An Instantaneous and Highly Selective Chromofluorogenic Chemodosimeter for Fluoride Anion Detection in Pure Water

The fast and the fluoride: A pyridine derivative functionalized with tert-butyldimethylsilyl ether has been synthesized and used as a selective chromofluorogenic fluoride sensor in water/cetyltrimethylammonium bromide solutions. The chromofluorogenic response arises from the fluoride-induced hydrolysis of the silyl ether moiety, which generates a coloured and highly emissive phenolate anion.Financial support from the Spanish Government (project MAT2012-38429-C04-01) and the Generalitat Valencia (project PROMETEO/2009/016) is gratefully acknowledged. S. E. is grateful to the Generalitat Valenciana for his Santiago Grisolia fellowship.El Sayed Shihata Nasr, S.; Agostini, A.; Santos Figueroa, LE.; Martínez Mañez, R.; Sancenón Galarza, F. (2013). An Instantaneous and Highly Selective Chromofluorogenic Chemodosimeter for Fluoride Anion Detection in Pure Water. ChemistryOpen. 2(2):58-62. https://doi.org/10.1002/open.20130001058622

2,4-dinitrophenyl ether-containing chemodosimeters for the selective and sensitive 'in vitro' and 'in vivo' detection of hydrogen sulfide

[EN] Four probes (i.e. D1¿D4) for the selective and sensitive fluorogenic detection of HS2 have been prepared and characterised. HEPES (10 mM, pH 7.4)¿DMSO 99:1 v/v solutions of D1¿D4 are essentially non-fluorescent. Changes in the emission using D1¿D4 in the presence of anions (F2, Cl2, Br2, I2, N2 3 , CN2, SCN2, AcO2, CO22 3 , PO22 4 , SO22 4 , HS2 and OH2), biothiols (GSH, Cys, Hcy, Me ¿Cys and lipoic acid), reducing agents (SO22 3 and S2O22 3 ) and oxidants (H2O2) demonstrated that only HS2 is able to induce the appearance of intense emission bands in the 400¿ 520 nm range in the four probes. The selectivity observed was ascribed to a unique hydrogen sulfide-induced hydrolysis of the 2,4-dinitrophenyl ether moiety that yielded the corresponding free highly fluorescent alcohols. The potential detection of intracellular HS2 was also studied.Financial support from the Spanish Government (Project MAT2012-38429-C04-01) and the Generalitat Valencia (Project PROMETEO/2009/016) is gratefully acknowledged. S.E. is grateful to the Generalitat Valenciana for his Santiago Grisolia fellow. L.E.S.F. also thanks the Carolina Foundation and UPNFM-Honduras for his doctoral grant.El Sayed Shehata Nasr, S.; De La Torre, C.; Santos Figueroa, LE.; Martínez-Máñez, R.; Sancenón Galarza, F.; Orzáez, M.; Costero, AM.... (2015). 2,4-dinitrophenyl ether-containing chemodosimeters for the selective and sensitive 'in vitro' and 'in vivo' detection of hydrogen sulfide. Supramolecular Chemistry. 27(4):244-254. https://doi.org/10.1080/10610278.2014.977286S24425427

Azide and sulfonylazide functionalized fluorophores for the selective and sensitive detection of hydrogen sulfide

[EN] Three fluorescent probes (1–3) for the selective and sensitive detection of hydrogen sulfide have been synthesized and characterized. Probe 1 is a coumarin derivative functionalized with an azide moiety whereas 2 contain the azide reactive group into a naphthalene fluorophore backbone. Probe 3 is composed also by a naphthalene fluorophore but, in this case, functionalized with a sulfonylazide reactive moiety. Probes 1 and 3 are non-fluorescent whereas 2 is weakly emissive in HEPES (10 mM, pH 7.4)–DMSO 99:1 (v/v). The emission behavior of the three probes was tested against selected anions, bio-thiols and oxidant molecules. Of all the chemical species tested, only HS− is able to induce an enhancement in the emission intensity (50, 11 and 20-fold for 1, 2 and 3, respectively). The observed emission in the presence of hydrogen sulfide is ascribed, in the case of probes 1 and 2, to an azide–amine reduction induced by HS− anion, whereas for probe 3 the sensing mechanism is related with a sulfonylazide–sulfonamide conversion. The three probes are very sensitive to HS− anion with limits of detection of 0.17, 0.20 and 0.40 mM for 1, 2 and 3 respectively. Cell viability studies demonstrated that 1–3 probes are essentially non-toxic at concentrations 10–50 μM and are well suited for in vivo studies. Finally, probe 1 was used for the detection on intracellular HS− anion in HeLa cells by means of confocal microscopy.Financial support from the Spanish Government (Project MAT2012-38429-004-01) and the Generalitat Valenciana (Project PROMETEO/2009/016) is gratefully acknowledged. S.E. is grateful to the Generalitat Valenciana for his Santiago Grisolia fellow. C.T. also thanks the Ministerio de Ciencia e Innovacion for her FPU grant. L.E.S.F. thanks the Carolina Foundation and UPNFM-Honduras for his doctoral grant.El Sayed Shehata Nasr, S.; De La Torre Paredes, C.; Santos Figueroa, LE.; Marín Hernández, C.; Martínez Mañez, R.; Sancenón Galarza, F.; Costero Nieto, AM.... (2015). Azide and sulfonylazide functionalized fluorophores for the selective and sensitive detection of hydrogen sulfide. Sensors and Actuators B: Chemical. 207(B):987-994. https://doi.org/10.1016/j.snb.2014.04.047S987994207

Synthesis and evaluation of fluorimetric and colorimetric chemosensors for anions based on (oligo)thienyl-thiosemicarbazones

A family of heterocyclic thiosemicarbazone dyes (3a-d) containing thienyl groups has been synthesized, characterized and their chromo-fluorogenic response in acetonitrile in the presence of selected anions studied. Acetonitrile solutions of 3a-d show absorption bands in the 338-425 nm range which are modulated by the groups attached to the thiosemicarbazone moiety. The fluoride, chloride, bromide, iodide, dihydrogen phosphate, hydrogen sulfate, nitrate, acetate and anions were used in the recognition studies. Only sensing features were observed for fluoride, cyanide, acetate and dihydrogen phosphate anions. Two different chromogenic responses were found, (i) a small shift of the absorption band due to coordination of the anions with the thiourea protons and (ii) the appearance of a new red shifted band due to deprotonation of the receptor. For the latter process changes in the color solutions from pale-yellow to orange-red were observed. Fluorescence studies showed a different emission behavior according to the number of thienyl rings in the π-conjugated bridges. Stability constants for the two processes (complex formation + deprotonation) for receptors 3a-d in the presence of fluoride and acetate anions were determined from spectrophotometric titrations using the HypSpec program. The interaction of 3d with fluoride was also studied through 1H NMR titrations. Semiempirical calculations to evaluate the hydrogen-donating ability of the receptors were also performed.Fundação para a Ciência e a Tecnologia (FCT) , Acções Integradas Luso-Espanholas/CRUP, Generalitat Valenci

Synthesis and evaluation of thiosemicarbazones functionalized with furyl moieties as new chemosensors for anion recognition

A family of heterocyclic thiosemicarbazone dyes (3a-f and 4) containing furyl groups were synthesized in good yields, characterized and their response in acetonitrile in the presence of selected anions was studied. Acetonitrile solutions of 3a-f and 4 show absorption bands in the 335-396 nm range which are modulated by the electron donor or acceptor strength of the heterocyclic systems appended to the thiosemicarbazone moiety. Fluoride, chloride, bromide, iodide, dihydrogen phosphate, hydrogen sulphate, nitrate, acetate and cyanide anions, were used in recognition studies. From these anions, only sensing features were seen for fluoride, cyanide, acetate and dihydrogen phosphate. Two clearly different chromo-fluorogenic behaviours were observed, (i) a small shift of the absorption band due to the coordination of the anions with the thiourea protons and (ii) the appearance of a new red shifted band due to deprotonation. For the latter effect, a change in the colour solution from pale yellow to purple was observed. Fluorescence studies were also in agreement with the different effects observed in the UV/Vis titrations. In this case, hydrogen bonding interactions were visible through the enhancement of the emission band, whereas deprotonation induced the appearance of a new red-shifted emission. Logarithms of stability constants for the two processes (complex formation + deprotonation) for receptors 3a-f in the presence of fluoride and acetate anions were determined from spectrophotometric titrations using the HypSpec V1.1.18 program. Semi-empirical calculations to evaluate the hydrogen-donating ability of the receptors and a prospective electrochemical characterization of compound 3b in the presence of fluoride were also performed.Fundação para a Ciência e a Tecnologia (FCT), Acções Integradas Luso-espanholas/CRUP, Generalitat Valenciana

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly