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The aims of this study are to screen novel differentially expressed genes (DEGs) for intracerebral hemorrhage (ICH) and reveal the role of Lipocalin-2 (LCN2) in ICH.Methods: We constructed the ICH model by injection of autologous whole blood into the right basal ganglia in rats. RNA-sequencing and bioinformatics analyses were performed to identify the DEGs between ICH and sham rats, and some important ones were confirmed using quantitative real-time PCR (qRT-PCR). LCN shRNA was used to knockdown of LCN2 in ICH rats. Pathological examination was carried out using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Hematoxylin-eosin (HE) staining. Immunohistochemistry detected Caspase-3, and co-staining of Terminal dUTP nick end labeling (TUNEL) and NEUN staining were performed for neuron apoptosis assessment. Western blot analysis was performed to quantify pyroptosis-related proteins. Enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory cytokine levels.Results: ICH rats exhibited significant hematomas, higher brain water content, obvious interstitial edema, and inflammatory infiltration, as well as more apoptotic cells in brain tissues. RNA-seq analysis identified 103 upregulated and 81 downregulated DEGs. The expression of LCN2, HSPB1, CXCL10, and MEF2B were upregulated in ICH rats. ICH triggered the release of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-18, and promoted the expression of pyroptosis-related proteins Caspase-1, GSDMD, NLRP3, and ASC. LCN2 knockdown attenuated the pathological characteristics of ICH, and also reduced pyroptosis in brain tissues.Conclusion: Inhibition of LCN2 attenuates brain injury after ICH via suppressing pyroptosis, which provide guidance for ICH management. [ABSTRACT FROM AUTHOR]

Chronic subdural hematoma (CSDH) is a common neurosurgical disease with a high recurrence rate, especially among the elderly. Glucocorticoids have been tested for the treatment of CSDH in observational studies and randomized clinical trials. We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials database for randomized trials from the earliest date available to May 23, 2021 that had compared glucocorticoids and placebo as a postoperative treatment of CSDH. Trials were included if the study participants were aged ≥18 years and had had CSDH after surgery. The relative risk (RR) was used to evaluate the clinical outcomes. We included 5 eligible randomized controlled trials with a total of 1251 patients. The findings showed that the use of adjuvant glucocorticoid therapy can effectively reduce the recurrence risk of CSDH compared with placebo (RR, 0.40; 95% confidence interval [CI], 0.28–0.58; P < 0.001). No significant differences were found between the glucocorticoid and placebo groups regarding favorable neurological outcomes (RR, 1; 95% CI, 0.93–1.08; P = 0.92). We found that the use of adjuvant glucocorticoids resulted in a significant increase in psychiatric symptoms (RR, 3.22; 95% CI, 1.83–5.64; P < 0.001). No significant differences were found for infection between the 2 groups (RR, 1.86; 95% CI, 0.56–6.14; P = 0.31). Glucocorticoid therapy can effectively reduce the recurrence risk of CSDH after surgery without an increase in the postoperative infection rate. However, significantly increased psychiatric symptoms were reported in the glucocorticoid group. [ABSTRACT FROM AUTHOR]

Background: Aneurysmal subarachnoid hemorrhage is a relatively rare cause of stroke, carrying a bad prognosis of mortality and disability. The current standard procedure, neurosurgical clipping, has failed to achieve satisfactory outcomes. Therefore, endovascular detachable coils have been tested as an alternative. This meta-analysis was aimed to compare the outcomes of surgical clipping and endovascular coiling in aneurysmal subarachnoid hemorrhage. Materials and Methods: Relevant randomized trials up to June 2018 were identified from Medline, Central, and Web of Science. Data for poor outcomes (Modified Rankin Scale [mRS] scores 3 to 6) at 2–3 months, 1 year, and 3–5 years were extracted and analyzed as odds ratios (ORs) with 95% confidence intervals (CIs), using RevMan software. Results: Five studies (2780: 1393 and 1387 patients in the coiling and clipping arms, respectively) were included in the current analysis. The overall effect estimate favored endovascular coiling over surgical clipping in terms of reducing poor outcomes (death or dependency, mRS > 2) at 1 year (OR = 0.67, 95% CI: 0.57–0.79) and 3–5 years (OR = 0.8, 95% CI: 0.67–0.96). Moreover, coiling was associated with a significantly lower rate of cerebral ischemia (OR = 0.37, 95% CI: 0.16–0.86). Postprocedural mortality (OR = 0.79, 95% CI: 0.6–1.05) and rebleeding (OR = 1.15, 95% CI: 0.75–1.78) rates were comparable between the two groups. However, technical failure was significantly more common with coiling interventions than with clipping surgeries (OR = 2.84, 95% CI: 1.86–4.34). Conclusion: Our analysis suggests that coiling can be a better alternative to clipping in terms of surgical outcomes. Further improvements in the coiling technique and training may improve the outcomes of this procedure. [ABSTRACT FROM AUTHOR]

Abstract: The Gaijing Pb–Zn–Mo deposit and Shapinggou Mo deposit in the Yinshan region, Jinzhai, Anhui province, China, are hosted in various granitic intrusions with 40Ar/39Ar ages obtained for biotite and hornblende of 136.8±1.6Ma (medium-grained monzogranite), 130.4±1.2Ma (fine-grained granite), and 125.4±1.0Ma (fine-grained diorite). The modes of occurrence and cross-cutting relationships among the igneous intrusions indicate that alkali quartz-syenite and quartz-syenite porphyry (cryptoexplosive breccia) formed later than the calc-alkali monzogranite, granite, and diorite. Molybdenum mineralization occurs in pipe-like bodies hosted in cryptoexplosive breccia (pipe), quartz-syenite (porphyry), monzogranite, and granite, whereas Pb–Zn mineralization occurs in veins distally from the Mo mineralization. The Re–Os isotopic model ages of molybdenite from the Gaijing Pb–Zn–Mo deposit are 112.6±1.3 and 113.5±1.3Ma, consistent with the ages of other molybdenum deposits throughout the East Qinling–Dabie metallogenic belt. The geological characteristics and isotopic ages of the Gaijing Pb–Zn–Mo and Shapinggou Mo deposits indicate a genetic relationship to the emplacement of the quartz-syenite (porphyry) and to shallow-seated porphyry–cryptoexplosive breccia intrusions. The present results, combined with existing data, suggest that the Pb–Zn–Mo deposits and related igneous rocks were formed in a geodynamic setting of regional lithospheric thinning, delamination, and thermal erosion in East China. The deposits are part of the East Qinling–Dabie molybdenum belt, which in turn is part of a large-scale E–W-trending metallogenic belt in East China. [Copyright &y& Elsevier]

More and more studies had pointed out that the tumor microenvironment characteristics based on colorectal cancer (CRC) pretreatment biopsy specimens could effectively predict the efficacy of neoadjuvant therapy, but under hematoxylin and eosin (HE) staining, whether the tumor microenvironment characteristics observed by pathologists could predict the efficacy of neoadjuvant therapy remains to be discussed. We collected 106 CRC patients who received neoadjuvant treatment and surgical resection from 3 hospitals. The number of mitosis, inflammation degree, desmoplastic reaction (DR), necrosis, tumor-stroma ratio (TSR) and tumor budding (TB) of CRC pretreatment biopsy specimens were observed under HE staining, and the degree of tumor pathological remission of CRC surgical specimens after neoadjuvant treatment was evaluated. According to the tumor regression grade (TRG), patients were divided into good-responders (TRG 0-1) and non-responders (TRG 2-3). All data were analyzed with SPSS software (version 23.0) to evaluate the correlation between the number of mitosis, inflammation degree, DR, necrosis, TSR and TB in pretreatment biopsy samples and the treatment effect. In univariate analysis, mitosis (P = .442), inflammation degree (P = .951), DR (P = .186), necrosis (P = .306), TSR (P = .672), and TB (P = .327) were not associated with the response to neoadjuvant therapy. However, we found that for colon cancer, rectal cancer was more likely to benefit from neoadjuvant therapy (P = .024). In addition, we further analyzed the impact of mitosis, inflammation degree, DR, necrosis, TSR and TB on neoadjuvant therapy in rectal cancer, and found that there was no predictive effect. By analyzing the characteristics of tumor microenvironment of CRC pretreatment biopsy specimens under HE staining, such as mitosis, inflammation degree, DR, necrosis, TSR and TB, it was impossible to effectively predict the efficacy of neoadjuvant therapy for CRC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

IFN regulatory factor 7 (IRF7) exerts anti-infective effects by promoting the production of IFNs in various bacterial and viral infections, but its role in highly morbid and fatal Candida albicans infections is unknown. We unexpectedly found that Irf7 gene expression levels were significantly upregulated in tissues or cells after C. albicans infection in humans and mice and that IRF7 actually exacerbates C. albicans infection in mice independent of its classical function in inducing IFNs production. Compared to controls, Irf7-/- mice showed stronger phagocytosis of fungus, upregulation of C-type lectin receptor CD209 expression, and enhanced P53-AMPK-mTOR-mediated autophagic signaling in macrophages after C. albicans infection. The administration of the CD209-neutralizing Ab significantly hindered the phagocytosis of Irf7-/- mouse macrophages, whereas the inhibition of p53 or autophagy impaired the killing function of these macrophages. Thus, IRF7 exacerbates C. albicans infection by compromising the phagocytosis and killing capacity of macrophages via regulating CD209 expression and p53-AMPK-mTOR-mediated autophagy, respectively. This finding reveals a novel function of IRF7 independent of its canonical IFNs production and its unexpected role in enhancing fungal infections, thus providing more specific and effective targets for antifungal therapy., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Colorectal cancer (CRC) is a prevalent cause of cancer and mortality on a global scale. SNAI1, a member of the zinc finger transcription superfamily, is a significant contributor to embryonic development and carcinogenesis through the process of epithelial-mesenchymal transition (EMT). While prior research utilizing CRC cells and clinical data has demonstrated that SNAI1 facilitates CRC progression through diverse mechanisms, the precise manner in which epithelial SNAI1 regulates CRC development in vivo remains unclear. In this study, colitis and colitis-associated CRC were induced through the use of intestinal epithelium-specific Snai1 knockout (Snai1 cKO) mice. Our findings indicate that Snai1 cKO mice exhibit a reduced susceptibility to acute colitis and colitis-associated CRC compared to control mice. Western-blot analysis of colon tissues revealed that Snai1 cKO mice exhibited a higher overall apoptosis level during tumor formation than control mice. No significant differences were observed in the activation of the classical p53 signaling pathway. However, Snai1 cKO mice exhibited weakened EMT and Wnt/β-catenin pathway activation. In summary, our study has provided evidence in vivo that the intestinal epithelial SNAI1 protein suppresses apoptosis, amplifies the EMT, and activates the Wnt/β-catenin signaling pathways in both early and late phases of CRC formation, thus promoting the development and progression of colitis-associated CRC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Colorectal cancer (CRC) is one of the most common digestive tract malignancies and inflammation and gut microbiota are well-known key factors to influence CRC development. Akkermansia mucinipila is an important gram-negative anaerobic bacterium that can degrade mucin in gut. Previous studies suggested that A. muciniphila may affect inflammation and cell proliferation, but the relationship between A. muciniphila and CRC is not clarified. Here C57BL/6 mice were administrated with A. muciniphila or PBS and then treated with azoxymethane (AOM)/dextran sodium sulphate (DSS) to induce CRC. The mice receiving A. muciniphila administration had more serious weight loss, shorter colon length and more intestinal tumors than those receiving PBS administration after AOM/DSS treatment. More colon damage and less goblet cells were also observed in A. muciniphila treated mice. Furthermore, A. muciniphila administration induced more Ki67 + proliferating cells, higher PCNA expression and elevated gene expression of proliferation-associated molecules including Snrpd1 , Dbf4 or S100A9 . At early stage of CRC development, in comparison with controls, the mice receiving A. muciniphila administration also had more body weight loss and shorter colon length, as well as higher gene expression of inflammatory cytokines. Furthermore, the in vitro experimental results showed that the co-culture of colon epithelial cells with A. muciniphila enhanced the cell proliferation and gene expression of proliferation-associated molecules. Therefore, A. mucinipila may promote the formation of CRC in mice through increasing the early level of inflammation and the proliferation of intestinal epithelial cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)