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Concurrent chemical reaction and cluster restructuring in a frustrated fluxional catalytic system identified via simple kMC model

Endophyte diversity and its correlation with naphthoquinone metabolites in cultivated Arnebia euchroma across different growth years

Previous studies on Arnebia euchroma (Royle) Johnst. have focused on its physicochemical and pharmacological properties, and studies on the differences in metabolites in A. euchroma have also highlighted the effects of external environmental factors. In this study, we compared the differences in the diversity of endophytes in the root tissue of A. euchroma grown for 1–4 years in Hejing County using high-throughput sequencing and analyzed their relationship with eight secondary metabolites, including alkannin, β , β -dimethylacrylshikonin, deoxyshikonin, acetylshikonin, β -acetoxyisovalerylshikonin, β -hydroxyisovalerylshikonin, isobutyrylshikonin, and isovalerylshikonin. The results indicate that a total of 1161 amplicon sequence variants (ASVs) of endophytic fungi from cultivated A. euchroma were classified into 12 phyla, 32 classes, 76 orders, 153 families, 259 genera, and 367 species. Additionally, 673 amplicon sequence variants (ASVs) of endophytic bacteria were classified into 18 phyla, 37 classes, 89 orders, 139 families, 226 genera, and 267 species. The α-diversity of endophytic fungi and bacteria in cultivated A. euchroma peaked in four-year-old (X-4Z) and two-year-old (X-2Z) respectively. Spearman’s correlation analysis showed that β -hydroxyisovalerylshikonin, acetylshikonin, isobutyrylshikonin, β,β -dimethylacrylshikonin, and isovalerylshikonin were correlated with endophytic fungal diversity and abundance ( P ≤ 0.05 ). FUNGuild and PICRUSt2 predictive analyses showed that the dominant trophic modes of endophytic fungi in all samples were saprotrophic and pathotrophic, with the highest relative abundance in X-4Z, while the main trophic mode of endophytic bacteria was metabolic. Our results help to elucidate the importance of plant-microbe interactions and provide key information on the role of endophytes in promoting the cultivation of A. euchroma and the accumulation of its important secondary metabolites. They also provide a reference for further research on the effects of differences in the community composition of endophytes on the accumulation of medicinal compounds in A. euchroma and for the development of resources for its cultivation.

No overall increased risk of death in individuals with sickle cell trait: a study of 467 779 general population adults

Uncertainty remains about whether sickle cell trait (SCT) shortens life or predispose to disease. Therefore, we examined whether SCT-carriers had increased risk of death or diseases linked to SCT. We studied 467,779 general population individuals from the UK Biobank. All had whole-exome sequencing performed and were followed prospectively for a median of 15 years. Individuals with SCT (n=1,253) were not at increased risk of all-cause death (hazard ratio[HR]:1.04;95%CI:0.84-1.29), cardiovascular death (1.34;0.90-2.00), or for having myocardial infarction (0.72;0.42-1.24), ischemic stroke (1.30;0.88-1.94), pulmonary embolism (1.29;0.84-1.99), or heart failure (0.79;0.55-1.14) compared to non-carriers. However, SCT-carriers had increased risk of diabetes (HR:1.30;95%CI:1.12-1.50), chronic kidney disease (HR:1.46;95%CI:1.18-1.80), and hypertension (odds ratio:1.24;95%CI:1.08-1.42). Surprisingly, risk of cardiovascular death was increased in SCT-carriers with diabetes when compared to non-carriers with diabetes (HR:2.17;95%CI:1.14-4.12). To examine whether selection bias may explain why previous studies based on hospital-diagnosed SCT found increased risk of cardiovascular disease, we repeated our analyses using hospital diagnoses of SCT from national registries, instead of defining SCT from genotyping. Individuals registered as SCT-carriers in hospital registries had markedly increased risk of all-cause death (HR:2.24;95%CI:1.42-3.52) and ischemic stroke (2.92;1.30-6.60), likely due to selection bias. In conclusion, SCT-carriers were not at increased risk of all-cause death or cardiovascular disease.

Author Correction: Proteasome-guided haem signalling axis contributes to T cell exhaustion

Investigation of the effects of a Kiperin Bromelain & Papain complex in normal colon, mammary, and skin cells

Abstract Bromelain is a proteolytic enzyme complex naturally found in the stem, fruit, and juice of pineapple, while papain is a proteolytic enzyme derived from the latex of the papaya plant. These bioactive components have attracted increasing scientific interest due to their reported roles in cell proliferation and wound healing, suppression of oxidative stress through free radical scavenging, and apoptosis-related pathways. Although bromelain and papain have been associated with various health-related effects, their effects on healthy cells remain largely unexplored. In this study, different concentrations of Kiperin Bromelain & Papain (KBP) (1.0–3.5 µg/mL) were tested in healthy cell lines. Based on the concentration showing the highest cell viability, 2.5 µg/mL was selected for further analyses, and CCD-18Co (colon fibroblasts), HME-1 (mammary epithelial cells), and HaCaT (keratinocytes) were treated accordingly. Cell viability was assessed by cell counting, and wound healing was evaluated. Gene expression levels of MMP9 , IVL , FLG , IL-6 , IL-10 , NFKβ , and TNF-α were measured by real-time PCR. KBP exposure increased cell viability in all cell lines, with the most pronounced effect observed at 2.5 µg/mL. Wound-healing assays indicated changes in wound closure following KBP exposure. In addition, KBP treatment was associated with decreased expression of inflammation-related genes ( IL-6 , IL-10 , NFKβ , and TNF-α ) and increased expression of genes related to skin barrier/keratinization ( IVL and FLG ). The magnitude of these effects differed across cell types, indicating cell-specific responses. Further research is warranted to validate these findings in in vivo models and to clarify the potential applications of KBP in dermatological contexts.

Investigating the application value of the “Forward-Deployed Position” model in operating room support by the central sterile supply department

Objective To investigate the application effects of the “Forward-Deployed Position” model in operating room support provided by the Central Sterile Supply Department (CSSD). Methods This study employed a historical control design. Data from the period when the “Forward-Deployed Position” model was implemented in our hospital in 2024 were set as the observation group, while data from 2023 under the traditional model served as the control group. The two groups were compared regarding indicators including the instrument re-cleaning rate, packaging qualification rate, clinical department satisfaction, and on-time start rate for the first scheduled surgery of the day. Results Compared with the control group, the observation group demonstrated a significant increase in the packaging qualification rate (99.05% vs 98.05%), clinical department satisfaction, and the on-time start rate for the first scheduled surgery (95.05% vs 85.63%), alongside a significant decrease in the instrument re-cleaning rate (0.37% vs 1.05%). All these differences were statistically significant (p < 0.05). Conclusion Provided that implementation conditions such as human resources are fully considered, the “Forward-Deployed Position” model can effectively enhance the work quality of the CSSD and the efficiency of surgical support. Its successful implementation relies on a specialized team and sustained inter-departmental collaboration, offering a valuable reference for optimizing surgical workflow management.

Prognostic factors and progression biomarkers in AL amyloidosis: mapping current knowledge and critical gaps

Abstract The therapeutic landscape for systemic immunoglobulin light chain (AL) amyloidosis has been revolutionized by daratumumab-based regimens, achieving 76% 5-year overall survival in the landmark ANDROMEDA trial. However, the current prognostic models were developed using patient populations treated with now-suboptimal therapies, creating a critical gap between risk stratification models and contemporary outcomes. This comprehensive review analyzes prognostic factors and progression biomarkers in AL, categorizing them into disease-specific (clone-related and organ-related) and patient-specific factors. Notably, traditional baseline biomarkers including difference between involved and uninvolved free light chains and bone marrow plasma cell burden are losing prognostic significance with effective clone-directed therapies. Emerging approaches show promise, including dynamic markers such as minimal residual disease by free light chain mass spectrometry, cardiac imaging parameters such as global longitudinal strain, and functional measures. There is an urgent need for validation studies and prognostic model refinement to identify patients at high risk who may benefit from interventions beyond anti–plasma cell therapy.

Development and validation of a machine learning-based risk prediction model for hyperkalemia in patients with chronic kidney disease

A collaborative approach to applying Natural Language Processing (NLP) to Domestic Homicide Reviews (DHRs): A study protocol

Since 2011, there has been a statutory requirement in England and Wales to conduct a Domestic Homicide Review (DHR) into any domestic abuse-related death: a multi-agency review into the death of a person aged 16 or over that appears resulting from violence, abuse or neglect from an intimate partner, family member or household member. However, analyses of large numbers of DHRs are rare. One of the core challenges is the time and effort required to analyse narrative text within reports. Doing so manually is both time-consuming and resource-intensive and is a primary reason why researchers typically focus on only a portion of the available data. Natural Language Processing (NLP)—a sub-branch of artificial intelligence that enables computers to interpret and process natural language—provides a viable and scalable alternative by offsetting much of the heavy data processing to a computer. This protocol outlines a study to assess the feasibility of applying NLP to DHRs. The study will take a collaborative approach which balances the speed and scale of automation with the embedded knowledge and expertise of practitioners. This approach helps to ensure that outputs of NLP are sensitive and transparent about the biases common within datasets on violence and abuse. Based on initial consultations, we identify the priority research questions for investigation. In addition, we outline details of an ongoing collaboration with one partner, Imkaan. The protocol describes the data access, and retrieval and analysis stages before summarising how feasibility will be evaluated. We anticipate that several challenges will emerge within this study and identify strategies for mitigation. We suggest that working with practitioners who hold deep contextual knowledge about the social realities of violence and abuse, including language, risks, and experiences, mean that tools can be developed that are accountable to communities and appropriately applied to real-world problems.

<i>TCF3</i> :: <i>HLF</i> drives fatal B-ALL thriving on inflammation

Negative-space 3D printed reconstruction of the pterygopalatine fossa: anatomical design and educational evaluation

Developmental transition of visual and nonvisual photoreception and circadian clock during smoltification in the eye and brain of Atlantic salmon

Seasonal variation in photoperiod is an important cue that regulates changes in physiology and behavior during the anadromous lifestyle of Atlantic salmon. The parr-smolt transformation or smoltification, where fish migrate from rivers to the ocean, is promoted by an increased photoperiod in the spring. Photoperiodic information is transferred through the light-brain-pituitary axis, resulting in pituitary hormones stimulating changes related to this transition. The light environment is perceived by ocular photopigments in the rods and cones that convey image formation and via nonvisual photoreceptors entraining biological processes that synchronize with circadian and circannual light rhythms through the molecular clock mechanism. In this study, the dynamic expression of visual and nonvisual opsin genes and clock genes through smoltification were revealed by RNA sequencing. The results showed a dramatic transition of the teleost visual system by changes in expression of the tandem duplicated medium-wavelength-sensitive ( mws or “green”) and long-wavelength-sensitive ( lws or “red”) opsin genes during seawater migration, shifting the spectral sensitivity of the green opsins by up to 40 nm towards shorter wavelengths. Concomitantly, the expression of the lws opsin gene that forms a photopigment with the most extreme absorbance maximum was upregulated. Among the nonvisual opsins, the pineal-specific exorhodopsin was greatly upregulated in seawater, coinciding with an increased expression of important enzymes that dictate melatonin synthesis. Analyzing the components of the salmonid molecular clock expressed during smoltification showed that clock genes were dynamically expressed with changes in expression both related to changes in the photoperiod and the developmental transition from freshwater to seawater. The transcriptomic profile of the teleost brain through smoltification was shown to coincide with important genes that underpin the mammalian model of photoperiodism that drive summer and winter physiology, supporting common photoperiodic pathways that regulate seasonality in vertebrates.

Refractoriness in TTP: challenges and solutions

For income or for recognition: a comparative study of happiness among employees in state-owned and private enterprises

Dietary cholesterol reduces blood pressure and alters lipid profiles in stroke-prone spontaneously hypertensive rats

Although cholesterol (Chol) is widely recognized as a risk factor for cardiovascular disease, dietary Chol intake has been reported to extend the lifespan of stroke-prone spontaneously hypertensive rats (SHRSP). The mechanisms responsible for this paradoxical effect remain unclear. The present study examined changes in organ lipid profiles and associated molecular factors in SHRSP rats fed a Chol-enriched diet. Four-week-old male SHRSP/Izm rats were assigned to three groups and fed ad libitum for 12 weeks with either a control diet (Ctr), a diet supplemented with 1% w/w Chol (Chol), or a diet containing 1% w/w Chol plus 0.025% w/w lovastatin to suppress endogenous Chol synthesis. Systolic blood pressure was measured before and after the feeding period, and tissues were collected for analyses of sterol content, fatty acid composition, prostaglandin E 2 (PGE 2 ) levels, and renal histopathology. Relative to the Ctr group, the Chol group exhibited a significant 9–10% reduction in systolic blood pressure. This reduction was accompanied by pronounced alterations in lipid profiles, including changes in phytosterol content and decreased arachidonic acid ratios in serum and kidney. There was a downward trend in hepatic PGE 2 levels, and a similar tendency was observed in the kidney. Comparable changes in lipid profiles were observed in the Chol + lovastatin group. Histological analysis revealed modest attenuation of renal pathological features in Chol-fed rats. This study demonstrates for the first time that dietary Chol reduces renal phytosterol accumulation and suppresses the AA-PGE 2 axis, changes that coincide with a 9–10% reduction in systolic blood pressure and attenuated glomerular inflammation. These integrated findings provide a mechanistic framework linking dietary Chol to the previously reported lifespan extension in this stroke-prone model. Although these changes may contribute to improved renal pathology, further studies are required to clarify causal relationships.

Early-career researchers do more ‘disruptive’ science than veterans

Effects of adjuvant propofol on antitumoral effects of carboplatin in experimental endometrial cancer: possible epigenetic associations

Eigen-guided transformer: A data-driven approach for chronic kidney disease forecasting

Accurate prediction of Chronic Kidney Disease (CKD) development is essential for prompt therapeutic intervention; nevertheless, it is difficult due to the highly individualized disease trajectories and intricate multivariate risk profiles. Contemporary deep learning models provide substantial predictive capability; yet, they frequently exhibit computational inefficiency and a lack of interpretability, akin to a “black box.” To overcome these limitations, we present the Eigen-Guided Transformer, an innovative architecture that systematically enhances model topology by data-driven eigenvalue analysis of clinical feature correlations. Our methodology independently establishes: (1) the optimal quantity of attention heads by ascertaining the intrinsic dimensionality necessary to account for 95% of data variance (h = 11), (2) an eigenvector-informed weight initialization to encapsulate a priori feature interactions, and (3) validation-driven depth optimization. Upon assessing daily-aggregated longitudinal sequences from the MIMIC-IV dataset for creatinine prediction, the model attained a Mean Squared Error (MSE) of 0.089 ± 0.004 and a Mean Absolute Error (MAE) of 0.132 + 0.0001, indicating an 11.1% enhancement over the most robust baseline (TFT). The Eigen-Guided Transformer exhibited exceptional parameter efficiency, achieving a FLOPs/accuracy ratio of 142.4M, markedly lower than that of TFT (300M) and Autoformer (1.0B). External validation of the eICU dataset demonstrated strong cross-institutional generalizability (MSE 0.0117 ± 0.0001; MAE 0.0254 + 0.0008). To guarantee clinical dependability, we incorporated Monte Carlo Dropout for uncertainty quantification, resulting in precisely calibrated prediction intervals with 95.8% observed coverage. Additionally, a demographic fairness audit encompassing age, gender, and ethnicity demonstrated equitable performance, with a maximum discrepancy ratio of merely 1.32. The Eigen-Guided Transformer offers a transparent, efficient, and reliable paradigm for the individualized therapy of chronic renal disease by matching attention mechanisms with the intrinsic biological structure of clinical data.

Optimizing PV/T collector performance using coupled solid and porous layer configurations

Abstract Recent research on photovoltaic/thermal (PV/T) collectors has focused on two key strategies to enhance performance: geometric modifications of the thermal flow channel (such as fins, baffles, and ribbed structures) and the integration of advanced materials like phase change materials (PCMs) and porous media to improve heat transfer and overall efficiency. In this direction, this numerical study investigates the performance enhancement of a photovoltaic/thermal (PV/T) solar collector through the integration of a solid layer along the lower wall of the airflow channel, coupled with a porous medium. The solid layer is introduced to accelerate the airflow and intensify convective heat transfer, thereby improving the thermal management of the photovoltaic cells. To solve the governing transport equations, an in-house computational code was developed in the Fortran programming language based on the finite volume method, coupled with the SIMPLER algorithm. The effects of solid-layer thickness and length, porous-layer thickness, and Darcy number are systematically investigated under a constant Reynolds number (Re = 500) and a uniform heat flux of 1000 W/m². The obtained results show that increasing the solid-layer thickness significantly enhances airflow acceleration and leads to a pronounced reduction in PV cell temperature of up to 33 °C. Extending the solid-layer length further improves the convective cooling process and increases both electrical and thermal efficiencies. When combined with a sufficiently permeable porous layer, additional performance gains are achieved, particularly at high Darcy numbers (Da = 10 − 1 ). Compared to a conventional PV/T collector, the optimized configuration demonstrates enhancements of up to 60% in thermal efficiency and 28% in electrical efficiency.

Getting psychiatry on the move—Implementation and evaluation of Braining, a structured physical exercise intervention in outpatient psychiatry: A convergent-parallel mixed methods study

Background Physical exercise can improve mental health outcomes, yet patients with mental illness often require structured support. Braining is a 12-week structured physical exercise intervention developed within Swedish outpatient psychiatry as a clinical package. Although preliminary unpublished findings suggest positive patient outcomes, its implementation within psychiatric services has not previously been evaluated. This study aimed to explore and explain healthcare workers’ perceptions of the acceptability, appropriateness, and feasibility of Braining in an outpatient psychiatric setting to inform future implementation efforts. Methods A convergent parallel mixed-methods design was used with healthcare workers from outpatient psychiatry units specialising in substance use disorders. Quantitative data from the Acceptability of Intervention Measure, Intervention Appropriateness Measure, and Feasibility of Intervention Measure were collected at 1, 4, and 12 months and analysed descriptively. Qualitative data from three focus group discussions with eight Braining team members at 4 and 12 months were analysed abductively using qualitative content analysis. Results Acceptability, appropriateness, and feasibility ratings remained favourable over 12 months (≥16/20). Qualitative findings reflected participants’ positive views on Braining’s relevance for patients, its fit with clinical workflows, and its support for interprofessional collaboration. Participants perceived improvements in patients’ quality of life, benefits of joint staff–patient exercise sessions, and enhanced social connectedness. Reported barriers included variable engagement among healthcare workers outside the Braining team and challenges in reaching younger patients. Conclusions Braining was perceived by healthcare workers as acceptable, appropriate, and feasible in outpatient psychiatry, with sustained implementation outcomes linked to its adaptable design, team delivery, and organisational support. As a formative evaluation, the findings reflect perceived relevance rather than effectiveness, highlighting the need for strategies to enhance equitable reach and sustainability. Trial registration number NCT05111756.