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In recent years, the application of gas injection, particularly carbon dioxide (CO2) dissolved in water, known as carbonated water (CW), has gained increasing attention. In this context, the current study is designed to examine the effect of CO2 dissolution in water under pressures ranging from 500 to 4500 psi, covering subcritical to supercritical conditions, and at temperatures between 25°C-65°C. Additionally, the synergistic effects of surfactants, namely dioctyl sulfosuccinate sodium salt (AOT) and sodium dodecyl polyoxyethylene ether sulfate (AES), were examined at concentrations ranging from 0 to 700 ppm, along with the dissolved CO2 on IFT and swelling factors. The measurements revealed that as the pressure increased, the swelling factor reached a maximum value of 19.3% when it was contacted with crude oil, while the maximum swelling factor for the solutions contacted with synthetic mixed resinous and asphaltenic oil (SMRAO) was reached at a value of 22.3%. The second oil type was selected as SMRAO since crude oil comprises thousands of components, making it hard to extract any generalized conclusions based on the obtained results. In this way, using only one or two specific fractions, especially resin and asphaltene which acts as natural surfactants, providing the chance to examine the generalized interactions between chemicals and oil fractions. The measurements revealed that the presence of surfactant in the carbonated water (CW) reduced the swelling factor up to 50% for AOT and 38% for AES as the pressure and temperature and surfactant concentration increases. The reason of this observed trend was correlated to the bulky structure of AOT compared with the linear chain-like structure of AES. Besides, the measurements revealed the positive impact of pressure and temperature on a higher swelling factor regardless of the used surfactants, which can be due to the higher dissolution of CO2 under higher pressures and better movement and migration of CO2 molecules, which means a penetration of higher amount of CO2 into the oil drop leading to higher swelling factors. In the next stage, the IFT of different solutions under different temperatures (25 °C-65 °C) and pressures (0-4500 psi) was measured. The obtained IFT values showed that using SMRAO instead of crude oil has a reducing impact on the IFT values with minimum value of 19.2 mN/m, while the IFT value for similar thermodynamic condition and crude oil was 23.1 mN/m. Besides, further IFT measurements revealed that although increasing pressure has a reducing impact on the IFT, increasing temperature increases the IFT values regardless of the presence of surfactant or even the type of surfactant. The measurements also revealed that the effect of AES on the IFT reduction was better than AOT, leading to a minimum IFT value of 1.1 mN/m for AES concentration of 700 ppm dissolved in CW with pressure and temperature of 4500 psi and 65 °C, respectively due to longer alkyl chain length and easier packing in the interface compared with AOT which has a bulky structure prevents the high number of AOT molecules to be packed in the interface. The measured IFT values revealed the linear IFT variation behavior for the systems were in contact with SMRAO compared with crude oil due to this fact that the SMRAO has less complexities than crude oil comprises of thousands of components makes the IFT variations more straightforward for SMRAO.

Hepatocellular carcinoma represents a major global health challenge, with its link to the commensal microbiota being clearly established. However, developing reproducible microbial biomarkers for early-stage hepatocellular carcinoma diagnosis across diverse populations remains challenging. We conducted an integrative analysis of 13 studies, examining 16S rRNA sequencing data from 607 fecal samples and 263 liver tissue samples. Data processing utilized VSEARCH, QIIME, and R packages (vegan, phyloseq, cooccur, random forest), with PICRUSt for functional prediction. Alpha diversity analysis revealed significant differences in liver microbiota but not in gut microbiota between hepatocellular carcinoma patients and non-cancer individuals. Linear Discriminant Analysis Effect Size identified Blautia and Streptococcus as biomarker shared across the gut and liver micro-niches. Based on the internal data, the models constructed using gut and liver microbiome characteristics demonstrated high discriminative ability (gut model AUC = 0.8064; liver model AUC = 0.9645). Mendelian randomization analysis revealed a potential association between Streptococcus and the development of hepatocellular carcinoma. KEGG enrichment analysis further indicated marked functional differences in microbiota, primarily linked to metabolic irregularities, between cancer patients and controls. Therefore, this study reveals unique gut-liver microbial community features in patients with hepatocellular carcinoma, identifies potential cross-site diagnostic biomarkers, and constructs gut and liver predictive model with good performance, providing preliminary evidence for the application of microbial biomarkers in the early diagnosis and screening of hepatocellular carcinoma.

Probiotic supplements are marketed for diverse health benefits, yet species inclusion often lacks functional rationale. Our survey of 352 over-the-counter probiotic products available in the USA revealed 36 unique microbial species. However, there is no clear link between species inclusion and the intended health benefit. Here, to address this gap, we developed HaPaPro, a collection of 1,012 genome-scale metabolic models spanning pathogenic, probiotic and host-associated bacteria, constructed from publicly available genome sequences. Flux balance analysis revealed that probiotic species fail to capture the metabolic diversity of host-associated microbes. Focusing on vaginal health, we computationally identified vaginal microbes with metabolic profiles overlapping Gardnerella vaginalis. In vitro spent media assays using 11 vaginal isolates showed variable inhibition of G. vaginalis, primarily driven by D-lactic acid production, which was also produced by non-Lactobacillus species. These findings highlight the need for function-based probiotic design and demonstrate a scalable framework integrating metabolic modelling with experimental validation.

Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous hematological malignancy. Here, to better define this clinically taxing and translationally challenging malignancy, we applied a multiomics approach, consisting of 13 modalities to analyze 173 treatment-naive individuals with AML. By integrating these 'omes', we identified distinct AML subtypes, genotype-phenotype associations, biomarkers and pathobiological mechanisms. Across the spectrum of primitive and committed AML, we found extensive metabolomic and lipidomic reprogramming driven by divergent MYC and mTOR activity. We linked metabolic changes to striking hyperacetylation of mitochondrial proteins in CEBPA-mutant AML. Protein-centric subtyping revealed a distinct NPM1-mutant subset characterized by outlier expression of FOXC1 and HOXB8/9. To nominate therapeutic targets across subtypes, we developed a multiomic machine-learning approach and validated MTA1 as a contributor to panobinostat resistance. Altogether our findings underscore the complex nature of AML and provide a clinically and translationally informed unified view that reveals coalescent phenotypes across multiomic layers.

To examine the surgical outcomes of surgical aortic valve replacement in the transcatheter aortic valve replacement era and propose a novel patient-specific prognostic model. We randomly divided 772 patients with aortic stenosis who underwent surgical aortic valve replacement in 2016-2021 into two cohorts (derivation, 515; validation, 257). In the derivation cohort, no data were missing for any patients for the candidate predictors including age, sex, body mass index, left ventricular ejection fraction, levels of albumin, hemoglobin, and serum creatinine, presence of chronic atrial fibrillation, and end-stage renal disease requiring hemodialysis. We developed possible scoring models using Cox proportional hazards regression with overall survival as the endpoint and calculated the cross-validated 5-year C-statistics to assess accuracy. The mean patient age was 74.2 years, and 46.9% were female. Kaplan-Meier analysis revealed overall 1- and 5-year survival rates of 96.6 and 88.7%, respectively. The 5-year C-statistic of the derivation cohort was 0.785 (95% confidence interval: 0.716-0.853), while the estimated 1-, 3-, and 5-year C-statistics of the validation cohort were 0.885 (0.806-0.965), 0.888 (0.824-0.953), and 0.801 (0.702-0.901), respectively. Calibration plots revealed good agreement between predicted and actual 5-year survival (intraclass correlation coefficient = 0.955; 95% confidence interval: 0.827-0.989). This novel survival prediction model after isolated surgical aortic valve replacement in the transcatheter aortic valve replacement era showed good survival prediction, and may guide the decision-making process for surgical aortic valve replacement versus transcatheter aortic valve replacement with lifetime management.

The manchette is a transient microtubule (MT)-based structure that is vital for the correct shaping of sperm during spermiogenesis. Throughout spermiogenesis, the manchette retains structural integrity for several days, raising the question of how its MTs are regulated. Here, using cryo-electron tomography of manchettes isolated from rat testes, we find that manchette MT ends are structurally diverse. We show that the MT-binding protein CLASP2 is present throughout the manchette and likely regulates both MT ends. Using cryo-electron microscopy single particle analysis and super-resolution microscopy, we reveal that SPACA9 and MNMIP1 (SH3D21) bind to the seam of manchette MTs from the luminal side. SPACA9 binds to both α- and β-tubulin of protofilament 1 but does not interact directly with protofilament 13, while MNMIP1 binds directly to protofilament 13. MNMIP1 further extends and threads through the MT lattice at the seam. Our study reveals a novel seam MT inner protein complex with a unique binding mode, providing a plausible explanation for MT regulation that maintains manchette integrity over an extended period.

End-of-life decision-making in the intensive care unit (ICU) is ethically complex, particularly for very old patients with limited physiological reserve. Decisions to limit life-sustaining treatment are shaped by medical prognosis, patient values, cultural and socioeconomic contexts, and uncertainty regarding outcomes. Non-beneficial treatment refers to interventions unlikely to provide meaningful benefit while imposing additional burden or suffering, and avoiding such treatment is central to high-quality end-of-life care. Limitation of life-sustaining treatment may involve withholding or withdrawing therapies, which are distinct from euthanasia, and should be accompanied by a transition toward comfort-focused care. Frailty, pre-illness functional status, and illness severity are key determinants of outcomes and treatment decisions in very old ICU patients. Large international studies, including the VIP, VIP2, and COVIP cohorts, demonstrate that frailty is strongly associated with mortality, functional decline, and treatment limitation, while revealing substantial regional variation in end-of-life practices. Prognostication remains imprecise, often leading to prolonged aggressive care despite poor long-term outcomes. Shared decision-making, grounded in transparent communication and alignment with patient goals, is the ethical standard but is frequently undermined by discordance between documented preferences and delivered care. When decision-making capacity is lost, in the majority of countries shared decision-making extends to surrogate decision-makers, who often experience emotional burden and limited accuracy in predicting patient preferences. Ongoing, structured conversations, meticulous documentation, and time-limited trials of intensive therapy can support iterative reassessment of goals of care.

The growing interest in plant-based therapeutics has led to increased exploration of medicinal flora for their nutritional and pharmacological potential. The objective of this study was to determine the nutritional composition, phytochemical profile, and antioxidant activity of Cotoneaster microphyllus from Shimla, Himachal Pradesh. The proximate analysis revealed high levels of ash and fat in the leaves, while high fiber levels in the fruits. According to mineral profiling, leaves showed an abundance of Mg, Ca, Na, and Zn, while fruits indicated predominant presence of P and K. Phytochemical extractions were performed using hydromethanol, methanol, and aqueous solvents, with hydromethanol extract exhibiting the highest phytochemical content and antioxidant activity, followed by methanol and aqueous extracts. DPPH and FRAP antioxidant assays confirmed that C. microphyllus scavenges free radicals and reducing antioxidant potential effectively. Based on GC-MS and LC-MS analyses, cyclosiloxanes and phthalate ester compounds were identified via GC-MS and 50 unique compounds were identified via LC-MS, reported for the first time in Cotoneaster. UHPLC was also used to quantify chlorogenic acid, with fruit extracts showing the highest concentration. In this study, we provide a novel insight into the phytochemical composition and bioactive potential of C. microphyllus. There is a significant lack of systematic biochemical and functional evaluation of this species, so this study represents the first comprehensive integration of nutrition profiling, multi-solvent phytochemical quantification, and advanced characterization (GC-MS, LC-MS, and UHPLC) of different plant parts. These findings provide new insight into phytochemical composition of C. microphyllus and point to its potential as a source of bioactive chemicals with potential pharmacological and nutraceutical applications, which need for more biological validation.

Savannas are globally important ecosystems and unique in supporting abundant and diverse populations of wild large mammals. Mound building fungus-farming Macrotermitinae are key determinants of savanna structure and function. Termite colonies are sensitive to shade, and their lifetime reproductive success is substantially reduced in forests compared to open savanna areas. Here we experimentally show how ungulates, predominantly impala modify mound soil and vegetation cover and consequently internal temperature in Macrotermes subhyalinus epigeal nests. There are large differences in soil nutrient concentrations between the eastern and western termite mound sector. Ungulates selectively feed on the eastern side of the mounds, reducing vegetation cover and exposing that sector to the warming morning sun. Soil sodium concentration, an essential nutrient for heterotrophs is high on the eastern open mound sector on termite mounds. Important plant nutrients are accumulated on the western side of mounds, facilitating growth of vegetation that shade mounds from the hot afternoon sun. When excluding large herbivores from mounds by fencing, differences in sodium soil concentrations between the eastern and western side of the mound are no longer evident while other soil concentration differences are less pronounced. Following fencing, trees gradually established on the eastern side and eventually mounds were completely covered by trees. Shading arising from ungulate exclusion reduce internal mound temperature by 1.6 degrees, resulting in sub-optimal conditions for termite colonies. This study reveals unknown relationships between key functional groups in tropical savannas. The abundance of large iconic wild herbivores is declining over large African savanna areas. Reduced ungulate populations could in turn lead to sub-optimal conditions for Macrotermes termites with subsequent adverse consequences for litter decomposition and plant and animal diversity across African savannas.

Apicobasal polarity plays key roles in airway epithelial maturation and regeneration. Once polarized, the airway epithelium functions as a barrier against opportunistic pathogens. Yet, the mechanisms that temporally regulate polarization, a process which is disrupted in cystic fibrosis (CF), remain unclear. Here, we demonstrate the functional importance of connexin 43 (Cx43), a gap junction protein, which is normally repressed during regeneration of the airway epithelium. We show that prolonged post-transcriptional stabilization of Cx43 leads to altered collective cell orientation and compromised CF airway epithelial barrier. We report a bidirectional cooperation between Cx43 hemichannel function and adenosine signaling in disrupting ER-Golgi secretory axis, cytoskeleton dynamic and ectopic apical fibronectin production. Genetic and pharmacological inhibition of Cx43 channels re-established polarity and spatial organization of CF airway epithelial cells. Finally, targeting Cx43 hemichannels with mimetic peptides normalizes the CF-dependent fibronectin ectopic expression and prevents the enhanced Pseudomonas aeruginosa trapping to the CF epithelium. Our findings reveal a mechanism in which temporally controlled Cx43-mediated intercellular communication is crucial for coordinating intrinsic polarity programs and maintaining airway epithelium integrity.

Variants in TPMT and NUDT15 genes that affect thiopurine metabolism can guide personalized dosing to minimize toxicity. Decreased or no appreciable NUDT15 activity demonstrates impaired breakdown of active thiopurine metabolites which can lead to severe adverse events including potentially life-threatening myelosuppression. Recently, the NUDT15*6 allele was re-classified from having uncertain function to no function by the Clinical Pharmacogenetics Implementation Consortium. Here, we present a pediatric patient with a NUDT15*1/*6 genotype who experienced significant thiopurine-induced myelosuppression. The patient is a 4-year-old female with standard risk-average precursor B-cell acute lymphoblastic leukemia treated per AALL1731. Exome sequencing determined TPMT*1/*1 (normal metabolizer) and NUDT15*1/*6 (indeterminate metabolizer). After 75 mg/m2/day mercaptopurine, myelosuppression necessitated a three-week delay prior to the next phase of therapy. With 60 mg/m2/day thioguanine in a subsequent phase of therapy, she was admitted twice for fever and neutropenia. In the final phase of therapy, mercaptopurine at standard dosing of 75 mg/m2/day caused severe neutropenia and thrombocytopenia with elevated metabolite levels that required stopping mercaptopurine. After neutrophil recovery, a trial of 50% standard dosing was not tolerated and her dose was reduced to 27%, which was tolerated. Among 339 patients with cancer, sequencing revealed an allele frequency of 0.88% for NUDT15*6. In a larger cohort sequenced for suspicion of rare genetic disease, the frequency of NUDT15*6 was 0.15% among 1011 unrelated individuals. This brief report supports the recent update that patients with the NUDT15*1/*6 genotype should be classified as intermediate metabolizers.

Quantum kernel methods map clinical features into exponentially large Hilbert spaces where overlapping biological markers can become more separable than in fixed-dimensional classical feature spaces, but existing work evaluates single quantum feature maps, ignores barren-plateau failure modes, and relies on single train-test splits vulnerable to data leakage. Classical diagnostics for Parkinson's disease, breast cancer, and diabetes remain limited by the Specificity-Recall trade-off that fixed-dimensional kernels impose on overlapping biomarker distributions. We propose an adaptive hybrid quantum framework routing clinical data through three distinct quantum feature maps, namely Angle, Amplitude, and ZZ-entanglement, computing fidelity-based Gram matrices for Quantum SVM and Quantum KNN classifiers. A Logistic Regression meta-learner, trained on strictly out-of-fold predictions from nested cross-validation (5-fold inner, 10-fold outer), learns which quantum kernel generalizes on each dataset and suppresses those that do not. Evaluated on Parkinson's (195 patients), Breast Cancer (569), and Diabetes (768) with 1,000-iteration bootstrapping, the ensemble raised Parkinson's Specificity from 0.585 to 0.813 ([Formula: see text]) while maintaining Recall above 0.95, matched classical RBF-SVM on Breast Cancer (all [Formula: see text]), and improved Diabetes Recall from 0.553 to 0.621 ([Formula: see text]). A standalone Variational Quantum Classifier failed on all datasets (ROC-AUC 0.51 to 0.57), confirming barren plateau limitations. Explainability via SHAP, LIME, and Permutation Importance revealed dataset-dependent kernel trust: the meta-learner suppressed QKNN Amplitude on Diabetes (coefficient [Formula: see text]) while amplifying it on Parkinson's (1.761). PCA-based feature backtracking recovered established biomarkers including Insulin and Glucose for Diabetes, vocal perturbation measures for Parkinson's, and nucleus geometry for Breast Cancer. Noise simulations confirmed graceful degradation under NISQ conditions. The framework performs data-driven kernel selection, removing the need to pre-specify an encoding strategy.

Living organisms have thermal limits above which they are unable to operate and survive. Our previous genetic screen identified proteins that impede the high-temperature growth of fission yeast, including the RNA-binding protein Dri1 and a fission yeast-specific protein termed Rhs1. Here, we show that Dri1 and Rhs1 form a complex and physically interact with the Ccr4-Not complex, a master regulator of mRNA metabolism. Gene expression analysis revealed that the Dri1-Rhs1 and Ccr4-Not complexes negatively regulate a set of genes implicated in ribosome biogenesis (Ribi genes). Loss of the Dri1-Rhs1 complex results in the augmented expression of Ribi genes, thereby suppressing the translation defects and the growth inhibition under high-temperature conditions. The thermosensitivity of the translational processes may be a determinant of the upper limit of the growth temperature in fission yeast.

The propylene methoxycarbonylation is a potential atom-economical reaction for the synthesis of butyrate esters, which minimizes wastewater discharge and alleviates subsequent separation difficulties. However, to the best of our knowledge, the mechanism of this reaction has not been thoroughly investigated, and the regioselectivity enhancement remains challenging. Herein, we studied the structure-performance relationship of Palladium-based homogeneous catalysts with different monophosphine and bisphosphine ligands by combining experiments and theoretical calculations. The ligands primarily influence the catalytic activity through electronic effects, while regulating product regioselectivity through steric effects. Using an optimized catalyst, the turnover frequency reaches 12,500 h-1 with a normal-to-iso selectivity ratio of 15.8, representing 13.9-fold and 6.6-fold improvements over a conventional palladium-phosphine catalyst. Mechanistic calculations reveal that regioselectivity is determined by the hydrogen insertion position in the first elementary step. Our work fills a gap in propylene methoxycarbonylation research and provides a basis for rational design of regioselective catalysts.

The accurate ability to predict the distribution of contact stress under reinforced concrete (RC) footings is important for the safety and serviceability of shallow foundations. Conventional analytical models idealizing the footing as rigid and soil as homogenous fail to capture the stress concentration and redistribution effects, especially under non-uniform loading. Earlier studies are mostly concentrated on sand; however, basalt soil has different mechanical characteristics as it possesses high stiffness, angularity, and interlocking effects. It also ignores stiffness loss due to concrete cracking. This study aims to fill these gaps through an experimental and numerical investigation of RC square footings resting on basaltic soil and the influence of the reinforcement ratio, yield strength of steel and strength of concrete. Within the laboratory conditions, four footings having different reinforcement ratios of 0.19%, 0.36%, 0.54% and 3.43% were tested under monotonic loading. Central and edge displacements were measured. Using a validated finite element model, a parametric study expanded the investigation to include reinforcement ratios of 0.54% to 4.80%, steel yield stresses of 240 MPa to 450 MPa and concrete compressive strengths of 20 MPa to 60 MPa, allowing systematic consideration of these parameters on central contact stress, ultimate load, deformation and energy absorption. The findings revealed that enhancing the reinforcement ratio from 0.54% to 4.80% resulted in an increase of 73.4% in central contact stress, 34.1% in ultimate load, and 55% in energy absorption, respectively. Increase in steel yield stress from 240 MPa to 450 MPa caused a 25.2% increase in central contact stress, 13% in ultimate load and 3.74% in energy absorption in laminated composite panel. The increase of concrete compressive strength from 20 MPa to 60 MPa increased central contact stress by 117.4% ultimate load by 70.4% and energy absorption by 270% showing this factor as dominant. These results show that the performance of footing on stiff basaltic soil mainly depends on the concrete strength and amount of reinforcement whereas careful use of steel yield stress. The insights provided by the study are critical for practical design. Furthermore, non-uniform contact stresses, stiffness degradation, and soil-structure interaction need to be accounted for optimizing strength and ductility.