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It is well known that chemical compositions and structural arrangements of materials have a great influence on their resultant properties. Diverse functional materials have been constructed by using either biomolecules (peptides, DNA, and RNA) in nature or artificially synthesized molecules (polymers and pillararenes). The relationships between traditional building blocks (such as peptides) have been widely investigated, for example how hydrogen bonds work in the peptide multistage assembly process. However, in contrast to traditional covalent bond-based building blocks-based assembly, suprastructures formed by noncovalent bonds are more influenced by specific bond features, but to date only a few results have been reported based on noncovalent bond-based building block multistage assembly. Here, three metal-organic cycles (MOCs) were used to show how coordination bonds influence the bimetallacycle conformation then lead to the topology differences of MOC multilevel ordered materials. It was found that the coordination linker (isophthalate-Pt-pyridine) is an important factor to tune the shape and size of the MOC-derived suprastructures. [ABSTRACT FROM AUTHOR]

Abstract In this study, nitrobenzene (NB) as typical refractory organic pollutants was effectively degraded by a new green approach, which was achieved by the chemical effect of natural organic matters (NOMs) under solar illumination as a potential natural degradation process. 4-hydroxycoumarin (4HC), which is natural compound and can be extracted from many plants, was found as an efficient photosensitizer to promote the photoreduction of NB to 4-aminophenol under the solar illumination. The reaction products were definitely identified by LC-MS/MS and 1H NMR. The response spectrum of 4HC excited state (4H-chromene-2,4-diol radical, S 1) as key intermediate was also obtained by transient absorption spectroscopy (TAS) measurements, which showed that the decay time of S 1 was around 250 ps. Then, the measurements of electron paramagnetic resonance (EPR) confirmed the existence of OH. As a result, the reaction mechanism between 4HC and NB was proposed. In addition, the influence parameters such as light sources, gas surroundings, solvents, pH values were investigated to further reveal the reaction process. Graphical abstract The degradation pathway of refractory nitrobenzene in water through the natural 4-hydroxycoumarin under solar illumination. Image 1 Highlights • A new natural organic matter could be activated as reducing agent under illumination. • 4-hydroxycoumarin as natural compound was found to be an efficient photosensitizer. • The refractory nitrobenzene was degraded to 4-aminophenol by 4HC as green process. • 4HC excited state (4H-chromene-2,4-diol radical) as key intermediate was confirmed. • Reaction pathway between 4HC and NB was completely proposed by product analysis. [ABSTRACT FROM AUTHOR]

Abstract A novel electro-generated hydroxyl radical (OH) technique was constructed to effectively degrade the anti-epilepsy carbamazepine (CBZ) representing typical recalcitrant pharmaceutical only through electrochemical method as an alterative peroxone process. The technique involves simultaneously electro-generated H 2 O 2 using a carbon-polytetrafluoroethylene (C/PTFE) cathode to reduce the injected O 2 and electro-generated O 3 using H 2 O oxidation with a Ti mesh/PbO 2 anode in membrane electrode assembly (MEA). The significant OH formation through the synergetic system of in-situ produced H 2 O 2 and O 3 electrochemically could achieved carbamazepine decomposition and total organic carbon (TOC) removal as compared to electro-generated H 2 O 2 or O 3 alone. The main influential factors including current density and aqueous pH were investigated to reveal their effect on CBZ removal efficiencies. Under optimal parameters, CBZ decomposition and TOC mineralization could be completely accomplished after 10 min and 90 min electrolysis, respectively. According to intermediates distribution (e.g. hydroxylated CBZ, phenolics, and carboxylic acids) identified by HPLC-MS/MS, the degradation pathways were proposed for CBZ removal by the synergetic system of C/PTFE-O 2 and MEA. The above results indicated that this electrochemically synergetic system is a potential technique to further purify the water contaminated by recalcitrant pharmaceuticals. Graphical abstract Image 1 Highlights • A novel electrochemical advanced oxidation process was devised for water treatment. • Dual-cell system was innovatively assembled to achieve electro-generated H 2 O 2 /O 3. • Hydroxyl radicals can be effectively formed by the electrochemical peroxone process. • The synergetic process could degrade ozone-refractory pharmaceutical contaminants. • The degradation pathway of carbamazepine by the synergetic system was proposed. [ABSTRACT FROM AUTHOR]

Hydraulic retention time (HRT), as an important parameter in the wastewater treatment process, has a great impact on water quality and energy consumption. With the rapid advances in computer technology and deepened understanding of in microbial metabolism, a series of activated sludge models (ASMs) have been developed and applied in wastewater treatment. However, ASMs simulation based on the nexus of HRT, water treatment process, water quality and energy consumption has yet to be verified. In this study, HRT was creatively linked to water treatment process variation. And a novel combined process model (CPM) was developed based on the operational data and treatment performance data from 4 full-scale coking wastewater treatment processes. In the CPM, an array of biological treatment processes were represented by setting the HRT in respective treatment units of the anaerobic-oxic-hydrolytic & denitrification-oxic (A/O/H/O) process. The relationships between HRT, effluent quality and energy consumption were systematically analyzed. Results showed that: (i) for A/O/H/O process, the HRT of first oxic (O1) reactor has a key effect on the effluent water quality and energy consumption, while the impact of the anaerobic (A) reactor HRT was limited; (ii) the O/H/O process has a clear advantage in treating coking wastewater due to the carbon removal and detoxification function of O1 reactor; (iii) the lowest energy consumption (with the total system HRT below 210 h) to meet the biological effluent quality requirements (COD = 200 mg/L, TN = 50 mg/L) is 4.429 kWh/m3. Since the CPM could effectively work out the optimal process configuration and break the boundaries between HRT and process variation, it has enormous potential to be extended to the design of other wastewater treatment processes. [Display omitted] • A novel modeling idea for wastewater biological treatment process selection or design. • The relationship between hydraulic retention time, water quality, and energy consumption was revealed. • The boundaries between hydraulic retention time and process variation can be broken. [ABSTRACT FROM AUTHOR]

[Display omitted] • Variations of the B/C ratio in theory, laboratory and engineering were revealed. • B/C characterizes capacities in biodegradation and chemical oxidation of wastewater. • The B/C ratio serves as a guide in the design of biological treatment units. • The B/C ratio is used as a probing index in evaluation of the treatment performance. Biodegradation of coking wastewater (CWW) containing high concentrations of toxic pollutants with nutritional imbalance is challenging. Biodegradability estimated as the ratio of 5-day biochemical oxygen demand (BOD 5) to chemical oxygen demand (COD) was studied along with the influential operational factors in a full-scale oxic/hydrolytic & denitrification/oxic (O/H/O) plant for CWW treatment. The influential factors for the B/C ratio in each unit of the O/H/O provided by the experimental and theoretical BOD 5 were elucidated. Batch experiment with various sludge inoculation settings showed that the B/C ratio of raw CWW increased from 0.38 ± 0.04 to 0.47 ± 0.05 after flocculation pretreatment due to the removal of sulfide and cyanide. In the O1 reactor, quickly depleted biodegradable pollutants resulted in a drastic decrease of the B/C ratio to 0.1 ± 0.02 together with a reduction in the CWW toxicity. In the H reactor, the B/C ratio increased to 0.28 ± 0.04 because of the hydrolysis of residual macromolecular organic matter and nitrite accumulation from the denitrification process. The B/C ratio in the O2 reactor dropped below 0.06 along with the complete nitrification. The relative abundance of organic pollutants, the structure and function of bacterial community were analyzed in each reactor to explain the changes in the B/C ratio. On the whole, the monitoring of the B/C ratio along different stages of the CWW treatment is an approach suitable to follow the efficacy of functional bacterial groups and their responses to the water characteristics. The B/C ratio thus becomes a marker of the extent of nitrogen transformations, CWW detoxification and mineralization of organic compounds. More broadly, the B/C ratio helps optimize the operation parameters of biological processes and indicate the functionality of each unit. [ABSTRACT FROM AUTHOR]

In this study, physicochemical pre- and post-treatment of highly polluting coking wastewater (CWW) for the removal of refractory compounds and recovery of high-energy substances/components was investigated. An economic optimization model targeting the development of a cost-effective and sustainable treatment technology was proposed. At the post-treatment stage, powdered activated carbon (PAC) was used to separate the refractory and toxic pollutants from the bio-treated CWW, with the adsorption capacity ranging from 50 to 120 mg chemical oxygen demand (COD) g−1 PAC. Then, the spent PAC, together with a coagulant, was reused in the pre-treatment of highly concentrated raw CWW, which lifted the adsorption capacity to 800–1200 mg COD g−1 PAC. Results showed that the adsorbent's high selectivity towards macromolecular and complicated pollutants could remove 25–65 % of COD in both CWW flows. Analysis of pollutants' molecular weight distribution and GC-MS indicated a good affinity between PAC and high-energy pollutants (phenolic compounds and alkanes), which could transfer 144,555 kJ m−3 of energy from CWW to the adsorption-coagulation sludge. The economic optimization model suggested that the cost of the adsorbent was compensated by the net benefits of energy recovery and that profit was achieved when the PAC price was less than 5562 CNY t−1. The proposed two-stage PAC/coagulant approach offers a way to sustainable water quality and sludge management, plus energy recycling, in CWW treatment. It may also be applied to the treatment of other industrial wastewaters. [Display omitted] • Adsorption in coking wastewater (CWW) treatment provides energy recovery in recycled coking. • Pre-adsorption/coagulation reduces CWW toxicity improving the biotreatment result. • Post-adsorption of biological effluent reduces the environmental risk. • Economic model of adsorption/coagulation technology confirms energy self-sufficiency in CWW treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • The zero-discharge integrated process (ZDIP) was successfully applied to treat coking wastewater. • The ZDIP is made up of A/O/H/O/A biochemical, pre-processing, membrane and end-processing units. • Membrane barriers for water reuse technology were identified and preliminarily removed. • The operating costs of the ZDIP can be reduced by the principle of hierarchical circulation. • Zero-discharge refers to the resourceization of all gas-liquid-solid substances in the treatment process to be environment-friendly. The wastewater from coke making is characterized by high toxicity, high concentration of pollutants and complex composition. Therefore, it is difficult to treat using conventional methods such as advanced oxidation and ion exchange processes. In this study, a zero-discharge integrated process (ZDIP) composed of pre-physicochemical – oxic – hydrolytic & denitrification – oxic – post-physicochemical (A/O/H/O/A) biological, pre-processing, membrane and end-processing units was created to treat coking wastewater. The results showed that most of the chemical oxygen demand, sulfide, cyanide and NH 4 +-N in the coking wastewater were removed in A/O/H/O/A biochemical unit. Hardness, F− and turbidity were further eliminated in the pre-processing unit, while more than 98 % of the effluent was reused in the membrane unit. Finally, zero discharge treatment of residual liquid and sludge was realized in the end-processing unit. The operating cost was about 2.49 USD/m3 and the carbon emissions 9.17 kg CO 2 -eq/m3 of influent for the entire ZDIP. Theoretically, the ZDIP based on hierarchical cycle drive, which is applicable to handling complex wastewaters, cutting carbon emissions and recycling water, can be taken as an effective wastewater treatment process in the next decade. [ABSTRACT FROM AUTHOR]

Fatty acid ethanolamides (FAEs) and endocannabinoids (ECs) have been shown to alleviate pain and inflammation, regulate motility and appetite, and produce anticancer, anxiolytic, and neuroprotective efficacies via cannabinoid receptor type 1 (CB1) or type 2 (CB2) or via peroxisome proliferator-activated receptor α (PPAR-α) stimulation. FAEs and ECs are synthesized by a series of endogenous enzymes, including N-acylphosphatidylethanolaminephospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), or phospholipase C (PLC), and their metabolism is mediated by several metabolic enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamine acid amidase (NAAA), or cyclooxygenase 2 (COX-2). Over the past decades, increasing the concentration of FAEs and ECs through the inhibition of degrading enzymes has been considered to be a viable therapeutic approach to enhance their antinociceptive and anti-inflammatory effects, as well as to protect the nervous system. [ABSTRACT FROM AUTHOR]

A small library of ferrocene-containing amides has been synthesized using standard amide coupling chemistry with ferrocenylamine. Ferrocene analogues of known bioactive adamantylamides were shown to be effective cannabinoid receptor (CB1 and CB2) agonists, displaying, in many cases, single-digit nanomolar potency. Three final ferrocene-containing derivatives have been characterized in the solid state by X-ray crystallography and display intramolecular hydrogen bonding of the type NH---C═O. N-Methylation of the amide, confirmed by X-ray crystallography, leads to both loss of hydrogen bonding and biological activity. [ABSTRACT FROM AUTHOR]

By its unique advantages over traditional medicine, nanomedicine has offered new strategies for cancer treatment. In particular, the development of drug delivery strategies has focused on nanoscale particles to improve bioavailability. However, many of these nanoparticles are unable to overcome tumor resistance to chemotherapeutic agents. Recently, new opportunities for drug delivery have been provided by oligonucleotides that can self-assemble into three-dimensional nanostructures. In this work, we have designed and developed functional DNA nanostructures to deliver the chemotherapy drug doxorubicin (Dox) to resistant cancer cells. These nanostructures have two components. The first component is a DNA aptamer, which forms a dimeric G-quadruplex nanostructure to target cancer cells by binding with nucleolin. The second component is double-stranded DNA (dsDNA), which is rich in -GC- base pairs that can be applied for Dox delivery. We demonstrated that Dox was able to efficiently intercalate into dsDNA and this intercalation did not affect the aptamer's three-dimensional structure. In addition, the Aptamer-dsDNA (ApS) nanoparticle showed good stability and protected the dsDNA from degradation in bovine serum. More importantly, the ApS&Dox nanoparticle efficiently reversed the resistance of human breast cancer cells to Dox. The mechanism circumventing doxorubicin resistance by ApS&Dox nanoparticles may be predominantly by cell cycle arrest in S phase, effectively increased cell uptake and decreased cell efflux of doxorubicin. Furthermore, the ApS&Dox nanoparticles could effectively inhibit tumor growth, while less cardiotoxicity was observed. Overall, this functional DNA nanostructure provides new insights into the design of nanocarriers to overcome multidrug resistance through targeted drug delivery. [ABSTRACT FROM AUTHOR]

Poor penetration of therapeutic drugsinto tumors is a major challengein anticancer therapy, especially in solid tumors, leading to reducedtherapeutic efficacy in vivo. In the study, we used a new tumor-penetratingpeptide, CRGDK, to conjugate onto the surface of doxorubicin encapsulatednanoscale micelles. The CRGDK peptide triggered specific binding toneuropilin-1, leading to enhanced cellular uptake and cytotoxicityin vitro and highly accumulation and penetration in the tumors invivo. [ABSTRACT FROM AUTHOR]

mRNA-based therapeutics have emerged as a promising approach to treat cancer. However, creation of theranostic strategies to both deliver mRNA and simultaneously detect cancer is an important unmet goal. Here, we report the development of theranostic dendrimer-based lipid nanoparticle (DLNP) system containing PEGylated BODIPY dyes (PBD) for mRNA delivery and near-infrared (NIR) imaging in vitro and in vivo. DLNPs formulated with a pH-responsive PBD-lipid produced 5- to 35-fold more functional protein than control DLNPs formulated with traditional PEG-lipid in vitro and enabled higher mRNA delivery potency in vivo at a low dose of 0.1 mg kg-1 when formulated with a PBD-lipid containing a BODIPY core, indole linker, and PEG length between 1000 and 5000 g/mol. Moreover, we found the intensity of mRNA expression in the liver correlated with the pKa of DLNPs, indicating that DLNPs with a pKa close to 6.3 could generally produce more protein in livers. Notably, 4A3-SC8&PEG2k 5d formulated DLNPs successfully mediated mRNA expression in tumors and simultaneously illuminated tumors via pH-responsive NIR imaging. The described theranostic lipid nanoparticles that combine mRNA delivery and NIR imaging hold promise as an applicable future approach to simultaneously detect and treat cancer. Theranostic nanomedicines have the potential to both detect cancer and provide therapeutically active drugs. Herein, a theranostic DLNP system containing PBD-lipids is developed for effective mRNA delivery and non-invasive NIR imaging. This unique combination of PDB-lipids with DLNPs enhanced mRNA production in cancer cells, mediated mRNA expression in tumors, and simultaneously illuminated tumors via pH-responsive NIR imaging. Unlabelled Image [ABSTRACT FROM AUTHOR]

Germline or somatic loss-of-function mutations of fumarate hydratase (FH) predispose patients to an aggressive form of renal cell carcinoma (RCC). Since other than tumor resection there is no effective therapy for metastatic FH-deficient RCC, an accurate method for early diagnosis is needed. Although MRI or CT scans are offered, they cannot differentiate FH-deficient tumors from other RCCs. Therefore, finding noninvasive plasma biomarkers suitable for rapid diagnosis, screening, and surveillance would improve clinical outcomes. Taking advantage of the robust metabolic rewiring that occurs in FH-deficient cells, we performed plasma metabolomics analysis and identified 2 tumor-derived metabolites, succinyl-adenosine and succinic-cysteine, as excellent plasma biomarkers for early diagnosis. These 2 molecules reliably reflected the FH mutation status and tumor mass. We further identified the enzymatic cooperativity by which these biomarkers are produced within the tumor microenvironment. Longitudinal monitoring of patients demonstrated that these circulating biomarkers can be used for reporting on treatment efficacy and identifying recurrent or metastatic tumors. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the impacts of SIRT1 activation on rheumatoid arthritis (RA)-related angiogenesis. Methods: HUVECs were cultured by different human serum. Intracellular metabolites were quantified by UPLC-MS. Next, HUVECs and rat vascular epithelial cells under different inflammatory conditions were treated by a SIRT1 agonist resveratrol (RSV). Cytokines and biochemical indicators were detected by corresponding kits. Protein and mRNA expression levels were assessed by immunoblotting and PCR methods, respectively. Angiogenesis capabilities were evaluated by migration, wound-healing and tube-formation experiments. To down-regulate certain signals, gene-specific siRNA were applied. Results: Metabolomics study revealed the accelerated glycolysis in RA serum-treated HUVECs. It led to ATP accumulation, but did not affect GTP levels. RSV inhibited pro-angiogenesis cytokines production and glycolysis in both the cells, and impaired the angiogenesis potentials. These effects were mimicked by an energy metabolism interrupter bikini in lipopolysaccharide (LPS)-primed HUVECs, largely independent of HIF-1α. Both RSV and bikinin can inhibit the activation of the GTP-dependent pathway Rho/ROCK and reduce VEGF production. Abrogation of RhoA signaling reinforced HIF-1α silencing-brought changes in LPS-stimulated HUVECs, and overshadowed the anti-angiogenesis potentials of RSV. Conclusion: Glycolysis provides additional energy to sustain Rho/ROCK activation in RA subjects, which promotes VEGF-driven angiogenesis and can be inhibited by SIRT1 activation. [ABSTRACT FROM AUTHOR]

Epigenetic reprogramming plays a critical role in chondrocyte senescence during osteoarthritis (OA) pathology, but the underlying molecular mechanisms remain to be elucidated. Here, using large-scale individual datasets and genetically engineered (Col2a1-CreERT2; Eldr flox/flox and Col2a1-CreERT2; ROSA26 -LSL- Eldr +/+ knockin) mouse models, we show that a novel transcript of long noncoding RNA ELDR is essential for the development of chondrocyte senescence. ELDR is highly expressed in chondrocytes and cartilage tissues of OA. Mechanistically, exon 4 of ELDR physically mediates a complex consisting of hnRNPL and KAT6A to regulate histone modifications of the promoter region of IHH , thereby activating hedgehog signaling and promoting chondrocyte senescence. Therapeutically, GapmeR-mediated silencing of ELDR in the OA model substantially attenuates chondrocyte senescence and cartilage degradation. Clinically, ELDR knockdown in cartilage explants from OA-affected individuals decreased the expression of senescence markers and catabolic mediators. Taken together, these findings uncover an lncRNA-dependent epigenetic driver in chondrocyte senescence, highlighting that ELDR could be a promising therapeutic avenue for OA. [Display omitted] Ji and colleagues identify ELDR as a critical regulator of chondrocyte senescence. Mechanistically, the core region of ELDR physically mediates a complex consisting of hnRNPL and KAT6A to regulate histone modifications of the promoter region of IHH , thereby activating hedgehog signaling. [ABSTRACT FROM AUTHOR]

Ruthenium (Ru) complexes are developed as latent emissive photosensitizers for cancer and pathogen photodiagnosis and therapy. Nevertheless, most existing Ru complexes are limited as photosensitizers in terms of short excitation and emission wavelengths. Herein, we present an emissive Ru(II) metallacycle (herein referred to as 1) that is excited by 808-nm laser and emits at a wavelength of ~1,000 nm via coordinationdriven self-assembly. Metallacycle 1 exhibits good optical penetration (~7 mm) and satisfactory reactive oxygen species production properties. Furthermore, 1 shows broadspectrum antibacterial activity (including against drug-resistant Escherichia coli) as well as low cytotoxicity to normal mammalian cells. In vivo studies reveal that 1 is employed in precise, second near-infrared biomedical window fluorescent imaging-guided, photo-triggered treatments in Staphylococcus aureus-infected mice models, with negligible side effects. This work thus broads the applications of supramolecular photosensitizers through the strategy of lengthening their wavelengths. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases and vascular trauma can be commonly found in the population. Scholars worldwide hope to develop small-diameter vascular grafts that can replace autologous vessels for clinical use. Decellularized blood vessels can retain the original morphology, structure, and physical properties of blood vessels, which is conducive to cell growth, proliferation, and differentiation. In this study, porcine coronary arteries (PCAs) were decellularized to prepare decellularized porcine coronary artery (DPCA), and bilayer hybrid scaffolds were prepared by coating gelatin and sodium alginate mixed hydrogel of seven different proportions and combined with mouse fibroblasts (L929 cells) to study the construction of tissue engineering vessels in vitro. The obtained bilayer hybrid scaffolds were 3–7 cm in length, 5 mm in external diameter, and 1 mm in average wall thickness. All seven bilayer hybrid scaffolds showed good biocompatibility after cell inoculation. Compared with 2D culture, cells on 3D scaffolds grew relatively slowly in the first 4 days, and the number of cells proliferated rapidly at 7 days. In the same culture days, different concentrations of hydrogel also had an impact on cell proliferation. With the increase of hydrogel content, cells on the 3D scaffold formed cell colonies faster. The results showed that the scaffold had good biocompatibility and could meet the needs of artificial blood vessel construction. [ABSTRACT FROM AUTHOR]

A novel approach of ECG baseline wander correction based on mean-median filter and empirical mode decomposition is presented in this paper. The low frequency parts of the original signals were removed by the mean median filter in a nonlinear way to obtain the baseline wander estimation, then its series of IMFs were sifted by t-test after empirical mode decomposition. The proposed method, tested by the ECG signals in MIT-BIH Arrhythmia database and European ST_T database, is more effective compared with other baseline wander removal methods. [ABSTRACT FROM AUTHOR]

A novel approach of ECG baseline wander correction based on mean-median filter and empirical mode decomposition is presented in this paper. The low frequency parts of the original signals were removed by the mean median filter in a nonlinear way to obtain the baseline wander estimation, then its series of IMFs were sifted by t-test after empirical mode decomposition. The proposed method, tested by the ECG signals in MIT-BIH Arrhythmia database and European ST_T database, is more effective compared with other baseline wander removal methods. [ABSTRACT FROM AUTHOR]

Abstract: A group of amphiphilic cationic polymers, methoxy polyethylene glycol-block-(polycaprolactone-graft-poly(2-(dimethylamino)ethyl methacrylate)) (PECD), were synthesized by combining ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) methods to form nanoparticles (NPs). The structures of these amphiphilic cationic polymers were characterized by 1H NMR measurement. The PECD NPs have hydrophobic cores covered with hydrophilic PEG and cationic PDMAEMA chains. These self-assembly nanoparticles were characterized by dynamic light scattering (DLS) technique. PECD NPs can effectively condense DNA to form compact complexes of the size 65–160 nm suitable for gene delivery. The in vitro gene transfection studies of HeLa and HepG2 cells show that PECD NPs have better transfection efficiency compared to polyethylenimine (PEI) and Lipofectamine 2000 at low dose (N/P = 5). The cytotoxicity result shows that PECD NPs/DNA complexes at the optimal N/P ratio for transfection have comparable toxicity with PEI and Lipofectamine. These results indicate that PECD NPs have a great potential to be used as efficient polymeric carriers for gene transfection. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) continue to attract increasing interest with respect to their applications as luminescent materials. The ordered structure of the metal-organic complex facilitates the selective integration of PAHs that can be tuned to function cooperatively. Here, a unique highly twisted anthracene-based organoplatinum metallacycle was prepared via coordination-driven selfassembly. Single-crystal X-ray diffraction analysis revealed that the metallacycle was twisted through the cooperation of strong π···π stacking interactions and steric hindrance between two anthracenebased ligands. Notably, the intramolecular twist and aggregation behavior introduced restrictions to the conformational change of anthracenes, which resulted in increased emission intensity of the metallacycle in solution. The emission behaviors and suprastructures based on the highly twisted metallacycle can be modulated by the introduction of different solvents. This study demonstrates that this metallacycle with highly twisted structure is a promising candidate for sensing and bioimaging applications. [ABSTRACT FROM AUTHOR]

The preparation of high-efficiency, stable, and low-cost oxygen evolution reactions (OER) and hydrogen evolution reactions (HER) electrocatalysts remains a challenge for new energy systems. In this study, three-dimensional (3D) cobalt-nickel bimetal MOFs were used as precursors to synthesize catalysts through thermal decomposition, carbonization, nitriding, oxidation, phosphating, sulfurizing, and selenization, respectively. In 1.0 M KOH electrolyte, the overpotential of Co/Ni-MOFs@Se for OER was 238 mV and the that of Co/Ni-MOFs@P for HER was 194 mV at a current density of 10 mA cm−2. Based on the excellent OER and HER performances of Co/Ni-MOFs@Se and Co/Ni-MOFs@P, these two materials were further assembled into electrodes for overall water splitting. Results showed that a potential of only 1.59 V was required to provide a current density of 10 mA cm−2. The electrodes also exhibited long-term durability in a 2000 min stability test without significant changes in the catalytic performances. According to the difference in the doped non-metal elements, an electrode pair with a suitable matching degree was constructed, thereby improving the overall water splitting performance. Thus, the controllable modification of the metal-organic frameworks (MOFs)-derived carbon materials (CMs) effectively improved the materials' catalytic water splitting performance. It was possible to further develop an efficient, inexpensive, and low-cost assembled electrode pair. Schematic illustration of the preparation of Co/Ni-MOFs@X (X = C, N, O, P, S or Se) materials, and their direct utilization for water splitting. Image 1 • 3D-Co/Ni-MOFs derivatized materials were developed as bifunctional for HER and OER. • High-efficiency electrocatalyst based on heteroatom doping. • The fabricated electrode presents an excellent overall water splitting activity. [ABSTRACT FROM AUTHOR]

Municipal sludge can be utilized as a resource despite its polluting nature. However, the presence of heavy metals lowers its resource value, and their uniform dispersion in conventional biological processes because of sludge reflux poses enormous difficulties for the subsequent separation/recovery. In this study, the enrichment strategies of Cu and Zn in simulated wastewater based on a new biological process named oxic-hydrolytic & denitrification-oxic (O1/H/O2 or O/H/O) combination were investigated and the influence mechanisms of pH, chelate, operating parameters, and denitrification reaction control were illustrated. Results showed that the amount Cu and Zn in the sludge of H reactor exceeded those of both O1 and O2 when pH of O1＜6.5. The maximum sludge-water partition coefficients (K d) of Cu and Zn in H reactor were 3128 and 3421 times when the influent concentration of NH 3 –N was at a certain value (210 mg/L NH 4 Cl for Cu and 140 mg/L NH 4 Cl for Zn). This was ascribed to the control of nitrification rate, ammonification/nitrosation in the O1 reactor, anaerobic ammonia oxidation combined with autotrophic denitrification in the H reactor, optimal hydraulic retention time (HRT) and sludge retention time (SRT). Under the pre-set conditions of water quality and operation parameters, the precipitates in the sludge were found to be Cu(OH) 2 , Zn(OH) 2 , CuS, ZnS which were theoretically and instrumentally characterized. In sum, the joint regulation of biological combination and biochemical reaction will provide new enrichment/separation strategies for heavy metals in municipal sludge management. • Cu and Zn can be enriched in the H-unit sludge of a new biological process named O/H/O process. • Enrichment of Cu and Zn was the coupling of ammonization, complexation and precipitation regulated by pH. • The O/H/O process can realize the collaborative management of wastewater and sludge. [ABSTRACT FROM AUTHOR]

[Display omitted] • 4,7-DHC is used as a novel green photocatalyst for complete degradation of nitrobenzene; • A symbiotic reduction–oxidation process is found during the degradation; • Both reductive S 2 radicals and oxidative OH could be generated sustainably during irradiation. In this study, a synergistic reduction–oxidation process was proposed using natural organic matters (NOMs) as an organic photocatalyst for complete degradation of nitrobenzene (NB) that was difficult to oxidative decomposition directly. It has been verified by electron spin resonance (ESR) that both reductive organic free radical (4H-chromene-2,4,7-triol radical, S 2) and oxidative OH radicals could be generated sustainably by using 4,7-dihydroxycoumarin (4,7-DHC) as a green photocatalyst under UV light irradiation, and 95.07% of NB degradation efficiency was achieved after 4-h irradiation with 40 µM 4,7-DHC. The formation of aniline as a reductive product was convenient for the attack of OH radicals, making it easier for the complete degradation of NB. In addition, 4,7-DHC showed high photocatalytic activity in a wide range of pH from 1 to 13, and the best photocatalytic activity was achieved with a pH value of 4.56. Besides, the effect of common coexisted ions (SO 4 2−, Cl− and NO 3 −) on the NB degradation was discussed, and the highest k value was obtained with SO 4 2− (80 µM), NO 3 − (120 µM) or Cl− (20 µM). Moreover, 4,7-DHC exhibited extensive degradability to the frequently coexisted pollutants in NB-contaminated wastewater including humic acid (HA), aniline (AN) and m-dinitrobenzene (m-DNB), which might be extended into a potential approach for environmental remediation of NB-contaminated water due to its low cost and accessibility of 4,7-DHC as NOMs. [ABSTRACT FROM AUTHOR]

Due to their biodegradable character, polyesters such as polycaprolactone (PCL), poly( d , l -lactide) (PDLLA), and polylactic-co-glycolic acid (PLGA) were widely used as the hydrophobic cores of amphiphilic cationic nanoparticles (NPs) for siRNA delivery. However, fewer researches focused on facilitating siRNA delivery by adjusting the polyester composition of these nanoparticles. Herein, we investigated the contribution of polyester segments in siRNA delivery in vitro by introducing different ratio of DLLA moieties in PCL segments of mPEG-block-PCL-graft-poly(dimethylamino ethyl methacrylate)(PEG-b-PCL-g-PDMAEMA). It was noticed that compared with the other ratios of DLLA moieties, a certain molar ratio (about 70%) of the NPs, named mPEG 45 -P(CL 21 -co-DLLA 48 )-g-(PDMAEMA 29 ) 2 (PECLD-70), showed the highest gene knockdown efficiency but poorest cellular uptake ability in vitro. Further research revealed that NPs with various compositions of the polyester cores showed different physicochemical properties including particle size, zeta potential and stiffness, leading to different endocytosis mechanisms thus influencing the cellular uptake efficiency. Subsequently, we observed that the cells treated by PECLD-70 NPs/Cy5 siRNA complexes exhibited more diffuse Cy5 signal distribution than other NPs by confocal laser scanning microscope, which suggested that siRNA delivered by PECLD-70 NPs/Cy5 siRNA complexes possessed of stronger capabilities in escaping from endosome/lysosome, entering the RNA-induced silencing complex (RISC) and cutting the target mRNA efficiently. The different siRNA release profile was dominated by the degradation rate of polyester segments. Therefore, it could be concluded that the adjustment of hydrophobic core of cationic nanoparticles could significantly affect their transfection behavior and appropriate polyester composition should be concerned in designing of analogous siRNA vectors. [ABSTRACT FROM AUTHOR]

The Co/Ni-MOFs@CS composite derived from Co/Ni bimetallic organic framework was synthesized and characterized. Compared with a single O 3 system, the synergy between carbon sphere (CS) and metal organic frameworks (MOFs) improved the electron transfer efficiency and the formation rate of •OH. The coexistence of Co and Ni in various valence states might accelerate the cyclic process of Co(II)/Co(III) and Ni(II)/Ni(III), thereby improving the catalytic activity. Taking levofloxacin as a model pollutant, the mechanism of catalytic process was discussed, and the catalytic reaction was successfully applied to the removal of residual organics in bio-treated coking wastewater (BTCW). The removal rates of chemical oxygen demand (COD) and total organic carbon (TOC) in 60 min were 50.85%–53.71% and 39.98%–43.48%. From the perspective of UV absorption and 3D EEM, catalytic ozonation was more conducive to breaking the electronic protection of inert organic molecules such as heterocyclic compounds, and achieving higher efficiency of mineralization. It provides a new idea for catalytic ozonation technology of wastewater treatment in the future from theory, technology and application. [Display omitted] • The Co/Ni-MOFs@CS was successfully synthesized by hydrothermal method. • High specific surface areas and coexistence of multiple valence metals. • Strong nonselective oxidation capacity of OH was the mian factor for mineralization. • From the mineralization of single organic pollutant to the application of BTCW. [ABSTRACT FROM AUTHOR]

The Co/Ni-MOFs@CS composite derived from Co/Ni bimetallic organic framework was synthesized and characterized. Compared with a single O 3 system, the synergy between carbon sphere (CS) and metal organic frameworks (MOFs) improved the electron transfer efficiency and the formation rate of •OH. The coexistence of Co and Ni in various valence states might accelerate the cyclic process of Co(II)/Co(III) and Ni(II)/Ni(III), thereby improving the catalytic activity. Taking levofloxacin as a model pollutant, the mechanism of catalytic process was discussed, and the catalytic reaction was successfully applied to the removal of residual organics in bio-treated coking wastewater (BTCW). The removal rates of chemical oxygen demand (COD) and total organic carbon (TOC) in 60 min were 50.85%–53.71% and 39.98%–43.48%. From the perspective of UV absorption and 3D EEM, catalytic ozonation was more conducive to breaking the electronic protection of inert organic molecules such as heterocyclic compounds, and achieving higher efficiency of mineralization. It provides a new idea for catalytic ozonation technology of wastewater treatment in the future from theory, technology and application. [Display omitted] • The Co/Ni-MOFs@CS was successfully synthesized by hydrothermal method. • High specific surface areas and coexistence of multiple valence metals. • Strong nonselective oxidation capacity of OH was the mian factor for mineralization. • From the mineralization of single organic pollutant to the application of BTCW. [ABSTRACT FROM AUTHOR]

Abstract: Coating the polycation/DNA binary complexes with PEGylated polyanions can improve long-circulation and biocompatibility in vivo. However, it has been certificated PEG dilemma can reduces gene transfection efficiency because of inhibition in cellular uptake and endosomal escape. Herein, two PEGylated anionic polymers, PEGylated hyaluronic acid (HgP) and PEGylated polyglutamic acid (PGgP) were synthesized to coat the binary complexes of core–shell cationic polycaprolactone-graft-poly (N, N-dimethylaminoethyl methacrylate) nanoparticles/DNA (NP-D). The effects of polyanion structure were evaluated in terms of particle size, zeta potential, cytotoxicity, cellular uptake and transfect efficiency in vitro and in vivo. In vitro study illustrated that HgP coated complexes showed better efficiencies in both cell uptake and transfection than PGgP coated complexes. The coating of HgP on NP-D improved the biocompatibility without reduction in cell uptake and transfection efficacy, and resulted in higher accumulation and gene expression in tumor after IV injection. The success of HgP coating in overcoming PEG dilemma is attributed to the hyaluronic acid (HA)-receptor-mediated endocytosis and outer shell-detachment through the hyaluronidases catalyzed degradation of HA. These results demonstrated that HgP was a promising anionic polymer for coating the polycation/DNA complexes and ternary complexes (HgP coated NP-D) hold promising potential for cancer therapy. [Copyright &y& Elsevier]

Messenger RNA (mRNA) has generated great attention due to its broad potential therapeutic applications, including vaccines, protein replacement therapy, and immunotherapy. Compared to other nucleic acids (e.g., siRNA and pDNA), there are more opportunities to improve the delivery efficacy of mRNA through systematic optimization. In this report, we studied a high-throughput library of 1200 functional polyesters for systemic mRNA delivery. We focused on the chemical investigation of hydrophobic optimization as a method to adjust mRNA polyplex stability, diameter, pKa, and efficacy. Focusing on a region of the library heatmap (PE4K-A17), we further explored the delivery of luciferase mRNA to IGROV1 ovarian cancer cells in vitro and to C57BL/6 mice in vivo following intravenous administration. PE4K-A17-0.2C8 was identified as an efficacious carrier for delivering mRNA to mouse lungs. The delivery selectivity between organs (lungs versus spleen) was found to be tunable through chemical modification of polyesters (both alkyl chain length and molar ratio in the formulation). Cre recombinase mRNA was delivered to the Lox-stop-lox tdTomato mouse model to study potential application in gene editing. Overall, we identified a series of polymer-mRNA polyplexes stabilized with Pluronic F-127 for safe and effective delivery to mouse lungs and spleens. Structure–activity relationships between alkyl side chains and in vivo delivery were elucidated, which may be informative for the continued development of polymer-based mRNA delivery. [ABSTRACT FROM AUTHOR]

Abstract: Small interfering RNA (siRNA) has a huge potential for the treatment or prevention of various diseases. However, to realize the therapeutic potential of siRNA drugs, efficient, tissue-specific and safe delivery technologies must be developed. Here we synthesized two kinds of polymers (PEGylated poly(2-aminoethyl methacrylate) labeled as PEG-b-PAEM or PEA, and guanidinylated PEGylated poly(2-aminoethyl methacrylate) marked as PEG-b-PAEM-co-PGEM or PEAG) using atom transfer radical polymerization and evaluated their capability of mediating siRNA delivery in vitro and in vivo. Both polymers presented excellent siRNA encapsulation ability, formed regular nanostructures with siRNA, robustly mediated cellular internalization and cytoplasmic localization of siRNA, and resulted in targeted gene knockdown efficiently. However, PEAG showed much more outstanding abilities referring to above evaluating indicators compared with PEA. Both PEA/siRNA and PEAG/siRNA polyplexes displayed strong liver, lung and spleen accumulation in mice for a long time after intravenous administration. PEAG/siApoB polyplexes (single dose at 1 mg/kg) further repressed ApoB expression in liver and resulted in block of lipid transportation. In addition, both polymers delivered high amounts of siRNA into tumor tissue in the Hela-Luc xenograft murine model. More siRNA accumulated in tumor with the increase of N/P ratio and PEAG/siRNA polyplexes showed higher siRNA accumulation than PEA/siRNA polyplexes at the same N/P ratio. These findings set the stage for further studies of structural–functional mechanisms and developments of siRNA therapeutics. [Copyright &y& Elsevier]

Background: Human xenograft models, resulting from orthotopic transplantation (implantation into the anatomically correct site) of histologically intact tissue into animals, are important for investigating local tumor growth, vascular and lymphatic invasion at the primary tumor site and metastasis. Methodology/Principal Findings: We used surgical orthotopic transplantation to establish a nude mouse model of primary hepatic lymphoma (PHL), HLBL-0102. We performed orthotopic transfer of the HLBL-0102 tumor for 42 generations and characterized the tumor cells. The maintenance of PHL characteristics were supported by immunohistochemical and cytogenetic analysis. We also report the antitumor effect of Cantide, an antisense phosphorothioate oligonucleotide against hTERT, on the growth of HLBL-0102 tumors. We showed a significant, dose-dependent inhibition of tumor weight and serum LDH activity in the orthotopically transplanted animals by Cantide. Importantly, survival was prolonged in Cantidetreated HLBL-0102 tumor-bearing mice when compared to mock-treated mice. Conclusions/Significance: Our study provided the basis for the development of a clinical trial protocol to treat PHL. [ABSTRACT FROM AUTHOR]

Abstract: Functionalization of nanostructures such as gold nanoparticles (AuNPs) with different biological molecules has many applications in biomedical imaging, clinical diagnosis and therapy. Researchers mostly employed AuNPs larger than 10 nm for different biological and medicinal applications in previous studies. Herein, we synthesized a novel small (2 nm) AuNPs, which were functionalized with the therapeutic peptide, PMI (p12), and a targeted peptide, CRGDK for selective binding to neuropilin-1(Nrp-1) receptors which overexpressed on the cancer cells and regulated the process of membrane receptor-mediated internalization. It was found that CRGDK peptides increased intracellular uptake of AuNPs compared to other surface conjugations quantified by ICP-MS. Interestingly, CRGDK functionalized AuNPs resulted in maximal binding interaction between the CRGDK peptide and targeted Nrp-1 receptor overexpressed on MDA-MB-321 cell surface, which improved the delivery of therapeutic P12 peptide inside targeted cells. Au@p12 + CRGDK nanoparticles indicated with highly effective cancer treatment by increasing p53 expression upregulated with intracellular enhanced p12 therapeutic peptide. These results have implications to design and functionalize different molecules onto AuNPs surfaces to make hybrid model system for selective target binding as well as therapeutic effects for cancer treatment. [Copyright &y& Elsevier]

Abstract: Binary complexes of cationic polymers and DNA were used commonly for DNA delivery, whereas, the excess cationic charge of the binary complexes mainly leads to high toxicity and unstability in vivo. In this paper, ternary complexes by coating polyglutamic acid-graft-poly(ethylene glycol)(PGA-g-mPEG) onto binary complexes of polycaprolactone-graft-poly(N,N-dimethylaminoethyl methacrylate) (PCL-g-PDMAEMA) nanoparticles (NPs)/DNA were firstly developed for effective and targeted gene delivery. The coating of PGA-g-mPEG was able to decrease the zeta potential of the nano-sized DNA complexes nearly to electroneutrality without interferring with DNA condensation ability. As a result, the stability, the escape ability from endosomes and the transfection efficiency of the complexes were enhanced. The ternary complexes of PCL-g-PDMAEMA NPs/DNA/PGA-g-mPEG demonstrated lower cytotoxicity in CCK-8 measurements and higher gene transfection efficiency than the binary complexes in vitro. In addition, Lactate dehydrogenase (LDH) assay was performed to quantify the membrane-damaging effects of the complexes, which is consistent with the conclusion of CCK-8 measurement for cytotoxicity assay. The in vivo imaging measurement and histochemical analysis of tumor sessions confirmed that the intravenous administration of the ternary complexes with red fluorescent protein (RFP) as payload led to protein expression in tumor, which was further enhanced by the targeted coating of PGA-g-PEG-folate. [Copyright &y& Elsevier]

Aim: The type I insulin-like growth factor receptor (IGF-IR) is overexpressed in many tumors including human hepatocellular carcinoma (HCC). It is a critical signaling molecule for tumor cell proliferation and survival. In the present study, IGF-IR expression was down-regulated by phosphorothioate antisense oligonucleotides (AS[S]ODN) to evaluate their specific effects on growth of hepatoma cells in vitro and in vivo. Methods: HepG2 cells were transfected with different doses of AS[S]ODN, sense [S]ODN, mismatch [S]ODN, or Lipofectin for 72 h, and cell proliferation was analyzed by MTS assay. In vivo, an orthotopic transplant model of HCC was established in nude mice, which were then injected with AS[S]ODN, sense [S]ODN, 5-fluorouracil or saline. At the endpoint of treatment, the tumors were excised and evaluated. Results: Compared to sense and mismatched oligonucleotides, AS[S]ODN targeting to IGF-IR mRNA significantly inhibited hepatoma cell lines HepG2 proliferation and IGF-IR expression at both mRNA and protein levels. The in vivo results showed that systemic treatment also resulted in significant inhibition in tumor growth. Tumor growth in mice treated with AS[S]ODN (50 and 75 mg/kg per day) was significantly inhibited (71.81% and 61.74%, respectively) compared to the saline-treated group ( P < 0.01) in a dose-dependent manner. The antitumor effect of IGF-IR AS[S]ODN was associated with down-regulation of IGF-IR in tumor xenografts. Furthermore, IGF-IR AS[S]ODN prevented liver recurrence tumor growth and metastasis in the lung, showing a dose-dependent response. The level of serum α-fetoprotein in AS[S]ODN-treated groups was also decreased in a dose-dependent manner, and a good correlation was observed between tumor volume and serum α-fetoprotein concentration. Conclusions: These data suggest that IGF-IR AS[S]ODN can effectively and specifically inhibit HCC growth in vitro and in vivo. Blockage of IGF-IR expression could be a promising therapeutic approach for the management of patients with HCC. [ABSTRACT FROM AUTHOR]