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PubMed2026

Engineered MXene-based nanozyme platform: NIR-II photothermal and dual enzyme-mimetic potentiated chemodynamic synergy for precision tumor eradication.

The antioxidant defense barrier in the tumor microenvironment, particularly glutathione (GSH), considerably restricts the therapeutic efficacy of chemodynamic therapy (CDT). Moreover, CDT generally exhibits relatively mild therapeutic efficacy owing to its intrinsic reaction kinetics, making it difficult to achieve complete tumor eradication within a short time. To address these issues, we construct a functionalized nanotherapeutic platform, Nb2CTx@Ru-PEG2000-FA (NCRPF), for tumor photothermal ablation and enhanced CDT resulting from GSH depletion. NCRPF possesses three key advantages: 1. Efficient near-infrared II photothermal conversion (η = 42.08%), raising the tumor temperature above 45 °C within 90 s for rapid ablation; 2. Dual peroxidase-like and glutathione peroxidase-like activities, simultaneously depleting GSH and generating a burst of ·OH to eliminate residual tumors; 3. Targeted tumor accumulation with 2.9-fold higher efficiency than passive diffusion. Both in vitro and in vivo results confirm that this combined strategy achieves complete tumor eradication with favorable biosafety. Collectively, the NCRPF nanotherapeutic system provides a powerful new paradigm with high translational potential for the complete eradication of breast cancer.

Animals↗

PubMed2026

Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 × 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

Humans↗

PubMed2026

The effect of monetary versus point-based rewards on effort-cost decision making in individuals at clinical high risk for psychosis.

OBJECTIVE: The dissemination of inexpensive computerized behavioral tasks indexing amotivation may enhance the assessment of clinical high risk (CHR) across settings. However, the impact of varying reward value in such tasks is unclear. If point-based rewards engage participants, this could improve the scalability of computerized assessments. We tested how point-based rewards versus money impacted effort-cost decision-making in CHR individuals. We further assessed how negative symptom severity and household income interacted with reward-type to impact behavior. METHODS: Participants completed the Effort Expenditure for Reward Task (EEfRT). Participants were randomly assigned to receive either money or points for their performance during the EEfRT. Data from a large sample of CHR (N = 233) individuals and healthy controls (HC; N = 157) were collected. RESULTS: Across diagnostic groups, we observed heightened effort expenditure when money was used as a reward (b = 0.13, p = 0.018). We did not find an interaction of CHR status (b = 0.07, p = 0.845) or negative symptoms (b = 0.01, p = 0.429) with reward-type. Within CHR individuals, heightened negative symptom severity was associated with reduced expended effort (b = -0.03, p = 0.016), regardless of reward type. In an exploratory analysis, we found that individuals in the money condition with relatively high household income expended less effort during high reward, high probability trials (b = -0.24, p = 0.046). CONCLUSIONS: Across CHR and HC individuals, individuals pursuing money expended greater effort. While we did not find a group by reward type interaction, CHR individuals with heightened negative symptom severity expended less effort across trials, replicating prior work. Present findings support further study of point-based rewards in tasks indexing amotivation.

Humans↗

PubMed2026

A STORM-based protocol for nanoscale imaging and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber.

Stochastic Optical Reconstruction Microscopy (STORM) enables nanoscale mapping of molecular components beyond the diffraction limit; however, its reproducible implementation in hydrophobic polymer matrices remains challenging because fluorescence-labeling specificity, fluorophore photoswitching, three-dimensional localization, chromatic registration, and quantitative image analysis must be carefully controlled. This protocol presents a standardized experimental workflow for dual-color labeling, astigmatism-based three-dimensional STORM acquisition, and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber (NR). The workflow covers sample pretreatment, Cy5 NHS ester labeling of protein-associated primary amines, DiI labeling of phospholipid-rich domains, STORM imaging-buffer preparation, three-dimensional single-molecule localization, dual-channel registration, generation of standardized xy projections, aggregate-size analysis, and projected lateral spatial correlation assessment. Reproducibility is supported by defined acquisition and localization criteria, three independent sample preparations with at least five fields of view analyzed per condition, and unlabeled, single-color, dye-only matrix, and processing-associated Cy5 controls. Mean lateral localization precisions of 11.8 ± 2.3 nm for Cy5 and 13.5 ± 2.9 nm for DiI were obtained, while two-dimensional Fourier ring correlation analysis of the xy projections yielded effective lateral image resolutions of approximately 25 and 28 nm, respectively. Image-based particle segmentation and localization-coordinate-based density-based spatial clustering of applications with noise (DBSCAN) were applied to standardized xy projections as complementary quantitative approaches. Application of the protocol to untreated, centrifuged, and protease-treated NR samples demonstrated treatment-associated changes in the detected abundance and projected size distributions of protein- and phospholipid-associated aggregates, together with a non-monotonic change in their projected lateral spatial correlation. These observations describe alterations in nanoscale organization but do not, by themselves, establish stable protein-phospholipid complex formation. Unlike previous studies that primarily demonstrated the feasibility of STORM imaging in rubber materials, the principal contribution of this work is an end-to-end, step-by-step protocol incorporating defined controls, three-dimensional localization, image-quality metrics, chromatic-registration procedures, and complementary quantitative-analysis pipelines for non-expert users. The workflow may be adaptable to other hydrophobic polymers and soft-material systems after appropriate optimization and validation.

Rubber↗

PubMed2026

Opioid-sparing anesthesia based on opioid-free principles for early recovery after total knee arthroplasty: A randomized controlled trial.

OBJECTIVE: To evaluate whether an opioid-sparing anesthesia strategy (OSA), based on opioid-free anesthesia (OFA), improves early postoperative recovery quality and optimizes functional outcomes after total knee arthroplasty (TKA), compared with conventional opioid-based anesthesia (OBA). DESIGN: A randomized controlled trial with blinding of patients, surgeons, and outcome assessors. SETTING: Single center, July 2025 to February 2026. PATIENTS: 98 adult patients scheduled for elective unilateral TKA. INTERVENTION: Patients were randomized to the OSA or OBA group. The OSA regimen used esketamine and dexmedetomidine as the primary analgesic backbone, whereas the OBA regimen was opioid-based. Both groups received preoperative femoral nerve block and were administered oxycodone at skin incision and closure. Postoperatively, both groups received the same multimodal analgesia and patient-controlled analgesia. MEASUREMENTS: The primary outcome was the 24-h postoperative Quality of Recovery-15 (QoR-15) score. Secondary outcomes included 48-h QoR-15; Oxford Knee Score (OKS) and EQ-5D-3L at 1 and 3 months; high pain at 1 month and chronic postsurgical pain at 3 months. Exploratory outcomes included postoperative C-reactive protein (CRP), and postoperative nausea and vomiting (PONV), among others. RESULTS: At 24 h postoperatively, QoR-15 was higher in the OSA group than in the OBA group (118.4 ± 11.5 vs 113.3 ± 12.2; adjusted difference 5.12, 95% CI 0.51-9.74; P = 0.029), and this advantage persisted at 48 h (adjusted difference 5.54, 95% CI 1.57-9.52; P = 0.007). The OSA group had a lower incidence of PONV (P = 0.025) and lower postoperative CRP levels (P = 0.001). At 1 month, OKS was higher in the OSA group (adjusted difference 2.31, 95% CI 0.34-4.27; P = 0.022), with no significant differences in other secondary outcomes. CONCLUSION: In TKA, this OFA-based OSA strategy improved early postoperative QoR-15 scores. However, the QoR-15 difference did not reach the minimal clinically important difference, so its clinical relevance remains uncertain.

Humans↗

PubMed2026

Effectiveness and implementation of task-sharing cognitive-behavioral interventions for perinatal mental health: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of cognitive-behavioral interventions (CBIs) delivered by nonspecialist providers (NSPs) on perinatal depressive (PND) and anxiety symptoms, and to narratively synthesize their implementation processes and reported implementation outcomes, including acceptability, feasibility, fidelity, cost, and sustainability. METHODS: We systematically searched eight databases from inception to April 8, 2025. Eligible studies were randomised controlled trials (RCTs) assessing CBIs delivered by NSPs for PND and/or anxiety. Two reviewers independently screened, extracted, and assessed trials. Meta-analyses employed random-effects models, with subgroup, sensitivity, meta-regression, and publication bias analyses conducted in Stata 18.0. Implementation processes and outcomes were reported as frequencies or percentages across trials. RESULTS: A total of 47 trials (11, 357 participants) were included in the systematic review, of which 37 trials (8,709 participants) were included for meta-analyses. CBIs were conducted in 12 countries. Nurses and midwives delivered 45% of CBIs. CBIs were associated with reduced PND post-intervention compared with control conditions (standardized mean difference [SMD] -0.49, 95% CI -0.63 to -0.35; I² = 86.8%). Limited evidence from four trials suggested a small sustained effect at 12 months (SMD -0.14, 95% CI -0.27 to -0.02; I² = 26.4%). Reductions in anxiety symptoms were observed immediately post-intervention (SMD, -0.45, 95% CI -0.65 to -0.25; I²=81%), but evidence for longer-term effects was limited. Subgroup analyses confirmed consistent effects across diverse settings, populations, and intervention characteristics. Reporting of implementation processes (e.g., training, supervision, fidelity) was limited, with only 23.4% of trials assessing fidelity and 10.6% evaluating costs. CONCLUSIONS: NSP-delivered CBIs showed beneficial effects on PND and anxiety, with generally encouraging evidence for acceptability and feasibility. However, evidence for sustained effects beyond the immediate post-intervention period remains limited. Future studies should strengthen long-term follow-up and improve reporting of implementation processes and outcomes, particularly in rural and adolescent perinatal populations, to inform scalable and equitable task-sharing models.

Humans↗

PubMed2026

Acceptability of alcohol-based hand rub during neonatal care in rural Ugandan households: a qualitative study nested within the BabyGel trial.

BACKGROUND: Poor access to water, sanitation and hygiene exacerbates the spread of infections among newborns. The BabyGel cluster randomised trial assessed the effectiveness of a community-level alcohol-based hand rub with a training component in reducing infection or death rates among newborns in Uganda. OBJECTIVE: Nested in the BabyGel trial, this study investigated the acceptability of the BabyGel intervention among mothers and household members in Eastern Uganda, using the Theoretical Framework of Acceptability. METHODS: In 2022, we conducted individual semistructured interviews with mothers, and group interviews with mothers and other household members, all recruited from intervention-arm clusters. Thematic analysis combined inductive and deductive coding, structured by the framework's seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy. RESULTS: Twenty mothers and 14 household members participated in 10 individual and 10 small group interviews. Participants found the intervention generally acceptable, appreciating its convenience and perceived protection against infection. Many described hand hygiene changes that persisted beyond the intervention period. However, concerns related to its harmful effects, spiritual beliefs and social tensions with visitors occasionally influenced its use. CONCLUSION: Alcohol-based hand rub combined with a training component was generally well accepted, driven by perceived health and practical benefits, although concerns related to safety, belief systems and social dynamics remained. Because data collection coincided with the COVID-19 pandemic, a period of heightened hygiene awareness, the acceptability observed could differ in nonpandemic periods. Culturally adapted education, community engagement and reinforcement of correct use may enhance acceptability and sustainability in similar settings.

Humans↗

PubMed2026

Home-Based Cardiac Rehabilitation Using a Smart Ring and Telephone Counselling: A Randomized Controlled Trial.

BACKGROUND: Home-based cardiac rehabilitation (HB-CR) is a promising alternative to center-based cardiac rehabilitation as it can address several barriers impeding CR implementation because of its enhanced accessibility. However, to date, HB-CR has not garnered adequate attention due to a lack of communication between patients and medical staff. In this study, we aimed to investigate the effectiveness of HB-CR by monitoring the pulse rate (PR) using a smart ring equipped with photoplethysmography. METHODS: Patients with cardiovascular disease were educated on structured HB-CR methods following a symptom-limited cardiopulmonary exercise test (CPET), and were instructed to wear the device during the exercise session. The recorded PR was uploaded to a website via a smartphone and monitored by medical staff. Patients were randomly assigned to one of two groups: intervention or control group. The intervention group received weekly telephone counselling and was encouraged to maintain optimal levels of physical activity. In contrast, the control group only recorded their exercise data without additional interventions. After 3 months of training, the CPET was performed. RESULTS: Among the 64 randomized patients (32 in each group), an intention-to-treat analysis showed that peak oxygen consumption increased over time in both the groups, with a significantly greater improvement in the intervention group. The group-by-time interaction for peak oxygen consumption was statistically significant (estimated mean difference, 2.0 mL/kg/min; 95% confidence interval, 0.7-3.3; P = 0.004). CONCLUSION: HB-CR using a smart device was effective in improving oxygen consumption. However, appropriate monitoring and timely counselling by medical professionals are important for improved outcomes. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005893.

Humans↗

PubMed2026

Prothrombin complex concentrate (PCC) vs. non-PCC strategies for warfarin reversal in left ventricular assist device recipients: A systematic review and meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) prolong survival in end-stage heart failure, and warfarin thromboprophylaxis is recommended to prevent device thrombosis and thromboembolic complications. When bleeding occurs or emergency surgery is required, rapid anticoagulation reversal is critical. Prothrombin complex concentrate (PCC) provides rapid reversal; however, its risk-benefit profile in LVAD recipients remains unclear. We conducted a systematic review and meta-analysis comparing PCC with non-PCC strategies for warfarin reversal in LVAD recipients. METHODS: MEDLINE, Embase, and Scopus were searched through June 2025 for studies of PCC versus non-PCC strategies for warfarin reversal in LVAD recipients. Two reviewers independently extracted data. Random-effects models were used to pool arm-level estimates and to pool head-to-head comparisons using mean differences or risk ratios (RRs). RESULTS: Eighteen studies involving 779 patients were included. Arm-level pooled estimates for PCC versus non-PCC comparators were 24.0% versus 15.8% for mortality, 16.5% versus 12.1% for thrombotic events, and 3.1 versus 5.7 for FFP units. Arm-level time to INR correction was longer with PCC overall (16.5 versus 13.6 h), driven by one elective cohort, but faster within the ICH subgroup (6.0 versus 13.7 h). In head-to-head comparisons, PCC achieved faster INR correction than non-PCC comparators (mean difference - 7.6 h; p = 0.001) and required fewer FFP units (-2.6 units; p = 0.019), with no significant difference in all-cause mortality (RR 1.14; p = 0.490) or thrombotic events (RR 1.43; p = 0.176). CONCLUSIONS: In head-to-head studies, PCC was associated with faster INR correction and lower FFP requirements than non-PCC strategies, whereas mortality and thrombotic events did not differ significantly. Given the observational evidence, wide confidence intervals, and heterogeneity, equivalent safety cannot be established, and prospective studies are needed to define the relative safety and effectiveness of the two approaches. IMPLICATIONS FOR CLINICAL PRACTICE: PCC-based strategies may be considered for urgent warfarin reversal in LVAD recipients, particularly when rapid INR reduction or avoidance of large-volume plasma transfusion is clinically important. Treatment decisions should account for the indication, bleeding severity, and underlying thrombotic risk. TRIAL REGISTRATION: CRD42024573925.

Humans↗

PubMed2026

Machine learning-based prediction of unplanned readmission and construction of an online calculator for elderly patients with mild ischemic stroke.

OBJECTIVE: To screen for independent risk factors for unplanned readmission in elderly patients with mild ischemic stroke, and to construct and validate an online risk prediction calculator based on an interpretable machine learning model, thereby providing a promising practical tool for accurate clinical assessment of 30‑day all‑cause unplanned readmission risk in this population. METHODS: A prospective cohort study was conducted, including 1050 patients aged ≥ 60 years with mild ischemic stroke admitted between August 2023 and September 2024. Participants were randomly divided into a training set (840 cases) and a test set (210 cases) at a ratio of 8:2. Risk factors were screened by univariate analysis and multivariable Logistic regression. Four machine learning models, namely LightGBM, XGBoost, Random Forest, and K‑Nearest Neighbors (KNN), were developed and their performance was evaluated using AUC, accuracy, sensitivity, and specificity as metrics. The SHAP framework was used for interpretability analysis, and an online calculator was subsequently developed based on the optimal model. RESULTS: Univariate analysis showed significant differences (P < 0.05) in 13 factors including age, smoking, AIP, TyG index, HALP score, etc. Multivariable Logistic regression identified age (OR = 9.752), smoking (OR = 5.171), AIP (OR = 6.691), TyG index (OR = 4.393), HALP score (OR = 2.831), and ≥ 2 comorbidities (OR = 3.664) as independent risk factors. All four machine learning models demonstrated good predictive performance. Based on a comprehensive evaluation of multiple metrics and computational efficiency, the LightGBM model exhibited the best predictive performance (AUC = 0.884, accuracy = 0.829, sensitivity = 0.812, specificity = 0.875). SHAP analysis showed that age, AIP, TyG index, smoking, and HALP score were key predictors. An online calculator developed based on this model enables individualized risk predictions. CONCLUSION: Key risk factors associated with 30‑day unplanned readmission in elderly patients with mild ischemic stroke were identified. The LightGBM model demonstrated high predictive accuracy, and together with the interpretability analysis and online calculator, offers a practical tool to support clinical risk assessment. However, this tool requires future external validation.

Humans↗

PubMed2026

Effectiveness of an AI-based home exercise app for rehabilitation of rotator cuff-related shoulder pain: A randomized controlled trial.

BACKGROUND: Rotator cuff-related shoulder pain contributes to disability and healthcare use. Although therapeutic exercise is first-line treatment, limited supervision and adherence may reduce its effectiveness; digital rehabilitation with real-time feedback may address these limitations. OBJECTIVES: To evaluate the effectiveness of adding a digital rehabilitation program to standard physiotherapy on pain, function, fear-avoidance beliefs, and healthcare utilization. DESIGN: Single-center, assessor-blinded, randomized controlled trial with two parallel groups. METHOD: Forty-six adults (mean age 59 years) with rotator cuff-related shoulder pain were randomized to 12 weeks of conventional physiotherapy or physiotherapy plus an AI-based digital rehabilitation program using computer vision for real-time feedback and performance monitoring. Outcomes were assessed at baseline and at 2, 4, and 12 weeks. Pain intensity (NPRS) was primary outcome; secondary outcomes included upper limb function (QuickDASH), fear-avoidance beliefs (FABQ), and post-intervention healthcare utilization. Analyses followed an intention-to-treat approach. RESULTS: Pain reduction exceeded the MCID (1.3) at 4 and 12 weeks. Between-group differences favoured the intervention at Weeks 2 and 4 (MD -0.7; 95% CI -1.13 to -0.14 and MD -1.01; 95% CI -1.8 to -0.2, respectively). Upper limb function improved more at Week 4 (MD -7.3; 95% CI -12.3 to -2.2). FABQ scores decreased more at Week 12 (MD -7.6; 95% CI -14 to -0.5). Fewer participants in the experimental group required post-intervention healthcare (3 vs 10; p = 0.02). CONCLUSION: Adding AI-based home exercise app to conventional treatment improve pain and may improve function and reduce healthcare utilization in rotator cuff-related shoulder pain.

Humans↗

PubMed2026

Associations of Illness Perception, Resignation Coping, and Social Support With Self-Regulatory Fatigue in Patients With Type 2 Diabetes: A Cross-Sectional Study.

AIMS: To examine the associations among illness perception, resignation coping, social support, and self-regulatory fatigue (SRF) in patients with Type 2 diabetes mellitus. The study specifically explores whether resignation coping and social support exhibit indirect associations with SRF in the context of illness perception. DESIGN: A cross-sectional study. METHODS: From November 2024 to October 2025, a convenience sample of 302 adult patients with T2DM was recruited from a tertiary general hospital in China. Participants completed validated instruments with established psychometric properties, namely the Brief Illness Perception Questionnaire, the Medical Coping Modes Questionnaire, the Perceived Social Support Scale, and the Self-Regulatory Fatigue Scale. Statistical analyses included Spearman correlation and serial mediation analysis using the PROCESS Macro (Model 6) with bias-corrected bootstrapping. RESULTS: SRF was positively correlated with negative illness perception (r = 0.579, p < 0.01) and resignation coping (r = 0.612, p < 0.01), and negatively correlated with social support (r = -0.598, p < 0.01). Serial mediation analysis revealed that illness perception was associated with SRF through indirect pathways involving resignation coping and social support. Resignation coping and social support mediated the association between illness perception and self-regulatory fatigue, both individually and sequentially. CONCLUSIONS: Negative illness perception correlates with higher SRF. This observed correlation is additionally linked to indirect pathways involving resignation coping and lower social support. Collectively, these findings highlight a pattern of interrelated cognitive (illness perception), behavioural (resignation coping), and resource (social support) factors that are associated with self-regulatory fatigue in this cross-sectional study. IMPLICATIONS FOR THE PROFESSION: The findings offer a clear, evidence-based framework for nursing practice. They highlight the potential value of integrated assessment and intervention that simultaneously addresses patients' illness beliefs, maladaptive coping strategies, and social support systems, which are associated with lower SRF and better diabetes self-management. REPORTING METHOD: This study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: Patients participated solely as research participants by providing survey data. They were not involved in the study design, implementation, data analysis, interpretation, or manuscript preparation. All patients provided written informed consent prior to questionnaire completion.

Humans↗

PubMed2026

Longitudinal Prediction of Retinal Sensitivity Based on Disease Progression Quantified From Optical Coherence Tomography in Geographic Atrophy.

PURPOSE: The purpose of this study was to analyze the association between disease progression of geographic atrophy (GA) from optical coherence tomography (OCT) with retinal sensitivity (RS) in microperimetry (MP) over a 2-year follow-up period. METHODS: This is a longitudinal analysis of the OAKS Phase-III clinical trial. Both study and fellow eyes with GA that underwent imaging with the Spectralis OCT and consecutive MP examination were eligible. Pointwise quantification of ellipsoid zone (EZ) thickness, EZ and retinal pigment epithelium (RPE) loss from OCT volumes was correlated with localized RS. A longitudinal predictive model using a Markov Chain framework was implemented to predict RS change over time based on OCT biomarkers. The modeling of morphological and functional progression was based on the fellow-eye cohort. RESULTS: A total of 39,681 MP points from 406 patients were analyzed. In the fellow eye cohort, baseline (BSL) EZ thickness was positively associated with RS (0.3 decibel [dB]/µm, P < 0.001). Decrease in EZ thickness between visits during follow-up was significantly associated with decrease in RS (0.1 dB / 1 µm change). RS was significantly lower in MP points within EZ loss during follow-up compared with MP points within the retina with measurable EZ (P < 0.001). The largest functional decline was observed within RPE loss, also associated with the highest probability of absolute scotoma (P < 0.001). Morphological progression to EZ and RPE loss was influenced by EZ thickness and the morphology of adjacent MP points (P < 0.001). CONCLUSIONS: Two exploratory endpoints were developed, namely quantification of EZ thickness and loss, and localized RS within high-risk OCT areas. RS decline during follow-up is associated with automatically quantified disease progression in OCT.

Humans↗

PubMed2026

Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12 cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B) ≈ 9, coefficient of variance (CV) < 10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus↗

PubMed2026

Unconfined compressive strength prediction for the ordinary Portland cement-steel slag-silica fume ternary system based on response surface methodology.

This research was undertaken to address environmental concerns associated with industrial solid waste and to reduce cement consumption in geotechnical engineering. It specifically investigates the feasibility of using steel slag (SS) and silica fume (SF) as partial substitutes for ordinary Portland cement (OPC) in soil stabilization. The effects of SS, SF, OPC, and initial moisture content on the unconfined compressive strength (UCS) of stabilized soil were investigated through single-factor experiments and response surface methodology (RSM). The results show that SS and SF can synergistically enhance the strength of stabilized soil, although their interaction effect was not statistically significant within the investigated ranges. Compared with soil stabilized solely with OPC, the addition of 18 % SS and 10 % SF reduced OPC consumption by 3 % without compromising strength. Microstructural and compositional analyses further revealed that SS mainly supplied calcium- and silica-bearing components, while SF provided highly reactive silica and micro-filling effects, jointly promoting hydration reactions and improving the compactness of the stabilized soil matrix. As a result, more hydration products were formed in the OPC/SS/SF-stabilized soil than in the OPC-stabilized soil, which contributed to pore filling and strength enhancement. This study provides useful guidance for the sustainable utilization of industrial solid waste and the low-carbon development of soil stabilization materials.

Construction Materials↗

PubMed2026

Revealing potential biomarkers and metabolic mechanisms of ovarian aging in hens during late laying period based on machine learning and metabolomics.

Ovarian function decline during the late laying period represents a major bottleneck for the economic efficiency of the global poultry industry. However, the underlying metabolic mechanisms and reliable early-warning biomarkers for ovarian aging remain poorly understood. In this study, we performed the first untargeted LC-MS/MS metabolomics analysis of ovarian tissues from Taihe silky fowls at peak laying (30 weeks) and late laying (50 weeks) stages, and employed an ensemble machine learning strategy integrating LASSO, random forest, and support vector machine (SVM) algorithms to identify high-confidence core biomarkers of ovarian aging. Gene expression analysis was further conducted to validate the potential molecular mechanisms. Our results showed that the metabolic profiles of ovarian tissues differed significantly between the two groups. A total of 6 core biomarkers were identified, 4 of which were long-chain acylcarnitines. Mechanistic analysis revealed that downregulation of key genes in the carnitine shuttle system led to impaired mitochondrial fatty acid β-oxidation, which in turn triggered excessive oxidative stress and compromised ovarian endocrine function. In conclusion, this study identifies long-chain acylcarnitines as potential metabolic biomarkers for ovarian aging in Taihe silky fowls. These findings provide novel insights into the metabolic basis of poultry ovarian aging and lay a theoretical foundation for the precise regulation of reproductive performance in indigenous poultry breeds.

Animals↗

PubMed2026

Role of bioprocessing in modifying cardiometabolic outcomes of an oat-based dairy alternative in a randomised controlled clinical intervention.

BACKGROUND & AIMS: A healthy diet rich in fibre-containing foods such as oats supports cardiometabolic health. Bioprocessing methods, including fermentation and enzymatic treatment, may further enhance the health benefits of oat-based foods by altering their physicochemical properties. The aims of this study were to investigate the effects of consuming fermented and non-fermented oat-based products enriched with fibre and protein on cardiometabolic outcomes gastrointestinal symptoms, and to consider how assessed physicochemical and nutritional differences between the products might relate to any observed effects. METHODS: In a 12-week randomised crossover trial, 56 adults with mild metabolic deterioration consumed fermented (gurt) and non-fermented (porridge) oat-based products enriched with fibre and protein as part of their habitual diet for three weeks each. The study products were specifically developed and prepared for this study using identical ingredients. Primary cardiometabolic factors and gastrointestinal symptoms (GSRS) were measured at four time points, while secondary outcomes were assessed at baseline and after both product periods. Physicochemical and nutritional characterization of the study products included cereal β-glucan (BG) and protein molecular weight distribution, starch and sugar analysis, microscopy, acidity, and viscosity. RESULTS: During the gurt consumption, non-high-density lipoprotein (non-HDL) and low-density lipoprotein (LDL) cholesterol concentrations decreased (-0.15 ± 0.51 mmol/L, p = 0.028; and -0.12 ± 0.46 mmol/L, p = 0.047, respectively), with a minimal impact on blood pressure and GSRS scores. Additionally, ferritin was lower after the gurt compared with baseline (-4.00 [-16.50, 6.25] μg/L, p = 0.015). Similarly, ferritin levels were lower after the porridge period (-7.50 [-20.50, 4.25] μg/L), accompanied with a modest decrease in blood pressure and HbA1c. These effects, however, did not substantially differ between the product periods. Insulin showed a significant sequence effect (psequence∗time <0.05) and was analysed in sequence groups. Insulin levels significantly decreased during the gurt consumption in the group that started with the porridge (-2.22 ± 6.16 mU/L, p = 0.015). Fermentation and enzymatic treatment induced significant changes in BG MW, starch, and composition in the gurt, which may alongside with increased fibre intake during the intervention explain the observed results. CONCLUSION: Consuming a fermented, oat-based gurt as part of habitual diet may improve cholesterol metabolism, likely due to increased oat fibre intake rather than fermentation as such. Moreover, greater intake of oat-based products, regardless of processing, can reduce ferritin concentrations and marginally improve other cardiometabolic factors. The study was registered in ClinicalTrials.gov as NCT06393114.

Humans↗

PubMed2026

Construction of precision clinical-proteomics risk model based on machine learning for predicting heart failure in type II diabetes mellitus.

BACKGROUND AND AIMS: Heart failure (HF) is a severe complication in type 2 diabetes mellitus (T2DM), but current risk stratification scores have limited predictive accuracy. We aimed to develop novel prediction tools integrating clinical variables with proteomics to improve risk stratification of hospitalization for HF in T2DM. METHODS AND RESULTS: In this study, we included 2111 UK Biobank participants with T2DM but no prior HF, and profiled 2920 proteins to predict 10-year incident HF hospitalization. Participants were randomly divided into training (70%), tuning (10%), and validation (20%) sets.Three prediction models were developed: a Clinical model based on demographic characteristics, comorbidities, medication use, and laboratory indices; a Protein model based on 40 proteins selected by the Light Gradient Boosting Machine (LGBM); and the Clinical OMics and Protein ASSessment for Heart Failure (COMPASS-HF) model, which integrated both clinical variables and the LGBM-selected proteins. Models were evaluated for area under the curve (AUC), sensitivity, and specificity. During follow-up, 168 participants (7.96%) developed incident HF. The COMPASS-HF model showed better discrimination than the Clinical model, with an AUC of 0.897 (95% CI: 0.850-0.945) versus 0.790 (95% CI: 0.723-0.856). It also demonstrated higher sensitivity (0.882; 95% CI: 0.725-0.967) and consistent performance in subgroups. COMPASS-HF effectively stratified risk of hospitalization for HF, with cumulative incidence rates of 31.9% in the high-risk group and 1.2% in the low-risk group. CONCLUSIONS: By combining clinical and proteomic variables, we developed a high-performance HF prediction model for T2DM, enabling precise risk stratification and informing early intervention strategies.

Humans↗