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This study investigated the effects of three low-temperature conditioning (LTC) treatments on the storage quality and postharvest physiology of "Dajixin" wampee (Clausena lansium) fruit during cold storage at 3 °C for 16 days. Treatments included LTC 1 (12 °C, 4 d), LTC 2 (8 °C, 4 d), and LTC 3 (stepwise 12 °C for 2 d then 8 °C for 2 d). Compared with direct cold storage (control), LTC 2 reduced the browning index by 22.9% (from 3.80 to 2.93, P < .05), suppressed weight loss (7.17% vs. 7.90%, P < .05), and maintained higher total soluble solids (19.58% vs. 17.11%, P < .05). LTC 2 inhibited malondialdehyde accumulation (6.37 vs. 7.52 µmol/g, P < .05), enhanced superoxide dismutase and phenylalanine ammonia lyase activities, and suppressed peroxidase and polyphenol oxidase activities relative to the control. Furthermore, LTC 2 maintained higher total phenolic content (1.72 mg GAE/100 g FW at day 12) and DPPH radical scavenging activity (75.5% at day 12). Among the three protocols, LTC 2 (8 °C, 4 d) was the most effective in delaying postharvest senescence and reducing browning, providing a practical protocol for extending the shelf life of cold-sensitive wampee fruit.
A rapid method for triaging febrile patients by aetiology (e.g., viral or bacterial infection) using gene expression in peripheral blood (PB) is an intensively researched area. However, gene expression in blood represents a composite sum of gene expression of all the component cell types present in the sample. As a result, numerous genes are measured in most proposed signatures. Herein, we propose a simple ratio-based biomarker (RBB) called direct leukocyte subpopulation-transcript abundance assay (DIRECT LS-TA) that recapitulates gene expressions of a single cell type in PB (i.e., monocytes). Based on single-cell RNA sequencing (scRNAseq) data and bulk expression data, IFI27 and SIGLEC1 are found as interferon-stimulated genes (ISGs) predominantly expressed by monocytes. The DIRECT LS-TA method can use a simple ratio of two genes measured in PB as an RBB to represent the target gene expression in monocytes without the need for monocyte purification. Both scRNAseq and bulk RNA sequencing datasets were used to evaluate the correlation between ISG expression in monocytes and PB, with a particular focus on monocyte expression of IFI27. An iceberg plot of bulk transcriptome data was used to identify genes that were predominantly expressed by monocytes in PB. DIRECT LS-TA RBBs of the three genes (IFI27, IFI44L and SIGLEC1) were evaluated by group-wise comparison, receiver operating characteristic and meta-analysis. In addition, the conventional interferon (IFN) score was evaluated for comparison of diagnostic performance. In viral infection datasets, DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) was most intensely activated (p value by t test <1e-9) and had the best area under the curve (0.94) among the three potential monocyte ISGs analysed. DIRECT LS-TA SIGLEC1 was also another monocyte biomarker but showed a lower activation (p<9e-5). IFI27/PSAP showed better diagnostic performance than the conventional IFN score. On the other hand, IFI44L was not a predominant monocyte expression gene. DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) measured in PB was the best biomarker of viral infection and IFN activation among ISGs predominantly expressed by monocytes. It performed even better than the conventional IFN score which required quantification of eight genes. The results suggest that DIRECT LS-TA of IFI27 is a monocyte-informative biomarker which is easy to determine in PB without the need for cell sorting.
Bepotastine possesses a short half-life (~2 h) and a narrow absorption window limited to the upper small intestine, necessitating a gastro-retentive drug delivery system for once-daily administration. In this study, we developed a low-density gastro-retentive tablet designed for instantaneous floating (zero lag time) to prevent premature gastric emptying-a critical limitation of conventional floating systems. This was achieved through a rational engineering approach using AutoCAD-based geometric integration to precisely control the initial apparent density below 1.004 g/cm3. The synergistic combination of low viscosity hypromellose (15 cP) and magnesium aluminometasilicate facilitated immediate buoyancy and sustained it for over 4 h through wicking-induced air entrapment and robust gel layer formation. In beagle dogs, the gastro-retentive tablet achieved 95.7% systemic exposure relative to a twice-daily reference, whereas non-floating sustained-release formulations reached only 64.5-88.6%, highlighting the necessity of gastric retention. Notably, a randomized clinical study in 28 healthy subjects confirmed that the scaled-up gastro-retentive formulation was bioequivalent to the reference product. Produced via standard manufacturing processes, the 100,000-tablet batch also demonstrated no clinically significant food effect. Species-specific physiologically based pharmacokinetic modeling mechanistically estimated gastric residence times of approximately 180 min in beagles and 360 min in humans, supporting the interpretation that the system may withstand multiple interdigestive migrating motor complex cycles. These findings validate the proposed gastro-retentive platform as a clinically viable, industrially scalable strategy for drugs with site-specific absorption.
The green tide alga Ulva prolifera shifts from an attached to a floating state during bloom formation, yet the physiological basis of this transition remains unclear. Here, using attached and floating thalli derived from a single parental clonal line and cultured under identical controlled conditions, we combined physiological measurements, protein-fraction analysis, and transcriptomics to compare growth and resource-allocation patterns between the two states. Despite similar bulk carbon and nitrogen contents, floating thalli reached significantly greater thallus length than attached thalli. Attached thalli showed higher maximum photosynthetic rate (Pmax), dark respiration (Rd), effective PSII quantum yield (Y(II)), and photosynthetic nitrogen-use efficiency (PNUE), whereas floating thalli showed higher maximum PSII efficiency (Fv/Fm) but lower Pmax, Rd, and PNUE. Together, these physiological patterns suggest that floating thalli maintain PSII efficiency while operating with lower photosynthetic capacity and respiratory demand. Floating thalli also exhibited higher levels of water-soluble (Pr) and SDS-soluble (Pp) proteins, together with lower levels of the SDS-insoluble fraction (Pw), consistent with reduced investment in detergent-insoluble structural pools. Transcriptomic analysis further showed enrichment of chloroplast- and photosynthesis-related functions in attached thalli, but cytoskeletal, cell-cycle, and DNA-repair functions in floating thalli. Together, these results support a lower-cost, resilience-oriented state in floating U. prolifera, in which rapid proliferation is associated with reduced structural investment rather than maximized instantaneous photosynthetic capacity. This resilience-associated strategy may help explain how floating thalli sustain rapid proliferation and contribute to the persistence of large-scale green tides under the fluctuating light and physical stress encountered at the sea surface.
Cyanobacterial harmful algal blooms (cyanoHABs) threaten ecosystems and public health through the production of diverse bioactive toxic secondary metabolites, including cyanopeptides. However, environmental factors regulating non-microcystin cyanopeptides remain poorly understood. This study investigates how nutrient availability, initial pH, and species interactions influence the growth and cyanopeptide production in two understudied toxic Microcystis species, M. flos-aquae and M. viridis. Using high-resolution mass spectrometry, we identified 43 cyanopeptides, most of which were non-microcystins, and documented distinct, species-specific profiles. Elevated initial pH showed a trend toward increased M. flos-aquae growth and reduced cyanopeptide production, whereas M. viridis maintained high cyanopeptide levels at intermediate pH. Reduced nitrogen availability increased cyanopeptide quotas in M. flos-aquae despite reduced biomass. Coculture experiments revealed increased cyanopeptide production by M. viridis and the cross-detection of species-specific cyanopeptides, suggesting the transfer of dissolved metabolites between compartments. These results show that cyanopeptide production is a finely tuned, species-specific trait that is shaped by key environmental drivers. Our findings also demonstrate that non-microcystin cyanopeptides represent a substantial and dynamic fraction of the intracellular cyanopeptide pool, responding sensitively to environmental conditions. Effective risk assessment and management frameworks must therefore account for the full spectrum of cyanopeptides and the toxic cyanobacterial species that produce them.
This study aims to elucidate the molecular mechanisms by which Polyphyllin I (PPI), a potent steroidal saponin, attenuates non-small cell lung cancer (NSCLC) progression via mechanistic reprogramming of an autophagy-dependent immunogenic response. Integrated in vitro (A549, H460) and in vivo (LLC xenograft) models were deployed to evaluate PPI's efficacy on autophagic flux and the tumour immune microenvironment. The regulatory role of autophagy in macrophage-mediated antigen presentation was scrutinised via ATG3-mediated genetic silencing or overexpression in tumour-macrophage co-culture systems. Concurrently, the capacity of PPI to sensitise NSCLC cells to cisplatin (DDP) and counteract chemoresistance was evaluated. PPI activated the AMPK/p53/mTOR signalling axis, robustly inducing core autophagic markers (LC3-II and Beclin-1) in a dose-dependent manner. Mechanistically, PPI-induced autophagic flux served as a prerequisite for antitumoural M1 macrophage polarisation, characterised by significant upregulation of iNOS and MHC-II in co-cultured THP-1 cells. Genetic knockdown of ATG3 effectively abrogated these immunostimulatory profiles, whereas ATG3 overexpression potentiated PPI-driven antigen presentation. Furthermore, PPI administration markedly delayed the onset of DDP resistance sustained by functional autophagic flux. In vivo, PPI significantly suppressed tumour burden, accompanied by enhanced CD8+ T-cell infiltration and elevated cytotoxic effector levels (IFN-γ and Granzyme B). Our findings establish PPI as a dual autophagic-immune modulator that re-engineers the immunosuppressive microenvironment. By coupling intracellular autophagic stress with macrophage-mediated antigen presentation, PPI reinstates antitumour immunity and abrogates chemoresistance, offering a compelling therapeutic framework for managing recalcitrant NSCLC.
Beyond their nutritional value, amino acids are of relevance in medicine and, due to their chemical properties, they are indispensable for applications in many different realms, such as pharmaceutics, cosmetics, animal feed, food, and the beverage industry. In this research article, we report an archaeal cell factory for leucine production from CO2 that has been generated by rational design, random mutagenesis, and pathway engineering. The cell factory has been bioprocess-technologically examined and successfully scaled up with regard to productivity, product quality, and operational stability. In a 2-day fed-batch campaign, we produced 181 g of leucine from CO2 at the 150-L pilot-plant scale with a mean volumetric leucine productivity of 65 mg L-1 h-1. A thorough techno-economic analysis indicates that the rollout of leucine production from CO2 is nearly economically feasible on a global scale.
Microbial biosurfactants are emerging as sustainable alternatives to synthetic surfactants due to their biodegradability, low toxicity, and multifunctional biological activities. Their potential in biomedical and pharmaceutical applications is increasingly recognized, yet integrated evaluations that link production strategies to translational outcomes remain limited. This review critically examines recent advances in biosurfactant production, optimization, and purification, as well as their applications in drug delivery, nanomedicine, antimicrobial therapy, vaccine formulation, wound healing, and immunomodulation. Major classes, including glycolipids, lipopeptides, phospholipids, and polymeric biosurfactants, are compared in terms of physicochemical properties and therapeutic potential. Evidence shows biosurfactants can reduce bacterial adhesion by up to 90%, inhibit biofilm formation by over 80%, and enhance antibiotic efficacy against multidrug-resistant pathogens. Biosurfactant-based carriers such as liposomes, micelles, nanoemulsions, and nanoparticles improve drug solubility, stability, bioavailability, and targeted release. Advances in engineered microbial platforms, low-cost substrates, and process optimization have enhanced production feasibility, though clinical translation remains constrained by cost, downstream processing, formulation stability, safety, and regulatory hurdles. Emerging approaches, including AI-assisted optimization and multiomics-guided discovery, promise next-generation biosurfactants with superior therapeutic performance. This comprehensive review underscores the transformative potential of biosurfactants in green nanotherapeutics, particularly in wound care and targeted drug delivery systems. While these microbial compounds exhibit potent antibiofilm and antibacterial properties, their large-scale production and clinical translation remain significant hurdles. We explore the synergistic integration of biosurfactants with non-viral nanocarriers to enhance re-epithelization, cellular uptake, and therapeutic stability. Anchored in the principles of the circular bioeconomy, this strategy promotes sustainable innovation. By critically examining current opportunities, limitations, safety concerns, and translational challenges, this review aims to guide future research toward the successful clinical and commercial adoption of biosurfactant-based therapies.
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An advanced theory based on statistical physics was applied to microscopically investigate androstenone adsorption and its relationship with olfactory perception in chimpanzees and gorillas. For this purpose, dose-response curves of androstenone on olfactory receptors of chimpanzee OR7D4 and gorilla OR7D4 were analyzed by statistical physics. The two-energy adsorption model fits the chimpanzee data well, and the gorilla data are best fit by the one-energy adsorption model. The stereographic parameter analysis indicated that the studied pheromones were docked in a nonparallel manner in both species via a multimolecular mechanism. The analysis showed that the molecules interacted with different amino acid residues, resulting in distinct olfactory responses. The positive values of the molar adsorption energies indicate that an exothermic and physisorption process occurred in both olfactory systems. The docking analysis revealed that androstenone binds to the olfactory receptors of chimpanzees and gorillas through specific interactions with amino acid residues in the binding pockets. The docking results indicated distinct binding modes in each species, involving van der Waals, alkyl, and C-H interactions, which corroborated the energy trends predicted by the statistical physics model. These findings provided insights into the molecular mechanisms underlying the differential olfactory responses in chimpanzees and gorillas. Statistical physics was an excellent tool for evaluating and interpreting the interactions between androstenone and olfactory receptors.
Parkinson's disease (PD) is a multifactorial neurodegenerative disorder shaped by interactions between genetic susceptibility, environmental exposures, and broader ecological change. Although pesticides, industrial solvents, heavy metals, and air pollutants have long been implicated as potentially modifiable PD risk factors, climate change is now reshaping and amplifying these hazards through rising temperatures, worsening air quality, increased pesticide demand, extreme weather events, and wildfire-related particulate matter.This narrative review moves beyond a conventional exposure-based summary by integrating environmental toxicology, climate science, epidemiology, and mechanistic neuroscience to reframe PD risk within the context of planetary health. We summarize evidence linking major environmental hazards to PD pathogenesis, emphasizing convergent mechanisms such as oxidative stress, mitochondrial dysfunction, impaired proteostasis, neuroinflammation, blood-brain barrier disruption, and α-synuclein aggregation. We further discuss how climate-related changes may intensify these pathways and disproportionately affect vulnerable populations, including agricultural workers, older adults, socioeconomically disadvantaged communities, and individuals living in rapidly industrializing or climate-sensitive regions. Importantly, we highlight clinical and public health implications by proposing that structured environmental and occupational exposure assessment should be incorporated into PD risk evaluation, early recognition, preventive counseling, and research design. We also discuss exposure reduction, workplace protection, environmental monitoring, and regulatory policy as prevention-oriented strategies. By positioning environmental hazards and climate change as interconnected, underrecognized, and potentially modifiable contributors to PD, this review provides a framework for clinicians, researchers, and policymakers seeking to reduce the future global burden of neurodegenerative disease. Parkinson's disease (PD) is a common neurodegenerative disorder that develops over time and affects movement, balance, and many daily activities. While genes play a role, most cases of PD do not arise solely from genetics. Growing evidence shows that environmental exposures, such as pesticides, industrial chemicals, heavy metals, and air pollution, can increase the risk of developing PD. Importantly, many of these exposures can be reduced or prevented. Climate change is worsening these environmental risks. Higher temperatures, poorer air quality, increased pesticide use, and more frequent wildfires are increasing human exposure to harmful pollutants worldwide. Together, these changes may increase the number of people affected by PD, especially in communities already facing environmental or social disadvantages. This review explains how environmental toxins can damage brain cells through shared biological processes, including oxidative stress, inflammation, and abnormal protein buildup. It also highlights regions and populations that may be more vulnerable to these risks. From a healthcare perspective, understanding a person's environmental and work-related exposures can help identify those at higher risk, support earlier recognition of PD, and guide prevention advice. Overall, environmental toxins and climate change are underrecognized yet actionable determinants of PD. Increasing awareness, improving environmental protections, and integrating exposure history into clinical care are key steps toward reducing the future global burden of PD.
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Though comprising only 2-3% of body weight, the liver performs more than 500 distinct biochemical tasks, despite a parenchyma built almost entirely of hepatocytes-a single cell type that alone metabolizes carbohydrates, lipids, and proteins, synthesizes plasma proteins, produces bile, and detoxifies xenobiotics. How one cell type achieves this breadth turns out to depend on three-dimensional architecture and the zonal gradients it creates. Anatomists have offered many frameworks for this organization: the classical hexagonal lobule, the portal lobule, the metabolic acinus, and the modular polyhedral architecture recovered by serial reconstruction of human tissue. Position within the lobule dictates function: roughly half the hepatocyte transcriptome is zonated along the portal-to-central axis, organized by a Wnt gradient from central-vein endothelium, and the zonation is so strong that drug toxicities, steatosis, and fibrosis each strike preferentially in different zones. This review surveys the methods used to study liver architecture across scales-vascular corrosion casting, serial sectioning, micro-CT, tissue clearing, light-sheet microscopy, and single-cell and spatial transcriptomics-and their findings, together with the computational models that attempt to integrate these scales and predict tissue-level behavior. A remarkable feature of the liver is its capacity to regenerate: lost mass, and much of its architecture, can be restored. Regeneration in the adult liver recapitulates much of development, raising the prospect that bioengineered and synthetic-biology approaches may eventually rescue failing human tissue. The tools to pursue this are increasingly available, though substantial gaps remain before such approaches reach the clinic.
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Immunosenescence refers to the progressive decline in immune system functionality associated with aging, with thymic involution identified as a primary driver of this process. The thymus, the central organ for T cell development, begins to atrophy from puberty onward, resulting in a marked reduction in naive T cell output and a significant decrease in the diversity of T cell receptor (TCR) repertoires. This decline compromises the immune system's capacity to mount effective responses against neoantigens and is associated with a state of chronic low-grade inflammation, termed inflammaging. The structural and functional deterioration of the thymus not only directly impairs adaptive immunity but also participates in a bidirectional crosstalk with systemic aging, creating a self-reinforcing vicious cycle. Consequently, reversing thymic involution and achieving thymic regeneration are fundamental strategies for restoring immune homeostasis, delaying immunosenescence, and ultimately combating aging. Recent years have witnessed significant advancements in thymic regeneration, with various interventional approaches demonstrating efficacy, including modulation of the growth hormone/IGF-1 axis, cytokine-based therapies, mTOR inhibitors, sex steroid ablation, stem cell and cell-based therapies, gene therapy, and tissue engineering. This review aims to systematically summarize the mechanisms of action, current research status, advantages, and limitations of these strategies. Furthermore, we explore the potential value of combinatorial approaches and future directions, providing a theoretical foundation for the clinical translation of thymic regeneration and the optimization of anti-immunosenescence interventions.