Novel mycophenolic acid precursor-based fluorescent probe for intracellular H2O2 detection in living cells and Daphnia magna and Zebrafish model systems.

Innovative for the scientific community and attracting attention in the extensive biomedical field are novel compact organic chemosensing systems built upon unique core molecular frameworks. These systems may demonstrate customized responses and may be adaptable to analytes, showing promise for potential in vivo applications. Our recent investigation focuses on a precursor of Mycophenolic acid, resulting in the development of LBM (LOD = 13 nM) - a specialized probe selective for H2O2. This paper details the synthesis, characterization, and thorough biological assessments of LBM. Notably, we conducted experiments involving living cells, daphnia, and zebrafish models, utilizing microscopy techniques to determine probe nontoxicity and discern distinct patterns of probe localization. Localization involved the distribution of the probe in the Zebrafish model within the gut, esophagus, and muscles of the antennae.

Antifungal activity of synthetic xanthenone against fluconazole-resistant Candida auris and its mechanism of action.

Candida auris, an emerging multidrug-resistant fungal pathogen discovered in Japan in 2009, poses a significant global health threat, with infections reported in about 25 countries. The escalation of drug-resistant strains underscores the urgent need for new treatment options. This study aimed to investigate the antifungal potential of 2,3,4,4a-tetrahydro-1H-xanthen-1-one (XA1) against C. auris, as well as its mechanism of action and toxic profile. The antifungal activity of XA1 was first evaluated by determining the minimum inhibitory concentration (MIC), time-kill kinetics and biofilm inhibition. In addition, structural changes, membrane permeability, reactive oxygen species (ROS) production, and in vitro and in vivo toxicity of C. auris after exposure to XA1 were investigated. The results indicated that XA1 exhibited an MIC of 50 µg/mL against C. auris, with time-kill kinetics highlighting its efficacy. Field emission scanning electron microscopy (FE-SEM) showed structural damage in XA1-treated cells, supported by increased membrane permeability leading to cell death. Furthermore, XA1 induced ROS production and significantly inhibited biofilm formation. Importantly, XA1 exhibited low cytotoxicity in human epidermal keratinocytes (HaCaT), with a cell viability of over 90% at 6.25 µg/mL. In addition, an LD50 of 17.68 µg/mL was determined in zebrafish embryos 24 hours post fertilization (hpf), with developmental delay observed at prolonged exposure at 6.25 µg/mL (48-96 hpf). These findings position XA1 as a promising candidate for further research and development of an effective antifungal agent.

Evaluation of Fluorescence-Based Screening Assays for the Detection and Quantification of Silyl Hydrolase Activity.

This study reports the development of fluorometric assays for the detection and quantification of silyl hydrolase activity using silicatein as a model enzyme. These assays employed a series of organosilane substrates containing either mycophenolate or umbelliferone moieties, which become fluorescent upon hydrolysis of a scissile Si-O bond. Among these substrates, the mycophenolate-derived molecule MycoF, emerged as the most promising candidate due to its relative stability in aqueous media, which resulted in good differentiation between the enzyme-catalyzed and uncatalyzed background hydrolysis. The utility of MycoF was also demonstrated in the detection of enzyme activity in cell lysates and was found to be capable of qualitative identification of positive "hit" candidates in a high-throughput format. These fluorogenic substrates were also suitable for use in quantitative kinetic assays, as demonstrated by the acquisition of their Michaelis-Menten parameters.

Lyso-H2S: A Mycophenolic Acid-Derived Probe for Ultra-Low Toxicity, Intracellular H2S Detection, and Zebrafish Model Validation.

In several biological processes, H2S is known to function as an endogenous gaseous agent. It is very necessary to monitor H2S and relevant physiological processes in vivo. Herein, a new type of fluorophore with a reliable leaving group allows for excited-state intramolecular transfer characteristics (ESIPT), inspired by mycophenolic acid. A morpholine ring was connected at the maleimide position to target the lysosome. Subsequently, the dinitrophenyl group known for a photoinduced electron transfer (PET) effect, was connected to allow for an effective "turn-on" probe Lyso-H2S. Lyso-H2S demonstrated strong selectivity towards H2S, large Stokes shift (111 nm), and an incredibly low detection limit (41.8 nM). The imaging of endogenous and exogenous H2S in living cells (A549 cell line) was successfully achieved because of the specificity and ultra-low toxicity (100 % cell viability at 50 µM concentration of Lyso-H2S.) Additionally, Lyso-H2S was also employed to visualize the activity of H2S in the gallbladder and intestine in a living zebrafish model. This is the first report of a fluorescent probe to track H2S sensing in specific organ systems to our knowledge.

Risk factors for labour induction and augmentation: a multicentre prospective cohort study in India.

Background: Guidelines for labour induction/augmentation involve evaluating maternal and fetal complications, and allowing informed decisions from pregnant women. This study aimed to comprehensively explore clinical and non-clinical factors influencing labour induction and augmentation in an Indian population. Methods: A prospective cohort study included 9305 pregnant women from 13 hospitals across India. Self-reported maternal socio-demographic and lifestyle factors, and maternal medical and obstetric histories from medical records were obtained at recruitment (≥28 weeks of gestation), and women were followed up within 48 h after childbirth. Maternal and fetal clinical information were classified based on guidelines into four groups of clinical factors: (i) ≥2 indications, (ii) one indication, (iii) no indication and (iv) contraindication. Associations of clinical and non-clinical factors (socio-demographic, healthcare utilisation and lifestyle related) with labour induction and augmentation were investigated using multivariable logistic regression analyses. Findings: Over two-fifths (n = 3936, 42.3%, 95% confidence interval [CI] 41.3-43.3%) of the study population experienced labour induction and more than a quarter (n = 2537, 27.3%, 95% CI 26.4-28.2%) experienced augmentation. Compared with women with ≥2 indications, those with one (adjusted odds ratio [aOR] 0.50, 95% CI 0.42-0.58) or no indication (aOR 0.24, 95% CI 0.20-0.28) or with contraindications (aOR 0.12, 95% CI 0.07-0.20) were less likely to be induced, adjusting for non-clinical characteristics. These associations were similar for labour augmentation. Notably, 34% of women who were induced or augmented did not have any clinical indication. Several maternal demographic (age at labour, parity and body mass index in early pregnancy), healthcare utilization (number of antenatal check-ups, duration of iron-folic acid supplementation and individuals managing childbirth) and socio-economic factors (religion, living below poverty line, maternal education and partner's occupation) were independently associated with labour induction and augmentation. Interpretation: Although decisions about induction and augmentation of labour in our study population in India were largely guided by clinical recommendations, we cannot ignore that more than a third of the women did not have an indication. Decisions could also be influenced by non-clinical factors which need further research. Funding: The MaatHRI platform is funded by a Medical Research Council Career Development Award (Grant Ref: MR/P022030/1) and a Transition Support Award (Grant Ref: MR/W029294/1).

An indole-based near-infrared fluorescent "Turn-On" probe for H2O2: Selective detection and ultrasensitive imaging of zebrafish gallbladder.

Fluorescent probes play essential roles in medical imaging, where the researchers can select one of many molecules to use to help monitor the status of living systems under investigation. To date, a few scaffolds that allow the in vivo detection of H2O2 are available only. Herein, we provide a highly sensitive and selective near-infrared fluorescent probe that detects H2O2 based on the ICT sensing mechanism. We report the first indole-incorporated fluorescent probe Indo-H2O2 that allows H2O2 detection with a LOD of 25.2 nM featuring a boronate group conjugated to an indole scaffold; the boronate cleaves upon reaction with H2O2. A 5-membered malononitrile derivative was incorporated; Indo-H2O2 has near-infrared (NIR) properties and the reaction time is low (∼25 min) compared to other related probes. Indo-H2O2 was successfully employed in both endogenous and exogenous imaging trials of H2O2 in living cells. Indo-H2O2 also allows the real-time monitoring of H2O2in vivo. It preferentially accesses the gallbladder of zebrafish. Our findings support Indo-H2O2 as a highly sensitive fluorescent NIR probe for detecting H2O2, and an idea to incorporate a central indole unit in future fluorescent probe designs.

Haemophagocytic lymphohistiocytosis in pregnancy and the postpartum period: A retrospective case series analysis.

Introduction: Haemophagocytic lymphohistiocytosis (HLH) is an extremely rare condition characterised by excessive immune activation leading to haemophagocytic activity and has seldom been reported in pregnancy. HLH manifests as relapsing fevers with features of multi- organ failure and has a high mortality. Methods: A retrospective case series analysis using national data from MBRRACE-UK maternal death reports (n=5) and case notes from patients diagnosed with HLH during pregnancy at New Cross Hospital, Wolverhampton (n=2) between 2012 and 2021. Results: A total of seven cases were included. Cases uniformly presented with fever and experienced prodromal illnesses consisting of lymphadenopathy, fevers, and malaise. Gestation at presentation ranged from 9/40 to 11 months postpartum. All patients had multiple cytopaenias. Other common features included elevated liver enzymes (n=5), hyperferritinaemia (n=5), splenomegaly (n=4), hypofibrinogenemia (n=4) and elevated soluble interleukin-2 receptor α (CD25) levels (n=3). Underlying causes were identified in four cases. Median time from presentation to diagnosis was 35 days. Bone marrow biopsy was diagnostic in a majority of cases. Corticosteroids and ciclosporin were the most frequently used treatments. In some cases early delivery by caesarean section or termination of pregnancy was necessary to permit maternal treatment. Progression to multi-organ failure resulting in maternal death occurred in five cases: two cases survived. Pregnancy outcomes were: livebirth at term (n=2), preterm livebirth (n=3), termination of pregnancy (n=1), and miscarriage (n=1). Of the surviving infants, one had bone marrow suppression with anaemia at birth and sensorineural deafness. Conclusions: Due to the rarity of the condition, diagnosis is often delayed. In view of the high mortality, clinicians should consider HLH early when reviewing pregnant patients with unexplained pyrexia and multi-organ dysfunction. Early involvement of haematology should be sought, as prompt diagnosis is crucial for meaningful attempts at curative therapy. Important treatment considerations include fetal viability, maternal condition and treatment toxicity.

Haemophagocytic lymphohistiocytosis (HLH) is an extremely rare and life threatening condition. It is a disorder where the body reacts to any stimulus which produces an excessive immune response causing severe inflammation and damage to multiple major organs. If not diagnosed and treated on time, it can lead to major organ failure and even death. HLH affecting pregnant women can be life threatening affecting both mother and the baby. Early diagnosis and treatment by specialist teams of doctors can help in improving the outcomes. Our case series aims to bring awareness about this serious disorder, so that it can be identified early and treated accordingly.

The Ferritin, Hepcidin and Cytokines Link in the Diagnoses of Iron Deficiency Anaemia during Pregnancy: A Review.

Following a diagnosis of iron deficiency anaemia in pregnancy, iron supplements are prescribed using UK guidelines; however, despite this, the condition remains highly prevalent, affecting up to 30% of pregnant women in the UK. According to the World Health Organisation, it globally accounts for 45% in the most vulnerable groups of pregnant women and infants (<5 years old). Recently, the efficacy of iron replacement therapy and the effectiveness of current standard testing of iron parameters have been reviewed in order to evaluate whether a more accurate diagnosis can be made using alternative and/or supplementary markers. Furthermore, many questions remain about the mechanisms involved in iron metabolism during pregnancy. The most recent studies have shed more light on serum hepcidin and raised questions on the significance of pregnancy related inflammatory markers including cytokines in iron deficiency anaemia. However, research into this is still scarce, and this review aims to contribute to further understanding and elucidating these areas.

Highly sensitive and rapid detection of hypochlorous acid in aqueous media and its bioimaging in live cells and zebrafish using an ESIPT-driven mycophenolic acid-based fluorescent probe.

Excessive production of potent biological oxidants such as HOCl has been implicated in numerous diseases. Thus, it is crucial to develop highly specific and precise methods to detect HOCl in living systems, preferably with molecules that can show a distinct therapeutic effect. Our study introduces the synthesis and application of a highly sensitive fluorescence "turn-on" probe, Myco-OCl, based on the mycophenolic acid scaffold with exceptional water solubility. The ESIPT-driven mechanism enables Myco-OCl to specifically and rapidly detect (<5 s) HOCl with an impressive Stokes shift of 105 nm (λex = 417 nm, λem = 522 nm) and a sub-nanomolar (97.3 nM) detection limit with the detection range of 0 to 50 µM. The potential of Myco-OCl as an excellent biosensor is evident from its successful application for live cell imaging of exogenous and endogenous HOCl. In addition, Myco-OCl enabled us to detect HOCl in a zebrafish inflammatory animal model. These underscore the great potential of Myco-OCl for detecting HOCl in diverse physiological systems. Our findings thus offer a highly promising tool for detecting HOCl in living organisms.

The complex relationship between iron status and anemia in pregnant and postpartum women in India: Analysis of two Indian study cohorts of uncomplicated pregnancies.

Low hemoglobin is widely used as an indicator of iron deficiency anemia in India and other low-and-middle income counties, but anemia need not accurately reflect iron deficiency. We examined the relationship between hemoglobin and biomarkers of iron status in antenatal and postnatal period. Secondary analysis of uncomplicated singleton pregnancies in two Indian study cohorts: 1132 antenatal women in third trimester and 837 postnatal women 12-72 h after childbirth. Associations of hemoglobin with ferritin in both data sets, and with sTfR, TSAT, and hepcidin in the postnatal cohort were examined using multivariable linear regression. Multinomial logistic regression was used to examine the association between severity of anemia and iron status. Regression models were adjusted for potential confounders. Over 55% of the women were anemic; 34% of antenatal and 40% of postnatal women had low ferritin, but 4% antenatal and 6% postnatal women had high ferritin. No evidence of association between hemoglobin and ferritin was observed (antenatal: adjusted coefficient [aCoef] -0.0004, 95% confidence interval [CI] -0.001, 0.001; postnatal: aCoef -0.0001, 95% CI -0.001, 0.001). We found a significant linear association of hemoglobin with sTfR (aCoef -0.04, 95% CI -0.07, -0.01), TSAT (aCoef -0.005, 95% CI -0.008, -0.002), and hepcidin (aCoef 0.02, 95% CI 0.02, 0.03) in postnatal women. Likelihood of low ferritin was more common in anemic than non-anemic women, but high ferritin was also more common in women with severe anemia in both cohorts. Causes of anemia in pregnant and postpartum women in India are multifactorial; low hemoglobin alone is not be a useful marker of iron deficiency.

Nontoxic Levels of Se-Containing Compounds Increase Survival by Blocking Oxidative and Inflammatory Stresses via Signal Pathways Whereas High Levels of Se Induce Apoptosis.

Selenium is a main group element and an essential trace element in human health. It was discovered in selenocysteine (SeC) by Stadtman in 1974. SeC is an encoded natural amino acid hailed as the 21st naturally occurring amino acid (U) present in several enzymes and which exquisitely participates in redox biology. As it turns out, selenium bears a U-shaped toxicity curve wherein too little of the nutrient present in biology leads to disorders; concentrations that are too great, on the other hand, pose toxicity to biological systems. In light of many excellent previous reviews and the corpus of literature, we wanted to offer this current review, in which we present aspects of the clinical and biological literature and justify why we should further investigate Se-containing species in biological and medicinal contexts, especially small molecule-containing species in biomedical research and clinical medicine. Of central interest is how selenium participates in biological signaling pathways. Several clinical medical cases are recounted; these reports are mainly pertinent to human cancer and changes in pathology and cases in which the patients are often terminal. Selenium was an option chosen in light of earlier chemotherapeutic treatment courses which lost their effectiveness. We describe apoptosis, and also ferroptosis, and senescence clearly in the context of selenium. Other contemporary issues in research also compelled us to form this review: issues with CoV-2 SARS infection which abound in the literature, and we described findings with human patients in this context. Laboratory scientific studies and clinical studies dealing with two main divisions of selenium, organic (e.g., methyl selenol) or inorganic selenium (e.g., sodium selenite), are discussed. The future seems bright with the research and clinical possibilities of selenium as a trace element, whose recent experimental clinical treatments have so far involved dosing simply and inexpensively over a set of days, amounts, and time intervals.

"Lighting up" fluoride: cellular imaging and zebrafish model interrogations using a simple ESIPT-based mycophenolic acid precursor-based probe.

The discovery and implementation of media that derive from bioinspired designs and bear optical readouts featuring large Stokes shifts are of continued interest to a wide variety of researchers and clinicians. Myco-F, a novel mycophenolic acid precursor-based probe features a cleavable tert-butyldimethylsiloxy group to allow for fluoride detection. Myco-F exhibits high selectivity and specificity towards F- (Stokes shift = 120 nm). All measurements were performed in complete aqueous media (LOD=0.38 µM). Myco-F enables detection of fluoride ions in living HEK293 cells and localizes in the eye region (among other regions) of the zebrafish. DFT calculations support the proposed ESIPT working photomechanism.

Milestones in corrole chemistry: historical ligand syntheses and post-functionalization.

Corroles are synthetic porphyrin analogs that contain one meso carbon atom lesser and bear a trianionic N4 metal-chelating core. They require in-depth preparative chemistry, demonstrate unique coordination chemistry and have impressive and diverse physical properties, and these are commonly compared to their respective porphyrins. The corrole's macrocyclic system is inherently electron rich and chelates metal ions in a more compact, less symmetric tetranitrogen cavity compared to that of porphyrins. Herein, we cover the highlights of the corrole research through the decades by first reviewing, in a chronological sense, multi-step syntheses; some routes have since been discontinued. This is followed by describing post-functionalization of already formed corroles via reactions performed on either the macrocycle's periphery or the inner nitrogen atoms or on the existing substituents. We do also mention milestones in literature reviewing, publication of encyclopedias, and the creation of professional organizations and conferences (ICPP) which make up the corrole/porphyrin research landscape. Also highlighted are still existing challenges and future perspectives.

A foundational theoreticalAl12E12(E = N, P) adsorption and quinolone docking study: cage-quinolone pairs, optics and possible therapeutic and diagnostic applications.

This combined Al12E12 (E = N, P) surface adsorption and docking study describes the new possibility of prospective potential probing(photophysical/optical) and therapy(medicinal/biochemical) with these adsorbent conjugates. DFT investigations were undertaken herein to help generate geometrical models and better understand the possible favorable adsorption energetics. We attempt to explain their adsorption behaviors and docking involving SARS-CoV-2 viruses (PDB)to assess their possible pharmaceutical potential against the pandemic virus (COVID-19). The adsorption behavior of 8-hydroxy-2-methylquinoline (MQ) and its halogenated derivatives, 5,7-diiodo-8-hydroxy-2-methylquinoline (MQI), 5,7-dichloro-8-hydroxy-2-methylquinoline (MQCl), and 5,7-dibromo-8-hydroxy-2-methylquinoline (MQBr), with aluminum-nitrogen (AlN), and aluminum-phosphorous (AlP) fullerene-like nanocages is reported. A decrease in the hardness of the nanoclusters when adsorbed with drug molecules resulted in an incrementally improved chemical softness (see e.g., Hard-Soft Acid Base theory) indicating that reactivity of the drug molecule in the resulting complex increases upon cluster chemical adsorption. The energy gap is found to be maximized for AlN-MQ and minimized for AlP-MQI; the reduced density gradient (RDG) iso-surfaces and AIM studies also corroborated this. Therefore, these two were found, respectively, to be the least and most electrically conductive of the species under study. We selected a simple medicinal building block (chelator)in addition to selecting the cluster based on previous literature reports. Important parameters such as gap energies and global indices were determined. We assessed NLO properties. The SARS-CoV-2 virus PDB docking data for 6VW1, 6VYO, 6WKQ, 7AD1, 7AOL, 7B3C, were enlisted as ligand targets for studies of docking (PatchDock Server) using the requisite PDB geometries (For the structure of 6VW1, kindly see reference, 2020; For the structure of 6VYO kindly see reference, 2020; For the structure of 6WKQ kindly see reference, 2020; For the structure of 7AD1 kindly see reference, 2021; For the structure of 7AOL kindly see reference, 2021; For the structure of 7B3C kindly see reference, 2021). Such findings indicate that the AlN-drug conjugation have inhibitory effect against these selected receptors.Communicated by Ramaswamy H. Sarma.

Theoretical study of glycoluril by highly symmetrical magnesium oxide Mg12O12 nanostructure: adsorption, detection, SERS enhancement, and electrical conductivity study.

Using metal substrates that are nanoscale in size, surface-enhanced Raman scattering (SERS) is a technique for enhancing the Raman signal of biomolecules. Numerous industries including sensing materials, adsorption and medical devices, use nanomaterials like nanocages and nanoclusters. To discover a possible novel sensor platform involving a small metal cluster and a curved rigid substrate, we used density functional theoretical (DFT) simulations to explore the adsorption of glycoluril (GLC), a prospective drug intermediate, on a pure magnesium oxide cage (Mg12O12). This well defined cage was used as (i) an exact probable structure that could be used as well as (ii) a general model for MgO nanostructures. We also investigated the mono Al-doped Mg12O12 nanocage version Mg11AlO12. All computations were performed at the M06-2X level of theory. The GLC binds to the Mg12O12 nanocage by way of strong donor-acceptor interactions. The adsorption is releasing - 45.80 kcal mol-1 of energy. Due to Al doping, the energy gap of GLC-Mg11AlO12 (1.91 eV) is reduced from that of GLC-Mg12O12 (4.28 eV) and hence there is an increase in electrical conductivity of GLC-Mg11AlO12. The electronic change in the nanocage's conductivity can be transformed into an electrical signal which can be used to detect the presence of the drug analyte. In addition, when a GLC molecule is present, the work function of the nanocage is also reduced. The MgO nanocage, we conclude, is a work function type as well as a possible electronic sensor for GLC drug detection. GLC desorption from the Mg11AlO12 surface recovers more quickly in comparison with Mg12O12 recovery time. The AIM and NCIs assessed in this study were performed to help analyze the electronic structures of the complexes. Our findings pave the possibility for Mg11AlO12 nanostructures to be used in drug recognition.

Maternal iron deficiency anaemia in pregnancy: Lessons from a national audit.

We describe the management and the prevalence of iron deficiency anaemia (IDA) during pregnancy by comparison to standards. A cross-sectional national cohort study of women who had given birth six weeks prior to data collection was conducted at maternity units in the UK and Ireland. Participating centres collected data from 10 consecutive pregnant women. Analysis was descriptive to define the prevalence of IDA in pregnancy and the puerperium, and to compare the outcomes in women who had IDA with women who did not have anaemia anytime during pregnancy. Eighty-six maternity units contributed data on 860 pregnancies and births. The overall prevalence of IDA during pregnancy was 30.4% and in the puerperium 20%. Anaemic women were more likely to be from ethnic minorities, odds ratio 2.23 (1.50, 3.32). Adherence to national guidance was suboptimal, and the prevalence of anaemia in pregnancy remains very high. There is pressing need to explore barriers to early identification and effective management of iron deficiency. IDA should be considered a major public health problem in the UK.

Macro and micro thermal investigation of nanoarchitectonics-based coatings on cotton fabric using new quaternized starch.

Implementation of a new cationizing reagent and its incorporation onto the backbone of starch was performed successfully, confirmed from the remarkable micro- and macro anti-flammable properties. The morphologies and localized compositional analysis of the modified starch-based LBL coatings on the cotton surface were carried out using LV-SEM and EDX: highly uniform coating layers and uptake of solution species for intermediate implant reagent concentrations were confirmed. The subject samples were further analyzed through thermogravimetric analysis (TGA), microcombustion experiments (MCC), flame testing (VFT) and afterburn measurements. The peak range of the degradation was highly improved from the lower range to the higher range (329.92-394.48 °C), together with significant mass residue for TBAB-0.7-17.02%. Moreover, a significant decrease in the absolute heat loss (THR ∼ 30%), heat dissipation competence (HRC ∼ 27.86%), and peak heat output (PHRR ∼ 23%) was achieved for a TBAB loading of ∼0.7 g. The results were further confirmed from the increase in the limiting oxygen index (LOI) to a higher rate of ∼23.2, improved structural integrity and higher quality of char obtained in the VFT and after-burn analysis.

Phosphinate-benzoindocyanin fluorescent probe for endogenous mitochondrial peroxynitrite detection in living cells and gallbladder access in inflammatory zebrafish animal models.

Potent oxidants such as peroxynitrite (ONOO-) play important roles in the regulation of different physiopathological processes; their overproduction is thought to potentially cause several diseases in living organisms. Hence, the precise and selective monitoring of ONOO- is imperative for elucidating its interplay and roles in pathological and physiological processes. Herein, we present a novel diphenyl phosphinate-masked benzoindocyanin "turn-on" fluorogenic probe to help detect mitochondrial ONOO- in living cells and zebrafish models. A pale yellow color solution of BICBzDP turns rose-red upon the addition of ONOO-, selectively, contrary to that of other competitive bioactive molecules. BICBzDP displays an ultra-sensitivity detection limit (47.8 nM) with outstanding selectivity and sensitivity towards mitochondrial ONOO- and possesses a notable 68-fold fluorescence enhancement involving a large redshift of 91 nm. Importantly, further biological experimental investigations with BICBzDP indicate specific sensitivity and reliability of the probe to track the ONOO- level, not only in live cells, but also demonstrates dynamic fluctuations in the inflammatory zebrafish animal models. Thus, BICBzDP could be employed as a future potential biological tool for exploiting the role of ONOO- in a variety of different physiological systems.

A study of diabetic ketoacidosis in the pregnant population in the United Kingdom: Investigating the incidence, aetiology, management and outcomes.

AIM: To estimate the incidence of diabetic ketoacidosis (DKA) among pregnant women, describe its clinical features, management and outcomes and identify the risk factors for the condition. METHODS: A national population-based case-control study was conducted in the UK using the UK Obstetric Surveillance System between April 2019 and September 2020 including all pregnant women with DKA irrespective of the level of blood glucose. The incidence rate of DKA in pregnancy was estimated. A case-control analysis limited to women with type 1 diabetes was performed comparing characteristics of women with DKA (cases) to those of women whose pregnancies were not complicated by DKA (controls). RESULTS: In all, 82 women were identified with DKA in pregnancy; 6.3 per 100,000 maternities (95% CI: 5.0-7.9). No maternal deaths occurred, but perinatal mortality was 12/73 (16%) with 11 stillbirths and one neonatal death. DKA episodes mostly occurred in women with type 1 diabetes (85%) and in the 3rd trimester of pregnancy (71%). Episodes were mainly precipitated by infection (21%), vomiting (21%), steroid therapy (13%) and medication errors (10%). Fifteen percent of women had more than one episode of DKA during their pregnancy. Risk factors associated with DKA among women with type 1 diabetes identified through the case-control analysis were the woman and/or partner not being in a paid employment and having at least one microvascular complication of diabetes before pregnancy. CONCLUSION: DKA in pregnancy was associated with high perinatal mortality and was linked with factors related to socio-economic deprivation, mental health problems and long-term difficulties with glycaemic control.

Adsorption properties of dacarbazine with graphene/fullerene/metal nanocages - Reactivity, spectroscopic and SERS analysis.

Drug delivery devices are an effective way to minimize anticancer drug toxicity and nanostructures are used in the targeted drug delivery. In the present work, adsorption and interaction behavior of 4-(dimethylaminodiazenyl)-1H-imidazole-5-carboxamide (DAIC) with nano complexes (graphene, fullerene and fullerene like metal cages) are reported theoretically. From the reactivity studies, the electrophilicity index of DAIC-nanoclusters are increasing and this gives the bioactivity of the nanocluster systems. Adsorption energy is highest in the case of AlP and lowest in the case of BP clusters. Mulliken charge distribution of all systems is an evidence for chemical enhancement. DAIC adsorption over nanocages causes changes in electronic properties resulting in chemical enhancement and variation in Raman spectra which suggests that nanocages could be a good candidate for DAIC detection.