Microplastics enhance the adsorption capacity of zinc oxide nanoparticles: Interactive mechanisms and influence factors.

Microplastics (MPs) are of particular concern due to their ubiquitous occurrence and propensity to interact and concentrate various waterborne contaminants from aqueous surroundings. Studies on the interaction and joint toxicity of MPs on engineered nanoparticles (ENPs) are exhaustive, but limited research on the effect of MPs on the properties of ENPs in multi-solute systems. Here, the effect of MPs on adsorption ability of ENPs to antibiotics was investigated for the first time. The results demonstrated that MPs enhanced the adsorption affinity of ENPs to antibiotics and MPs before and after aging showed different effects on ENPs. Aged polyamide prevented aggregation of ZnONPs by introducing negative charges, whereas virgin polyamide affected ZnONPs with the help of electrostatic attraction. FT-IR and XPS analyses were used to probe the physicochemical interactions between ENPs and MPs. The results showed no chemical interaction and electrostatic interaction was the dominant force between them. Furthermore, the adsorption rate of antibiotics positively correlated with pH and humic acid but exhibited a negative correlation with ionic strength. Our study highlights that ENPs are highly capable of accumulating and transporting antibiotics in the presence of MPs, which could result in a widespread distribution of antibiotics and an expansion of their environmental risks and toxic effects on biota. It also improves our understanding of the mutual interaction of various co-existing contaminants in aqueous environments.

Estimation of gaseous polycyclic aromatic hydrocarbons (PAHs) and characteristics of atmospheric PAHs at a traffic site in Kanazawa, Japan.

Size-fractionated particulate matter (PM2.5 and PM>2.5) was collected at a traffic site in Kanazawa, Japan in a seasonal sampling work in 2020. Nine polycyclic aromatic hydrocarbons (4- to 6-ring PAHs) were determined in fine and coarse particles. The gas/particle partitioning coefficients (Kp) of the PAHs were calculated from the supercooled liquid vapour pressure and octanol-air partitioning coefficient based on the relationships obtained in previous traffic pollution-related studies. Gaseous PAHs were estimated by Kp and the concentrations of PM and particulate PAHs. The concentrations of total PAHs were 32.5, 320.1 and 5646.2 pg/m3 in the PM>2.5, PM2.5 and gas phases, respectively. Significant seasonal trends in PAHs were observed (particle phase: lowest in summer, gas phase: lowest in spring, particle and gas phase: lowest in spring). Compared to 2019, the total PAH concentrations (in particles) decreased in 2020, especially in spring and summer, which might be due to reduced traffic trips during the COVID-19 outbreak. The incremental lifetime cancer risk (ILCR) calculated from the toxic equivalent concentrations relative to benzo[a]pyrene (BaPeq) was lower than the acceptable limit issued by the US Environmental Protection Agency, indicating a low cancer risk in long-term exposure to current PAH levels. It is notable that gaseous PAHs considerably contributed to BaPeq and ILCR (over 50%), which highlighted the significance of gaseous PAH monitoring for public health protection. This low-cost estimation method for gaseous PAHs can be expected to reliably and conveniently obtain PAH concentrations as a surrogate for traditional sampling in the future work.

Artificial Bacteriophages for Treating Oral Infectious Disease via Localized Bacterial Capture and Enhanced Catalytic Sterilization.

With the rapid emergence of antibiotic-resistant pathogens, nanomaterial-assisted catalytic sterilization has been well developed to combat pathogenic bacteria by elevating the level of reactive oxygen species including hydroxyl radical (·OH). Although promising, the ultra-short lifetime and limited diffusion distance of ·OH severely limit their practical antibacterial usage. Herein, the rational design and preparation of novel virus-like copper silicate hollow spheres (CSHSs) are reported, as well as their applications as robust artificial bacteriophages for localized bacterial capture and enhanced catalytic sterilization in the treatment of oral infectious diseases. During the whole process of capture and killing, CSHSs can efficiently capture bacteria via shortening the distance between bacteria and CSHSs, produce massive ·OH around bacteria, and further iinducing the admirable effect of bacterial inhibition. By using mucosal infection and periodontitis as typical oral infectious diseases, it is easily found that the bacterial populations around lesions in animals after antibacterial treatment fall sharply, as well as the well-developed nanosystem can decrease the inflammatory reaction and promote the hard or soft tissue repair. Together, the high Fenton-like catalytic activity, strong bacterial affinity, excellent antibacterial activity, and overall safety of the nanoplatform promise its great therapeutic potential for further catalytic bacterial disinfection.

Integration of Gut Mycobiota and Oxidative Stress to Decipher the Roles of C-Type Lectin Receptors in Inflammatory Bowel Diseases.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of inflammatory bowel disease (IBD) with rapidly increased incidence worldwide. Although multiple factors contribute to the occurrence and progression of IBD, the role of intestinal fungal species (gut mycobiota) in regulating the severity of these conditions has been increasingly recognized. C-type lectin receptors (CLRs) on hematopoietic cells, including Dectin-1, Dectin-2, Dectin-3, Mincle and DC-SIGN, are a group of pattern recognition receptors (PRRs) that primarily recognize fungi and mediate defense responses, such as oxidative stress. Recent studies have demonstrated the indispensable role of CLRs in protecting the colon from intestinal inflammation and mucosal damage. METHODS AND RESULTS: This review provides a comprehensive overview of the role of CLRs in the pathogenesis of IBD. Given the significant impact of mycobiota and oxidative stress in IBD, this review also discusses recent advancements in understanding how these factors exacerbate or ameliorate IBD. Furthermore, the latest developments in CLR-guided IBD therapy are examined to highlight the modulation of CLRs in fungal recognition and oxidative burst during the IBD process. CONCLUSION: This review emphasizes the importance of CLRs in IBD, offering new perspectives on the etiology and therapeutic approaches for this disease.

Exercise Enhances Anti-contractile Effects of PVAT Through Endogenous H2S in High-Fat Diet-Induced Obesity Hypertension.

PURPOSE: Hydrogen sulfide (H2S) secreted by perivascular adipose tissue (PVAT) is a critical vasodilator, which might be involved during the pathogenesis of hypertension. The present study aimed to investigate the exact role of H2S on the regulation of PVAT anti-contraction by long-term exercise in obesity hypertension. METHODS: After the establishment of obesity hypertension (24 weeks) through a high-fat diet, male Sprague-Dawley rats were randomly assigned to control group (HC), exercise group (HE), cystathionine γ-lyase (CSE) blocking group (HCB), and exercise combined with CSE blocking group (HEB). Exercise and CSE inhibitor regimens were performed throughout 13 weeks. RESULTS: After 13 weeks of intervention, blood pressure was significantly decreased by long-term exercise (HC vs. HE, P < 0.05) but not by exercise combined with the CSE inhibitor regimen. Meanwhile, the CSE inhibitor significantly blocked the production of H2S in PVAT even after exercise (HE vs. HEB, P < 0.05). Furthermore, long-term exercise altered the expressions of voltage-dependent K+ (Kv) channel subunits 7 (KCNQs), which were diminished by CSE inhibition in mesenteric arteries. As for vascular tension assessment, after incubation with or without KCNQ opener (retigabine), the anti-contractile effect of PVAT (with or without transferred bath solution of PVAT) was significantly enhanced by long-term exercise and eliminated by the CSE inhibitor regimen (P < 0.05); KCNQ inhibitor (XE991) blunted this effect except for HE. CONCLUSIONS: These results collectively suggest that endogenous H2S is a strong regulator of the anti-contractile effect of PVAT in obesity hypertension by long-term exercise, and KCNQ in the resistance artery might be involved during this process but not the only target channel mediated by H2S.

Major depressive disorder elevates the risk of dentofacial deformity: a bidirectional two-sample Mendelian randomization study.

Background: The association between psychiatric disorders and dentofacial deformities has attracted widespread attention. However, their relationship is currently unclear and controversial. Methods: A two-sample bidirectional MR analysis was performed to study the causal relationship between dentofacial deformity and eight psychiatric disorders, including major depressive disorder, panic disorder, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, Alzheimer's disease, autism spectrum disorder, and neuroticism. Inverse variance weighted, weighted median, MR-Egger regression, weighted mode four methods, and further sensitivity analyses were conducted. Results: The major depressive disorder affected dentofacial deformity, with an OR = 1.387 (95% CI = 1.181-1.629, P = 6.77×10-5). No other psychiatric disorders were found to be associated with dentofacial deformity. In turn, dentofacial deformity were associated with neuroticism, with an OR = 1.050 (95% CI = 1.008-1.093, P = 0.018). And there was no evidence that dentofacial deformity would increase the risk of other psychiatric disorders. Conclusions: Major depressive disorder might elevate the risk of dentofacial deformities, and dentofacial deformity conditions would increase the risk of the incidence of neuroticism.

Cooperation between SIX1 and DHX9 transcriptionally regulates integrin-focal adhesion signaling mediated metastasis and sunitinib resistance in KIRC.

High invasive capacity and acquired tyrosine kinase inhibitors (TKI) resistance of kidney renal clear cell carcinoma (KIRC) cells remain obstacles to prolonging the survival time of patients with advanced KIRC. In the present study, we reported that sine oculis homeobox 1 (SIX1) was upregulated in sunitinib-resistant KIRC cells and metastatic KIRC tissues. Subsequently, we found that SIX1 mediated metastasis and sunitinib resistance via Focal adhesion (FA) signaling, and knockdown of SIX1 enhanced the antitumor efficiency of sunitinib in KIRC. Mechanistically, Integrin subunit beta 1 (ITGB1), an upstream gene of FA signaling, was a direct transcriptional target of SIX1. In addition, we showed that DExH-box helicase 9 (DHX9) was an important mediator for SIX1-induced ITGB1 transcription, and silencing the subunits of SIX1/DHX9 complex significantly reduced transcription of ITGB1. Downregulation of SIX1 attenuated nuclear translocation of DHX9 and abrogated the binding of DHX9 to ITGB1 promoter. Collectively, our results unveiled a new signal axis SIX1/ITGB1/FAK in KIRC and identified a novel therapeutic strategy for metastatic KIRC patients.

Effects of degreasing pretreatment on immunohistochemistry and molecular analysis of gastrointestinal and breast cancer samples.

Lymph node status is a key factor in determining stage, treatment, and prognosis in cancers. Small lymph nodes in the fat-rich gastrointestinal and breast cancer specimens are easily missed in conventional sampling methods. This study examined the effectiveness of degreasing pretreatment with dimethyl sulfoxide (DMSO) in lymph node detection and its impact on the analysis of clinical treatment-related proteins and molecules. Thirty-three cases of gastrointestinal cancer specimens from radical gastrectomy and 63 cases of breast cancer specimens from modified radical mastectomy were included. After routine sampling of lymph nodes, the specimens were immersed in DMSO for 30 minutes for defatting. We assessed changes in the number of detected lymph nodes and pN staging in 33 gastrointestinal cancer specimens and 37 breast cancer specimens. Additionally, we analyzed histological characteristics, Masson's trichrome special staining, and immunohistochemistry (gastrointestinal cancer: MMR, HER2, PD-L1; breast cancer: ER, PR, AR, HER2, Ki-67, PD-L1). Molecular status was evaluated for colorectal cancer (KRAS, NRAS, BRAF, MSI) and breast cancer (HER2) in gastrointestinal cancer specimens and the remaining 26 breast cancer specimens. Compared to conventional sampling, DMSO pretreatment increased the detection rate of small lymph nodes (gastrointestinal cancer: p<0.001; breast cancer: p<0.001) and improved pN staging in one case each of gastric cancer, colon cancer, and rectal cancer (3/33, 9.1%). No significant difference in the morphology, special staining, protein, and molecular status of cancer tissue after DMSO treatment were found. Based on these results and our institutional experience, we recommend incorporating DMSO degreasing pretreatment into clinical pathological sampling practices.

Metrnl: a promising biomarker and therapeutic target for cardiovascular and metabolic diseases.

Modern human society is burdened with the pandemic of cardiovascular and metabolic diseases. Metrnl is a widely distributed secreted protein in the body, involved in regulating glucose and lipid metabolism and maintaining cardiovascular system homeostasis. In this review, we present the predictive and therapeutic roles of Metrnl in various cardiovascular and metabolic diseases, including atherosclerosis, ischemic heart disease, cardiac remodeling, heart failure, hypertension, chemotherapy-induced myocardial injury, diabetes mellitus, and obesity.

An unusual presentation of solitary ovarian metastasis from colorectal cancer in an elderly woman: a case report.

Background: There have been cases of colorectal cancer (CRC) metastasizing into the ovary. This study reports a case involving solitary ovarian metastasis (OM) from CRC, which is very rare in the absence of other pelvic and peritoneal metastases. This atypical clinical presentation added to the complexity of the diagnosis. Case Description: We report a case of solitary OM-CRC in a 48-year-old woman. The patient underwent CRC surgery and refused follow-up after three rounds of chemotherapy. Approximately 14 months later, the patient presented with vaginal bleeding for 2 months. The magnetic resonance imaging (MRI) showed a huge solid cystic mass in the right adnexa. Intraoperatively, the right ovary was found to be enlarged and smooth without adhesions. By careful examination of the abdominal cavity, no metastatic lesions were found in the left ovary and uterus, and no seedings were found in the rest of the pelvis and abdomen. After removal of the uterus and bilateral adnexa, the histologic examination revealed metastatic adenocarcinoma of the right ovary with a considered rectal carcinoma of origin. Positive staining for multiple tumor-associated markers, which further established the primary nature of CRC. These findings support a possible diagnosis of primary CRC and ovarian metastases. The patient recovered well after the operation and no recurrence or metastasis was seen 18 months after the operation. Conclusions: Solitary ovarian metastases from CRC can be better managed and treated by increasing clinicians' vigilance for this rare condition. This helps to improve the patient's prognosis and quality of life.

IGF2BP3 participates in the pathogenesis of recurrent spontaneous abortion by regulating ferroptosis.

The aberrant invasive capability of trophoblast cells is widely acknowledged as a primary mechanism underlying RSA. Recently, IGF2BP3 has been implicated in various cancers due to its influence on cellular invasion and migration. However, whether IGF2BP3 involve in the occurrence of RSA and the specific functions it assumes in the development of RSA remain elusive. In our study, we firstly collected villous tissues from RSA and those with normal pregnancies individuals to performed Protein sequencing and then detected the expression of IGF2BP3 through Western blot, qRT-PCR and immunohistochemistry. Secondly, we analyzed the single-cell data (GSE214607) to assess the expression of IGF2BP3 in invasive EVT trophoblasts. Thirdly, we utilized lentivirus technology to establish HTR-8/SVneo cell lines with stable IGF2BP3 knockdown and RNA-seq analysis was employed to investigate the GO functional pathway enrichment of IGF2BP3. Meanwhile, the effect of IGF2BP3 knockdown on trophoblast cells apoptosis, migration, and ferroptosis was evaluated through functional experiments. Additionally, LPS-induced abortion animal model was constructed to evaluate IGF2BP3 expression in placental tissues. A significant downregulation of IGF2BP3 was observed in the villous tissues of RSA patient, a finding corroborated by subsequent single cell sequencing results. Furthermore, it suggested that IGF2BP3 may be involved in the migration and apoptotic processes of trophoblast cells. Mechanistic research indicated that IGF2BP3 knockdown could compromise GPX4 mRNA stability, leading to the promotion of ferroptosis. Finally, our investigation observed the down-regulation of IGF2BP3 expression in placental villous tissues of an LPS-induced abortion animal model. Our findings revealed that IGF2BP3 was downregulated in the villous tissues of RSA patients. Mechanically, down-regulation of IGF2BP3 may induce RSA by promoting GPX4-mediated ferroptosis and inhibiting trophoblast invasion and migration. Our study may provide new targets and research directions for the pathogenesis of RSA.

Long-term effects of COVID-19 on endothelial function, arterial stiffness, and blood pressure in college students: a pre-post-controlled study.

BACKGROUND: The COVID-19 has been shown to have negative effects on the cardiovascular system, but it is unclear how long these effects last in college students. This study aimed to assess the long-term impact of COVID-19 on arterial stiffness, endothelial function, and blood pressure in college students. METHODS: We enrolled 37 college students who had been infected with COVID-19 for more than 2 months. Brachial artery flow-mediated dilation (FMD) was used to assess endothelial function, while arterial stiffness was evaluated using the ABI Systems 100, including variables such as ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), carotid-femoral pulse wave velocity (cfPWV), heart rate (HR), and blood pressure (BP). RESULTS: Our results showed that FMD was significantly impaired after COVID-19 infection (p < 0.001), while cfPWV and systolic blood pressure (SBP) were significantly increased (p < 0.05). Simple linear regression models revealed a significant negative correlation between post-COVID-19 measurement time and baPWV change (p < 0.01), indicating an improvement in arterial stiffness over time. However, there was a significant positive correlation between post-COVID-19 measurement time and diastolic blood pressure (DBP) change (p < 0.05), suggesting an increase in BP over time. There were no significant differences in ABI and HR between pre- and post-COVID-19 measurements, and no significant correlations were observed with other variables (p > 0.05). CONCLUSION: Our study demonstrated that COVID-19 has long-term detrimental effects on vascular function in college students. However, arterial stiffness tends to improve over time, while BP may exhibit the opposite trend.

Artesunate induces melanoma cell ferroptosis and augments antitumor immunity through targeting Ido1.

Artesunate (ART), a natural product isolated from traditional Chinese plant Artemisia annua, has not been extensively explored for its anti-melanoma properties. In our study, we found that ART inhibited melanoma cell proliferation and induced melanoma cell ferroptosis. Mechanistic study revealed that ART directly targets Ido1, thereby suppressing Hic1-mediated transcription suppression of Hmox1, resulting in melanoma cell ferroptosis. In CD8+ T cells, ART does not cause cell ferroptosis due to the low expression of Hmox1. It also targets Ido1, elevating tryptophan levels, which inhibits NFATc1-mediated PD1 transcription, consequently activating CD8+ T cells. Our study uncovered a potent and synergistic anti-melanoma efficacy arising from ART-induced melanoma cell ferroptosis and concurrently enhancing CD8+ T cell-mediated immune response both in vivo and in vitro through directly targeting Ido1. Our study provides a novel mechanistic basis for the utilization of ART as an Ido1 inhibitor and application in clinical melanoma treatment.

The classification of melanocytic gene signatures.

Gene expression profiling technologies have revolutionized cell biology, enabling researchers to identify gene signatures linked to various biological attributes of melanomas, such as pigmentation status, differentiation state, proliferative versus invasive capacity, and disease progression. Although the discovery of gene signatures has significantly enhanced our understanding of melanocytic phenotypes, reconciling the numerous signatures reported across independent studies and different profiling platforms remains a challenge. Current methods for classifying melanocytic gene signatures depend on exact gene overlap and comparison with unstandardized baseline transcriptomes. In this study, we aimed to categorize published gene signatures into clusters based on their similar patterns of expression across clinical cutaneous melanoma specimens. We analyzed nearly 800 melanoma samples from six gene expression repositories and developed a classification framework for gene signatures that is resilient against biases in gene identification across profiling platforms and inconsistencies in baseline standards. Using 39 frequently cited published gene signatures, our analysis revealed seven principal classes of gene signatures that correlate with previously identified phenotypes: Differentiated, Mitotic/MYC, AXL, Amelanotic, Neuro, Hypometabolic, and Invasive. Each class is consistent with the phenotypes that the constituent gene signatures represent, and our classification method does not rely on overlapping genes between signatures. To facilitate broader application, we created WIMMS (what is my melanocytic signature, available at https://wimms.tanlab.org/), a user-friendly web application. WIMMS allows users to categorize any gene signature, determining its relationship to predominantly cited signatures and its representation within the seven principal classes.

The neurobiological mechanisms underlying the effects of exercise interventions in autistic individuals.

Autism spectrum disorder is a pervasive and heterogeneous neurodevelopmental condition characterized by social communication difficulties and rigid, repetitive behaviors. Owing to the complex pathogenesis of autism, effective drugs for treating its core features are lacking. Nonpharmacological approaches, including education, social-communication, behavioral and psychological methods, and exercise interventions, play important roles in supporting the needs of autistic individuals. The advantages of exercise intervention, such as its low cost, easy implementation, and high acceptance, have garnered increasing attention. Exercise interventions can effectively improve the core features and co-occurring conditions of autism, but the underlying neurobiological mechanisms are unclear. Abnormal changes in the gut microbiome, neuroinflammation, neurogenesis, and synaptic plasticity may individually or interactively be responsible for atypical brain structure and connectivity, leading to specific autistic experiences and characteristics. Interestingly, exercise can affect these biological processes and reshape brain network connections, which may explain how exercise alleviates core features and co-occurring conditions in autistic individuals. In this review, we describe the definition, diagnostic approach, epidemiology, and current support strategies for autism; highlight the benefits of exercise interventions; and call for individualized programs for different subtypes of autistic individuals. Finally, the possible neurobiological mechanisms by which exercise improves autistic features are comprehensively summarized to inform the development of optimal exercise interventions and specific targets to meet the needs of autistic individuals.

Exosomal miRNAs in prenatal diagnosis: Recent advances.

Exosomes, small membranous microvesicles released by cells, contain a range of bioactive molecules, including proteins and miRNAs, which play critical roles in intercellular communication and physiological and pathological processes. Current research suggests that exosomal miRNAs could serve as valuable biomarkers for prenatal diseases, offering a noninvasive method for early detection and monitoring. Studies linking exosomal miRNAs to various birth defects, including fetal growth restriction, urinary tract malformations, cardiovascular system malformations, and hereditary diseases like Down syndrome, were discussed. However, there are some conflicting study findings due to different exosome separation methods. Here, we also discussed exosome separation methods, emphasizing the importance of method selection based on specific purposes and sample types. Further studies are needed to standardize isolation techniques, understand the specific mechanisms underlying exosomal miRNA function, and develop reliable noninvasive prenatal diagnostic indicators. Overall, exosomal miRNAs show promise as potential biomarkers for prenatal diagnosis, but further research is necessary to validate their clinical utility.

Enhanced immune reconstitution with albuvirtide in HIV-infected immunological non-responders.

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.

Healthcare resource utilization and economic burden of multiple sclerosis in Chinese patients: results from a real-world survey.

Multiple sclerosis (MS) is uncommon in China and the standard of care is underdeveloped, with limited utilization of disease-modifying treatment (DMT). An understanding of real-world disease burden (including direct medical, non-medical, and indirect costs, such as loss of productivity), is currently lacking in this population. To investigate the overall burden of managing patients with MS in China, a cross-sectional survey of physicians and their consulting patients with MS was conducted in 2021. Physicians provided information on healthcare resource utilization (HCRU; consultations, hospitalizations, tests, medication) and associated costs. Patients provided data on changes in their life, productivity, and impairment of daily activities due to MS. Results were stratified by disease severity using generalized linear models, with a p value < 0.05 considered statistically significant. Patients with more severe disease had greater HCRU, including hospitalizations, consultations and tests/scans, and incurred higher direct and indirect costs and productivity loss, compared with those with milder disease. However, the use of DMT was higher in patients with mild disease severity. With the low uptake and limited efficacy of non-DMT drugs, Chinese patients with MS experience a high disease burden and significant unmet needs. Therapeutic interventions could help save downstream costs and lessen societal burden.

Stress-induced NLRP3 inflammasome activation and myelin alterations in the hippocampus of PTSD rats.

Inflammatory and myelin changes may contribute to the pathophysiology of post-traumatic stress disorder (PTSD). The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3), a brain inflammasome, is activated in the hippocampus of mice with PTSD. In other psychiatric disorders, NLRP3 expression has been associated with axonal myelination and demyelination. However, the association between NLRP3 and myelin in rats with PTSD remains unclear. Therefore, this study aims to investigate the relationship between the NLRP3 inflammasome and myelin in the hippocampus of rats with PTSD. A rat model of post-traumatic stress disorder was established using the single-prolonged stress (SPS) approach. Hippocampal tissues were collected for the detection of NLRP3 inflammasome-associated proteins and myelin basic protein at 3, 7, and 14 days after SPS. To further explore the relationship between NLRP3 and myelin, the NLRP3-specific inhibitor MCC950 was administered intraperitoneally to rats starting 72 h before SPS, and then alterations in NLRP3 inflammasome-associated proteins and myelin were observed in the PTSD and control groups. We found that NLRP3 and downstream related proteins were activated in the hippocampus of rats 3 days after SPS, and the myelin content in the hippocampus increased after SPS stress. MCC950 reduced the expression of NLRP3-related pathway proteins, improved anxiety behaviour and spatial learning memory impairment, and inhibited the increase in myelin content in the hippocampal region of rats after SPS. In conclusion the study indicates that NLRP3 has a significant role in the hippocampal region of rats with PTSD. Inhibition of the NLRP3 inflammasome could be a potential target for treating PTSD.