The magic of algae-based biochar: advantages, preparation, and applications.

Compared with other biomass sources, the use of algae as a raw material to prepare biochar (BC) has important advantages including safety, high yield and economy. The protein content of algae cells is as high as 3.2 mg DCW/L, and the graphitic-N and N-O functional groups generated by the pyrolysis of proteins could effectively activate free radicals. Combined with the generated pore structure, the electron transfer/exchange capability was enhanced, which is conducive to improving its catalytic performance. Algae as a natural N source, the manuscript analyzed the surface properties and physicochemical properties of algae-based BC, and investigated its degradation effect on organic/inorganic pollutants in wastewater. Subsequently, the effect of nitrogen-doped BC on the adsorption/catalysis capacity was discussed. Finally, the directed preparation of algae-based BC applied in different scenarios was summarized. Algae-based BC has the property of N doping, which broadens its application efficiency in the environmental field. Overall, this manuscript reviews how to achieve efficient utilization of algae-based BC in wastewater.

Toxin type and domain sequence affect accumulation of recombinant immunotoxins.Transient expression in plant cell packs and intact plants correlates well.IC50 values of toxicity correlate with the cell surface receptor concentration.

Molecular dynamics simulation study of adsorption of anionic-nonionic surfactants at oil/water interfaces.

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.

Discovery of Novel cccDNA Reducers toward the Cure of Hepatitis B Virus Infection.

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 59 demonstrated good potency and oral bioavailability with no cellular toxicity. In an HBVcircle mouse model, compound 59 showed excellent efficacy in significantly reducing HBV antigens, DNA, and intrahepatic cccDNA levels.

Versatile strategy of sulfanilamide antibiotics removal via microalgal biochar: Role of oxygen-enriched functional groups.

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 (EHOMO-ELUMO gap = 0.29) under the influence of thiazolyl. The electrophilic sulfonamide group and the nucleophilic thiazole were identified as the main active sites of STZ. In summary, the results of this research provide a guiding role for the preparation of adsorbents driven by the structural characteristics of pollutants.

Adsorption of sulfamethoxazole via biochar: The key role of characteristic components derived from different growth stage of microalgae.

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 (CBCL-M) possessed the best adsorption capacity (287.89 mg/g) owing to the higher decomposition of the microalgal cellular protein concentration (70%). Meanwhile, a higher protein content contributed to the largest specific surface area (42.16 m2/g), maximum pore volume (0.037 cm3/g) and abundant surface functional groups of the CBCL-M. Furthermore, based on the theoretical calculation of the structural analysis, the adsorption mechanism was a multilayer adsorption process in accordance with the Freundlich isotherm. Additionally, the strong hydrogen bond, electron donor-acceptor interaction and electrostatic attraction were the main adsorption mechanisms due to the carboxyl/ester functional groups. The results of this research provide a novel perspective on the reasonable harvest of microalgal biomass for BC fabrication and large-scale implementation of microalgal BC in future applications.

Efficiency assessment of ZVI-based media as fillers in permeable reactive barrier for multiple heavy metal-contaminated groundwater remediation.

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.

Effect of pig manure-derived sulfadiazine on species distribution and bioactivities of soil ammonia-oxidizing microorganisms after fertilization.

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 (<0.5%) was the lowest. The SDZ exhibited a significant effect on the AOM abundance. Specifically, SDZ exerted the highest inhibitory effect on comammox growth, followed by AOA, whereas negligible for AOB. The community diversity of AOMs within the pig manure-fertilized soils was affected by SDZ, and AOA Nitrososphaera cluster 3 played a key role in potential ammonia oxidation capacity (PAO) maintenance. This study provides new insights into the inhibition mechanisms of pig manure-derived antibiotics on AOMs within the fertilized soil.

A patent review of aldosterone synthase inhibitors (2014-present).

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.

Microalgae-based bioplastics: Future solution towards mitigation of plastic wastes.

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.

Small molecule approaches to treat autoimmune and inflammatory diseases (Part III): Targeting cytokines and cytokine receptor complexes.

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.

Discovery of Pyrido[2,3-b]indole Derivatives with Gram-Negative Activity Targeting Both DNA Gyrase and Topoisomerase IV.

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.

Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors.

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.

Sorption of ionized dyes on high-salinity microalgal residue derived biochar: Electron acceptor-donor and metal-organic bridging mechanisms.

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.

Advanced in developmental organic and inorganic nanomaterial: a review.

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.

Flow-regulated endothelial glycocalyx determines metastatic cancer cell activity.

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.

Real-time particle-by-particle detection of erythrocyte-camouflaged microsensor with extended circulation time in the bloodstream.

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.

Fluorescence monitoring of rare circulating tumor cell and cluster dissemination in a multiple myeloma xenograft model in vivo.

Circulating tumor cells (CTCs) are of great interest in cancer research because of their crucial role in hematogenous metastasis. We recently developed "diffuse in vivo flow cytometry" (DiFC), a preclinical research tool for enumerating extremely rare fluorescently labeled CTCs directly in vivo. In this work, we developed a green fluorescent protein (GFP)-compatible version of DiFC and used it to noninvasively monitor tumor cell numbers in circulation in a multiple myeloma (MM) disseminated xenograft mouse model. We show that DiFC allowed enumeration of CTCs in individual mice overtime during MM growth, with sensitivity below 1 CTC mL − 1 of peripheral blood. DiFC also revealed the presence of CTC clusters (CTCCs) in circulation to our knowledge for the first time in this model and allowed us to calculate CTCC size, frequency, and kinetics of shedding. We anticipate that the unique capabilities of DiFC will have many uses in preclinical study of metastasis, in particular, with a large number of GFP-expressing xenograft and transgenic mouse models.

In Vivo Flow Cytometry of Extremely Rare Circulating Cells.

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.

Potassium Iodide-Promoted One-Pot Synthesis of Fluoroalkylated Quinoxalines via a Tandem Michael Addition/Azidation/Cycloamination Approach.

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.

Highly Chemo- and Regioselective Vinylation of N-Heteroarenes with Vinylsulfonium Salts.

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.