Persulfidation is a post-translational modification involving the specific conversion of thiols (-SH) to persulfide groups (-SSH) on cysteine residues in target proteins. This modification plays critical roles in numerous physiological and cellular processes. Previously, we demonstrated that host cell persulfidation levels influence the effectiveness of antifungal immunity against the fungal pathogen Aspergillus fumigatus. In this study, we sought to further elucidate the relationship between persulfidation and the immune response. To this end, we defined the persulfidated proteins (the persulfidome) in alveolar epithelial cells that were challenged with A. fumigatus and/or exposed to a sulfide donor, which increases cellular persulfidation. Our findings suggest that persulfidation indirectly modulates immunity through changes in RNA metabolism and translation. Additionally, calprotectin was persulfidated in response to A. fumigatus exposure, and this modification is essential for maintaining its immune-related function under oxidative stress. Our results suggest that persulfidation positively influences generalized and specific immune responses.
Infection due to the chikungunya virus (CHIKV) can cause chronic disease characterized by persistent arthralgia. While the humoral immune response to CHIKV is well characterized, the contribution of Fc-mediated effector functions in disease pathogenesis remains poorly understood. We assessed the quantitative and qualitative aspects of CHIKV-specific antibodies in patients with self-resolving or chronic chikungunya, including IgG/IgM titers and effector functions such as antibody-dependent cell phagocytosis (ADCP), complement deposition (ADCD), cell cytotoxicity (ADCC), and NK cell activation (ADNKA). Anti-CHIKV IgG and IgM titers declined between 3 and 6 months post-infection, and the lower titers at 6 months were associated with the chronic disease. The ADCP and ADCD capacities were similar between patients with self-resolving or chronic chikungunya. Patients with the chronic disease showed reduced ADCC but no reduced ADNKA. Females exhibited higher anti-CHIKV E2 antibody concentrations and ADCP. This study provides a comprehensive overview of Fc-mediated effector functions in chikungunya patients with differential disease outcomes.
Halide perovskites have demonstrated great potential for next-generation X-ray detectors owing to their strong X-ray absorption, excellent charge-transport properties, tunable band structures, and low-cost processability. These advantages enable high-sensitivity, low-dose, and fast-response X-ray detection for medical imaging, security screening, and industrial inspection. Recently, heterostructure engineering has become an effective strategy for improving detector performance and stability by regulating band alignment, interfacial coupling, and carrier transport. In this review, we highlight recent advances in heterostructure-engineered halide perovskite X-ray detectors, including perovskite/perovskite and perovskite/functional-material heterostructures. Particular emphasis is placed on how heterointerfaces improve charge separation and transport, suppress recombination losses, inhibit ion migration, and enhance device stability and imaging performance. Finally, we discuss the remaining challenges and future opportunities for developing high-performance, stable, and scalable perovskite X-ray detection technologies.
Cancer risk in Latin America is shaped by lifestyle exposures whose regional patterns are usually represented through extrapolated global estimates. We systematically reviewed observational studies on tobacco smoking, alcohol consumption, adiposity, physical inactivity, and dietary patterns and cancer risk in Latin American adults, searching four databases through September 2025 and appraising risk of bias with QUIPS. Forty-seven studies were included, almost all case-control. Pooling was restricted to site-specific sets sharing one exposure contrast, and only two qualified: a higher dietary inflammatory index with prostate cancer (OR 1.38, 95% CI 1.11–1.73) and obesity with endometrial cancer (OR 3.81, 1.08–13.45). In a direction-of-effect synthesis, healthy dietary exposures were protective in 9 of 9 estimates, whereas smoking and unhealthy diets were predominantly associated with increased risk. These associations are directional rather than causal, and they indicate where prospective regional cohorts are most needed.
Approximately 1.5 billion end-of-life tires accumulate globally each year, presenting major environmental and human health challenges. Although recycling pathways such as devulcanization, pyrolysis, and mechanical grinding are promoted to conserve resources, their real-world sustainability is limited by technical, economic, and environmental constraints. These recycling processes can release hazardous pollutants, including volatile organic compounds, polycyclic aromatic hydrocarbons, heavy metals, microplastics, and 6PPD-quinone, posing long-term ecological and toxicological risks. Integrating technical, regulatory, and toxicological perspectives, this review evaluates the risks and benefits of current tire management strategies. It uncovers overlooked downstream impacts and calls for advanced recycling technologies, high-fidelity monitoring systems, and strengthened regulations to enhance the overall sustainability of tire recycling practices.
Carboxypeptidase M (CPM) metabolizes several bioactive peptides by removing their C-terminal arginine residues. It was postulated that the substrates include the anaphylatoxins C3a and C5a generating their less active desArg forms. C3a and C5a are potent mediators of inflammation, shaping both innate and adaptive immune responses. Considering that CPM is a membrane-bound enzyme expressed in multiple organs, we hypothesized that it may protect tissues from anaphylatoxin-driven damage. Using mass spectrometry, we confirmed that CPM efficiently converts C3a and C5a into their desArg forms. We then generated CPM-deficient rats and subjected them to a complement-dependent model of acute lung injury. Compared to controls, CPM-deficient rats exhibited consistently exacerbated lung damage, including higher histological injury scores, increased neutrophil and macrophage infiltration, and elevated expression of inflammatory marker genes. These findings indicate that CPM protects the lung from complement-mediated injury and highlight it as a potential therapeutic target in inflammatory diseases.
Post-stroke neurological decline is associated with persistent vascular and metabolic dysfunction, including long-term alterations in lipid homeostasis. We performed targeted lipidomic analyses in the hippocampus and plasma from rats subjected to transient middle cerebral artery occlusion at 6 h, 24 h, 7 days, 15 days, 1 month, and 4 months after stroke. Lipid profiles were integrated with behavioral, histological, immunofluorescence, western blot, flow cytometric, and bioinformatic analyses. At 4 months, an increased plasma lysophosphatidylcholine/phosphatidylcholine ratio was associated with late neurological deterioration and cognitive impairment. This change coincided with hippocampal lipid remodeling, region-specific astrogliosis, changes in PLA2, LPCAT1, MBOAT1, and SREBF2, and altered circulating BODIPY+ lipophilic particles associated with apolipoproteins. These findings support coordinated central and peripheral lipid remodeling during chronic post-ischemic progression with potential relevance for peripheral biomarker development.
We develop a cluster-level optimization framework to design brownfield transition pathways toward net-zero chemical clusters by 2050, applied to existing ammonia-olefin clusters in the Netherlands. The model represents sequential investment decisions for 2030, 2040, and 2050, includes scope 1–3 emissions, and enables a systematic comparison of greenfield and brownfield configurations. Thirteen olefin and eight ammonia production routes are considered. The results show that, despite reduced flexibility due to legacy assets, net-zero brownfield configurations remain feasible. Plastic gasification combined with methanol-to-olefins emerges as a low-regret option for olefins, while electric steam methane reforming and electrolyzers are robust choices for ammonia. The results support early investment rather than strategic delay. Excluding scope 3 emissions leads to lock-in of fossil-based options that appear cost-effective short-term but raise long-term system costs. Sensitivity analyses highlight uncertainties related to infrastructure and technology availability, bio-feedstock prices, and plastic waste emission accounting.
Cell surface receptor dynamics regulate signaling and endocytosis and can be quantified by single-particle tracking using total internal reflection fluorescence microscopy. We developed an interpretable machine-learning framework that combines geometric features of trajectories with a random forest classifier to distinguish five motion classes: Brownian motion, directed motion, fractional Brownian motion, Ornstein-Uhlenbeck motion, and continuous-time random walk. Applied to trajectories of the HIV co-receptor C-C chemokine receptor type 5 (CCR5), the method shows that stimulation with the agonist PSC-RANTES shifts receptor dynamics from intermittent and correlated diffusion toward confined, attraction-driven motion, consistent with receptor clustering and internalization. By providing accurate classification together with interpretable descriptors of receptor behavior, this framework links stochastic motion models to biologically meaningful cellular states. The approach enables quantitative analysis of complex receptor dynamics and is broadly applicable to live-cell imaging studies of membrane proteins and other single-particle tracking datasets.
Live imaging in whole-organism models is often limited in both resolution and repeatability by the lack of relatively non-invasive, reversible immobilization methods. To enable real-time in vivo imaging in the highly regenerative planarian S. mediterranea, we systematically evaluated linalool as a sedation strategy. We identified 2.16 mM linalool as an effective concentration that induces rapid, reversible immobilization without compromising survival or causing detectable stress phenotypes. Acute exposure before amputation or repeated daily exposures during regeneration did not impair blastema growth, stem cell proliferation, or gross brain morphology, demonstrating compatibility with regeneration studies under imaging-relevant conditions. In contrast, continuous exposure throughout regeneration induced stress phenotypes and impaired regenerative outcomes. Together, our findings define operational exposure windows for linalool, establishing a robust, regeneration-compatible immobilization strategy that enables stable, high-resolution imaging across biological scales, from whole-organism organization to cellular dynamics, while remaining compatible with fluorescent dyes and allowing full recovery after imaging.
Sound localization is essential for insect survival, enabling them to pinpoint predators and conspecifics. However, their minute size hinders the use of inter-aural time or intensity differences, a strategy employed by mammals for localizing sound. In this study, we numerically demonstrate that tree cricket hearing systems can act as an interferometer to support sound localization by first splitting the sound wave into two parts, sending one wave to an anterior tympanic membrane and sending the second to a posterior tympanic membrane. The membranes then carry the split waves to a common point, the tracheal wall, where the re-assembly of the wave causes mechanical interference that is sensitive to microsecond time delays. This principle, interferometry, is usually thought of in terms of light and can measure extremely small time delays. Tree cricket ears are equipped to use the same principle as the light interferometer, except with sound, to measure extremely precise locations.
Methionine adenosyltransferase 2A (MAT2A) links metabolic reprogramming to epigenetic regulation via S-adenosylmethionine (SAM) production, but its role in non-small cell lung cancer (NSCLC) remains unclear, and current inhibitors require combination strategies. Using proteomics and metabolomics in NSCLC cells treated with MAT2A-targeting siRNA or the inhibitor AG-270, we characterized MAT2A-driven metabolic rewiring. In fatty acid biosynthesis, MAT2A regulates FASN and SCD; exogenous palmitic acid reverses AG-270-induced growth inhibition, supporting combination with the FASN inhibitor TVB-2640. In cholesterol metabolism, MAT2A modulates biosynthesis and efflux, and an LXR agonist promoting cholesterol efflux enhances AG-270 efficacy. In energy metabolism, MAT2A governs glycolysis via HIF1A, and a GLUT1 inhibitor synergizes with AG-270. In the transsulfuration pathway, MAT2A transcriptionally regulates CBS and shows synergy with inhibitors of PHGDH (producing serine for cysteine biosynthesis) and SLC7A11 (mediating cysteine uptake). Collectively, our findings establish MAT2A as a central metabolic regulator in NSCLC and propose rational combination strategies.
Rapid threat processing is a fundamental and evolutionarily conserved function of the brain. In vision, influential models of emotion propose the existence of a fast subcortical pathway for threat processing, connecting the visual thalamus with the amygdala, driven by coarse visual inputs. In audition, whether such a “shortcut” operates in humans has remained unknown. Here, using psychophysiology and neuroimaging, we provide convergent human evidence for an auditory pathway that is sensitive to fast temporal acoustic cues, previously linked to salient alarm signals and coarse auditory processing. Threatening sounds with fast temporal cues elicited rapid neural and autonomic responses at early post-stimulus latencies. Notably, right amygdala responses to these cues covaried with individual differences in strength of a direct auditory thalamo-amygdala pathway. Together, these findings identify a previously uncharacterized “low road” for auditory threat processing in humans, and establish fast temporal acoustic structure as a key feature supporting rapid affective responses.
How does the human brain represent how far apart in time two remembered moments occurred? Healthy adults played a first-person interactive video game and subsequently judged the temporal order of pairs of event moments during functional MRI. Using representational similarity analysis, we identified a distributed multivoxel activity pattern in the precuneus and surrounding posterior medial cortex whose representational geometry tracked retrieved temporal-distance magnitude across intervals ranging from less than 1 s to approximately 18 min. This representation could not be explained by perceptual similarity, situational change, or task difficulty, and was stronger for events sharing a common episodic context. Applying inhibitory brain stimulation to the precuneus before retrieval attenuated this representational pattern while leaving overall BOLD activity levels unchanged. These findings suggest that the precuneus contributes to organizing temporal relationships among remembered events, representing temporal distance within structured episodic contexts rather than as a simple metric of elapsed time.
The evolutionary origins of tool use remain poorly understood. Drawing inferences from living apes is challenging due to striking differences between chimpanzees (Pan troglodytes) and bonobos (P. paniscus), our two closest living relatives. Chimpanzees routinely use tools in both the wild and captivity. Conversely, wild bonobos rarely use tools, whereas captive bonobos show diverse tool use. We examined the individual (i.e., age, sex, and rearing history), social (i.e., past and present exposure to conspecifics using tools), and environmental (i.e., tool availability) tool-use drivers in sanctuary-living bonobos using a novel group-based extractive foraging task. Tool use was more frequent in adult females than in males, in human-reared than in mother-reared immatures, after greater exposure to tool use, and when tools were provided. Hence, tool use in sanctuary-living bonobos is driven by social learning opportunities and developmental biases, providing insight into the conditions that may have favored the emergence of tool use during hominin evolution.
Accurate deformable registration between planning CT (computed tomography) and cone-beam CT (CBCT) is essential for adaptive radiotherapy in nasopharyngeal carcinoma, but cross-modality intensity differences, low soft-tissue contrast, and CBCT artifacts complicate alignment. We propose NJTransMorph, an unsupervised transformer-based registration framework that integrates normalized gradient field loss and Jacobian determinant regularization to improve multimodal structural alignment and deformation plausibility. NJTransMorph was evaluated against VoxelMorph, UTSRMorph, and TransMorph on an internal cohort (n = 35), an external scanner cohort (n = 27), and an external multi-center cohort (n = 61). Compared with TransMorph, NJTransMorph improved Dice score from 86.44% to 87.35% and reduced Hausdorff distance (HD95) from 2.01 to 1.87 mm on the internal cohort. It also reduced non-positive Jacobian determinants on the external scanner cohort (0.27%–0.23%) and multi-center cohort (0.21%–0.15%). Thus, among the evaluated deep learning methods, NJTransMorph improved registration accuracy and deformation regularity across scanner and center shifts.
Pulmonary surfactant lipids support lung homeostasis and innate immunity, and their dysregulation contributes to acute respiratory distress syndrome. Whether mitochondrial phosphatidylglycerol (PG) biosynthesis influences epithelial lipid secretion and inflammatory responses remains unclear. Using A549 cells, we disrupted PGS1, which encodes phosphatidylglycerophosphate synthase, and found that partial loss of PGS1 altered cellular PG levels and changed the secreted phospholipid profile. Valproic acid (VPA), a clinically used antiepileptic drug, similarly remodeled secreted lipids and increased the relative abundance of the anti-inflammatory PG species palmitoyl-oleoyl-phosphatidylglycerol (POPG), an effect not seen with partial PGS1 loss. Functionally, conditioned media from VPA-treated epithelial cells reduced lipopolysaccharide-induced inflammatory responses in PMA-differentiated U937 macrophage-like cells, with lipid extracts contributing to this effect. In a vascularized quail chorioallantoic membrane model, both VPA and POPG decreased inflammation and maintained tissue structure. Overall, these findings connect mitochondrial PG metabolism to epithelial lipid-mediated control of inflammation.
