Biomimetic Design of 3D Fe3O4/V-EVOH Fiber-Based Self-Floating Composite Aerogel to Enhance Solar Steam Generation Performance.

An interfacial solar steam generation evaporator for seawater desalination has attracted extensive interest in recent years. Nevertheless, challenges still remain in relatively low evaporation rate, unsatisfactory energy conversion efficiency, and salt accumulation. Herein, we have demonstrated a biomimetic bilayer composite aerogel consisting of bottom hydrophilic and vertically aligned EVOH channels and an upper hydrophobic conical Fe3O4 array. Thanks to the design merits, the 3D Fe3O4/V-EVOH evaporator exhibits a high evaporation rate of ∼2.446 kg m-2 h-1 and an impressive solar energy conversion efficiency of ∼165.5% under 1 sun illumination, which is superior to those of state-of-the-art evaporators reported so far. Moreover, the asymmetrical wettability not only allows the evaporator to self-float on the water but also facilitates the salt ion diffusion in the channels; thus, the evaporator shows no salt crystals on its surface and only a 6% decrease in evaporation performance even after the salt concentration increases from 0 to 10.0 wt %.

Soil selenium enhanced the resistance of oilseed rape to Sclerotinia sclerotiorum by optimizing the plant microbiome.

Plant can recruit beneficial microbes to enhance their ability to resist disease. Selenium is well established as a beneficial element in plant growth, but its role in mediating microbial disease resistance remained poorly understood. Here, we investigated the correlation between selenium, oilseed rape rhizosphere microbes and Sclerotinia sclerotiorum. Soil application of 0.5 and 1.0 mg/kg selenium significantly increased the resistance of oilseed rape to Sclerotinia sclerotiorum compared with no selenium application, and the disease inhibition rate was higher than 20%. The disease resistance of oilseed rape was related to rhizosphere microorganisms, and beneficial bacteria isolated from the rhizosphere inhibited Sclerotinia stem rot. Burkholderia cepacia, and synthetic community enhanced plant disease resistance through transcriptional regulation and activated plant-induced systemic resistance to protect plants. Besides, inoculation of isolated bacteria optimized the bacterial community structure of leaves and enriched beneficial microorganisms such as Bacillus, Pseudomonas and Sphingomonas. Bacillus isolated from the leaves were sprayed on the detached leaves, and it also performed a significant inhibition effect on Sclerotinia sclerotiorum. Overall, our results suggested that selenium drive plant rhizosphere microorganisms to increase resistance to Sclerotinia sclerotiorum in oilseed rape.

Understanding the Poly (Triazine Imide) Crystals Formation Process: The Conversion from Heptazine to Triazine.

Poly (triazine imide) (PTI) generally obtained via ionothermal synthesis features extended π-conjugation and enhanced crystallinity. However, in-depth investigation of the polycondensation process for PTI is an onerous task due to multiple influencing factors and limited characterization techniques. Herein, to simplify the polymerization route and exclude non-essential factors, PTI was prepared by calcining only melamine and LiCl. This study aims to identify the pivotal role of LiCl in PTI formation, which can convert heptazine-based intermediates into more stable triazine-based PTI framework. Based on this discovery, we demonstrate the transformation process of the prepared samples from amorphous Bulk g-C3 N4 to regular PTI, and further prove that the reaction with LiCl causes disruption of heptazine covalent organic frameworks. Additionally, the PTI exhibits higher photocatalytic water splitting performance due to efficient charge carrier mobility and separation, as well as faster reaction kinetics. This discovery deepens understanding of the polycondensation process of PTI crystals and provides insights toward the rational design of crystalline carbon nitride-based semiconductors.

Facet-Dependent Photocatalytic Behavior of Rutile TiO2 for the Degradation of Volatile Organic Compounds: In Situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy and Density Functional Theory Investigations.

In this study, a custom rutile titanium dioxide (TiO2) photocatalyst with a single exposed surface was utilized to investigate the facet-dependent photocatalytic mechanism of toluene. The degradation of toluene was dynamically monitored using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) technology coupled with theoretical calculations. The findings demonstrated that the photocatalytic degradation rate on the TiO2 (001) surface was nearly double that observed on the TiO2 (110) surface. This remarkable enhancement can be attributed to the heightened stability in the adsorption of toluene molecules and the concurrent reduction in the energy requirement for the ring-opening process of benzoic acid on the TiO2 (001) surface. Moreover, the TiO2 (001) surface generated a greater number of reactive oxygen species (ROS), thereby promoting the separation of photogenerated charge carriers and concurrently diminishing their recombination rates, amplifying the efficiency of photocatalysis. This research provides an innovative perspective for a more comprehensive understanding of the photocatalytic degradation mechanism of TiO2 and presents promising prospects for significant applications in environmental purification and energy fields.

Photo-thermal Catalytic Hydrogenation of Halogenated Nitrobenzenes over Ni/P25 Catalyst.

As haloanilines (HANs) are important organic intermediates and fine chemicals, their preparation over non-noble-metal-based catalysts by catalytic hydrogenation has attracted wide attention. However, the reaction suffers from relatively harsh conditions. Herein, we found that a 3.5%Ni/P25 catalyst exhibited superior photo-thermal catalytic activity with a TOFs of 5207 h-1 for hydrogenation of p-chloronitrobenzene (p-CNB) to p-chloroaniline under a 300 W full spectrum, which was much higher than that of photo- and thermal catalysis alone. Moreover, the 3.5%Ni/P25 catalyst could be recycled 4 times and was effective for the hydrogenation of various halonitrobenzenes (HNBs) with superior selectivity. Furthermore, the kinetic research showed that the excellent catalytic performance could be attributed to the better activation and dissociation of H2 by photo-thermal catalysis and the hydrogenation of p-CNB obeyed the condensation routine by ionic hydrogenation over 3.5%Ni/P25.

Limited threat of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletion to the utility of HRP2-based malaria RDTs in Northern Uganda.

BACKGROUND: Rapid diagnostic tests (RDTs) that detect Plasmodium falciparum histidine-rich protein-2 (PfHRP2) are exclusively deployed in Uganda, but deletion of the pfhrp2/3 target gene threatens their usefulness as malaria diagnosis and surveillance tools. METHODS: A cross-sectional survey was conducted at 40 sites across four regions of Uganda in Acholi, Lango, W. Nile and Karamoja from March 2021 to June 2023. Symptomatic malaria suspected patients were recruited and screened with both HRP2 and pan lactate dehydrogenase (pLDH) detecting RDTs. Dried blood spots (DBS) were collected from all patients and a random subset were used for genomic analysis to confirm parasite species and pfhrp2 and pfhrp3 gene status. Plasmodium species was determined using a conventional multiplex PCR while pfhrp2 and pfhrp3 gene deletions were determined using a real-time multiplex qPCR. Expression of the HRP2 protein antigen in a subset of samples was further assessed using a ELISA. RESULTS: Out of 2435 symptomatic patients tested for malaria, 1504 (61.8%) were positive on pLDH RDT. Overall, qPCR confirmed single pfhrp2 gene deletion in 1 out of 416 (0.2%) randomly selected samples that were confirmed of P. falciparum mono-infections. CONCLUSION: These findings show limited threat of pfhrp2/3 gene deletions in the survey areas suggesting that HRP2 RDTs are still useful diagnostic tools for surveillance and diagnosis of P. falciparum malaria infections in symptomatic patients in this setting. Periodic genomic surveillance is warranted to monitor the frequency and trend of gene deletions and its effect on RDTs.

RU-SLAM: A Robust Deep-Learning Visual Simultaneous Localization and Mapping (SLAM) System for Weakly Textured Underwater Environments.

Accurate and robust simultaneous localization and mapping (SLAM) systems are crucial for autonomous underwater vehicles (AUVs) to perform missions in unknown environments. However, directly applying deep learning-based SLAM methods to underwater environments poses challenges due to weak textures, image degradation, and the inability to accurately annotate keypoints. In this paper, a robust deep-learning visual SLAM system is proposed. First, a feature generator named UWNet is designed to address weak texture and image degradation problems and extract more accurate keypoint features and their descriptors. Further, the idea of knowledge distillation is introduced based on an improved underwater imaging physical model to train the network in a self-supervised manner. Finally, UWNet is integrated into the ORB-SLAM3 to replace the traditional feature extractor. The extracted local and global features are respectively utilized in the feature tracking and closed-loop detection modules. Experimental results on public datasets and self-collected pool datasets verify that the proposed system maintains high accuracy and robustness in complex scenarios.

Identification of Cu(111) as Superior Active Sites for Electrocatalytic NO Reduction to NH3 with High Single-Pass Conversion Efficiency.

Opting for NO as an N source in electrocatalytic NH3 synthesis presents an intriguing approach to tackle energy and environmental challenges. However, blindly pursuing high NH3 synthesis rates and Faradaic efficiency (FE) while ignoring the NO conversion ratio could result in environmental problems. Herein, Cu nanosheets with exposed (111) surface is fabricated and exhibit a NO-to-NH3 yield rate of 371.89 µmol cm-2 h-1 (flow cell) and the highest FE of 93.19±1.99 % (H-type cell). The NO conversion ratio is increased to the current highest value of 63.74 % combined with the development of the flow cell. Additionally, Crystal Orbital Hamilton Population (COHP) clearly reveals that the "σ-π* acceptance-donation" is the essence of the interaction between the Cu and NO as also supported by operando attenuated total reflection infrared spectroscopy (ATR-IRAS) in observing the key intermediate of NO- . This work not only achieves a milestone NO conversion ratio for electrocatalytic NO-to-NH3 , but also proposes a new descriptor that utilizes orbital hybridization between molecules and metal centers to accurately identify the real active sites of catalysts.

Cytochrome P450 2D6 profiles and anti-relapse efficacy of tafenoquine against Plasmodium vivax in Australian Defence Force personnel.

Plasmodium vivax infections and relapses remain a major health problem for malaria-endemic countries, deployed military personnel, and travelers. Presumptive anti-relapse therapy and radical cure using the 8-aminoquinoline drugs primaquine and tafenoquine are necessary to prevent relapses. Although it has been demonstrated that the efficacy of primaquine is associated with Cytochrome P450 2D6 (CYP2D6) activity, there is insufficient data on the role of CYP2D6 in the anti-relapse efficacy of tafenoquine. We investigated the relationship between CYP2D6 activity status and tafenoquine efficacy in preventing P. vivax relapses retrospectively using plasma samples collected from Australian Defence Force personnel deployed to Papua New Guinea and Timor-Leste who participated in clinical trials of tafenoquine during 1999-2001. The CYP2D6 gene was amplified from plasma samples and fully sequenced from 92 participant samples, comprised of relapse (n = 31) and non-relapse (n = 61) samples, revealing 14 different alleles. CYP2D6 phenotypes deduced from combinations of CYP2D6 alleles predicted that among 92 participants 67, 15, and 10 were normal, intermediate, and poor metabolizers, respectively. The deduced CYP2D6 phenotype did not correlate with the corresponding participant's plasma tafenoquine concentrations that were determined in the early 2000s by high-performance liquid chromatography or liquid chromatography-mass spectrometry. Furthermore, the deduced CYP2D6 phenotype did not associate with P. vivax relapse outcomes. Our results indicate that CYP2D6 does not affect plasma tafenoquine concentrations and the efficacy of tafenoquine in preventing P. vivax relapses in the assessed Australian Defence Force personnel.

Steroidal saponin profiles and their key genes for synthesis and regulation in Asparagus officinalis L. by joint analysis of metabolomics and transcriptomics.

BACKGROUND: Asparagus officinalis L. is a worldwide cultivated vegetable enrichened in both nutrient and steroidal saponins with multiple pharmacological activities. The upstream biosynthetic pathway of steroidal saponins (USSP) for cholesterol (CHOL) synthesis has been studied, while the downstream pathway of steroidal saponins (DSSP) starting from cholesterol and its regulation in asparagus remains unknown. RESULTS: Metabolomics, Illumina RNAseq, and PacBio IsoSeq strategies were applied to different organs of both cultivated green and purple asparagus to detect the steroidal metabolite profiles & contents and to screen their key genes for biosynthesis and regulation. The results showed that there is a total of 427 compounds, among which 18 steroids were detected with fluctuated concentrations in roots, spears and flowering twigs of two garden asparagus cultivars. The key genes of DSSP include; steroid-16-hydroxylase (S16H), steroid-22-hydroxylase (S22H) and steroid-22-oxidase-16-hydroxylase (S22O-16H), steroid-26-hydroxylase (S26H), steroid-3-ß-glycosyltransferase (S3ßGT) and furostanol glycoside 26-O-beta-glucosidases (F26GHs) which were correlated with the contents of major steroidal saponins were screened, and the transcriptional factors (TFs) co-expressing with the resulted from synthetic key genes, including zinc fingers (ZFs), MYBs and WRKYs family genes were also screened. CONCLUSIONS: Based on the detected steroidal chemical structures, profiles and contents which correlated to the expressions of screened synthetic and TFs genes, the full steroidal saponin synthetic pathway (SSP) of asparagus, including its key regulation networks was proposed for the first time.

Oligomeric phloroglucinols with hAChE inhibitory and antibacterial activities from tropic Rhodomyrtus tomentosa.

Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (hAChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a, 3b, 4b, and 5a), six new phloroglucinol trimers (6a, 6b, 7a, 7b, 8a, and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a/3b shared a rare C-5' formyl group, whereas 6a/6b possessed a unique C-7' aromatic ring. In addition, 7a/7b and 8a/8b were rare phloroglucinol trimers with a bis-furan and a C-6' hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (hAChE) inhibitory activity with an IC50 value of 1.21 ± 0.16 µM. The molecular docking studies of 3a and 3b in the hAChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 µg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents.

A new oleanane-type triterpenoid saponin with α-glucosidase inhibitory activity from Camellia nitidissima.

A new oleanane-type triterpenoid saponin, 21ß, 22α-di-O-angeloyl-15α, 16α, 28-trihydroxyolean-12-ene 3ß-O-α-L-rhamnopyranosyl-(1→3)-α-D-xylopyranosyl-(1→3)-ß-D-glucopyranoside (1), together with five known compounds (2-5), were isolated from Camellia nitidissima. Their structures were elucidated based on spectroscopic methods, including extensive NMR and MS spectra. Compound 1 showed potential inhibitory activity on α-glucosidase with the IC50 values of 185.9 ± 44.5 µmol/L.

Two new dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus.

Two undescribed dammarane triterpenoid saponins, cypaliurusides O and P (1 and 2), were isolated from the ethanol extracts of the leaves of Cyclocarya paliurus. Bioactivity assay results showed that compound 1 has potential cytotoxic activities against selected human cancer cell lines in vitro, with IC50 values ranging from 14.55 ± 0.55 to 22.75 ± 1.54 µM. Compound 1 showed better antitumor activity against HepG2 cells with IC50 of 14.55 ± 0.55 µM. In addition, compound 2 showed no obvious antitumor activity.

Synthesis and biological evaluation of esculetin derivatives as potential anti-HBV agents.

Previous in vivo and in vitro studies revealed that esculetin (Fig. 1) has anti-hepatitis B virus (anti-HBV) activity as well as a protective effect on liver damage caused by duck hepatitis B virus. We designed and synthesized a series of esculetin derivatives, introduced side chains containing various amino groups into site 7 of the parent structure, and synthesized C-4 and C-8 substituted derivatives with the goal of investigating their anti-HBV activities. In vitro anti-HBV activity was performed against HepG2.2.15 cells by using Enzyme-Linked Immunosorbent Assay(ELISA) kit and cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay with lamivudine as the positive control. The results demonstrated that several compounds showed moderate anti-HBV activity, while the introduction of morpholine groups could significantly inhibit the expression of hepatitis B e antigen (HBeAg) and the introduction of the 2-methylimidazole group could significantly inhibit the expression of Hepatitis B surface antigen (HBsAg). Among all tested compounds, compound 4a demonstrated the best anti-HBeAg activity (IC50 = 15.8 ± 4.2 µM), while compound 6d demonstrated the best anti-HBsAg activity (IC50 = 21.4 ± 2.8 µM). Compounds 6b and 6c showed moderate anti-HBV activity and HBsAg inhibition. Compounds 4b showed moderate anti-HBV activity and an inhibitory effect on HBeAg. In addition, compounds 4a, 4c, 4d, 6b, 6c and 6d showed improved metabolic stability. This study provides useful guidance for the discovery of anti-HBV drugs, which merits further investigation.

Plasmodium falciparum pfhrp2 and pfhrp3 Gene Deletions and Relatedness to Other Global Isolates, Djibouti, 2019-2020.

Deletions of pfhrp2 and paralogue pfhrp3 (pfhrp2/3) genes threaten Plasmodium falciparum diagnosis by rapid diagnostic test. We examined 1,002 samples from suspected malaria patients in Djibouti City, Djibouti, to investigate pfhrp2/3 deletions. We performed assays for Plasmodium antigen carriage, pfhrp2/3 genotyping, and sequencing for 7 neutral microsatellites to assess relatedness. By PCR assay, 311 (31.0%) samples tested positive for P. falciparum infection, and 296 (95.2%) were successfully genotyped; 37 (12.5%) samples were pfhrp2+/pfhrp3+, 51 (17.2%) were pfhrp2+/pfhrp3-, 5 (1.7%) were pfhrp2-/pfhrp3+, and 203 (68.6%) were pfhrp2-/pfhrp3-. Histidine-rich protein 2/3 antigen concentrations were reduced with corresponding gene deletions. Djibouti P. falciparum is closely related to Ethiopia and Eritrea parasites (pairwise GST 0.68 [Ethiopia] and 0.77 [Eritrea]). P. falciparum with deletions in pfhrp2/3 genes were highly prevalent in Djibouti City in 2019-2020; they appear to have arisen de novo within the Horn of Africa and have not been imported.

Priority Occupation of C-Sites by N-Confining P-Implantation in Pyrrodic N-Sites in NCNT@P,N-Mo2C for Highly Efficient Electrocatalytic Hydrogen Evolution.

Optimizing the electronic configuration of Mo2C by activating heteroatom(s)-neighboring carbon atoms to enhance the activity of hydrogen evolution reaction (HER) has been demonstrated. However, the development of heteroatom-doped Mo2C to fabricate a water electrolyzer is still a challenge because of the limitation of a well-defined electronic structure of hybridization of Mo with heteroatom(s). Here, nitrogen (N) and phosphor (P) codoped Mo2C embedded carbon nanotubes (NCNT@P,N-Mo2C) with the priority occupation of C-sites by N, which well confines the P-implantation at the pyrrodic N-sites and brings out N-O bonding on the surface, which favorably modifies the electronic configuration of adjacent Mo, resulting in highly efficient pH-tolerant HER activity. This study not only presents a potential HER electrocatalyst candidate but also provides a strategy for the construction of a well-defined electronic structure of heteroatom(s)-neighboring carbon-based materials.

Screening strategies and laboratory assays to support Plasmodium falciparum histidine-rich protein deletion surveillance: where we are and what is needed.

Rapid diagnostic tests (RDTs) detecting Plasmodium falciparum histidine-rich protein 2 (HRP2) have been an important tool for malaria diagnosis, especially in resource-limited settings lacking quality microscopy. Plasmodium falciparum parasites with deletion of the pfhrp2 gene encoding this antigen have now been identified in dozens of countries across Asia, Africa, and South America, with new reports revealing a high prevalence of deletions in some selected regions. To determine whether HRP2-based RDTs are appropriate for continued use in a locality, focused surveys and/or surveillance activities of the endemic P. falciparum population are needed. Various survey and laboratory methods have been used to determine parasite HRP2 phenotype and pfhrp2 genotype, and the data collected by these different methods need to be interpreted in the appropriate context of survey and assay utilized. Expression of the HRP2 antigen can be evaluated using point-of-care RDTs or laboratory-based immunoassays, but confirmation of a deletion (or mutation) of pfhrp2 requires more intensive laboratory molecular assays, and new tools and strategies for rigorous but practical data collection are particularly needed for large surveys. Because malaria diagnostic strategies are typically developed at the national level, nationally representative surveys and/or surveillance that encompass broad geographical areas and large populations may be required. Here is discussed contemporary assays for the phenotypic and genotypic evaluation of P. falciparum HRP2 status, consider their strengths and weaknesses, and highlight key concepts relevant to timely and resource-conscious workflows required for efficient diagnostic policy decision making.

An EVOH nanofibrous sterile membrane with a robust and antifouling surface for high-performance sterile filtration via glutaraldehyde crosslinking and a plasma-assisted process.

Constructing a sterile membrane with a robust and antifouling surface is a powerful means to improve the sterile filtration efficiency of sterile membranes. In this work, a robust EVOH nanofibrous sterile membrane was facilely fabricated by the method of in situ crosslinking with glutaraldehyde and surface plasma treatment. The resultant EVOH nanofibrous sterile membrane possessed a carboxylated-crosslinked surface, with high hydrophilicity, which generated high chemical stability, high-temperature steam resistance, and an ultrahigh antifouling performance against bovine serum albumin, ribonucleic acid and nanoparticle pollutants. Moreover, the membrane also exhibited a reasonably high primary water permeance (4522.2 LMH bar-1 at 0.2 MPa), as well as an absolute interception rate (100%) of Escherichia coli, Staphylococcus aureus cells and Brevundimonas diminuta superior to the state-of-the-art sterile membrane. Moreover, the modified membrane packed syringe-driven filter presented 100% interception (LRV ≥ 7) to Brevundimonas diminuta and high permeation flux (from 10.8 to 41.8 L·h-1) in a wide operating pressure range of 0.1 MPa to 0.6 MPa, indicating its potential in real bio-separation applications. This work provides a facile strategy for the preparation of a high-performance sterile membrane for biological drug product sterilization.

Integrating Tank Model and adsorption/desorption characteristics of filter media to simulate outflow water quantity and quality of a bioretention basin: A case study of biochar-based bioretention basin.

Reliable approaches for accurately assessing the performance of stormwater treatment systems is essential for their effective design, including filter media selection which can be a significant constituent in stormwater treatment systems. This study presents an innovative modelling approach integrating the Tank Model with the adsorption-desorption characteristics of the filter media. The resulting modelling approach was applied to simulate a field-scale bioretention basin where biochar was used as filter media with over ten years of rainfall records. The resulting outflow and overflow volumes were compared with observed data for calibration. The Stormwater Treatment Tank Model (STTM) was validated using the Leave-One-Out-Cross-Validation (LOOCV) method. The simulation outcomes include water outflow and overflow (quantity) from the bioretention basin as well as outflow water quality represented by three heavy metals (Pb, Cu, and Zn). The modelling approach developed was found to be capable of accurately simulating outflow and overflow volumes, with outlet water quantity being significantly influenced by the total rainfall depth. The modeling results also suggested that a sole treatment system would not be adequate, particularly for large rainfall events (>100 mm) and a treatment train would be more effective. Simulating long-term (over ten years) pollutant removal performance in the bioretention basin indicated that heavy metals outflow event mean concentration (EMCs) values calculated using simulated results of 30% biochar application rate generated the best pollutant removal with consistent values (2.7 µg/L, 3.0 µg/L, 17.2 µg/L for Pb, Cu, and Zn, respectively). These results confirm that the modelling approach is reliable for assessing long-term treatment performance, as well as a robust tool able to contribute to more effective treatment system design, particularly filter media selection and evaluation.

Dormant Plasmodium falciparum Parasites in Human Infections Following Artesunate Therapy.

BACKGROUND: Artemisinin monotherapy of Plasmodium falciparum infection is frequently ineffective due to recrudescence. Artemisinin-induced dormancy, shown in vitro and in animal models, provides a plausible explanation. To date, direct evidence of artemisinin-induced dormancy in humans is lacking. METHODS: Blood samples were collected from Plasmodium falciparum 3D7- or K13-infected participants before and 48-72 hours after single-dose artesunate (AS) treatment. Parasite morphology, molecular signature of dormancy, capability and dynamics of seeding in vitro cultures, and genetic mutations in the K13 gene were investigated. RESULTS: Dormant parasites were observed in post-AS blood samples of 3D7- and K13-infected participants. The molecular signature of dormancy, an up-regulation of acetyl CoA carboxylase, was detected in 3D7 and K13 samples post-AS, but not in pre-AS samples. Posttreatment samples successfully seeded in vitro cultures, with a significant delay in time to reach 2% parasitemia compared to pretreatment samples. CONCLUSIONS: This study provides strong evidence for the presence of artemisinin-induced dormant parasites in P. falciparum infections. These parasites are a likely reservoir for recrudescent infection following artemisinin monotherapy and artemisinin combination therapy (ACT). Combination regimens that target dormant parasites or remain at therapeutic levels for a sufficient time to kill recovering parasites will likely improve efficacy of ACTs.