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Polycyclic aromatic hydrocarbons (PAHs) and their oxygenated derivates (O-PAHs) are identified in soils and groundwater of industrialized sites and contribute to the risk for Humans and the Environment. Nevertheless, data are scarce in literature concerning their retention and transfer in soils and no soil - water partition coefficients are available for these compounds. Sorption of two PAHs, fluorene and acenaphthene and two O-PAHs, 9H-fluorenone and dibenzofuran onto two soils with different organic carbon contents was evaluated and compared by determining their sorption isotherms. Effect of ionic strength and liquid to solid ratio, on fluorene and fluorenone sorption was also evaluated. Sorption equilibrium is achieved within less than 24 hr of mixing and linear sorption models best fit the isotherm data. Acenaphthene and dibenzofuran are similarly sorbed onto the soil. K

Nitrated polycyclic aromatic hydrocarbons (NPAHs) are widespread organic pollutants that possess carcinogenic and mutagenic properties, so they may pose a risk to the environment and human health. In this study, the concentrations of 15 NPAHs and 16 polycyclic aromatic hydrocarbons (PAHs) in 30 surface water samples and 26 sediment samples were measured in 2018 from the Taige Canal, one of the main rivers flowing into Taihu Lake, China. The total NPAH concentrations in water and sediment ranged from 14.7 to 235 ng/L and 22.9 to 96.5 ng/g dw, respectively. 9-nitrophenanthrene (nd-76.3 ng/L) was the dominant compound in surface water, while 2+3-nitrofluoranthene (1.73-18.1 ng/g dw) dominated in sediment. Among PAHs, concentration ranging from 1,097 to 2,981 ng/L and 1,089 to 4,489 ng/g dw in surface water and sediment, respectively. There was a strong positive correlation between the log octanol-water partition coefficient (K

Bio-endogenous peptide molecules are ideal components for fabrication of biocompatible and environmentally friendly semiconductors materials. However, to date, their applications have been limited due to the difficulty in obtaining stable, high-performance devices. Herein, simple amino acid derivatives fluorenylmethoxycarbonyl-leucine (Fmoc-L) and fluorenylmethoxycarbonyl-tryptophan (Fmoc-W) are utilized to form long-range ordered supramolecular nanostructures by tight aromatic stacking and extensive hydrogen bonding with mechanical, electrical and optical properties. For the first time, without addition of any photosensitizers, pure Fmoc-L microbelts and Fmoc-W microwires exhibit Young's modulus up to 28.79 and 26.96 GPa, and unprecedently high values of photocurrent responses up to 2.2 and 2.3 μA/cm

We aimed to analyze the association between certain types of urinary polycyclic aromatic hydrocarbons (PAHs) and bone mineral density (BMD) at specific sites of the body.A total of 2978 eligible participants from the National Health and Nutrition Examination Survey 2001 to 2004 were included in this study. Data of 8 urinary PAHs and BMDs of 3 skeleton sites and the total body were analyzed. Univariate and multivariate linear regression analyses were performed to explore the association between urinary PAHs and BMDs. Subgroup analyses stratified by sex and body mass index were also performed.After adjustment for all confounders, elevated 3-fluorene (β = 0.046; 95% confidence intervals [CIs], 0.007-0.084) and 2-fluorene (β = 0.054; 95% CI, 0.007-0.100) levels were associated with greater left arm BMD, whereas no statistical differences were observed in the relationship between other PAHs and BMDs (all P.05). Higher 3-fluorene and 2-fluorene levels were still associated with increased left arm BMD in men (P.05), whereas the higher 2-phenanthrene level was related to decreased left arm BMD (β = -0.062; 95% CI, -0.105 to -0.019), right arm BMD (β = -0.059; 95% CI, -0.091 to -0.027), and total BMD (β = -0.065; 95% CI, -0.119 to -0.012) in women. Similar results were also found in different body mass index populations (all P.05).Certain urinary PAHs are associated with BMDs at specific body sites. Future studies are needed to illustrate the mechanisms behind the association to establish a causal relationship.

We describe a stereocontrolled synthesis of 3, the fully glycosylated monomeric unit of the dimeric cytotoxic bacterial metabolite (−)-lomaiviticin A (2). A novel strategy involving convergent, site- and stereoselective coupling of the β,γ-unsaturated ketone 6 and the naphthyl bromide 7 (92%, 15:1 diastereomeric ratio (dr)), followed by radical-based annulation and silyl ether cleavage, provided the tetracycle 5 (57% overall), which contains the carbon skeleton of the aglycon of 3. The β-linked 2,4,6-trideoxy-4-aminoglycoside l-pyrrolosamine was installed in 73% yield and with 15:1 β:α selectivity using a modified Koenigs–Knorr glycosylation. The diazo substituent was introduced via direct diazo transfer to an electron-rich benzoindene (4 → 27). The α-linked 2,6-dideoxyglycoside l-oleandrose was introduced by gold-catalyzed activation of an o-alkynyl glycosylbenzoate (75%, >20:1 α:β selectivity). A carefully orchestrated endgame sequence then provided efficient access to 3. Cell viability studies indicated that monomer 3 is not cytotoxic at concentrations up to 1 μM, providing conclusive evidence that the dimeric structure of (−)-lomaiviticin A (2) is required for cytotoxic effects. The preparation of 3 provides a foundation to complete the synthesis of (−)-lomaiviticin A (2) itself.

Pamiparib is a poly ADP-ribose polymerase (PARP) inhibitor used in clinical studies, which can penetrate the blood-brain barrier efficiently. At present, there are few studies on its effect on vertebrate neurodevelopment. In this study, we exposed zebrafish embryos to 1, 2 and 3 µM of Pamiparib from 6 to 72 h post-fertilisation (hpf). Results showed that pamiparib can specifically induce cerebral haemorrhage, brain atrophy and movement disorders in fish larvae. In addition, pamiparib exposure leads to downregulation of acetylcholinesterase (AChE) and adenosine triphosphate (ATPase) activities, and upregulation of oxidative stress which then leads to apoptosis and disrupts the gene expression involved in the neurodevelopment, neurotransmitter pathways and Parkinson's disease (PD) like symptoms. Meanwhile, astaxanthin can partially rescue neurodevelopmental defects by downregulating oxidative stress. After exposure to pamiparib, the Notch signalling is downregulated, and the use of an activator of Notch signalling can partially rescue neurodevelopmental toxicity. Therefore, our research indicates that pamiparib may induce zebrafish neurotoxicity by downregulating Notch signalling and provides a reference for the potential neurotoxicity of pamiparib during embryonic development.

Tetramethyl bisphenol A (TMBPA) is a widely used flame retardant. TMBPA has been a toxic to Leydig cells in puberty, but it remains unclear whether TMBPA has a similar inhibitor effect on fetal Leydig cells (FLCs). This study reported morphological and functional alterations of FLCs in the testes of male offspring at birth after in utero exposure to TMBPA. Pregnant Sprague Dawley rats were dosed via continuous gavage of TMBPA (0, 10, 50, and 200 mg/kg/day) from gestational day 14 to 21. TMBPA markedly raised serum total testosterone level, testicular volume, and FLC number of male offspring at 200 mg/kg dose. The up-regulation of Insl3, Star, and Cyp11a1 mRNAs was observed after 200 mg/kg TMBPA exposure. After normalization to the number of FLCs, TMBPA significantly reduced Lhcgr and Hsd3b1 expressions at 10 mg/kg, and Cyp17a1 at 200 mg/kg paralleling with their protein levels. TMBPA compromised the expression of Esr1, while increased the expression of Cdk2 and Cdk4 as well as their protein levels. TMBPA particularly increased the phosphorylation of AKT1 and AKT2 at 200 mg/kg. In conclusion, the present study suggests that TMBPA may promote FLC proliferation via ESR1-CDK2/4-AKT pathway, while inhibits the function of FLCs by reducing steroidogenic enzyme activity.

The unique four-level photocycle characteristics of excited-state intramolecular proton transfer (ESIPT) materials enable population inversion and large spectral separation between absorption and emission through their respective enol and keto forms. This leads to minimal or no self-absorption losses, a favorable feature in acting as an optical gain medium. While conventional ESIPT materials with an enol-keto tautomerism process are widely known, zwitterionic ESIPT materials, particularly those with high photoluminescence, are scarce. Facilitated by the synthesis and characterization of a new family of 2-hydroxyphenyl benzothiazole (HBT) with fluorene substituents

The PRIORITIZE trial (clinicaltrials.gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV). A secondary aim of this study was to compare LDV/SOF and EBR/GZR on sustainable changes in several HCV-associated symptoms and functional well-being in patients who achieved sustained virological response (SVR). PRIORITIZE, a randomized controlled trial conducted between 2016 and 2020, evaluated change in six PROMIS® symptom scores (fatigue, sleep disturbance, cognitive disturbance, nausea, diarrhoea, abdominal pain) and functional well-being using the disease-specific HCV-PRO instrument. Survey assessments were administered at baseline, early post-treatment (median = 6 months) and late post-treatment (median = 21 months). Constrained longitudinal linear mixed-effects models were used to evaluate within-treatment change and between-treatment differences. Data from 793 participants (average 55 years old, 57% male, 44% black, 17% with cirrhosis) were analysed. From baseline to early post-treatment, 5 out of 6 symptoms and functional well-being significantly improved (all p's .05). In the LDV/SOF arm, mean changes ranged from -3.73 for nausea to -6.41 for fatigue and in the EBR/GZR, mean changes ranged from -2.19 for cognitive impairment to -4.67 for fatigue. Change of3 points was consider clinically meaningful. Improvements in most symptoms slightly favoured LDV/SOF, although the magnitude of differences between the regimens were small. Both regimens demonstrated significant improvements in symptoms and functional well-being that were sustained during the late post-treatment phase. EBR/GZR and LDV/SOF regimens had clinically equivalent and durable improvements in HCV symptoms and functional well-being up to two years after SVR.

COVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to the hepatitis C virus (HCV) in the replication process. Sofosbuvir/ledipasvir is an approved drug to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection. This is a single-blinded parallel-randomized controlled trial. The participants were randomized equally into the intervention group that received Sofosbuvir/ledipasvir (S.L. group), and the control group received Oseltamivir, Hydroxychloroquine, and Azithromycin (OCH group). The primary outcomes were the cure rate over time and the incidence of serious adverse events. The secondary outcomes included the laboratory findings. 250 patients were divided equally into each group. Both groups were similar regarding gender, but age was higher in the S.L. group (p=0.001). In the S.L. group, 89 (71.2%) patients were cured, while only 51 (40.8%) patients were cured in the OCH group. The cure rate was significantly higher in the S.L. group (RR=1.75, p

Based on our previous study in minimal medium, Kocuria rosea and Aspergillus sydowii were identified as the best microbes for degradation of mixture of polyaromatic hydrocarbons (PAHs). The present study reports PAH degradation potential of these microbes in free and immobilized form. PAHs were extracted using QuEChERS-mediated process followed by quantification by high performance liquid chromatography. The microbial consortium of Kocuria rosea + Aspergillus sydowii was formulated in three bio-formulations, namely (i) bentonite-alginate composite beads; (ii) water dispersible granule composite using guar gum-nanobentonite; and (iii) composites of carboxymethyl cellulose-bentonite and were applied in PAH fortified (100 µg g

Foliar uptake, as an important pathway of polycyclic aromatic hydrocarbons (PAHs) accumulation in winter wheat, has a great contribution to wheat PAHs, which mainly depends on atmospheric PAHs level. An indoor simulation experiment was conducted to explore the effects of foliar exposure to PAHs at different growth stages on PAHs uptake in wheat. Three levels (0, 0.75, 4.5 mg L

One sustainable concept emerges to implement the selective oxidation of sulfides with dioxygen (O2) at ambient conditions and has received increasing attention. As such, three donor–acceptor (D–A) type conjugated microporous polymers (CMPs) were connected via robust C C bonds prepared from FeCl3-promoted polymerization of monomers of 3,6-di(9H-carbazol-9-yl)-9H-fluorene with the 9H position of the fluorene moiety occupied by 1,1′-biphenyl-, difluoro-, or keto- group, furnishing 9,9′-(9,9′-spirobi[fluorene]-2,7-diyl)-bis-9H-carbazole-CMP (SFC-CMP), 9,9′-(9,9-difluoro-9H-fluorene-2,7-diyl)bis(9H-carbazole)-CMP (FFC-CMP), and 2,7-di(carbazol-9-yl)-fluoren-9-one-CMP (OFC-CMP), respectively. These three carbazole–fluorene CMPs could implement blue light-driven highly selective oxidation of sulfides into sulfoxides with O2 in methanol (CH3OH). Intriguingly, the SFC-CMP imparted the best photocatalytic activity for selective oxidation of sulfides in a broad scope. Besides, the SFC-CMP photocatalyst could be fully recovered even outperforming the fresh one. This work highlights that the properties of CMPs could be regulated by the D–A units like carbazole–fluorene to execute selective chemical transformations ambiently.

Matrices formed by self-assembly of amino acids and their derivatives are suitable for cell spreading, migration and proliferation, and widely used in tissue engineering and organ regeneration, due to the biological endogenous molecules and weak intermolecular forces. The self-assembly process is not only affected by dynamic and thermodynamic factors, but also the assembled space. In this work, capillary tubes with different diameters are chosen to mimic a confined environment and the effect of capillary space on the self-assembly behavior of Fmoc-amino acids with different oil-water partition coefficients (log

Self-assembled peptide hydrogels have emerged as alternatives to the conventional approaches employed in controlled drug release, wound-healing, and drug delivery, and as anti-infective agents. However, peptide hydrogels possessing antibacterial properties are less explored. In this work, we have designed three ultrashort antibacterial peptide hydrogels: Fmoc-FFH-CONH

As a commercially available and orthogonally protected amino acid building block, Fmoc-Dab(Mtt)-OH showed abnormally poor coupling efficiency during solid-phase peptide synthesis (SPPS). Herein, we reveal that Fmoc-Dab(Mtt)-OH undergoes rapid lactamization under a series of conditions with various coupling reagents. Although the complete incorporation of Fmoc-Dab(Mtt)-OH can be achieved using a multi-time and preincubation-free protocol with the coupling reagent DEPBT, alternative orthogonally protected building blocks are suggested to be used for avoiding such a costly and tedious procedure.

Fluorene-based analogues of fluorescein, rhodol, and rhodamine exhibit absorption and fluorescence beyond 800-900 nm in water, 300-400 nm red-shifted compared to the original oxygen-bridged xanthene dyes, giving potential access to low molecular weight fluorescent markers for the second biological window (NIR-II

Background Plasmodium falciparum gametocytaemia has been associated with anaemia. The aim of this review was to synthesize available evidence on the comparative effect of dihydroartemisinin-piperaquine (DHA-PQ) and artemether-lumefantrine (AL) on gametocyte clearance and haemoglobin recovery in children with uncomplicated P. falciparum malaria in Africa. Methods A systematic literature search was undertaken to identify relevant articles from online databases. The search was performed from August 2020 to 30 April 2021. Extracted data from eligible studies were pooled as risk ratios with 95% confidence intervals (CI). Results Gametocyte carriage was reduced in both treatment groups, with no significant difference found between the groups. However, on days 28 and 42, a significant increase in serum haemoglobin level from baseline was observed in the DHA-PQ group (standardized mean difference 0.15, 95% CI 0.05–0.26; participants=2715; studies=4; I2=32%, high quality of evidence) compared with the AL group (mean difference 0.35, 95% CI 0.12–0.59; participants=1434; studies=3; I2=35%, high quality of evidence). Conclusion DHA-PQ had a greater impact on haemoglobin recovery than AL on days 28 and 42; this difference was significant.

Substituted fluorene structures have demonstrated unusual photochemical properties. Previous reports on the substituted fluorene Schiff base FR0-SB demonstrated super photobase behavior with a ΔpK(b) of ~14 upon photoexcitation. In an effort to understand the basis for this unusual behavior, we have examined the electronic structure and relaxation dynamics of the structural precursor of FR0-SB, the aldehyde FR0, in protic and aprotic solvents using time-resolved fluorescence spectroscopy and quantum chemical calculations. The calculations show three excited singlet states in relatively close energetic proximity. The spectroscopic data are consistent with relaxation dynamics from these electronic states that depend on the presence and concentration of solvent hydroxyl functionality. These results underscore the central role of solvent hydrogen bonding to the FR0 aldehyde oxygen in mediating the relaxation dynamics within this molecule.

A DABCO-promoted annulation reaction of bindone ([1,2'-biindenylidene]-1',3,3'-trione) and 3-methyleneoxindoles showed very interesting molecular diversity under different reaction conditions. The base-promoted annulation reaction of bindone and 3-phenacylideneoxindoles in DCM at room temperature afforded spiro[indeno[1,2-a]fluorene-5,3'-indoline] derivatives in good yields and with high diastereoselectivity. However, the similar reaction of 2-(2-oxoindolin-3-ylidene) acetates resulted in Z/E-isomeric spiro[indeno[1,2-a]fluorene-5,3'-indolines] with diastereomeric ratios of 2:1 to 10:1. On the other hand, the DABCO-promoted annulation reaction of bindone and 3-methyleneoxindoles in acetonitrile at different temperatures selectively gave spiro[benzo[5,6]pentaleno[1,6a-b]naphthalene-7,3'-indoline] derivatives and complex dispiro[indoline-3,6'-[4b,6a]ethanoindeno[1,2-a]fluorene-14',3″-indolines] in satisfactory yields.

Pseudomonas aeruginosa DN1 can efficiently utilize fluoranthene as its sole carbon source, and the initial reaction in the biodegradation process is catalyzed by a ring-hydroxylating dioxygenase (RHD). To clarify the binding interaction of RHD with fluoranthene in the strain DN1, the genes encoding alpha subunit (RS30940) and beta subunit (RS05115) of RHD were functionally characterized through multi-technique combination such as gene knockout and homology modeling as well as molecular docking analysis. The results showed that the mutants lacking the characteristic alpha subunit and/or beta subunit failed to degrade fluoranthene effectively. Based on the translated protein sequence and Ramachandran plot, 96.5% of the primary amino-acid sequences of the alpha subunit in the modeled structure of the RHD were in the permitted region, 2.3% in the allowed region, but 1.2% in the disallowed area. The catalytic mechanism mediated by key residues was proposed by the simulations of molecular docking, wherein the active site of alpha subunit constituted a triangle structure of the mononuclear iron atom and the two oxygen atoms coupled with the predicted catalytic ternary of His217-His222-Asp372 for the dihydroxylation reaction with fluoranthene. Those amino acid residues adjacent to fluoranthene were nonpolar groups, and the C7-C8 positions on the fluoranthene ring were estimated to be the best oxidation sites. The distance of C7-O and C8-O was 3.77 Å and 3.04 Å respectively, and both of them were parallel. The results of synchronous fluorescence and site-directed mutagenesis confirmed the roles of the predicted residues during catalysis. This binding interaction could enhance our understanding of the catalytic mechanism of RHDs and provide a solid foundation for further enzymatic modification.

BACKGROUND Hepatitis C virus (HCV)-related decompensated cirrhosis is a severe life-threatening illness. The safety of direct-acting antivirals (DAAs) has opened a gate of hope for that subgroup of patients who were previously contraindicated for interferon therapy. OBJECTIVE We aimed at the investigation of the safety and efficacy of different DAAs regimens in the treatment of HCV-related decompensated cirrhosis patients, to determine sustained virological response (SVR)12 rates and to analyze the factors associated with response. METHODS A retrospective, single-center study including HCV-related decompensated cirrhosis patients who received DAAs. Demographic, laboratory and clinical data were analyzed. The SVR12 rate was the primary outcome measure. Secondary outcomes included the predictors of response, changes in the baseline model for end-stage liver disease and child-turcotte-pugh (CTP) scores, and fibroindices (APRI and fibrosis-4 index) at 12 weeks after treatment. RESULTS In total, 145 eligible patients (141 with CTP class B and 4 with class C) were enrolled in this study. SVR12 was achieved by 88.06% (118/134) of efficacy population on different DAAs regimens, Treatment was discontinued in 11 patients because of severe side effects without any deaths. Younger age showed a significant positive association with SVR12. CONCLUSIONS DAAs can be used for the treatment of HCV-related decompensated liver disease, with acceptable SVR12 rates and safety profiles.

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Two new recyclable silicon-based hydrophobic tags were developed for installing them at the C-terminal of peptides to increase the solubility in organic solvents and the reactivity of the peptides during liquid-phase peptide synthesis (LPPS). They comprise a siloxy group containing tag and an arylsilyl group containing tag. The hydrophobicity of these tags is much greater than those of previously reported examples. The siloxy group containing tag is compatible with Fmoc-deprotection conditions (Fmoc-chemistry) and hydrogenation conditions (Cbz-chemistry), while the arylsilyl group containing one is resistant to Fmoc-deprotection conditions (Fmoc-chemistry) and Boc-deprotection conditions (Boc-chemistry). Using the siloxy group containing tag, protected DRGN-1, a peptide containing 14 amino acid residues was prepared successfully by using linear synthesis combined with one convergent synthesis step. Using the arylsilyl group containing tag, a poly alanine chain containing 7 alanine residues was synthesized. The arylsilyl group containing tag can also be installed at the N-terminal to elongate the peptides from the N-terminal to the C-terminal. The yields and the solubility of the products in organic solvents in each step were good to excellent with the assistance of these silicon-based tags.

Landfill fires pose a real threat to the environment as they cause the migration of pollutants to the atmosphere and water sources. A greater risk is observed in the case of wild landfills, which do not have adequate isolation from the ground. The aim of this article is to present the results of studies on the toxicity of waste from a fire in a landfill in Trzebinia (southern Poland). Both soil and waste samples were investigated. The samples were analyzed using the GC-MS method and the leachates using ICP-OES. A total of 32 samples of incinerated waste and soil were collected. The organic compounds included naphthalene, fluorene, phenanthrene, anthracene, acenaphthene, acenaphthylene, fluoranthene, pyrene, benzo (c) phenanthrene, benzo (a) anthracene, chrysene, benzo (ghi) fluoranthene, benzo (b + k) fluoranthene, benzo (a) fluoranthene, benzo (c) fluoranthene, benzo (a) pyrene, benzo (e) pyrene, perylene, indeno[1,2,3-cd] pyrene, benzo (ghi) perylene, and dibenzo (a + h) anthracene. Among the inorganic parameters, sulfates, chlorides, arsenic, boron, cadmium, copper, lead, and zinc were taken into account. Phenanthrene reached values exceeding 33 mg/L. Fluoranthene dominated in most of the samples. Sulfates and chlorides were present in the samples in concentrations exceeding 400 and 50 mg/L, respectively. Compounds contained in burnt waste may have a negative impact on soil and water health safety. Therefore, it is important to conduct research and counteract the negative effects of waste fires.

Dynamic covalent polymers (DCPs) offer opportunities as adaptive materials of particular interest for targeting, sensing and delivery of biological molecules. In this view, combining cationic units and fluorescent units along DCP chains is attractive for achieving optical probes for the recognition and delivery of nucleic acids. Here, we report on the design of acylhydrazone-based DCPs combining cationic arginine units with π-conjugated fluorescent moieties based on thiophene-ethynyl-fluorene cores. Two types of fluorescent building blocks bearing neutral or cationic side groups on the fluorene moiety are considered in order to assess the role of the number of cationic units on complexation with DNA. The (chir)optical properties of the building blocks, the DCPs, and their complexes with several types of DNA are explored, providing details on the formation of supramolecular complexes and on their stability in aqueous solutions. The DNA-templated formation of DCPs is demonstrated, which provides new perspectives on the assembly of fluorescent DCP based on the nucleic acid structure.

Advancing the emerging area of chiral photonics requires modeling-guided concepts of chiral material design to enhance optical activity and associated optical rotatory dispersion. Herein, we introduce conformational engineering achieved by tuning polymer backbone conjugation through introduction of thiophene structural units in a chiral fluorene polymer backbone. Our theoretical calculations reveal a relationship between the structural conformation and the resultant rotational strength. We further synthesize a series of chiral fluorene-based polymers copolymerized with thiophene whose optical chirality trend is in qualitative agreement with predictions of our quantum chemical calculations. Varying the number of thiophene units in the monomer building block allows us to modulate the rotational strength by tuning the intrafibril helicity of single-stranded polymer chains, whereby the monomer conjugation is retained throughout the whole length of the polymer backbone. Our design concept delineates an underexamined approach: the concept of tuning backbone conjugation and helicity within the main chain to enhance the optical activity of chiral polymer systems.

Fluorene-chloroquine hybrids have been identified as a new promising class of antiplasmodial agents. The most active compound 9 d exhibited good in vitro antiplasmodial activity against a chloroquine-sensitive NF54 strain of the human malaria parasite Plasmodium falciparum with an IC

Smoked cheeses are particularly popular among consumers for their flavor and aroma. Of interest, therefore, is the health aspect related to the likelihood of polycyclic aromatic hydrocarbons (PAHs), which are known carcinogens found in smoked products. Thus, the purpose of this study was to evaluate the occurrence of 15 polycyclic aromatic hydrocarbons (PAHs) in smoked and non-smoked cheeses purchased in Poland to monitor their safety. The level of selected PAHs in cheese samples was determined using the HPLC-DAD-FLD method. Most of the cheeses tested met the maximum level of benzo[a]pyrene (2 μg/kg) and the sum of benz[a]anthracene, chrysene, benzo[b]fluoranthene and benzo[a]pyrene (12 μg/kg) established for these products. However, all the cheeses studied in this work had relatively low amounts of the sum of these compounds compared to the information available in the cheese literature, ranging from

Herein, fluorescent gold nanoclusters (AuNCs) and horseradish peroxidase (HRP) were simultaneously embedded into self-assembled dipeptide supramolecular films of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) on the surface of ITO electrodes (Fmoc-FF/AuNCs/HRP) by using a simple single-step process. In the films, both the fluorescence property of AuNCs and the bioelectrocatalytic property of HRP were well maintained and could be reversibly regulated by pH-sensitive structural changes in the Fmoc-FF hydrogel films. Cu(II)/EDTA in the solution could lead to the aggregation/disaggregation of AuNCs and further quenching/dequenching the fluorescence signal from the films. Meanwhile, the blue complexes formed by Cu(II) and EDTA could produce a UV-vis signal in the solution. In addition, the coordinated Cu(II) in the films enhanced the electrocatalytic capacity toward the reduction of H2O2 and could switch the current signal. A biomolecular logic circuit was built based on the smart film electrode system by using pH, the concentrations of EDTA, Cu(II) and H2O2 as inputs, while the fluorescence intensity (FL), current (I) and UV-vis extinction (E) of the solution as outputs. Various logic devices were fabricated using the uniform platform, consisting of an encoder/decoder, demultiplexer, dual-transfer gate, keypad lock, digital comparator, half adder, and controlled NOT (CNOT) gate. Specifically, an electronic three-value logic gate, gullibility (ANY) gate, was first mimicked in this biocomputing system. This work not only demonstrated the construction of a new type of multivalued logic gate by using a dipeptide micromolecular matrix but also provided a new approach for designing sophisticated biologic functions, establishing smart multianalyte biosensing or fabricating biology information processing through the use of a simple film system.

5-Spirofluorenehydantoin derivatives show efflux modulating, cytotoxic and antiproliferative effects in sensitive and resistant mouse T-lymphoma cells. In order to extend the knowledge available about the pharmacophoric features responsible for the glycoprotein P (P-gp) inhibitory properties of arylpiperazine derivatives of 3-methyl-5-spirofluorenehydantoin, we have performed crystal structure analyses for 1-[3-(3′-methyl-2′,4′-dioxospiro[fluorene-9,5′-imidazolidin]-1′-yl)propyl]-4-phenylpiperazine-1,4-diium dichloride monohydrate, C29H32N4O2 2+·2Cl−·H2O (1), 3′-methyl-1′-{3-[4-(4-nitrophenyl)piperazin-1-yl]propyl}spiro[fluorene-9,5′-imidazolidine]-2′,4′-dione, C29H29N5O4·H2O (2), 3′-methyl-1′-{5-[4-(4-nitrophenyl)piperazin-1-yl]pentyl}spiro[fluorene-9,5′-imidazolidine]-2′,4′-dione, C31H33N5O4 (3), and 1-benzyl-4-[5-(3′-methyl-2′,4′-dioxospiro[fluorene-9,5′-imidazolidin]-1′-yl)pentyl]piperazine-1,4-diium dichloride 0.613-hydrate, C32H38N4O2 2+·2Cl−·0.613H2O (4). Structure 3 is anhydrous but the other three structures crystallize with water present. The investigated compounds crystallize in the monoclinic crystal system, with the space group P21/n for 1 and 3, and P21/c for 2 and 4. The cations of salts 1 and 4 are doubly protonated, with the protons located on the N atoms of the piperazine rings. The packing of 1 and 4 in the crystals is dominated by intermolecular N—H...Cl and O—H...Cl hydrogen bonds. In the crystal structure of 2, the intermolecular interactions are dominated by O—H...O and O—H...N hydrogen bonds, while in 3, which is lacking in classic hydrogen-bond donors, it is C—H...O contacts that dominate. Additionally, we have performed induced-fit docking studies for the investigated compounds docked to the P-gp human homology model.

The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp out of which two retained binding even using molecular dynamic simulations. We propose these two drugs as potential RdRp inhibitors which need further in-depth testing.

Objectives The aim of this study was to evaluate the efficacy and safety of sofosbuvir/ledipasvir ± ribavirin in Malagasy patients with hepatitis C virus genotypes 1 and 2, in real conditions. Patients and methods This was a retrospective monocentric clinical study, carried out over a period of 3 years from March 1, 2017 to February 28, 2020, in a hospital hepato-gastroenterology department. Results In total, 26 patients (M/F: 11/15) with hepatitis C virus genotype 1 (n = 13) or genotype 2 (n = 13), were treated with sofosbuvir/ledipasvir without (n = 21) or with (n = 5) ribavirin for 12 weeks. The mean age was 61.38 ± 7.09 years. Seventeen patients (65.4%) had cirrhosis. The overall sustained virological response was 96.2% (95% CI = 80.4–99.9%). There was no significant difference between the sustained virological responses of genotypes 1 and 2 (92.3% vs 100%; p = 0.31) or those of cirrhotic or non-cirrhotic patients (94.1% vs 100%; p = 0.46). A relapse was observed in one patient (5.9%) — cirrhotic and genotype 1b — under sofosbuvir/ledipasvir with ribavirin. Seven patients (26.9%) experienced mild adverse reactions, including asthenia (57.1%) and insomnia (42.9%). Conclusion Treatment with sofosbuvir/ledipasvir ± ribavirin for infection with hepatitis C virus genotype 1 has been shown to be safe and effective, even in the presence of cirrhosis. The sofosbuvir/ledipasvir combination is a good option for genotype 2 non-cirrhotic patients.

A practical synthesis of 1,8-difluorofluorenone and of its (2,7)-dibromo and (2,4,5,7)-tetrabromo derivatives has been developed. Fluorinated fluorenones are the starting materials for polyhalogenated dibenzochrysenes as well as for geodesic hydrocarbons. 2,7-Dibromo-1,8-difluoro-9iH/i-fluoren-9-one was converted to 3,14-dibromo-4,13-difluorodibenzo[ig/i,ip/i]chrysene through a novel strategy.

A highly stable and reusable fluorescent multisample nanobiosensor for the detection of α-glucosidase inhibitors has been developed by coupling fluorescent liposomal nanoparticles based on conjugated polymers (L-CPNs) to the enzyme α-glucosidase, one of the main target enzymes in the treatment of type 2 diabetes. The mechanism of sensing is based on the fluorescence "turn-on" of L-CPNs by p-nitrophenol (PNP), the end product of the enzymatic hydrolysis of p-nitrophenyl-α-d-glucopyranoside. L-CPNs, composed of lipid vesicles coated with a blue-emitting cationic polyfluorene, were designed and characterized to obtain a good response to PNP. Two nanobiosensor configurations were developed in this study. In the first step, a single-sample nanobiosensor composed of L-CPNs and α-glucosidase entrapped in a sol-gel glass was developed in order to characterize and optimize the device. In the second part, the nanobiosensor was integrated and adapted to a multiwell microplate and the possibility of reusing it and performing multiple measurements simultaneously with samples containing different α-glucosidase inhibitors was investigated. Using super-resolution confocal microscopy, L-CPNs could be visualized within the sol-gel matrix, and the quenching of their fluorescence, induced by the substrate, was directly observed in situ. The device was also shown to be useful not only as a platform for screening of antidiabetic drugs but also for quantifying their presence. The latter application was successfully tested with the currently available drug, acarbose.

Introduction We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis. Methods Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs). Results Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment. Discussion Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.