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Oxygen depletion in biomolecular condensates is dominated by macromolecular density
Pepsin-driven corrosion of orthodontic titanium alloys in candidiasis-simulated saliva: electrochemical and statistical insights
Abstract Ti-6Al-4 V titanium alloy is widely utilized in orthodontic applications due to its favorable biocompatibility and mechanical properties. However, its long-term performance can be adversely affected by the dynamic and hostile oral environment, particularly under pathological conditions such as gastroesophageal reflux disease (GERD). Herein, In vitro corrosion behavior of Ti-6Al-4 V over a 240-hour immersion period at 37 °C in artificial saliva simulating GERD, with pepsin and Candida albicans , both individually and combined. Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization revealed that pepsin significantly improved corrosion resistance, achieving a maximum inhibition efficiency (IE) of 87.4%, while C. albicans showed a time-dependent decline in protection, with lower IE 71.8%. The combined presence of both agents further reduced IE to 55.6%, indicating a complex synergistic effect accelerating corrosion. Surface characterization by scanning electron microscopy (SEM) confirmed biofilm formation and surface degradation. Response Surface Methodology (RSM) modeling identified immersion time and component interactions as key factors influencing corrosion behavior. These findings offer novel insights into the interplay among enzymatic activity and microbial colonization, highlighting clinical implications for implant stability in GERD-affected oral environments.
Interpretable and generative deep learning models explicate phase separating intrinsically disordered motifs
Near-care assay of plasma glial fibrillary acid protein and ubiquitin carboxyl-terminal hydrolase isozyme L1 with shorter and prolonged duration exercise
Abstract Neurobiomarkers measured in peripheral blood can supplement management strategies following traumatic brain injury (TBI). Dual-assay of glial fibrillary acid protein (GFAP) and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) is FDA-approved to inform a decision threshold approach (GFAP > 30 µg.L − 1 and/or UCHL1 > 360 µg.L − 1 ) for post-TBI neuroimaging. As physical activity and thermal strain often accompany TBI-prone activities, we investigated whether each molecule’s quantification - and, by extension, clinical decisions - could be influenced by exercise-heat stress. In healthy volunteers monitored continuously for body core temperature (Tc), we used the i-STAT Alinity to assess plasma GFAP and UCHL1 responses to exercise in the laboratory (four female, eighteen male trained participants, cycling for 45 min in 32 °C) and field (three female and 22 male recreational marathon runners, finishing time 231 ± 34 min, peak ambient temperature 11 °C). Respective ΔTc overall were 1.42 ± 0.37 °C and 1.87 [1.53, 2.31] °C. With laboratory exercise, GFAP and UCHL1 did not exceed the manufacturer’s decision threshold. Across the marathon, GFAP was stable, whereas UCH-L1 more than doubled (200 [200, 200] vs. 462 [310, 782] µg.L-1, P < 0.0001), breaching the decision threshold for neuroimaging in 18/25 runners. Confounding from more severe exercise-heat stress should be considered when interpreting near-care assay of UCHL1 for TBI management.
Sustained interfacial powering through self-generated mantle and siphon of a gelling droplet
Abstract Autonomous motion in a persistent manner such as spinning of Euler’s disk is long-sought-after by natural or artificial microsystems due to their limited energy loading and is particularly challenging for Marangoni motors as inhomogeneity of active molecules is difficult to sustain. Here we show that by releasing a droplet containing hydrogel precursor and non-small active molecules on a diluted crosslinking-agent solution, the droplet self-propels with a lifetime 300-to-1000-fold longer. It is found that continuously crosslinking hydrogel shell cuts rapid surfactant diffusion and accompanying volumetric contraction perforates the shell and generates a vent through which active molecules are unidirectionally released. The mechanism echoes squid’s jet propulsion wherein water is expelled out of a siphon by contracting mantle. Such self-generated contracting mantle-siphon configuration of a gelling droplet maximizes the localized concentration inhomogeneity and protracts adsorption saturation on water surface, improving the efficiency and lifetime of Marangoni motors for sustained powering of interfacial machines. The unfolded strategy potentially provides solutions for microscale release control which will be of interest to microrobots, materials assembly, and biomolecules transport.
The construction and refined extraction techniques of knowledge graph based on large language models
Opposite effects of chronic HIV infection and antiretroviral medication on organismal and organ-specific biological aging
Protective effect of Baicalin against doxorubicin-induced cytotoxic and electrophysiological damage in human iPSC-cardiomyocytes
Abstract Doxorubicin (DOX) remains one of the most effective chemotherapeutic agents for a variety of solid tumors and hematological malignancies. Nevertheless, its clinical utility is restricted by DOX-induced cardiotoxicity (DIC), primarily driven by oxidative stress, inflammation, and apoptosis. Baicalin (BAI), a natural compound with antioxidant, anti-inflammatory, and anti-cancer properties, has shown cardioprotective effects in DOX-treated animal cardiac models, but its impact on human cardiomyocytes remains unexplored. This study was designed to assess the cardioprotective effects of BAI against human cardiac DIC using induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). hiPSC-CMs were pretreated with BAI and exposed to acute (1 µM for 24 h) and long-term (0.3 µM for 7d) DOX treatments, with or without different BAI concentrations (1 µM, 10 µM, and 25 µM). Multielectrode array (MEA) analysis, Tunel and cleaved-caspase 3 staining, reactive oxygen species (ROS) analysis, and sarcomere protein staining were performed to assess the effects of BAI on human DIC. BAI treatment alleviates DOX-induced cytotoxic injury, reducing apoptosis, oxidative stress, and preventing sarcomere disorganization. Moreover, BAI attenuated the long-term DOX-induced electrophysiological alterations, stabilizing field potential duration, beat rate, spike amplitude, and conduction velocity. These findings suggest the potential protective role of BAI against the DOX-induced human cardiac toxicity, supporting a potential clinical application in cancer patients.
Latent transition analysis for longitudinal studies of post-acute infection syndromes
Abstract Post-Acute Infectious Syndromes (PAIS) refer to the symptoms persisting months after initial infection. Clinical research studies on this topic often collect rich, multi-modal datasets. Yet, the complexity of the datasets and the lack of a precise clinical case definition pose difficulties in creating comprehensive analyses. Here, we present a generalisable framework for analysing data from longitudinal studies of PAIS using Latent Transition Analysis (LTA). It enables the identification of disease phenotypes and the patient-level analysis of transitions between them, without relying on predefined clinical categorisations. Furthermore, we introduce a method for incorporating covariate information, which enables exploration of how patient characteristics influence disease trajectories. We apply this methodology to the ORCHESTRA dataset, composed of individuals affected by SARS-CoV-2 infection from multiple European centres, for investigation into Post-COVID-19 condition (PCC). 5094 patient assessments were collected at SARS-CoV-2 infection, and at 6, 12, 18, and 24 months of follow-up. Our model identifies distinct PCC phenotypes with patient trajectories impacted by age and sex. Our results highlight how LTA can enhance the interpretability of complex, time-resolved clinical data, support personalized patient monitoring and management, and accelerate therapeutic development for other PAISs, too.
Identification of ubiquitination-related signature genes for predicting kidney transplant rejection
Abstract Kidney transplant rejection (KTR) poses significant challenges to long-term graft survival, with involvement from ubiquitination-related genes (URGs) in immune modulation. This study aimed to identify key URGs linked to KTR and develop a predictive model for rejection risk. mRNA array data from the Gene Expression Omnibus were analyzed to find differentially expressed genes in GSE98320, which were intersected with URGs to yield 16 DE-URGs. Gene Ontology and KEGG enrichment analysis highlighted the NF-kappa B and TNF signaling pathways. A URGScore model stratified patients and revealed significant differences in immune cell infiltration, especially among Treg cells, demonstrating strong predictive performance in the discovery cohort (AUC = 0.774, 95% CI 0.747–0.800). Six signature genes ( DTX3L , MARCH1 , NCF4 , RNF125 , TRIM21 , TRIM22 ) were identified, and their expression displayed a subtype-dependent gradient, increasing from antibody-mediated rejection to T cell-mediated rejection and reaching the highest levels in mixed rejection. These genes were incorporated into a nomogram, which achieved an AUC of 0.771 (95% CI 0.745–0.798). Validation in independent datasets confirmed the model’s reliability. In the two transplant rejection cases, MARCH1 and RNF125 showed higher expression than the other biopsy samples, while generalized high expression of all marker genes was observed in an IgA nephropathy patient. Together, these findings demonstrate the clinical relevance of URG-based biomarkers in KTR and provide molecular insight into immune-mediated rejection.
Severe and widespread coral reef damage during the 2014-2017 Global Coral Bleaching Event
Abstract Ocean warming is increasing the frequency, extent, and severity of tropical-coral bleaching and mortality. During 2014–2017, marine heatwaves caused the Third Global Coral Bleaching Event. We analyze data from 15,066 reef surveys globally during 2014–2017. Across all surveyed reefs, 80% and 35% experienced moderate or greater (affecting >10% of corals) bleaching and mortality, respectively. We assess the global extent of coral bleaching and mortality by applying bleaching response curves calibrated from surveyed reefs to predict bleaching globally, based on comprehensive remote-sensing of heat stress. These models predict that 51% and 15% of the world’s coral reefs suffered moderate or greater bleaching and mortality, respectively, during one or multiple years, surpassing damage from any prior global coral bleaching event. Our findings demonstrate that the impacts of ocean warming on coral reefs are accelerating, with the near certainty that ongoing warming will cause large-scale, possibly irreversible, degradation of these essential ecosystems. With heat stress levels during this event surpassing those observed previously, the National Oceanic and Atmospheric Administration developed more extreme Bleaching Alert levels that are now being used during the ongoing Fourth Global Coral Bleaching Event.
AI based optimization of injection pressure for hydrogen and spirogyra biodiesel dual fuel engine to enhance combustion performance and emission characteristics
Abstract The principal objective of this research is to employ modern machine learning techniques to optimize high-pressure biofuel injection strategies for sustainable energy applications. An engine powered with biofuel and hydrogen (H₂) under dual-fuel (DF) mode was tested under a varied fuel injection pressure range from 180 to 240 bar for optimization and modeling. The results demonstrate that an injection pressure of 220 bar produces enhanced engine performance. At this pressure, enhancements were noted in combustion characteristics, efficiency, and emission levels. The ignition delay (ID) at 220 bar injection pressure was 9.4% longer than at 240 bar injection pressure. The 220 bar IP mix demonstrated reduced peak cylinder pressure (PCP) and heat release rate (HRR) compared to the 240 bar. A 12.4% rise in brake-specific fuel consumption (BSFC) was observed at 220 bar inlet pressure. Nevertheless, although brake thermal efficiency (BTE) increased with increasing injection pressure (IP), the increase at 220 bar was somewhat less than that at 240 bar. Despite elevated nitrogen oxide (NOx) emissions with the 220 bars compared to pure diesel, carbon monoxide (CO) and hydrocarbon (HC) emissions were markedly decreased. Smoke emissions were reduced with the 220 bars in comparison to diesel and other fuel combinations. Three machine learning models were employed to establish a predictive control framework. The decision tree (DT) model had the greatest accuracy, with R² values of 0.9792 for PCP and 0.9710 for HC, alongside near-zero MAPE for BTE and HC This study underscores the potential of AI-driven biofuel optimization for fostering sustainable transportation and renewable fuel strategies, paving the way for large-scale adoption of low-carbon, high-efficiency energy solutions.
Ship wake-induced water column mixing and meter-scale seabed erosion in the Baltic Sea
Abstract Commercial shipping is a cornerstone of global trade. Its impact on the marine environment, however, remains underexplored. This study combines hydroacoustic data, sediment samples, propeller-induced shear stress calculations and vessel tracking information to assess the effects of shipping in one of the busiest maritime regions in the Baltic Sea, the Bay of Kiel. We unveil substantial seafloor erosion, including up to 1.5 m variation in water depths, over 10 years that clearly relates to vessel traffic. By imaging water column disturbance behind passing ships, we trace wake turbulence to the seafloor and show the breakdown of a strongly stratified water column and a possible excitement of internal waves, likely increasing the mixing of oxygen, nutrients, and greenhouse gases. While the environmental consequences of this anthropogenic stressor are unquantified, our findings leave little doubt that they include modifications to marine ecosystems and element budgets on a Baltic-wide scale.
Comparison of TyG indices and atherogenic index of plasma with hypertension in the PERSIAN Guilan cohort
Targeting NHEJ activates STING signaling through MYC degradation to boost antitumor immunity in SCLC
Removal of Sr (II) from aqueous solutions by adsorption using amberlite XAD-7 resin impregnated with TOPO extractant
Surface hole polaron site tuning governs charge carrier separation in BiVO4 photoanodes
Abstract The self-trapping of charge carriers, resulting in the formation of polarons, significantly restricts the separation and transport of charge carriers in photoelectrochemical systems. Herein, using bismuth vanadate as a model photoanode, we propose a surface-selective strategy to regulate hole polarons. Density functional theory calculations predict that substituting bismuth ions with indium ions suppresses hole polaron formation by weakening electron-phonon coupling. This substitution is achieved through a liquid-phase cation exchange method, enabling precise surface modification. The electron paramagnetic resonance, temperature-dependent photoluminescence spectroscopy, in situ irradiation X-ray photoelectron spectroscopy, and femtosecond time-resolved absorption spectroscopy all confirm the suppression of hole polaron formation. After loading co-catalyst, the optimized photoanode achieves a water-splitting photocurrent density of 6.46 mA cm -2 at 1.23 V versus the reversible hydrogen electrode, with an applied bias photo-to-current efficiency of 2.19%. The unbiased tandem system exhibits a solar-to-hydrogen conversion efficiency of 6%. Here, we show that suppressing surface hole polaron formation facilitates hole carrier release, offering a pathway for enhancing photoelectrochemical performance.