CRISPR-Cas9 Editing of the HBG1 and HBG2 Promoters to Treat Sickle Cell Disease.

BACKGROUND: Sickle cell disease is caused by a defect in the ß-globin subunit of adult hemoglobin. Sickle hemoglobin polymerizes under hypoxic conditions, producing deformed red cells that hemolyze and cause vaso-occlusion that results in progressive organ damage and early death. Elevated fetal hemoglobin levels in red cells protect against complications of sickle cell disease. OTQ923, a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-edited CD34+ hematopoietic stem- and progenitor-cell (HSPC) product, has a targeted disruption of the HBG1 and HBG2 (γ-globin) gene promoters that increases fetal hemoglobin expression in red-cell progeny. METHODS: We performed a tiling CRISPR-Cas9 screen of the HBG1 and HBG2 promoters by electroporating CD34+ cells obtained from healthy donors with Cas9 complexed with one of 72 guide RNAs, and we assessed the fraction of fetal hemoglobin-immunostaining erythroblasts (F cells) in erythroid-differentiated progeny. The gRNA resulting in the highest level of F cells (gRNA-68) was selected for clinical development. We enrolled participants with severe sickle cell disease in a multicenter, phase 1-2 clinical study to assess the safety and adverse-effect profile of OTQ923. RESULTS: In preclinical experiments, CD34+ HSPCs (obtained from healthy donors and persons with sickle cell disease) edited with CRISPR-Cas9 and gRNA-68 had sustained on-target editing with no off-target mutations and produced high levels of fetal hemoglobin after in vitro differentiation or xenotransplantation into immunodeficient mice. In the study, three participants received autologous OTQ923 after myeloablative conditioning and were followed for 6 to 18 months. At the end of the follow-up period, all the participants had engraftment and stable induction of fetal hemoglobin (fetal hemoglobin as a percentage of total hemoglobin, 19.0 to 26.8%), with fetal hemoglobin broadly distributed in red cells (F cells as a percentage of red cells, 69.7 to 87.8%). Manifestations of sickle cell disease decreased during the follow-up period. CONCLUSIONS: CRISPR-Cas9 disruption of the HBG1 and HBG2 gene promoters was an effective strategy for induction of fetal hemoglobin. Infusion of autologous OTQ923 into three participants with severe sickle cell disease resulted in sustained induction of red-cell fetal hemoglobin and clinical improvement in disease severity. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT04443907.).

Off-Design Operation and Cavitation Detection in Centrifugal Pumps Using Vibration and Motor Stator Current Analyses.

Centrifugal pumps are essential in many industrial processes. An accurate operation diagnosis of centrifugal pumps is crucial to ensure their reliable operation and extend their useful life. In real industry applications, many centrifugal pumps lack flowmeters and accurate pressure sensors, and therefore, it is not possible to determine whether the pump is operating near its best efficiency point (BEP). This paper investigates the detection of off-design operation and cavitation for centrifugal pumps with accelerometers and current sensors. To this end, a centrifugal pump was tested under off-design conditions and various levels of cavitation. A three-axis accelerometer and three Hall-effect current sensors were used to collect vibration and stator current signals simultaneously under each state. Both kinds of signals were evaluated for their effectiveness in operation diagnosis. Signal processing methods, including wavelet threshold function, variational mode decomposition (VMD), Park vector modulus transformation, and a marginal spectrum were introduced for feature extraction. Seven families of machine learning-based classification algorithms were evaluated for their performance when used for off-design and cavitation identification. The obtained results, using both types of signals, prove the effectiveness of both approaches and the advantages of combining them in achieving the most reliable operation diagnosis results for centrifugal pumps.

Evaluation of ergosterol composition and esterification rate in fungi isolated from mangrove soil, long-term storage of broken spores, and two soils.

Ergosterol is an important fungal-specific biomarker, but its use for fungal biomass estimation is still varied. It is important to distinguish between free and esterified ergosterols, which are mainly located on the plasma membrane and the cytosolic lipid particles, respectively. The present study analyzes free and esterified ergosterol contents in: (1) the fifty-nine strains of culturable fungi isolated from mangrove soil, (2) the broken spores of the fungus Ganoderma lucidum stored in capsule for more than 12 years, and (3) the mangrove soil and nearby campus wood soil samples by high performance liquid chromatography (HPLC). The results show that the contents of free and esterified ergosterols varied greatly in fifty-nine strains of fungi after 5 days of growth, indicating the diversity of ergosterol composition in fungi. The average contents of free and total ergosterols from the fifty-nine strains of fungi are 4.4 ± 1.5 mg/g and 6.1 ± 1.9 mg/g dry mycelia, respectively, with an average ergosterol esterification rate of 27.4%. The present study suggests that the fungi might be divided into two classes, one is fungi with high esterification rates (e.g., more than 27%) such as Nectria spp. and Fusarium spp., and the other is fungi with low esterification rates (e.g., less than 27%) such as Penicillium spp. and Trichoderma spp. Moreover, the ergosterol esterification rate in the spores of G. lucidum is 91.4% with a very small amount of free ergosterol (0.015 mg/g), compared with 41.9% with a higher level of free ergosterol (0.499 mg/g) reported in our previous study in 2007, indicating that free ergosterol degrades more rapidly than esterified ergosterol. In addition, the ergosterol esterification rates in mangrove soil and nearby campus wood soil samples range from 0 to 39.0%, compared with 80% in an old soil organic matter reported in a previous study, indicating the potential relationship between aging degree of fungi or soil and esterification rate. The present study proposes that both free and esterified ergosterols should be analyzed for fungal biomass estimation. When the ergosterol esterification rates in soils are higher, free ergosterol might be a better marker for fungal biomass. It is speculated that the ergosterol esterification rate in soils might contain some important information, such as the age of old-growth forests over time scales of centuries to millennia, besides the senescence degree of fungal mycelia in soils. KEY POINTS: • Fungi might be divided into two classes depending on ergosterol esterification rates. • Ergosterol esterification rate of broken spores stored for long time raised evidently. • Both free and esterified ergosterols should be analyzed for fungal biomass estimate. • Free ergosterol is a better marker for fungal biomass with a high esterification rate.

Research on the Single-Value Indicators for Centrifugal Pump Based on Vibration Signals.

Off-design operation conditions might not only seriously affect the internal flow status of a centrifugal pump, but also result in additional energy loss and potential mechanical damage. Therefore, early-stage monitoring and predication on off-design operation conditions for centrifugal pumps have become essential. Single-value indicators have favorable factors such as a smaller amount of calculation and easier identification. As a result, industries prefer the more straightforward approach: obtaining single-value indicators directly from the signals which could be easier compared with accepted standards. The possibility of applying the single-value indicators of vibration into operation condition monitoring for a centrifugal pump is studied theoretically and experimentally, which shows that the statistical features of vibration might be suitable for hydraulic instability detection for a centrifugal pump.

A numerical coupling method for particle tracking in electromagnetic fields.

With the arrival of the information age, the electromagnetic energy in space increases constantly, resulting in the influence of electromagnetic waves on the charged aerosol particles in the environment which should be taken into account. Here, a numerical coupling method based on temporal and spatial scales is proposed to solve the difficulty in obtaining the trajectory of particles under the action of high-frequency electromagnetic waves. In the temporal scale, two constant forces with linear relationship are used to equilibrate the electromagnetic field forces under different conditions, however the above-mentioned equivalent method has the space limitation; in addition, on the spatial scale, the model with larger geometry should be divided into multiple basic modules spatially, the domain division method is adopted and due to the above method it can be used well in the basic module. Verified the correctness through the comparison of the results, and compared with the traditional method, the above method greatly reduces the computational complexity. Some interesting results were obtained by calculating the modulated waves with the above method, which indicate that special forms of electromagnetic waves will significantly affect the motion of particles.

Study on the method of compensation for the heading effect of the rate offset frequency laser inertial measurement unit.

For the rate offset frequency laser inertial measurement unit (IMU), the errors of its three attitude angles, laser gyroscope, and accelerometer are coupled, which will affect the initial alignment result of the IMU and will make the measurement results of the IMU at different positions and angles deviate from the truth value. Meanwhile, with the increase of tilt angle, the heading effect becomes more obvious, and the error value is distributed positively cosine with the heading angle. In order to ensure the adaptability of the IMU to various operating conditions, it is necessary to compensate for the heading effect. The contribution of each error source of IMU to the heading effect is theoretically studied in this paper. We present a new method for compensating for the heading effect of the rate offset frequency laser IMU, in which the normal drift error of the vertical direction laser gyroscope and the zero bias error of the accelerometer under the turntable coordinate system are compensated. Based on the above method, simulation analysis and test verification are carried out. The experimental results show that the compensation method has a remarkable effect. In the case of two horizontal attitude angles tilted 0.0873 rad and 5 min initial alignment, the error of the rate offset frequency laser IMU reduced from 5.02E-04 rad $({3}\sigma)$(3σ) to 1.45E-04 rad $({3}\sigma)$(3σ), and the accuracy increased by 71%. High-precision initial alignment is achieved, which can meet the requirements of high-precision engineering applications.

An Interdigital Electrode Probe for Detection, Localization and Evaluation of Surface Notch-Type Damage in Metals.

Available microwave notch-type damage detection sensors are typically based on monitoring frequency shift or magnitude changes. However, frequency shift testing needs sweep-frequency data that make scanning detection becomes difficult and time-consuming. This work presents a microwave near-field nondestructive testing sensor for detecting sub-millimeter notch-type damage detection in metallic surfaces. The sensor is loaded with an interdigital electrode element in an open-ended coaxial. It is simple to fabricate and inexpensive, as it is etched on the RC4003 patch by using printed circuit board technology. The detection is achieved by monitoring changes in reflection amplitude, which is caused by perturbing the electromagnetic field around the interdigital structure. The proposed sensor was tested on a metallic plate with different defects, and the experimental results indicated that the interdigital electrode probe can determine the orientation, localization and dimension of surface notch-type damage.

Molecular characterization and gene expression of cathepsin L in Nile tilapia (Oreochromis niloticus).

Cathepsin L (CatL) has been widely known for its involvement in the innate immunity. However, it still remains poorly understand how CatL modulates the immune system of teleosts. Moreover, the CatL of Nile tilapia (NtCatL) has not been cloned or characterized. In this study, the gene encoding NtCatL was cloned, and was characterized by bioinformatics analysis, heterologous expression and protease activity assay. The coding sequence of NtCatL is 1017 bp in length and encodes 338 amino acid residues with a predicted molecular weight of 38.487 kDa and a theoretical isoelectric point of 5.79. NtCatL possesses the features of a typical cathepsin L, including one signal peptide, one propeptide region, and one papain family cysteine protease domain containing four active site residues (Gln135, Cys141, His281, and Asn305). The prediction of protein-protein interaction shows that NtCatL may interact with some functional proteins for realizing an immune function. Real-time quantitative PCR revealed the widespread transcriptional expression of NtCatL in six tissues of healthy Nile tilapia, and the NtCatL mRNA is significantly up-regulated after Streptococcus agalactiae challenge. These results suggest that NtCatL is likely to be involved in the immune reaction of Nile tilapia. Recombinant proteins from the mature domain (residues 117-337) of NtCatL were obtained by heterologous expression using pET28a and Rosetta (DE3) competent cells. A protein product with the high purity was obtained by using TALON Superflow purification rather than adopting HisTrap HP columns. The protease activity of the recombinant protein was verified by using a substrate hydrolyzing assay. This work has cloned and characterized the CatL from Nile tilapia for the first time, and contributes to elucidating the immunological functions of CatL.

Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy.

The recent approval of a prostate cancer vaccine has renewed hope for anticancer immunotherapies. However, the immunosuppressive tumor microenvironment may limit the effectiveness of current immunotherapies. Antiangiogenic agents have the potential to modulate the tumor microenvironment and improve immunotherapy, but they often are used at high doses in the clinic to prune tumor vessels and paradoxically may compromise various therapies. Here, we demonstrate that targeting tumor vasculature with lower vascular-normalizing doses, but not high antivascular/antiangiogenic doses, of an anti-VEGF receptor 2 (VEGFR2) antibody results in a more homogeneous distribution of functional tumor vessels. Furthermore, lower doses are superior to the high doses in polarizing tumor-associated macrophages from an immune inhibitory M2-like phenotype toward an immune stimulatory M1-like phenotype and in facilitating CD4(+) and CD8(+) T-cell tumor infiltration. Based on this mechanism, scheduling lower-dose anti-VEGFR2 therapy with T-cell activation induced by a whole cancer cell vaccine therapy enhanced anticancer efficacy in a CD8(+) T-cell-dependent manner in both immune-tolerant and immunogenic murine breast cancer models. These findings indicate that vascular-normalizing lower doses of anti-VEGFR2 antibody can reprogram the tumor microenvironment away from immunosuppression toward potentiation of cancer vaccine therapies. Given that the combinations of high doses of bevacizumab with chemotherapy have not improved overall survival of breast cancer patients, our study suggests a strategy to use antiangiogenic agents in breast cancer more effectively with active immunotherapy and potentially other anticancer therapies.

An effective method for the detoxification of cyanide-rich wastewater by Bacillus sp. CN-22.

The biodetoxification of cyanide-rich wastewater has become increasingly popular because of its cost-effectiveness and environmental friendliness. Therefore, we have developed an effective method, optimised by response surface methodology, for detoxifying cyanide-rich wastewater using Bacillus sp. CN-22, which was newly isolated from a cyanide-contaminated electroplating sludge and could tolerate a CN⁻ concentration of 700 mg L⁻¹. The concentration of CN⁻ in the treated wastewater decreased from 200 to 6.62 mg L⁻¹ after cultivation with 2.38 % inocula for 72 h on the medium, consisting of 0.05 % KH2PO4, 0.15 % K2HPO4, 1.0 mM MgCl2, 1.0 mM FeCl3, 0.1 % NH4Cl, and 0.1 % glycerol. The CN⁻ degradability of 96.69 % is similar to the predicted value of 96.82 %. The optimal cultivation conditions were controlled as follows: initial pH, 10.3; temperature, 31 °C; and rotary speed, 193 rpm. The maintenance of higher pH in the overall treatment procedures may avoid the production of volatile HCN and the risk associated with cyanide detoxification. Additionally, the bacterial strain Bacillus sp. CN-22, with its potent cyanide-degrading activity at the initial CN⁻ concentration of 200 mg L⁻¹, may be employed to effectively treat cyanide-rich wastewater, especially electroplating effluent.

Depth-related coupling relation between methane-oxidizing bacteria (MOBs) and sulfate-reducing bacteria (SRBs) in a marine sediment core from the Dongsha region, the South China Sea.

The vertical distributions of methane-oxidizing bacteria (MOBs) and sulfate-reducing bacteria (SRBs) in the marine sediment core of DH-CL14 from the Dongsha region, the South China Sea, were investigated. To enumerate MOBs and SRBs, their specific genes of pmoA and apsA were quantified by a culture-independent molecular biological technique, real-time polymerase chain reaction (RT-PCR). The result shows that the pmoA gene copies per gram of sediments reached the maximum of 1,118,679 at the depth of 140-160 cm. Overall considering the detection precision, sample amount, measurement cost, and sensitivity to the seepage of methane from the oil/gas reservoirs or gas hydrates, we suggest that the depth of 140-160 cm may be the optimal sampling position for the marine microbial exploration of oils, gases, and gas hydrates in the Dongsha region. The data of the pmoA and apsA gene copies exhibit an evident coupling relation between MOBs and SRBs as illustrated in their vertical distributions in this sediment core, which may well be interpreted by a high sulfate concentration inhibiting methane production and further leading to the reduction of MOBs. In comparison with the numbers of the pmoA and apsA copies at the same sediment depth, we find out that there were two methane-oxidizing mechanisms of aerobic and anaerobic oxidation in this sediment core, i.e., the aerobic oxidation with free oxygen dominantly occurred above the depth of 210-230 cm, while the anaerobic oxidation with the other electron acceptors such as sulfates and manganese-iron oxides happened below the depth of 210-230 cm.

The comparative transient prediction on hydrodynamic characteristics and flow field properties of pump-jets with accelerating and decelerating ducts.

Pump-jet holds a pivotal position in various marine applications, underscoring the need for comprehending their transient behavior for the purpose of design enhancement and performance refinement. This paper employs Reynolds-averaged Navier-Stokes equations method in conjunction with Detached Eddy Simulation model. The study delves into the ramifications of accelerating and decelerating ducts, distinguished by camber f and attack angles α, on transient hydrodynamic characteristics. The hydrodynamic characteristics are investigated numerically, after the validation of the numerical methodology by comparing simulation outcomes against experimental results. Subsequently, the study delves into propulsion characteristics, followed by an exploration of time-domain and frequency-domain data transformed through fast Fourier transform to analyze thrust fluctuations and pulsating pressures. Additionally, a detailed examination of pressure distribution and velocity field is provided, aiming to dissect the mechanisms through the variations in f and α influence the flow field. Findings suggest that the outlet velocity of accelerating ducts significantly surpasses the inlet velocity, a behavior contrasted by decelerating ducts. Notably, the patterns of accelerating and decelerating ducts resulting from alterations in f exhibit consistent characteristics with those brought about by changes in α. However, several opposite characteristics surface in transient flow field due to the distinct modifications in the duct profile. Furthermore, by considering vorticity magnitude distribution and vortices, a comparative analysis elucidates the effects of varying f and α on rotor and stator trailing vortices. This contributes to understanding the flow instability mechanism under differing duct configurations. It is evident that changes in f and α exert significant influence on both performance and flow field.

sEMG-based technology for silent voice recognition.

Silent speech recognition (SSR) is a system that implements speech communication when a sound signal is not available using surface electromyography (sEMG)-based speech recognition. Researchers have used surface electrodes to record the electrically-activated potential of human articulation muscles to recognize speech content. SSR can be used for pilot-assisted speech recognition, communication of individuals with speech impairment, private communication, and other fields. In this feasibility study, we collected sEMG data for ten single Mandarin numeric words. After reducing power frequency interference and power supply noise from the sEMG signal, short-term energy (STE) was used for voice activity detection (VAD). The power spectrum features were extracted and fed into the classifier for final identification results. We used the Hold-out method to divide the data into training and test sets on a 7-3 scale, with an average accuracy of 92.3% and a maximum of 100% using a support vector machine (SVM) classifier. Experimental results showed that the proposed method has development potential, and is effective in identifying isolated words from the sEMG signal of the articulation muscles.

Efficient phosphate elimination from aqueous media by La/Fe bimetallic modified bentonite: Adsorption behavior and inner mechanism.

Nowadays, eutrophication problem in surface waterbodies has attracted specific attention. Herein, we reported facile synthesis and application of La/Fe engineered bentonite (LFB) for efficient phosphate elimination. Results indicated that bimetallic modified LFB composite could achieve efficient phosphate removal at pH 2-6, and satisfactory selectivity was implied by stable phosphate capturing within the interference of competing species (Cl-, NO3-, HCO3-, SO42-, F- and HA). Pseudo-second-order model could satisfactorily depict the kinetic behavior at different initial concentrations, indicating chemisorption of phosphate on LFB surface. Isotherm study suggested that phosphate adsorption behavior could be fitted well with Sips isotherm equation, indicating that both homogeneous monolayer adsorption and heterogeneous multilayer coverage of phosphate on LFB surface occurred within the investigated conditions. Adsorption thermodynamics implied the spontaneous and endothermic feature of phosphate loading on LFB composite. Characterization analysis confirmed successful La and Fe loading on bentonite, and electrostatic attraction and ligand exchange were the main adsorption mechanism. The high adsorption capacity, cost-effective feature and strong affinity towards phosphate demonstrated certain potential of as-prepared LFB composite for phosphate separation from eutrophic water.

Microneedle Patch Loaded with Exosomes Containing MicroRNA-29b Prevents Cardiac Fibrosis after Myocardial Infarction.

Myocardial infarction (MI) is a cardiovascular disease that poses a serious threat to human health. Uncontrolled and excessive cardiac fibrosis after MI has been recognized as a primary contributor to mortality by heart failure. Thus, prevention of fibrosis or alleviation of fibrosis progression is important for cardiac repair. To this end, a biocompatible microneedle (MN) patch based on gelatin is fabricated to load exosomes containing microRNA-29b (miR-29b) mimics with antifibrotic activity to prevent excessive cardiac fibrosis after MI. Exosomes are isolated from human umbilical cord mesenchymal stem cells and loaded with miR-29b mimics via electroporation, which can be internalized effectively in cardiac fibroblasts to upregulate the expression of miR-29b and downregulate the expression of fibrosis-related proteins. After being implanted in the infarcted heart of a mouse MI model, the MN patch can increase the retention of loaded exosomes in the infarcted myocardium, leading to alleviation of inflammation, reduction of the infarct size, inhibition of fibrosis, and improvement of cardiac function. This design explored the MN patch as a suitable platform to deliver exosomes containing antifibrotic biomolecules locally for the prevention of cardiac fibrosis, showing the potential for MI treatment in clinical applications.

Small hydropower generation using pump as turbine; a smart solution for the development of Pakistan's energy.

Energy supply that is sustainable, effective, and economical has a strong association with socio-economic growth, particularly in developing countries such as Pakistan. Due to the ever-increasing gap between supply and demand, Pakistan has become an energy-deficient nation, with most people having no-to-limited access to power. Pakistan has been suffering from power shortages and an energy crisis because of its strong reliance on fossil-fuels to provide expensive electricity. Therefore, this paper offers a novel concept for developing Pakistan's energy by producing small-hydropower using Pump-As-Turbine (PAT), which is a form of Renewable-energy with lower environmental-impact and has not been used in Pakistan previously. PATs have shown several advantages over traditional hydro-turbines, such as minimum expenses, low-complexity, short delivery time, ease of spare parts, easy installation, availability in a large number of standard sizes, and massive production for broad-range of heads and flow rates. According to technical standards, any sort of pump could be used as PAT, including radial, mixed, single-stage, multi-stage etc. for power generation, which are capable of producing 5kW-1000kW of power, depending on their usage. However, Pakistan has shown little to no interest in exploring small/micro hydropower generation (PATs technology). Thus, this study offers public awareness and forward thinking regarding the use of advanced SHPs and draws the interests of legislators and different investors via solid recommendations about the cost-effective and environmental-friendly technology (PAT).

Response surface optimization of product yields and biofuel quality during fast hydrothermal liquefaction of a highly CO2-tolerant microalgae.

The effects of biochemical components and processing variables (e.g., temperatures, solid-liquid ratio, ethanol concentration, and time) during fast hydrothermal liquefaction of a highly CO2-tolerant microalgae (Micractinium sp.) on the product yields and biofuel quality were explored using response surface methodology coupled with central composite design. Results showed that the maximum bio-oil yield (51.4 %) was obtained at 321 °C for 49 min at ethanol concentration of 75 % and solid-liquid ratio of 15.3 %. Among different studied parameters, ethanol concentration showed the highest significant impact on the bio-oil yield due to the low P-value and high F-value in ANOVA analysis. Furthermore, the chemical compositions of bio-oils were determined, which showed that the increase of ethanol concentration in the solvent not only increased the bio-oil yield but also promoted the bio-oil quality by reduction of carboxylic acids and nitrogen-containing compounds with simultaneous enhancement of esters in the bio-oil. The present results show that fast hydrothermal liquefaction is a promising approach to convert the microalgae into high quality biofuels rich in esters.

Dissipativity-Based Disturbance Attenuation Control for T-S Fuzzy Markov Jumping Systems With Nonlinear Multisource Uncertainties and Partly Unknown Transition Probabilities.

This article is concerned with the dissipativity-based disturbance attenuation control for a class of Takagi-Sugeno (T-S) fuzzy Markov jump systems (FMJSs) suffering from nonlinear multisource disturbances. The considered system possesses nonlinear and stochastic jumping disturbances generated by multiple sources, constituting the main challenge to control design and dissipativity analysis. By proposing an adaptive fuzzy disturbance observer and a hybrid feedback controller, a novel fuzzy disturbance attenuation control structure has been constructed. In terms of strict linear matrix inequalities (LMIs), a new sufficient condition is established to guarantee the (Z, Y, X)-ε- dissipative and stochastic exponentially stability of the closed-loop FMJSs. Furthermore, for the concerned FMJSs with partly unknown transition probabilities, the sufficient conditions are also derived and the gains of controller or observer can be computed immediately. Finally, a numerical example is provided to verify the effectiveness of the proposed theory.

Removal of levofloxacin by an oleaginous microalgae Chromochloris zofingiensis in the heterotrophic mode of cultivation: Removal performance and mechanism.

Microalgae-based technology is an environmental-friendly and cost-effective method for treating antibiotics-contaminated wastewater. This work investigated the removal of levofloxacin (LEV) by an oleaginous microalgae Chromochloris zofingiensis under photoautotrophic and heterotrophic conditions. The results showed that the significantly higher biomass production, accumulation of extracellular polymeric substance and LEV removal efficiency were achieved in heterotrophic C. zofingiensis compared with the photoautotrophic ones. The removal efficiencies under the heterotrophic condition were 97%, 88% and 76% at 1, 10, and 100 mg/L LEV, respectively. HPLC-MS/MS and RNA-Seq analyses suggested that LEV could be bioaccumulated and biodegraded by heterotrophic C. zofingiensis through the reactions of defluorination, hydroxylation, demethylation, ring cleavage, oxidation, dehydrogenation, denitrification, and decarboxylation. The chemical composition of the algal biomass obtained after LEV treatment indicated the potential of this alga for removing LEV from wastewaters and simultaneously producing biodiesel, astaxanthin, and other products. Collectively, this research shows that the heterotrophic C. zofingiensis can be identified as a promising candidate for removing LEV in wastewater remediation.

Fucoxanthin, a marine carotenoid present in brown seaweeds and diatoms: metabolism and bioactivities relevant to human health.

The marine carotenoid fucoxanthin can be found in marine brown seaweeds, the macroalgae, and diatoms, the microalgae, and has remarkable biological properties. Numerous studies have shown that fucoxanthin has considerable potential and promising applications in human health. In this article, we review the current available scientific literature regarding the metabolism, safety, and bioactivities of fucoxanthin, including its antioxidant, anti-inflammatory, anticancer, anti-obese, antidiabetic, antiangiogenic and antimalarial activities, and its protective effects on the liver, blood vessels of the brain, bones, skin, and eyes. Although some studies have shown the bioavailability of fucoxanthin in brown seaweeds to be low in humans, many studies have suggested that a dietary combination of fucoxanthin and edible oil or lipid could increase the absorption rate of fucoxanthin, and thus it might be a promising marine drug.