Synthesis of metal-organic frameworks with multiple nitrogen groups for selective capturing Ag(I) from wastewater.

As a noble metal with extremely high economic benefits, the recovery of silver ions has attracted a particular deal of attention. However, it is a challenge to recover silver ions efficiently and selectively from aqueous solutions. In this research, the novel metal-organic frameworks (MOFs) adsorbent (Zr-DPHT) is prepared for the highly efficient and selective recovery of silver ions from wastewater. Experimental findings reveal that Zr-DPHT's adsorption of Ag(I) constitutes an endothermic process, with an optimal pH of 5 and exhibits a maximum adsorption capacity of 268.3 mg·g-1. Isotherm studies show that the adsorption of Ag(I) by Zr-DPHT is mainly monolayer chemical adsorption. Kinetic studies indicate that the internal diffusion of Ag(I) in Zr-DPHT may be the rate-limiting step. The mechanism for Ag(I) adsorption on Zr-DPHT involves electrostatic interactions and chelation. In competitive adsorption, Ag(I) has the largest partition coefficient (9.64 mL·mg-1), indicating a strong interaction between Zr-DPHT and Ag(I). It is proven in the adsorption-desorption cycle experiments that Zr-DPHT has good regeneration performance. The research results indicate that Zr-DPHT can serve as a potential adsorbent for efficiently and selectively capturing Ag(I), providing a new direction for MOFs in the recycling field of precious metals.

Circulating cardiac MicroRNAs safeguard against dilated cardiomyopathy.

BACKGROUND: Cardiac-resident or -enriched microRNAs (miRNAs) could be released into the bloodstream becoming circulating cardiac miRNAs, which are increasingly recognized as non-invasive and accessible biomarkers of multiple heart diseases. However, dilated cardiomyopathy (DCM)-associated circulating miRNAs (DACMs) and their roles in DCM pathogenesis remain largely unexplored. METHODS: Two human cohorts, consisting of healthy individuals and DCM patients, were enrolled for serum miRNA sequencing (10 vs. 10) and quantitative polymerase chain reaction validation (46 vs. 54), respectively. Rigorous screening strategy was enacted to define DACMs and their potentials for diagnosis. DCM mouse model, different sources of cardiomyocytes, adeno-associated virus 9 (AAV9), gene knockout, RNAscope miRNA in situ hybridization, mRFP-GFP-LC3B reporter, echocardiography and transmission electron microscopy were adopted for mechanistic explorations. RESULTS: Serum miRNA sequencing revealed a unique expression pattern for DCM circulating miRNAs. DACMs miR-26a-5p, miR-30c-5p, miR-126-5p and miR-126-3p were found to be depleted in DCM circulation as well as heart tissues. Their expressions in circulation and heart tissues were proven to be correlated significantly, and a combination of these miRNAs was suggested potential values for DCM diagnosis. FOXO3, a predicted common target, was experimentally demonstrated to be co-repressed within cardiomyocytes by these DACMs except miR-26a-5p. Delivery of a combination of miR-30c-5p, miR-126-5p and miR-126-3p into the murine myocardium via AAV9 carrying an expression cassette driven by cTnT promoter, or cardiac-specific knockout of FOXO3 (Myh6-CreERT2 , FOXO3 flox+/+ ) dramatically attenuated cardiac apoptosis and autophagy involved in DCM progression. Moreover, competitively disrupting the interplay between DACMs and FOXO3 mRNA by specifically introducing their interacting regions into murine myocardium crippled the cardioprotection of DACMs against DCM. CONCLUSIONS: Circulating cardiac miRNA-FOXO3 axis plays a pivotal role in safeguarding against myocardial apoptosis and excessive autophagy in DCM development, which may provide serological cues for DCM non-invasive diagnosis and shed light on DCM pathogenesis and therapeutic targets.

CIRBP-OGFR axis safeguards against cardiomyocyte apoptosis and cardiotoxicity induced by chemotherapy.

Cold-inducible RNA-binding protein (CIRBP) is documented to be required for maintaining cardiac function, however, its role in chemotherapy-induced cardiotoxicity remains obscured. Herein, we report that CIRBP decreases cardiomyocyte apoptosis and attenuates cardiotoxicity through disrupting OGF-OGFR signal. CIRBP deficiency is involved in diverse chemotherapeutic agents induced cardiomyocyte apoptosis. Delivery of exogenous CIRBP to the mouse myocardium significantly mitigated doxorubicin-induced cardiac apoptosis and dysfunction. Specifically, OGFR was identified as a downstream core effector responsible for chemotherapy-induced cardiomyocyte apoptosis. CIRBP was shown to interact with OGFR mRNA and to repress OGFR expression by reducing mRNA stability. CIRBP-mediated cytoprotection against doxorubicin-induced cardiac apoptosis was demonstrated to largely involve OGFR repression by CIRBP. NTX as a potent antagonist of OGFR successfully rescued CIRBP ablation-rendered susceptibility to cardiac dyshomeostasis upon exposure to doxorubicin, whereas another antagonist ALV acting only on opioid receptors did not. Taken together, our results demonstrate that CIRBP confers myocardium resistance to chemotherapy-induced cardiac apoptosis and dysfunction by dampening OGF/OGFR axis, shedding new light on the mechanisms of chemo-induced cardiotoxicity and providing insights into the development of an efficacious cardioprotective strategy for cancer patients.

Adenosine-functionalized UiO-66-NH2 to efficiently remove Pb(II) and Cr(VI) from aqueous solution: Thermodynamics, kinetics and isothermal adsorption.

A new zirconium-based adsorption material (UiO-66-AMP) was prepared by modifying UiO-66-NH2 with 5-adenosine to effectively remove Pb(II) and Cr(VI) from wastewater. The SEM, EDS, XRS and FT-IR characterization confirmed the successful synthesis of UiO-66-AMP. We conducted a sets of experiments to test the adsorption effectiveness of UiO-66-AMP for Pb(II) and Cr(VI). The maximum adsorption capacity of UiO-66-AMP for Cr(VI) (pH=2) and Pb(II) (pH=4) are 196.60 and 189.69 mg/g, respectively. The adsorption process conforms to the pseudo-second-order and Langmuir models, which indicates that the adsorption is a single-layer chemical process. Gibbs free energy (∆G) indicates that the adsorption of Pb(II) is an exothermic reaction, while the adsorption of Cr(VI) is an endothermic reaction. At the same time, the adsorbent maintains excellent adsorption capacity at least after 4 cycles. The good adsorption performance of UiO-66-AMP towards the metal ions was attributed to the surface complexation and electrostatic interactions. Therefore, the new adsorbent has obvious application prospect to remove Pb(II) and Cr(VI) from wastewater.

Candidate Effectors from Botryosphaeria dothidea Suppress Plant Immunity and Contribute to Virulence.

Fungal effectors play important roles in host-pathogen interactions. Botryosphaeria dothidea is an ascomycetous fungus that is responsible for the diseases of hundreds of woody plant species, including apple ring rot, which seriously affects apples worldwide. However, little is known about the effectors of B. dothidea. In this study, we analyzed the B. dothidea genome and predicted 320 candidate effector genes, 124 of which were successfully amplified and cloned. We investigated the effects of these genes on plant cell death in Nicotiana benthamiana while using a transient expression system. Twenty-four hours after initial inoculation with Agrobacterium tumefaciens cells carrying candidate effectors, the infiltrated leaves were challenged with A. tumefaciens cells carrying the BAX gene. In total, 116 candidate effectors completely inhibited, while one partially inhibited, the programmed cell death (PCD) of N. benthamiana induced by BAX, whereas seven candidate effectors had no effect. We then further tested seven candidate effectors able to suppress BAX-triggered PCD (BT-PCD) and found that they all completely inhibited PCD triggered by the elicitors INF1, MKK1, and NPK1. This result suggests that these effectors were activated in order to suppress pathogen-associated molecular pattern-triggered immunity. The signal peptides of these candidate effectors exhibited secretory activity in yeast (pSUC2 vector). Moreover, the respective deletion of Bdo_11198 and Bdo_12090 significantly reduced the virulence of B. dothidea. These results suggest that these effectors play important roles in the interaction of B. dothidea with its hosts.

Upconversion optogenetic micro-nanosystem optically controls the secretion of light-responsive bacteria for systemic immunity regulation.

Chemical molecules specifically secreted into the blood and targeted tissues by intestinal microbiota can effectively affect the associated functions of the intestine especially immunity, representing a new strategy for immune-related diseases. However, proper ways of regulating the secretion metabolism of specific strains still remain to be established. In this article, an upconversion optogenetic micro-nanosystem was constructed to effectively regulate the specific secretion of engineered bacteria. The system included two major modules: (i) Modification of secretory light-responsive engineered bacteria. (ii) Optical sensing mediated by upconversion optogenetic micro-nanosystem. This system could regulate the efficient secretion of immune factors by engineered bacteria through optical manipulation. Inflammatory bowel disease and subcutaneously transplanted tumors were selected to verify the effectiveness of the system. Our results showed that the endogenous factor TGF-ß1 could be controllably secreted to suppress the intestinal inflammatory response. Additionally, regulatory secretion of IFN-γ was promoted to slow the progression of B16F10 tumor.

Design of l-Cysteine Functionalized UiO-66 MOFs for Selective Adsorption of Hg(II) in Aqueous Medium.

Mercury ions can cause a series of hazards to humans and the environment, even in trace amounts. Here, we designed a novel adsorbent (Cys-UiO-66) by functionalizing NH2-UiO-66 with l-cysteine for selective removal of Hg(II) from solution. The Cys-UiO-66 was characterized by different instruments. The adsorption property of Cys-UiO-66 was evaluated by batch methods. The maximum adsorption capacity was 350.14 mg/g at pH 5.0. Furthermore, the adsorption isotherm and kinetics models were in accord with the Langmuir and pseudo-second-order models, respectively, evidencing that the adsorption behavior was dominated by monolayer chemisorption. The Cys-UiO-66 had better affinity for Hg(II) than other coexisting ions in wastewater and could be regenerated for at least five cycles. The results prove that Cys-UiO-66 is a talented and efficient sorbent for mercury ions.

A novel miRNA identified in GRSF1 complex drives the metastasis via the PIK3R3/AKT/NF-κB and TIMP3/MMP9 pathways in cervical cancer cells.

microRNAs (miRNAs) play an important role in carcinogenesis. Typically, miRNAs downregulate the target expression by binding to the 3' UTR of mRNAs. However, recent studies have demonstrated that miRNAs can upregulate target gene expression, but its mechanism is not fully understood. We previously found that G-rich RNA sequence binding protein (GRSF1) mediates upregulation of miR-346 on hTERT gene. To explore whether GRSF1 mediate other miRNA's upregulation on their target genes, we obtained profile of GRSF1-bound miRNAs by Flag-GRSF1-RIP-deep sequencing and found 12 novel miRNAs, named miR-G. In this study, we focused on miR-G-10, which is highly expressed in cervical cancer tissues and cell lines and serum from patients with metastatic cervical cancer. miR-G-10 in cervical cancer cells significantly promoted migration/invasion and anoikis resistance in vitro and lung metastasis in vivo. Furthermore, miR-G-10 bound to the 3' UTR of PIK3R3 and upregulated its expression to activate the AKT/NF-κB signal pathway in a GRSF1-dependent manner, whereas miR-G-10 suppressed TIMP3 in the AGO2 complex to modulate the MMP9 signaling pathway in cervical cancer cells. Taken together, our findings may provide a new insight into the upregulation mechanism mediated by miRNAs and a potential biomarker for cervical cancer.

One pot preparation of magnetic chitosan-cystamine composites for selective recovery of Au(III) from the aqueous solution.

A novel magnetic chitosan adsorbent (CDF-CS) was synthesized by inserting magnetic particles into the crosslinked compound of chitosan (CS) and cystamine based on one-step method for selectively recovering Au(III) from aqueous solution. The characterization and adsorption mechanism of CDF-CS were studied by SEM-EDS, VSM, FT-IR and XPS, respectively. The experimental results show that the adsorption capacity of CDF-CS is still large in a wide range of pH values (from 1 to 7) and has a higher adsorption capacity for Au(III) than the raw chitosan, the maximum adsorption capacity of CDF-CS for Au(III) was 478.47 mg/g about 6 h at pH = 7.0. The adsorption behavior is most consistent with this pseudo-second-order kinetic model. The adsorption process of gold ions by CDF-CS follows the Langmuir adsorption isotherm. Furthermore, the thermodynamic parameter indicates that the adsorption reaction of gold ions by CDF-CS is an endothermic chemisorption. CDF-CS has great potential for removing gold ions from aqueous solutions due to the excellent repeatability and selectivity. Finally, the adsorption mechanism is that chelation reaction and ion exchange mainly occurred between CDF-CS and Au(III). Therefore, CDF-CS is very promising in recovery of Au(III) from aqueous solutions.

GRSF1-mediated MIR-G-1 promotes malignant behavior and nuclear autophagy by directly upregulating TMED5 and LMNB1 in cervical cancer cells.

Emerging evidence has revealed that miRNAs could upregulate the expression levels of target genes. However, the molecular mechanism underlying upregulation of targets mediated by miRNAs remains unclear. In this study, we found a novel miRNA named MIR-G-1 by GRSF1-RNA immunoprecipitation (RIP)-deep sequencing, which could directly target and upregulate LMNB1 and TMED5 in a GRSF1-dependent manner in cervical cancer cells. In addition, upregulated MIR-G-1 in cervical cancer promoted a malignant phenotype in vitro and in vivo. TMED5 could interact with WNT7B and thus activated the canonical WNT-CTNNB1/ß-catenin signaling pathway. MIR-G-1 mediated the activation of this pathway. Furthermore, MIR-G-1 promoted serum starvation-induced nuclear macroautophagy/autophagy, and accelerated taxol (TAX)-induced DNA-damage repair in cervical cancer cells. Collectively, these findings may provide a new insight into the upregulation mechanism and nuclear autophagy mediated by miRNAs and provide a potential biomarker for cervical cancer. Abbreviations: 3'UTR: 3' untranslated region; EMSA: electrophoretic mobility shift assay; EMT: epithelial-mesenchymal transition; GRSF1: G-rich RNA sequence binding factor 1; IF: immunofluorescence; IP: immunoprecipitation; IHC: immunohistochemistry; lnc: long noncoding; miRNA:microRNA; TAX: taxol; TMED5: transmembrane p24 trafficking protein 5.

DCLK1 promotes epithelial-mesenchymal transition via the PI3K/Akt/NF-κB pathway in colorectal cancer.

Double cortin-like kinase 1 (DCLK1) plays important roles during the epithelial-mesenchymal transition (EMT) process in human colorectal cancer (CRC). However, the role of DCLK1 in regulating the EMT of CRC is still poorly understood. In this study, we report evidence that DCLK1 acts as a potent oncogene to drive its extremely malignant character of EMT in an NF-κB-dependent manner in CRC cells. Mechanistic investigations showed that DCLK1 induced the NF-κBp65 subunit expression through the PI3K/Akt/Sp1 axis and activated NF-κBp65 through the PI3K/Akt/IκBα pathway during the EMT of CRC cells. Moreover, we found that silencing the expression of DCLK1 inhibited the invasion and metastasis of CRC cells in vivo. Collectively, our findings identify DCLK1 as a pivotal regulator of an EMT axis in CRC, thus implicating DCLK1 as a potential therapeutic target for CRC metastasis.

Cross-talk of the related bioactivity mediators in serum after injection of soluble TNF-α receptor on silicosis model of rats.

This study investigates cross-talk of the related bioactivity mediators in silica-induced pulmonary inflammatory and fibrosis on rats, which contributes to the preventive and therapeutic effect of soluble TNF-α receptor. Wistar rats received saline or 50 mg of quartz by intratracheal instillation. Rats in drug-treated groups were given soluble tumor necrosis factor-α (TNF-α) receptor (500 µg) by hypodermic injection on days 1, 5 and 8 after operation. At 7 days or 14 days after instillation, rats were killed to observe the degree of injury and expression of the related bioactivity mediators including nuclear factor KB (NF-KB), nitric oxide, interleukin-1ß, interleukin-10, transforming growth factor beta 1 (TGF-ß1), TNF-α, interferon-Y (IFN-Y) and granulocyte macrophage colony-stimulating factor (GM-CSF). The area percentages of type I and III collagens in intervention group were lower than those in silica group. The expression of NF-κB, TGF-ß1, and COL I were lower in intervention group than in silica group(p < 0.05) and GM-CSF was significantly higher (p < 0.05) at 7 days after instillation, however, NF-κB, TGF-ß1, and COL I were identically lower in intervention group than in silica group, and TNF-α, IFN-γ, and GM-CSF were higher at 14 days after instillation. It may be concluded that soluble TNF-α receptor upregulating or downregulating the expression of the related bioactivity mediators results in decreasing lung injury induced by silica.