Acquisition of non-olfactory encoding improves odour discrimination in olfactory cortex.

Olfaction is influenced by contextual factors, past experiences, and the animal's internal state. Whether this information is integrated at the initial stages of cortical odour processing is not known, nor how these signals may influence odour encoding. Here we revealed multiple and diverse non-olfactory responses in the primary olfactory (piriform) cortex (PCx), which dynamically enhance PCx odour discrimination according to behavioural demands. We performed recordings of PCx neurons from mice trained in a virtual reality task to associate odours with visual contexts to obtain a reward. We found that learning shifts PCx activity from encoding solely odours to a regime in which positional, contextual, and associative responses emerge on odour-responsive neurons that become mixed-selective. The modulation of PCx activity by these non-olfactory signals was dynamic, improving odour decoding during task engagement and in rewarded contexts. This improvement relied on the acquired mixed-selectivity, demonstrating how integrating extra-sensory inputs in sensory cortices can enhance sensory processing while encoding the behavioural relevance of stimuli.

Silicone oil emulsification: A literature review and role of widefield imaging and ultra-widefield imaging with navigated central and peripheral optical coherence tomography technology.

Silicone oil (SO) emulsification is a significant concern in vitreoretinal surgery, leading to various complications. Despite the high prevalence of SO emulsification within the eye, there is currently no standardized method for its early detection. The recent introduction of widefield (WF) imaging and ultra-WF (UWF) imaging with navigated central and peripheral optical coherence tomography (OCT) techniques have shown promising results in providing high-resolution images of the peripheral vitreous, vitreoretinal interface, retina, and choroid. This enhanced visualization capability enables the early identification of emulsified SO droplets, facilitating a proactive therapeutic approach, and mitigating associated adverse events. This comprehensive literature review aims to provide an updated overview of the topic, focusing on the role of WFimaging and UWF imaging and navigated central and peripheral swept-source OCT (SS-OCT) in the early detection and management of SO emulsification. The review discusses the current understanding of SO emulsification, its associated complications, and the limitations of existing detection methods. In addition, it highlights the potential of WF and UWF imaging and peripheral OCT as advanced imaging modalities for improved visualization of SO emulsification. This review serves as a valuable resource for clinicians and researchers, providing insights into the latest advancements in the field of vitreoretinal surgery and the promising role of WF imaging and UWF imaging and navigated central and peripheral SS-OCT in the management of SO.

Computational approaches for lead compound discovery in dipeptidyl peptidase-4 inhibition using machine learning and molecular dynamics techniques.

The prediction of possible lead compounds from already-known drugs that may present DPP-4 inhibition activity imply a advantage in the drug development in terms of time and cost to find alternative medicines for the treatment of Type 2 Diabetes Mellitus (T2DM). The inhibition of dipeptidyl peptidase-4 (DPP-4) has been one of the most explored strategies to develop potential drugs against this condition. A diverse dataset of molecules with known experimental inhibitory activity against DPP-4 was constructed and used to develop predictive models using different machine-learning algorithms. Model M36 is the most promising one based on the internal and external performance showing values of Q2CV = 0.813, and Q2EXT = 0.803. The applicability domain evaluation and Tropsha's analysis were conducted to validate M36, indicating its robustness and accuracy in predicting pIC50 values for organic molecules within the established domain. The physicochemical properties of the ligands, including electronegativity, polarizability, and van der Waals volume were relevant to predict the inhibition process. The model was then employed in the virtual screening of potential DPP4 inhibitors, finding 448 compounds from the DrugBank and 9 from DiaNat with potential inhibitory activity. Molecular docking and molecular dynamics simulations were used to get insight into the ligand-protein interaction. From the screening and the favorable molecular dynamic results, several compounds including Skimmin (pIC50 = 3.54, Binding energy = -8.86 kcal/mol), bergenin (pIC50 = 2.69, Binding energy = -13.90 kcal/mol), and DB07272 (pIC50 = 3.97, Binding energy = -25.28 kcal/mol) seem to be promising hits to be tested and optimized in the treatment of T2DM. This results imply a important reduction in cost and time on the application of this drugs because all the information about the its metabolism is already available.

Correction: Towards control of excitonic coupling in DNA-templated Cy5 aggregates: the principal role of chemical substituent hydrophobicity and steric interactions.

Correction for 'Towards control of excitonic coupling in DNA-templated Cy5 aggregates: the principal role of chemical substituent hydrophobicity and steric interactions' by Sebastián A. Díaz et al., Nanoscale, 2023, 15, 3284-3299. https://doi.org/10.1039/D2NR05544A.

Endogenous glucocorticoids are required for normal macrophage activation and gastric Helicobacter pylori immunity.

Glucocorticoids are steroid hormones well-known for their potent anti-inflammatory effects. However, their immunomodulatory properties are multifaceted. Increasing evidence suggests that glucocorticoid signaling promotes effective immunity and that disruption of glucocorticoid signaling impairs immune function. In this study, we conditionally deleted the glucocorticoid receptor (GR) in the myeloid lineage using the LysM-Cre driver (myGRKO). We examined the impact on macrophage activation and gastric immune responses to Helicobacter pylori, the best-known risk factor of gastric cancer. Our results indicate that, compared to WT, GRKO macrophages exhibited higher expression of proinflammatory genes in steroid-free conditions. However, when challenged in vivo, GRKO macrophages exhibited aberrant chromatin landscapes and impaired proinflammatory gene expression profiles. Moreover, gastric colonization with Helicobacter pylori revealed impaired gastric immune responses and reduced T cell recruitment in myGRKO mice. As a result, myGRKO mice were protected from atrophic gastritis and pyloric metaplasia development. These results demonstrate a dual role for glucocorticoid signaling in preparing macrophages to respond to bacterial infection but limiting their pathogenic activation. In addition, our results support that macrophages are critical for gastric Helicobacter pylori immunity.

Influence of adjuvant therapies on organ-specific recurrence of cutaneous melanoma: A multicenter study on 1383 patients of the prospective DeCOG registry ADOReg.

This study investigated whether adjuvant treatments in stage III cutaneous melanoma (CM) influenced patterns of recurrence. Patients with primary (n = 1033) or relapsed CM (n = 350) who received adjuvant therapies with Nivolumab (N), Pembrolizumab (P), or Dabrafenib and Trametinib (D + T) were extracted from the prospective multicenter real-world skin cancer registry ADOReg. Endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), organ-specific DMFS, and overall survival (OS). For primary cases, D + T indicated an improved PFS (1- and 2-year PFS: 90.9%; 82.7%) as compared to P (81.0%, 73.9%; p = .0208), or N (83.8%, 75.2%; p = .0539). BRAF-mutated(mut) CM demonstrated significantly lower PFS (p = .0022) and decreased DMFS (p = .0580) when treated with immune checkpoint inhibitor (ICI) instead of D + T. Besides, NRAS-mut CM tended to perform worse than wt CM upon ICI (PFS: p = .1349; DMFS: p = .0540). OS was similar between the groups. Relapsed cases showed decreased PFS, DMFS, and OS in comparison to primary (all: p < .001), without significant differences between the subgroups. Organ-specific DMFS was significantly altered for primary cases with bone (p = .0367) or brain metastases (p = .0202). In relapsed CM, the frequency of liver (D + T: 1.5%; P: 12%; N: 9%) and LN metastases (D + T: 1.5%; P: 12%; N: 10.2%) was significantly lower with adjuvant D + T than ICI. NRAS-mut CM showed increased recurrence in primary and relapsed cases. These data show that adjuvant D + T is superior to ICI in primary BRAF-mut CM.

Oriented Antibody Coupling to an Antifouling Polymer Using Glycan Remodeling for Biosensing by Particle Motion.

Biosensors based on immobilized antibodies require molecular strategies that (i) couple the antibodies in a stable fashion while maintaining the conformation and functionality, (ii) give outward orientation of the paratope regions of the antibodies for good accessibility to analyte molecules in the biofluid, and (iii) surround the antibodies by antibiofouling molecules. Here, we demonstrate a method to achieve oriented coupling of antibodies to an antifouling poly(l-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG) substrate, using glycan remodeling to create antibody-DNA conjugates. The coupling, orientation, and functionality of the antibodies were studied using two analysis methods with single-molecule resolution, namely single-molecule localization microscopy and continuous biosensing by particle motion. The biosensing functionality of the glycan-remodeled antibodies was demonstrated in a sandwich immunosensor for procalcitonin. The results show that glycan-remodeled antibodies enable oriented immobilization and biosensing functionality with low nonspecific binding on antifouling polymer substrates.

Square-planar imido complexes of cobalt: synthesis, reactivity and computational study.

Treatment of [Co(N2)(tBuPNP)] (tBuPNP = anion of 2,5-bis(di-tert-butylphosphinomethyl)pyrrole) with one equivalent of an aryl azide generates the four-coordinate imido complexes [Co(NAr)(tBuPNP)] (Ar = mesityl, phenyl, or 4-tBu-phenyl). X-ray crystallographic analysis of the compounds shows an unusual square-planar geometry about cobalt with nearly linear imido units. In the presence of the hydrogen atom donor, TEMPOH, [Co(NPh)(tBuPNP)] undergoes addition of the H atom to the imido nitrogen to generate the corresponding amido complex, [Co(NHPh)(tBuPNP)], whose structure and composition were verified by independent synthesis. Despite the observation of H atom transfer reactivity with TEMPOH, the imido complexes do not show catalytic activity for C-H amination or aziridination for several substrates examined. In the case of [Co(NPh)(tBuPNP)], addition of excess azide produced the tetrazido complex, [Co(N4Ph2)(tBuPNP)], whose bond metrics were most consistent with an anionic Ph2N4 ligand. Density Functional Theory (DFT) investigations of the imido and tetrazido species suggest that they adopt a ground state best described as possessing a low-spin cobalt(II) ion ferromagnetically coupled to an iminyl radical.

Malignant skin neoplasms in goats in Sicily, Italy: clinical, virological and pathological investigations.

Neoplasms in small ruminants are considered uncommon and their reported incidence is variable. The aims of this investigation were to characterize malignant skin neoplasms in adult goats reared in Sicily, Italy, and to evaluate potential correlations between gross and histopathology features of the tumours and signalment, tumour location and/or viral infections. A total of 75 malignant skin masses were examined. In selected animals with perineal masses (n = 28) virological and serological investigations on tissues and blood were also conducted. According to the histological features, the lesions were classified as 67 squamous cell carcinomas (SCCs) (of which 65 were located in the perineum), six melanomas and two fibrosarcomas. In three cases, neoplasms at the base of the horn were associated with nasal polyps. Among the selected perineal SCCs, papillomaviruses (PVs), caprine herpesvirus 1 and parapoxvirus were not detected on polymerase chain reaction or on serological examination. However, further investigation on a larger sample size is required to evaluate the potential role of PVs in the pathogenesis of skin tumours in goats.

Commercially traded fish portfolios mask household utilization of biodiversity in wild food systems.

The global biodiversity that underpins wild food systems-including fisheries-is rapidly declining. Yet, we often have only a limited understanding of how households use and benefit from biodiversity in the ecosystems surrounding them. Explicating these relationships is critical to forestall and mitigate the effects of biodiversity declines on food and nutrition security. Here, we quantify how biodiversity filters from ecosystems to household harvest, consumption, and sale, and how ecological traits and household characteristics shape these relationships. We used a unique, integrated ecological (40 sites, quarterly data collection) and household survey (n = 414, every 2 mo data collection) dataset collected over 3 y in rice field fisheries surrounding Cambodia's Tonlé Sap, one of Earth's most productive and diverse freshwater systems. While ecosystem biodiversity was positively associated with household catch, consumption, and sold biodiversity, households consumed an average of 43% of the species present in the ecosystem and sold only 9%. Larger, less nutritious, and more common species were disproportionally represented in portfolios of commercially traded species, while consumed species mirrored catches. The relationship between ecosystem and consumed biodiversity was remarkably consistent across variation in household fishing effort, demographics, and distance to nearest markets. Poorer households also consumed more species, underscoring how wild food systems may most benefit the vulnerable. Our findings amplify concerns about the impacts of biodiversity loss on our global food systems and highlight that utilization of biodiversity for consumption may far exceed what is commercially traded.

Toxoplasma gondii Exposure and Dietary Habits of Two Sympatric Carnivores in the Valdivian Temperate Rainforest, Southern Chile.

ABSTRACT: Toxoplasma gondii, a parasitic protozoan, may infect most warm-blooded animals, including humans and carnivores. Our study focused on alien-invasive American minks (Neogale vison) and domestic cats (Felis catus) in the Valdivian Temperate Rainforest, Chile. The main goal was to investigate the relationship between their dietary habits and T. gondii exposure in the Valdivia River watershed. To detect T. gondii exposure, blood serum samples from 49 domestic cats and 40 American minks were analyzed using an ELISA, and stable isotope analysis of δ15N and δ13C from vibrissae was performed to determine the dietary habits of both species. Relationships between T. gondii exposure and dietary habits were explored using generalized linear mixed-effects models. American minks that were T. gondii seropositive exhibited a broader prey range compared to seropositive domestic cats, with minimal dietary overlap between the two groups. Exposure of domestic cats to T. gondii had no significant association with any isotope value or prey item in their diet. In American minks, we found a positive and significant association between the proportion of Domestic chicken (Gallus gallus domesticus) in the diet and high δ15N values with T. gondii exposure. This suggests that domestic species prey related to anthropogenic areas, and the consumption of high-trophic-level prey, may contribute to T. gondii exposure in American minks. Conversely, contrary to previous hypotheses, consumption of rodents showed no significant association with T. gondii exposure in either species. Our findings emphasize the importance of further research to investigate trophic interactions in the transmission dynamics of T. gondii in the Valdivian Temperate Rainforest.

The molecular basis of tRNA selectivity by human pseudouridine synthase 3.

Pseudouridine (Ψ), the isomer of uridine, is ubiquitously found in RNA, including tRNA, rRNA, and mRNA. Human pseudouridine synthase 3 (PUS3) catalyzes pseudouridylation of position 38/39 in tRNAs. However, the molecular mechanisms by which it recognizes its RNA targets and achieves site specificity remain elusive. Here, we determine single-particle cryo-EM structures of PUS3 in its apo form and bound to three tRNAs, showing how the symmetric PUS3 homodimer recognizes tRNAs and positions the target uridine next to its active site. Structure-guided and patient-derived mutations validate our structural findings in complementary biochemical assays. Furthermore, we deleted PUS1 and PUS3 in HEK293 cells and mapped transcriptome-wide Ψ sites by Pseudo-seq. Although PUS1-dependent sites were detectable in tRNA and mRNA, we found no evidence that human PUS3 modifies mRNAs. Our work provides the molecular basis for PUS3-mediated tRNA modification in humans and explains how its tRNA modification activity is linked to intellectual disabilities.

Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights.

OBJECTIVE: To evaluate the cerebrospinal fluid (CSF) cytokine/chemokine profile of central nervous system (CNS) neurosarcoidosis (NS), and its utility in differential diagnosis, treatment, and prognostication. METHODS: In this case-control study, we validated 17 cytokines/chemokines (interleukin [IL]-1-beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17A, BAFF, IL-8/CXCL8, CXCL9, CXCL10, CXCL13, GM-CSF, interferon-gamma, and tumor necrosis factor [TNF]-alpha) in a multiplexed automated immunoassay system (ELLA; Bio-Techne, Minneapolis, MN, USA), and assessed them in CSF and serum of symptomatic patients with probable or definite CNS NS (01/2011-02/2023) with gadolinium enhancement and/or CSF pleocytosis. Patients with multiple sclerosis, primary CNS lymphoma, aquaporin-4 immunoglobulin G positivity, non-inflammatory disorders, and healthy individuals were used as controls. RESULTS: A total of 32 NS patients (59% women; median age, 59 years [19-81]) were included; concurrent sera were available in 12. CSF controls consisted of 26 multiple sclerosis, 8 primary CNS lymphoma, 84 aquaporin-4 immunoglobulin G positive, and 34 patients with non-inflammatory disorders. Gadolinium enhancement was present in 31 of 32 NS patients, and CSF pleocytosis in 27 of 32 (84%). CSF IL-2, IL-6, IL-10, IL-13, BAFF, IL-8/CXCL8, CXCL9, CXCL10, CXCL13, GM-CSF, interferon-gamma, and TNF-alpha levels were significantly higher in NS patients compared with non-inflammatory controls (p ≤ 0.02); elevations were more common in CSF than serum. Concurrent elevation of IL-6, CXCL9, CXCL10, GM-CSF, interferon-gamma, and TNF-alpha was present in 18 of 32 NS patients, but only in 1 control. Elevated IL-6, IL-10, IL-13, CXCL9, CXL10, GM-CSF, and TNF-alpha associated with measures of disease activity. INTERPRETATION: NS CSF cytokine/chemokine profiles suggest T cell (mainly T helper cell type 1), macrophage, and B-cell involvement. These signatures aid in NS diagnosis, indicate disease activity, and suggest therapeutic avenues. ANN NEUROL 2024.

Interobserver Agreement and Performance of Concurrent AI Assistance for Radiographic Evaluation of Knee Osteoarthritis.

Background Due to conflicting findings in the literature, there are concerns about a lack of objectivity in grading knee osteoarthritis (KOA) on radiographs. Purpose To examine how artificial intelligence (AI) assistance affects the performance and interobserver agreement of radiologists and orthopedists of various experience levels when evaluating KOA on radiographs according to the established Kellgren-Lawrence (KL) grading system. Materials and Methods In this retrospective observer performance study, consecutive standing knee radiographs from patients with suspected KOA were collected from three participating European centers between April 2019 and May 2022. Each center recruited four readers across radiology and orthopedic surgery at in-training and board-certified experience levels. KL grading (KL-0 = no KOA, KL-4 = severe KOA) on the frontal view was assessed by readers with and without assistance from a commercial AI tool. The majority vote of three musculoskeletal radiology consultants established the reference standard. The ordinal receiver operating characteristic method was used to estimate grading performance. Light kappa was used to estimate interrater agreement, and bootstrapped t statistics were used to compare groups. Results Seventy-five studies were included from each center, totaling 225 studies (mean patient age, 55 years ± 15 [SD]; 113 female patients). The KL grades were KL-0, 24.0% (n = 54); KL-1, 28.0% (n = 63); KL-2, 21.8% (n = 49); KL-3, 18.7% (n = 42); and KL-4, 7.6% (n = 17). Eleven readers completed their readings. Three of the six junior readers showed higher KL grading performance with versus without AI assistance (area under the receiver operating characteristic curve, 0.81 ± 0.017 [SEM] vs 0.88 ± 0.011 [P < .001]; 0.76 ± 0.018 vs 0.86 ± 0.013 [P < .001]; and 0.89 ± 0.011 vs 0.91 ± 0.009 [P = .008]). Interobserver agreement for KL grading among all readers was higher with versus without AI assistance (κ = 0.77 ± 0.018 [SEM] vs 0.85 ± 0.013; P < .001). Board-certified radiologists achieved almost perfect agreement for KL grading when assisted by AI (κ = 0.90 ± 0.01), which was higher than that achieved by the reference readers independently (κ = 0.84 ± 0.017; P = .01). Conclusion AI assistance increased junior readers' radiographic KOA grading performance and increased interobserver agreement for osteoarthritis grading across all readers and experience levels. Published under a CC BY 4.0 license. Supplemental material is available for this article.

Immunoaffinity Intact-Mass Spectrometry for the Detection of Endogenous Concentrations of the Acetylated Protein Tumor Biomarker Neuron Specific Enolase.

Intact-mass spectrometry has huge potential for clinical application, as it enables both quantitative and qualitative analysis of intact proteins and possibly unlocks additional pathophysiological information via, e.g., detection of specific post-translational modifications (PTMs). Such valuable and clinically useful selectivity is typically lost during conventional bottom-up mass spectrometry. We demonstrate an innovative immunoprecipitation protein enrichment assay coupled to ultrahigh performance liquid chromatography quadrupole time-of-flight high resolution mass spectrometry (UPLC-QToF-HRMS) for the fast and simple identification of the protein tumor marker Neuron Specific Enolase Gamma (NSEγ) at low endogenous concentrations in human serum. Additionally, using the combination of immunoaffinity purification with intact mass spectrometry, the presence of NSEγ in an acetylated form in human serum was detected. This highlights the unique potential of immunoaffinity intact mass spectrometry in clinical diagnostics.

Isolation and characterization of persisters of the pathogenic microorganism Staphylococcus aureus.

The presence of antibiotic persisters is one of the leading causes of recurrent and chronic diseases. One challenge in mechanistic research on persisters is the enrichment of pure persisters. In this work, we validated a proposed method to isolate persisters with notorious Staphylococcus aureus cultures. With this, we analyzed the proteome profile of pure persisters and revealed the distinct mechanisms associated with vancomycin and enrofloxacin induced persisters. Furthermore, morphological and metabolic characterizations were performed, indicating further differences between these two persister populations. Finally, we assessed the effect of ATP repression, protein synthesis inhibition, and reactive oxygen species (ROS) level on persister formation. In conclusion, this work provides a comprehensive understanding of S. aureus vancomycin and enrofloxacin induced persisters, facilitating a better mechanistic understanding of persisters and the development of effective strategies to combat them.

[Ready to Care for Pregnant Women with Breech Presentation? - Results from an Online Survey for Midwives and Midwifery Students in Germany, Austria, and Switzerland]. / Bereit für die Betreuung von Schwangeren mit Beckenendlage? ­ Ergebnisse aus einer Onlinebefragung für Hebammen und werdende Hebammen in Deutschland, Österreich und der Schweiz.

The vaginal birth of breech presentation is an option for pregnant women supported by current German and international guidelines when favorable conditions and appropriately trained personnel are available. According to midwifery laws in the D-A-CH region, midwives should be able to provide care for a vaginal breech birth in emergencies. Therefore, imparting skills for breech delivery is enshrined in the curriculum for midwifery students. This study evaluated the knowledge and training needs of midwives and midwifery students in the German-speaking region. In May 2022, experiences, specific knowledge, and further training needs regarding vaginal breech birth were assessed through an online survey. Analysis of 467 questionnaires showed that only 30% of respondents currently attend vaginal breech births in their professional environment, but 50% would like to offer this service. 94% of respondents indicated that they would feel more confident if regular training opportunities, particularly simulations and virtual offerings, were provided for vaginal breech birth. However, currently only 10% of respondents receive regular training opportunities for vaginal breech births. The results suggest an increased provision of training opportunities for vaginal breech births to enhance midwives' safety in managing such births.

PPARG is dispensable for bovine embryo development up to tubular stages.

Following blastocyst hatching, ungulate embryos undergo a prolonged preimplantation period termed conceptus elongation. Conceptus elongation constitutes a highly susceptible period for embryonic loss and the embryonic requirements during this process are largely unknown, but multiple lipid compounds have been identified in the fluid nourishing the elongating conceptuses. Peroxisome proliferator-activated receptors (PPARs) mediate the signaling actions of prostaglandins and other lipids and, between them, PPARG has been pointed out to play a relevant role on conceptus elongation by a functional study that depleted PPARG in both uterus and conceptus. The objective of this study has been to determine if embryonic PPARG is required for bovine embryo development. To that aim, we have generated bovine PPARG KO embryos in vitro by two independent gene ablation strategies and assess their developmental ability. In vitro development to Day (D) 8 blastocyst was unaffected by PPARG ablation, as total, inner cell mass and trophectoderm cell numbers were similar between WT and KO D8 embryos. In vitro post-hatching development to D12 was also comparable between different genotypes, as embryo diameter, epiblast cell number, and embryonic disc formation and hypoblast migration rates were unaffected by the ablation. The development to tubular stages equivalent to E14 was assessed in vivo, following a heterologous embryo transfer experiment, observing that the development of extra-embryonic membranes and of the embryonic disc was not altered by PPARG ablation. In conclusion, PPARG ablation did not impaired bovine embryo development up to tubular stages.

Oxidative photocatalysis on membranes triggers non-canonical pyroptosis.

Intracellular membranes composing organelles of eukaryotes include membrane proteins playing crucial roles in physiological functions. However, a comprehensive understanding of the cellular responses triggered by intracellular membrane-focused oxidative stress remains elusive. Herein, we report an amphiphilic photocatalyst localised in intracellular membranes to damage membrane proteins oxidatively, resulting in non-canonical pyroptosis. Our developed photocatalysis generates hydroxyl radicals and hydrogen peroxides via water oxidation, which is accelerated under hypoxia. Single-molecule magnetic tweezers reveal that photocatalysis-induced oxidation markedly destabilised membrane protein folding. In cell environment, label-free quantification reveals that oxidative damage occurs primarily in membrane proteins related to protein quality control, thereby aggravating mitochondrial and endoplasmic reticulum stress and inducing lytic cell death. Notably, the photocatalysis activates non-canonical inflammasome caspases, resulting in gasdermin D cleavage to its pore-forming fragment and subsequent pyroptosis. These findings suggest that the oxidation of intracellular membrane proteins triggers non-canonical pyroptosis.