A simple suspension method has been widely used in Japan, however, chemical interactions among drugs in co-suspensions have not been fully clarified. Magnesium oxide (MgO), which is frequently prescribed as a laxative, can interact with various drugs. Eplerenone and spironolactone, potassium-sparing diuretics, are sometimes co-prescribed with MgO to older patients. In this study, we investigated the chemical stability of eplerenone and spironolactone in a co-suspension with MgO and characterized the structures of the degradation products that were formed under the conditions. An eplerenone or spironolactone tablet was soaked with or without an MgO tablet in warm water in a tube according to a standard simple suspension method. The contents in the tube were mixed by inversion after 10 min, 1 h or 5 h to prepare a simple suspension. In separate experiments, the suspension prepared after 10 min soaking was allowed to stand for 50 min or 4.8 h at room temperature. The suspensions were immediately analyzed by high-performance liquid chromatography. The recovery rates of the diuretics from the suspensions were calculated relative to the labeled amounts. The degradation products were isolated and the structures analyzed by high-resolution mass spectrometry. The high-performance liquid chromatographic analysis showed that the diuretics were stable in their simple suspensions without MgO under any of the conditions. When co-suspended with MgO, a slight degradation was observed for eplerenone after just 10 min soaking and the degradation was statistically significant after 5 h soaking, whereas spironolactone was stable even after 5 h soaking. On the other hand, when the co-suspensions with MgO were left alone after mixing, eplerenone significantly degraded in 50 min, and spironolactone slightly degraded in the same period. Based on the mass spectra from the degradation products, hydrolysis of the lactone ring was shown to have occurred in both diuretics co-suspended with MgO. For spironolactone, hydrolysis and elimination of the thioester were also shown to have occurred in the co-suspensions. Eplerenone is more unstable than spironolactone in the simple co-suspension with MgO. As such, the simple co-suspensions of eplerenone are preferably prepared immediately before administration.
Computed tomography is the gold standard for visually assessing gas trapping, a hallmark of early lung disease in people with cystic fibrosis (pwCF), but its use is limited in children. Lung proton magnetic resonance imaging (¹H-MRI) offers a simple, non-ionising alternative. This work aimed to use breath-hold 1H-MRI to visualise and quantify gas trapping in pwCF. 24 normal controls (9 adults, 15 children) and 27 pwCF underwent breath-hold 1H-MRI at residual volume (RV) and total lung capacity (TLC). For each participant, a threshold was defined from the TLC image and applied to the RV image to quantify low-signal areas, presumed to be gas trapping, as a gas trapping volume (GTV). An upper limit of normal (ULN) was defined based on the normal distribution of GTV, and GTV was compared to spirometry, body plethysmography, multiple breath washout and 129Xe Ventilation MRI. Gas trapping was visualised in pwCF as regions of low signal intensity on RV images. Healthy volunteers had a median GTV of 2.93% (0.32-14.37%). PwCF had a GTV of 21.80% (2.04-82.68%) and FEV1 z-scores of -1.14 (-5.43, 2.17), with 14 having normal FEV1. The ULN of GTV was 7.01%; 9/14 pwCF with normal spirometry exceeded this. In pwCF, GTV is strongly correlated with FEV1 z-scores, 129Xe-MRI ventilation defect percentage, and gas trapping measured by body plethysmography (RV/TLC%). Using a standard, easily implementable breath-hold 1H-MRI protocol, gas trapping in CF can be clearly visualised and quantified. Preliminary evidence shows lung function impairment in pwCF who have normal FEV1.
Currently, no unified standardized protocols exist for myocardial longitudinal strain measurement in functional single ventricle (FSV) patients, causing inconsistent methodologies in clinical practice and related studies. Some studies use only the apical four-chamber view, while others employ three apical views. This study aimed to determine whether longitudinal strain (LS-4CH) measured from the apical four-chamber view can serve as an effective substitute for the average global longitudinal strain (GLS-AV) derived from multiple apical views in different subtypes of FSV patients. This retrospective study enrolled 34 FSV patients. The consistency between LS-4CH and GLS-AV was assessed via Bland-Altman analysis, intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC), and Passing-Bablok regression, with Two One-Sided Tests (TOST) for formal equivalence verification. Intra- and inter-observer ICC were used to evaluate the repeatability of the two methods. Spearman's correlation analyzed the associations of LS-4CH and GLS-AV with cardiac magnetic resonance-derived ejection fraction (CMR-EF). Receiver operating characteristic (ROC) curve analysis evaluated the predictive value of each index for predicting CMR-EF < 50%; DeLong test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used for predictive efficacy comparison and incremental value assessment. LS-4CH and GLS-AV exhibited good consistency (all ICC > 0.87, CCC > 0.83) and excellent intra- and inter-observer repeatability, with TOST confirming their statistical equivalence within a predefined margin of ± 3% (all P < 0.05). Both GLS-AV and LS-4CH showed significant negative correlations with CMR-EF in the overall cohort and both SLV/SRV subgroups (all P < 0.05). ROC curve analysis showed that GLS-AV had significant predictive value for CMR-EF < 50% in the SLV group (AUC = 0.86, P = 0.02). When multi-view measurement of GLS-AV is impractical due to poor image quality, technical limitations, or urgent assessment needs, LS-4CH may serve as an effective alternative assessment indicator for patients with functional single ventricle. However, GLS-AV remains the preferred method when feasible, since LS-4CH cannot reflect regional dysfunction beyond the apical four-chamber view.
This study investigates how emotional intelligence mediates the link between future temporal orientation and depressive symptoms in university students and explores whether physical activity moderates this connection. Data were collected from 1,014 undergraduate students (490 males and 524 females) across three universities in Fujian Province, China, between 1 March and 5 July 2024. Participants were selected via random sampling and completed the Future Time Perspective Scale, Emotional Intelligence Scale, Physical Activity Rating Scale, and Epidemiologic Studies Depression Scale. Statistical analyses included Pearson's correlation, linear regression, and moderated mediation analysis (PROCESS Model 7) using SPSS 22.0. (1) Future time perspective significantly and negatively predicted depression (β = -0.32, p < 0.001). (2) Emotional intelligence partially mediated the association between future time perspective and depression (indirect effect = -0.11, SE = 0.02, 95% CI [-0.15, -0.08]). (3) Physical exercise moderated the first-stage path of the mediation model (FTP → EI). Simple slope analyses showed that the FTP-EI association was significant at both low (M - 1 SD) and high (M + 1 SD) levels of physical exercise, but was stronger at high physical exercise (simple slope: β = 0.41, p < 0.01) than at low physical exercise (simple slope: β = 0.25, p < 0.01). Future time perspective influences depression both directly and indirectly through emotional intelligence. Additionally, physical exercise enhances the predictive effect of future time perspective on emotional intelligence, suggesting that active individuals exhibit a stronger link between future-oriented thinking and emotion regulation.
We present a novel yet simple approach to measuring individual differences in visual imagery, in which people compare the quality of voluntarily generated visual images to the quality of (eyes-closed) negative afterimages. In laboratory testing (n = 98), many participants rated their own imagery of a face or a letter A to be similar or even stronger - on each of several experiential dimensions - than an afterimage of a face or letter. Dimensions were brightness, sharpness, detail, and two dimensions which deconstruct and challenge a simple distinction between associator-versus projector-imagers. Other participants rated their voluntary images to be weaker than afterimages, indicating qualitative differences between participants. This replicated data from a large-sample pilot, conducted under less formal conditions. Participants mostly expressed that their comparative ratings were accurate. Over the pilot and main study, ratings correlated with 3 standard self-report instruments for visual imagery, supporting the construct validity of our measure. Participants visually rendered the brightness and sharpness of their afterimages on a computer screen, allowing (a) depiction of the baseline against which voluntary images were being compared and (b) calculation that variation in afterimagery strength was independent of the strength of voluntary images, and cannot account for variance in our comparative ratings of voluntary imagery. As a method of quantifying the range of visual imagery experience from aphantasics to hyperphantasics, in healthy and clinical populations, our approach may be less metacognitively contaminated and more accurate than widely-used yet criticised self-report instruments of imagery, e.g. those comparing imagery vividness to real seeing.
Alzheimer's disease (AD) is a common neurodegenerative disorder with increasing cases worldwide. Early screening is important for AD prevention and treatment, but current methods still face many challenges. To address these challenges, we developed a simple and novel molecular beacon (MB) fluorescent biosensor. This sensor combines aptamers with exponential amplification reaction (EXPAR). Through special design of the EXPAR templates, the sensor achieves triple signal amplification. It showed a limit of detection (LOD) of 110 fM for Aβ42 and 300 fM for Aβ40, exhibits high sensitivity. The coefficient of variation (CV) for detecting different target concentrations ranged from 4.42% to 8.85%, showing good repeatability. We also applied this sensor to detect these biomarkers in plasma samples from AD patients. The spike recovery rates were 104.67%-109.3% for Aβ42 and 104.2%-106.93% for Aβ40, demonstrating strong resistance to plasma matrix interference. Due to the specificity of aptamers and nucleic acid design, this method allows simultaneous detection of multiple targets (e.g., Aβ42, Aβ40) in the same system, improving detection efficiency and reliability in complex samples. Compared with traditional Aβ detection methods such as ELISA and colorimetry, our method shows 10-104 times higher sensitivity. Compared with emerging techniques like electrochemical detection and single-molecule array, our sensor has the advantages of stronger resistance to plasma matrix interference, more stable results, lower cost and biotoxicity, simpler operation and better biocompatibility and potential of multiple-target detection. These features make it a promising tool for high-throughput early screening of AD, with potential to advance early diagnosis.
Periodontitis, a chronic inflammatory disease, is increasingly prevalent among young people and impairs their quality of life. Adverse childhood experiences (ACE), depressive symptoms, and suboptimal health status (SHS) are linked to health risks and chronic diseases, but their interrelationships with periodontitis in Chinese young adults remain unclear. This study aimed to explore associations among these factors. From December 2024 to May 2025, 2,888 participants (aged 18-35) from Tongji Hospital completed surveys on demographics, ACE, depressive symptoms, and SHS. Periodontitis was diagnosed according to the 2018 criteria. Simple, parallel, and chain mediation models were used, controlling for age, sex, marital status, and smoking. Periodontitis prevalence was 25.00% and higher in married individuals (P < 0.001) and smokers (P = 0.004). ACE correlated positively with depressive symptoms (r = 0.28, P < 0.001), SHS (r = 0.19, P < 0.001), and periodontitis (r = 0.16, P < 0.001). Mediation analyses showed: Simple model: Depressive symptoms and SHS partially mediated the effect of ACE on periodontitis (indirect effect = 0.011 for both). Parallel model: Only SHS significantly mediated the effect (indirect effect = 0.011). Chain model: ACE was related to periodontitis via "depressive symptoms → SHS" (indirect effect = 0.010), with significant direct and indirect effects. ACE associated with higher periodontitis risk in young people. This association included both a direct link between ACE and periodontitis, and an indirect link through the chain pathway of "depressive symptoms → SHS"; among these pathways, SHS was a key mediator. The study was registered in the Chinese Clinical Trial Registry (ChiCTR) with the registration number ChiCTR2500103464. Childhood trauma can exert long‐term impacts on health, including oral health. This study involving 2,888 Chinese young adults aged 18‐35 found that 25% of the participants had periodontitis. Those who experienced childhood abuse, neglect, or family issues showed a higher association with the disease. The research revealed two pathways linking early trauma to periodontitis: a direct association and an indirect chain of “depressive symptoms → suboptimal health status (e.g., persistent fatigue).” While depressive symptoms played a role, suboptimal health status was the critical mediator. Higher periodontitis rates in married individuals and smokers may relate to stress or lifestyle factors. The findings suggested that early identification of childhood trauma, combined with interventions targeting mental health or overall well‐being (e.g., counseling, health management), could be more effective than oral care alone in prevention. This underscored the association between early‐life experiences and long‐term health and the need for integrated interventions.
Seed germination is the most vital yet challenging stage of tropical palms and the ecophysiology of this process remains undefined. Arenga wightii, an endemic palm of the Southern Western Ghats, is of key interest for toddy harvest and other value-added products. Under natural conditions, this palm regenerates from seeds with low germination. However, the reasons behind the decline in regeneration of this threatened species remain unexplored. We hypothesize that the localised distribution of the palm in the shady regions of the Southern Western Ghats is due to ecophysiological factors related to seed germination and dormancy type. We investigated the imbibition time, and the optimum temperature for germination was determined using seed germinators. Dormancy was defined using treatment with dormancy breaking methods. Features of early seedlings were examined through anatomical and histochemical methods. Mature seeds shed with a moisture content of 35%. The physiological, morphoanatomical and histochemical results indicate recalcitrant traits. The seeds exhibit non-deep simple morphophysiological dormancy. Germination of fresh seeds was below 35%; removal of the operculum increased germination to 97% and reduced the mean germination time (MGT) to 5 days. Germination was of a remote non-ligular type, and the seedlings exhibited adaptations to swampy habitats. Our findings indicate that slow seed germination, coexistence of dormancy, coupled with recalcitrant traits, indicate the critical nature of temperature requirement, and are an adaptation for survival in humid and shady areas of the Southern Western Ghats. Habitat protection and removal of the operculum from mature seeds are effective for generating seedlings for large scale restoration.
Single-emission fluorescent sensors are susceptible to environmental interference, which limits their application in complicated detection systems. In this study, a dual-emission lanthanide-functionalized MOF hybrid (Eu3+@Cd-MOF-1) [Cd-MOF-1: {[Cd5(Htphca)2(H2O)6]·7H2O}n (H6tphca = 1,1':3,1″-terphenyl -2,2″,4',5,5″,6'-hexacarboxylic acid)] was fabricated by taking Cd-MOF-1 as the pristine framework, and Eu3+ ions were introduced into its frameworks through a simple and non-destructive coordinated post-synthesis modification (PSM) strategy. Crystallographic studies revealed that Cd-MOF-1 displayed a 2D layerpillared 3D framework in which the Cd2+ layers with the mixed carboxylate and oxygen bridges are interconnected by the Htphca5- ligands. Cd-MOF-1 exhibited good water and chemical stability. Furthermore, Eu3+@Cd-MOF-1 also exhibited excellent solvent stability and a wide pH durability over the range of pH 2-12. More interestingly, Eu3+@Cd-MOF-1 presented two distinct emission peaks at 424 nm and 616 nm, which were attributed to the ligand-based fluorescence emission and the characteristic emission of Eu3+ ions, respectively. As expected, Eu3+@Cd-MOF-1 can act as a stable dual-emission fluorescence sensor for detecting Fe3+ and Cr3+, with the low limit of detection (LOD) values and rapid response time, in which the two emission peaks were completely quenched by Fe3+, whereas only Eu3+ characteristic emission was quenched by Cr3+, showing a ratiometric fluorescence detection behavior. In addition, Eu3+@Cd-MOF-1 could also achieve rapid detection of antibiotics (ornidazole: ODZ; metronidazole: MDZ) in water through the quenching effect. The detection process exhibited high selectivity and sensitivity, with high quenching efficiencies Ksv and low LODs. Moreover, the sensing mechanism was investigated by PXRD, UV-vis absorption, fluorescence lifetime and density functional theory (DFT) calculations. The results indicated that the fluorescence quenching of Eu3+@Cd-MOF-1 after adding Fe3+ arises from the synergistic effects of energy absorption competition and the weak interaction between Eu3+@Cd-MOF-1 and Fe3+ ions. Meanwhile, the fluorescence response of Eu3+@Cd-MOF-1 toward Cr3+ was mainly attributed to the coordination interaction between Eu3+@Cd-MOF-1 and Cr3+ ions. Furthermore, the quenching of Eu3+@Cd-MOF-1 with ODZ and MDZ was caused by the photo-induced electron transfer process (PET) and energy competition absorption. Additionally, a mixed-matrix film based on Eu3+@Cd-MOF-1 (PVDF/Eu3+@Cd-MOF-1) was fabricated, which could be used as a portable and convenient approach for visual detection of metal ions (Fe3+, Cr3+) and antibiotics (ODZ, MDZ). This work provided a promising MOF-based dual-emission fluorescent sensor for rapid and sensitive detection of heavy metal ions and antibiotics in the aqueous solution.
The overuse of laboratory tests in hospitals contributes to increased healthcare costs and a larger environmental footprint. This study aimed to evaluate the impact of a rational laboratory test-ordering strategy in an internal medicine department. We conducted a prospective, single-center study in an internal medicine department. The study consisted of a baseline phase without intervention followed by an intervention phase during which internal guidelines promoting rational test ordering were implemented and supervised. The primary outcomes were changes in the volume and cost of the most frequently ordered laboratory tests. Secondary outcomes included hospital activity indicators and morbidity and mortality data. A total of 1,816 patients were admitted for inpatient care between November 2023 and April 2024. Following implementation of the rational prescribing strategy, the volume of orders significantly decreased for the ten targeted laboratory tests (complete blood count, C-reactive protein, vitamins B9 and B12, lipid panel, serum protein electrophoresis, HbA1c, vitamin D, B-type natriuretic peptide [BNP], and thyroid-stimulating hormone [TSH]), with reductions ranging from 33% to 69%. The overall cost of these tests decreased by €11,334 over three months. No significant differences were observed between the two periods in terms of number of admissions, mean length of stay, transfers to intensive care, or in-hospital mortality. Implementing a rational laboratory test-ordering strategy in an internal medicine department significantly reduced the volume and cost of testing without adversely affecting hospital activity indicators or morbidity and mortality outcomes. This simple, reproducible, and well-accepted approach represents a practical opportunity for clinical, economic, and environmental optimization.
The fast-evolving IT sector necessitates intelligent electromagnetic interference (EMI) shielding materials capable of real-time, environment-responsive. While current approaches based on reconstructing conductive networks through mechanical strain enable dynamically responsive shielding, but face a narrow tuning range, inadequate stability, and practical limitations. To address this, we propose an electric/magnetic field synergistic regulation strategy. This approach enables precise control over the alignment angle between reduced graphene oxide (rGO) and nickel nanowires (NiNWs) by manipulating the external field direction, producing rGO@NiNWs/polyimide aerogels with 3D ordered networks. Leveraging this design, the aerogels achieve reversible, wide-range tuning of EMI shielding performance through simple physical rotation, enabling reliable "on/off" switching capability. The oriented structure also optimizes both filler interconnection efficiency and interfacial polarization. With an rGO@NiNWs content of 80 wt.% and an inter-phase angle of 90°, the aerogels demonstrate excellent ultra-wideband EMI shielding performance across gigahertz and terahertz bands, with an average shielding effectiveness of 85 dB in the terahertz band, alongside good stability in extreme environments. Finite element simulations further reveal how the spatial configuration of rGO@NiNWs governs the shielding behavior and intelligent response mechanism. This study paves the way for next-generation intelligent electromagnetic protection materials, with promising potential for aerospace and wearable applications.
Chronic hepatitis B (CHB) is characterized by progressive structural and functional liver impairment involving hepatic dysfunction, fibrosis accumulation, and nutritional-immune imbalance. Although non-invasive indices derived from routine laboratory parameters-such as the albumin-bilirubin (ALBI) score, fibrosis-4 (FIB-4) index, and prognostic nutritional index (PNI)-are widely used, their integrated value for stage-based risk stratification in HBV-related liver disease remains unclear. To develop and internally validate a clinically applicable, non-invasive risk stratification framework based on ALBI, FIB-4, and PNI, and to evaluate its performance across different clinical stages of HBV-related liver disease. We conducted a single-center retrospective cross-sectional study including 842 hospitalized patients with HBV-related liver disease. Patients were categorized as chronic hepatitis B, compensated cirrhosis, or decompensated cirrhosis at admission. ALBI, FIB-4, and PNI were calculated from routine laboratory data. Ordinal logistic regression was used to identify factors associated with advanced disease stage. Discriminative performance was assessed using receiver operating characteristic (ROC) analysis, and calibration was evaluated. Factors associated with hepatic encephalopathy were explored in patients with decompensated cirrhosis. ALBI and FIB-4 increased with higher disease stage, whereas PNI declined significantly (all P < 0.001). Multivariable analysis identified age, ALBI, and FIB-4 as independent factors associated with advanced stage, while PNI and platelet count were inversely associated. The combined framework was associated with improved discrimination for disease stages compared with individual indices, with further enhancement after incorporation of prothrombin time (PT). Higher ALBI values were independently associated with hepatic encephalopathy among patients with decompensated cirrhosis. An integrated framework combining ALBI, FIB-4, PNI, and PT may provide a simple, interpretable, and cost-accessible tool for stage-based risk stratification in HBV-related liver disease within hospitalized populations.
Depressive disorders are characterized by heterogeneous symptoms and variable treatment response. Current interventions primarily aim to manage symptoms, yet their effectiveness remains limited. This highlights the need for early neurobiological markers to improve understanding of depression pathophysiology and guide treatment development. In this study, 38 healthy participants aged 18-40 years (21 females and 17 males) completed the self-report version of the Montgomery-Åsberg Depression Rating Scale (MADRS-S), followed by proton magnetic resonance spectroscopy (1H-MRS) data acquisition from the anterior cingulate cortex (ACC). Spectra were acquired from the dorsal (dACC) and pregenual (pgACC) subdivisions, and analyses focused on metabolite levels of γ-aminobutyric acid (GABA), glutamate + glutamine (Glx), total N-acetyl aspartate (tNAA), and total creatine (tCr). Simple and multiple linear regression analyses, controlling for age, sex, tobacco use, and alcohol consumption, revealed a negative association between depressive symptom scores and tNAA/tCr levels in both the pgACC and dACC. However, no significant associations were observed for GABA/tCr or Glx/tCr. These findings suggest that reduced tNAA/tCr levels in the dACC and pgACC may be associated with depressive symptom severity in non-clinical individuals. Given that tNAA reflects neuronal integrity and mitochondrial function, its reduction may reflect early neuronal and metabolic variation associated with depressive symptom scores. Thus, tNAA may represent an in vivo biomarker for early affective vulnerability, potentially enabling detection of depressive symptom scores in healthy individuals.
Low handgrip strength (HGS) and sarcopenia are common in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to explore associations between baseline HGS, fat-free mass index (FFMI), nutritional indices, and survival. This was a prospective observational sub-study of a randomized nutritional intervention trial, including 50 male patients with HNSCC undergoing curative-intent treatment (surgery and/or (chemo)radiotherapy). Sarcopenia was defined as low HGS (<27 kg) and FFMI (<17 kg/m2). Chi-square, Kaplan-Meier, and Cox analyses were used. Low HGS was observed in 16%, low FFMI in 46%, and sarcopenia in 12%. Patients with low HGS had lower body weight, BMI, and FFMI, alongside more malnutrition, elevated CRP, and heavy smoking. Low HGS and sarcopenia were associated with shorter overall survival (HR 3.7, [95% CI 1.5-9.1] and 5.5, [2.2-14.5], respectively); FFMI was not. Adjustment removed significance. Findings should be interpreted cautiously due to the small, all-male cohort size. In this small exploratory cohort HGS may serve as a simple screening surrogate for sarcopenia and survival. www. gov, identifier NCT02159508.
At the end of 2024 over 3,500 women were living in prison in England, many of whom have experienced prior trauma and domestic abuse and are more likely than men in prison to self-harm. Compared to women living in the community, they also have higher levels of social care needs, yet little research has been conducted to explore social care provision for this population. We conducted surveys of healthcare managers and governors in eleven women's prisons in England and their corresponding nine local authorities (LAs), to establish how they addressed their responsibilities for women with social care needs eight years on from the 2014 Care Act. Numerical and pre-coded data were analysed in Microsoft Excel using simple descriptive methods (e.g., frequencies, percentages). Descriptive qualitative analysis was used on free-text data. The LA survey was completed by 9/9 LA staff; the prison governor survey by 8 staff (representing 10/11 prisons); and the healthcare manager survey by 7/11 staff. Considerable variation was found between establishments in Care Act assessment rates (1% to 36%). Some prisons relied on prison officers or peer supporters who had not received adequate training/supervision to identify social care needs, although all respondents agreed that social care provision had improved since the Care Act. There was less agreement regarding arrangements for transferring assessments between LAs on release. Qualitative analysis provided insight into this and other problems, including identifying women with social care needs; transferring information; gaining access into the prison; and resolving disputes/disagreements between LAs. Several proactive initiatives to improve identification/provision, and promote wellbeing, were described (e.g., regular drop-ins; scoping the use of telecare; linking with external agencies (e.g., neurodiversity and sensory services); an enablement/reablement pathway; and advocacy). This paper is the first to explore social care provision for women in prison in relation to the 2014 Care Act. Although provision has grown and improved since the implementation of the Act, it is patchy and often suboptimal or "gets forgotten". Potential ways forward include standardised, flexible screening processes; gender-specific adaptation of screening/assessment tools; and social care training and supervision for officers and peer supporters.
The CRISPR/Cas12a system has emerged as a powerful tool for biosensing due to its high specificity, sensitivity and programmability. However, direct RNA detection is hindered by its inherent DNA-targeting trans-cleavage activity, which typically necessitates a reverse transcription amplification to convert RNA into DNA. Herein, we report a one-pot assay that enables direct detection of microRNA-21 without target amplification. The method employs a molecular switch probe (MSP) that recognizes miRNA-21 and activates Cas12a activity, along with an amplifier probe (AMP) that establishes a self-driven cascade signal amplification. This biosensor achieves a detection limit of 2.88 pM, with high accuracy (recovery of 95.5%-108.6%) and good precision (RSD: 2.35%-7.18%), and exhibits excellent specificity against homologous miRNAs. Using this assay, we successfully quantified the elevated levels of miRNA-21 in lung squamous carcinoma (H520) cells compared to normal bronchial epithelial cells (BEAS-2B). Furthermore, a methodological comparison with RT-qPCR revealed a similar trend between the two methods. This study provides a simple and reliable strategy for direct RNA detection using CRISPR/Cas12a.
Traditional aptamer screening methods often prove ineffective for small molecule targets, primarily due to the inherent structural limitations of such compounds. Their simple architecture, limited functional groups, and restricted spatial complexity drastically reduce the probability of identifying nucleic acid sequences that bind with both high affinity and specificity. Consequently, the screening process becomes inefficient and labor-intensive, frequently failing to yield aptamers of satisfactory performance for practical applications. This represents a significant technical hurdle in expanding the use of aptamers in small-molecule detection and therapeutics. Based on this, this study innovatively proposes an aptamer design method based on single-nucleotide docking assembly, using the small molecule temicloxacin as an example. Through molecular dynamics simulations (50 ns, RMSD convergence threshold of 0.15 nm), the dynamic conformational characteristics of tilmicosin were analyzed. Subsequently, saturated docking was performed on four classes of mononucleotides, screening out 32 high-affinity mononucleotides (atomic contact distance ≤4 Å). Methods such as depth-first search algorithm (DFS) and weighted graph theory model were introduced to obtain the representative single nucleotides of eight classes of functional modules and linkage assembly, and finally 63 non-redundant candidate sequences were screened. Molecular docking results indicate that the optimal aptamer Til-14 exhibits high binding affinity with tilmicosin. with an affinity of 298.16 ± 95.588 nM measured via SYBR Green I fluorescence assay. Colloidal gold colorimetric analysis confirmed its high affinity (Kd = 279.323 ± 87.234 nM) and excellent specificity. This innovative method successfully addresses the key limitations of the traditional SELEX process in screening aptamers for small molecule targets. By enhancing the efficiency and specificity of selection, it not only facilitates the discovery of high-performance aptamers but also establishes a novel, generalizable framework for the construction of nucleic acid aptamers targeting other small molecules.
Microbubbles are clinically approved as ultrasound contrast agents because they oscillate in response to ultrasound (cavitation) and are increasingly explored for therapeutic applications. Microbubble diameter governs dynamic behaviour under ultrasound; therefore, a narrow size distribution is essential for predictable performance and optimal responsiveness. However, producing phospholipid-coated microbubbles with narrow distributions using simple methods remains challenging. This study evaluated a bead-type tissue homogeniser as an alternative to probe sonication for generating DSPC-PEG40S (9:1), air-filled microbubbles, using design of experiments (DoE) to identify influential parameters. A three-level full-factorial design assessed effects on mean diameter, concentration, and polydispersity index (PDI). Optical microscopy with an ImageJ analysis pipeline quantified size and concentration, while passive cavitation detection characterised acoustic response. Liquid volume significantly affected mean diameter, concentration, and PDI, whereas homogenisation speed significantly influenced PDI only. Response optimisation identified 5 m·s⁻1, 45 s, and 500 µl as optimal speed, time, and volume settings. Compared with sonication, homogenisation generated less heat and achieved higher production rates. Resulting microbubbles were smaller, more uniform in size, and higher in concentration. At 37 °C, homogenised suspensions remained above 108 MB/ml at 6 h, indicating improved short-term stability. Acoustic emissions increased with pressure and were comparable between methods when normalised to gas volume. Overall, bead homogenisation offers a simple, less thermogenic, high-throughput method for reproducible phospholipid microbubble production.
Men show a higher mortality than women, especially at a young age (between 15 and 39 years). They are more likely to engage in unhealthy behaviours and tend not to implement preventative efforts or to seek help. While (mental) health promotion programmes aim to foster healthy behaviours, men often do not feel addressed by them and are therefore reluctant to participate. This synthesis aims at drawing together barriers to and facilitators of male participation in (mental) health promotion programmes and identifying how to best address men in health communication and programme promotion. This rapid qualitative evidence synthesis includes a sample of 21 studies. 18 are qualitative studies and 3 are mixed-methods studies with separately reported qualitative findings that captured the perspectives of males aged 12 to 79 years and of professionals working in men's health on the barriers to and facilitators of participation in (mental) health promotion programmes and on preferred health communication. Studies were purposefully selected to maximise variation across interview content, context, and participant characteristics (e.g., age, occupation). The selection was restricted to studies published between 2015 and 2025. Gender norms were one of the main barriers to participation in men's (mental) health promotion programmes. Preferably such programmes should be integrated into settings attractive or familiar to men, such as sport clubs or handicraft workshops, or the workplace. Peers and peer support played a crucial role within men's health promotion and were found to facilitate positive behavioural changes. When reaching out to men, clinical and stigmatising terminology should be avoided in favour of action-oriented language that emphasises control and practical solutions while keeping the messaging simple and focused on tangible benefits. Health promotion programmes for men require embedding interventions within male-relevant contexts, such as sports, workplaces, and peer networks, that ease participation and reduce stigma. To reach and benefit men, communication strategies should use relatable, non-stigmatising language from credible messengers and should frame self-care as compatible with masculine identities.
With increasing global life expectancy, population aging has become a major public health issue. Poor sleep quality and fatigue are prevalent among older adults, negatively impacting their quality of life and daily functions. While pharmacological interventions for sleep disorders are common, they carry significant side effects, especially in the older individuals. Non-pharmacological alternatives like white noise are simple, safe, and cost-effective, yet evidence for their effectiveness among community-dwelling older adults remains limited. This study aims to evaluate the effectiveness of white noise on improving sleep quality and reducing fatigue among community-dwelling older adults. This parallel RCT was conducted among 60 individuals 65 years and older attending healthcare centers in Mashhad, Iran. After the initial screening, eligible participants were randomly assigned into two groups. Both groups received standard sleep hygiene recommendations based on provincial guidelines. Additionally, the intervention group was provided with audio options and were instructions to use them over the next 30 consecutive nights. Constant follow-ups ensured adherence. Sleep quality and fatigue were measured using PSQI and IFS pre- and post-intervention. Group differences over time were examined using repeated measures and baseline adjusted analyses. Descriptive and inferential data analysis was performed using SPSS 27 at a significance level of p < 0.05. Post-intervention results show that there is a statistically significant difference between the two groups in both PSQI and IFS scores. Our results show significant improvement in the intervention group's PSQI (from 11.5 ± 2.8 to 9.2 ± 3.1, P < 0.001) and IFS scores (from 35.1 ± 3.5 to 32.4 ± 4.9, P < 0.001), with no significant changes in the control group. Our findings suggest that the use of white noise can result in improving sleep quality and may be helpful in reducing fatigue in community-dwelling older adults and can be recommended as an low effort, low-cost and safe strategy to enhance sleep and reduce fatigue in older individuals. (IRCT20240812062732N1), Date of registration August 28, 2024.