Respiratory infections have high mortality, exacerbated by frequent co-infections and antimicrobial resistance, posing challenges for timely, accurate diagnostics. Arrays offer multiplex pathogen detection, but remain limited by complex instrumentation, complex probe design, and poor universality. Here, a programmable and universally applicable array platform, termed the universal cascade amplification molecular signal conversion system (UCSC), is established with a core based on flap endonuclease 1 (FEN1)-mediated linear amplification reaction (LIAR) coupled with hybridization chain reaction (HCR). Target-independent flap sequences encoded in the primers serve as universal mediators, decoupling target recognition from signal output. Upon recognition, the flap initiates LIAR to amplify the universal sequence, which subsequently triggers HCR-driven isothermal selfassembly of DNA nanowires on the array for direct visual readout. This cascade amplification strategy establishes precise correspondence between recognition, amplification, and signal output, overcoming the "application-specific" limitation of traditional arrays. The platform enables multiplexed detection of nine respiratory pathogens with high sensitivity (1.13-1.25 copies & sdot;mu L- 1) and specificity, completing the workflow within 70 min without sophisticated equipment. Unlike qPCR requiring thermocycling or most isothermal methods needing target-specific redesign of both recognition and amplification primers, UCSC interrogates new targets by replacing only the recognition primers, while downstream amplification modules and arrayed probes remain fixed, enabling a single chip to perform versatile, multiplexed diagnostics across pathogens and molecular analyses, including serotyping, antibiotic resistance, methylation, and single-nucleotide polymorphisms, establishing a broadly deployable toolkit that operates without reliance on dedicated laboratory instruments and supports smartphone-based readout, offering strong potential for pathogen detection in resource-limited and epidemiological surveillance.
Rapid and sensitive detection of airborne respiratory viruses from exhaled breath is essential for early diagnosis and outbreak control, yet current strategies suffer from low capture efficiency and sample dilution. Here, we present a fully automated, noninvasive Phase-change Drywall Cyclone Sampler (PDC-sampler), which integrates phase-change condensation with a CFD-optimized cyclone gas-liquid separator. This design rapidly condenses viral aerosols─particularly those <5 μm─into microdroplets and directs them into a stable spiral liquid stream, thereby enhancing capture efficiency and producing a small-volume, high-concentration liquid sample. The collected condensate is directly coupled to a microfluidic RNA-release chip, enabling on-chip viral RNA lysis. From a single tidal exhalation (∼0.5 L), the system generates ∼20 μL of high-concentration RNA lysate in 10 s of on-device processing (sample-to-lysate), directly compatible with nucleic acid detection. Combined with ddPCR, it achieves detection limits as low as 5-9 copies per exhalation for pathogens including SARS-CoV-2 and H1N1 influenza. This ultrarapid, small-volume, sample-to-result workflow provides a scalable, field-deployable solution for point-of-care diagnosis and real-time respiratory virus surveillance.
OBJECTIVE:To assess the effectiveness of dry needling (DN) in reducing spasticity among post-stroke patients through meta-analysis. DATA SOURCES:PubMed, Web of Science, PEDro, Cochrane Library, CINAHL, and Embase were searched up to April 2026, alongside manual searches of reference lists. STUDY SELECTION:Randomized controlled trials (RCTs) involving adults (>18 years) with post-stroke spasticity, investigating DN alone or as part of a multimodal intervention, were included. DATA EXTRACTION:Two reviewers independently extracted data, primarily focusing on changes in the Modified Ashworth Scale (MAS) and the Modified Modified Ashworth Scale (MMAS). DATA SYNTHESIS:Eleven RCTs (276 patients) were included. Overall, DN significantly reduced spasticity compared to the control group (mean difference [MD] = -0.65). DN was effective for both upper (MD = -0.40) and lower limbs (MD = -1.02), with the most robust effect in ankle plantar flexors (MD = -1.05). Significant improvements occurred whether DN was compared to sham interventions (MD = -0.45) or added to conventional neurorehabilitation (MD = -0.76). While study quality was generally high (PEDro scores 5-9/10), GRADE certainty was Moderate to Low due to small sample sizes and blinding bias. CONCLUSIONS:DN is an effective short-term intervention and a potent adjunct to standard rehabilitation for reducing post-stroke spasticity in both upper and lower extremities. Further research is needed to evaluate its long-term functional impact.
Exhaled breath is a noninvasive and repeatable biological matrix offering new opportunities for respiratory microbiome analysis, yet its extremely low microbial biomass limits current high-throughput applications. Building on our previously developed phase-change drywall cyclone sampler (PDC-sampler), which integrates condensational growth with dry-wall cyclone separation, we established a validated workflow for efficient aerosol collection and multi-Omics sequencing of exhaled breath. Using this platform, exhaled breath from 15 febrile patients and 6 healthy volunteers was analyzed via shotgun metagenomic and 16 S rRNA sequencing to assess microbial composition, diversity, and functional features. The PDC-sampler significantly increased microbial DNA yield, enabling stable detection of bacterial taxa dominated byPseudomonadota, Bacillota, Bacteroidota, andActinomycetota. Functional annotations and diversity metrics revealed distinct microbial and metabolic patterns between individuals, confirming the platform's analytical sensitivity and biological representativeness. This work experimentally validates the feasibility of exhaled breath microbiome sequencing using the PDC-sampler, providing a practical and generalizable framework for noninvasive respiratory microecology studies and future diagnostic applications.
ObjectiveTo examine the psychometric properties of the Chinese version of the Survey of Activities and Fear of Falling in the Elderly (SAFE-C) in community-dwelling patients with chronic stroke using the Rasch analysis model and to generate a keyform to enhance its clinical utility.MethodsA secondary data analysis was conducted based on an original study that recruited 108 community-dwelling patients with chronic stroke in Hong Kong. Rasch analysis was performed on the 11 items of the SAFE-C using Winsteps software (version 3.72.3) to evaluate the rating scale structure, unidimensionality, item fit, reliability, local independence, matching, and differential item functioning (DIF), and to generate a key form.ResultsThe 4-level rating scale of the SAFE-C demonstrated a valid structure, and its unidimensionality was substantially supported. All items showed good fit to the Rasch model (MNSQ: 0.5-1.5). The person separation reliability was 0.81, and the person separation index was 2.06, indicating that the scale could differentiate patients into three ability strata. No substantial DIF related to age or gender was found. The key form identified a "transition zone" of fear perception, which included Item 8 (reaching for an object above the head), Item 1 (going to a store), Item 10 (walking several blocks outdoors), and Item 7 (visiting relatives or friends). Local dependence was observed for three item pairs: Item 4 (getting up) with Item 5 (walking for exercise) (r=0.44), Item 3 (bathing in a tub) with Item 5 (r=0.35), and Item 5 with Item 9 (going to crowded places) (r=0.33). The person-item map showed that the mean person ability (1.38 logits) was higher than the mean item difficulty (set at 0 logits), with a slight ceiling effect (4.63%), and the item difficulty was insufficiently distributed in the high-ability region, which restricted measurement precision for patients with better functional mobility.ConclusionThe SAFE-C demonstrates acceptable reliability, unidimensionality, and item fit in community-dwelling patients with chronic stroke, and the key form enhances its clinical translation potential. The survey presents limitations including local dependence and insufficient differentiation for high-ability patients. Future revisions may consider merging relevant items, adding more challenging activities, and bridging difficulty gaps to further optimize its measurement performance.
Objective To estimate the effect of focal muscle vibration (FMV) on post-stroke upper limb spasticity and explore whether frequency, amplitude, or target joint moderates effects. Data Sources PubMed, EMBASE, Web of Science, CINAHL, PEDro, and Cochrane Central Register of Controlled Trials were searched from inception through March 2026. Study Selection Studies of adults with post-stroke upper limb spasticity were eligible if they applied FMV to the upper limb and reported the Modified Ashworth or Tardieu Scale. Controlled parallel, randomized crossover, and comparative repeated-measures studies were eligible, including peer-reviewed reports and preprints with sufficient outcome data. Data Extraction Two reviewers independently extracted data and assessed risk of bias. Hedges' g was calculated from pre-to-post change scores and synthesized with a three-level random-effects model (restricted maximum likelihood). Certainty was assessed with GRADE. The review was registered in PROSPERO (CRD420251181549). Data Synthesis Eleven reports representing 11 independent participant samples contributed 32 effect estimates from 285 participants assigned to or receiving an FMV condition. The three-level pooled effect was g=-0.526 (95% CI, -0.742 to -0.310; p<.001). All three frequency-band estimates favored FMV, with 95% CIs below zero, and no differences were detected among frequency bands (Wald; p=.948); continuous frequency was not associated with effect size (β=0.00117 per Hz; 95% CI, -0.00117 to 0.00352; p=.326). All 12 finger estimates were negative. Leave-one-out analyses retained confidence intervals below zero, and Egger's regression on 10 independent report-level aggregates suggested possible small-study effects (bias coefficient=-6.10; p=.002). Certainty in the primary outcome was moderate. Conclusions FMV probably reduces post-stroke upper limb spasticity. The antispasticity effect was observed across the 30-300 Hz range studied, with no frequency-related modification detected, and finger estimates showed the most uniform effect direction. These findings support flexible frequency selection within studied protocols. Larger trials are needed to refine amplitude, dose, and muscle targeting.
Objective This study aimed to precisely quantify the individual and interactive effects of ankle-knee angles and spasticity grades on passive acoustic and biomechanical properties of the Achilles tendon in post-stroke patients, using shear wave elastography (SWE) - an angle-specific, non-invasive biomarker for static passive tendon assessment. Methods A prospective cohort study was carried out. Two - dimensional ultrasound and SWE were employed to measure the structural parameters and material properties of the triceps surae/Achilles tendon (AT) at various ankle/knee positions in 35 post - stroke patients. Spasticity was evaluated using the Modified Ashworth Scale (MAS). Log - transformed mean Young's modulus (YM) and shear - wave velocity (SWV) data were analyzed via a linear mixed - effects (LME) model. Results The injured side had higher: gastrocnemius medialis (GM)/soleus (SOL) YM and SWV (all P ≤ 0.027) and increased AT thickness in neutral ankle positions (P ≤ 0.039). LME models explained 68.6% (YM) and 71.9% (SWV) of total variance. Ankle dorsiflexion significantly increased AT stiffness (YM β = 0.270; SWV β = 0.320, all P < 0.001), whereas knee extention produced smaller but significant increments (YM β = 0.140, SWV β = 0.160, all P < 0.001). with marginal ankle - knee interaction (P = 0.060–0.084). Spasticity grade (MAS 0 - 2) and higher - order interactions had no significant effects (all P > 0.05). Conclusion Joint angle has a greater impact than spasticity grade on prone-measured passive post-stroke Achilles tendon stiffness, with marginally significant ankle-knee interactions. SWE is a non-invasive, angle-specific biomarker for static passive AT mechanical assessment.
Photonic crystal (PC) biosensors have been widely used in protein detection, leveraging their cost-effectiveness and operational simplicity. However, they confront challenges in balancing detection sensitivity and analysis speed. In this paper, an intelligent biosensing platform integrating a PC-plasmonic nanoantenna (PC-PN) coupling system with an optimized UNet model was constructed. By precisely tuning the localized surface plasmon resonance (LSPR) properties of Au@Ag-Au core-shell nanoparticles, efficient coupling with the intrinsic resonance of PC is achieved. Angle-resolved spectroscopy (ARS) was employed to acquire multi-dimensional spectral datasets in 10 s, replacing conventional single-point reflectance spectral measurements that require 1-2 h. An optimized UNet model, featuring hierarchical feature fusion and anti-noise convolutional layers, was designed to establish a regression model for target protein concentration. Using interleukin-6 (IL-6) as target protein, the system exhibits linear detection over the range of 5-100 pg/mL, with a detection limit as low as 5 pg/mL. Notably, the entire detection process, from biosensing interface identification to AI-driven concentration prediction, can be completed within 15 min, which satisfies the requirements of both high sensitivity and rapid PC-based sensing.
OBJECTIVE:This study aimed to investigate the activation characteristics of submental muscle (SM) and infrahyoid muscle (IM) in response to expiratory and inspiratory muscle training (EMT/IMT) at varying resistance loads in patients with poststroke dysphagia. METHOD:Twenty participants with poststroke dysphagia underwent surface electromyography during 5-ml water swallowing and graded EMT/IMT tasks. Key parameters including amplitude, duration, and root mean square (RMS) were analyzed. Statistical analysis was performed using repeated-measures analysis of variance or the Friedman test, with post hoc Bonferroni correction for multiple comparisons. RESULTS:The peak amplitude of SM at 75% and 100% maximum expiratory pressure (MEP) was significantly higher than at lower MEP intensities (e.g., vs. 25% MEP, p = .002 and p < .001; vs. 50% MEP, p = .012 and p = .003) and all IMT intensities (all ps < .05). IM amplitude increased significantly at 80%-100% maximum inspiratory pressure (MIP), exceeding both the swallowing task and all EMT tasks (all ps < .05). Except for the affected-side IM during the 80% and 100% MIP tasks, the activity duration of both SM and IM was significantly longer during the 100% MEP task compared to other MEP intensities and all IMT tasks (all ps < .05). RMS values for both muscle groups were elevated at higher respiratory muscle training (RMT) levels. No consistent side-to-side differences were found in most parameters. Borg Dyspnea Scale scores increased progressively with training intensity, with significant differences between high-intensity tasks (e.g., 100% MEP vs. 25% MEP, p < .001; 100% MEP vs. 50% MEP, p = .002; 100% MIP vs. 30% MIP, p < .001). CONCLUSIONS:EMT preferentially activates the SM group in a load-dependent manner, while IMT selectively recruits IM. These findings support the use of targeted, intensity-specific RMT for enhancing swallowing-related muscle activation in rehabilitation.
BackgroundClosed-loop motor imagery brain-computer interface (MI-BCI) training may support post-stroke upper-limb rehabilitation by coupling motor intention with contingent multisensory feedback. This randomized pilot trial examined its feasibility, safety, short-term clinical effects, and exploratory EEG correlates in patients with subacute stroke.MethodsIn this single-center, assessor-blinded, two-arm pilot trial, 40 patients with first-ever subcortical stroke in the subacute phase were randomized 1:1 to a BCI group or an active control group after a 2-day motor imagery familiarization phase. Both groups received routine medical management, standardized conventional rehabilitation, and dose-matched motor imagery-based hand training for 4 weeks. The BCI group received EEG-contingent closed-loop MI-BCI-assisted training with a soft rehabilitation glove, whereas the control group received non-EEG-contingent glove-assisted motor imagery training under matched training duration, task instructions, device exposure, and multisensory feedback. The primary outcome was the Fugl-Meyer Assessment for the Upper Extremity (FMA-UE). Secondary outcomes included the Action Research Arm Test (ARAT) and Modified Barthel Index (MBI). Exploratory EEG outcomes included FFT%α and FFT%β during motor imagery. Clinical and EEG outcomes were analyzed using baseline-adjusted ANCOVA models, with week-4 values as dependent variables and corresponding baseline values as covariates.ResultsAll randomized participants completed the 4-week assessment. In baseline-adjusted ANCOVA models, the BCI group showed higher week-4 scores than the control group for FMA-UE (adjusted mean difference, 13.40 points; 95% CI, 10.71–16.08; p < 0.001), ARAT (7.31 points; 95% CI, 4.55–10.07; p < 0.001), and MBI (12.21 points; 95% CI, 8.55–15.87; p < 0.001). Exploratory EEG analyses also showed higher week-4 FFT%α and FFT%β in the BCI group, with adjusted mean differences of 6.78 percentage points (95% CI, 5.22–8.34; p < 0.001) and 3.95 percentage points (95% CI, 2.53–5.36; p < 0.001), respectively. No serious adverse events occurred.ConclusionClosed-loop MI-BCI-assisted training was feasible and well tolerated in selected patients with subacute stroke. The observed short-term improvements in upper-limb impairment and activity capacity provide preliminary signals of potential benefit beyond dose-matched non-EEG-contingent feedback training. Exploratory EEG findings suggest task-related modulation of alpha- and beta-band sensorimotor rhythmic activity, but should be interpreted as hypothesis-generating rather than confirmatory evidence of neural reorganization. Larger multicenter trials with longer follow-up, rigorous neurophysiological analyses, and real-world upper-limb use outcomes are needed.Clinical Trial RegistrationChiCTR2400083992. https://www.chictr.org.cn/showproj.html?proj=229529
Background:There have been many studies on the relationship between sex hormones and stress, mood, blood pressure, etc., but its impact on the incidence of stroke remains unknown. Objective:To investigate the expression levels of hypothalamic-pituitary-gonadal (HPG) axis related hormones such as testosterone (T) and progesterone (P) in hair before stroke and their effects on the risk of stroke. Methods:48 patients with stroke were recruited from November 2022 to May 2023 as the observation group and 35 healthy subjects were recruited as the control group. There was no obvious difference in age, gender and BMI between the two groups (p > 0.05). T and P levels in hair were tested by LC-MS/MS, and the correlation with the risk of stroke was analyzed. Results:The T and P levels of hair before the onset of stroke in the observation group were significantly lower than those in the control group (p < 0.01). The T level of men's hair before the onset of stroke in the observation group was significantly lower than those in the control group (p < 0.05). The T and P levels of women's hair before the onset of stroke in the observation group were significantly lower than those in the control group (p < 0.01). The results of ROC curve showed that the cut-off value of T level in men's hair before the onset of stroke was 4.35 pg/mg, the AUC was 0.690 (0.545, 0.835), the sensitivity was 62.50%, and the specificity was 82.61%. The cut-off value of T level in women's hair before the onset of stroke was 5.00 pg/mg, the AUC was 0.818 (0.658, 0.978), the sensitivity was 75.00%, and the specificity was 83.33%. The cut-off value of P level in women's hair before the onset of stroke was 8.00 pg/mg, the AUC was 0.891 (0.754, 1.000), the sensitivity was 81.25%, and the specificity was 100.00%. Conclusion:This preliminary report is the first to suggest that HPG axis hormones such as T and P in hair could have predictive value in screening for stroke risk.
This study established human cerebral organoids as a promising platform for investigating central nervous system oxygen toxicity (CNS-OT). Through integrated transcriptomic, functional, and pharmacological analyses, we demonstrate that hyperbaric oxygen (HBO) exposure triggers pressure-dependent neurotoxicity mediated by the reactive oxygen species (ROS)–lysosome–mechanistic target of rapamycin (mTOR) axis. Key findings include the following: mechanistic hierarchy: Five atmospheres absolute (ATA) HBO induces metabolic dysregulation and cell cycle arrest, whereas six ATA exceeds compensatory thresholds, triggering overt apoptotic signatures; pathway crosstalk: Lysosomal permeabilization activates mTOR complex 1 (mTORC1) via cathepsin release, while mTORC1 hyperactivation suppresses transcription factor EB (TFEB)-mediated lysosomal regeneration, creating a self-amplifying loop; therapeutic potential: Mouse validation confirmed that mTOR inhibition (temsirolimus) attenuates neurotoxicity, with hippocampus-specific efficacy. The cerebral organoid model offers a human-relevant system to overcome species limitations in neurotoxicity research, facilitating mechanistic discovery and therapeutic target identification.
Investigating the transcriptome while preserving cellular spatial information facilitates a comprehensive understanding of cellular fates in multicellular organisms. However, the precise and flexible isolation of micro-regions of interest (mROIs) for profiling spatial transcriptomics (ST) remains a challenge. We established a capillary-based tissue microdissection system (CMS), which enables the high-efficiency acquisition of mROIs from cultured cerebral organoids for mRNA sequencing (CMS-seq). Subsequently, neural progenitor cells (NPCs), intermediate progenitors (IPs), mature neurons, and astrocytes were annotated in the cerebral organoids at the stages of days 20 and 60, respectively. Furthermore, astrocytes in the samples from day 20 were found to exhibit a higher tendency to express the SPARC gene whereas those from day 60 showed a stronger tendency to express the NTRK2 gene. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes indicated a higher degree of neural development at the stage of day 60. Finally, a spatial annotation map of cell types of the mROIs was constructed, enabling rapid identification of the cellular composition in each mROI. Therefore, we established an efficient method for ST analysis in cerebral organoids and further exploration of the spatial developmental trajectory.
Bacterial infections are highly prevalent globally, and the health issues they induce often lead to numerous severe problems for human well-being, demanding timely and accurate detection strategies. Herein, We developed a universal electrochemical biosensor for pathogen screening, offering high sensitivity, specificity, rapidity, and multiplex detection. The platform integrates interdigitated electrodes for low-voltage pathogen lysis and nucleic acid release with asymmetric recombinase polymerase amplification (aRPA) to produce single-stranded DNA, simplifying extraction and reducing detection time. Screen-printed electrodes were carboxylated using diazonium salts to immobilize Fc-labeled hairpin DNA via amide bonds. Upon applying a positive voltage, amplified DNA hybridizes with the hairpin probes, distancing Fc molecules from the electrode surface and diminishing electrochemical signals, effectively eliminating false positives. Optimized conditions enabled detection sensitivities of 10 CFU/mL for Staphylococcus aureus and 5 CFU/mL for Acinetobacter baumannii. Additionally, Spiked testing in tap water, milk, and lake water demonstrated consistency with plate counting, validating the rapid system's accuracy and applicability. Remarkably, the assay time was reduced from 6 to 8 h to 25 min while maintaining pathogen specificity. This biosensor shows promise for foodborne pathogen surveillance, environmental monitoring, and point-of-care diagnostics, offering a streamlined platform for rapid, accurate pathogen identification.
BACKGROUND:Ultrasound (US) has been widely used in the treatment of plantar fasciitis (PF); however, its therapeutic effect remains unclear. OBJECTIVE:This meta-analysis aimed to investigate the effects of ultrasound (US) on pain intensity and foot function in patients with PF. METHODS:PubMed, Web of Science, Cochrane Library, and other databases were systematically searched from inception to July 2024. Meta-analysis was performed using RevMan 5.3. RESULTS:Thirteen trials were performed. There was no difference in pain relief between US alone and no treatment, as was US plus conventional physical exercises (CPE) compared with CPE alone. In the comparison between the US plus CPE group and the other interventions plus CPE group, there was a statistically significant difference in pain intensity (MD = 0.78, 95%CI= 0.12 to 1.44, p = 0.02), except in the case where extracorporeal shock wave therapy (ESWT) acted as an "other intervention" (MD = 0.75, 95%CI= -0.28 to 1.78, p = 0.15). The foot function measured in the Foot Function Index (FFI) showed a statistically significant difference between the two groups (MD =9.20, 95%CI = 0.77 to 17.63, p = 0.03), while the American Orthopaedic Foot showed no statistically significant difference. CONCLUSION:Whether applied alone or in combination with CPE, US cannot reduce pain intensity in patients with PF. However, US in combination with CPE may improve foot function.
BACKGROUND:Aspiration is the most severe complication of dysphagia in patients with poststroke dysphagia (PSD). However, the risk factors associated with aspiration remain inadequately understood. OBJECTIVE:To determine the associated risk factors for aspiration in patients with PSD. METHODS:A total of 321 dysphagia patients with first-ever stroke were retrospectively enrolled. We differentiated patients with aspiration from those without aspiration via swallowing function screening, clinical swallowing function examinations, and videofluoroscopic swallowing studies. We conducted a comparative analysis of the basic demographic data, disease-related information, and clinical characteristics between the two groups via multivariate logistic regression. RESULTS:Multivariate logistic regression analysis revealed that age ≥ 65 years (OR = 3.596, 95% CI: 1.251-10.335), history of pneumonia (OR = 3.617, 95% CI: 1.174-11.148), severe dysarthria (OR = 7.331, 95% CI: 1.314-40.889), number of chronic diseases > 2 (OR = 4.814, 95% CI: 1.61-14.397), bilateral brain injury (OR = 6.673, 95% CI: 1.926-23.115), a lesion location in the brainstem (OR = 4.581, 95% CI: 1.05-19.987), and a higher water swallowing test score (OR = 1.806, 95% CI: 1.113-2.93) were risk factors for aspiration. Conversely, a high Montreal Cognitive Assessment (MoCA) score (OR = 0.919, 95% CI: 0.849-0.995) and a high cut-off value of the repetitive saliva swallowing test (RSST) (OR = 0.149, 95% CI: 0.067-0.332) were identified as protective factors. DISCUSSION:Timely diagnosis and intervention for aspiration should prioritise patient populations aged 65 years and older, individuals with a history of pneumonia, those exhibiting severe dysarthria, patients with multiple chronic conditions, individuals with bilateral brain injuries, patients with lesions situated in the brainstem, and those exhibiting higher WST scores. TRIAL REGISTRATION:This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2500097142).
Interleukin-6 (IL-6) is a crucial cytokine involved in inflammation and immune regulation. However, the detection of IL-6 with ultrasensitivity and high specificity remains a significant challenge due to the inherent complexity of biofluids. Herein, we present a digital surface enhanced Raman scattering (SERS) immunoassay using core-shell Au@Ag-Au nanotags for IL-6 detection with ultrasensitivity and high reliability. A low-cost silicon chip was functionalized as capture substrates, employing novel SERS nanotags that exhibit strong, robust and reproducible signals at single-nanoparticle resolution as the amplification element. We proposed two analytical methods to validate single-molecule events follow a Poisson distribution and to quantify protein biomarkers over a broad linear dynamic range, respectively. The strong alignment between theoretical and experimental results enhances the method's reliability. Our assay provides two readouts: colorimetric analysis by naked eyes for high concentrations (>1 ng/mL) and digital SERS analysis for low concentrations. Following method optimization, we obtained a linear range from 100 fg/mL to 1 ng/mL (R2 = 0.994) with a limit of detection (LOD) of 12.4 fg/mL, suitable for clinical applications. The method was tested for IL-6 quantification in healthy human serum and saliva, with recoveries from 92.4% to 105.3%. Finally, the immunoassay demonstrated strong consistency with the standard clinical laboratory method when tested with clinical serum samples. Thus, our proposed the digital SERS immunoassay is a promising tool for the precision clinical diagnosis of IL-6-related diseases or other conditions.
BACKGROUND:During intense exercise, anaerobic metabolism predominantly produces energy in the body, resulting in lactic acid (LA) accumulation, which contributes to muscle fatigue and soreness and may also impair neurological and cardiovascular functions. In endurance sports, the lactate threshold (LT) is a key indicator of an athlete's capacity to clear and utilize LA, directly influencing athletic performance and endurance. Therefore, LA detection is crucial for assessing the physical condition of both athletes and the general population, as well as for optimizing training programs. RESULTS:A set of surface-enhanced Raman scattering (SERS)-active microneedle (MN) arrays, developed by integrating gold nanoshells (GNSs), 4-mercaptobenzeneboronic acid (4-MPBA) and lactate oxidase (LOD) onto a MN array in turn, were inserted into skins to sense LA. Then mice in different physiological states and under different exercise intensities were used to verify the feasibility of the SERS-active MN array, respectively. After swimming for 3 and 6 min, the LA concentration of forelimb and hindlimb ISF of normal mice increased from 1.94 ± 0.33 mM and 2.41 ± 0.67 mM to 2.71 ± 0.28 mM and 8.12 ± 1.05 mM, and 6.43 ± 3.79 mM and 13.85 ± 2.51 mM, respectively, and the LA concentration of forelimb and hindlimb ISF of fasting mice increased from 2.97 ± 0.26 mM and 2.84 ± 0.23 mM to 3.62 ± 0.66 mM and 7.25 ± 1.40 mM, and 5.32 ± 1.99 mM and 13.07 ± 1.05 mM, respectively. SIGNIFICANCE:This study is the first to identify differences in LA production between fasting and normally fed animals. Furthermore, fasting led to an increase in baseline LA levels, though the rate of LA accumulation during exercise was lower compared to normal feeding conditions. With further optimization, this method would become a safer and more effective tool for exercise training and rehabilitation guidance for both athletes and the general population.
The evaluation of balance and postural stability holds significant importance in both medical rehabilitation and daily life. However, the clinical method is hindered by the inconvenience of immobility and relatively high costs associated with the force platforms. Wearable sensors, such as accelerometers, have emerged as an alternative solution, overcoming the limitations of traditional force platforms. Thus, the purpose of this study is to utilize data obtained from a low-cost, portable, small-sized IMU (specifically an accelerometer) to predict indicators derived from force platform devices. A miniaturized and portable acceleration test equipment was proposed. Together with the random forest algorithm, our classification method achieved classification results with accuracy, recall, precision, f1-score, and specificity scores above 95%, This study provides a more portable and highly accurate tool for assessing balance ability.
Objectives Stroke-induced cognitive and mood disorders are closely related to glucocorticoids released during hypothalamic-pituitary-adrenal (HPA) axis activation. There are many studies on the relationship between cortisol levels and post-stroke cognitive impairment (PSCI) and post-stroke depression (PSD). This paper provides a scoping review of these studies to clarify the effect of cortisol on PSCI and PSD, thereby providing a theoretical basis for clinical diagnosis and treatment. Materials and methods We searched for literature published up to October 2023 on the association of cortisol with post-stroke cognitive and emotional disorders in the PubMed, Web of Science, Cochrane Library, CNKI and Wanfang databases. Relevant papers were identified and the effects of cortisol on cognitive and emotional disorders after stroke were analyzed by literature induction. Results Eighteen papers were included, including cross-sectional studies and cohort studies. The subjects suffered ischemic stroke or hemorrhagic stroke. Cortisol levels were measured from samples of blood, saliva or hair. Most patients showed increased basal cortisol levels and changes in cortisol circadian rhythms. Most studies report that patients with high cortisol levels on admission (acute phase of stroke) are more likely to experience cognitive decline and depression later in life. Conclusions Admission cortisol level may be a promising biomarker for predicting cognitive and emotional prognosis after stroke.