Staying isolated indoors means that nobody sees me": ontological (in)security and living with significant appearance concerns before, during, and 'since' COVID-19.

PURPOSE: Though a worldwide period of uncertainty (COVID-19) has 'ended', there exists a legacy of maladaptive experiences among people with significant appearance concerns (SAC) that requires care and attention. METHODS: Using Giddens' concept of ontological security, we explored how people experienced their SAC before, during and "since" COVID-19. Qualitative surveys allowed us to capture diverse perspectives from individuals transnationally, analysed with deductive reflexive thematic analysis using ontological security as our theoretical foundation. RESULTS: Themes named "More Mirror(ed) Time" and "Locked Out, Shut Down, and Shut Out" gave a contextual grounding for the embodied experiences of this group through times of social restrictions, and the theme "Redefining Relevance" explored the continued legacy of COVID-19 - and continued global uncertainties such as economic hardship and warfare - that impact the wellbeing of people with SAC. CONCLUSIONS: People with SAC are still 'locked out' from essential healthcare support as those providing healthcare are overworked, under-resourced and rely on efficient interactive methods such as tele-health that may be triggers for people with SAC. Care providers may consider expanding appearance concerns verbiage, look to involve trusted others in the care-seeking process, and utilize modalities beyond digital health to support people with SAC.

Cohort profile: the Environmental Reproductive and Glucose Outcomes (ERGO) Study (Boston, Massachusetts, USA) - a prospective pregnancy cohort study of the impacts of environmental exposures on parental cardiometabolic health.

PURPOSE: Pregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk of pregnancy complications that are associated with long-term cardiometabolic risk. However, the impact of perinatal EDC exposure on subsequent cardiometabolic risk post-pregnancy is less understood. The Environmental Reproductive and Glucose Outcomes (ERGO) Study was established to investigate the associations of environmental exposures during the perinatal period with post-pregnancy parental cardiometabolic health. PARTICIPANTS: Pregnant individuals aged ≥18 years without pre-existing diabetes were recruited at <15 weeks of gestation from Boston, Massachusetts area hospitals. Participants completed ≤4 prenatal study visits (median: 12, 19, 26, 36 weeks of gestation) and 1 postpartum visit (median: 9 weeks), during which we collected biospecimens, health histories, demographic and behavioural data, and vitals and anthropometric measurements. Participants completed a postpartum fasting 2-hour 75 g oral glucose tolerance test. Clinical data were abstracted from electronic medical records. Ongoing (as of 2024) extended post-pregnancy follow-up visits occur annually following similar data collection protocols. FINDINGS TO DATE: We enrolled 653 unique pregnancies and retained 633 through delivery. Participants had a mean age of 33 years, 10% (n=61) developed gestational diabetes and 8% (n=50) developed pre-eclampsia. Participant pregnancy and postpartum urinary phthalate metabolite concentrations and postpartum glycaemic biomarkers were quantified. To date, studies within ERGO found higher exposure to phthalates and phthalate mixtures, and separately, higher exposure to radioactive ambient particulate matter, were associated with adverse gestational glycaemic outcomes. Additionally, certain personal care products used in pregnancy, notably hair oils, were associated with higher urinary phthalate metabolite concentrations, earlier gestational age at delivery and lower birth weight. FUTURE PLANS: Future work will leverage the longitudinal data collected on pregnancy and cardiometabolic outcomes, environmental exposures, questionnaires, banked biospecimens and paediatric data within the ERGO Study.

Proteasomal control of anti-CRISPRs for the regulation of CRISPR/Cas9 activity using Cas9-ACROBAT.

Small molecule-mediated proteasomal degradation of proteins is a powerful tool for synthetic regulation of biological activity. To control Cas9 activity in cells, we engineered an anti-CRISPR protein, AcrIIA4, fused to a degradation (dTAG) or small molecule assisted shutoff (SMASh) tag. Co-expression of the tagged AcrIIA4 along with Cas9 and riboswitch-regulated sgRNAs enables precise tunable control of CRISPR activity by small molecule addition.

A digital microscope for the diagnosis of Plasmodium falciparum and Plasmodium vivax, including P. falciparum with hrp2/hrp3 deletion.

Sensitive and accurate malaria diagnosis is required for case management to accelerate control efforts. Diagnosis is particularly challenging where multiple Plasmodium species are endemic, and where P. falciparum hrp2/3 deletions are frequent. The Noul miLab is a fully automated portable digital microscope that prepares a blood film from a droplet of blood, followed by staining and detection of parasites by an algorithm. Infected red blood cells are displayed on the screen of the instrument. Time-to-result is approximately 20 minutes, with less than two minutes hands-on time. We evaluated the miLab among 659 suspected malaria patients in Gondar, Ethiopia, where P. falciparum and P. vivax are endemic, and the frequency of hrp2/3 deletions is high, and 991 patients in Ghana, where P. falciparum transmission is intense. Across both countries combined, the sensitivity of the miLab for P. falciparum was 94.3% at densities >200 parasites/µL by qPCR, and 83% at densities >20 parasites/µL. The miLab was more sensitive than local microscopy, and comparable to RDT. In Ethiopia, the miLab diagnosed 51/52 (98.1%) of P. falciparum infections with hrp2 deletion at densities >20 parasites/µL. Specificity of the miLab was 94.0%. For P. vivax diagnosis in Ethiopia, the sensitivity of the miLab was 97.0% at densities >200 parasites/µL (RDT: 76.8%, microscopy: 67.0%), 93.9% at densities >20 parasites/µL, and specificity was 97.6%. In Ethiopia, where P. falciparum and P. vivax were frequent, the miLab assigned the wrong species to 15/195 mono-infections at densities >20 parasites/µL by qPCR, and identified only 5/18 mixed-species infections correctly. In conclusion, the miLab was more sensitive than microscopy and thus is a valuable addition to the toolkit for malaria diagnosis, particularly for areas with high frequencies of hrp2/3 deletions.

Phthalates and sex steroid hormones across the perimenopausal period: A longitudinal analysis of the Midlife Women's Health Study.

BACKGROUND: The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. METHODS: Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.

LYVE-1-expressing Macrophages Modulate the Hyaluronan-containing Extracellular Matrix in the Mammary Stroma and Contribute to Mammary Tumor Growth.

Macrophages represent a heterogeneous myeloid population with diverse functions in normal tissues and tumors. While macrophages expressing the cell surface marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) have been identified in stromal regions of the normal mammary gland and in the peritumoral stroma, their functions within these regions are not well understood. Using a genetic mouse model of LYVE-1+ macrophage depletion, we demonstrate that loss of LYVE-1+ macrophages is associated with altered extracellular matrix remodeling in the normal mammary gland and reduced mammary tumor growth in vivo. In further studies focused on investigating the functions of LYVE-1+ macrophages in the tumor microenvironment, we demonstrate that LYVE-1 expression correlates with an increased ability of macrophages to bind, internalize, and degrade hyaluronan. Consistent with this, we show that depletion of LYVE-1+ macrophages correlates with increased hyaluronan accumulation in both the normal mammary gland and in mammary tumors. Analysis of single-cell RNA sequencing of macrophages isolated from these tumors reveals that depletion of LYVE-1+ macrophages in tumors drives a shift in the majority of the remaining macrophages toward a proinflammatory phenotype, as well as an increase in CD8+ T-cell infiltration. Together, these findings indicate that LYVE-1+ macrophages represent a tumor-promoting anti-inflammatory subset of macrophages that contributes to hyaluronan remodeling in the tumor microenvironment. SIGNIFICANCE: We have identified a macrophage subset in mouse mammary tumors associated with tumor structural components. When this macrophage subset is absent in tumors, we report a delay in tumor growth and an increase in antitumor immune cells. Understanding the functions of distinct macrophage subsets may allow for improved therapeutic strategies for patients with breast cancer.

FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy.

Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of haematological malignancies such as acute lymphoblastic leukaemia, B cell lymphoma and multiple myeloma1-4, but the efficacy of CAR T cell therapy in solid tumours has been limited5. This is owing to a number of factors, including the immunosuppressive tumour microenvironment that gives rise to poorly persisting and metabolically dysfunctional T cells. Analysis of anti-CD19 CAR T cells used clinically has shown that positive treatment outcomes are associated with a more 'stem-like' phenotype and increased mitochondrial mass6-8. We therefore sought to identify transcription factors that could enhance CAR T cell fitness and efficacy against solid tumours. Here we show that overexpression of FOXO1 promotes a stem-like phenotype in CAR T cells derived from either healthy human donors or patients, which correlates with improved mitochondrial fitness, persistence and therapeutic efficacy in vivo. This work thus reveals an engineering approach to genetically enforce a favourable metabolic phenotype that has high translational potential to improve the efficacy of CAR T cells against solid tumours.

Contributions of Synthetic Chemicals to Autoimmune Disease Development and Occurrence.

PURPOSE OF REVIEW: Exposure to many synthetic chemicals has been linked to a variety of adverse human health effects, including autoimmune diseases. In this scoping review, we summarize recent evidence detailing the effects of synthetic environmental chemicals on autoimmune diseases and highlight current research gaps and recommendations for future studies. RECENT FINDINGS: We identified 68 recent publications related to environmental chemical exposures and autoimmune diseases. Most studies evaluated exposure to persistent environmental chemicals and autoimmune conditions including rheumatoid arthritis (RA), systemic lupus (SLE), systemic sclerosis (SSc), and ulcerative colitis (UC) and Crohn's disease. Results of recent original research studies were mixed, and available data for some exposure-outcome associations were particularly limited. PFAS and autoimmune inflammatory bowel diseases (UC and CD) and pesticides and RA appeared to be the most frequently studied exposure-outcome associations among recent publications, despite a historical research focus on solvents. Recent studies have provided additional evidence for the associations of exposure to synthetic chemicals with certain autoimmune conditions. However, impacts on other autoimmune outcomes, particularly less prevalent conditions, remain unclear. Owing to the ubiquitous nature of many of these exposures and their potential impacts on autoimmune risk, additional studies are needed to better evaluate these relationships, particularly for understudied autoimmune conditions. Future research should include larger longitudinal studies and studies among more diverse populations to elucidate the temporal relationships between exposure-outcome pairs and to identify potential population subgroups that may be more adversely impacted by immune modulation caused by exposure to these chemicals.

First trimester plasma PER- AND Polyfluoroalkyl Substances (PFAS) and blood pressure trajectories across the second and third trimesters of pregnancy

BACKGROUND: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. OBJECTIVES: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. METHODS: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. RESULTS: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. CONCLUSION: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother.

The Neo-Open Reading Frame Peptides That Comprise the Tumor Framome Are a Rich Source of Neoantigens for Cancer Immunotherapy.

Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate the whole-genome and long-read transcript sequencing of cancers to identify the collection of neo-open reading frame peptides (NOP) expressed in tumors. We termed this collection of NOPs the tumor framome. NOPs represent tumor-specific peptides that are different from wild-type proteins and may be strongly immunogenic. We describe a class of hidden NOPs that derive from structural genomic variants involving an upstream protein coding gene driving expression and translation of noncoding regions of the genome downstream of a rearrangement breakpoint, i.e., where no gene annotation or evidence for transcription exists. The entire collection of NOPs represents a vast number of possible neoantigens particularly in tumors with many structural genomic variants and a low number of missense mutations. We show that NOPs are immunogenic and epitopes derived from NOPs can bind to MHC class I molecules. Finally, we provide evidence for the presence of memory T cells specific for hidden NOPs in peripheral blood from a patient with lung cancer. This work highlights NOPs as a major source of possible neoantigens for personalized cancer immunotherapy and provides a rationale for analyzing the complete cancer genome and transcriptome as a basis for the detection of NOPs.

Estimating the cost of Rh testing and prophylaxis in early pregnancy: A time-driven activity-based costing study.

OBJECTIVE: To estimate the cost of Rhesus (Rh) testing and prophylaxis for first-trimester vaginal bleeding in the ambulatory setting. STUDY DESIGN: We used time-driven, activity-based costing to analyze tasks associated with Rh testing and prophylaxis of first-trimester vaginal bleeding at one hospital-based outpatient and two independent reproductive health clinics. At each site, we observed 10 patients undergoing Rh-typing and two patients undergoing Rh prophylaxis. We computed the costs of blood Rh-typing by both fingerstick and phlebotomy, cost of locating previous blood type in the electronic health record (available for 69.8% of hospital-based patients), and costs associated with Rh immune globulin prophylaxis. All costs are reported in 2021 US dollars. RESULTS: The hospital-based clinic reviewed the electronic health record to confirm Rh-status (cost, $26.18 per patient) and performed a phlebotomy, at $47.11 per patient, if none was recorded. The independent clinics typed blood by fingerstick, at a per-patient cost of $4.07. Rh-immune globulin administration costs, including the medication, were similar across facilities, at a mean of $145.66 per patient. Projected yearly costs for testing and prophylaxis were $55,831 for the hospital-based clinic, which was the lowest-volume site, $47,941 for Clinic A, which saw 150 patients/month, and $185,654 for Clinic B, which saw 600 patients/month. CONCLUSIONS: Rh testing and prophylaxis for first-trimester vaginal bleeding generates considerable costs for outpatient facilities, even for Rh-positive patients with a prior blood type on record. IMPLICATIONS: Rh testing and prophylaxis for first-trimester bleeding generate considerable costs even for Rh-positive patients and those with a previously known blood type. These findings highlight the need to reconsider this practice, which is no longer supported by evidence and already safely waived in multiple medical settings in the United States and around the world.

Other Secondary Headaches: Odontogenic Pain and Other Painful Orofacial Conditions.

This article discusses extremely common odontogenic pain conditions, which may occasionally present to the neurology clinic mimicking headache, and other uncommon orofacial pain conditions, which may do the same. Typical presentations, investigative strategies, and management are discussed, as well as highlighting key diagnostic criteria and the importance of involving oral or dental specialists where diagnostic uncertainty exists.

Metabolic maturation in the infant urine during the first 3 months of life.

The infant urine metabolome provides a body metabolic snapshot, and the sample collection can be done without stressing the fragile infant. 424 infant urine samples from 157 infants were sampled longitudinally at 1-, 2-, and 3 months of age. 49 metabolites were detected using proton nuclear magnetic resonance spectroscopy. Data were analyzed with multi- and univariate statistical methods to detect differences related to infant age-stage, gestational age, mother's pre-pregnancy BMI, C-section, infant birth weight, and infant sex. Significant differences were identified between age-stage (pbonferoni < 0.05) in 30% (15/49) of the detected metabolites. Urine creatinine increased significantly from 1 to 3 months. In addition, myo-inositol, taurine, methionine, and glucose seem to have conserved levels within the individual over time. We calculated a urine metabolic maturation age and found that the metabolic age at 3 months is negatively correlated to weight at 1 year. These results demonstrate that the metabolic maturation can be observed in urine metabolome with implications on infant growth and specifically suggesting that the systematic age effect on creatinine promotes caution in using this as normalization of other urine metabolites.

Defining and reporting adverse events of special interest in comparative maternal vaccine studies: a systematic review.

Introduction: The GAIA (Global Alignment on Immunisation Safety Assessment in Pregnancy) consortium was established in 2014 with the aim of creating a standardised, globally coordinated approach to monitoring the safety of vaccines administered in pregnancy. The consortium developed twenty-six standardised definitions for classifying obstetric and infant adverse events. This systematic review sought to evaluate the current state of adverse event reporting in maternal vaccine trials following the publication of the case definitions by GAIA, and the extent to which these case definitions have been adopted in maternal vaccine safety research. Methods: A comprehensive search of published literature was undertaken to identify maternal vaccine research studies. PubMed, EMBASE, Web of Science, and Cochrane were searched using a combination of MeSH terms and keyword searches to identify observational or interventional studies that examined vaccine safety in pregnant women with a comparator group. A two-reviewer screening process was undertaken, and a narrative synthesis of the results presented. Results: 14,737 titles were identified from database searches, 435 titles were selected as potentially relevant, 256 were excluded, the remaining 116 papers were included. Influenza vaccine was the most studied (25.0%), followed by TDaP (20.7%) and SARS-CoV-2 (12.9%).Ninety-one studies (78.4%) were conducted in high-income settings. Forty-eight (41.4%) utilised electronic health-records. The majority focused on reporting adverse events of special interest (AESI) in pregnancy (65.0%) alone or in addition to reactogenicity (27.6%). The most frequently reported AESI were preterm birth, small for gestational age and hypertensive disorders. Fewer than 10 studies reported use of GAIA definitions. Gestational age assessment was poorly described; of 39 studies reporting stillbirths 30.8% provided no description of the gestational age threshold. Conclusions: Low-income settings remain under-represented in comparative maternal vaccine safety research. There has been poor uptake of GAIA case definitions. A lack of harmonisation and standardisation persists limiting comparability of the generated safety data.

Transferability of Human and Environmental Microbiome on Clothes as a Tool for Forensic Investigations.

Considering the growing importance of microbiome analyses in forensics for identifying individuals, this study explores the transfer of the skin microbiome onto clothing, its persistence on fabrics over time, and its transferability from the environment and between different garments. Furthermore, this project compares three specific QIAGEN microbiome extraction kits to test their extraction efficiency on fabric samples. Additionally, this study aims to check if these extracts contain human DNA, providing a chance to obtain more information from the same evidence for personal identification. The results obtained show: (1) variations in the skin microbiome between the volunteers, potentially due to their different sex; (2) differences in microbial composition between worn and unworn clothing; (3) the influence of the environment on the microbial signature of unworn clothing; (4) the potential use of certain phyla as biomarkers to differentiate between worn and unworn garments, even over extended periods; (5) a tendency towards extraction biases in the QIAampMP® DNA microbiome kit among the three tested ones; and (6) none of the extraction kits allow for the typing of human genetic profiles suitable for comparison. In conclusion, our study offers supplementary insights into the potential utility of time-transferred microbiome analysis on garments for forensic applications.

Temporal Patterns in Fruit and Vegetable Intake Among Racially and Ethnically Diverse Children and Adolescents in California.

Introduction: Childhood dietary behaviors, including fruit and vegetable intake, are associated with adult health. Most children do not meet daily recommended servings of fruits and vegetables. Less is known about temporal patterns in fruit and vegetable consumption or if they vary by race and ethnicity. We investigated temporal patterns in fruit and vegetable intake among California school-age children and adolescents overall and by race and ethnicity. Methods: We used 2-year cross-sectional datasets from the child and adolescent samples in the California Health Interview Surveys from 2011-2012 through 2019-2020 and modified Poisson regression models to estimate the likelihood of consuming 5 or more servings of fruits and vegetables in 2013-2016 and 2017-2020 compared with 2011-2012. Models controlled for age, race and ethnicity, gender, citizenship status, family income, and adult education and tested for differences by race and ethnicity. The samples included 16,125 children aged 5 to 11 years and 9,672 adolescents aged 12 to 17 years. Results: Overall, 29.3% of children and 25.9% of adolescents reported intake of 5 or more fruits and vegetables per day. Among children, adjusted prevalence ratios (PR) of fruit and vegetable intake were higher in 2013-2016 (PR,1.25; 95% CI, 1.11-1.42) and 2017-2020 (PR,1.13; 95% CI, 0.99-1.30) compared with 2011-2012. Among adolescents, the adjusted prevalence did not differ significantly over time. We found no evidence of differential associations by race and ethnicity for children and adolescents. Conclusion: We found favorable temporal changes in fruit and vegetable consumption among children, but not among adolescents. Monitoring temporal patterns in fruit and vegetable intake remains critical for planning population-level interventions to increase consumption.

Estimating the effect of latent time-varying count exposures using multiple lists.

A major challenge in longitudinal built-environment health studies is the accuracy of commercial business databases that are used to characterize dynamic food environments. Different databases often provide conflicting exposure measures on the same subject due to different source credibilities. As on-site verification is not feasible for historical data, we suggest combining multiple databases to correct the bias in health effect estimates due to measurement error in any 1 datasource. We propose a joint model for the time-varying health outcomes, observed count exposures, and latent true count exposures. Our model estimates the time-specific quality of sources and incorporates time dependence of true count exposure by Poisson integer-valued first-order autoregressive process. We take a Bayesian nonparametric approach to flexibly account for location-specific exposures. By resolving the discordance between different databases, our method reduces the bias in the longitudinal health effect of the true exposures. Our method is demonstrated with childhood obesity data in California public schools with respect to convenience store exposures in school neighborhoods from 2001 to 2008.

Brazilin is a natural product inhibitor of the NLRP3 inflammasome.

Excessive or aberrant NLRP3 inflammasome activation has been implicated in the progression and initiation of many inflammatory conditions; however, currently no NLRP3 inflammasome inhibitors have been approved for therapeutic use in the clinic. Here we have identified that the natural product brazilin effectively inhibits both priming and activation of the NLRP3 inflammasome in cultured murine macrophages, a human iPSC microglial cell line and in a mouse model of acute peritoneal inflammation. Through computational modeling, we predict that brazilin can adopt a favorable binding pose within a site of the NLRP3 protein which is essential for its conformational activation. Our results not only encourage further evaluation of brazilin as a therapeutic agent for NLRP3-related inflammatory diseases, but also introduce this small-molecule as a promising scaffold structure for the development of derivative NLRP3 inhibitor compounds.