Cu,Ce-containing phosphotungstates as laccase-like nanozyme for colorimetric detection of Cr(VI) and Fe(â ¢).

Herein, a nanocomposite of Cu,Ce-containing phosphotungstates (Cu,Ce-PTs) with outstanding laccase-like activity was fabricated via a one-pot microwave-assisted hydrothermal method. Notably, it was discovered that both Fe3+ and Cr6+ could significantly enhance the electron transfer rates of Ce3+ and Ce4+, along with generous Cu2+ with high catalytic activity, thereby promoting the laccase-like activity of Cu,Ce-PTs. The proposed system can be used for the detection of Fe3+ and Cr6+ in a range of 0.667-333.33 µg/mL and 0.033-33.33 µg/mL with a low detection limit of 0.135 µg/mL and 0.0288 µg/mL, respectively. The proposed assay exhibits excellent reusability and selectivity and can be used in traditional Chinese medicine samples analysis.

Association between thyroid function and prognosis of severe COVID-19 among patients with SARS-CoV-2 infection: a retrospective cohort study in China.

Objective: This study aims to examine the thyroid hormone profile and its association with severe coronavirus disease 2019 (COVID-19) in patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This retrospective cohort study enrolled patients admitted to a tertiary hospital due to SARS-CoV-2 infection between February 18 and May 18, 2022. Clinical data were collected retrospectively from the electronic medical record system. Based on the thyroid function, patients were divided into five groups: normal, non-thyroid illness syndrome (NTIS), hypothyroidism, thyrotoxicosis, and unclassified. The association between thyroid function and severe COVID-19 was detected using multivariable logistic regression and restricted cubic splines analysis. Results: This study included 3,161 patients, with 7.7% of them developing severe COVID-19. 44.9% of the patients had normal thyroid function, 36.5% had NTIS, 6.7% had hypothyroidism, and 1.0% had thyrotoxicosis on admission. After adjusting for age, sex, and relevant clinical characteristics, NTIS and hypothyroidism were associated with increased risks of severe COVID-19 (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.59-3.56 and OR 2.29, 95% CI 1.23-4.26, respectively), compared to normal thyroid function group. Among patients with NTIS or hypothyroidism, higher levels of total triiodothyronine (TT3) are associated with lower risks of severe COVID-19 (OR 0.73, 95% CI 0.64-0.82, for every 0.1nmol/L increase in TT3 level). Conclusion: Thyroid hormone profiles of NTIS or hypothyroidism are associated with increased risks of severe COVID-19. The decreased level of TT3 correlated with the increased risk of severe COVID-19 in patients with NTIS or hypothyroidism.

MOF-mediated cascade reaction system for ultrasensitive detection of alkaline phosphatase activity and organophosphorus pesticides.

A metal-organic-framework (MOF) fluorescent sensor is reported based on NH2-MIL-101(Fe) propelled pesticide and alkaline phosphatase (ALP) catalytic reaction. Different from previous reports, a cascade reaction system combined with MOF structural changes to generate fluorescence was employed. The rationale is that ALP can hydrolyze L-ascorbic acid 2-phosphate (AAP) into L-ascorbic acid (AA), which can reduce Fe3+ to decompose structurally NH2-MIL-101(Fe), resulting in 2-aminoterephthalic acid (NH2-BDC) with intense fluorescence. The  fluorescence can be decreased to different degrees due to inhibition of organophosphate pesticides (OPPs) on the activity of ALP. By taking chlorpyrifos (CPY) as the model compound of an OPP pesticide and adding ALP and CPY into the NH2-MIL-101(Fe) framework, the resulting cascade reaction fluorescence sensors exhibit a good sensitivity for CPY and ALP sensing. The working ranges are  0.02-2 µg/L and 0.2-20 mU/mL with detection limits (LOD) of 5.31 ng/L and 0.05 mU/mL, respectively. The proposed sensor has been actually applied to satisfactory detection of CPY and ALP in food and serum samples. This fluorescence-based assay may extend the application of MOF-based biosensors.

Heart failure and major haemorrhage in people with atrial fibrillation.

BACKGROUND: Heart failure (HF) is not included in atrial fibrillation (AF) bleeding risk prediction scores, reflecting uncertainty regarding its importance as a risk factor for major haemorrhage. We aimed to report the relative risk of first major haemorrhage in people with HF and AF compared with people with AF without HF ('AF only'). METHODS: English primary care cohort study of 2 178 162 people aged ≥45 years in the Clinical Practice Research Datalink from January 2000 to December 2018, linked to secondary care and mortality databases. We used traditional survival analysis and competing risks methods, accounting for all-cause mortality and anticoagulation. RESULTS: Over 7.56 years median follow-up, 60 270 people were diagnosed with HF and AF of whom 4996 (8.3%) had a major haemorrhage and 36 170 died (60.0%), compared with 8256 (6.4%) and 34 375 (27.2%), respectively, among 126 251 people with AF only. Less than half those with AF were prescribed an anticoagulant (45.6% from 2014 onwards), although 75.7% were prescribed an antiplatelet or anticoagulant. In a fully adjusted Cox model, the HR for major haemorrhage was higher among people with HF and AF (2.52, 95% CI 2.44 to 2.61) than AF only (1.87, 95% CI 1.82 to 1.92), even in a subgroup analysis of people prescribed anticoagulation. However, in a Fine and Gray competing risk model, the HR of major haemorrhage was similar for people with AF only (1.82, 95% CI 1.77 to 1.87) or HF and AF (1.71, 95% CI 1.66 to 1.78). CONCLUSIONS: People with HF and AF are at increased risk of major haemorrhage compared with those with AF only and current prediction scores may underestimate the risk of haemorrhage in HF and AF. However, people with HF and AF are more likely to die than have a major haemorrhage and therefore an individual's expected prognosis should be carefully considered when predicting future bleeding risk.

Depressive symptoms during pregnancy and postpartum: associations with mode of conception and demographic and obstetric factors.

An increasing number of women are conceiving through assisted reproductive technology; however, few studies have investigated their mental health after successful conception. This study investigated the changes in depressive symptoms in women using assisted reproductive technology and the association between the mode of conception and perinatal depressive symptoms. A longitudinal observational study was conducted from 2015 to 2019, 542 pregnant women completed questionnaires on depressive symptoms at eight timepoints during the prepregnancy, pregnancy and first-year postpartum periods. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. A generalized estimating equation regression model was employed for repeated measures. In the assisted reproductive technology group, depressive symptoms were more prevalent during early pregnancy and at 1 month postpartum than before pregnancy, and more prevalent before pregnancy and at 1 month after childbirth than in the spontaneous conception group. No significant association was identified between the mode of conception and depressive symptoms during the antenatal or postnatal period. The lack of full-time employment and prepregnancy depressive symptoms were associated with antenatal depressive symptoms. Primipara status and depressive symptoms during prepregnancy and pregnancy were associated with depressive symptoms during the first-year postpartum. Assisted reproductive technology was not a risk factor for depressive symptoms during the pregnancy and postpartum periods, whereas primipara status, lack of full-time employment and prepregnancy depressive symptoms were negative predictors. Therefore, targeted mental health interventions should address these specific factors to effectively support maternal mental health.

Carbon dots based AuAg@AuNPs with oxidase-like activity for SERS dual-readouts detection of D-penicillamine.

An oxidase (OXD) -like AuAg@AuNPs nanozyme was prepared by Au seeds growth using dopamine carbon dots as reducing and capping agents. The AuAg@AuNPs show excellent OXD-like and surface-enhanced Raman spectroscopy (SERS) activities and can oxidize the non-Raman-active leucomalachite green (LMG) into the Raman-active malachite green (MG). The research displays that D-penicillamine (D-PA) can effectively inhibit the OXD-like activity of Au@AgNPs and enhance the SERS signals as substrate. It is attributed to the formation of S-Au bond due to thiol (-SH) in D-PA. Therefore, a highly sensitive and specific SERS dual-readout sensing platform was proposed to assay D-PA with a limit of detection of 0.1 µg/mL (direct SERS mode) and 6.64 µg/L (indirect SERS mode). This approach was successfully used to determine D-PA in actual pharmaceutical formulations.

Fluorescent/colorimetric probe for the detection of Cr(â ¥) based on MIL-101(Fe)-NH2 with peroxidase-like activity.

In the present research, Fe-based metal-organic frameworks (MIL-101(Fe)-NH2) nanoparticles were synthesized by simple solvothermal methods and used to assay Cr(Ⅵ). The MIL-101(Fe)-NH2 performs dual functions: the 2-aminoterephthalic acid (NH2-BDC) ligand endows a strong fluorescence emission, and the Fe metal nodes are able to facilitate the oxidation of 3,3',5,5'- tetramethylbenzidine (TMB) directly, resulting in the generation of oxidized-TMB (ox-TMB). Our research results showed that reducing agents such as ascorbic acid (AA) can collapse the structures of MIL-101(Fe)-NH2 because of the reduction of Fe3+ by AA, resulting in release of NH2-BDC. In the presence of Cr(Ⅵ), the fluorescence intensity of the MIL-101(Fe)-NH2 + AA system will be decreased due to the competitive reduction of Fe3+ and Cr(Ⅵ). Nevertheless, Cr(Ⅵ) can significantly accelerate the oxidation of TMB by MIL-101(Fe)-NH2 as it boosts the electron transfer rate between Fe3+ and Fe2+. Therefore, a fluorescent/colorimetric dual-mode platform was developed for the detection of Cr(Ⅵ) with an extensive linear range (7.5-750 µg/L and 13.3-1000 µg/L) as well as a remarkably low detection limit (0.99 µg/L and 1.98 µg/L). This MOF with the ability to release ligands not only provides inspiration for the design of new luminescent materials, but also offers a novel and reliable solution for the detection of Cr(Ⅵ).

MicroRNA 29a alleviates mitochondrial stress in diet-induced NAFLD by inhibiting the MAVS pathway.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder characterized by fat accumulation in the liver. This leads to aggravated hepatocyte inflammation due to impaired mitochondrial function, mitochondrial double-stranded RNA (mt-dsRNA) release, elevated oxidative stress, and reactive oxygen species (ROS) production. MicroRNA-29a (miR-29a) is used to reduce hepatic fibrosis in cases of cholestatic liver damage and lessen the severity of non-alcoholic steatohepatitis in animal studies by influencing mitochondrial protein balance. However, the effectiveness of miR-29a in diminishing mt-dsRNA-induced exacerbation of NAFLD remains poorly understood, particularly in the context of a Western diet (WD). Our results have found that mice with increased miR-29a levels and fed a WD showed notably decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, and low-density lipoprotein cholesterol levels. They also experienced less weight gain and lower final body and liver weights. In addition, overexpression of miR-29a reduced the severity of fibrosis, alleviated hepatic oxidative stress, misfolded protein aggregates, and the release of mt-dsRNA. Moreover, miR-29a attenuated the innate immune mitochondrial antiviral-signaling protein (MAVS) pathway response. In vitro, the research using HepG2 cells confirmed that miR-29a reduces MAVS expression and decreases the release of mt-dsRNA and superoxide initiated by palmitic acid (PA). Analysis of luciferase activity further established that the specific binding of miR-29a to the 3'UTR of MAVS led to a repression of its expression. In conclusion, these groundbreaking findings underscore the potential of miR-29a in improving the treatment of NAFLD and liver steatofibrosis by inhibiting the MAVS signaling pathway.

Nurse-delivered sleep restriction therapy to improve insomnia disorder in primary care: the HABIT RCT.

Background: Insomnia is a prevalent and distressing sleep disorder. Multicomponent cognitive-behavioural therapy is the recommended first-line treatment, but access remains extremely limited, particularly in primary care where insomnia is managed. One principal component of cognitive-behavioural therapy is a behavioural treatment called sleep restriction therapy, which could potentially be delivered as a brief single-component intervention by generalists in primary care. Objectives: The primary objective of the Health-professional Administered Brief Insomnia Therapy trial was to establish whether nurse-delivered sleep restriction therapy in primary care improves insomnia relative to sleep hygiene. Secondary objectives were to establish whether nurse-delivered sleep restriction therapy was cost-effective, and to undertake a process evaluation to understand intervention delivery, fidelity and acceptability. Design: Pragmatic, multicentre, individually randomised, parallel-group, superiority trial with embedded process evaluation. Setting: National Health Service general practice in three regions of England. Participants: Adults aged ≥ 18 years with insomnia disorder were randomised using a validated web-based randomisation programme. Interventions: Participants in the intervention group were offered a brief four-session nurse-delivered behavioural treatment involving two in-person sessions and two by phone. Participants were supported to follow a prescribed sleep schedule with the aim of restricting and standardising time in bed. Participants were also provided with a sleep hygiene leaflet. The control group received the same sleep hygiene leaflet by e-mail or post. There was no restriction on usual care. Main outcome measures: Outcomes were assessed at 3, 6 and 12 months. Participants were included in the primary analysis if they contributed at least one post-randomisation outcome. The primary end point was self-reported insomnia severity with the Insomnia Severity Index at 6 months. Secondary outcomes were health-related and sleep-related quality of life, depressive symptoms, work productivity and activity impairment, self-reported and actigraphy-defined sleep, and hypnotic medication use. Cost-effectiveness was evaluated using the incremental cost per quality-adjusted life-year. For the process evaluation, semistructured interviews were carried out with participants, nurses and practice managers or general practitioners. Due to the nature of the intervention, both participants and nurses were aware of group allocation. Results: We recruited 642 participants (n = 321 for sleep restriction therapy; n = 321 for sleep hygiene) between 29 August 2018 and 23 March 2020. Five hundred and eighty participants (90.3%) provided data at a minimum of one follow-up time point; 257 (80.1%) participants in the sleep restriction therapy arm and 291 (90.7%) participants in the sleep hygiene arm provided primary outcome data at 6 months. The estimated adjusted mean difference on the Insomnia Severity Index was -3.05 (95% confidence interval -3.83 to -2.28; p < 0.001, Cohen's d = -0.74), indicating that participants in the sleep restriction therapy arm [mean (standard deviation) Insomnia Severity Index = 10.9 (5.5)] reported lower insomnia severity compared to sleep hygiene [mean (standard deviation) Insomnia Severity Index = 13.9 (5.2)]. Large treatment effects were also found at 3 (d = -0.95) and 12 months (d = -0.72). Superiority of sleep restriction therapy over sleep hygiene was evident at 3, 6 and 12 months for self-reported sleep, mental health-related quality of life, depressive symptoms, work productivity impairment and sleep-related quality of life. Eight participants in each group experienced serious adverse events but none were judged to be related to the intervention. The incremental cost per quality-adjusted life-year gained was £2075.71, giving a 95.3% probability that the intervention is cost-effective at a cost-effectiveness threshold of £20,000. The process evaluation found that sleep restriction therapy was acceptable to both nurses and patients, and delivered with high fidelity. Limitations: While we recruited a clinical sample, 97% were of white ethnic background and 50% had a university degree, which may limit generalisability to the insomnia population in England. Conclusions: Brief nurse-delivered sleep restriction therapy in primary care is clinically effective for insomnia disorder, safe, and likely to be cost-effective. Future work: Future work should examine the place of sleep restriction therapy in the insomnia treatment pathway, assess generalisability across diverse primary care patients with insomnia, and consider additional methods to enhance patient engagement with treatment. Trial registration: This trial is registered as ISRCTN42499563. Funding: The award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/84/01) and is published in full in Health Technology Assessment; Vol. 28, No. 36. See the NIHR Funding and Awards website for further award information.

Insomnia refers to problems with falling asleep or staying asleep, which affects 10% of the adult population. The recommended treatment for insomnia is a psychological treatment called cognitive­behavioural therapy. Research shows this to be a very effective and long-lasting treatment, but there are not enough trained therapists to support the large number of poor sleepers in the United Kingdom. We have developed a brief version of cognitive­behavioural therapy, called sleep restriction therapy, which involves supporting the patient to follow a new sleep­wake pattern. We carried out this study to see if sleep restriction therapy, given by nurses working in general practice, can improve insomnia and quality of life. We searched general practice records and invited people with insomnia to take part. Six hundred and forty-two participants were assigned, by chance, to either sleep restriction therapy or a comparison treatment, called sleep hygiene. Sleep restriction therapy involved meeting with a nurse on four occasions and following a prescribed sleep schedule. Sleep hygiene involved receiving a leaflet of sleep 'do's and dont's'. Those receiving sleep restriction therapy were also provided with the same sleep hygiene leaflet so that the difference between the two groups was whether or not they received nurse treatment. We measured sleep, quality of life, daytime functioning and use of sleep medication through questionnaires, before and after treatment. We calculated the cost to deliver the treatment, as well as the cost of other National Health Service treatments that participants accessed during the study. We also interviewed participants and nurses to understand their views of the treatment. We found that participants in the sleep restriction therapy group experienced greater reduction in their insomnia symptoms compared to sleep hygiene. They also experienced improved sleep, mental health, quality of life and work productivity. The two groups did not differ in their use of prescribed sleep medication. Our results suggest that the treatment is likely to represent good value for money for the National Health Service. Both nurses and participants considered the treatment to be acceptable and beneficial, and they suggested some potential refinements. The study shows that nurse-delivered sleep restriction therapy is likely to be a clinically effective approach to the treatment of insomnia, and good value for money for the National Health Service.

A colorimetric platform for sensitive sensing of Hg2+ and S2- based on Se-AuNPs with Hg2+-activated peroxidase-like activity.

Herein, the selenium (Se) modified gold nanoparticles (Se-AuNPs) was synthesized using cerium doped carbon dots (Ce-CDs) as a reducing agent and template. As desired, Se-AuNPs displays enhanced peroxidase (POD)-like activity in the presence of Hg2+. The mechanism for the enhanced activity was attributed to the increased affinity between Se-AuNPs-Hg2+ and the substrate, in which Se and Au elements have a strong binding capacity to Hg2+, forming Hg-Se bonds and Au-Hg amalgam to generate more ·OH. This POD-like activity of Se-AuNPs-Hg2+ correlates with the colorimetric reaction by the catalytic reaction between 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2. The oxidation of TMB was completely inhibited by the introduction of the reductive S2-. Based on the above findings, a strategy for the colorimetric detection of Hg2+ and S2- by Se-AuNPs was established with linear ranges of 0.33-66 µg/L and 0.625-75 µg/L, and low detection limits of 0.17 µg/L and 0.12 µg/L (3.3 δ/k), respectively. When the colorimetric probes for detection of Hg2+ and S2- was applied in environmental water samples, the recoveries were in the range of 90.3-108.0 %. This method will provide a new idea for the colorimetric detection strategy of Hg2+ due to the strong interaction between Hg and Se.

Fluorescence detection of valence speciation of Cr(III) based on the catechol oxidase mimic enzyme activity of CuSeNP nanozymes.

Copper selenide nanoparticles (CuSeNP) were synthesized using histidine, ethylenediamine, and sodium selenate as precursors by one-step microwave digestion methods. The as-prepared CuSeNPs exhibit excellent catechol oxidase mimic enzyme and catalase (CAT)-like activities. Dopamine (DA) can be oxidized to aminochrome with H2O2 by CuSeNPs, and the intermediate product aminochrome can further react with α-naphthol to yield a highly fluorescent derivative. It was confirmed that Cr(III) could adsorb on the surface of CuSeNPs and inhibit the production of semiquinone radicals in the reaction system, and the catalytic activity of CuSeNPs was inhibited. The detection mechanisms, kinetics, and catalytic properties of CuSeNPs were systematically investigated. As a result, a novel fluorescence method for the assay of Cr(III) was established. The feasibility of CuSeNP nanozyme in detecting speciation Cr(III) in food samples was explored with satisfactory results. It showed the obvious potential for developing effective and dependable fluorescent detection method for protecting food safety.

Colorimetric-SERS dual-mode aptasensor for Staphylococcus aureus based on MnO2@AuNPs oxidase-like activity.

The nanozyme-linked aptamer-sorbent assay (NLASA) is a rapid way to screen and characterize aptamer binding to targets. In this paper, a MnO2@AuNPs@aptamer (Apt) based NLASA coupled with colorimetric-SERS dual-mode for Staphylococcus aureus (S. aureus) detection is presented. Cu,Fe-CDs were used as the reducing agent to synthesize MnO2 and gold nanoparticles (AuNPs). Then, they were fabricated to obtain MnO2@AuNPs with oxidase (OXD)-like and SERS activities. The S. aureus aptamer was conjugated to MnO2@AuNPs and enhanced the OXD-like activity, which realized the specific capture of S. aureus in food matrices. In addition, S. aureus improves the oxidation of 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid (ABTS) but inhibits 3,3',5,5'-tetramethylbenzidine (TMB) to generate Raman-active oxTMB with MnO2@AuNPs@Apt. This sensor was used for detections of S. aureus in a concentration ranged from 101 to 107 CFU/mL with a detection limit of 0.926 CFU/mL (colorimetric) and 1.561 CFU/mL (SERS), and the recovery is 85%-105% in real samples.

ZmNF-YA1 Contributes to Maize Thermotolerance by Regulating Heat Shock Response.

Zea mays (maize) is a staple food, feed, and industrial crop. Heat stress is one of the major stresses affecting maize production and is usually accompanied by other stresses, such as drought. Our previous study identified a heterotrimer complex, ZmNF-YA1-YB16-YC17, in maize. ZmNF-YA1 and ZmNF-YB16 were positive regulators of the drought stress response and were involved in maize root development. In this study, we investigated whether ZmNF-YA1 confers heat stress tolerance in maize. The nf-ya1 mutant and overexpression lines were used to test the role of ZmNF-YA1 in maize thermotolerance. The nf-ya1 mutant was more temperature-sensitive than the wild-type (WT), while the ZmNF-YA1 overexpression lines showed a thermotolerant phenotype. Higher malondialdehyde (MDA) content and reactive oxygen species (ROS) accumulation were observed in the mutant, followed by WT and overexpression lines after heat stress treatment, while an opposite trend was observed for chlorophyll content. RNA-seq was used to analyze transcriptome changes in nf-ya1 and its wild-type control W22 in response to heat stress. Based on their expression profiles, the heat stress response-related differentially expressed genes (DEGs) in nf-ya1 compared to WT were grouped into seven clusters via k-means clustering. Gene Ontology (GO) enrichment analysis of the DEGs in different clades was performed to elucidate the roles of ZmNF-YA1-mediated transcriptional regulation and their contribution to maize thermotolerance. The loss function of ZmNF-YA1 led to the failure induction of DEGs in GO terms of protein refolding, protein stabilization, and GO terms for various stress responses. Thus, the contribution of ZmNF-YA1 to protein stabilization, refolding, and regulation of abscisic acid (ABA), ROS, and heat/temperature signaling may be the major reason why ZmNF-YA1 overexpression enhanced heat tolerance, and the mutant showed a heat-sensitive phenotype.

Cu,Zn,I-Doped Carbon Dots with Boosted Triple Antioxidant Nanozyme Activity for Treatment of DSS-Induced Colitis.

Nanozyme-mediated antioxidative therapy is a promising star for treating a myriad of important diseases through eliminating excessive reactive oxygen species (ROS) such as O2·- and H2O2, a critical mechanism for inflammatory bowel disease (IBD). This work provides a high biocompatibility iodine-copper-zinc covalent doped carbon dots (Cu,Zn,I-CDs) with the catalase (CAT)-, superoxide dismutase (SOD)- and glutathione peroxidase (GPx)-like catalytic activities for treating ulcerative colitis (UC) by scavenging overproduced ROS. We found that I dopant aids in counteracting the positive charge at Cu,Zn dopants brought on by low pH, enabling Cu,Zn,I-CDs to process strong triple antioxidant nanozyme activities rather than Cu,Zn-CDs. Vitro experiments displayed that the Cu,Zn,I-CDs could scavenge the excessive ROS to protect cellular against oxidative stress and reduce the expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6. In sodium dextran sulfate (DSS)-induced colitis mice models, Cu,Zn,I-CDs with excellent biocompatibility could effectively relieve the inflammation of the colon, containing the reduction of the colon length, the damaged epithelium, the infiltration of inflammatory cells, and upregulation of antioxidant genes. Therefore, the therapy of Cu,Zn,I-CD antioxidant nanozymes is an effective approach and provides a novel strategy for UC treatment.

Integrated Clinical Genotype-Phenotype Characteristics of STAT3-Mutated Myeloid Neoplasms.

PURPOSE: STAT3 is a key transcription factor that mediates cancer progression through phosphorylation or gain-of-function mutations. STAT3 activation in myeloid neoplasms (MN) is primarily mediated through phosphorylation. STAT3 mutation has only rarely been reported in MNs. EXPERIMENTAL DESIGN: We assessed the clinicopathologic and molecular genetic features of 32 STAT3-mutated MNs. RESULTS: The frequency of STAT3 mutation in MNs was <0.5%. Twenty (62.5%) cases were classified as acute myeloid leukemia, 7 (21.9%) as myelodysplastic syndrome, and 5 (15.6%) as chronic myelomonocytic leukemia, but none as myeloproliferative neoplasms. STAT3 mutations occurred at initial diagnosis in 22 (88%) cases or at relapse or upon leukemic transformation. Clonal hierarchy analysis revealed that STAT3 mutations represented the dominant clone in 30% of acute myeloid leukemia cases but were subclonal in myelodysplastic syndrome and chronic myelomonocytic leukemia. Most were missense mutations located at the SH2 domain, Y640F being the most common. STAT3 mutation was accompanied by coexisting mutations in all cases, most frequently SRSF2, TET2, ASXL1, and SETBP1. STAT3 mutations were usually associated with morphologic dysplasia, increased blasts, and monosomy 7/del7q. With a median follow-up of 24.5 months, 21 patients died, 6 had persistent disease, and 5 achieved complete remission after stem cell transplantation. CONCLUSIONS: STAT3 mutation is present in various MNs but not in myeloproliferative neoplasms. It is often an early event or occurs upon leukemic transformation, which suggests an important role in the pathogenesis and progression of MNs by activating the JAK-STAT pathway. It may help determine a subset of patients with MNs who may benefit from targeted therapy. See related commentary by Hochman and Frank, p. 4554.

Aptamer-functionalized Fe3O4/MWCNTs@Mo-CDs nanozyme for rapid colorimetric detection toward Escherichia coli.

The pathogenic bacteria induced foodborne disease has been detrimental to public health worldwide. Herein, the peroxidase (POD)-like Fe3O4/MWCNTs@Mo-CDs (FMMC) nanozyme was applied for the detection of Escherichia coli (E. coli). The E. coli aptamer was conjugated with the surface of the FMMC, which effectively enhanced the POD-like activity attributing to the higher affinity to the substrate, and then specific capture of E. coli in food matrices, leading to the reduction of POD-like activity. Therefore, a robust and facile colorimetric aptasensor was developed for detecting E. coli with a wide linear range of 101-106 CFU/mL, low LOQ of 101 CFU/mL and LOD of 0.978 CFU/mL. The aptasensor demonstrated the satisfied selectivity for E. coli compared to the other strains. This method possessed the potential application for fast in situ screening of foodborne pathogens in food products.

Rapid implementation of blood pressure self-monitoring in pregnancy at a UK NHS Trust during the COVID-19 pandemic: a quality improvement evaluation.

BACKGROUND: This service evaluation describes the rapid implementation of self-monitoring of blood pressure (SMBP) into maternity care at a tertiary referral centre during the COVID-19 pandemic. It summarises findings, identifies knowledge gaps and provides recommendations for further research and practice. INTERVENTION: Pregnant and postpartum women monitored their blood pressure (BP) at home, with instructions on actions to take if their BP exceeded pre-determined thresholds. Some also conducted proteinuria self-testing. DATA COLLECTION AND ANALYSIS: Maternity records, app data and staff feedback were used in interim evaluations to assess process effectiveness and guide adjustments, employing a Plan-Do-Study-Act and root cause analysis approach. RESULTS: Between March 2020 and August 2021, a total of 605 women agreed to self-monitor their BP, including 10 women with limited English. 491 registered for telemonitoring (81.2%). 21 (3.5%) took part in urine self-testing. Engagement was high and increased over time with no safety issues. Biggest concerns related to monitor supply and postnatal monitoring. In December 2020, SMBP was integrated into the standard maternity care pathway. CONCLUSIONS: This project demonstrated successful integration of SMBP into maternity care. Early stakeholder engagement and clear guidance were crucial and community midwifery support essential. Supplying BP monitors throughout pregnancy and post partum could improve the service and fully digitised maternity records would aid data collection. More research is needed on SMBP in the postnatal period and among non-English speakers. These findings support efforts to implement app-supported self-monitoring and guide future research.

d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women: A Randomized Clinical Trial.

Importance: Recurrent urinary tract infection (UTI) is a common debilitating condition in women, with limited prophylactic options. d-Mannose has shown promise in trials based in secondary care, but effectiveness in placebo-controlled studies and community settings has not been established. Objective: To determine whether d-mannose taken for 6 months reduces the proportion of women with recurrent UTI experiencing a medically attended UTI. Design, Setting, and Participants: This 2-group, double-blind randomized placebo-controlled trial took place across 99 primary care centers in the UK. Participants were recruited between March 28, 2019, and January 31, 2020, with 6 months of follow-up. Participants were female, 18 years or older, living in the community, and had evidence in their primary care record of consultations for at least 2 UTIs in the preceding 6 months or 3 UTIs in 12 months. Invitation to participate was made by their primary care center. A total of 7591 participants were approached, 830 responded, and 232 were ineligible or did not proceed to randomization. Statistical analysis was reported in December 2022. Intervention: Two grams daily of d-mannose powder or matched volume of placebo powder. Main Outcomes and Measures: The primary outcome measure was the proportion of women experiencing at least 1 further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months of study entry. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions. Results: Of 598 women eligible (mean [range] age, 58 [18-93] years), 303 were randomized to d-mannose (50.7%) and 295 to placebo (49.3%). Primary outcome data were available for 583 participants (97.5%). The proportion contacting ambulatory care with a clinically suspected UTI was 150 of 294 (51.0%) in the d-mannose group and 161 of 289 (55.7%) in the placebo group (risk difference, -5%; 95% CI, -13% to 3%; P = .26). Estimates were similar in per protocol analyses, imputation analyses, and preplanned subgroups. There were no statistically significant differences in any secondary outcome measures. Conclusions and Relevance: In this randomized clinical trial, daily d-mannose did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI. d-Mannose should not be recommended for prophylaxis in this patient group. Trial Registration: isrctn.org Identifier: ISRCTN13283516.

Zirconium-porphyrin-MOF-based oxidase-like nanozyme with oxygen vacancy for aflatoxin B1 colorimetric sensing.

In this study, a porous coordination network zirconium-porphyrin-based nanoparticle with oxygen vacancies (OVs) was prepared using acetic acid and benzoic acid as modulators via a simple hydrothermal method. The presence of OVs was confirmed by various characterization methods and was found to enhance oxygen uptake and activation. This resulted in the generation of more reactive peroxyl radicals (•O2 -) and led to an improved oxidase (OXD) mimetic activity. Additionally, it promoted 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) oxidation, with a low Km value of 0.07 mM and a high Vmax of 1.47 × 10-7 M·s-1. As aflatoxin B1 (AFB1) inhibits the Pt@PCN-222-ABTS nanozyme system, a colorimetric probe for AFB1 detection was constructed. The limit of detection (LOD) was 0.074 µg·L-1. This research presents a novel approach for designing a nanozymatic-based colorimetric method to analyze trace AFB1 residues in food.

MiR-29a efficiently suppresses the generation of reactive oxygen species and α-synuclein in a cellular model of Parkinson's disease by potentially targeting GSK-3ß.

MicroRNA-29a (miR-29a) has been suggested to serve a potential protective function against Parkinson's disease (PD); however, the exact molecular mechanisms remain elusive. This study explored the protective role of miR-29a in a cellular model of PD using SH-SY5Y cell lines through iTRAQ-based quantitative proteomic and biochemistry analysis. The findings showed that using a miR-29a mimic in SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+) significantly decreased cell death and increased mitochondrial membrane potential. It also reduced mitochondrial reactive oxygen species (ROS) and the production of α-synuclein. Subsequent heatmap analysis using iTRAQ-based quantitative proteomics revealed remarkably contrasting protein expression profiles for 882 genes when comparing the groups treated with miR-29a mimic plus MPP + against the control group treated solely with MPP+. The KEGG pathway analysis of these 882 genes indicated the substantial role of miR-29a in the PD pathway (P = 1.58x10-5) and highlighted its function in mitochondrial genes. Furthermore, treatment with a miR-29a mimic in SH-SY5Y cells reduced the levels of GSK-3ß, phosphorylated GSK-3ß, and cleaved caspase-7 following exposure to MPP+. The miR-29a mimic also upregulated the expressions of α-synuclein clearance proteins FYCO1 and Rab7 in this cellular PD model, thereby inhibiting the production of α-synuclein. Luciferase activity analysis confirmed the specific binding of miR-29a to the 3' untranslated region (3'UTR) of GSK-3ß, leading to its repression. Our findings demonstrated miR-29a's neuroprotective role in mitochondrial function and highlighted its potential to inhibit ROS and α-synuclein production, offering possible therapeutic avenues for PD treatment.