Fluoranthene degradation in a persulfate system activated by sulfidated nano zero-valent iron (S-nZVI): performance and mechanisms.

Fluoranthene (FLT) has received mounting focus due to its hazardous properties and frequent occurrence in groundwater. In this study, sulfidated nano zero-valent iron (S-nZVI) was selected as an efficient catalyst for activating persulfate (PS) to degrade FLT. The effects of reagent doses, various water conditions (pH, anions, and humic acid), and the presence of surfactants on FLT degradation were investigated. Radical probe experiments, electron paramagnetic resonance (EPR) spectrum detection, and scavenging tests were performed to identify the major reactive oxygen species (ROS) in the system. The results showed that in the PS/S-nZVI system, 96.2% of FLT was removed within 120 min at the optimal dose of PS = 0.07 mM and S-nZVI = 0.0072 g L-1. S(-II) in the S-nZVI surface layer promoted Fe(II) regeneration. Furthermore, HO• and SO4-• were identified as the main contributors to FLT degradation. The intermediates of FLT degradation were detected by gas chromatograph-mass spectrometry (GC-MS) and a possible FLT degradation pathway was proposed. Finally, the effective degradation of two other common polycyclic aromatic hydrocarbons (PAHs) (naphthalene and phenanthrene) demonstrated the broad-spectrum reactivity of the PS/S-nZVI process. In conclusion, these findings strongly demonstrate that the PS/S-nZVI process is a promising alternative for the remediation of PAH-contaminated groundwater.

Assessing the therapeutic efficacy of artemether-lumefantrine for uncomplicated malaria in Lagos, Nigeria: a comprehensive study on treatment response and resistance markers.

BACKGROUND: The burden of malaria persists in sub-Saharan Africa and the emergence of artemisinin resistance has introduced complexity to control efforts. Monitoring the efficacy of artemisinin-based treatment for malaria is crucial to address this challenge. This study assessed treatment efficacy of artemether-lumefantrine (AL) and genetic diversity of Plasmodium falciparum isolates in a Nigerian population. METHODS: Participants presenting with clinical symptoms of uncomplicated malaria at a health centre in Lagos, Nigeria, were screened for P. falciparum. Enrolled participants were treated with AL and monitored through scheduled check-up visits, clinical and laboratory examinations for 28 days. Parasite clearance and genetic diversity were assessed through polymerase chain reaction (PCR) analysis of merozoite surface proteins (msp1 and msp2). The prevalence of drug resistance mutations was assessed by P. falciparum multidrug resistance gene 1 (mdr1) genotyping followed by P. falciparum ubiquitin-specific protease 1 (ubp1) gene sequencing. RESULTS: The PCR-uncorrected treatment outcome revealed 94.4% adequate clinical and parasitological response (ACPR) and 5.6% late parasitological failure (LPF) rates. After PCR correction, no suspected LPF case was detected and ACPR 67/67 (100%) was achieved in all the individuals. Moreover, a high prevalence of wild-type alleles for mdr1 N86Y (93.7%), and mdr1 D1246Y (87.5%) was observed. Genetic diversity analysis revealed predominant K1 allelic family for msp1 (90.2%) and FC27 for msp2 (64.4%). Estimated multiplicity of infection (MOI) was 1.7, with the highest MOI observed in the 5-15 years age group. ubp1 sequence analysis identified one nonsynonymous E1528D polymorphism at a low frequency (1.6%). CONCLUSION: The study demonstrated sustained efficacy of AL for treating uncomplicated P. falciparum malaria. Genetic diversity analysis revealed various allelic types, suggesting occurrences of polyclonal infections. Nonetheless, the detection of a significant ubp1 polymorphism could have future implications for the epidemiology of anti-malarial drug resistance in the population.

A broad-spectrum antibacterial hydrogel based on the synergistic action of Fmoc-phenylalanine and Fmoc-lysine in a co-assembled state.

Multicomponent biomolecular self-assembly is fundamental for accomplishing complex functionalities of biosystems. Self-assembling peptides, amino acids, and their conjugates serve as a versatile platform for developing biomaterials. However, the co-assembly of multiple building blocks showing synergistic interplay between individual components and producing biomaterials with emergent functional attributes is much less explored. In this study, we have formulated minimalistic co-assembled hydrogels composed of Fmoc-phenylalanine and Fmoc-lysine. The co-assembled systems display broad-spectrum antimicrobial potency, a feature absent in individual building blocks. A comprehensive biophysical analysis demonstrates the physicochemical features of the hydrogels eliciting the antibacterial response. MD simulation further reveals a unique fibrillar architecture with Fmoc-phenylalanine forming the fibril core surrounded by positively charged Fmoc-lysine surface residues, thereby enhancing the interaction with negatively charged bacterial membranes, causing membrane disruption and cell death. Thus, this study provides molecular-level insight into the emergent properties of a multicomponent system, affording an excellent paradigm for developing novel biomaterials.

Development of a non-separative screening strategy based on mass spectrometry for the semi-quantification of urinary polycyclic aromatic hydrocarbon metabolites.

A fast and non-separative screening strategy is presented for the analysis of five urinary metabolites of polycyclic aromatic hydrocarbons (PAHs), namely 2-naphthol, 1-acenaphthenol, 2-hydroxyfluorene, 9-phenanthrol and 1-hydroxypyrene. These hydroxylated derivatives (OH-PAHs) were subjected to enzymatic hydrolysis and were extracted from urine using a liquid-liquid extraction (LLE). The profile signals were obtained by direct injection of the sample into a programmed temperature vaporizer coupled to a quadrupole mass spectrometer via a deactivated fused silica tubing (PTV-qMS). Semi-quantitative determination was carried out by means of partial least squares regression (PLS1) using urine samples free of the analytes and spiked at several uncorrelated concentration levels. The multivariate calibration models worked satisfactorily, with errors ranging between 30 and 33 % for all the analytes except for 1-acenaphthenol that provided an error of 39 % when external validation set was considered. The repeatability and reproducibility, expressed as relative standard deviation (RSD), were ranged between 8-16 % and 11-18 %, respectively. The proposed method could be a useful tool for semi-quantification purposes of five OH-PAHs in urine samples, identifying positive samples for subsequent further chromatographic separation (confirmation), thus saving time and costs.

Push-Pull Fluorescent Dyes with Trifluoroacetyl Acceptor for High-Fidelity Sensing of Polarity and Heterogeneity of Lipid Droplets.

Imaging and sensing of lipid droplets (LDs) attracted significant attention due to growing evidence for their important role in cell life. Solvatochromic dyes are promising tools to probe LDs' local polarity, but this analysis is biased by their non-negligible emission from intracellular membranes and capacity to emit from both the apolar core and polar interface of LDs. Here, we developed two push-pull solvatochromic dyes based on naphthalene and fluorene cores bearing an exceptionally strong electron acceptor, the trifluoroacetyl group. The latter was found to boost the optical properties of the dyes by shifting their absorption and emission to red and increasing their extinction coefficient, photostability, and sensitivity to solvent polarity (solvatochromism). In contrast to classical solvatochromic dyes, such as parent aldehydes and reference Nile Red, the new dyes exhibited strong fluorescence quenching by millimolar water concentrations in organic solvents. In live cells, the trifluoroacetyl dyes exhibited high specificity to LDs, whereas the parent aldehydes and Nile Red showed a detectable backgrounds from intracellular membranes. Experiments in model lipid membranes and nanoemulsion droplets confirmed the high selectivity of new probes to LDs in contrast to classical solvatochromic dyes. Moreover, the new probes were found to be selective to the LDs oil core, where they can sense lipid unsaturation and chain length. Their ratiometric imaging in cells revealed strong heterogeneity in polarity within LDs, which covered the range of polarities of unsaturated triglyceride oils, whereas Nile Red failed to properly estimate the local polarity of LDs. Finally, the probes revealed that LDs core polarity can be altered by fatty acid diets, which correlates with their chain length and unsaturation.

Fluoranthene slow down sulfamethazine migration in soil via π-π interaction to increase the abundance of antibiotic resistance genes.

Sulfonamide antibiotics and polycyclic aromatic hydrocarbons (PAHs) often coexist in soil, leading to compound pollution through various pathways. This study focuses on sulfamethazine (SMZ) and PAHs (fluoranthene) as the subject for compound pollution research. Using a soil-groundwater simulation system, we investigated the migration characteristics of SMZ under coexistence with fluoranthene (Fla) and observed variations in the abundance of antibiotic resistance genes (ARGs). Through molecular docking simulations and isothermal adsorption experiments, we discovered that Fla bound with SMZ via π-π interactions, resulting in a 20.9% increase in the SMZ soil-water partition coefficient. Under compound conditions, the concentration of SMZ in surface soil could reach 1.4 times that of SMZ added alone, with an 13.4% extension in SMZ half-life. The deceleration of SMZ's vertical migration rate placed additional stress on surface soil microbiota, leading to a proliferation of ARGs by 66.3%-125.8%. Moreover, under compound pollution, certain potential hosts like Comamonadaceae and Gemmatimonas exhibited a significant positive correlation with resistance genes such as sul 1 and sul 2. These findings shed light on the impact of PAHs on sulfonamide antibiotic migration and the abundance of ARGs. They also provide theoretical insights for the development of technologies aimed at mitigating compound pollution in soil.

Enhanced fluorescence properties of polyfluorene-based polymer dots through an ascorbic acid-photoaging treatment for living cell imaging.

The polymer dots (Pdots) prepared by the conjugated polymer (PFO, poly (9,9-dihexylfluorene-2,7-diyl)) have high fluorescence intensity and are often used in biological fluorescence imaging. However, due to the chain defects, the PFO Pdots suffer from stability issues such as photoinactivation and photobleaching. To solve this problem, we drew inspiration from the preparation process of organic planar light-emitting devices and added an optimization processing after Pdots was prepared. We used illumination as the driving force to activate defects on its chain, and ascorbic acid as a reducing substance to restore the chain defects of the polymer to a more stable state. Through this method, we increased the fluorescence intensity by nearly 1.9 times, and significantly improving their long and short-term stability. In addition, it ensures other properties remain unchanged. This optimization scheme is also fully compatible with the entire biological imaging process, ensuring that other important properties such as cytotoxicity do not undergo unnecessary changes. Furthermore, we conducted material characterization and theoretical simulation, revealing that the optimization scheme mainly serves to repair C-9 alkyl defects on the polyfluorene unit. This study has improved and enhanced the fluorescence performance of PFO Pdots, and also provides a way to optimize the treatment of other similar conjugated polymer material systems.

A case study on microlitter and chemical contaminants: Assessing biological effects in the southern coast of the Gulf of Finland (Baltic sea) using the mussel Mytilus trossulus as a bioindicator.

Chemical and microlitter (ML) pollution in three Estonian coastal areas (Baltic Sea) was investigated using mussels (Mytilus trossulus). Polycyclic aromatic hydrocarbons (PAH) in mussel tissues were observed in moderate levels with high bioaccumulation factors for the more hydrophilic and low molecular weight PAH (LMW PAH), namely anthracene and fluorene. Tissue concentrations of polybrominated diphenyl ethers (PBDE) and cadmium within mussel populations exceeded the Good Environmental Status thresholds by more than 200% and 60%, respectively. Multiple contamination at the Muuga Harbour site by tributyltin, high molecular weight PAH, including the highly toxic benzo[c]fluorene and PBDE, coincided with the inhibition of acetylcholinesterase activity and a lower condition index of the mussels. The metabolization and removal of bioaccumulated LMW PAH, reflected in the dominance of oxy-PAH such as anthracene-9,10-dione, is likely associated with the increased activity of glutathione S-transferase in caged mussels. Only a few microplastic particles were observed among the ML in mussel tissues, with coloured cellulose-based microfibers being the most prevalent. The average concentration of ML in mussels was significantly higher at the harbour area than at other sites. The integrated biomarker response index values allowed for the differentiation of pollution levels across studied locations representing high, intermediate, and low pollution levels within the studied area.

Phase 1b study to assess the safety, tolerability, and clinical activity of pamiparib in combination with temozolomide in patients with locally advanced or metastatic solid tumors.

BACKGROUND: Pamiparib is a potent, selective, poly (ADP-ribose) polymerase 1/2 inhibitor that demonstrates synthetic lethality in cells with breast cancer susceptibility gene mutations or other homologous recombination deficiency. This two-stage phase 1b study (NCT03150810) assessed pamiparib in combination with temozolomide (TMZ) in adult patients with histologically confirmed locally advanced and metastatic solid tumors. METHODS: Oral pamiparib 60 mg was administered twice daily. During the dose-escalation stage, increasing doses of TMZ (40-120 mg once daily pulsed or 20-40 mg once daily continuous) were administered to determine the recommended dose to be administered in the dose-expansion stage. The primary objectives were to determine safety and tolerability, maximum tolerated/administered dose, recommended phase 2 dose and schedule, and antitumor activity of pamiparib in combination with TMZ. Pharmacokinetics of pamiparib and TMZ and biomarkers were also assessed. RESULTS: Across stages, 139 patients were treated (dose escalation, n = 66; dose expansion, n = 73). The maximum tolerated dose of TMZ, which was administered during dose expansion, was 7-day pulsed 60 mg once daily. The most common treatment-emergent adverse events (TEAEs) were anemia (dose escalation, 56.1%; dose expansion, 63.0%), nausea (dose escalation, 54.5%; dose expansion, 49.3%), and fatigue (dose escalation, 48.5%; dose expansion, 47.9%). In the dose-escalation stage, four patients experienced dose-limiting toxicities (three neutropenia and one neutrophil count decreased). No TEAEs considered to be related to study drug treatment resulted in death. Antitumor activity was modest, indicated by confirmed overall response rate (dose escalation, 13.8%; dose expansion, 11.6%), median progression-free survival (3.7 and 2.8 months), and median overall survival (10.5 and 9.2 months). Administration of combination therapy did not notably impact pamiparib or TMZ pharmacokinetics. CONCLUSIONS: Pamiparib in combination with TMZ had a manageable safety profile. Further investigation of the efficacy of this combination in tumor types with specific DNA damage repair deficiencies is warranted.

A co-assembly process for high strength and injectable dual network gels with sustained doxorubicin release performance.

Adopting a non-covalent co-assembly strategy shows great potential in loading drugs efficiently and safely in drug delivery systems. However, finding an efficient method for developing high strength gels with thixotropic characteristics is still challenging. In this work, by hybridizing the low molecular weight gelator fluorenylmethyloxycarbonyl-phenylalanine (Fmoc-F) (first single network, 1st SN) and alginate (second single network, 2nd SN) into a dual network (DN) gel, gels with high strength as well as thixotropy were prepared efficiently. The DN gels showed high strength (103 Pa in SN gels and 105 Pa in DN gels) and thixotropic characteristics (yield strain <25%; recovery ratio >85% within 100 seconds). The application performance was verified by loading doxorubicin (DOX), showing better encapsulation capacity (77.06% in 1st SN, 59.11% in 2nd SN and 96.71% in DN) and sustained release performance (lasting one week under physiological conditions) than single network gels. Experimental and DFT results allowed the elaboration of the specific non-covalent co-assembly mechanism for DN gel formation and DOX loading. The DN gels were formed by co-assembly driven by H-bond and π-π stacking interactions and then strengthened by Ca2+-coupling. Most DOX molecules co-assembled with Fmoc-F and alginate through π-π stacking and H-bond interactions (DOX-I), with a few free DOX molecules (DOX-II) left. Proven by the release dynamics test, DOX was released through a diffusion-erosion process, in an order of DOX-I first and then DOX-II. This work suggests that non-covalent co-assembly is a useful technique for effective material strengthening and drug delivery.

Dietary exposure to polyaromatic hydrocarbons of the Hong Kong population.

Polyaromatic hydrocarbons (PAHs) are ubiquitous in the environment and food. The Joint FAO/WHO Expert Committee on Food Additives concluded 13 individual PAHs are carcinogenic and genotoxic in vitro and in vivo. Food is recognized as the main source of exposure to PAHs for adult non-smokers, which contributed to more than 90% of total exposure. In this study, 300 food samples were collected in Hong Kong, analysed the levels of 16 European Union priority PAHs, the dietary exposure to these PAHs by the local adult population from these food items, and the associated health risk. The most predominant detectable PAH was chrysene (CHR) (14.4%), followed by benzo[c]fluorene (11.2%), benzo[a]anthracene (BaA) (10.6%) and benzo[b]fluoranthene (BbFA) (7.8%). The dietary exposures for average consumers of benzo[a]pyrene (BaP) and PAH4 (sum of BaP, CHR, BaA and BbFA) were 0.13-0.90 and 1.4-4.2 ng/kg bw/day respectively for lower and upper bound approaches. Cereal and its products contributed more than 50% to BaP and PAH4 for average consumers in a lower-bound approach. The margin of exposure (MOE) approach was used to assess the health risks of consumers. The calculated MOE values for both BaP and PAH4 of the average and high consumers (90th percentile) were >50,000, indicating a low concern for the health of the Hong Kong population.

Toxic effect of fluorene on Perinereis aibuhitensis body wall and its corresponding defense mechanisms: A metabolomics perspective.

Fluorene is a coastal sediment pollutant with high ecological risk. Perinereis aibuhitensis is an ecotoxicological model used for polycyclic aromatic hydrocarbon bioremediation; however, the effects of fluorene on the physiological metabolism of P. aibuhitensis and its corresponding responses remain unclear. This study explored the tolerance and defense responses of P. aibuhitensis in sediments with different fluorene concentrations using histology, ecological biomarkers, and metabolic responses. Metabolomics analyses revealed that P. aibuhitensis has high tolerance to fluorene in sediments. Fluorene stress disrupted the normal metabolism of the P. aibuhitensis body wall, resulting in excessive glycosphospholipid and stearamide accumulation and elevated oxygen consumption rates. To mitigate this, P. aibuhitensis has adopted tail cutting, yellowing, and modulation of metabolite contents in the body wall. This study provides novel insights into the potential ecological risk of fluorene pollution in marine sediments and proposes the use of P. aibuhitensis in the bioremediation of fluorene-contaminated sediments.

Analysis of the susceptibility of refractory hepatitis C virus resistant to nonstructural 5A inhibitors.

Resistance-associated substitutions (RASs) of hepatitis C virus (HCV) affect the efficacy of direct-acting antivirals (DAAs). In this study, we aimed to clarify the susceptibility of the coexistence of nonstructural (NS) 5A Q24K/L28M/R30Q (or R30E)/A92K RASs, which were observed in patients with DAAs re-treatment failure and to consider new therapeutic agents. We used a subgenomic replicon system in which HCV genotype 1B strain 1B-4 was electroporated into OR6c cells derived from HuH-7 cells (Wild-type [WT]). We converted WT genes to NS5A Q24K/L28M/R30Q/A92K or Q24/L28K/R30E/A92K. Compared with the WT, the Q24K/L28M/R30Q/A92K RASs was 36,000-fold resistant to daclatasvir, 440,000-fold resistant to ledipasvir, 6300-fold resistant to velpatasvir, 3100-fold resistant to elbasvir, and 1.8-fold resistant to pibrentasvir. Compared with the WT, the Q24K/L28M/R30E/A92K RASs was 640,000-fold resistant to daclatasvir and ledipasvir, 150,000-fold resistant to velpatasvir, 44,000-fold resistant to elbasvir, and 1500-fold resistant to pibrentasvir. The Q24K/L28M/R30E/A92K RASs was 816.3 times more resistant to pibrentasvir than the Q24K/L28M/R30Q/A92K RASs. Furthermore, a combination of pibrentasvir and sofosbuvir showed therapeutic efficacy against these RASs. Combination regimens may eradicate HCV with NS5A Q24K/L28M/R30E/A92K RASs.

Characteristics of pollutant generation from 3D-printed photocured waste combustion.

With the rapid advancement of photopolymerization-based 3D printing technology, the volume of PCW has experienced a sharp increase. The potential environmental ramifications of PCW disposal demand careful consideration, especially given its current practice of being incineration alongside MSW. In this study, the TG-MS/FTIR system was carried out to probe the thermogravimetric characteristics and volatile byproducts during combustion. Various product compositions resulting from different mixing ratios of PCW incineration with MSW were investigated. It was observed that fluorene (C13H10) and triphenylene (C18H12) produced by PCW combustion 0.52 mg/g and 0.43 mg/g respectively, which are twice as abundant as those generated from normal plastic. When PCW incineration along with MSW, compounds such as naphthalene (C10H8), cyclohexane (C6H12), and heptane (C7H16) were generated in concentrations of 1.25 mg/g, 1.05 mg/g, and 0.95 mg/g respectively, which are at least twice as much as with MSW incineration alone. The incineration of PCW with rubber and textiles resulted in the production of 2.34 mg/g to 3.76 mg/g more PAHs compared to PCW combustion alone. The incineration of PCW with paper resulted in the production of 3.12 mg/g to 5.15 mg/g more heptane, nonane, cyclohexane, pyrene, and anthracene than PCW combustion alone. Incineration of PCW with wood proved to be the cleanest method, with product contents primarily below 0.10 mg/g. When incinerated with food residues or normal plastic, most of the product content remained below 0.05 mg/g. Considering the environmental pollution resulting from PCW combustion, the disposal of PCW warrants careful consideration and management.

Benzo(b)fluoranthene and benzo(k)fluoranthene removal by microalgae in the presence of triazine herbicides: Matrix solid-phase dispersion and solid-phase extraction (MSPD/SPE) for HPLC-UV analysis of the different culture components.

Over the last decade, human activities in the industrial and agricultural sectors have significantly increased the concentration of persistent and harmful pollutants in aquatic ecosystems. The use of microorganisms is a green strategy for the bio-removal of certain contaminants. However, other pollutants in the same ecosystems can reduce their degrading activity and even affect their survival. Therefore, this study aimed to evaluate the efficiency of benzo(b)fluoranthene (BbF) and benzo(k)fluoranthene (BkF) removal by Selenastrum capricornutum in the presence of triazine herbicides, compounds mainly used in broadleaf weeds. The interest of this work focused on identifying in which of the microalgal components the degrading activity is best evidenced and affected. For this purpose, the use of solid-phase extraction (SPE) and matrix solid-phase dispersion (MSPD) extraction procedures and HPLC-UV analysis allowed the BbF and BkF trace quantification in biomass, liquid medium, and cell lysate separately from cultures exposed to these polycyclic aromatic hydrocarbons (PAHs) alone or with herbicides. The recovery percentages were between 78 and 94 %, good linearity (r2 ≈ 0.99), precision values measured as RSD < 15 %, and limits of detection (LOQs) at levels of ng mL-1 and ng mg-1 were obtained. The individual PAH amounts measured in the components of microalgae cultures show similar removal kinetics (removal percentages: 82-89 %). Likewise, the analysis demonstrated that the removal of PAHs is not affected in the presence of triazine herbicides (atrazine and cyanazine) and with similar removal percentages (79-86 %) compared to those cultures exposed to individual PAHs (74-83 %). These results support the possible real-world applications of PAH removal by extracts from S. capricornutum in aquatic environments contaminated with PAHs and near agriculture areas where triazine herbicides are used.

Fmoc Solid-Phase Peptide Synthesis.

Synthetic peptides are important as drugs and in research. Currently, the method of choice for producing these compounds is solid-phase peptide synthesis. Here, we describe the scope and limitations of Fmoc solid-phase peptide synthesis. Furthermore, we provide a detailed protocol for Fmoc peptide synthesis.

Hepatitis C virus diversity and treatment outcomes in Benin: a prospective cohort study.

BACKGROUND: 10 million people are chronically infected with the hepatitis C virus (HCV) in sub-Saharan Africa. The assessment of viral genotypes and treatment response in this region is necessary to achieve the WHO target of worldwide elimination of viral hepatitis by 2030. We aimed to investigate the prevalence of HCV genotypes and outcomes of treatment with direct-acting antiviral agents in Benin, a country with a national HCV seroprevalence of 4%. METHODS: This prospective cohort study was conducted at two referral hospitals in Benin. Individuals were eligible for inclusion if they were seropositive for HCV and willing to consent to participation in the study; exclusion criteria were an inability to give consent or incarceration. Viraemia was confirmed by PCR. The primary outcomes were to identify HCV genotypes and measure sustained virological response rates 12 weeks after completion of treatment (SVR12) with a 12-week course of sofosbuvir-velpatasvir or sofosbuvir-ledipasvir, with or without ribavirin. We conducted phylogenetic and resistance analyses after the next-generation sequencing of samples with a cycle threshold (Ct) value of 30 or fewer cycles. The in-vitro efficacy of NS5A inhibitors was tested using a subgenomic replicon assay. FINDINGS: Between June 2, 2019, and Dec 30, 2020, 148 individuals were screened for eligibility, of whom 100 were recruited prospectively to the study. Plasma samples from 79 (79%) of the 100 participants were positive for HCV by PCR. At the time of the study, 52 (66%) of 79 patients had completed treatment, with an SVR12 rate of 94% (49 of 52). 57 (72%) of 79 samples had a Ct value of 30 or fewer cycles and were suitable for whole-genome sequencing, from which we characterised 29 (51%) samples as genotype 1 and 28 (49%) as genotype 2. Three new genotype 1 subtypes (1q, 1r, and 1s) and one new genotype 2 subtype (2xa) were identified. The most commonly detected subtype was 2d (12 [21%] of 57 samples), followed by 1s (eight [14%]), 1r (five [9%]), 1b (four [7%]), 1q (three [5%]), 2xa (three [5%]), and 2b (two [3%]). 20 samples (11 genotype 2 and nine genotype 1) were unassigned new singleton lineages. 53 (93%) of 57 sequenced samples had at least two resistance-associated substitutions within the NS5A gene. Subtype 2d was associated with a lower-than-expected SVR12 rate (eight [80%] of ten patients). For one patient, with subtype 2b, treatment was not successful. INTERPRETATION: This study revealed a high SVR rate in Benin among individuals treated for HCV with sofosbuvir-velpatasvir, including those with highly diverse viral genotypes. Further studies of treatment effectiveness in genotypes 2d and 2b are indicated. FUNDING: Medical Research Council, Wellcome, Global Challenges Research Fund, Academy of Medical Sciences, and PHARMBIOTRAC.

A novel red-to-near-infrared AIE fluorescent probe for detection of Hg2+ with large Stokes shift in plant and living cells.

Due to the highly toxic nature of mercury ions to living organisms, accurately detecting Hg2+ in water samples and biological systems is of great significance. In this study, we designed and synthesized a novel red-to-near-infrared Aggregation-Induced Emission (AIE) fluorescent probe (named as DS) based Fluorene derivatives on specifically for Hg2+ detection. Probe DS can visually identify Hg2+ through an red-to-near-infrared fluorescence enhancement change, characterized by a large Stokes shift (130 nm) and AIE feature. This probe offers a fast response, high selectivity and sensitivity. The Hg2+-induced deprotection reaction of the thioketal mechanism was thoroughly investigated using nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS) and density functional theory (DFT) calculation. Additionly, dynamic light scattering (DLS) results indicated that the aggregation states changes of the molecular play a crucial role in the AIE fluorescence response of probe DS toward Hg2+. The red-to-near-infrared response with AIE feature not only avoids the interference of auto-fluorescence signals in complex environments, but also reduces the fluorescence quenching caused by probe molecular aggregation. This makes probe DS highly suitable for high-quality imaging detection of Hg2+ in aqueous environments. Furthermore, probe DS demonstrates the capability for visual fluorescence detection of Hg2+ concentrations in water sample, plant roots and living cells.

Mechanisms of intestinal injury in polychaete Perinereis aibuhitensis caused by low-concentration fluorene pollution: Microbiome and metabonomic analyses.

The polychaete Perinereis aibuhitensis is used for bioremediation; however, its ability to remove fluorene, a common environmental pollutant, from sediments remains unclear, especially at low concentrations of fluorene (10 mg/kg). In this study, we explored the mechanism of intestinal injury induced by low concentrations of fluorene and the reason intestinal injury is alleviated in high fluorene concentration groups (100 and 1000 mg/kg) using histology, ecological biomarkers, gut microbiome, and metabolic response analyses. The results show that P. aibuhitensis showed high tolerance to fluorene in sediments, with clearance rates ranging 25-50 %. However, the remediation effect at low fluorene concentrations (10 mg/kg) was poor. This is attributed to promoting the growth of harmful microorganisms such as Microvirga, which can cause metabolic disorders, intestinal flora imbalances, and the generation of harmful substances such as 2-hydroxyfluorene. These can result in severe intestinal injury in P. aibuhitensis, reducing its fluorene clearance rate. However, high fluorene concentrations (100 and 1000 mg/kg) may promote the growth of beneficial microorganisms such as Faecalibacterium, which can replace the dominant harmful microorganisms and improve metabolism to reverse the intestinal injury caused by low fluorene concentrations, ultimately restoring the fluorene-removal ability of P. aibuhitensis. This study demonstrates an effective method for evaluating the potential ecological risks of fluorene pollution in marine sediments and provides guidance for using P. aibuhitensis for remediation.