Facilely tuning the intrinsic catalytic sites of the spinel oxide for peroxymonosulfate activation: From fundamental investigation to pilot-scale demonstration.

Heterogeneous peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) have shown a great potential for pollutant degradation, but their feasibility for large-scale water treatment application has not been demonstrated. Herein, we develop a facile coprecipitation method for the scalable production (∼10 kg) of the Cu-Fe-Mn spinel oxide (CuFeMnO). Such a catalyst has rich oxygen vacancies and symmetry-breaking sites, which endorse it with a superior PMS-catalytic capacity. We find that the working reactive species and their contributions are highly dependent on the properties of target organic pollutants. For the organics with electron-donating group (e.g., -OH), high-valent metal species are mainly responsible for the pollutant degradation, whereas for the organics with electron-withdrawing group (e.g., -COOH and -NO2), hydroxyl radical (•OH) as the secondary oxidant also plays an important role. We demonstrate that the CuFeMnO-PMS system is able to achieve efficient and stable removal of the pollutants in the secondary effluent from a municipal wastewater plant at both bench and pilot scales. Moreover, we explore the application prospect of this PMS-based AOP process for large-scale wastewater treatment. This work describes an opportunity to scalably prepare robust spinel oxide catalysts for water purification and is beneficial to the practical applications of the heterogeneous PMS-AOPs.

Ginsenoside Rh2 shifts tumor metabolism from aerobic glycolysis to oxidative phosphorylation through regulating the HIF1-α/PDK4 axis in non-small cell lung cancer.

BACKGROUND: Ginsenoside Rh2 (G-Rh2), a steroidal compound extracted from roots of ginseng, has been extensively studied in tumor therapy. However, its specific regulatory mechanism in non-small cell lung cancer (NSCLC) is not well understood. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in various malignant tumors. We investigated the impact of G-Rh2 on the malignant progression of NSCLC and how it regulated PDK4 to influence tumor aerobic glycolysis and mitochondrial function. METHOD: We examined the inhibitory effect of G-Rh2 on NSCLC through I proliferation assay, migration assay and flow cytometry in vitro. Subsequently, we verified the ability of G-Rh2 to inhibit tumor growth and metastasis by constructing subcutaneous tumor and metastasis models in nude mice. Proteomics analysis was conducted to analyze the action pathways of G-Rh2. Additionally, we assessed glycolysis and mitochondrial function using seahorse, PET-CT, Western blot, and RT-qPCR. RESULT: Treatment with G-Rh2 significantly inhibited tumor proliferation and migration ability both in vitro and in vivo. Furthermore, G-Rh2 inhibited the tumor's aerobic glycolytic capacity, including glucose uptake and lactate production, through the HIF1-α/PDK4 pathway. Overexpression of PDK4 demonstrated that G-Rh2 targeted the inhibition of PDK4 expression, thereby restoring mitochondrial function, promoting reactive oxygen species (ROS) accumulation, and inducing apoptosis. When combined with sodium dichloroacetate, a PDK inhibitor, it complemented the inhibitory capacity of PDKs, acting synergistically as a detoxifier. CONCLUSION: G-Rh2 could target and down-regulate the expression of HIF-1α, resulting in decreased expression of glycolytic enzymes and inhibition of aerobic glycolysis in tumors. Additionally, by directly targeting mitochondrial PDK, it elevated mitochondrial oxidative phosphorylation and enhanced ROS accumulation, thereby promoting tumor cells to undergo normal apoptotic processes.

Ferromagnetic Mn3+ Sawtooth Chains in A2(Mn2O)(SeO3)3 (A = K, Rb) Quaternary Selenites.

Two quaternary manganese selenites, A2(Mn2O)(SeO3)3 (A = K, Rb), have been synthesized by hydrothermal reactions. They both crystallize in a complex triclinic (P-1) structure built of Jahn-Teller (JT) distorted Mn3+O4+2 octahedra, connected into nearly isosceles [Mn3O14] triangles, themselves arranged into so-called "sawtooth (ST) chains". The K and Rb compounds show subtle variations in the orientations of the MnO4 planes inside the elementary triangles. The ST chains are structurally and magnetically isolated by SeO3 groups and alkali cations. In the ST chains, predominant ferromagnetic interactions were calculated and verified experimentally, which finally order antiferromagnetically between the chains around TN ≈ 22 K. The spin exchanges calculated by DFT + U and fitted by Monte Carlo simulations allow for the quantification of an effective "overall" model. The specific role of the µ3-O bridge on the ferromagnetic (FM) exchanges is discussed, together with spin reorientations observed in the ordered state. Magnetocrystalline anisotropy along the [110] direction stabilized by ∼50 meV per Mn by spin-orbit coupling (SOC) was found by DFT + U + SOC.

Oncogenic circ-SLC16A1 promotes progression of non-small cell lung cancer via regulation of the miR-1287-5p/profilin 2 axis.

BACKGROUND: Circular RNAs (circRNAs) are single-stranded RNAs with covalently closed structures that have been implicated in cancer progression. However, the regulatory mechanisms remain largely unclear. So, the aim of this study was to reveal the role and regulatory mechanisms of circ-SLC16A1. METHODS: In this study, next-generation sequencing was used to identify abnormally expressed circRNAs between cancerous and para-carcinoma tissues. Fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction were performed to assess the expression patterns of circ-solute carrier family 16 member 1 (SLC16A1) in non-small cell lung cancer (NSCLC) cells and tissue specimens. The dual-luciferase reporter assay was utilized to identify downstream targets of circ-SLC16A1. Transwell migration, wound healing, 5-ethynyl-2'-deoxyuridine incorporation, cell counting, and colony formation assays were conducted to assess the proliferation and migration of NSCLC cells. A mouse tumor xenograft model was employed to determine the roles of circ-SLC16A1 in NSCLC progression and metastasis in vivo. RESULTS: The results found that circ-SLC16A1 was upregulated in NSCLC cells and tissues. Downregulation of circ-SLC16A1 inhibited tumor growth by reducing proliferation, lung metastasis, and lymphatic metastasis of NSCLC cells, and arrested the cell cycle in the G1 phase. Also, silencing of circ-SLC16A1 promoted apoptosis of NSCLC cells. The results of bioinformatics analysis and the dual-luciferase reporter assay confirmed that microRNA (miR)-1287-5p and profilin 2 (PFN2) are downstream targets of circ-SLC16A1. PFN2 overexpression or circ-SLC16A1 inhibition restored proliferation and migration of NSCLC cells after silencing of circ-SLC16A1. PFN2 overexpression restored migration and proliferation of NSCLC cells post miR-1287-5p overexpression. CONCLUSIONS: Collectively, these findings show that miR-1287-5p/PFN2 signaling was associated with downregulation of circ-SLC16A1 and reduced invasion and proliferation of NSCLC cells. So, circ-SLC16A1 is identified as a mediator of multiple pro-oncogenic signaling pathways in NSCLC and can be targeted to suppress tumor progression.

The relationship between proportions of carbohydrate and fat intake and hyperglycemia risk in Chinese adults.

OBJECTIVE: To address the relationship between the proportions of carbohydrates and fat and hyperglycemia in the Chinese population. DESIGN: A cross-section research involving data from the China Health and Nutrition Survey in 2009, and nutritional status and health indicators were mainly focused. SETTING: China. PARTICIPANTS: 8197 Chinese individuals aged over 16 years, including 1345 subjects had a low carbohydrate and high fat diet (LCHF), 3951 individuals had a medium proportion of carbohydrate and fat (MPCF) diet, 2660 participants had a high carbohydrate and low fat (HCLF) diet and 241 people had the very high carbohydrate and low fat (VHCLF) diet. RESULTS: Subjects with the HCLF diet were significantly associated with an increased risk of hyperglycemia (OR:1.142, 95%CI:1.022-1.276) when compared with the individuals with the MPCF diet. Meanwhile, people with a VHCLF diet had a higher risk of hyperglycemia (OR:1.829, 95%CI:1.377-2.429). In contrast, the association between participants with an LCHF diet and hyperglycemia was not significant (OR:1.082, 95%CI:0.942-1.243) with adjusting a series of confounding factors. Furthermore, people with a VHCLF diet were significantly associated with a higher risk of hyperglycemia in the major energy levels and social characteristics subgroup. CONCLUSION: We found the HCLF and VHCLF diets were significantly associated with a high risk of hyperglycemia. And, the association between LCHF diets and the risk of hyperglycemia was not significant.

Bidirectional Regulation of Intracellular Enzyme Activity Using Light-Driven Nano-Inhibitors.

Photochemical regulation provides precise control over enzyme activities with high spatiotemporal resolution. A promising approach involves anchoring "photoswitches" at enzyme active sites to modulate substrate recognition. However, current methods often require genetic mutations and irreversible enzyme modifications for the site-specific anchoring of "photoswitches", potentially compromising the enzyme activities. Herein, we present a pioneering reversible nano-inhibitor based on molecular imprinting technique for bidirectional regulation of intracellular enzyme activity. The nano-inhibitor employs a molecularly imprinted polymer nanoparticle as its body and azobenzene-modified inhibitors ("photoswitches") as the arms. By using a target enzyme as the molecular template, the nano-inhibitor acquires oriented binding sites on its surface, resulting in a high affinity for the target enzyme and non-covalently firm anchoring of the azobenzene-modified inhibitor to the enzyme active site. Harnessing the reversible isomerization of azobenzene units upon exposure to ultraviolet and visible light, the nano-inhibitor achieves bidirectional enzyme activity regulation by precisely docking and undocking inhibitor at the active site. Notably, this innovative approach enables the facile in situ regulation of intracellular endogenous enzymes, such as carbonic anhydrase. Our results represent a practical and versatile tool for precise enzyme activity regulation in complex intracellular environments.

Nitazoxanide inhibits acetylated KLF5-induced bone metastasis by modulating KLF5 function in prostate cancer.

BACKGROUND: Castration-resistant prostate cancer often metastasizes to the bone, and such bone metastases eventually become resistant to available therapies, leading to the death of patients. Enriched in the bone, TGF-ß plays a pivotal role in bone metastasis development. However, directly targeting TGF-ß or its receptors has been challenging for the treatment of bone metastasis. We previously found that TGF-ß induces and then depends on the acetylation of transcription factor KLF5 at K369 to regulate multiple biological processes, including the induction of EMT, cellular invasiveness, and bone metastasis. Acetylated KLF5 (Ac-KLF5) and its downstream effectors are thus potential therapeutic targets for treating TGF-ß-induced bone metastasis in prostate cancer. METHODS: A spheroid invasion assay was applied to prostate cancer cells expressing KLF5K369Q, which mimics Ac-KLF5, to screen 1987 FDA-approved drugs for invasion suppression. Luciferase- and KLF5K369Q-expressing cells were injected into nude mice via the tail artery to model bone metastasis. Bioluminescence imaging, micro-CT), and histological analyses were applied to monitor and evaluate bone metastases. RNA-sequencing, bioinformatic, and biochemical analyses were used to understand nitazoxanide (NTZ)-regulated genes, signaling pathways, and the underlying mechanisms. The binding of NTZ to KLF5 proteins was evaluated using fluorescence titration, high-performance liquid chromatography (HPLC), and circular dichroism (CD) analysis. RESULTS: NTZ, an anthelmintic agent, was identified as a potent invasion inhibitor in the screening and validation assays. In KLF5K369Q-induced bone metastasis, NTZ exerted a potent inhibitory effect in preventive and therapeutic modes. NTZ also inhibited osteoclast differentiation, a cellular process responsible for bone metastasis induced by KLF5K369Q. NTZ attenuated the function of KLF5K369Q in 127 genes' upregulation and 114 genes' downregulation. Some genes' expression changes were significantly associated with worse overall survival in patients with prostate cancer. One such change was the upregulation of MYBL2, which functionally promotes bone metastasis in prostate cancer. Additional analyses demonstrated that NTZ bound to the KLF5 protein, KLF5K369Q bound to the promoter of MYBL2 to activate its transcription, and NTZ attenuated the binding of KLF5K369Q to the MYBL2 promoter. CONCLUSIONS: NTZ is a potential therapeutic agent for bone metastasis induced by the TGF-ß/Ac-KLF5 signaling axis in prostate cancer and likely other cancers.

TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy.

BACKGROUND: Neuroinflammation mediated by microglial pyroptosis is an important pathogenic mechanism of septic encephalopathy (SAE). It has been reported that TRIM45 is associated with tumours and inflammatory diseases. However, the role of TRIM45 in SAE and the relationship between TRIM45 and microglial pyroptosis are unknown. In this study, we found that TRIM45 played an important role in regulating microglial pyroptosis and the molecular mechanism. METHODS: SAE was induced by intraperitoneal injection of LPS in WT and AAV-shTRIM45 mice. BV2 cells were treated with LPS/ATP in vitro. Cognitive function was assessed by the Morris water maze. Nissl staining was used to evaluate histological and structural lesions. ELISA was used to dectect neuroinflammation. qPCR was used to detect the mRNA levels of inflammatory cytokines, NLRP3, and autophagy genes. Western blotting and immunofluorescence analysis were used to analyse the expression of the proteins. Changes in reactive oxygen species (ROS) in cells were observed by flow cytometry. Changes in mitochondrial membrane potential in BV2 cells were detected by JC-1 staining. Peripheral blood mononuclear cells were extracted from blood by density gradient centrifugation and then used for qPCR, western blotting and flow detection. To further explore the mechanism, we used the overexpression plasmids TRIM45 and Atg5 as well as siRNA-TRIM45 and siRNA-Atg5 to analyse the downstream pathway of NLRP3. The protein and mRNA levels of TRIM45 in peripheral blood mononuclear cells from sepsis patients were examined. RESULTS: Knocking down TRIM45 protected against neuronal damage and cognitive impairment in septic mice. TRIM45 knockdown inhibited microglial pyroptosis and the secretion of inflammatory cytokines in vivo and in vitro, which was mediated by NLRP3/Gsdmd-N activation. Overexpression of TRIM45 could activate NLRP3 and downstream proteins. Further examination showed that TRIM45 regulated the activation of NLRP3 by altering Atg5 and regulating autophagic flux. It was also found that overexpression and knockdown of TRIM45 affected the changes in ROS and mitochondrial membrane potential. Thus, knocking down TRIM45 could reduce microglial pyroptosis, the secretion of proinflammatory cytokines, and neuronal damage and improve cognitive function. In addition, the level of TRIM45 protein in septic patients was increased. There was a positive linear correlation between APACHE II score and TRIM45, between SOFA score and TRIM45. Compared to group GCS > 9, level of TRIM45 were increased in group GCS ≤ 8. CONCLUSION: TRIM45 plays a key role in neuroinflammation caused by LPS, and the mechanism may involve TRIM45-mediated exacerbation of microglial pyroptosis via the Atg5/NLRP3 axis.

Investigation of Charge-Ordered Barium Iron Fluorides with One-Dimensional Structural Diversity and Complex Magnetic Interactions.

Three mixed-valence barium iron fluorides, Ba7Fe7F34, Ba2Fe2F9, and BaFe2F7, were prepared through hydrothermal redox reactions. The characteristic structures of these compounds feature diverse distributions of FeIIF6 octahedra and FeIIIF6 groups. Ba7Fe7F34 contained one-dimensional infinite ∞[FeIIFeIII6F34]14- double chains, comprising cis corner-sharing octahedra along the b direction; Ba2Fe2F9 contained one-dimensional ∞[Fe2F9]4- double chains, consisting of cis corner-sharing octahedra along the chain (a-axis direction) and trans corner-sharing octahedra vertical to the chain, while BaFe2F7 revealed three-dimensional (3D) frameworks that consist of isolated edge-sharing dinuclear FeII2F10 units linked via corners by FeIIIF6 octahedra. Magnetization and Mössbauer spectroscopy measurements revealed that Ba7Fe7F34 exhibits an antiferromagnetic phase transition at ∼11 K, where ferrimagnetic ∞[FeIIFeIII6F34]14- double chains are arranged in a paralleling manner, while Ba2Fe2F9 shows canted antiferromagnetic ordering at ∼32.5 K, leading to noncollinear spin ordering.

Self-Destructive Nanoscavengers Capture and Clear Neurotoxic Soluble ß-Amyloid Aggregates.

Cerebral soluble ß-amyloid aggregates (sAßs) accumulation is one of the most important causes in Alzheimer's disease (AD) progression. In order to mitigate the neurotoxicity induced by sAßs and achieve enhanced AD therapeutic outcomes, robust sAßs clearance become an emerging task. Herein, a self-destructive nanoscavenger (SDNS) is reported based on multifunctional peptide-polymer complexes that can capture extracellular sAßs via hydrogen-bonding interactions and deliver them into microglial lysosomes. The internalized SDNS then occurs self-destruction within lysosomes and upregulates autophagy, thereby promoting the degradation of neurotoxic sAßs. Importantly, the enhanced autophagy also significantly suppresses the secretion of inflammatory factors by microglia, which is induced by internalized sAßs. Given that cerebral persistent inflammatory environment disturbs microglia-mediated phagocytosis and degradation, it is believed that this synergistic approach has valuable potential as a therapeutic strategy for AD.

Effects of mercapto-palygorskite application on cadmium accumulation of soil aggregates at different depths in Cd-contaminated alkaline farmland.

Mercapto-palygorskite (MP) is a novel immobilization material for cadmium (Cd) pollution, but the immobilization mechanism on alkaline Cd contaminated soil is not completely clear. In this paper, field experiment was carried out to study the effect of MP on the transfer of Cd in aggregates at different depth, the contribution of soil aggregates to the reduction of Cd in bulk soil and the immobilization mechanism of MP. The results showed that MP had no significant influence on the total Cd content, soil aggregates distribution, pH value, CEC value and enzyme activities no matter at any depth. At the depth of 0-20 cm, MP significantly reduced the DTPA-Cd in bulk soil by 60.7%, and increased the GWD and R0.25 value. Similarly, the content of DTPA-Cd in the soil aggregates was deceased by 40.2-63.6%, the OM, DOC, available Fe, Mn and S in soil aggregates were significantly increased by 15.0-19.1%, 19.2-41.7%, 24.7-41.2% and 12.5-35.1% respectively. The Cd fraction of aggregates, especially exchangeable Cd (EXE-Cd) and bound to Fe/Mn oxide Cd (OX-Cd), was reduced by 5.4-28.1% and increased by 22.3-50.4%. In addition, MP had different effects on the GSF value of soil aggregates, but there was a downward trend for AFX value at 0-20 cm soil depth. MP almost had no significant influence on the above indexes at the depth of 20-40 cm and 40-60 cm, but except the Cd fraction, the GSF and AFX value in individual aggregates. Small aggregates (<1 mm) and large aggregates (>1 mm) contributed 59.1% and 22% to the reduction of Cd in bulk soil. Partial Least Structural Equation Model (PL-SEM) revealed that S promoted the production of available Fe, Mn, OM and DOC, while the content of DOC inhibited the formation of EXE-Cd and the available Fe and Mn boosted the production of OX-Cd.

Application of ferromanganese functionalized biochar simultaneously reduces Cd and Pb uptake of wheat in contaminated alkaline soils.

The reduction of Cd and Pb accumulation in wheat grains grown on Cd and Pb contaminated alkaline soils is a pressing issue that needs to be solved. In this study, ferromanganese functionalized biochar (FM-BC) was used to remediate Cd and Pb contaminated alkaline soils and mitigate Cd and Pb accumulation in wheat grains. The immobilization capacity and mechanism of FM-BC were investigated by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) characterization and chemical analysis. Fe and Mn loaded on FM-BC improved the removal efficiencies of DTPA-Cd and DTPA-Pb in soil with DTPA-Cd removal of 22.99%- 52.04% (JM22) and 25.54%- 53.32 (AK58) and DTPA-Pb removal of 11.39%- 22.36% (JM22) and 5.38%- 13.00% (AK58). The FT-IR and XRD results indicated that the complexation and precipitation of Cd and Pb with the Fe-Mn oxides and the oxygen-containing functional groups on biochar surface stabilized the Cd and Pb in soil for the observation of Cd2Mn3O8, PbHPO4, CdCO3, and PbO2 on FM-BC isolated from contaminated soils. FM-BC with excellent adsorption capacity reduced the available Cd and Pb in the soil, therefore, thereby inhibiting the Cd and Pb accumulation in wheat. In the 3% FM-BC treatment, Cd and Pb contents in wheat grains were lower than 0.10 mg/kg and 0.20 mg/kg, respectively, reaching the national safety standards. And FM-BC increased the Fe, Mn, Na and Zn contents in wheat grains, and improved the growth and yield of wheat. These findings suggest that FM-BC can be considered a prospective and effective material for remediation of alkaline soils contaminated with Cd and Pb.

Mercapto-palygorskite efficiently immobilizes cadmium in alkaline soil and reduces its accumulation in wheat plants: A field study.

Cadmium (Cd) contamination in wheat fields has become a major environmental issue in many regions of the world. Mercapto-palygorskite (MPAL) is a high-performance amendment that can effectively immobilize Cd in alkaline wheat soil. However, MAPL as an in-situ Cd immobilization strategy for alkaline wheat soil remains to be evaluated on a field-scale and the underlying mechanisms requires further evaluation. Here, MPAL were used as soil amendment to evaluate their immobilization efficiency on Cd-contaminated alkaline soil in the field experiments. The field experiments showed that MPAL application significantly reduced wheat grain Cd concentration from 0.183 mg/kg to 0.056 mg/kg, with Cd concentration in wheat grain treated with MPAL all falling below the limit value of 0.1 mg/kg as defined in China's food safety standard (GB 2762-2022). The maximal immobilization efficiency of MPAL on soil Cd figured out by diethylenetriaminepentaacetic acid (DTPA) extraction was 61.5%. The mechanisms involved in Cd immobilization by MPAL were mainly related to the enhanced sorption of Cd onto Fe oxides, and the removal of amorphous or free Fe oxides from soil had a substantial impact on Cd immobilization efficiency by MPAL. Furthermore, the antagonistic effect between Mn and Cd uptake may also contribute to the reduction of wheat Cd accumulation after MPAL application. The current research can provide theoretical and technical support for the large-scale application of MPAL in Cd-contaminated wheat fields.

Tfcancer: a manually curated database of transcription factors associated with human cancers.

SUMMARY: Transcription factors (TFs) are critical regulation elements and its dysregulation can lead to a variety of cancers. However, currently, there are no such online resources for large-scale collection, storage and analysis of TF-cancer associations in those cancers. To fill this gap, we present a database called TFcancer (http://lcbb.swjtu.edu.cn/tfcancer/), which contains 3136 experimentally supported associations between 364 TFs and 33 TCGA cancers by manually curating more than 1800 literature. TFcancer mainly concentrates on four aspects: TF expression, molecular alteration, regulatory relationships between TFs and target genes, and biological processes and signaling pathways of TFs in cancers. TFcancer not only provides a user-friendly interface for browsing and searching but also allows flexible data downloading and user data submitting. It is believed that TFcancer is a helpful and valuable resource for researchers who seek to understand the functions and molecular mechanisms of TFs involved in human cancers. AVAILABILITY AND IMPLEMENTATION: The TFcancer are freely available at http://lcbb.swjtu.edu.cn/tfcancer/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PEGylated Poly-HDACi: A Designer Polyprodrug from Optimized Drug Units.

We designed, synthesized, and characterized a tri-block copolymer. Its hydrophobic part, a chain of histone deacetylase inhibitor (HDACi) prodrug, was symmetrically flanked by two identical PEG blocks, whereas the built-in HDACi was a linear molecule, terminated with a thiol at one end, and a hydroxyl group at the other. Such a feature facilitated end-to-end linkage of prodrugs through alternatively aligned disulfides and carbonates. The disulfides served dual roles: redox sensors of smart nanomedicine, and warheads of masked HDACi drugs. This approach, carefully designed to benefit both control-release and efficacy, is conceptually novel for optimizing drug units in nanomedicine. Micelles from this designer polyprodrug released only PEG, CO2 and HDACi, and synergized with DOX against HCT116 cells, demonstrating its widespread potential in combination therapy. Our work highlights, for the first time, the unique advantage of thiol-based drug molecules in nanomedicine design.

Dexmedetomidine preconditioning ameliorates lung injury induced by pulmonary ischemia/reperfusion by upregulating promoter histone H3K4me3 modification of KGF-2.

Keratinocyte growth factor (KGF)-2 has been highlighted to play a significant role in maintaining the endothelial barrier integrity in lung injury induced by ischemia-reperfusion (I/R). However, the underlying mechanism remains largely unknown. The aims of this study were to determine whether dexmedetomidine preconditioning (DexP) modulates pulmonary I/R-induced lung injury through the alteration in KGF-2 expression. In our I/R-modeled mice, DexP significantly inhibited pathological injury, inflammatory response, and inflammatory cell infiltration, while promoted endothelial barrier integrity and KGF-2 promoter activity in lung tissues. Bioinformatics prediction and ChIP-seq revealed that I/R significantly diminished the level of H3K4me3 modification in the KGF-2 promoter, which was significantly reversed by DexP. Moreover, DexP inhibited the expression of histone demethylase JMJD3, which in turn promoted the expression of KGF-2. In addition, overexpression of JMJD3 weakened the protective effect of DexP on lung injury in mice with I/R. Collectively, the present results demonstrated that DexP ameliorates endothelial barrier dysfunction via the JMJD3/KGF-2 axis.

Removal mechanisms of Cd from water and soil using Fe-Mn oxides modified biochar.

The development of remediation materials simultaneously suitable for Cd-contaminated water and soil is of great significance. In this study, the functional biochar (FM-RBC and FM-DBC) was prepared using branch and durian shell biochar (RBC and DBC, respectively) with iron-manganese oxide (Fe-Mn oxide) modification. The behaviors and mechanisms of Cd adsorption and stabilization in water and alkaline soil treated with FM-RBC and FM-DBC were explored. The results showed that the adsorption capacities of RBC and DBC for Cd had increased by 40-80 mg/g after the Fe-Mn oxide modification. The Cd adsorption was conformed to pseudo-second-order kinetic and the Langmuir isothermal models. After 35 days of soil cultivation, the maximum reduction rate of DTPA-Cd occurred in 3% FM-DBC treatments (37.73%), followed by in 3% FM-RBC (30.08%), all of which were significantly higher than that observed in 3% BC treatments (12.55-18.91%). Notably, the FM-RBC and FM-DBC treatments promoted the conversion of the exchangeable to the carbonate-bound and Fe/Mn oxyhydroxide fractions of Cd. The XRD, FTIR, and XPS analyses demonstrated that the loading amount of Fe-Mn oxide was positively correlated with the oxygen-containing functional group of biochar. CdO, Cd2Mn3O8 and CdCO3 were loaded on the FM-BC, indicating the existence of two main adsorption mechanisms: (1) the complexation with M-O (M: Fe, Mn) and acid oxygen-containing functional groups, (2) the precipitation with carbonate of Cd. In this work, we prepared two functional biochar that rapidly removes Cd from water and effectively fixes Cd in alkaline soil, thus, debasing the risk of Cd entry into the food chain.

Molecular Variation and Genomic Function of Citrus Vein Enation Virus.

In this study, we identified a new citrus vein enation virus (CVEV) isolate (named CVEV-DT1) through sRNA high-throughput sequencing and traditional sequencing. Phylogenetic analysis based on whole genome sequences of all known CVEV isolates revealed that CVEV-DT1 was in an evolutionary branch with other isolates from China. Molecular variation analysis showed that the single nucleotide variability along CVEV full-length sequences was less than 8%, with more transitions (60.55%) than transversions (39.43%), indicating a genetically homogeneous CVEV population. In addition, non-synonymous nucleotide mutations mainly occurred in ORF1 and ORF2. Based on disorder analysis of all encoded ORF by CVEV-DT1, we identified that the CVEV-DT1 coat protein (CP) formed spherical granules, mainly in the cell nucleus and partly throughout the cytoplasm, with liquid properties through subcellular localization and photobleaching assay. Furthermore, we also confirmed that the CVEV P0 protein has weak post-transcriptional RNA-silencing suppressor activity and could elicit a strong hypersensitive response (HR) in tobacco plants. Collectively, to the best of our knowledge, our study was the first to profile the genomic variation in all the reported CVEV isolates and reveal the functions of CVEV-DT1-encoded proteins.

Effects of sepiolite and biochar on the photosynthetic and antioxidant systems of pakchoi under Cd and atrazine stress.

Sepiolite and biochar effectively immobilize Cd and atrazine in vegetable soils. This study further investigated the effects of sepiolite and biochar on the photosynthetic and antioxidative defence systems of pakchoi under Cd and atrazine stress. The results showed that after adding sepiolite and biochar to contaminated soil, the chlorophyll content was restored and the photosynthetic rate increased, whereas the soluble sugar content of pakchoi decreased. In the antioxidant system of the plants, the activities of peroxidase, ascorbate peroxidase, and superoxide dismutase decreased, while the activity of catalase increased. The content of malondialdehyde, glutathione, and O2·- increased, but the content of H2O2 decreased. In general, remediation materials reduced the bioavailability of Cd and atrazine, reduced the stress on pakchoi, and restored and improved the rate of photosynthesis and function of antioxidants.

Higher fibrotic content of endometriotic lesions is associated with diminished prostaglandin E2 signaling.

PURPOSE: While the prevailing view holds that the prostaglandin E2 (PGE2) signaling plays a vital role in endometriosis, PGE2 also is known to be anti-fibrotic. We investigated the immunostaining of COX-2, EP2, and EP4, along with fibrotic content in ovarian endometrioma (OE) and deep endometriosis (DE) lesions, and in OE lesions from adolescent and adult patients. In addition, we evaluated the effect of substrate stiffness on the expression of COX-2, EP2, and EP4 in endometrial stromal cells. METHODS: Immunohistochemistry analysis of COX-2, EP2, and EP4, along with the quantification of lesional fibrosis, was conducted for OE and DE lesion samples and also OE lesion samples from adolescent and adult patients. The effect of substrate rigidity on fibroblast-to-myofibroblast transdifferentiation (FMT) and the expression of COX-2, EP2, and EP4, with or without TGF-ß1 stimulation, were investigated. RESULTS: The immunostaining of COX-2, EP2, and EP4 was substantially reduced in endometriotic lesions as lesions became more fibrotic. Both TGF-ß1 stimulation and stiff substrates induced FMT and reduced the expression of COX-2, EP2, and EP4. CONCLUSIONS: Since fibrosis is a common feature of endometriosis, our results thus cast doubts on the use of therapeutics that suppresses the PGE2 signaling pathway, either by inhibiting COX-2 or EP2/EP4.