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Metabolomic and structural signatures of pigmented and non-pigmented Himalayan rice landraces.

BACKGROUND: This study investigated the anti-oxidant properties, starch composition, pasting behavior, structural properties, textural properties and non-targeted metabolomic profiles of pigmented and non-pigmented rice landraces as potential next-generation functional food ingredients. RESULTS: Pigmented rice demonstrated 1.34 times more anti-oxidant activity as compared to non-pigmented rice. Pigmented landraces showcased superior nutritional and functional attributes, including higher total dietary fiber and starch content. Fourier-transform infrared (FTIR) analysis revealed distinct molecular signatures with enhanced peak transmittance, while X-ray diffraction (XRD) indicated greater crystallinity ranging from 36-44.3% in pigmented rice compared with 30-40% in non-pigmented rice, suggesting improved digestibility and processing versatility. Pigmented rice recorded less amylose content hence tended to possess increased adhesiveness values whereas non-pigmented rice revealed greater amylose content hence was coupled with greater hardness values. Field-emission scanning electron microscopy (FE-SEM) images revealed that pigmented rice had densely packed and polygonal starch granules whereas non-pigmented rice had loosely packed starch granules with intergranular voids. Untargeted gas chromatography-mass spectrometry (GC-MS) profiling identified 84 metabolites, including unique compounds such as 3,3-dimethylbutanol and ethanoic acid, along with shared metabolites such as sucrose and linoleic acid, highlighting notable biochemical diversity. Multivariate statistical analyses using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping further differentiated the metabolomic landscapes, with variable importance in the projection (VIP) scores identifying key bioactive contributors. CONCLUSION: Pigmented rice landraces exhibited significant functional and nutritional advantages, making them promising candidates for functional food development and nutritional improvement programs. These findings support their potential role in advancing sustainable and health-oriented food systems. © 2026 Society of Chemical Industry.

Oryza

Low Carbohydrate Availability in Energy Balance Alters Bone Turnover and Muscle Proteomic Response With Limited Endocrine Disruption.

Training with low carbohydrate availability (LCA) has been proposed as an independent determinant of physiological perturbations commonly attributed to low energy availability (LEA) and to increase skeletal muscle oxidative machinery, yet the effects of LCA in isolation from LEA remain unclear. We examined whether short-term carbohydrate restriction under energy balance alters endocrine and metabolic markers associated with LEA and skeletal muscle proteomic response. In a randomized crossover design, eight trained males completed 4 days of either a low-carbohydrate high-fat diet (LOW; 12% carbohydrate, 69% fat, 19% protein) or a normal-carbohydrate diet (NORM; 62% carbohydrate, 19% fat, 19% protein), while undertaking daily cycloergometer exercise (15 kcal kg FFM-1 day-1) and maintaining energy availability at 45 kcal kg FFM-1 day-1. LOW induced a clear metabolic shift consistent with LCA, evidenced by elevated circulating free fatty acids, glycerol and β-hydroxybutyrate, in fasting conditions and fat oxidation at rest and during exercise, alongside reduced exercise glucose concentrations. Despite these responses, LOW did not alter insulin, testosterone, triiodothyronine, leptin, hepcidin, or P1NP. In contrast, β-CTX increased and IGF-1 decreased relative to NORM. Muscle glycogen concentration decreased only in LOW (40% ± 14%). Proteomic analysis identified 671 proteins; 57 differentially expressed in LOW relative to NORM were limited to fatty acid metabolism pathways and suppression of ribosomal, sarcomeric, and extracellular matrix proteins. These findings indicate that isolated LCA exerts limited endocrine disruption but may selectively compromise bone turnover and muscle anabolic response, suggesting that without acute LEA, LCA has limited influence on muscle oxidative phenotype.

Male

Outcomes of Response-Based Watch-and-Wait and Surgical Management After Total Neoadjuvant Therapy for Rectal Cancer: A Systematic Review and Meta-analysis.

BackgroundTotal neoadjuvant therapy (TNT) increases clinical complete response rates in locally advanced rectal cancer (RC), allowing response-based management strategies such as watch-and-wait (WW) as an alternative to total mesorectal excision (TME). Outcomes associated with WW after TNT remain incompletely defined. This study aimed to compare oncologic and organ-preservation outcomes between WW and surgical management following TNT.MethodsA systematic search was conducted in PubMed, Scopus, and Cochrane Central up to April 2025. Observational studies comparing WW and TME following TNT were included. Pooled odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed with I2 statistics. Secondary outcomes included tumor regrowth, salvage surgery, and permanent stoma. Risk of bias was evaluated using ROBINS-I.ResultsSix studies comprising 793 patients were analyzed. WW showed no significant difference compared with TME regarding local recurrence (OR 1.36, 95% CI 0.07-26.17; I2 = 80%), distant metastases (OR 0.62, 95% CI 0.29-1.33; I2 = 49%), 5-year disease-free survival (HR 0.97, 95% CI 0.71-1.31; I2 = 51.7%), or overall survival (HR 1.03, 95% CI 0.81-1.30; I2 = 27.9%). Permanent stoma rates were lower with WW (OR 0.12, 95% CI 0.01-1.23; I2 = 71%), becoming significant after sensitivity analysis (OR 0.04, 95% CI 0.01-0.19).ConclusionWW after TNT offers oncologic outcomes comparable to TME, with high organ preservation and reduced surgical morbidity in highly selected patients.

Humans

Physiological and molecular responses of coelomocytes to low- to mid-frequency acoustic exposure in the sea urchin Strongylocentrotus intermedius.

Underwater noise is a widespread environmental pollutant in marine ecosystems, yet the effects of low- to mid-frequency acoustic exposure on immune physiology and molecular responses in echinoderms remain unclear. In this study, the sea urchin Strongylocentrotus intermedius was exposed to continuous pure-tone acoustic stimulation at 80, 125, 250, 500, 750, and 1000 Hz for 3 h. Results showed that acoustic exposure significantly affected redox homeostasis, energy metabolism, and immune function in S. intermedius coelomocytes: the antioxidant system and glutathione redox balance were altered, as indicated by increased superoxide dismutase (SOD) and catalase (CAT) activities, elevated reduced glutathione (GSH) content, and a higher GSH/GSSG ratio; glycolysis-related enzyme activities were enhanced, with increased pyruvate kinase (PK) activity under 125-500 Hz exposure and elevated hexokinase (HK) activity at 250 Hz; and immune function was impaired, as shown by increased coelomocyte mortality, reduced phagocytic activity, and inhibited acid phosphatase (ACP) and alkaline phosphatase (AKP) activities, whereas respiratory burst activity showed no significant change. Among all treatments, 250 Hz induced the most pronounced physiological responses. Transcriptomic analysis of coelomocytes from the 250 Hz group identified 663 differentially expressed genes, including 537 upregulated and 126 downregulated genes, mainly enriched in pathways related to apoptosis, phagosome, lysosome, glutathione metabolism, arachidonic acid metabolism, and carbohydrate metabolism. These findings indicate that low- to mid-frequency acoustic exposure can act as a physiological and molecular stressor to S. intermedius coelomocytes by affecting redox homeostasis, enhancing energy metabolism, and suppressing immune effector processes, with 250 Hz showing the strongest effect under the present exposure conditions. This study provides experimental evidence for evaluating the potential biological effects of low- to mid-frequency acoustic exposure on benthic echinoderms.

Animals

Form and function of actin impacts actin health and aging.

The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin structure and function influence lifespan and various hallmarks of aging in Caenorhabditis elegans. Whole-animal and tissue-specific knockdown of actin and key actin-binding proteins (ABPs)-arx-2 (Arp2/3), unc-60 (cofilin), and lev-11 (tropomyosin)-led to premature disruption of filament organization, reduced lifespan, and tissue-specific physiological defects. Actin dysfunction also displayed a more "aged" transcriptome using previously validated transcriptomics clocks, and broadly exacerbated many age-associated phenotypes, including mitochondrial dysfunction, lipid dysregulation, loss of proteostasis, impaired autophagy, and intestinal barrier failure. Pharmacological destabilization with Latrunculin A mirrored genetic knockdowns, while mild stabilization with Jasplakinolide modestly extended lifespan, emphasizing that optimal and finely tuned actin function is critical for healthy aging. Finally, analysis of human genome-wide association data revealed that common ACTB polymorphisms correlate with differences in age-related decline in gait speed, suggesting some links between aging and actin across organisms. Taken together, our results provide a comprehensive and publicly accessible resource that maps, for the first time, how changes in actin integrity correlate with diverse aging phenotypes across tissues. This descriptive framework is intended to enable future mechanistic discovery by offering a deep, unbiased dataset that can be integrated with emerging studies to define how actin dynamics can potentially influence aging.

actin

Longitudinal comparison of treat-to-target states and clinical outcomes in patients with late-onset versus early-onset systemic lupus erythematosus.

OBJECTIVE: We compared demographic and clinical characteristics between patients with late-onset (LO) and early-onset (EO) systemic lupus erythematosus (SLE) and examined their longitudinal associations with treatment targets and long-term outcomes, irreversible organ damage accrual and health-related quality of life (HRQoL). METHODS: We analyzed prospectively collected data from patients enrolled in the Asia Pacific Lupus Collaboration cohort. Patients diagnosed with SLE at age >50 years were classified as LO-SLE and compared with those diagnosed at age ≤50 years (EO-SLE). Longitudinal associations with treatment targets (LLDAS and DORIS remission), organ damage accrual (SLICC/ACR Damage Index), and HRQoL (SF36v2 physical and mental component summary (PCS and MCS) scores) were examined using multivariable multilevel logistic, recurrent-event survival, and linear mixed-effects models, respectively. Disease activity, flares, medication exposure, and other clinical characteristics were also compared between groups. RESULTS: Among 3,917 patients studied, 346 (8.8%) had LO-SLE. Compared with EO-SLE, patients with LO-SLE had lower disease activity, lower glucocorticoid and immunosuppressant exposure, and higher attainment of treatment targets; LO-SLE was associated with higher odds of attaining LLDAS (OR: 2.33 (1.66, 3.28)) and DORIS remission (OR: 2.22 (1.45, 3.38)). However, they were at a greater risk of damage accrual (HR:1.82 (1.50, 2.21)) and lower PCS scores, meaning poorer physical health (regression coefficient (RC) = -3.63 (-4.58, -2.68)) but not MCS (RC= 0.68 (-.50, 1.86)). CONCLUSION: Despite higher attainment of treatment targets, patients with LO-SLE experienced greater damage accrual and poorer physical health, suggesting that disease activity targets alone may not fully capture outcome risk in LO-SLE.

Journal Article

Adaptive proteomic remodeling and eNOS upregulation in luminal endothelium and perivascular adipose tissue of patent saphenous vein grafts after CABG.

OBJECTIVE: Long-term patency of saphenous vein grafts (SVGs) remains a significant challenge in coronary artery bypass grafting (CABG). The biological factors underlying successful human grafts are poorly understood. We aimed to characterize the structural and molecular features associated with successful graft function. METHODS: Patent and occluded SVG and internal thoracic artery (ITA) grafts were obtained from explanted hearts of CABG patients undergoing heart transplantation for end-stage heart failure not attributable to graft failure, along with freshly harvested ITA and SVG controls. Samples underwent histomorphological analysis, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics. RESULTS: Patent ITA (ITA-P) showed minimal intimal hyperplasia with medial reinforcement, whereas patent SVGs (SVG-P) had organized, α-smooth muscle actin (αSMA)-positive myofibroblast-rich neointima. Endothelial nitric oxide synthase (eNOS) was markedly upregulated in patent grafts at two sites-the luminal endothelium and adventitial microvessels within perivascular adipose tissue (PVAT)-and lost at both sites in occluded SVG (SVG-O). Adventitial CD31-positive microvessels were significantly increased in patent grafts. Proteomically, ITA-P and SVG-P shared a largely common adaptive proteome enriched in translation, RNA processing, and extracellular matrix (ECM) organization, with shared upstream activation of NR4A3, EGFR, and STAT1, and conduit-specific signatures (IGF-1/RUNX2 in ITA-P; RETN/SRC/PTGES in SVG-P). PTGES was strongly expressed in the adventitia of SVG-P. CONCLUSIONS: Patent arterial and venous bypass grafts exhibited a shared adaptive phenotype characterized by dual-site upregulation of eNOS in both the luminal endothelium and the perivascular microvessels/PVAT. In SVG-P, PTGES was co-upregulated alongside eNOS, indicating a mechanistic link between the proteomic and IHC findings. These findings highlight the perivascular compartment as a site of adaptive, eNOS-associated changes in patent vein grafts.

Humans

Congenital Laryngomalacia: Pathophysiology, Clinical Spectrum, and Holistic Management.

Congenital laryngomalacia is the most common cause of infant stridor and arises from interacting structural, neuromuscular, and inflammatory mechanisms that produce dynamic supraglottic collapse. Disease severity spans mild stridor to significant obstruction, aspiration, and failure to thrive, often influenced by comorbid medical conditions. Diagnosis relies on flexible laryngoscopy supported by instrumental swallowing studies and microdirect laryngoscopy and bronchoscopy when indicated. Most infants respond to conservative management, particularly targeted feeding modifications, while acid suppression offers benefit in selective cases. Supraglottoplasty provides effective, durable improvement for severe disease and significantly enhances infant outcomes and family quality of life.

Humans

Temporal shifts in gyrA mutation types and sublineage replacement in ST11 Salmonella enterica serovar Enteritidis over a decade (2014-2023): A genomic epidemiological study in Guangxi, China.

The overuse or abuse of antibiotics drives the global health threat of antimicrobial resistance. Although bans on certain veterinary antibiotics, such as colistin, have proven effective, the impact of fluoroquinolone stewardship on the evolution of the foodborne pathogen Salmonella enterica serovar Enteritidis (S. Enteritidis) remains unclear. Here, we conducted a decade-long (2014-2023) retrospective longitudinal genomic epidemiological analysis of 441 ST11 S. Enteritidis isolates from Guangxi, China, alongside a global reference dataset of 4297 genomes. Our aim was to elucidate the effect of real-world antibiotic stewardship on the shift of gyrA point mutations and lineage distribution. Surveillance identified three global epidemic clade sublineages (GEC-L2, L3, L4), with the multidrug-resistant GEC-L4 (i.e., GC-c or MMC2), characterized by the gyrA mutation with amino acid substitution D87Y, being domestically dominant (70.07%, 309/441). Following China's 2016 ban on the veterinary use of critical fluoroquinolones, the proportion of the highly resistant GEC-L4 sublineage decreased continuously (from 86.84% in 2017 to 56.00% in 2023), while the less resistant GEC-L3 sublineage (i.e., GC-b or MMC1), mainly characterized by gyrA D87G, increased simultaneously (from 13.16% to 44.00%). This phenomenon might be attributed to the fact that the GEC-L4 sublineage exhibited a higher fitness cost compared with the GEC-L3 sublineage, as confirmed by the competition assay. A Random Forest Model validated that the gyrA mutation with amino acid substitution D87Y was the paramount feature for these sublineages' identification. In contrast, global data showed a continuous increase in gyrA mutations (from 8.63% in 2006 to 68.85% in 2024), primarily D87Y (from 1.44% to 31.15%) and D87N (from 4.32% to 22.95%), correlating with rising average fluoroquinolone consumption. This study provides direct genomic evidence that national-level antibiotic stewardship can drive the replacement of highly resistant sublineages with moderately resistant ones. These findings offer crucial scientific evidence for evaluating the impact of antibiotic management policies and inform strategies for the rational use of antimicrobials.

China

Effects of an actuated ankle exoskeleton on walking stability in healthy adults: a controlled laboratory study.

BACKGROUND: Ankle exoskeletons are widely used to reduce the metabolic cost of walking, yet their effects on walking stability during unperturbed gait remain insufficiently understood. Walking stability can be characterized using complementary measures that capture stride-to-stride variability, global temporal organization, and local dynamic stability. Understanding how walking with an actuated ankle exoskeleton system influences these different aspects of gait stability is essential for the safe design and control of wearable robotic devices. METHODS: Eighteen healthy adults walked on a treadmill at a constant speed (1.1&#xa0;m/s) with and without an actuated bilateral ankle exoskeleton in a randomized crossover design. Spatiotemporal variability was quantified using coefficients of variation (CoV) of stride length, step width, and stance ratio. Global gait stability was assessed using detrended fluctuation analysis of stride time. Local dynamic stability was evaluated using maximum Lyapunov exponent calculated for the trunk, hip, upper leg, lower leg, and foot. Paired-samples two-sided t-tests were used to compare conditions. RESULTS: Walking with the ankle exoskeleton resulted in increased stride-to-stride spatiotemporal variability, reflected by higher CoV values for stride length (p&#x2009;<&#x2009;0.001) and stance ratio (p&#x2009;=&#x2009;0.005), while mean stride length and step width remained unchanged. Mean stance ratio was reduced in the exoskeleton condition (p&#x2009;<&#x2009;0.001). Global gait stability did not differ between conditions, indicating preserved long-range temporal gait organization. Local dynamic stability increased at the lower leg (p&#x2009;<&#x2009;0.001) and foot (p&#x2009;=&#x2009;0.019) when walking with the exoskeleton. CONCLUSIONS: Walking with the actuated ankle exoskeleton alters gait control across multiple levels during steady walking. While stride-to-stride variability in stride length and stance ratio increased, global gait stability remained unchanged. Local dynamic stability was increased at the lower leg and foot, suggesting segment-specific effects of ankle-level assistance close to the assisted joint. However, these findings should be interpreted as the combined effect of wearing the exoskeleton and receiving active assistance, rather than the isolated effect of plantarflexion assistance. These&#xa0;results provide insight for the design and control of ankle exoskeletons with respect to stability-related effects during walking.

Humans

Selective monitoring of trace-level catechin and myricetin in herbal and aqueous matrices using magnetic MIP-DSPME: Optimization via design of experiments.

A novel dispersive solid-phase microextraction approach utilizing a magnetic molecularly imprinted polymer (MMIP) integrated with HPLC-UV detection was developed for the concurrent quantification of catechin and myricetin in herbal extracts and aqueous samples. The sorbent was engineered as a core-shell nanocomposite, consisting of a selective polymer layer deposited onto Fe3O4@SiO2-APTMS magnetic nanoparticles. Dual-template imprinting using catechin and myricetin generated complementary binding cavities within the polymer framework. Experimental variables influencing extraction were systematically screened and subsequently optimized. A Plackett-Burman design was first applied to identify the most influential factors, with pH and sorption time identified as the dominant variables. These parameters were subsequently fine-tuned using a central composite design, and the optimization process was completed in only 30 experimental runs. The sorption characteristics of the imprinted sorbent (MMIP) were compared with those of its non-imprinted counterpart (MNIP). The MMIP demonstrated markedly higher maximum binding capacities (Qmax), reaching 119.3&#xa0;mg&#xa0;g-1 for myricetin and 112.1&#xa0;mg&#xa0;g-1 for catechin, whereas the corresponding values for the MNIP were 32.55 and 32.08&#xa0;mg&#xa0;g-1, respectively. Moreover, the affinity constants (KL&#xa0;=&#xa0;0.760-0.950&#xa0;L&#xa0;mg-1) were approximately 2.3-fold higher for the MMIP, confirming its stronger and more selective interactions with the target analytes. The selectivity coefficients for the targeted flavonoids relative to structurally related compounds, including ferulic acid, p-coumaric acid, melatonin, and curcumin, exceeded 3.5 for the MMIP, whereas the corresponding values for the MNIP were close to 1.1, demonstrating the high molecular recognition capability of the imprinted sorbent. Method validation demonstrated limits of detection (LODs) of 0.33-0.59&#xa0;ng&#xa0;mL-1 and limits of quantification (LOQs) of 1.10-1.96&#xa0;ng&#xa0;mL-1, and excellent linearity over the concentration range of 5.0-5500&#xa0;ng&#xa0;mL-1 (R2&#xa0;>&#xa0;0.998). The method achieved recoveries of 93.96% to 105.69% with RSDs below 5.5%, while the preconcentration factors ranged from 209 to 229. Furthermore, the sorbent retained more than 95% of its extraction efficiency after four consecutive reuse cycles and more than 80% after six cycles, demonstrating excellent stability and reusability. The proposed method was successfully applied to the analysis of six medicinal plant extracts and water samples, showing negligible matrix interference and superior sensitivity, selectivity, and operational simplicity compared with conventional solid-phase extraction methods.

Flavonoids

Insights into the fate and dynamics of antibiotic resistance in multidrug-resistant Bacillus cereus during in vitro simulated gastrointestinal digestion.

Bacillus cereus, an important pathogen responsible for causing foodborne diseases worldwide, releases pore-forming enterotoxins, which target host epithelial cells, leading to osmotic lysis and ultimately manifesting as diarrheal syndrome. Moreover, some B. cereus strains carry antimicrobial resistance genes that confer multidrug resistance against a spectrum of antibiotics. Characterizing the survival traits of multidrug-resistant (MDR) B. cereus strains in the intestinal microenvironment is essential for developing targeted strategies to effectively manage diarrheal foodborne diseases caused by this pathogen. This study used whole-genome sequencing (WGS) to evaluate the pre- and post-digestion toxigenic potential, antimicrobial resistance profiles, and genetic diversity of MDR B. cereus strains isolated from food samples in Guangdong Province, China. The four B. cereus isolates investigated in this study exhibited a genetic diversity, as determined by multilocus sequence typing analysis of WGS data. All four isolates produced the diarrheal toxins Hbl, Nhe, and CytK to varying levels, indicative of their potential to cause outbreaks of foodborne diseases. Each of the four isolates exhibited resistance to more than three classes of antibiotics, fulfilling the criterion for multidrug resistance. At an initial concentration of 9 log colony-forming units (CFU)/mL, the intestinal concentration of these four isolates crossed the threshold required to induce widespread diarrhea in the general population. Under rice slurry protection, all tested isolates maintained intestinal concentration beyond the threshold when the initial concentration was increased to &#x2265;8 log CFU/mL. Moreover, the upregulations of genes associated with acid tolerance, bile tolerance and stress response were observed in the surviving MDR B. cereus isolates. Digestion markedly altered the antibiotic resistance profiles of the MDR B. cereus isolates. In the absence of a food matrix, the MDR isolates lost their resistance to imipenem, meropenem, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole post-digestion and was influenced by the initial concentration of the strains. In the presence of food matrix rice slurry, the effects of digestion on the antibiotic resistance of MDR B. cereus isolates can be mitigated, enabling them to maintain their antibiotic resistance to the greatest extent. Most remarkably, after digestion, the isolates Bce055 and Bce166 exhibited newly emergent resistance to cefotetan and trimethoprim-sulfamethoxazole, respectively. Our findings clarify the fate of MDR B. cereus isolates in the gastrointestinal tract and inform the development of prevention and control strategies for foodborne diseases caused by this pathogen.

Drug Resistance, Multiple, Bacterial

The landscape of pruning for large language models: A systematic review and unified taxonomy.

Confronting the inherent tension between the exceptional capabilities and the immense computational costs of Large Language Models (LLMs), pruning has become a crucial technique for achieving efficient deployment. However, a systematic analytical framework dedicated specifically to LLM pruning remains absent. In this paper, we aim to bridge this gap. We first elucidate the theoretical foundations that underpin the effectiveness of pruning, namely overparameterization and redundancy, and then propose a multidimensional taxonomy that organizes existing approaches along the axes of granularity, timing, and criteria. Building upon this unified perspective, we further analyze performance recovery mechanisms and the broader evaluation ecosystem, while also exploring forward-looking challenges such as interpretability, automation, and hardware-algorithm co-design. Through this comprehensive synthesis, we seek to provide an integrated and coherent analytical lens for advancing both research and practice in LLM pruning.

Large Language Models

Design, rationale, and baseline patient characteristics for the Sickle Cell Disease and CardiovAscular Risk-Red cell Exchange (SCD-CARRE) trial.

BACKGROUND: Despite wide utilization of automated red blood cell exchange (RBCX) transfusion in adult patients with sickle cell disease (SCD), no consensus or quality efficacy data exist on its use. The Sickle Cell Disease and CardiovAscular Risk- Red cell Exchange (SCD-CARRE) trial tests the hypothesis that an automated chronic RBCX transfusion strategy reduces acute health care encounters and death while improving quality of life and end-organ function (cardiac, pulmonary and renal) in participants with SCD that are at high risk of death. METHODS: Adult patients with SCD with elevated tricuspid regurgitant jet velocity (TRV) and/or chronic kidney disease were considered to be at high risk of death and were randomly assigned to RBCX plus standard of care vs standard of care alone. Participants assigned to RBCX received 12 months of exchange transfusions to maintain target pretransfusion hemoglobin S% < 30%, post-transfusion hemoglobin S% < 20%, and post-transfusion hemoglobin concentration &#x2265;10 g/dL. All study participants were managed according to NHLBI/ASH/ATS Expert Panel guidelines. The primary endpoint was the number of SCD acute health care encounters or death over 13 months. Secondary endpoints included measures of cardiovascular and renal function, exercise capacity, patient reported outcomes (all collected at baseline, and months 4, 8, and 12), and transfusion-related adverse events (collected monthly). RESULTS: Between 2020 and 2025, the SCD-CARRE trial randomized 173 participants at 23 sites across 3 countries. Enrolled participants had mean (SD) age of 45.8 (11.8) years and 54% were female. At baseline, participants had average TRV of 2.8 (0.5) m/s such that 45.9% had a TRV between 2.5 to 2.9 m/sec and 28.1% had a TRV &#x2265; 3.0 m/sec. The median (Q1, Q3) eGFR in this cohort was 60 (36, 110) mL/min/1.73 m2. The median (Q1, Q3) 6-minute walk test distance was 375 meters (309, 439), the median daily steps were 3,728 (2,187, 5,821), and participants experienced a median (Q1, Q3) of 2 (1, 5) pain episodes in the year prior to randomization. The trial results are pending. CONCLUSIONS: The SCD-CARRE trial successfully enrolled a cohort of n = 173 adults with SCD. This study highlights a rationale to evaluate the effect of automated chronic RBCX transfusion strategy plus standard of care as compared to standard of care alone in SCD patients at high risk of death with a focus on patient centered outcomes, preservation of cardiovascular function, end-organ complications and death. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT04084080, https://clinicaltrials.gov/study/NCT04084080.

Adult

Rare clinical complications following scorpion envenomation worldwide: A systematic review.

Scorpion envenomation is an important public health problem in many tropical and subtropical regions and may result in rare but life-threatening grade III complications involving multiple organ systems. This systematic review synthesizes published articles from 2000 to 2025 that describe uncommon, severe clinical manifestations following scorpion stings. A total of 71 rare clinical complications were identified, encompassing cardiovascular, neurological, respiratory, renal, hematological, ocular, dermatological, and other systemic manifestations. Cardiovascular complications were the most frequently reported, whereas neurological complications exhibited the greatest clinical diversity. Mesobuthus tamulus and Hemiscorpius lepturus were most commonly associated with severe complications, and children younger than 10 years appeared to be at increased risk of serious neurological involvement. These findings highlight the remarkable clinical heterogeneity of grade III scorpion envenomation and emphasize the importance of early recognition, species-specific clinical awareness, and timely management to reduce severe outcomes in endemic regions.

Humans

Hierarchical modeling of tumor subtypes in cell lines using large-scale genomic datasets.

Cancer cell lines (CLs) are widely used to study tumor biology and drug response, yet their translational relevance is often limited by inaccurate subtype annotations. Existing CL-tumor matching approaches are frequently constrained by flat classification schemes, weak subtype definitions, and the exclusion of normal tissue references, leading to potential confounding of tumor-specific and tissue-of-origin signals. To address these limitations, a hierarchical classification (HC) framework is presented in which CLs are aligned with patient tumors across biological resolutions, from organ to molecular subtype. Gene expression profiles from 802 CLs, 5,612 tumors from The Cancer Genome Atlas (TCGA) , and 8,939 non-cancerous tissues were integrated to separate oncogenic signals from tissue-specific signals. Node-specific features were selected using maximum relevance minimum redundancy, and balanced accuracies of 89% in cross-validation and 75%, and 80% on external datasets were achieved. Through the framework, 43 CLs were reassigned, and clinically relevant underrepresented subtypes were identified.

cancer cell lines

First Report of Fibromyxoma in a Greater Amberjack (Seriola dumerili) From Aquarium of Genoa.

In teleosts, mesenchymal tumours like fibromas are frequently observed, whereas their malignant counterparts, fibrosarcomas, occur only sporadically. In our study, an adult female greater amberjack (Seriola dumerili) reared at the Aquarium of Genoa developed a slow-growing mass protruding from the ventral right side of the head. The tissue was firm and white greyish with localized cranial haemorrhaging on the external surface. Cut-section examination showed a homogeneous, dry, whitish and richly vascularized tissue layout. Tissue samples from the mass were stained with Masson's Trichrome, Alcian Blue-PAS (pH&#x2009;2.5), and Toluidine blue for differential diagnosis. Microscopically, it was characterized by alternating collagenous spindle-cell septa and hypocellular metachromatic myxoid areas positive for acidic mucopolysaccharides and glycosaminoglycans. The absence of cellular atypia, mitotic activity and necrosis confirms the diagnosis of fibromyxoma. Documenting rare tumours in aquarium fish expands comparative pathology literature and highlights public aquaria as valuable research platforms for long-term health monitoring under controlled husbandry conditions.

fibromyxoma

Recent advances in supramolecular macrocycle-based artificial light-harvesting systems.

Artificial light-harvesting systems (ALHSs) inspired by the antenna function of natural photosynthesis provide molecular platforms for collecting excitation energy and directing it to emissive or reactive acceptors. In many supramolecular ALHSs, however, practical performance is limited by poorly defined donor-acceptor orientation, aggregation-caused quenching (ACQ), interfacial defects, and limited stability in aqueous or complex media. Supramolecular macrocycles-particularly pillar[n]arenes (PAs), cucurbit[n]urils (CBs), calixarenes (CAs), cyclodextrins (CDs), and supramolecular coordination complexes (SCCs)-offer a useful design space because their cavities, pre-organized scaffolds, and reversible non-covalent interactions can confine chromophores, tune local donor/acceptor ratios, and modulate F&#xf6;rster resonance energy transfer (FRET). This Review systematically examines the unique structural advantages and assembly mechanisms of the five macrocyclic families, with an emphasis on their use in constructing ALHSs-from single-step to cascaded FRET-and in advancing aqueous photocatalysis, near-infrared bioimaging, panchromatic fluorescence modulation, and singlet oxygen generation. The resulting structure-property-application framework is intended to guide the rational design of macrocycle-assisted photofunctional materials while avoiding overextension of the photosynthesis analogy.

Journal Article