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Helicobacter pylori can infect most people worldwide to cause hazardous consequences to health; the bacteria could not easily be controlled or disinfected. Toward exploring of innovative biocidal nanoformulations to control H. pylori, broccoli seeds (Brassica oleracea var. italica) mucilage (MBS) was employed for biosynthesizing selenium nanoparticles (MBS/SeNPs), which was intermingled with chitosan nanoparticles (NCT) to generate bioactive nanocomposites for suppressing H. pylori. The MBS could effectually generate and stabilize SeNPs with 13.61 nm mean diameter, where NCT had 338.52 nm mean diameter and positively charged (+ 39.62 mV). The cross-linkages between NCT-MBS-SeNPs were verified via infrared analysis and the nanocomposites from NCT:MBS/SeNPs at 1:2 (T1), 1:1 (T2) and 2:1 (T3) ratios had mean diameters of 204, 132 and 159 nm, respectively. The entire nanomaterials/composites exhibited potent anti- H. pylori activities using various assaying methods; the T2 nanocomposite was the utmost bactericidal agent with 0.08-0.10 mg/L minimal concentration and 25.9-27.3 mm inhibition zones. The scanning microscopy displayed the ability of nanocomposite to attach the bacterial cells, disrupt their membranes, and completely lyse them within 10 h. The NCT/MBS/SeNPs nanocomposites provided effectual innovative approach to control H. pylori.

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Space radiation is a notable hazard for long-duration human spaceflight1. Associated risks include cancer, cataracts, degenerative diseases2 and tissue reactions from large, acute exposures3. Space radiation originates from diverse sources, including galactic cosmic rays4, trapped-particle (Van Allen) belts5 and solar-particle events6. Previous radiation data are from the International Space Station and the Space Shuttle in low-Earth orbit protected by heavy shielding and Earth's magnetic field7,8 and lightly shielded interplanetary robotic probes such as Mars Science Laboratory and Lunar Reconnaissance Orbiter9,10. Limited data from the Apollo missions11-13 and ground measurements with substantial caveats are also available14. Here we report radiation measurements from the heavily shielded Orion spacecraft on the uncrewed Artemis I lunar mission. At differing shielding locations inside the vehicle, a fourfold difference in dose rates was observed during proton-belt passes that are similar to large, reference solar-particle events. Interplanetary cosmic-ray dose equivalent rates in Orion were as much as 60% lower than previous observations9. Furthermore, a change in orientation of the spacecraft during the proton-belt transit resulted in a reduction of radiation dose rates of around 50%. These measurements validate the Orion for future crewed exploration and inform future human spaceflight mission design.

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BACKGROUND: Organizational-level interventions (i.e., Baby-Friendly Hospital Initiative) that support breastfeeding and target breastfeeding initiation are critical to reducing breastfeeding disparities and promoting breastfeeding equity. RESEARCH AIM: To determine the association between delivery in a Baby-Friendly accredited hospital and breastfeeding initiation among United States recipients of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in Washington DC, the majority of whom report their race as Black. METHOD: We conducted a secondary analysis of de-identified program data collected as part of routine WIC visits from the Washington DC WIC program, 2017-2020. Women who delivered a firstborn, singleton infant were included (N = 8,225). Multivariable logistic regression models accounted for social determinants of health and other factors. One set of models included a binary exposure variable (Baby-Friendly accredited vs. non-accredited hospitals), and another set included a categorical exposure variable for hospitals (1) Baby-Friendly accredited, (2) Baby-Friendly activities but not accredited, and (3) neither Baby-Friendly activities nor accredited. RESULTS: Breastfeeding initiation was 57.4% (n = 1988) for women delivering in accredited hospitals versus 55.4% (n = 2540) in non-accredited hospitals and multivariable model results were non-significant (OR = 0.95, 95% CI [0.86, 1.05]). However, more women initiated breastfeeding who delivered in either accredited hospitals (57.4%, n = 1988) or hospitals with Baby-Friendly activities but not accredited (55.9%, n = 2430) compared to those delivering in hospitals with neither (45.3%, n = 110), and multivariable models results concurred (Baby-Friendly accredited hospitals OR = 1.44, 95% CI [1.07, 1.94]; Baby-Friendly activities but not accredited, (OR = 1.55, 95% CI [1.16, 2.09]). CONCLUSION: Organizational-level interventions that create hospital environments supportive of breastfeeding initiation are important to promote equity in breastfeeding, but underlying social determinants of breastfeeding outcomes must be addressed.

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Severe thermal skin burns are complicated by inflammation and apoptosis, which delays wound healing and contributes to significant morbidity. Diverse treatments demonstrate limited success with mitigating these processes to accelerate healing. Agents that alter cell behavior to improve healing would alter treatment paradigms. We repurposed 4-aminopyridine (4-AP), a drug approved by the US FDA for multiple sclerosis, to treat severe burns. We found that 4-AP, in the early stages of burn healing, significantly reduced the expression of pro-inflammatory cytokines IL1ß and TNFα while increasing the expression of anti-inflammatory markers CD206, ARG-1, and IL10. 4-AP attenuated apoptosis, with decreases in apoptotic markers BAX, caspase-9, and caspase-3 and increases in anti-apoptotic markers BCL2 and BCL-XL. Furthermore, 4-AP promoted angiogenesis through increases in the expression of CD31, VEGF, and eNOS. Together, these likely contributed to accelerated burn wound closure, as demonstrated in increased keratinocyte proliferation (K14) and differentiation (K10) markers. In the later stages of burn healing, 4-AP increased TGFß and FGF levels, which are known to mark the transformation of fibroblasts to myofibroblasts. This was further demonstrated by an increased expression of α-SMA and vimentin, as well as higher levels of collagen I and III, MMP 3, and 9 in animals treated with 4-AP. Our findings support the idea that 4-AP may have a novel, clinically relevant therapeutic use in promoting burn wound healing.

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Endometrial cancer (EC) is the most common gynaecological cancer among women in high-income countries, with both incidence and mortality continuing to increase. The complexity of the management of patients with EC has evolved with greater comprehension of the underlying biology and heterogeneity of this disease. With a growing number of novel therapeutic agents available, emerging treatment regimens seem to have the potential to help to address the concerning trends in EC-related mortality. In this Review, we describe the epidemiology, histopathology and molecular classification of EC as well as the role of the new (2023) International Federation of Gynecologists and Obstetricians (FIGO) staging model. Furthermore, we provide an overview of disease management in the first-line and recurrent disease settings. With increasing use of molecular profiling and updates in treatment paradigms, we also summarize new developments in this rapidly changing treatment landscape.

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In gastrointestinal stromal tumors (GISTs), identifying prototypical mutations in the KIT/PDGFRA oncogenes, or in rare alternate genes, is essential for prognostication and predicting response to tyrosine kinase inhibitors. Conversely, wild-type GISTs (WT-GIST), which lack known mutations, have limited treatment options. Data on the mutational landscape of GISTs and their impact on disease progression are very limited in Kuwait. Using a targeted next-generation sequencing panel, we investigated the spectrum and frequency of KIT, PDGFRA, and RAS-pathway-related mutations in 95 out of 200 GISTs diagnosed at Kuwait Cancer Center from 2005 to 2023 and assessed their correlation with clinicopathological parameters. Among the 200 tumors (median age 55 years; 15-91), 54% originated in the stomach, 33% in the small bowel, 7% in the colorectum, 1.5% in the peritoneum, and 4.5% had an unknown primary site. Of the 95 molecularly profiled cases, 88% had a mutation: KIT (61%), PDGFRA (25%), NF1 (2%), and one NTRK1 rearrangement. Ten WT-GISTs were identified (stomach = 6, small bowel = 2, and colorectum = 2). WT-GISTs tended to be smaller (median 4.0 cm; 0.5-8.0) (p = 0.018), with mitosis ≤5/5 mm2, and were of lower risk (p = 0.019). KIT mutations were an adverse indicator of disease progression (p = 0.049), while wild-type status did not significantly impact progression (p = 0.934). The genetic landscape in this cohort mirrors that of global studies, but regional collaborations are needed to correlate outcomes with genetic variants.

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BACKGROUND: In recent years, obstructive sleep apnea (OSA) has been increasingly recognized as a significant health concern. No previous studies assessed the effect of recommended treatment modalities of patients with OSA on the temporomandibular joint (TMJ). The current study aimed to evaluate the effect of different treatment modalities of OSA, such as continuous positive airway pressure (CPAP), mandibular advancement device (MAD), and oral myofunctional therapy (OMT) on subjective symptoms, clinical, and radiographic signs of temporomandibular disorders. PATIENTS & METHODS: This hospital-based prospective randomized controlled clinical trial study was approved by the institutional review board and formal patient consent, 39 OSA patients, ranging in age from 19 to 56 after confirmation with full night Polysomnography (PSG) with healthy TMJ confirmed clinically and radiographically with magnetic resonance imaging (MRI) were randomly allocated into three treatment groups. Group 1: 13 patients were managed with CPAP after titration, group 2: 13 patients were managed with digitally fabricated MAD, and group 3: 13 patients were managed with OMT. The following parameters were evaluated before and 3 months after the intervention. Pain using a visual analogue scale (VAS), maximum inter-incisal opening (MIO), lateral movements, and clicking sound of TMJ. MRI was done before and 3 months after the intervention. RESULTS: Out of the 83 patients enrolled, 39 patients completed the treatment. There were no statistically significant differences in lateral jaw movements or clicking, and no significant difference in MRI findings between the three studied groups before and after the intervention. The OMT group showed a statistically significant difference in pain (p = 0.001), and MIO (p = 0.043) where patients experienced mild pain and slight limitation in mouth opening after 3 months of follow-up in comparison to MAD and CPAP groups. CONCLUSION: CPAP and MAD are better for preserving the health of TMJ in the treatment of OSA patients. While OMT showed mild pain and slight limitation of MIO (that is still within the normal range of mouth opening) compared to CPAP and MAD. TRIAL REGISTRATION: The study was listed on www. CLINICALTRIALS: gov with registration number (NCT05510882) on 22/08/2022.

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Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance of METI on ST data generated from various tumor tissues, including gastric, lung, and bladder cancers, as well as premalignant tissues. We also conduct a quantitative comparison of METI with existing clustering and cell deconvolution tools, demonstrating METI's robust and consistent performance.

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As the medical complexity of pregnant patients increases, the rate of maternal morbidity has risen. Maternal cardiovascular disease is a leading cause of maternal morbidity and mortality followed closely by sepsis and infection, both of which may be associated with respiratory failure. There has been an expansion in the application of extracorporeal life support in pregnant and peripartum patients which requires obstetric anesthesiologists to understand the indications, obstetric and medical considerations, relative advantages and potential complications of this invasive technology in this population. Obstetricians and anesthesiologists who care for women on the labor floor must strive to recognize at-risk and deteriorating patients, facilitate escalation of care when appropriate, and engage consultant teams to consider the need for extracorporeal support in high-risk circumstances. This article reviews the epidemiology, indications, specific considerations, potential complications, and outcomes of extracorporeal life support in pregnant and peripartum patients.

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INTRODUCTION: A retained sponge after spine surgery can cause serious medical complications and medicolegal problems. Intraoperative radiographs are commonly used to detect it. This study evaluated intraoperative radiographs under routine clinical conditions that most spine surgeons experience to detect retained sponges. METHODS: In this prospective randomized clinical trial, two patient groups undergoing open posterior lumbar surgery were studied. In one, a sponge was intentionally present; in the other, none was present. Standard intraoperative lateral (LAT) and anteroposterior (AP) radiographs were acquired before closing. Radiographs were analyzed for sensitivity, specificity, inter- and intraobserver reliability for three viewing conditions: one LAT radiograph versus one AP radiograph versus one LAT and one AP X-ray (LAT+AP). RESULTS: A total of 111 patients were included. Accuracy, interobserver reliability, and intraobserver reliability were best for LAT+AP (80%, 96%, and 96%, respectively). Sensitivity was best for LAT+AP (87%) and specificity was best for LAT (95%). Positive predictive value was best for LAT (94%); negative predictive value was best for LAT+AP (88%). The probability of being right is better for female sex (odds ratio 1.6), younger age (odds ratio 1.02), and higher BMI (odds ratio 1.06). CONCLUSIONS: We recommend AP with LAT images rather than either an AP or a LAT image alone.

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Background  Orthopedic surgery is one of the most competitive specialties to match into a residency. With a plethora of qualified applicants and the subjective nature of matching into any residency program, it can be difficult to accurately assess the chances of successfully matching into orthopedic surgery and the types of programs an applicant will match into. The purpose of this study is to compare the types of programs that students from medical schools with and without home programs match. Methods This was a five-year retrospective study (2019 to 2023) analyzing 155 United States Doctor of Medicine (M.D.) programs and their orthopedic residency-matched students. Of the 155 programs, 40 were excluded from the study due to the lack of obtainable data. For each medical school, we analyzed several variables: the presence of a home program, the total number of orthopedic residency matches, residency program matches, and residency program affiliation (academic, community, university-affiliated community-based, military). Results Of the 2066 total matched applicants from institutions with home programs, 1508 (73%) matched into academic centers, 315 (15.3%) into university-affiliated community programs, 172 (8.3%) into community programs, and 71 (3.4%) into military programs. In contrast, of the 219 total matched applicants from institutions without home programs (orphan applicants), 144 (67.8%) matched into academic programs, 36 (16.4%) into university-affiliated community programs, 28 (12.8%) into community programs, and 11 (5%) into military programs. Conclusion A greater proportion of students from institutions with home programs matched into academic centers compared to orphan applicants (73% vs. 65.8%). A greater proportion of orphan applicants matched into community programs (12.8% vs. 8.3%).

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Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second major cause of cancer-related death. Thus, we attempted to ascertain the relationship between the genotype and allele frequencies of phosphatase and tensin homolog (PTEN) and immunohistochemical PTEN expression with clinicopathological characteristics in patients with CRC. 150 individuals were allocated into two groups for this cross-sectional randomized case-control study: Group I consisted of 100 patients with histopathologically proven CRC of various stages. Group II: Fifty healthy volunteers. Genetic analysis of PTEN (rs701848 T / C) single nucleotide polymorphism (SNP) was performed using TaqManTM assays and real-time PCR, while PTEN expressions were assessed using immunohistochemical staining. PTN SNP genotypes and alleles did not significantly differ between CRC patients and controls. PTEN expression was lost in 28% of CRC patients, while all healthy controls exhibited PTEN expression. Negative PTEN expression was present in 16 (80%) of stage IV CRC cases, 9 (23.7%) of stage III cases, 3 (37.5%) of stage II cases, and none of stage I cases. It was shown that PTEN expression was weakly positive, moderately positive, and strongly positive in 15, 10, and 9 (respectively) cases of CRC stage I. However, the expression was only weekly positive in 4 (20%) of the patients in stage IV. In the stage IV group, neither moderately nor strongly positive PTEN expressions were found. So, Among Egyptians, the emergence or course of colorectal cancer is unrelated to the PTEN gene mutation. However, the formation and progression of CRC may be influenced by weak or lost PTEN expression.

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Hepatic sinusoids are highly specialized microcirculatory conduits within the hepatic lobules that facilitate liver functions. The sinusoids can be affected by various disorders, including sinusoidal dilatation, sinusoidal obstruction syndrome (SOS), sinusoidal cellular infiltration, perisinusoidal infiltration, and endothelial neoplasms, such as hemangioendothelioma and angiosarcoma. While these disorders, particularly SOS and neoplasms, can be life threatening, their clinical manifestation is often nonspecific. Patients may present with right upper quadrant pain, jaundice, hepatomegaly, ascites, splenomegaly, and unexplained weight gain, although the exact manifestation depends on the cause, severity, and duration of the disease. Ultimately, invasive tests may be necessary to establish the diagnosis. A comprehensive understanding of imaging manifestations of various sinusoidal disorders contributes to early diagnosis and can help radiologists detect subclinical disease. Additionally, specific imaging features may assist in identifying the cause of the disorder, leading to a more focused and quicker workup. For example, a mosaic pattern of enhancement of the liver parenchyma is suggestive of sinusoidal dilatation; peripheral and patchy reticular hypointensity of the liver parenchyma on hepatobiliary MR images is characteristic of SOS; and associated diffuse multiple hyperintensities on diffusion-weighted images may be specific for malignant sinusoidal cellular infiltration. The authors provide an overview of the pathogenesis, clinical features, and imaging appearances of various hepatic sinusoidal disorders, with a special emphasis on SOS. ©RSNA, 2024 Supplemental material is available for this article.

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Left ventricular non-compaction cardiomyopathy (LVNC) is an unusual congenital heart disease that predominantly affects the heart's left ventricle. This disease is characterized by deep intertrabecular recesses and hypertrabeculations of the myocardial wall that link with the ventricle cavity. During embryogenesis, the fetal myocardium has to undergo a compaction process, wherein the trabeculated and spongy myocardial tissue compacts into a dense, solid form. An incomplete compaction process results in persistent non-compacted spongy myocardial tissue and trabeculations prominent in the left ventricle. This disease could be marked alone or be present in coexistence with other congenital heart abnormalities. We present a rare case of a 57-year-old Saudi male who presented to the ER with chest pain and dyspnea. Due to severe chest pain, he was admitted to the coronary care unit. On further investigation, an echocardiogram revealed heavy trabeculations in the dilated left ventricle and a reduced ejection fraction. The case was diagnosed as LVNC and possible heart failure. The patient was discharged after he was kept under guideline-directed medical therapy (GDMT) along with certain medications and will be evaluated after six months of GDMT to decide on implantable cardiac resynchronization therapy. Although LVNC is rare, it can lead to severe heart conditions like arrhythmias, thromboembolism, and heart failure.

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Multifaceted interrogation of the proteome deepens the system-wide understanding of biological systems; however, mapping the redox changes in the proteome has so far been significantly more challenging than expression and solubility/stability analyses. Here, the first high-throughput redox proteomics approach integrated with expression analysis (REX) is devised and combined with the Proteome Integral Solubility Alteration (PISA) assay. The whole PISA-REX experiment with up to four biological replicates can be multiplexed into a single tandem mass tag TMTpro set. For benchmarking this compact tool, HCT116 cells treated with auranofin are analyzed, showing great improvement compared with previous studies. PISA-REX is then applied to study proteome remodeling upon stimulation of human monocytes by interferon α (IFN-α). Applying this tool to study the proteome changes in plasmacytoid dendritic cells (pDCs) isolated from wild-type versus Ncf1-mutant mice treated with interferon α, shows that NCF1 deficiency enhances the STAT1 pathway and modulates the expression, solubility, and redox state of interferon-induced proteins. Providing comprehensive multifaceted information on the proteome, the compact PISA-REX has the potential to become an industry standard in proteomics and to open new windows into the biology of health and disease.

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BACKGROUND: The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood. METHODS: In this single-arm phase 2 trial (this study was registered at ClinicalTrials.gov: NCT02520154), eligible patients received up to 4 cycles of neoadjuvant chemotherapy followed by interval cytoreduction, 3 cycles of adjuvant intravenous carboplatin/weekly paclitaxel/pembrolizumab, and finally maintenance pembrolizumab until progression or toxicity (maximum 20 cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included feasibility, toxicity, and overall survival (OS). PD-L1 staining, multiplex immunofluorescence staining, RNA sequencing, reverse-phase protein array analyses were performed on pre- and post-chemotherapy samples. FINDINGS: Thirty-one eligible patients were enrolled. Median PFS and OS was 14.88 (95% CI 12.39-23.00) and 57.43 months (95% CI 30.88-not reached), respectively. Among those with PD-L1 combined positive score (CPS) ≥10, the median PFS and OS were not reached compared to those with CPS <10 (10.50 and 30.90 months, respectively). Feasibility was met, with all patients completing their planned adjuvant cycles. Treatment discontinuation due to immune-related toxicity occurred in 6 patients (20%). Chemotherapy resulted in an infiltration of anti-tumor immune cells in the tumor microenvironment. Samples of patients with the best PFS demonstrated increased expression of NF-κB, TGF-ß, and ß-catenin signaling. CONCLUSIONS: Pembrolizumab with chemotherapy was feasible and resulted in PFS within the historical range for this EOC population. Patients with CPS ≥10 may benefit more from this regimen, and future studies should investigate this potential biomarker. FUNDING: This investigator-initiated trial was funded by Merck.

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We investigate interfacial instability in a lifting Hele-Shaw cell by experiments and theory. We characterize the unexplored transition from stable to unstable patterns under a wide range of controlling parameters. Surprisingly, we find that the perturbation growth rate-based criterion for the onset of instability from linear stability theory is too strict by over 3 orders of magnitude. To reconcile this striking discrepancy, we propose a new criterion based on perturbation amplitude, which is in excellent agreement with the experimental results. We further show that the fingering pattern evolves to produce a hierarchical fluid structure and derive a theoretical equation to predict the fingering evolution.

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BACKGROUND: There are marked sex differences in the prevalence and severity of asthma, both during childhood and adulthood. There is a relative lack of comprehensive studies exploring sexdifferences in pediatric asthma cohorts. OBJECTIVE: To identify the most relevant sex differences in sociodemographic, clinical, and laboratory variables in a well-characterized large pediatric asthma cohort. METHODS: We performed a cross-sectional analysis of the Mayo Clinic Olmsted County Birth Cohort. In the full birth cohort, we used a natural language-processing algorithm based on the Predetermined Asthma Criteria for asthma ascertainment. In a stratified random sample of 300 children, we obtained additional pulmonary function tests and laboratory data. We identified the significant sex differences among available sociodemographic, clinical, and laboratory variables. RESULTS: Boys were more frequently diagnosed with having asthma than girls and were younger at the time of asthma diagnosis. There were no sex differences in relation to socioeconomic status. We identified a male predominance in the presence of a tympanostomy tube and a female predominance in the history of pneumonia. A higher percentage of boys had a forced expiratory volume in 1 second/forced vital capacity ratio less than 0.85. Blood eosinophilia and atopic sensitization were also more common in boys. Finally, boys had higher levels of serum periostin than girls. CONCLUSION: This study described significant sex differences in a large pediatric asthma cohort. Overall, boys had earlier and more severe asthma than girls. Differences in blood eosinophilia and serum periostin provide insights into possible mechanisms of the sex bias in childhood asthma.

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Pathologic conditions of the biliary system, although common, can be difficult to diagnose clinically. Challenges in biliary imaging include anatomic variants and the dynamic nature of the biliary tract, which can change with age and intervention, blurring the boundaries of normal and abnormal. Choledochal cysts can have numerous appearances and are important to diagnose given the risk of cholangiocarcinoma potentially requiring surgical resection. Choledocholithiasis, the most common cause of biliary dilatation, can be difficult to detect at US and CT, with MRI having the highest sensitivity. However, knowledge of the imaging pitfalls of MRI and MR cholangiopancreatography is crucial to avoid misinterpretation. Newer concepts in biliary tract malignancy include intraductal papillary biliary neoplasms that may develop into cholangiocarcinoma. New paradigms in the classification of cholangiocarcinoma correspond to the wide range of imaging appearances of the disease and have implications for prognosis. Accurately staging cholangiocarcinoma is imperative, given expanding curative options including transplant and more aggressive surgical options. Infections of the biliary tree include acute cholangitis or recurrent pyogenic cholangitis, characterized by obstruction, strictures, and central biliary dilatation. Inflammatory conditions include primary sclerosing cholangitis, which features strictures and fibrosis but can be difficult to differentiate from secondary causes of sclerosing cholangitis, including more recently described entities such as immunoglobulin G4-related sclerosing cholangitis and COVID-19 secondary sclerosing cholangitis. The authors describe a wide variety of benign and malignant biliary tract abnormalities, highlight differentiating features of the cholangitides, provide an approach to interpretation based on the pattern of imaging findings, and discuss pearls and pitfalls of imaging to facilitate accurate diagnosis. ©RSNA, 2024 Supplemental material is available for this article.

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Repetitive traumatic brain injury (RTBI) is acknowledged as a silent overlooked public health crisis, with an incomplete understanding of its pathomechanistic signaling pathways. Mounting evidence suggests the involvement of thrombin and its receptor, the protease-activated receptor (PAR)1, in the development of secondary injury in TBI; however, the consequences of PAR1 modulation and its impact on ferroptosis-redox signaling, and NLRP3 inflammasome activation in RTBI, remain unclear. Further, the utilitarian function of PAR1 as a therapeutic target in RTBI has not been elucidated. To study this crosstalk, RTBI was induced in Wistar rats by daily weight drops on the right frontal region for five days. Three groups were included: normal control, untreated RTBI, and RTBI+SCH79797 (a PAR1 inhibitor administered post-trauma at 25 µg/kg/day). The concomitant treatment of PAR1 antagonism improved altered behavior function, cortical histoarchitecture, and neuronal cell survival. Moreover, the receptor blockade downregulated mRNA expression of PAR1 but upregulatedthat of the neuroprotective receptor PPAR-γ. The anti-inflammatory impact of SCH79797 was signified by the low immune expression/levels of NF-κB p65,TNF-α, IL-1ß, and IL-18. Consequently, the PAR1 blocker hindered the formation of inflammasome components NLRP3, ASC, and activated caspase-1. Ultimately, SCH79797 treatment abated ferroptosis-dependent iron redox signaling through the activation of the antioxidant Nrf2/HO-1 axis and its subsequent antioxidant machinery (GPX4, SOD) to limit lipid peroxidation, iron accumulation, and transferrin serum increment. Collectively, SCH79797 offered putative preventive mechanisms against secondary RTBI consequences in rats by impeding ferroptosis and NLRP3 inflammasome through activating the PPAR-γ/Nrf2 antioxidant cue.

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