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1.
Fertil Steril ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39260540

ABSTRACT

OBJECTIVE: To evaluate the P2X3 receptor antagonist, gefapixant, for treating moderate-to-severe endometriosis-related pain. DESIGN: Randomized, double-blind, Phase 2, proof-of-concept trial. PARTICIPANTS: Premenopausal women age 18-49y with moderate-to-severe endometriosis-related pain who were not using hormonal treatment. INTERVENTIONS: Gefapixant 45mg twice-daily or placebo over two menstrual cycles. MAIN OUTCOME MEASURES: Participants rated peak pelvic pain severity daily on a 0 (no pain) - 10 (extremely severe pain) scale. The primary endpoint was change-from-baseline in average daily peak pelvic pain severity during Treatment Cycle 2. RESULTS: All 187 participants randomized (gefapixant N=94, placebo N=93) took ≥1 dose of investigational treatment and all but 6 in each treatment group completed the trial. The model-based least squares mean reduction-from-baseline in average daily peak pelvic pain severity during Treatment Cycle 2 was -2.2 for gefapixant and -1.7 for placebo (difference = -0.5 [95% confidence interval: -1.01, 0.03], P=0.066). In secondary analyses, the difference between gefapixant and placebo in peak pelvic pain severity reduction-from-baseline on menstrual days was -0.6 [95% confidence interval: -1.18, -0.06], and -0.5 [95% confidence interval: -1.04, 0.03] on non-menstrual days. Taste-related adverse events were reported in 31.9% of participants for gefapixant versus 4.3% for placebo. Pharmacokinetic assessments at Month 1 and Month 2 clinic visits indicated that of the 94 participants in the gefapixant group, 39 had detectable levels of gefapixant in the blood for both assessments while 38 had no detectable levels for ≥1 assessment. CONCLUSION: Gefapixant 45mg twice-daily was not shown to be superior to placebo in reducing endometriosis-related pain, although the results directionally favored gefapixant. This trial result should be considered inconclusive given possible issues with treatment compliance. (Clinical trial registration: NCT03654326).

2.
ACS Appl Polym Mater ; 6(15): 9088-9098, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39144280

ABSTRACT

Mixed matrix membranes (MMMs) were formed by using seven polymeric matrices with a wide range of permeabilities. All of the polymeric matrices have been polyimides, namely: P84, Pi-DAPOH, Pi-DAROH, Matrimid, Pi-HABAc, PI-DAM, and PIM-1 in the order of increasing O2 permeability. A fixed (10%) concentration of a microporous organic polymer (TFAP-Trp), formed by the combination of trifluoroacetophenone and triptycene, was added as a porous filler. The material properties as well as their separation performances for multiple pure gases, specifically the permeabilities of He, N2, O2, CH4, and CO2, were measured. The correlation between the relative increase in permeability in MMMs and that of the matrix polymeric membrane has been quantitatively analyzed. This study proves that the increased permeability of MMMs is largely linked to the contribution of the high permeability of the filler. The addition of the TFAP-Trp porous filler proves to be especially beneficial for matrices with low to moderate permeabilities, significantly enhancing the matrix permeability overall. The fitted relationship is approximately linear in accordance with the existing models to predict permeability in dual-phase systems for low proportions of the dispersed phase. An extrapolation allows the evaluation of the permeability of the pure microporous organic polymer, which agrees with the previous values described by the group for different filler contents and in other polymeric matrices. In all cases, the selectivity remains approximately constant while the permeability increases. The addition of TFAP-Trp to all the polymeric matrices led to a moderate improvement of the MMM separation performances, mainly centered on their permeabilities.

3.
Int J Environ Health Res ; : 1-21, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39206834

ABSTRACT

The present review aimed to evaluate the current situation of pesticide residues detected in shrimp (commercial species) on the Mexican coasts. The organochlorine pesticides (OC), α-endosulfan (210.01 ng g-1), endosulfan sulfate (127.5 ng g-1), heptachlor (126.04 ng g-1 and γ-HCH (121.04 ng g-1) are identified as the most common pesticides in shrimp tissues, with the Northwest area reporting the highest concentrations of these OC. Given that there is an under-evaluation of pesticide residue levels, there was a greater contribution of studies directed at the Northwest of the country considering that there are states that are among the main shrimp-producing and consumers entities. The concentrations and types of pesticides banned nationally and globally, due to their toxic effects on the population, were reported. Therefore, since the most current information is 19 years out of date, it is necessary to perform recent evaluations with sensible and precise methods.

4.
Mikrochim Acta ; 191(9): 513, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39105990

ABSTRACT

An on-site extraction device is presented consisting of scotch tape modified with concentric domains of micrometric hydrophilic-lipophilic balance (HLB) particles surrounded by a ring of nanometric magnetic ones. On the one hand, HLB microparticles are readily available at the surface of the tape, exposed to interact with the target analytes, being responsible for the extraction capacity of the sorptive phase. On the other hand, the presence of magnetic nanoparticles enables the attachment of the modified tape onto a metallic screw via a magnet, which is then coupled to a wireless drill, enabling the stirring of the microextraction device. Both are simply fixed to the cost-effective, flexible, and versatile support, i.e., scotch tape, owing to their adhesive properties. The microextraction device has been applied to the determination of six benzophenones in swimming pool water samples. The variables that may affect the extraction process have been evaluated. Under the optimum conditions and using liquid chromatography-tandem mass spectrometry as the instrumental technique, the method provided a limit of detection of 0.03 µg L-1. The intra-day precision, evaluated at three different concentration levels and expressed as relative standard deviation, was lower than 10%, which also comprises the variability within single-use sorptive tapes. The accuracy, calculated with spiked samples and expressed as relative recovery, ranged from 71 to 138%. The method was applied to the analysis of swimming pool water, revealing the presence of such compounds.

5.
J Environ Manage ; 367: 121968, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39068787

ABSTRACT

Volatile organic compounds (VOCs) emitted into the atmosphere negatively affect the environment and human health. Biotrickling filtration, an effective technology for treating VOC-laden waste gases, faces challenges in removing hydrophobic VOCs due to their low water solubility and therefore limited bioavailability to microorganisms. Consequently, the addition of (bio)surfactants has proven to be a promising strategy to enhance the removal of hydrophobic VOCs in biotrickling filters (BTFs). Yet, up to now, no single study has ever performed a mass transfer characterization of a BTF under (bio)surfactants addition. In this study, the effect of (bio)surfactant addition on the gas-liquid mass transfer characteristics of two BTFs was measured by using oxygen (O2) as a model gas. Through an empirical correlation, the mass transfer coefficients (kLa) of two hydrophobic VOCs, toluene and hexane, which are of industrial and environmental significance, were estimated. One BTF was filled with expanded perlite, while the other with a mixture of compost and wood chips (C + WC). Both BTFs were operated under different liquid velocities (UL: 0.95 and 1.53 m h-1). Saponin, a biological surfactant, and Tween 80, a synthetic surfactant, were added to the recirculating liquid at different critical micelle concentrations (CMCs: 0-3 CMC). The higher interfacial and surface area of the perlite BTF compared to the C + WC BTF led to higher kLaO2 values regardless of the operational condition: 308 ± 18-612 ± 19 h-1 versus 42 ± 4-177 ± 24 h-1, respectively. Saponin addition at 0.5 and 1 CMC had positive effects on the perlite BTF, with kLaO2 values two times higher compared to those at 0 CMC. Tween 80 exhibited a neutral or slightly positive effect on the mass transfer of both BTFs under all conditions. Overall, the CMC, along with the physical characteristics of the packing materials and the operational conditions evaluated explained the results obtained. This study provides fundamental data essential to improve the performance and design of BTFs for hydrophobic VOCs abatement.


Subject(s)
Air Pollution , Filtration , Surface-Active Agents , Volatile Organic Compounds , Surface-Active Agents/chemistry , Air Pollution/prevention & control , Air Pollutants
6.
Biomolecules ; 14(7)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-39062452

ABSTRACT

Evidence suggests that immune system dysfunction and macrophages are involved in the disease establishment and progression of endometriosis. Among the factors involved in this alteration in macrophage activity, Small Extracellular Vesicles (sEVs) have been described to play a role favoring the switch to a specific phenotype with controversial results. This study aims to investigate the potential effect of circulating sEVs in the plasma of well-characterized patients with endometriosis on the polarization of macrophages. sEVs were isolated from the plasma of patients diagnosed with endometriosis confirmed by histopathological analysis. Two groups of patients were recruited: the endometriosis group consisted of patients diagnosed with endometriosis by imaging testing (gynecological ultrasonography and/or magnetic resonance imaging), confirmed by histopathologic study (n = 12), and the control group included patients who underwent laparoscopy for tubal sterilization without presurgical suspicion of endometriosis and without endometriosis or signs of any inflammatory pelvic condition during surgery (n = 12). Human THP1 monocytic cells were differentiated into macrophages, and the effect of sEVs on cell uptake and macrophage polarization was evaluated by fluorescent labeling and measurement of the IL1B, TNF, ARG1, and MRC1 expression, respectively. Although no changes in cell uptake were detected, sEVs from endometriosis induced a polarization of macrophages toward an M2 phenotype, characterized by lower IL1B and TNF expression and a tendency to increase MRC1 and ARG1 levels. When macrophages were stimulated with lipopolysaccharides, less activation was also detected after treatment with endometriosis sEVs. Finally, endometriosis sEVs also induced the expression of the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARG); however, treatment with rosiglitazone, a PPARG agonist, had no effect on the change in macrophage phenotype. We conclude that circulating sEVs in women with endometriosis have a certain capacity to shift the activation state of macrophages toward an M2 phenotype, but this does not modify the uptake level or the response to PPARG ligands.


Subject(s)
Endometriosis , Extracellular Vesicles , Macrophages , Phenotype , Humans , Endometriosis/pathology , Endometriosis/metabolism , Endometriosis/blood , Female , Extracellular Vesicles/metabolism , Macrophages/metabolism , Macrophages/pathology , Adult , THP-1 Cells
7.
ACS Photonics ; 11(5): 1844-1850, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38766499

ABSTRACT

Polariton organic light-emitting diodes (POLEDs) use strong light-matter coupling as an additional degree of freedom to tailor device characteristics, thus making them ideal candidates for many applications, such as room temperature laser diodes and high-color purity displays. However, achieving efficient formation of and emission from exciton-polaritons in an electrically driven device remains challenging due to the need for strong absorption, which often induces significant nonradiative recombination. Here, we investigate a novel POLED architecture to achieve polariton formation and high-brightness light emission. We utilize the blue-fluorescent emitter material 4,4'-Bis(4-(9H-carbazol-9-yl)styryl)biphenyl (BSBCz), which exhibits strong absorption and a highly horizontal transition-dipole orientation as well as a high photoluminescence quantum efficiency, even at high doping concentrations. We achieve a peak luminance of over 20,000 cd/m2 and external quantum efficiencies of more than 2%. To the best of our knowledge, these values represent the highest reported so far for electrically driven polariton emission from an organic semiconductor emitting in the blue region of the spectrum. Our work therefore paves the way for a new generation of efficient and powerful optoelectronic devices based on POLEDs.

8.
Article in English | MEDLINE | ID: mdl-38778575

ABSTRACT

INTRODUCTION: Uterus transplantation is a novel surgical procedure that allows women with absolute uterine factor infertility to carry a pregnancy and give birth. While previous studies have explored the attitudes of women with absolute uterine factor infertility toward uterus transplantation, none have surveyed and compare their views with other groups of interest (Morris syndrome women, relatives of Morris syndrome and Rokitansky syndrome women, infertile women and women of childbearing age) in the same sociocultural setting. The objective of this study was to evaluate attitudes and insights regarding uterus transplantation among women with Rokitansky syndrome and other groups of interest. MATERIAL AND METHODS: We designed a cross-sectional study including five groups of women: women with Rokitansky syndrome, women with Morris syndrome, relatives of women with Morris and Rokitansky syndrome, infertile women, and childbearing-age women. We conducted an online survey through the REDCap platform. The link was distributed by mail, telephone and in hospital outpatient visits. Baseline demographic information was assessed and information regarding motherhood preferences, attitude toward uterus transplantation, preferred uterus graft and perception of risk of the procedure was collected. RESULTS: We obtained a total of 200 responses, with a mean participant age of 34.5 years (±9.8). Overall, 17.5% (n = 35) were women with Rokitansky syndrome, 5.5% (n = 11) Morris syndrome women, 21.5% (n = 43) infertile women, 26.5% (n = 53) relatives of Morris and Rokitansky syndrome women and 29% (n = 58) childbearing-age women. 71.5% of women with Rokitansky syndrome would undergo uterus transplantations ahead of adoption and surrogacy with no statistically significant differences found between groups. Overall, more than one-half (58%) would prefer deceased over living donor. CONCLUSIONS: The results of this survey indicate that uterus transplantation is desired by most women who would benefit from the procedure, including those with either Morris syndrome or absolute uterine factor infertility. This was also the preferred option for motherhood if absolute uterine factor infertility was diagnosed among surveyed infertility patients or women of childbearing age with no known reproductive difficulties. Overall, most respondents indicated a deceased donor was preferable to a living donor and that patients may not be sufficiently aware of potential risks of uterus transplantation, highlighting the importance of adequate counseling by medical providers.

9.
Polymers (Basel) ; 16(10)2024 May 14.
Article in English | MEDLINE | ID: mdl-38794590

ABSTRACT

A good integration of the polymer materials that form a mixed-matrix membrane (MMM) for gas separation is essential to reaching interesting permselective properties. In this work, a porous polymer network (PPN), obtained by combining triptycene and trifluoroacetophenone, has been used as a filler, which was blended with two o-hydroxypolyamides (HPAs) that act as polymer matrices. These polymer matrices have been thermally treated to induce a thermal rearrangement (TR) of the HPAs to polybenzoxazoles (ß-TR-PBOs) through a solid-state reaction. For its structural study, various techniques have been proposed that allow us to undertake a morphological investigation into the integration of these materials. To access the internal structure of the MMMs, three different methods were used: a polishing process for the material surface, the partial dissolution of the polymer matrix, or argon plasma etching. The argon plasma technique has not only revealed its potential to visualize the internal structure of these materials; it has also been proven to allow for the transformation of their permselective properties. Force modulation and phase contrast in lift-mode techniques, along with the topographic images obtained via the tapping mode using a scanning probe microscope (SPM), have allowed us to study the distribution of the filler particles and the interaction of the polymer and the filler. The morphological information obtained via SPM, along with that of other more commonly used techniques (SEM, TGA, DSC, FTIR, WASX, gas adsorption, and permeability measurements), has allowed us to postulate the most probable structural configuration in this type of system.

10.
Fertil Steril ; 122(1): 12-19, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38729337

ABSTRACT

The aim of this review was to provide an updated assessment of the present diagnostic tools and clinical symptoms and signs to evaluate uterine fibroids (UFs) on the basis of current guidelines, recent scientific evidence, and a PubMed and Google Scholar search for peer-reviewed original and review articles related to clinical signs and diagnosis of UFs. Approximately 50%-75% of UFs are considered nonclinically relevant. When present, the most common symptoms are abnormal uterine bleeding, pelvic pain and/or bulk symptoms, and reproductive failure. Transvaginal ultrasound is recommended as the initial diagnostic modality because of its accessibility and high sensitivity, although magnetic resonance imaging appears to be the most accurate diagnostic tool to date in certain cases. Other emerging techniques, such as saline infusion sonohysterography, elastography, and contrast-enhanced ultrasonography, may contribute to improving diagnostic accuracy in selected cases. Moreover, artificial intelligence has begun to demonstrate its ability as a complementary tool to improve the efficiency of UF diagnosis. Therefore, it is critical to standardize descriptions of transvaginal ultrasound images according to updated classifications and to individualize the use of the different complementary diagnostic tools available to achieve precise uterine mapping that can lead to targeted therapeutic approaches according to the clinical context of each patient.


Subject(s)
Leiomyoma , Uterine Neoplasms , Humans , Female , Leiomyoma/diagnostic imaging , Leiomyoma/diagnosis , Uterine Neoplasms/diagnostic imaging , Uterine Neoplasms/diagnosis , Adolescent , Menopause , Adult , Young Adult , Middle Aged , Predictive Value of Tests , Ultrasonography/methods
11.
Fertil Steril ; 122(1): 20-30, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723935

ABSTRACT

Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large percentage of cases and may be identified incidentally using a transvaginal ultrasound or a magnetic resonance imaging scan. However, in approximately 30% of cases, UFs affect the quality of life and women's health, with abnormal uterine bleeding and heavy menstrual bleeding being the most common complaints, along with iron deficiency (ID) and ID anemia. Medical treatments used for UFs-related abnormal uterine bleeding include symptomatic agents, such as nonsteroidal antiinflammatory drugs and tranexamic acid, and hormonal therapies, including combined oral contraceptives, gonadotropin-releasing hormone agonists or antagonists, levonorgestrel intrauterine systems, selective progesterone receptor modulators, and aromatase inhibitors. Nevertheless, few drugs are approved specifically for UF treatment, and most of them manage the symptoms. Surgical options include fertility-sparing treatments, such as myomectomy, or nonconservative options, such as hysterectomy, especially in perimenopausal women who are not responding to any treatment. Radiologic interventions are also available: uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound, and radiofrequency ablation. Furthermore, the management of ID and ID anemia, as a consequence of acute and chronic bleeding, should be taken into account with the use of iron replacement therapy both during medical treatment and before and after a surgical procedure. In the case of symptomatic UFs, the location, size, multiple UFs, or coexistent adenomyosis should guide the choice with a shared decision-making process, considering long- and short-term treatment goals expected by the patient, including pregnancy desire or wish to preserve the uterus independently of reproductive goals.


Subject(s)
Leiomyoma , Uterine Hemorrhage , Uterine Neoplasms , Humans , Female , Leiomyoma/therapy , Leiomyoma/complications , Leiomyoma/diagnosis , Uterine Neoplasms/therapy , Uterine Neoplasms/complications , Uterine Neoplasms/diagnosis , Uterine Hemorrhage/therapy , Uterine Hemorrhage/etiology , Uterine Hemorrhage/diagnosis , Treatment Outcome , Uterine Myomectomy , Uterine Artery Embolization , Adult
12.
Acta Obstet Gynecol Scand ; 103(7): 1271-1282, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38661227

ABSTRACT

INTRODUCTION: Alterations in microbiota composition have been implicated in a variety of human diseases. Patients with adenomyosis present immune dysregulation leading to a persistent chronic inflammatory response. In this context, the hypothesis that alterations in the microbiota may be involved in the pathogenesis of adenomyosis, by affecting the epigenetic, immunologic, and biochemical functions of the host, has recently been postulated. The aim of the present study was to compare the microbiota composition in the vagina, endometrium, and gut of individuals with and without adenomyosis. MATERIAL AND METHODS: Cross-sectional study including 38 adenomyosis patients and 46 controls, performed between September 2021 and October 2022 in a university hospital-based research center. The diagnosis of adenomyosis was based on sonographic criteria. Fecal, vaginal, and endometrial samples were collected. Study of the microbiota using 16S rRNA gene sequencing. RESULTS: Patients with adenomyosis exhibited a significant reduction in the gut microbial alpha diversity compared with healthy controls (Chao1 p = 0.012, Fisher p = 0.005, Observed species p = 0.005). Beta-diversity analysis showed significant differences in the compositions of both gut and vaginal microbiota between adenomyosis patients and the control group (Adonis p-value = 0.001; R2 = 0.03 and Adonis p-value = 0.034; R2 = 0.04 respectively). Specific bacterial taxa were found to be either overrepresented (Rhodospirillales, Ruminococcus gauvreauii group, Ruminococcaceae, and Actinomyces) or underrepresented in the gut and endometrial microbiota of adenomyosis patients compared with controls. Distinct microbiota profiles were identified among patients with internal and external adenomyosis phenotypes. CONCLUSIONS: The study revealed reduced gut microbiota diversity in adenomyosis patients, accompanied by distinct compositions in gut and vaginal microbiota compared with controls. Overrepresented or underrepresented bacterial taxa were noted in the gut and endometrial microbiota of adenomyosis patients, with variations in microbiota profiles among those with internal and external adenomyosis phenotypes. These findings suggest a potential association between microbiota and adenomyosis, indicating the need for further research to comprehensively understand the implications of these differences.


Subject(s)
Adenomyosis , Endometrium , Gastrointestinal Microbiome , Vagina , Humans , Female , Adenomyosis/microbiology , Cross-Sectional Studies , Adult , Vagina/microbiology , Endometrium/microbiology , Middle Aged , Case-Control Studies , RNA, Ribosomal, 16S/genetics
13.
Talanta ; 272: 125774, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38359721

ABSTRACT

Direct mass spectrometry (MS) is an exciting strategy in bioanalysis, enabling rapid decision-making in different scenarios. Its application is usually hindered by matrix effects and the typically low concentration of the target compounds in the biofluids. In this sense, combining a previous sample preparation step minimizes or removes these shortcomings. This article describes sorptive tape-spray tandem mass spectrometry (STS-MS/MS) based on mixed-mode particles as a strategy to combine sample preparation and MS analysis in a single device. The technique uses a sorptive tape (ST) consisting of mixed-mode polymeric microparticles (combining ionic exchange and hydrophobic interactions) coated over aluminum foil in a spatial controlled way. The tapes act as the sorptive phases to isolate the analytes from the sample matrix and substrates for STS-MS/MS. The performance of the technique has been evaluated by developing a method to determine codeine in saliva as proof of concept. The affordability of the STs elements allows the preparation of many individual phases at low cost so that several samples can be extracted simultaneously, thus increasing the sample throughput. The extraction variables were optimized following a multivariate approach. Working under the optimum conditions, the limit of detection was 0.3 µg L-1, while the intraday precision, calculated as relative standard deviation (RSD) at three concentration levels, was better than 9.4 %. The accuracy, expressed as relative recovery, was in the range of 78-98 %. The method was also applied to the analysis of real samples. Despite being a powerful strategy, the direct combination of microextraction to MS is not always affordable in all laboratories. For this reason, the STs were also combined with commercial liquid chromatography-MS working under the direct infusion mode to demonstrate the usefulness of the ST in classical extraction workflows.


Subject(s)
Aluminum , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods
14.
J Assist Reprod Genet ; 41(4): 989-998, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38315420

ABSTRACT

A systematic review and meta-analysis were performed to identify if there is a subset of patients with POI who are more likely to show follicular growth after ovarian fragmentation for follicular activation (OFFA) or in vitro activation (IVA). Five studies met inclusion criteria for meta-analysis with a total of 164 patients. Forty-three patients showed follicle development (26.21%). Of those, the pregnancy rate was 35.58% (11/43) and the live birth rate was 20.93% (9/43). Our meta-analysis showed that age was not associated with follicle growth. However, lower baseline FSH, lower duration of amenorrhea/diagnosis, and presence of follicles remaining in biopsy were statistically significant for follicle development. Patients with basal characteristics mentioned before may have more chances to show follicle growth after OFFA or IVA. Taking into account that approximately 20% of patients with follicle growth had live birth, these results are very promising. Given the overall certainty of evidence, future studies are needed to confirm said results.


Subject(s)
Fertilization in Vitro , Ovarian Follicle , Ovulation Induction , Pregnancy Rate , Humans , Female , Ovarian Follicle/growth & development , Ovarian Follicle/pathology , Pregnancy , Ovulation Induction/methods , Fertilization in Vitro/methods , Live Birth/epidemiology , Primary Ovarian Insufficiency/pathology , Follicle Stimulating Hormone
15.
ACS Appl Mater Interfaces ; 16(8): 9900-9907, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38344949

ABSTRACT

Organophosphate (OP) toxicity is related to inhibition of acetylcholinesterase (AChE) activity, which plays a key role in the neurotransmission process. In this work, we report the ability of different zinc zeolitic imidazolate frameworks (ZIFs) to behave as potential antidotes against OP poisoning. The Zn-L coordination bond (L = purine, benzimidazole, imidazole, or 2-methylimidazole) is sensitive to the G-type nerve agent model compounds diisopropylfluorophosphate (DIFP) and diisopropylchlorophosphate, leading to P-X (X = F or Cl) bond breakdown into nontoxic diisopropylphosphate. P-X hydrolysis is accompanied by ZIF structural degradation (Zn-imidazolate bond hydrolysis), with the concomitant release of the imidazolate linkers and zinc ions representing up to 95% of ZIF particle dissolution. The delivered imidazolate nucleophilic attack on the OP@AChE adduct gives rise to the recovery of AChE enzymatic function. P-X bond breakdown, ZIF structural degradation, and AChE reactivation are dependent on imidazolate linker nucleophilicity, framework topology, and particle size. The best performance is obtained for 20 nm nanoparticles (NPs) of Zn(2-methylimidazolate)2 (sod ZIF-8) exhibiting a DIFP degradation half-life of 2.6 min and full recovery of AChE activity within 1 h. 20 nm sod ZIF-8 NPs are not neurotoxic, as proven by in vitro neuroblastoma cell culture viability tests.


Subject(s)
Acetylcholinesterase , Zeolites , Acetylcholinesterase/chemistry , Organophosphates/toxicity , Zeolites/chemistry , Antidotes/chemistry , Organic Chemicals , Zinc/chemistry
16.
Chemistry ; 30(2): e202303067, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-37902606

ABSTRACT

A new carbazole-substituted bisterpyridine with pronounced delayed fluorescence is presented. While the molecular donor-acceptor-donor design suggests the origin of this to be thermally activated delayed fluorescence (TADF), results from various photophysical characterizations, OLED characteristics, temperature-dependent NMR spectroscopy, and DFT calculations all point against the involvement of triplet states. The molecule exhibits blue emission at about 440 nm with two or more fast decay channels in the lower nanosecond range in both solution and thin films. The delayed emission is proposed to be caused by rotational vibrational modes. We suggest that these results are generally applicable, especially for more complex molecules, and should be considered as alternative or competitive emissive relaxation pathways in the field of organic light emitting materials.

17.
J Mater Chem B ; 12(1): 233-239, 2023 12 22.
Article in English | MEDLINE | ID: mdl-38084014

ABSTRACT

The exogenous administration of nitric oxide (NO) is considered a potential therapeutic treatment against a great variety of diseases due to its significant role in multiple physiological functions. Due to the gaseous nature, short lifetime and dose- and tissue-dependent activity of this molecule, the development of new administration procedures is required to control the NO delivery in terms of dosage, timing, and location. In this work, we propose a new molecular material based on robust metal-organic polyhedra (MOPs) for controlled NO release. We select dirhodium paddlewheel complex-based cuboctahedral MOPs (RhMOP), in which NO can chemically coordinate to the open-metal sites at the axial sites of dirhodium paddlewheel moieties. We further prepare amorphous coordination polymer particles (CPPs) by connecting RhMOP with bis(imidazole) linkers at the external axial sites. Both molecular MOPs and polymeric CPPs show relevant NO payloads and the release of NO can be triggered by two different stimuli: light and humidity. We show that imidazole ligands coordinating to the external axial sites of the paddlewheel moieties tune the light-triggered NO release property. We further demonstrate that the size and the extrinsic pores of CPPs are important for enhanced NO release.


Subject(s)
Nitric Oxide , Rhodium , Imidazoles , Polymers/chemistry
20.
Nat Commun ; 14(1): 6126, 2023 Oct 02.
Article in English | MEDLINE | ID: mdl-37779108

ABSTRACT

The orientation of luminescent molecules in organic light-emitting diodes strongly influences device performance. However, our understanding of the factors controlling emitter orientation is limited as current measurements only provide ensemble-averaged orientation values. Here, we use single-molecule imaging to measure the transition dipole orientation of individual emitter molecules in a state-of-the-art thermally evaporated host and thereby obtain complete orientation distributions of the hyperfluorescence-terminal emitter C545T. We achieve this by realizing ultra-low doping concentrations (10-6 wt%) of C545T and minimising background levels to reliably measure its photoluminescence. This approach yields the orientation distributions of >1000 individual emitter molecules in a system relevant to vacuum-processed devices. Analysis of solution- and vacuum-processed systems reveals that the orientation distributions strongly depend on the nanoscale environment of the emitter. This work opens the door to attaining unprecedented information on the factors that determine emitter orientation in current and future material systems for organic light-emitting devices.

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