Search Results (788)

Metabolic reprogramming constitutes a fundamental hallmark of malignancy, enabling cancer cells to sustain proliferation and survival under physiological stress. While aerobic glycolysis is well characterized, fatty acid oxidation (FAO) has emerged as a decisive driver of oncogenic progression and therapeutic resistance. Acylcarnitines (ACs), obligatory intermediates for the mitochondrial transport of long-chain fatty acids, have transcended their traditional categorization as passive metabolic byproducts to function as potent signaling entities and functional readouts of mitochondrial oxidative throughput. This review delineates the AC metabolic axis in oncology, examining the coordinated biochemical machinery, including the carnitine palmitoyltransferase (CPT) system, carnitine–acylcarnitine translocase (CACT; SLC25A20), and organic cation/carnitine transporter 2 (OCTN2), that governs cellular AC homeostasis. We further evaluate the clinical utility of altered AC profiles as non-invasive biomarkers for early diagnosis and risk stratification across diverse malignancies, highlighting their capacity to reflect metabolic bottlenecks and flux dynamics. Additionally, we scrutinize therapeutic strategies targeting the AC-FAO axis, demonstrating how the inhibition of key transporters and enzymes sensitizes tumors to conventional chemotherapy and immunotherapy. Ultimately, deciphering the systemic and spatial dynamics of ACs remains essential for advancing precision metabolic oncology and developing personalized therapeutic strategies based on metabolic profiling. Full article

Background/Objectives: Olfactory dysfunction and dysgeusia are common neurosensory manifestations of Coronavirus Disease 2019 (COVID-19), affecting approximately 60% of patients. These symptoms have been mechanistically linked to receptors involved in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) cell entry, including angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), furin, and neuropilin-1 (NRP1), which are highly expressed in the olfactory epithelium. Nevertheless, clinical evidence supporting a direct association between receptor expression and sensory impairment remains inconsistent. Methods: We conducted a multicenter, observational, cross-sectional study including 104 adults with polymerase chain reaction–confirmed SARS-CoV-2 infection during the first and second pandemic waves. Approximately 75 days after diagnosis, nasal and/or pharyngeal samples were obtained to quantify gene expression levels of ACE2, TMPRSS2, furin, and NRP1 using quantitative polymerase chain reaction. Olfactory dysfunction and dysgeusia were recorded as dichotomous variables. Logistic regression analyses were performed with adjustment for age, sex, and race, considering receptor expression as continuous variables and as tertiles. Missing data were addressed using multiple imputation methods. Results: Olfactory dysfunction was reported by 37.5% of participants, and dysgeusia by 36.5%. No statistically significant associations were observed between baseline expression levels of ACE2, TMPRSS2, furin, or NRP1 and the presence of olfactory dysfunction or dysgeusia in either adjusted continuous or categorical models. Although these associations did not reach statistical significance, higher ACE2 and furin expression showed a nonsignificant trend toward an increased probability of sensory alterations, whereas intermediate NRP1 levels were associated with lower disease severity. Conclusions: COVID-19-related olfactory dysfunction and dysgeusia do not appear to be directly determined by isolated baseline expression of SARS-CoV-2 entry receptors. These findings support a multifactorial and dynamic pathophysiological model involving temporal receptor regulation, inflammatory processes, and host-related factors, highlighting the need for longitudinal and interventional studies. Full article

Aldolases are powerful biocatalysts for the stereoselective formation of carbon–carbon bonds and are widely used in the synthesis of chiral intermediates for pharmaceutical applications. Among them, 2-deoxyribose-5-phosphate aldolase (DERA) has been extensively exploited for the preparation of the conserved side chain of statins. In this work, we report a novel chemoenzymatic approach for the synthesis of nucleobase-substituted lactol products as potential precursors of new statin analogues. A C49M variant of DERA from Pectobacterium atrosepticum (PaDERA C49M) was employed to catalyze sequential aldol additions using aldehyde-functionalized nucleobases as non-natural electrophilic substrates. The formation of nucleobase-containing lactols was confirmed, demonstrating for the first time the acceptance of nucleobase-derived aldehydes in DERA-catalyzed aldol reactions. This strategy provides access to structurally novel statin side-chain precursors and expands the synthetic potential of DERA toward the generation of new classes of bioactive compounds. Full article

As large language models (LLMs) are increasingly used as digital respondents and generative agents in computational social science, prior work has primarily focused on the fidelity of their expressed opinions, often overlooking a fundamental question: the behavioral stability of outputs across repeated runs of the same model when the persona specification and task conditions remain unchanged. This paper proposes a behavioral stability evaluation framework for role-playing tasks, using the Political Compass questionnaire as the testbed. The questionnaire maps responses onto a two-dimensional coordinate system defined by an economic axis and a social axis, enabling political orientations to be directly quantified and compared in a continuous space. To ground the simulation in realistic user behaviors, we construct personas from publicly available social media texts and stratify them based on Political Signal Clarity. Across three LLMs, we compare repeated questionnaire completions under different decoding temperatures and prompting strategies. We characterize it along two complementary dimensions: dispersion of the resulting two-dimensional coordinates across runs, measured by an Overall Stability Score (OSS), and dispersion of per-item choices across runs, quantified by response entropy. We further use linear mixed-effects models to account for persona-level heterogeneity and to estimate the effects of key factors on stability. Our results show that coordinate drift and item-level dispersion do not always move in tandem. Increasing temperature typically amplifies variability, although models differ in their sensitivity. Contrary to its success in reasoning tasks, Chain-of-Thought (CoT) prompting failed to enhance stability in this value-laden context. Instead, it frequently amplified coordinate drift by introducing stochasticity into intermediate reasoning steps. Results show that LLMs exhibit greater behavioral stability when role-playing personas with clearer political signals. These findings suggest that stability should be treated as a pre-study benchmark before deploying LLM-based role-playing simulations, and that key generation settings and stability statistics should be reported alongside substantive conclusions. Full article

Producer share indicators summarize how value is distributed along agrifood supply chains, yet their temporal dynamics remain difficult to compare across products and periods. This paper proposes a reproducible time-series analytics framework to characterize and group producer-share trajectories derived from paired origin–destination price series. We compute producer share time series for a set of agrifood products and quantify similarity using complementary measures capturing co-movement and shape, including Pearson-correlation-based proximity and Euclidean distance on standardized representations. To reduce dimensionality and mitigate noise, we apply principal component analysis and perform unsupervised clustering (k-means) to identify classes of products exhibiting comparable producer-share dynamics. The resulting clusters provide an interpretable typology of market behaviors, highlighting homogeneous groups that may share structural drivers (e.g., commercialization patterns or intermediation margins). We further discuss how cluster membership can support decision-making in crop substitution and market monitoring by revealing products with analogous temporal responses. The proposed pipeline is simple to implement, fully data-driven, and adaptable to other commodity-price settings. Full article

Identifying a metabolic rescue for mitochondrial toxins induced neurodegeneration is a promising therapeutic target. Dopaminergic neurons are high energy dependent neurons, owing to their metabolic functions, and this makes them vulnerable in conditions of bioenergetic failure and mitochondrial dysfunction. In this study, we explored the protective potential of sodium propionate, a short-chain fatty acid and metabolic precursor of succinate, against mitochondrial toxin-induced neurotoxicity in MN9D dopaminergic cells. Cells were treated with 200 µM sodium propionate after exposure to 1.5 µM rotenone or 10 µM antimycin A, and cell viability, intracellular ATP levels, reactive oxygen species (ROS) generation, and dopaminergic markers were assessed. Our results show that sodium propionate significantly attenuates mitochondrial toxin-induced loss of cell viability and ATP depletion while reducing oxidative stress and preserving the expression of enzymes involved in catecholamine biosynthesis pathway, including tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH). These findings suggest that sodium propionate confers functional protection to dopaminergic neurons under mitochondrial toxin stress. Sodium propionate is proposed to act as a metabolic precursor to succinyl-CoA, thereby replenishing tricarboxylic acid cycle intermediates and supporting cellular metabolic homeostasis. Under Complex I inhibition (rotenone) and complex III inhibition (antimycin A), sodium propionate treatment was associated with preservation of cellular ATP levels. Across conditions, sodium propionate treatment was associated with improved cell viability, reduced oxidative stress associated signals, and preservation of dopaminergic function. Together, these data indicate that sodium propionate supports dopaminergic neuronal resilience through toxin-dependent metabolic and cellular stress modulating effects. Full article

The effect of cold atmospheric plasma (CAP) (a pin-to-liquid DBD) (28–32 kV, 1–10 min) on virgin olive oil (VOO) lipid oxidation was kinetically investigated. Quality assessment was performed (bioactive compound concentrations and fatty acid profiles) while the samples were further characterized by Fourier Transform Infrared (FTIR) spectroscopy and proton Nuclear Magnetic Resonance (¹H NMR). Intense processing (>5 min and voltages > 31 kV) significantly affected the quality of VOO, enhancing the oxidative reactions. CAP treatment led to an eight-fold increase in peroxide values and to a decrease in total antioxidants by up to 80% compared to untreated VOO. Carbonyl compounds (aldehydes, carboxylic acids) and hydroperoxide intermediates were the main oxidation products, while polyunsaturated fatty acids (PUFAs) dropped from 81.17% to 76.51%. The double bonds in the acyl chains were also highly reactive and facilitate the oxidation and subsequent fragmentation of the VOO. Full article

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been identified as forever chemicals and pose a serious threat to the environment due to their stable C–F bond. The current methods are ineffective or costly for PFAS remediation. In response, this study develops a dielectric barrier discharge (DBD) air plasma system capable of simultaneously treating perfluorooctanoic acid (PFOA)-contaminated wastewater and enhancing waste-activated sludge (WAS) solubilization through the subsequent use of plasma-activated water (PAW). Air plasma achieved 94% PFOA degradation and 32% defluorination within 40 min—substantially outperforming Ar and N₂ plasma—due to the co-generation of hydrated electrons (e_aq⁻), ^•OH, and reactive nitrogen species (RNS). Scavenging experiments confirmed that e_aq⁻ is the primary initiator of C–F bond cleavage, while H₂O₂ and NO₂⁻ synergistically form peroxynitrous acid (ONOOH), further promoting chain-shortening reactions. UPLC-MS identified PFHpA, PFHxA, PFPeA, and PFBA as key intermediates. The air plasma effluent contained high concentrations of NO₂⁻-N and H₂O₂ under acidic conditions, enabling PAW to induce strong oxidative stress on WAS, resulting in significant extracellular polymeric substance (EPS) release (DOC up to 134 mg/L), improved sludge filterability (capillary suction time (CST) reduced by ~85%), and shifts in microbial community. This study presents a dual-functional air plasma approach that enables both PFAS degradation and sludge treatment, improving the overall competitiveness and applicability of plasma technology for advanced wastewater treatment. Full article

This paper provides a systematic review of urushiol-based antibacterial coatings for lacquer art applications, focusing on three key dimensions: molecular mechanisms, durability, and safety. Natural lacquer films form a dense three-dimensional network through laccase-catalyzed oxidative cross-linking, endowing them with excellent mechanical properties and corrosion resistance, while the catechol structure in urushiol confers broad-spectrum antibacterial potential. The article elaborates on the synergistic antibacterial mechanisms of urushiol, including covalent reactions with bacterial proteins via quinone intermediates, induction of oxidative stress, and metal ion chelation. It also reveals the dynamic change pattern of coating antibacterial activity over time, characterized by “high initial efficiency- gradual mid-term decline—long-term stabilization,” a process influenced collectively by side-chain unsaturation, degree of curing, and environmental factors such as temperature, humidity, and light exposure. From an application perspective, this review examines modification approaches such as silver/titanium dioxide composite systems, structurally regulated sustained-release strategies, and anti-adhesion surface designs, while pointing out current limitations in artistic compatibility, long-term durability, and safety assessment. Particularly in scenarios involving food contact and cultural heritage preservation, migration risks from unreacted urushiol monomers and metal nanoparticles, as well as the inherent sensitization potential of urushiol, remain critical challenges for safe application. Accordingly, this paper proposes the establishment of a holistic research framework covering “material design–process control–performance evaluation” and advocates for the development of functional coating systems with low migration, high biocompatibility, and preserved aesthetic value. Such advances are essential to promote the sustainable development and safe application of urushiol-based antibacterial coatings in fields such as cultural heritage conservation, daily-use utensils, and high-end decorative arts. Full article

Lignin, an abundant and renewable biopolymer, holds significant potential for asphalt modification owing to its unique aromatic structure and reactive functional groups. This review summarizes the main lignin preparation routes and key physicochemical attributes and assesses its applicability for enhancing asphalt performance. The physical incorporation of lignin strengthens the asphalt matrix, improving its viscoelastic properties and resistance to oxidative degradation. These enhancements are mainly attributed to the cross-linking effect of lignin’s polymer chains and the antioxidant capacity of its phenolic hydroxyl groups, which act as free-radical scavengers. At the mixture level, lignin-modified asphalt (LMA) exhibits improved aggregate bonding, leading to enhanced dynamic stability, fatigue resistance, and moisture resilience. Nevertheless, excessive lignin content can have a negative impact on low-temperature ductility and fatigue resistance at intermediate temperatures. This necessitates careful dosage optimization or composite modification with softeners or flexible fibers. Mechanistically, lignin disperses within the asphalt, where its polar groups adsorb onto lighter components to boost high-temperature performance, while its strong interaction with asphaltenes alleviates water-induced damage. Furthermore, life cycle assessment (LCA) studies indicate that lignin integration can substantially reduce or even offset greenhouse gas emissions through bio-based carbon storage. However, the magnitude of the benefit is highly sensitive to lignin production routes, allocation rules, and recycling scenarios. Although the laboratory research results are encouraging, there is a lack of large-scale road tests on LMA. There is also a lack of systematic research on the specific mechanism of how it interacts with asphalt components and changes the asphalt structure at the molecular level. In the future, long-term service-road engineering tests can be designed and implemented to verify the comprehensive performance of LMA under different climates and traffic grades. By using molecular dynamics simulation technology, a complex molecular model containing the four major components of asphalt and lignin can be constructed to study their interaction mechanism at the microscopic level. Full article

The solar-driven conversion of CO₂ into long-chain (C₃₊) products offers a sustainable pathway to mitigate climate change, produce carbon-neutral fuels and value-added chemicals. Over the past few decades, significant advances have been achieved in CO₂ photoreduction; however, most systems still favor C₁ products (CO, CH₄) or C₂ intermediates. However, the synthesis of C₃₊ products poses a formidable challenge due to the complex multi-electron transfer steps required for C–C bond formation. This review provides a concise overview of recent progress in solar-driven photocatalytic and photothermal CO₂ reduction, with a specific focus on the formation of C₃₊ products. The fundamental principles are discussed, including the critical role of C–C coupling mechanisms and the stepwise reaction pathways for C₃₊ products. It highlights how the extended carbon chain length significantly increases the complexity and reduces selectivity, with the suppression of side reactions being a primary research objective. Key catalytic strategies, such as the use of copper-based materials, are examined for their unique ability to facilitate these demanding transformations. Finally, the major challenges are outlined, and a future outlook for this field is provided, with an emphasis on the need for advanced catalyst design and in situ characterization to unlock the potential of solar fuels. Full article

A novel optimized bioactive lipid (OBL) rich in long-chain polyunsaturated omega-3 fatty acids (n-3 LCPUFA) was synthesized through enzymatic acidolysis using concentrated belly oil from rainbow trout (Oncorhynchus mykiss) (CB) and tocopherols obtained from cold-pressed maqui seed oil (Aristotelia chilensis (Mol.) Stuntz) (MSO) under supercritical CO₂ conditions. The reaction was catalyzed by Candida antarctica lipase B (CALB) and optimized using a 3² response surface design with 12 experimental runs and three central points, considering pressure (100–300 bar) and temperature (50–80 °C) as independent variables. The response variables included the concentrations of EPA, DHA, α-, β-, γ-, and δ-tocopherols, as well as β- and γ-tocotrienols. MSO contained 10.63, 25.62, and 53.55 g·100 g⁻¹ total fatty acids (TFAs) of α-linolenic, oleic, and linoleic acids, respectively, together with 280.95 mg α-tocopherol·kg⁻¹ and 89.75 mg β-tocotrienol·kg⁻¹. The CB contained 49.57 g EPA + DHA·100 g⁻¹ TFAs. Optimal conditions (72.7 °C and 248.9 bar), experimentally validated at the RSM-predicted point, yielded an OBL containing 41.28 g EPA + DHA·100 g⁻¹ TFAs, 0.39 mg α-tocopherol·kg⁻¹, 3.54 mg β-tocopherol·kg⁻¹, 18.48 mg β-tocotrienol·kg⁻¹, 6.92 mg γ-tocopherol·kg⁻¹, and 16.36 mg γ-tocotrienol·kg⁻¹. Oil quality evaluation using official AOCS methods showed that the OBL exhibited an acceptable oxidative status within international regulatory limits while retaining a measurable phenolic content and intermediate antioxidant capacity derived from MSO. This study demonstrates the successful synthesis of a stable OBL from agro-industrial by-products as a sustainable source of functional ingredients for food, nutraceutical, and cosmetic applications. Full article

Higher olefins are a class of alkenes widely used as intermediates in the production of essential consumer and industrial products. This radiolabel disposition and partial mass balance study investigated the distribution and excretion of four ¹⁴C-radiolabelled alpha higher olefins (i.e., 1-octene, 1-decene, 1-hexadecene, and 1-eicosene) in male Wistar rats following a single oral dose (100 mg/kg). Blood, liver, kidney, adipose tissue, urine, and faeces were collected and analysed for total ¹⁴C-derived radioactivity. Urinary elimination was rapid, with approximately 70% and 90% of total radioactivity recovered in urinary excreted within 24 and 48 h, respectively. Excretion patterns showed a clear chain-length-dependent trend: shorter-chain olefins (C8, C10) exhibited higher urinary excretion, indicating greater systemic absorption, while longer-chain olefins (C16, C20) were primarily eliminated via faeces, suggesting limited intestinal uptake. Tissue distribution was minimal in blood, liver, and kidney, but adipose tissue retention increased with chain length. Total recovery of administered radioactivity in the analysed matrices was low, ranging from 17% to 60%. Importantly, because exhaled ¹⁴CO₂ and volatile parent compounds were not captured, the missing fraction cannot be quantified and the balance cannot be considered closed. All in all, the current study describes the partial disposition of higher olefins and highlights the influence of molecular size and lipophilicity on the biological fat, though further studies are required to fully characterise their metabolic profile and total elimination kinetics. Full article

The growing emphasis on sustainable material design has intensified interest in bio-based additives as environmentally friendly alternatives to conventional synthetic modifiers. This study evaluates the effects of four natural compounds—cetyl alcohol, thymol, lanolin, and lecithin—on the thermal, rheological, mechanical, surface, and aging properties of regranulated low-density polyethylene (RLDPE). Post-consumer polyethylene waste was used as the polymer matrix, while biochar served as a sustainable reinforcing filler replacing carbon black. Differential scanning calorimetry, melt flow index measurements, rheological behavior, surface energy analysis, mechanical testing and thermo-oxidative aging assessments were conducted to assess structure–property relationships. Biochar increased stiffness, hardness, and impact resistance but reduced ductility and melt flow due to restricted chain mobility. The addition of natural compounds partially compensated for these effects by improving melt flow, modifying crystallization behavior, and enhancing resistance to thermo-oxidative degradation without severely diminishing mechanical performance. Cetyl alcohol promoted the highest crystallinity and flexural properties, lanolin exhibited the strongest plasticizing effect and improved post-aging ductility, while lecithin and thymol produced intermediate changes, with lecithin significantly increasing surface energy. These results indicate that selected natural additives can act as effective ecological plasticizers or processing aids in biochar-filled recycled polyethylene composites. Full article

This study examines how investment efficiency and risk jointly shape sustainable grain supply-chain upgrading. Using firm-level panel data for 25 listed grain supply-chain firms in China from 2015 to 2023, this study examines efficiency–risk structures and their heterogeneity across upstream, midstream, and downstream segments. A three-stage data envelopment analysis (DEA) is applied to measure investment efficiency while controlling for environmental heterogeneity and statistical noise, and a multidimensional investment risk index is constructed using principal component analysis (PCA), with an emphasis on sustainability metrics. The results reveal a clear supply-chain gradient: downstream firms exhibit the highest mean third-stage investment efficiency (crete = 0.633) and scale efficiency (scale = 0.634), midstream firms are intermediate (crete = 0.308; scale = 0.326), and upstream firms remain lowest (crete = 0.129; scale = 0.138). This ordering is also visible year by year, while risk profiles indicate higher exposure upstream and pronounced volatility midstream. Efficiency decomposition shows that upstream inefficiency is mainly driven by scale inefficiency rather than insufficient pure technical efficiency. Overall, efficiency–risk mismatch—manifested as persistent low scale efficiency and elevated risk exposure in upstream, volatility in midstream, and stability in downstream—constitutes a key micro-level barrier to long-term and resilient upgrading. The study thus offers policy-relevant insights for segment-specific interventions that align with sustainable agricultural development: facilitating land consolidation and integrated risk management for upstream scale inefficiency, promoting supply-chain finance and digital integration for midstream risk volatility, and leveraging downstream stability to drive coordinated upgrading and sustainable value creation through market-based incentives. Full article