[Ligusticum cycloprolactam inhibits IL-1ß-induced apoptosis and inflammation of rat chondrocytes via HMGB1/TLR4/NF-κB signaling pathway].

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.

Pressure-relief joints of initial support structural system used in tunnels with high-stress surrounding rock.

To address the problem of large deformations in weak surrounding rock tunnels under high ground stress, which cause damage to initial support structures, this study proposes a novel type of circumferential pressure-relief joint based on the concept of relieving deformation pressure of the surrounding rock. Key parameters of the pressure-relief joint, such as initial bearing capacity peak, constant bearing capacity, and allowable pressure-relief displacement, were obtained through numerical simulations and laboratory experiments. A comparison was made between the mechanical characteristics of rigid joints and the new type of pressure-relief joint. The applicability of the pressure-relief joint was verified through field tests, monitoring the surrounding rock pressure, internal forces in the steel frames, and the convergence displacement of the support structure. The results show that: (1) In the elastic stage, the stiffness of the new pressure-relief joint is similar to that of rigid joints. In the plastic stage, rigid joints fail directly, whereas the pressure-relief joint can control deformation and effectively release the deformation pressure of the surrounding rock while providing a constant bearing capacity. (2) The right arch foot in the experiment had poor rock quality, leading to high stress in the steel frame and significant horizontal displacement. After the deformation of the pressure-relief joint, the stress in the surrounding rock and steel frame significantly reduced, and the rate of horizontal deformation of the support structure slowed down. (3) The vertical and horizontal final displacements of the pressure-relief joint in the experiment were 61mm and 15mm, respectively, which did not exceed the allowable deformation values. The components of the support structure remained intact, ensuring safety. However, this study has limitations: the design of the new pressure-relief joint only allows for a vertical deformation of 150mm and a horizontal deformation of 50mm, limiting the range of pressure-relief deformation.

A novel lysosome-related prognostic signature associated with prognosis and immune infiltration landscape in oral squamous cell carcinoma.

Background: Predicting the outcome of oral squamous cell carcinoma (OSCC) is challenging due to its diverse nature and intricate causes. This research explores how lysosome-associated genes (LRGs) might forecast overall survival (OS) and correlate with immune infiltration in OSCC patients. Methods: We analyzed OSCC patients' LRGs' mRNA expression data and clinical details from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through univariate Cox regression, we pinpointed LRGs with prognostic potential. A signature comprising 12 LRGs linked to prognosis was developed via the Least Absolute Shrinkage and Selection Operator (LASSO) in a training dataset. Patients were classified as higher or lower risk based on their risk scores, and the prognostic independence of the risk score was assessed using multivariate analysis. The model's robustness and precision were confirmed through bioinformatics in the GEO test set. Differential gene expression analysis between risk groups highlighted functional disparities, while various immune evaluation methods elucidated immune differences. Results: The prognostic framework utilized 12 LRGs (SLC46A3, MANBA, NEU1, SDCBP, BRI3, TMEM175, CD164, GPC1, SFTPB, TPP1, Biglycan (BGN) and TMEM192), showing that higher risk was associated with poorer OS. This set of genes independently predicted OS in OSCC, linking LRGs to cellular adhesion and extracellular matrix involvement. Initial assessments using ssGSEA and CIBERSORT suggested that the adverse outcomes in the higher-risk cohort may be tied to immune system deregulation. Conclusion: Twelve-LRGs signature has been identified for OSCC prognosis prediction, offering novel directions for lysosome-targeted therapies against OSCC.

Preparation of Mesophase Pitch through Supercritical Fluid Extraction of Coal Tar Pitch.

This paper explores the preparation of mesophase pitch by employing supercritical fluid extraction on coal tar pitch sourced from a coal chemical company. The raw material undergoes pretreatment using various extraction solvents, and the resulting refined components are thermally polycondensed in a laboratory microreactor to create mesophase pitch. Qualitative and quantitative analyses of the mesophase pitch's structure are conducted through polarized light microscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, and other analytical methods to identify an optimal supercritical fluid extraction pretreatment solvent for coal tar pitch. The results reveal that using n-hexane solvent in the supercritical fluid extraction process yields a mesophase pitch with a remarkable mesophase content of 90.07%, displaying excellent optical texture distribution, superior directional arrangement and order, the closest lamellar accumulation, and the highest degree of anisotropy and graphitization.

Prediction Model for Unfavorable Outcome in Spontaneous Intracerebral Hemorrhage Based on Machine Learning.

OBJECTIVE: The spontaneous intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. The purpose of this retrospective study is to develop multiple models for predicting ICH outcomes using machine learning (ML). METHODS: Between January 2014 and October 2021, we included ICH patients identified by computed tomography or magnetic resonance imaging and treated with surgery. At the 6-month check-up, outcomes were assessed using the modified Rankin Scale. In this study, four ML models, including Support Vector Machine (SVM), Decision Tree C5.0, Artificial Neural Network, Logistic Regression were used to build ICH prediction models. In order to evaluate the reliability and the ML models, we calculated the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR). RESULTS: We identified 71 patients who had favorable outcomes and 156 who had unfavorable outcomes. The results showed that the SVM model achieved the best comprehensive prediction efficiency. For the SVM model, the AUC, accuracy, specificity, sensitivity, PLR, NLR, and DOR were 0.91, 0.92, 0.92, 0.93, 11.63, 0.076, and 153.03, respectively. For the SVM model, we found the importance value of time to operating room (TOR) was higher significantly than other variables. CONCLUSION: The analysis of clinical reliability showed that the SVM model achieved the best comprehensive prediction efficiency and the importance value of TOR was higher significantly than other variables.

Endorepellin downregulation promotes angiogenesis after experimental traumatic brain injury.

Endorepellin plays a key role in the regulation of angiogenesis, but its effects on angiogenesis after traumatic brain injury are unclear. This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice. Mice were randomly divided into four groups: sham, controlled cortical impact only, adeno-associated virus (AAV)-green fluorescent protein, and AAV-shEndorepellin-green fluorescent protein groups. In the controlled cortical impact model, the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+ proliferating endothelial cells and the functional microvessel density in mouse brain. These changes resulted in improved neurological function compared with controlled cortical impact mice. Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein. Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization, which may further improve neurobehavioral outcomes. Furthermore, an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control. Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor- and angiopoietin-1-related signaling pathways.

Catalpol ameliorates LPS-induced inflammatory response by activating AMPK/mTOR signaling pathway in rat intestinal epithelial cells.

Intestinal inflammation is a common clinical intestinal disease. Catalpol, a natural iridoid compound, has been shown to have anti-inflammatory, anti-oxidant and anti-apoptotic functions, but the mechanism of its protection against intestinal inflammation is still unclear. This study investigated the protective effect and potential mechanism of catalpol on the lipopolysaccharide (LPS)-induced inflammatory response of intestinal epithelial cell-6 (IEC-6). The results showed that catalpol could inhibit LPS-induced inflammatory response by dose-dependently reducing the release of inflammatory factors, such as tumor necrosis (TNF)-α, interleukin (IL)-1ß and IL-6, and inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. Catalpol ameliorated cellular oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) expression. Meanwhile, catalpol also inhibited cell apoptosis, decreased the expression of B-cell lymphoma 2 (Bcl-2) - associated X (Bax), caspase 3 and caspase 9, and increased the expression of Bcl-2. This study found that catalpol activates AMP-activated protein kinase (AMPK) signaling pathway and inhibit mammalian target of rapamycin (mTOR) phosphorylationthe. In a further study, after inhibiting AMPK with dorsomorphin, the anti-inflammatory effects of catalpol were significantly reduced. Therefore, catalpol ameliorates LPS-induced inflammatory response by activating AMPK/mTOR signaling pathway in IEC-6 cells.

Preparation and Hydration Properties of Steel Slag-Based Composite Cementitious Materials with High Strength.

Steel slag (SS) has been largely discharged but little utilized, causing an environmental problem in China. In this paper, SS-based composite cementitious materials with high strength were prepared by the high volume of SS (≥40%), granulated blast-furnace slag (GBFS), fly ash (FA), flue gas desulfurization gypsum (FGDG) and cement to promote the effective utilization of SS. The hydration and hardening properties were studied through setting time, compressive strength, length change, isothermal calorimetry (IC), X-ray diffraction (XRD), mercury intrusion porosimetry (MIP), and scanning electron microscopy equipped with energy dispersive spectroscopy (SEM-EDS) tests. The results show that SS-based composite cementitious material exhibited a lower hydration heat release, an appropriate setting time, and volume stability. The SS cementitious material with 40% SS could obtain high strength of over 65 MPa at 28 days and 80 MPa at 90 days. The strength value of > 60 MPa is present in the binder, with 50% SS at 56 days. GBFS promotes hydration reactions and the formation of AFt and C-(A)-S-H gel, thus enhancing compressive strength. FA has a beneficial effect on later strength. The small and fine pore structures contribute to the development of strength. The main hydration products of SS composite cementitious materials are C-(A)-S-H gel, and ettringite (AFt), with less Ca(OH)2. The C-(A)-S-H gel with a lower Ca/Si ratio and a higher Al/Ca ratio in cementitious material, promotes mechanical properties.

Adipose mesenchymal stem cells-derived exosomes alleviate osteoarthritis by transporting microRNA -376c-3p and targeting the WNT-beta-catenin signaling axis.

Osteoarthritis (OA), one of the major diseases afflicting the elderly, is a type of degenerative joint disease related to cartilage and synovium. This study aimed to clarify the role and mechanism of adipose mesenchymal stem cell (ADSC)-derived exosomes (Exos) in OA-induced chondrocyte degradation and synovial hyperplasia, thus improving the quality of life of patients. The rat OA model, chondrocytes, synovial fibroblast models and immunofluorescence were applied to observe the in vivo and in vitro functions of human ADSC (hADSC)-derived Exos in OA and its possible regulatory signaling pathways. Bioinformatics software and luciferase reporter assay were carried out to verify the mechanism of microRNA-376c-3p (miR-376c-3p) in hADSC-derived Exos in OA in vitro. Moreover, Safranine O-Fast Green Cartilage staining, Masson staining, immunohistochemistry and immunofluorescence were conducted to verify the role of miR-376c-3p in hADSC-derived Exos in OA in vivo. hADSC-derived Exos mitigated OA-induced chondrocyte degradation and synovial fibrosis both in vivo and in vitro models by repressing the WNT-beta-catenin signaling pathway. For the mechanism exploration in vitro, miR-376c-3p was raised in hADSC-derived Exos and mediated the fibrosis of synovial fibroblasts in OA, and miR-376c-3p targeted the 3'-untranslated region of WNT3 or WNT9a. Meanwhile, the in vivo experiments also corroborated that the miR-376c-3p in hADSC-derived Exos mitigated OA-induced chondrocyte degradation and synovial fibrosis. MiR-376c-3p in hADSC-derived Exos repressed the WNT-beta-catenin pathway by targeting WNT3 or WNT9a, and then mitigating OA-induced chondrocyte degradation and synovial fibrosis, thereby providing theoretical basis for clinical implementation of treatment.

Inhibiting phosphatase and actin regulator 1 expression is neuroprotective in the context of traumatic brain injury.

Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke, but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury. In this study we found that, in a mouse model of traumatic brain injury induced by controlled cortical impact, phosphatase actin regulatory factor 1 expression is increased in endothelial cells, neurons, astrocytes, and microglia. When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice, the water content of the brain tissue increased. However, when phosphatase actin regulatory factor 1 was knocked down, the water content decreased. We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway, decreased blood-brain barrier permeability, reduced aquaporin 4 and intercellular adhesion molecule 1 expression, inhibited neuroinflammation, and neuronal apoptosis, thereby improving neurological function. The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury.

Predictive nomogram for deep brain stimulation-related infections.

OBJECTIVE: Infection is one of the important and frequent complications following implantable pulse generator and deep brain stimulation (DBS) electrode insertion. The goal of this study was to retrospectively evaluate and identify potential risk factors for DBS infections. METHODS: From January 2015 to January 2021 in Qingdao municipal hospital (training cohort) and The First Affiliated Hospital of the University of Science and Technology of China (validation cohort), the authors enrolled patients with Parkinson disease who had undergone primary DBS placement or implantable pulse generator replacement. The cases were divided into infection or no-infection groups according to the 6-month follow-up. The authors used the logistic regression models to determine the association between the variables and DBS infection. Depending on the results of logistic regression, the authors established a nomogram. The calibration curves, receiver operating characteristic curve analysis, and decision curves were used to evaluate the reliability of the nomogram. RESULTS: There were 191 cases enrolled in the no-infection group and 20 cases in the infection group in the training cohort. The univariate logistic regression showed that BMI, blood glucose, and albumin were all significant predictors of infection after DBS surgery (OR 0.832 [p = 0.009], OR 1.735 [p < 0.001], and OR 0.823 [p = 0.001], respectively). In the crude, adjust I, and adjust II models, the three variables stated above were all considered to be significant predictors of infection after DBS surgery. The calibration curves in both training and validation cohorts showed that the predicted outcome fitted well to the observed outcome (p > 0.05). The decision curves showed that the nomogram had more benefits than the "All or None" scheme. The areas under the curve were 0.93 and 0.83 in the training and validation cohorts, respectively. CONCLUSIONS: The nomogram included BMI, blood glucose, and albumin, which were significant predictors of infection in patients with DBS surgery. The nomogram was reliable for clinical application.

MicroRNA-223 Attenuates Stretch-Injury-Induced Apoptosis in Brain Microvascular Endothelial Cells by Regulating RhoB Expression.

MiR-223 is a miRNA with important functions in apoptosis, carcinogenesis, and inflammation, and it was demonstrated to be over-expressed in brain tissue after traumatic brain injury (TBI). However, few studies have focused on its role in protecting brain microvascular endothelial cells (BMECs). This study evaluated the protective effect of miR-223 on BMECs after stretch injury (SI). bEnd.3 cells (BMECs of mouse) were transfected with overexpressing and blocking lentivirus of miR-223, then were subjected to SI. After immunofluorescence assay, it was demonstrated that miR-223 overexpression significantly rescued the SI-induced loss of ZO-1 (Zonula Occludens 1, tight junction protein) (p < 0.01), while miR-223 blocking exacerbated the loss of ZO-1 (p < 0.05). Flow cytometry confirmed a significant increase in the proportion of apoptotic bEnd.3 cells after SI, and miR-223 overexpression reduced this proportion (p < 0.001). The result of Western blot revealed that miR-223 overexpression significantly reduced the expression of cleaved caspase-3 (cl-caspase 3) (p < 0.05) and RhoB (p < 0.01), while miR-223 blocking increased the expression of these proteins (p < 0.05, p < 0.001). Additionally, knockdown of RhoB significantly reduced the expression of cl-caspase 3 (p < 0.001). These findings suggested that miR-223 can alleviate SI-induced apoptosis of BMECs, and this anti-apoptotic effect is at least partially achieved by inhibiting the expression of RhoB. Moreover, miR-223 may play a role in maintaining the integrity of BBB during TBI.

Expression and Clinical Significance of Serum Krüppel-Like Factor 7 (KLF7) in NSCLC Patients.

Nonsmall cell lung cancer (NSCLC) is a serious threat to the life and health of patients with high incidence rate and mortality. The present research was to assess the relationship between the serum Krüppel-like factor 7 (KLF7) level and the recurrence and metastasis of NSCLC patients. 150 patients with NSCLC treated by thoracoscopic radical resection of lung cancer in our hospital from January 2016 to February 2017 were selected. As the control group, 148 healthy people who went to the hospital for physical examination in the same period were screened. The expression levels of serum KLF7 in the observation group and the control group were compared and analyzed. According to the level of KLF7 expression, the patients in the observation group were divided into KLF7 high expression group (≥258.6 ng/L, n =75) and KLF7 low expression group (<258.6 ng/L, n =75). The 3-year recurrence and metastasis rate of patients in each group was compared and analyzed. It was found the concentration of serum KLF7 in peripheral blood of NSCLC (2.25 ± 0.65) ng/ml was significantly higher than that in healthy population (1.42 ± 0.38) ng/ml (P < 0.05). The expression level of serum KLF7 was not related to gender, age, smoking history, and tumor diameter of NSCLC patients (P > 0.05), but related to the degree of differentiation and TNM stage of NSCLC patients (P < 0.05). Univariate analysis showed that the degree of differentiation, TNM stage, and KLF7 were significantly correlated with 3-year recurrence and metastasis of NSCLC patients (P < 0.05). Cox regression analysis showed that low degree of differentiation, TNM stage IIIa, and KLF7 were independent risk factors for recurrence and metastasis in NSCLC patients in 3 years (P < 0.05). Taken together, the expression level of serum KLF7 in patients with NSCLC is significantly increased, which is an independent risk factor for recurrence and metastasis in 3 years, and is worthy of clinical application.

Effects of MICU1-Mediated Mitochondrial Calcium Uptake on Energy Metabolism and Quality of Vitrified-Thawed Mouse Metaphase II Oocytes.

BACKGROUND: Oocyte vitrification has been widely used in the treatment of infertility and fertility preservation. However, vitrification-induced mitochondrial damage adversely affects oocyte development. Several studies have reported that mitochondrial calcium uptake protein 1 (MICU1) regulates the uptake of mitochondrial calcium by the mitochondrial calcium uniporter (MCU) and subsequently controls aerobic metabolism and oxidative stress in mitochondria, but research considering oocytes remains unreported. We evaluated whether the addition of MICU1 modulators enhances mitochondrial activity, pyruvate metabolism, and developmental competence after warming of MII oocytes. METHODS: Retrieved MII oocytes of mice were classified as vitrified or control groups. After thawing, oocytes of vitrified group were cultured with or without DS16570511 (MICU1 inhibitor) and MCU-i4 (MICU1 activator) for 2 h. RESULTS: Mitochondrial Ca2+ concentration, pyruvate dephosphorylation level, and MICU1 expression of MII oocytes were significantly increased after vitrification. These phenomena were further exacerbated by the addition of MCU-i4 and reversed by the addition of DS16570511 after warming. However, the mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) in vitrified-warmed MII oocytes drop significantly after vitrification, which was improved after MCU-i4 treatment and decreased significantly after DS16570511 treatment. The vitrification process was able to elicit a development competence reduction. After parthenogenetic activation, incubation of the thawed oocytes with MCU-i4 did not alter the cleavage and blastocyst rates. Moreover, incubation of the thawed oocytes with DS16570511 reduced the cleavage and blastocyst rates. CONCLUSIONS: MICU1-mediated increasing mitochondrial calcium uptake after vitrification of the MII oocytes promoted the pyruvate oxidation, and this process may maintain oocyte development competence by compensating for the consumption of ATP under stress state.

Predictive Nomogram for Unfavorable Outcome of Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The goal of this retrospective study was to evaluate the effect of surgical timing on patient outcomes after spontaneous intracerebral hemorrhage (ICH). We also identified risk factors associated with poor prognosis. METHODS: We reviewed all patients who underwent surgery for ICH between January 2014 and January 2021. The outcome was measured using the modified Rankin Scale (mRS) score at 6 months after the surgery. Patients with mRS 0-2 were considered having favorable outcomes, and those with mRS 3-5 were considered having unfavorable outcomes. The relationships of surgical timing with the risk of unfavorable outcomes were identified using the interaction and stratified analyses, and generalized additive and logistic regression models. A nomogram was established and evaluated using a receiver operating characteristic curve analysis, plotted decision curve, and calibration curve. RESULTS: We identified 53 patients with favorable outcomes and 144 with unfavorable outcomes. The number of cases who underwent surgery at >12 hours and <36 hours in the favorable outcome group was more than that in the unfavorable outcome group (P < 0.001). When the time to operating room (TOR) was less than 21 hours, a shorter TOR was associated with unfavorable outcomes, using the smoothing spline analysis (odds ratio = 0.8, P < 0.001). Finally, we developed a nomogram using systolic blood pressure, Glasgow Coma Scale, midline shift, hematoma volume, and TOR for predicting the unfavorable outcome. The area under the curve, accuracy, specificity, and sensitivity of nomogram were 0.90, 0.87, 0.72, and 0.93, respectively. CONCLUSION: Surgical timing between 12 and 26 hours after ICH was associated with favorable outcomes. The nomogram including systolic blood pressure, Glasgow Coma Scale, midline shift, hematoma volume, and TOR was reliable for predicting the ICH outcome.

The minor allele of rs17427875 in long non-coding RNA-HOXA11-AS influences the prognosis of subarachnoid hemorrhage (SAH) via modulating miR-15a and STAT3 expression.

BACKGROUND: HOAX11-AS was reported to promote the progression of liver cancer via the signaling pathway of miR-15a-3p/STAT3. In this study, we investigated the effect of rs17427875 on the prognosis of subarachnoid hemorrhage (SAH) and its underlying molecular mechanisms. METHODS: 158 SAH patients were recruited and grouped according to their genotypes rs17427875. Peripheral blood and cerebrospinal fluid (CSF) samples were collected for subsequent analysis. Quantitative real-time PCR, luciferase assays, Western blot and ELISA were performed to analyze the correlations between the expression of lncRNA-HOXA11-AS, miR-15a, TNF-α and NF-κB. RESULTS: The survival rate was remarkably higher in SAH patients carrying the AA genotype of rs17427875 when compared with those carrying the AT genotype. The expression of miR-15a was significantly repressed in the peripheral blood and CSF of SAH patients carrying the AT allele when compared with that in patients carrying the AA allele. MiR-15a showed a remarkable efficacy in inhibiting the luciferase activity of wild type lncRNA-HOXA11-AS and STAT3 in THP-1 cells. P-HOXA11-AS-T showed a stronger ability to suppress the expression of miR-15a and activate the expression of STAT3, TNF-α and NF-κB in THP-1 cells when compared with P-HOXA11-AS-A. CONCLUSIONS: The findings demonstrated that the presence of the minor allele of rs17427875 in lncRNA-HOXA11-AS could increase the expression level of lncRNA-HOXA11-AS, thus elevating the expression level of STAT3 via down-regulating miR-15a, and increased STAT3 expression could aggravate inflammation to cause poor prognosis of SAH. Therefore, the rs17427875 polymorphism can be used as a potential biomarker for the prognosis of SAH.

ACT001 attenuates microglia-mediated neuroinflammation after traumatic brain injury via inhibiting AKT/NFκB/NLRP3 pathway.

BACKGROUND: Microglia-mediated neuroinflammatory response following traumatic brain injury (TBI) is considered as a vital secondary injury factor, which drives trauma-induced neurodegeneration and is lack of efficient treatment. ACT001, a sesquiterpene lactone derivative, is reportedly involved in alleviation of inflammatory response. However, little is known regarding its function in regulating innate immune response of central nervous system (CNS) after TBI. This study aimed to investigate the role and underlying mechanism of ACT001 in TBI. METHODS: Controlled cortical impact (CCI) models were used to establish model of TBI. Cresyl violet staining, evans blue extravasation, neurobehavioral function assessments, immunofluorescence and transmission electron microscopy were used to evaluate therapeutic effects of ACT001 in vivo. Microglial depletion was induced by administering mice with colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. Cell-cell interaction models were established as co-culture system to simulate TBI conditions in vitro. Cytotoxic effect of ACT001 on cell viability was assessed by cell counting kit-8 and activation of microglia cells were induced by Lipopolysaccharides (LPS). Pro-inflammatory cytokines expression was determined by Real-time PCR and nitric oxide production. Apoptotic cells were detected by TUNEL and flow cytometry assays. Tube formation was performed to evaluate cellular angiogenic ability. ELISA and western blot experiments were used to determine proteins expression. Pull-down assay was used to analyze proteins that bound ACT001. RESULTS: ACT001 relieved the extent of blood-brain barrier integrity damage and alleviated motor function deficits after TBI via reducing trauma-induced activation of microglia cells. Delayed depletion of microglia with PLX5622 hindered therapeutic effect of ACT001. Furthermore, ACT001 alleviated LPS-induced activation in mouse and rat primary microglia cells. Besides, ACT001 was effective in suppressing LPS-induced pro-inflammatory cytokines production in BV2 cells, resulting in reduction of neuronal apoptosis in HT22 cells and improvement of tube formation in bEnd.3 cells. Mechanism by which ACT001 functioned was related to AKT/NFκB/NLRP3 pathway. ACT001 restrained NFκB nuclear translocation in microglia cells through inhibiting AKT phosphorylation, resulting in decrease of NLRP3 inflammasome activation, and finally down-regulated microglial neuroinflammatory response. CONCLUSIONS: Our study indicated that ACT001 played critical role in microglia-mediated neuroinflammatory response and might be a novel potential chemotherapeutic drug for TBI. Video Abstract.

Chordoid Glioma: A Neoplasm Found in the Anterior Part of the Third Ventricle.

ABSTRACT: Chordoid glioma is a rare low-grade tumor that originates almost exclusively in the anterior part of the third ventricle. The diagnosis and treatment of the tumor remain controversial. In this article, the authors present a novel case of chordoid glioma of the third ventricle. The patient was treated with less invasive microsurgery followed by low-dose gamma knife radiosurgery. Magnetic resonance imaging revealed a decrease in tumor size and necrosis in the central region of the tumor, without significant complications at follow-up 14 months later. Based on these findings, the authors suggest that less invasive microsurgical resection followed by low-dose gamma knife radiosurgery is safe and effective for the treatment of chordoid glioma of the third ventricle.

Properties of Iron Bacteria Biofouling on Ni-P-rGO Coating under Flowing Conditions.

Biofouling on heat exchange devices can decrease heat transfer efficiency, corrode materials, and even lead safety accidents. Most heat exchange devices are made of carbon steel, which produces biofouling easily. In this paper, nickel-phosphorus-reduced graphene oxide (Ni-P-rGO) coating was prepared on carbon steel by electroless plating as a kind of advanced material to study the properties of iron bacteria biofouling under flowing conditions. The coating was analyzed via scanning electron microscopy and Raman spectroscopy. The properties of iron bacteria biofouling on carbon steel and Ni-P-rGO coating were then compared under flowing conditions. Compared with carbon steel, the asymptotic value of fouling resistance on the Ni-P-rGO coating significantly decreased. Additionally, the induction period and the time of reaching the asymptotic value greatly increased. The inhibition properties of biofouling of advanced materials Ni-P-rGO coating under different temperatures, flow velocities, and initial concentrations was also studied.

A cancer-specific activatable theranostic nanodrug for enhanced therapeutic efficacy via amplification of oxidative stress.

Rationale: Despite considerable advances, the reactive oxygen species (ROS)-mediated cancer treatment suffers from the problems of up-regulation of adaptive antioxidants in cancer cells as well as side effects to normal cells. Therefore, development of a new generation of cancer-specific nanomedicine capable of amplifying oxidative stress would be of great interest for accurate and effective cancer treatment. Methods: Herein, transferrin (Tf)-decorated, dihydroartemisinin (DHA), L-buthionine-sulfoximine (BSO), and CellROX-loaded liposomal nanoparticles (Tf-DBC NPs) were developed for precise cancer theranositcs. Tf-DBC NPs could specifically recognize cancer cells via Tf-Tf receptor binding and be uptaken into the lysosomes of cancer cells, where Tf-DBC NPs were activated to release Fe(II), DHA, and BSO. ROS was generated by DHA in the presence of Fe(II), and GSH was depleted by BSO to disrupt the redox balance in cancer cells. Furthermore, CellROX, as a fluorescent probe for imaging of intracellular oxidative stress, was used to monitor the therapeutic efficacy. Results: The integration of Tf, DHA, and BSO into the acidic pH-responsive liposomes selectively and effectively killed cancer cells and prevented the oxidative injury to normal cells. The high oxidative state was visualized at the tumor site and the amplification of oxidative stress enabled tumor eradication by Tf-DBC NPs, demonstrating the successful implementation of this novel strategy in vivo. Conclusion: Our study provides a new paradigm for the design of ROS-mediated therapeutics and offers a promising perspective for precise cancer treatment.