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For the first time, POSS and cobalt containing hyperbranched polymer (HP2-Co) was synthesized via a convenient A2+B3 strategy for solid-state pyrolysis to generate magnetoceramics. For comparison, its analogue (HP1-Co) without POSS group was also prepared. After pyrolysis, the ceramic obtained from HP2-Co with POSS groups, had a unique Co@C-SiOx architecture, and its diameter almost remained unchanged with increased pyrolysis temperature, showing good sinter-resistant properties. However, the nanoparticles obtained from HP1-Co sintered seriously with the increased temperature. More importantly, the ceramic yields of HP1-Co and HP2-Co were 82% and 90% respectively, much higher than those of the linear polymers (58-73%). The produced ceramics all showed good magnetic properties, with the saturation magnetization ranged from 40.8-69.0 emu g-1, making them promising candidates for the actual applications.

Introduction Aldosterone synthase (AS) is a key enzyme involved in the final three rate-limiting steps of the biosynthesis pathway of aldosterone, and its inhibition has been considered as an effective strategy to treat hypertension, heart failure and related cardio-metabolic diseases. Area covered This review provides an update on the discovery and development of aldosterone synthase inhibitors by means of patents published between January 2014 and March 2021. The molecules are classified by pharmaceutical company with progress that has been made in clinical trials being highlighted. Expert opinion Mineralocorticoid receptor antagonists (MRAs) and aldosterone synthase inhibitors (ASI) represent two of the main approaches for the blockade of aldosterone. Clinical success, as well as foreseen side effects of steroidal MRAs, prompted the discovery and development of ASI. Since the observation of decreased cortisol levels in clinical trials for LCI699, subsequent efforts have been largely focused on improving its selectivity over hCYP11B1. Candidates with improved potency and selectivity are under investigation across a wide range of indications. Whether ASI will provide an additional therapeutic advantage over current safe and selective non-steroidal MRAs is highly anticipated.

Chronic hepatitis B virus (HBV) infection is a worldwide disease that causes thousands of deaths per year. Currently, there is no therapeutic that can completely cure already infected HBV patients due to the inability of humans to eliminate covalently closed circular DNA (cccDNA), which serves as the template to (re)initiate an infection even after prolonged viral suppression. Through phenotypic screening, we discovered xanthone series hits as novel HBV cccDNA reducers, and subsequent structure optimization led to the identification of a lead compound with improved antiviral activity and pharmacokinetic profiles. A representative compound

Four anionic-nonionic surfactants with the same headgroups and different units of oxygen ethyl (EO) and oxygen propyl (PO) were adopted to investigate the influence on oil/water interfacial tensions in this article. Molecular dynamics (MD) simulations were conducted to study the interfacial property of the four surfactants. Four parameters were proposed to reveal the effecting mechanism of molecular structure on interfacial tension, which included the interfacial thickness, order parameter of the hydrophobic chain, radial distribution function, and the solvent accessible surface area. In addition, the electrostatic potential of the four surfactants was calculated. The research results indicated that the interface facial mask formed by the surfactants, which contained three EO or three PO units was more stable, and it was easier for the surfactants of six EO or six PO units to form a microemulsion at higher concentrations. The adsorption mechanism of the anionic-nonionic surfactant systems at the oil/water interfaces was supplemented at a molecular level, which provided fundamental guidance for an in-depth understanding of the optimal selection of the surfactants in enhancing oil recovery.

The rise of multidrug resistant (MDR) Gram-negative (GN) pathogens and the decline of available antibiotics that can effectively treat these severe infections are a major threat to modern medicine. Developing novel antibiotics against MDR GN pathogens is particularly difficult as compounds have to permeate the GN double membrane, which has very different physicochemical properties, and have to circumvent a plethora of resistance mechanisms such as multiple efflux pumps and target modifications. The bacterial type II topoisomerases DNA gyrase (GyrA2B2) and Topoisomerase IV (ParC2E2) are highly conserved targets across all bacterial species and validated in the clinic by the fluoroquinolones. Dual inhibitors targeting the ATPase domains (GyrB/ParE) of type II topoisomerases can overcome target-based fluoroquinolone resistance. However, few ATPase inhibitors are active against GN pathogens. In this study, we demonstrated a successful strategy to convert a 2-carboxamide substituted azaindole chemical scaffold with only Gram-positive (GP) activity into a novel series with also potent activity against a range of MDR GN pathogens. By systematically fine-tuning the many physicochemical properties, we identified lead compounds such as 17r with a balanced profile showing potent GN activity, high aqueous solubility, and desirable PK features. Moreover, we showed the bactericidal efficacy of 17r using a neutropenic mouse thigh infection model.

Global demand for plastic materials has severely harm the environment and marine sea life. Therefore, bioplastics have emerged as an environmentally friendly alternative due to sustainability, minimal carbon footprint, less toxicity and high degradability. This review highlights the sustainable and environmentally friendly approach towards bioplastic production by utilizing microalgae as a feed source in several ways. First, the microalgae biomass obtained through the biorefinery approach can be processed into PHA under certain nutrient limitations. Additionally, microalgae biomass can act as potential filler and reinforcement towards the enhancement of bioplastic either blending with conventional bioplastic or synthetic polymer. The downstream processing of microalgae via suitable extraction and pre-treatment of bioactive compounds such as lipids and cellulose are found to be promising for the production of bioplastics. Moving on, the intermediate processing of bioplastic via lactic acid synthesized from microalgae has favoured the microwave-assisted synthesis of polylactic acid due to cost efficiency, minimum solvent usage, low energy consumption, and fast rate of reaction. Moreover, the reliability and effectiveness of microalgae-based bioplastics are further evaluated in terms of techno-economic analysis and degradation mechanism. Future improvement and recommendations are listed towards proper genetic modification of algae strains, large-scale biofilm technology, low-cost cultivation medium, and novel avocado seed-microalgae bioplastic blend.

Personalized medicine offers great potential benefits for disease management but requires continuous monitoring of drugs and drug targets. For instance, the therapeutic window for lithium therapy of bipolar disorder is very narrow, and more frequent monitoring of sodium levels could avoid toxicity. In this work, we developed and validated a platform for long-term, continuous monitoring of systemic analyte concentrations in vivo. First, we developed sodium microsensors that circulate directly in the bloodstream. We used “red blood cell mimicry” to achieve long sensor circulation times of up to 2 wk, while being stable, reversible, and sensitive to sodium over physiologically relevant concentration ranges. Second, we developed an external optical reader to detect and quantify the fluorescence activity of the sensors directly in circulation without having to draw blood samples and correlate the measurement with a phantom calibration curve to measure in vivo sodium. The reader design is inherently scalable to larger limbs, species, and potentially even humans. In combination, this platform represents a paradigm for in vivo drug monitoring that we anticipate will have many applications in the future.

Here, a distinctive eco-friendly corn straw material with preferable superhydrophobicity and superoleophilicity for separating oil from liquid mixtures is proposed. The raw corn straw was successfully modified by deposition of SiO2/ZnO composite particles on the fiber surface and subsequent hydrophobic modification with octyltriethoxysilane. The modified corn straw was found to have preferable chemical durability and environmental continuance, with water and oil contact angles of 152° and 0°, respectively, allowing it to both selectively adsorb oils and completely repel water. In addition, it was provided with a high capacity of sorption, making it an ideal candidate for potential oil spill cleanup applications. Due to its natural attributes to float on water, it is convenient for transportation after the oil adsorption is completed. Hence, the modified corn straw provides an eco-friendly alternative for the cleanup of oil spills, as well as a means to relieve the environmental problem of agricultural waste disposal.

Ni204 ceramic composite coatings with different mass fractions of TiC, TiN and B4C were successfully prepared on the surface of 45 steel by laser cladding. Microstructures of different ceramic coatings were studied using X-ray diffraction, scanning electron microscopy and laser confocal microscopy. The friction coefficient and microhardness of ceramic coatings were measured with a reciprocating friction wear machine and microhardness tester. The results show that ceramic coating has 766.8HV0.5 average microhardness and friction coefficient of 0.47 when 10%TiC, TiN, and B4C are added to initial powder Ni204. The microstructure of cladding layer is uniform and compact, and the microhardness and friction coefficient of the coating increased and decreased by factors 2.6 and 1.393 compared with initial powder. This is due to the presence of multiple phase ((Ti, Mo, Nb) (C, B, N)), carbide, nitride, (Ti, Mo, Nb) (C, B, N), and (Ti, Mo, Nb) (C, N) ring phase around TiC, TiN, and Ti(C, N) ceramic phases. Uniformly distributed reinforced phases in the coating inhibit extrusion by grinding balls on the surface of the ceramic coating, thus changing original abrasive wear mechanism, making wear marks more shallow, and decreasing friction coefficient of the surface.

In the presence of Na2CO3, a variety of fluoroalkylated quinolones were efficiently synthesized from isatins and fluoroalk-2-ynoates in good to excellent yields at room temperature. The reaction can proceed via two different ways with Michael adduct or isatoic anhydride as the key intermediate.

Biochar (BC) adsorption has been widely acknowledged as an efficient approach for the removal of antibiotics. Despite the importance of oxygen-containing functional groups for the antibiotics removal, most of these may be obtained in BC only relying on the addition of oxidants. Herein, an environmentally friendly and oxygen-enriched functional groups adsorbent, namely Chlamydomonas BC (CBC), was fabricated via simple pyrolysis process. Then, the H-bonding, electron donor-acceptor and electrostatic attraction were identified as the main mechanisms regarding sulfathiazole (STZ) adsorption (506.38 mg/g). The carbon-oxygen functional groups on the surface of CBC (61%), especially -COOH and -OH, acted as a pivotal component. Additionally, further theoretical calculation led to the observation that STZ exhibited the highest chemical reactivity (η = 0.04), strong electron exchange capacity (μ = -0.16), remarkable electron accepting capacity (ω = 0.28) and excellent electron transfer efficiency (E

To evaluate the effect of pig manure-derived sulfadiazine (SDZ) on the species distribution and bioactivities of ammonia-oxidizing microorganisms (AOMs), ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA) and complete ammonia oxidizer (comammox) within the soil were investigated pre- and post-fertilization. Kinetic modeling and linear regression results demonstrated that the DT50 value of different SDZ fractions under initial SDZ concentrations of 50 and 100 mg·kg−1 exhibited the following trend: total SDZ>CaCl2-extractable SDZ>MeOH-extractable SDZ, whereas their inhibiting effect on AOMs showed an opposite trend. qPCR analysis suggested that comammox was the predominant ammonia oxidizer in soils regardless of SDZ addition, accounting for as much as 77.2–94.7% of the total amoA, followed by AOA (5.3–22.5%), whereas AOB (

Chronic and dysregulated cytokine signaling plays an important role in the pathogenic development of many autoimmune and inflammatory diseases. Despite intrinsic challenges in the disruption of interactions between cytokines and cytokine receptors, many first-in-class small-molecule inhibitors have been discovered over the past few years. The third part of the digest series presents recent progress in identifying such inhibitors and highlights the application of novel research tools in the fields of structural biology, computational analysis, screening methods, biophysical/biochemical assays and medicinal chemistry strategy.

Converting microalgal biomass residues into biochar (BC) after microalgal wastewater treatment is a popular approach that can produce an adsorbent to treat refractory organic pollutants. Moreover, the adsorption efficiency via BC is closely associated with the surface morphology, which may be determined by the composition of the microalgal biomass. However, the intrinsic relationship and advanced mechanism between the adsorption efficiency and microalgal composition have not been thoroughly investigated. In this work, four microalgal BCs were prepared from Chlamydomonas sp. QWY37 (CBC) after collection from four different growth stages of microalgal biomass during wastewater treatment. The adsorption performance for sulfamethoxazole indicates that the CBC collected in the mid-log phase (CBC

The rise of multidrug resistant (MDR) Gram-negative (GN) pathogens and the decline of available antibiotics that can effectively treat these severe infections are a major threat to modern medicine. Developing novel antibiotics against MDR GN pathogens is particularly difficult as compounds have to permeate the GN double membrane, which has very different physicochemical properties, and have to circumvent a plethora of resistance mechanisms such as multiple efflux pumps and target modifications. The bacterial type II topoisomerases DNA gyrase (GyrA

Aldosterone synthase (CYP11B2) inhibitors have been explored in recent years as an alternative therapeutic option to mineralocorticoid receptor (MR) antagonists to reduce elevated aldosterone levels, which are associated with deleterious effects on various organ systems including the heart, vasculature, kidney, and central nervous system (CNS). A benzamide pyridine hit derived from a focused screen was successfully developed into a series of potent and selective 3-pyridyl isoindolin-1-ones CYP11B2 inhibitors. Our systematic structure-activity relationship study enabled us to identify unique structural features that result in high selectivity against the closely homologous cortisol synthase (CYP11B1). We evaluated advanced lead molecules, exemplified by compound 52, in an in vivo cynomolgus monkey acute adrenocorticotropic hormone (ACTH) challenge model and demonstrated a superior 100-fold in vivo selectivity against CYP11B1.

Cancer metastasis and secondary tumor initiation largely depend on circulating tumor cell (CTC) and vascular endothelial cell (EC) interactions by incompletely understood mechanisms. Endothelial glycocalyx (GCX) dysfunction may play a significant role in this process. GCX structure depends on vascular flow patterns, which are irregular in tumor environments. This work presents evidence that disturbed flow (DF) induces GCX degradation, leading to CTC homing to the endothelium, a first step in secondary tumor formation. A 2-fold greater attachment of CTCs to human ECs was found to occur under DF conditions, compared to uniform flow (UF) conditions. These results corresponded to an approximately 50% decrease in wheat germ agglutinin (WGA)-labeled components of the GCX under DF conditions, vs UF conditions, with undifferentiated levels of CTC-recruiting E-selectin under DF vs UF conditions. Confirming the role of the GCX, neuraminidase induced the degradation of WGA-labeled GCX under UF cell culture conditions or in Balb/C mice and led to an over 2-fold increase in CTC attachment to ECs or Balb/C mouse lungs, respectively, compared to untreated conditions. These experiments confirm that flow-induced GCX degradation can enable metastatic CTC arrest. This work, therefore, provides new insight into pathways of secondary tumor formation.

An efficient chemo- and regioselective N-vinylation of N-heteroarenes has been developed using vinylsulfonium salts. The reaction proceeded under mild and transition-metal-free conditions and consistently provided moderate to high yields of vinylation products with 100% E-stereoselectivity. This reaction is also highly chemoselective, and compatible with a variety of functional groups, such as -NHR, -NH2, -OH, -COOH, ester, etc.

Four zero valent iron-based composites were prepared and applied as the reactive media of permeable reactive barriers. Batch tests and continuous-flow column experiments were conducted to assess the long-term performance of these composites for possible utilization as fillers for PRB. The experimental results of the batch tests revealed that in single-metal systems, the removal efficiency of Cu(Ⅱ), Co(Ⅱ), Cr(Ⅵ) and As(Ⅲ) could reach 98% at equilibrium. Equilibrium data showed that composites displayed different selectivity values in binary and quaternary-component systems. For the continuous tests, column filled with chitosan-zero valent iron-based composites, exhibited optimal removal efficiency and achieved average removal values of 98.84%, 88.28%, 95.65% and 87.10% for Cu(Ⅱ), Co(Ⅱ), Cr(Ⅵ) and As(Ⅲ) during the whole 30-day operation, respectively. Dynamic removal improvement of multiple metals was observed with further assembly media, with average removal of 99.11%, 90.05% and 87.34% for Cu(Ⅱ), Co(Ⅱ) and As(Ⅲ), respectively. Combined with superficial characteristic analysis, the functional groups distributed on the surface of composites played a key role in metal sorption. Moreover, the adsorbed Cu(Ⅱ), Co(Ⅱ) and Cr(Ⅵ) gradually transferred to the mobile phase when the operational periods were prolonged, while As(Ⅲ) became more stable.

Landfill leachate (LL) is endowed with double roles as refractory wastewater and nutrients/energy sources due to inherent vast inorganics and organics. Bioconversion of LL’s nutrients into biohydrogen and volatile fatty acids (VFAs) via eco-friendly dark fermentation (DF) is a promising approach to simultaneously deal with environment deterioration and energy crisis, but its application is severely restricted by poor fermentative performance attributing to strong toxicity of LL and vulnerable vitality of fermentative bacteria. Herein, a novel conversion strategy was proposed by coupling microalgal photosynthesis with DF, which was capable of reclaiming nutrients and organics from LL to produce biohydrogen and VFAs relying on robust microalgae coupled with DF. Results demonstrated that microalgae grew well in 10% LL with maximum biomass concentration of 1.41 g/L. More importantly, 86.12% NH4+ and 53.00% organics were recovered from LL and stored as carbohydrates (26.4%), proteins (48.7%) and lipid (15.9%) in microalgal cells. The accumulated intracellular carbohydrate and protein were then converted into biohydrogen and VFAs via DF, producing 16.37 kJ/L of output energy with overall energy conversion efficiency of 11.67%. Transformations of macromolecular organics and possible conversion mechanism of microalgae biomass to bioenergy were detailed discussed. Together, this work may provide a promising strategy for better dealing with LL disposal.

The present research aims to study the long-term impacts of soil extractable carbohydrate content from the conversion of forest to paddy field, using three environmentally friendly methods: ultrasound assist (37 Hz/30 min), hot water (80 °C/4 h), and cold water (25 °C/30 min). Soil samples collected at the depth of 0–15 cm from natural forest, rice paddy, and border area were extracted by distilled water at the ratio 1:10 (soil: water). Contents of soil organic carbon (SOC) and extracted carbohydrate (ECH) in the natural forest and rice paddy were similar, and higher than in border area by 50%. Results showed the highest content of ECH was extracted using hot water (304–691 mg.Carbohydrate/kg soil, 4% of SOC), followed by ultrasound (102–305 mg.Carbohydrate/kg soil, 1.7% of SOC), and the lowest amount addressed to cold-water extraction (65–252 mg.Carbohydrate/kg soil, 1.2% of SOC). The ECH/SOC ratios in three soil types were the same and ranged from 0.9% to 4.2%. We conclude the long-term conversion of forest to rice paddy maintain both SOC and ECH, furthermore, hot water extraction at 80 °C/4 h is the optimum method for extraction of carbohydrate using non-chemical solvents.

Biochar (BC) has attracted much attention owing to its superior sorption capacity towards ionized organic contaminants. However, the mechanism of ionized organics sorption occurring within BC containing large amounts of minerals is still controversial. In this study, we demonstrate the physicochemical structure of high-salinity microalgal residue derived biochar (HSBC) and elucidate the corresponding sorption mechanisms for four ionized dyes along with determining the crucial role of involved minerals. The results indicate that sodium and calcium minerals mainly exist within HSBCs, and the pyrolysis temperature can dramatically regulate the phases and interfacial property of both carbon matrix and minerals. As a result, the HSBC shows a higher sorption potential, benefiting from abundant functional groups and high content of inorganic minerals. Using theoretical calculations, the activities of electron donor-acceptor interaction between HSBCs and different dyes are clearly illustrated, thereby identifying the critical role of Ca2+ in enhancing the removal of ionized dyes in HSBCs. In addition, Ca-containing minerals facilitate the sorption of ionized dyes in HSBCs by forming ternary complexes through metal-bridging mechanism. These results of mineral-induced dye sorption mechanisms help to better understand the sorption of ionized organics in high-salt containing BC and provide a new disposal strategy for hazardous microalgal residue, as well as provide a breakthrough in making the remediation of ionized organic contaminated microalgal residue derived absorbent feasible.

With the unique properties such as high surface area to volume ratio, stability, inertness, ease of functionalization, as well as novel optical, electrical, and magnetic behaviors, nanomaterials have a wide range of applications in various fields with the common types including nanotubes, dendrimers, quantum dots, and fullerenes. With the aim of providing useful insights to help future development of efficient and commercially viable technology for large-scale production, this review focused on the science and applications of inorganic and organic nanomaterials, emphasizing on their synthesis, processing, characterization, and applications on different fields. The applications of nanomaterials on imaging, cell and gene delivery, biosensor, cancer treatment, therapy, and others were discussed in depth. Last but not least, the future prospects and challenges in nanoscience and nanotechnology were also explored.

A convenient method was developed for the cyclopropanation of aryl acetates and aryl acetonitrile using vinyl diphenyl sulfonium triflate salt. The newly developed conditions are simple, mild, and compatible with a wide range of functional groups, without the need to apply an inert atmosphere, or alkali bases.

The removal of oil from waste water is gaining increasing attention. In this study, a novel synthesis method of green superhydrophobic/superoleophilic wood flour is proposed using the deposition of nano&ndash, zinc oxide (nZnO) aggregated on the fiber surface and the subsequent hydrophobic modification of octadecanoic acid. The as-prepared wood flour displayed great superhydrophobicity and synchronous superoleophilicity properties with the water contact angle (WCA) of 156&deg, and oil contact angle (OCA) of 0&deg, for diesel oil. Furthermore, the as-prepared wood flour possessed an excellent stability, probably due to the strong adhesion of nZnO, which aggregates to the fiber surface of wood flour with the action of glutinous polystyrene. The maximum adsorption capacity of as-prepared wood flour was 20.81 g/g for engine oil, which showed that the as-prepared wood flour is a potential candidate as an efficient oil adsorbent in the field of water-oil separation. Moreover, it has good chemical steadiness and environmental durability. Taken together, all the information acquired from this research could be valuable in evaluating the potential of as-prepared wood flour as a competitive and sustainable oil-water separation material.

Circulating tumor cells (CTCs) are of great interest in cancer research, but methods for their enumeration remain far from optimal. We developed a new small animal research tool called “Diffuse in vivo Flow Cytometry” (DiFC) for detecting extremely rare fluorescently-labeled circulating cells directly in the bloodstream. The technique exploits near-infrared diffuse photons to detect and count cells flowing in large superficial arteries and veins without drawing blood samples. DiFC uses custom-designed, dual fiber optic probes that are placed in contact with the skin surface approximately above a major vascular bundle. In combination with a novel signal processing algorithm, DiFC allows counting of individual cells moving in arterial or venous directions, as well as measurement of their speed and depth. We show that DiFC allows sampling of the entire circulating blood volume of a mouse in under 10 minutes, while maintaining a false alarm rate of 0.014 per minute. In practice, this means that DiFC allows reliable detection of circulating cells below 1 cell per mL. Hence, the unique capabilities of DiFC are highly suited to biological applications involving very rare cell types such as the study of hematogenous cancer metastasis.

Photocatalytic degradation based on semiconductor is a potential technology for water pollution treatment by utilizing light irradiation. As a new p-type semiconductor material, CuBi2O4 is favored by researchers due to its excellent photocatalytic properties. Herein, a group of CuBi2O4 nanospheres were synthesized by simple hydrothermal method, in which the formation and transformation process of CuBi2O4 microsphere structure was studied by adjusting the hydrothermal reaction time. On this basis, a series Z-Scheme heterojunctions with different mass ratios of CuBi2O4/CdMoO4 nanocomposites were constructed and the formation mechanism of Z-scheme heterojunction was described detailedly. The results of the study confirmed that CuBi2O4/CdMoO4 (10 %) composites exhibited excellent photocatalytic activity, with a high degradation rate of 95.36 % for MB under visible light irradiation, by comparison with bare CuBi2O4 and CdMoO4. In order to improve the quantum efficiency, doping CdMoO4 onto CuBi2O4 greatly improved the surface charge migration rate of CuBi2O4 and reduced the rate of electron-hole pairs recombination. The degradation rate of CuBi2O4/CdMoO4 (10 %) remained over 85 % after three times cycling experiments, demonstrating that the heterojunction has good repeatability and stability. The free radical trapping experiments demonstrated that the h+ and O2– were the main substances involved in photocatalytic oxidation-reduction, which match the energy band, and was consistent with the mechanism of Z-Scheme heterojunctions. This study stated that establishment of a novel CuBi2O4/CdMoO4 heterojunction composite photocatalyst is a new ideal way to carry out environmental pollution treatment and clean energy.

This study has investigated on two objectives which are enhancing the microalgae Chlorella sorokiniana CY-1 cell disruption mechanism using thermal Fenton reaction and performing non-catalytic transesterification by ultra-sonication method. Radicles generated by Fenton reaction are rapid, dynamic, and the reaction was assisted by thermal heating to optimize the kinetic of the radical generation by obtained the lipid recovery for 53.3% and 977.41 mg/g at 36.5 °C with 4 min of contact time. The conversion of lipid into fatty acid methyl esters (FAME) through rapid non-catalytic transesterification using ultrasound was also performed. The significant parameters were done by varying the ratio of methanol to lipid, duration and pulse mode of sonication, to optimize the bonding reaction with methyl ester compound to free fatty acids. The formation of hydrocarbon chains with C4, C6, and C10 was observed at 8.20 mg/g, 0.33 mg/g, and 0.24 mg/g, respectively. This is a promising method as it is marketable and can be conducted in large scale with high process yield of F.A.M.E in a rapid manner.

Ionic liquid (IL) has been an attractive candidate for various industrial applications, especially in cellulose processing industry. The concerns over hazards of conventional volatile organic solvents can be overcome by ILs due to their unique and ‘green’ characteristics. However, the controversy over the usage of ILs in various fields remains on their toxicity toward living organisms and their environmental impact. This review intends to reveal the connection between sustainability of IL technology and the applications of IL in dissolution of lignocellulosic biomass as well as permeabilization of microalgae cells. The mechanism studies are comprehensively evaluated, and the molecular physicochemical aspects of ILs used in these cellulose-degrading processes are systematically presented. In addition, the techno-economic and sustainability analyses of these IL-based applications are compiled. The highlights in future prospect and challenges of adopting IL in these processes could align the future research effort to fill in the knowledge gaps. This review aims to deliver a different perspective on the consideration of “toxic” and “green” elements of IL used in biomass processing.

2-Perfluoroalkylated quinolines were efficiently synthesized via the Michael addition of perfluoroalk-2-ynoates with isatins, followed by the reaction with alcohols through an intramolecular rearrangement cyclization in the presence of Na2CO3. Under the mild and metal-free reaction conditions, a broad scope of quinolines was synthesized and the mechanism was proposed.

Valorisation of biowaste is a topic of closer scrutiny for its role in transition of fossil-based economy to bioeconomy. Increasing waste generation and climate change are among the issues that can be alleviated via biowaste valorisation. Various conversion methods have been consolidated as the most effective methods to valorise biowaste into value-added products such as biofuel, biochar and other biomaterials. Recognising the need to identify areas with higher demand for scientific effort, this review aims to provide a critical overview on current trend pertaining biowaste valorisation. The rheological limitations that hinder the upscaling feasibility of biowaste valorisation are provided and discussed. Survey of academic literature to showcase the recent efforts to alleviate technical constraints is also included. With critical approach, this review is expected to highlight the setbacks and avenues in biowaste valorisation field that are useful for future research. Specifically, process optimisation and development of new products with competitive edge from biowaste are the key avenues to close the loop of circular bioeconomy.

We recently developed ‘Diffusein vivoFlow Cytometry’ (DiFC), a new pre-clinical research tool for enumerating extremely rare fluorescently-labeled circulating cells directlyin vivo. In this paper, we developed a green fluorescent protein (GFP) compatible version of DiFC, and used it to non-invasively monitor the circulating tumor cell (CTC) burden over time in a multiple myeloma disseminated xenograft model. We show that DiFC allowed counting of CTCs at estimated concentrations below 1 cell per mL in peripheral blood with a negligible false alarm rate. DiFC also revealed the presence of CTC clusters in circulation to our knowledge for the first time in this model, and allowed us to calculate their size, kinetics, and frequency of shedding. We anticipate that the unique capabilities of DiFC will have many applications in the study of hematogenous metastasis, and as a powerful complementary methodology to liquid biopsy assays.

Fluoroalkylated quinoxlines with various groups were efficiently synthesized via a one-pot tandem Michael addition/azidation/cycloamination process. Under the mild and metal-free conditions, a bis-imine intermediate (4a) was detected and isolated for the first time. KI played a crucial role in this reaction. The mechanism was described.

Inappropriately high levels of aldosterone are associated with many serious medical conditions, including renal and cardiac failure. A focused screen hit has been optimized into a potent and selective aldosterone synthase (CYP11B2) inhibitor with in vitro activity against rat, mouse, human, and cynomolgus monkey enzymes, showing a selectivity factor of 160 against cytochrome CYP11B1 in the last species. The novel tetrahydroisoquinoline compound (+)-(R)-6 selectively reduced aldosterone plasma levels in vivo in a dose-dependent manner in db/db mice and cynomolgus monkeys. The selectivity against CYP11B1 as predicted by cellular inhibition data and free plasma fraction translated well to Synacthen challenged cynomolgus monkeys up to a dose of 0.1 mg kg(-1). This compound, displaying good in vivo potency and selectivity in mice and monkeys, is ideally suited to perform mechanistic studies in relevant rodent models and to provide the information necessary for translation to non-human primates and ultimately to man.

Human neutrophil elastase (HNE) represents a goodtherapeutic target for the treatment of inflammatory diseases aswell as invasion of microorganism. The methanol extract of aaerial part of Chelidonium majus L. showed high activity againstthe neutrophil elastase with an IC 50 value of 100µg/mL. Due toits potency, subsequent bioactivity-guided fractionation ofmethanol extract led to six alkaloids (1-6), which were identifiedas dihydrosanguinarine (1), (s)-stylopine (2), arnottianamide (3),(+)-chelidonine (4), spallidamine (5), and N-trans-feruloyltyramine (6). Among of them, three alkaloids (2, 5, and 6)inhibited HNE in a dose-dependent manner with IC 50 rangingbetween 11.6 and 51.0µM. Lineweaver-Burk and Dixon plots,and their secondary replots showed that alkaloids (2, 5, and 6)were mixed inhibitors of HNE. The analysis of K I and K IS valueproved that all inhibitors (2, 5, and 6) had reversible mixed typeI mechanism.Keywords Chelidonium majus L. · human neutrophil elastase ·inflammation · isoquinoline alkaloidIntroductionThe regulation of the enzymatic activity of human neutrophilelastase (HNE) has been the attractive field because neutrophilsare the first cells recruited to inflammatory sites and from theearliest line of defense against the invasion of microorganism(Brice et al., 2010). The human neutrophil elastase (EC 3. 4. 21.37) is the family of serine proteases that possess the ability tohydrolyze the extracellular matrix protein (Siedle et al., 2007). Itis present in azurophil granules in the neutrophil cytoplasm. HNEis a proteolytic enzyme involved in pathogenesis of emphysema,adult respiratory distress syndrome and rheumatoid arthritis(Crocetti et al., 2013). The catalytic site of HNE molecule iscomposed of the triad His41-Asp99-Ser173, of which the oxygenof serine attacks carbonyl group on the target substrate (Bode etal., 1989). The activity of HNE is controlled by inhibitor namedα1-antitrypsin produced in the liver. However, their HNE affinityis strongly decreased by oxidative stress and by proteases releasedfrom leukocytes that are recruited to inflammation sites (Brice etal., 2010). Thus, the imbalance between HNE and its inhibitors isimplicated in many inflammation diseases as like pulmonaryemphysema.Chelidonium majus L. is a perennial herbaceous plant of thefamily Papaveraceae, which is widely distributed around theworld. This plant has been traditionally used as an herbal medicinefor treatment of gastric ulcer, oral infection and liver disease(Lenfield et al., 1981). These effects are mainly due to the alkaloidspresent in milk sap. The major bioactive components of this plantare isoquinoline alkaloids such as chelidonine, chelerythrine,sanguianarine, bebeerine and coptisine (Barreto et al., 2003). Itincluded flavonoids and various acids such as ferulic, cumaric,caffeic and chelidonic acids (Barens J et al., 2007). The constituentsof C. majus L. have been found to exhibit antitumor, antiviral, andanti-inflammatory activities (Colombo and Bosisio, 1996). Additionally,the potent and selective acetylcholinesterase inhibition wasobserved on 8-hydroxydihydrochelerythrine in C. majus L (Cho etal., 2006).During a screening procedure on higher plant to find neutrophilelastase inhibitors, methanol extract of C. majus L. was shown toexhibit considerable inhibitory activity. In this study, we isolatedsix alkaloids targeting to HNE from the methanol extract of aerial