2N1 due to DNA Hypermethylation Mediated by DNMT1 that Promotes the Progression of Prostate Cancer.

Calcium/calmodulin-dependentprotein kinase II inhibitor I (CAMK2N1) as one of the tumor suppressor genes is significantly downregulated in prostate cancer (PCa). Reduced expression of CAMK2N1 is positively correlated with PCa progression. However, the mechanisms of CAMK2N1 downregulation in PCa are still unclear. The promoter region of CAMK2N1 contains a large number of CG loci, providing the possibility for DNA methylation. Consequently, we hypothesized that DNA methylation can result in the reduced expression of CAMK2N1 in PCa. In the presented study, the DNA methylation level of CAMK2N1 in prostate cells and clinical specimens was determined by bisulfite sequencing (BS), pyrosequencing, and in silico analysis. Results showed that CAMK2N1 was highly methylated in PCa cells and tissues compared to normal prostate epithelial cells and nonmalignant prostate tissues, which was associated with the clinicopathological characteristics in PCa patients. Afterwards, we explored the expression of CAMK2N1 and its DNA methylation level by qRT-PCR, western blot, BS, and methylation-specific PCR in PCa cells after 5-Aza-CdR treatment or DNMT1 genetic modification, which demonstrated that the reduced expression of CAMK2N1 can be restored by 5-Aza-CdR treatment via demethylation. Moreover, DNMT1 formed a positive feedback loop with CAMK2N1 in PCa cells. The expression of CAMK2N1 was downregulated by DNMT1-mediated DNA methylation, which reversely induced DNMT1 expression through activating AKT or ERK signaling pathway. Finally, functional assays including wound healing, invasion, and migration assay, as well as the xenograft model in nude mice indicated that CAMK2N1 inhibited the invasion, migration, and proliferation of PCa cells and these effects were reversed by DNMT1 overexpression. In conclusion, DNMT1-mediated hypermethylation of CAMK2N1 not only downregulates the gene expression but also promotes the progression of PCa.

Aspirin triggers ferroptosis in hepatocellular carcinoma cells through restricting NF-κB p65-activated SLC7A11 transcription.

A number of studies have shown that aspirin, as commonly prescribed drug, prevents the development of hepatocellular carcinoma (HCC). Ferroptosis as a dynamic tumor suppressor plays a vital role in hepatocarcinogenesis. In this study we investigated whether aspirin affected ferroptosis in liver cancer cells. RNA-seq analysis revealed that aspirin up-regulated 4 ferroptosis-related drivers and down-regulated 5 ferroptosis-related suppressors in aspirin-treated HepG2 cells. Treatment with aspirin (4 mM) induced remarkable ferroptosis in HepG2 and Huh7 cells, which was enhanced by the ferroptosis inducer erastin (10 µM). We demonstrated that NF-κB p65 restricted ferroptosis in HepG2 and Huh7 cells through directly binding to the core region of SLC7A11 promoter and activating the transcription of ferroptosis inhibitor SLC7A11, whereas aspirin induced ferroptosis through inhibiting NF-κB p65-activated SLC7A11 transcription. Overexpression of p65 rescued HepG2 and Huh7 cells from aspirin-induced ferroptosis. HCC patients with high expression levels of SLC7A11 and p65 presented lower survival rate. Functionally, NF-κB p65 blocked the aspirin-induced ferroptosis in vitro and in vivo, which was attenuated by erastin. We conclude that aspirin triggers ferroptosis by restricting NF-κB-activated SLC7A11 transcription to suppress the growth of HCC. These results provide a new insight into the mechanism by which aspirin regulates ferroptosis in hepatocarcinogenesis. A combination of aspirin and ferroptosis inducer may provide a potential strategy for the treatment of HCC in clinic.