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Sonic hedgehog subtype medulloblastoma is featured with overactivation of hedgehog pathway and can be targeted by SMO-specific inhibitors. However, the resistance is frequently developed leading to treatment failure of SMO inhibitors. W535L mutation of SMO (SMOIn this study, we profiled transcriptomes, methylomes, and interactomes of MB cells expression SMOWT or SMOW535L in the treatment of DMSO or SMO inhibitor, respectively.Analysis of transcriptomic data indicated that SMO inhibitor disrupted processes of endocytosis and cilium organization in MB cells with SMOTaken together, our work described SMO-related transcriptomes, metabolomes, and interactomes under different SMO status and treatment conditions, identifying CK2 and AKT as therapeutic targets for SHH-subtype MB cells with SMO inhibitor resistance.

With uncontrolled inflammatory progression, acute pancreatitis (AP) can progress to severe acute pancreatitis (SAP). Inflammation and parenchymal cell death are key pathologic responses of AP. Toll-like receptor 4 (TLR4) plays a pro-inflammatory role in AP. Myeloid differentiation primary response protein 88 (MyD88) is the most essential utilized adaptor of TLR4, but its role in AP remains unclear. We investigated the potential role of MyD88 in the pathogenesis of AP.An AP model was induced by administering either cerulein or L-arginine to wild-type or MyD88-deficient mice. Additionally, receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 (Nec-1) was administered to the MyD88The deletion of MyD88 resulted in more severe acute experimental pancreatitis as assessed by increased amylase and lipase activities, increased pancreatic MPO activity, a reduced anti-inflammatory response, reduced apoptosis, and increased necrosis. Additionally, Nec-1 treatment significantly reduced necrosis in the MyD88The deletion of MyD88 inhibited the TLR4/MyD88-dependent pathway mediated protective immune defense response and enhanced TLR4/MyD88-independent TRIF pathway-mediated pancreatic necrosis, which in turn aggravated the severity of AP. The critical role of MyD88 in immune defense response and cell death indicates that MyD88 represents a potential therapeutic target in the management of AP.

Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.

Invasive growth of glioblastoma makes residual tumor unremovable by surgery and leads to disease relapse. Temozolomide is widely used first-line chemotherapy drug to treat glioma patients, but development of temozolomide resistance is almost inevitable. Ferroptosis, an iron-dependent form of non-apoptotic cell death, is found to be related to temozolomide response of gliomas. However, whether inducing ferroptosis could affect invasive growth of glioblastoma cells and which ferroptosis-related regulators were involved in temozolomide resistance are still unclear. In this study, we treated glioblastoma cells with RSL3, a ferroptosis inducer, in vitro (cell lines) and in vivo (subcutaneous and orthotopic animal models). The treated glioblastoma cells with wild-type or mutant IDH1 were subjected to RNA sequencing for transcriptomic profiling. We then analyze data from our RNA sequencing and public TCGA glioma database to identify ferroptosis-related biomarkers for prediction of prognosis and temozolomide resistance in gliomas. Analysis of transcriptome data from RSL3-treated glioblastoma cells suggested that RSL3 could inhibit glioblastoma cell growth and suppress expression of genes involved in cell cycle. RSL3 effectively reduced mobility of glioblastoma cells through downregulation of critical genes involved in epithelial-mesenchymal transition. Moreover, RSL3 in combination with temozolomide showed suppressive efficacy on glioblastoma cell growth, providing a promising therapeutic strategy for glioblastoma treatment. Although temozolomide attenuated invasion of glioblastoma cells with mutant IDH1 more than those with wild-type IDH1, the combination of RSL3 and temozolomide similarly impaired invasive ability of glioblastoma cells in spite of IDH1 status. Finally, we noticed that both ferritin heavy chain 1 and ferritin light chain predicted unfavorable prognosis of glioma patients and were significantly correlated with mRNA levels of methylguanine methyltransferase as well as temozolomide resistance. Altogether, our study provided rationale for combination of RSL3 with temozolomide to suppress glioblastoma cells and revealed ferritin heavy chain 1 and ferritin light chain as biomarkers to predict prognosis and temozolomide resistance of glioma patients.

The severity of acute pancreatitis in pregnancy (APIP) is correlated with higher risks of maternal and fetal death.To develop a nomogram that could predict moderately severe and severe acute pancreatitis in pregnancy (MSIP).Patients with APIP admitted to West China Hospital between January 2012 and December 2018 were included in this study. They were divided into mild acute pancreatitis in pregnancy (MAIP) and MSIP. Characteristic parameters and laboratory results were collected. The training set and test set were randomly divided at a ratio of 7:3. Least absolute shrinkage and selection operator regression was used to select potential prognostic factors. A nomogram was developed by logistic regression. A random forest model was used to validate the stability of the prediction factors. Receiver operating characteristic curves and calibration curves were used to evaluate the model's predictive performance.A total of 190 patients were included in this study. A total of 134 patients (70.5%) and 56 patients (29.5%) were classified as having MAIP and MSIP, respectively. Four independent predictors (lactate dehydrogenase, triglyceride, cholesterol, and albumin levels) were identified for MSIP. A nomogram prediction model based on these factors was established. The model had areas under the curve of 0.865 and 0.853 in the training and validation sets, respectively. The calibration curves showed that the nomogram has a good consistency.A nomogram including lactate dehydrogenase, triglyceride, cholesterol, and albumin levels as independent predictors was built with good performance for MSIP prediction.

Circular RNAs (circRNAs) have been increasingly linked to cancer progression. However, the detailed biological functions of circRNAs in prostate cancer (PCa) remain unclear. Using high-throughput circRNA sequencing, we previously identified 18 urine extracellular vesicle circRNAs that were increased in patients with PCa compared with those with benign prostatic hyperplasia. Spearman correlation analysis of the expression levels of the 18 circRNAs between the tumor tissue and matched urine extracellular vesicles in 30 PCa patients showed that circSCAF8 had the highest R2 (R2 = 0.635, P P = 0.022). Mechanistically, circSCAF8 can function by binding to both miR-140-3p and miR-335 to regulate LIF expression and activate the LIF-STAT3 pathway that leads to the growth and metastasis of PCa. Collectively, our findings demonstrate that circSCAF8 contributes to PCa progression through the circSCAF8-miR-140-3p/miR-335-LIF pathway.

Acute lung injury (ALI) is a common and devastating clinical disorder featured by excessive inflammatory responses. Stimulator of interferon genes (STING) is an indispensable molecule for regulating inflammation and immune response in multiple diseases, but the role of STING in the ALI pathogenesis is not well elucidated. In this study, we explored the molecular mechanisms of STING in regulating lipopolysaccharide (LPS)-induced lung injury. Mice were pretreated with a STING inhibitor C-176 (15, 30 mg/kg, i.p.) before LPS inhalation to induce ALI. We showed that LPS inhalation significantly increased STING expression in the lung tissues, whereas C-176 pretreatment dose-dependently suppressed the expression of STING, decreased the production of inflammatory cytokines including TNF-α, IL-6, IL-12, and IL-1β, and restrained the expression of chemokines and adhesion molecule vascular cell adhesion protein-1 (VCAM-1) in the lung tissues. Consistently, in vitro experiments conducted in TNF-α-stimulated HMEC-1cells (common and classic vascular endothelial cells) revealed that human STING inhibitor H-151 or STING siRNA downregulated the expression levels of adhesion molecule and chemokines in HMEC-1cells, accompanied by decreased adhesive ability and chemotaxis of immunocytes upon TNF-α stimulation. We further revealed that STING inhibitor H-151 or STING knockdown significantly decreased the phosphorylation of transcription factor STAT1, which subsequently influenced its binding to chemokine CCL2 and adhesive molecule VCAM-1 gene promoter. Collectively, STING inhibitor can alleviate LPS-induced ALI in mice by preventing vascular endothelial cells-mediated immune cell chemotaxis and adhesion, suggesting that STING may be a promising therapeutic target for the treatment of ALI.

The exploitation of new photocatalysts based p-n heterojunction is attracting the attention of the researchers due to its high photocatalytic performance. In this study, ZnWO4/BiOBr heterojunction were successfully prepared via a hydrothermal and a simple deposition method. The obtained ZnWO4/BiOBr composite exhibited superior photocatalytic activity towards refractory pollutants tetracycline (TC) degradation. Among, the samples of ZB-2 (Zn/Bi molar ratios is 0.2) exhibited the best photocatalytic performance. Based on the LC–MS analysis, a possible degradation pathway of TC is also suggested. The optical and electrical properties of the obtained materials demonstrated that the fast transfer of electron-hole pairs was achieved in ZnWO4/BiOBr hybrid though constructing a p-n junction. Furthermore, the activity of the catalyst is still high level without significant loss up to four successive cycles. This work provided a new thought for enhanced visible light photocatalytic performance of zinc tungstate.

Rationale: Around 10%-20% patients with glioblastoma (GBM) are diagnosed with more than one tumor lesions or multifocal GBM (mGBM). However, the understanding on genetic, DNA methylomic, and transcriptomic characteristics of mGBM is still limited. Methods: In this study, we collected nine tumor foci from three mGBM patients followed by whole genome sequencing, whole genome bisulfite sequencing, RNA sequencing, and immunohistochemistry. The data were further examined using public GBM databases and GBM cell line. Results: Analysis on genetic data confirmed common features of GBM, including gain of chr.7 and loss of chr.10, loss of critical tumor suppressors, high frequency of PDGFA and EGFR amplification. Through profiling DNA methylome of individual tumor foci, we found that promoter methylation status of genes involved in detection of chemical stimulus, immune response, and Hippo/YAP1 pathway was significantly changed in mGBM. Although both CNV and promoter methylation alteration were involved in heterogeneity of different tumor foci from same patients, more CNV events than promoter hypomethylation events were shared by different tumor foci, implying CNV were relatively earlier than promoter methylation alteration during evolution of different tumor foci from same mGBM. Moreover, different tumor foci from same mGBM assumed different molecular subtypes and mesenchymal subtype was prevalent in mGBM, which might explain the worse prognosis of mGBM than single GBM. Interestingly, we noticed that LIF and CCL2 was tightly correlated with mesenchymal subtype tumor focus in mGBM and predicted poor survival of GBM patients. Treatment with LIF and CCL2 produced mesenchymal-like transcriptome in GBM cells. Conclusions: Together, our work herein comprehensively profiled multi-omics features of mGBM and emphasized that components of extracellular microenvironment, such as LIF and CCL2, contributed to the evolution and prognosis of tumor foci in mGBM patients.

The effect of different types of polymers, partly hydrolyzed polyacrylamide (HPAM), hydrophobically modified polyacrylamide (HMPAM) and co-polymer, on the dynamic interfacial tensions (IFTs) of benzyl substituted alkyl sulfobetaine (BSB) against n-alkanes, kerosene and crude oil have been investigated by a spinning drop interfacial tensiometer. The influence of polymer concentration on IFTs was expounded. The experimental results show that betaine has high interfacial activity and the addition of polymer has great influence on both dynamic IFT behaviors and equilibrium values between surfactant solution and n-alkanes mainly by modifying the interfacial molecular arrangement on the interface. However, the addition of polymer affects the dynamic IFTs of surfactant solution against kerosene and crude oil, but has little effect on the equilibrium IFT values. Active substances existing in kerosene and the in situ produced petroleum acidic soaps play a synergistic effect with betaine to reduce the IFTs. The increase of viscosity of aqueous phase caused by polymer influence the adsorption of the surfactant at the interface, slowing down the decrease of IFTs and changing the minimum transient IFT values.

Let(X, T) be topological space. A vietoris-type topology, called the locally finite topology, is defined on the hyperspace 2X of all closed, nonempty subsets of X . In this paper, we discuss m-compactness of the locally finite topology on hyperspace. And give the important conclusion, therefore this develops E. Micheal, J. Keesling some results.

The purpose of this analysis was to evaluate the technological viability, basic safety and consequence of central pancreatectomy (CP) with pancreaticogastrostomy in properly chosen sufferers with noncancerous central pancreatic pathology. This research is centered on the infirmary charts of West China hospital. We recruited 20 individuals from 2007 to 2009 diagnosed with benign cancerous growth of pancreatic body and neck. They underwent pancreatic body and neck resection adhering to pancreaticogastrostomy. We carried out central pancreatectomy following pancreaticogastrostomy in 20 patients: 8 with serous cyst adenomas, 11 with mucinous cystadenomas, and 1 with neuroendocrine tumor. The position of all tumors was restricted to body and neck of the pancreas, measuring a mean ± standard deviation of 2.6±1.3cm. The mean post-operative hospital stay was 7 days (ranging from 6 to 16 days).There was no intraoperative additional complications. From a technical perspective, CP is a safe and sound, pancreas-preserving pancreatectomy for non-enucleable non-cancerous pancreatic pathology restricted to the pancreatic body.

Background The objective of this paper was to study antimicrobial activity and safety of Enterococcus faecium KQ 2.6 (E. faecium KQ 2.6) isolated from peacock feces. Methods Agar well diffusion method was adopted in antimicrobial activity assay. Disk diffusion test was used to determine the antibiotic resistance. The identification and virulence potential of E. faecium KQ 2.6 were investigated using PCR amplification. Results The results indicated that cell free supernatant (CFS) of the strain had the good antimicrobial activity against selected gram-positive and gram-negative bacteria. The biochemical characteristics of antimicrobial substances were investigated. The results indicated that the antimicrobial substances were still active after treatment with catalase and proteinase, respectively. Moreover, the stability of antimicrobial substances did not change after heat treatment at 40, 50, 60, 70 and 80°C for 30 min, respectively. The activity of antimicrobial substances remained stable at 4 and −20°C after long time storage. The antimicrobial activity of CFS was compared with that of the buffer with similar strength and pH. The inhibitory zone of the buffer was apparently smaller than that of CFS, which meant that the acid in CFS was not the only factor that was contributed to antibacterial activity of CFS. The antibiotic resistance and virulence potential were evaluated using disk diffusion test and PCR amplification. The results showed that E. faecium KQ 2.6 did not harbor any tested virulence genes such as gelE, esp, asa1, cylA, efaA and hyl. It was susceptible to most of tested antibiotics except for vancomycin and polymyxin B. Conclusion E. faecium KQ 2.6 may be used as bio-preservative cultures for the production of fermented foods.

Pregnant adult C57BL/6J mice were randomly assigned to four groups: one sham and three irradiated groups that were exposed to β-irradiation from tritiated water (HTO) by a single intraperitoneal injection on Day 12.5 of gestation. The offspring received cumulative doses of 0.036, 0.071, and 0.213 Gy, respectively. The litters were observed for postnatal growth (body weight, brain weight), the development of four physiologic milestones (pinna detachment, eye opening, testes decent, vaginal opening), the acquisition age of several reflexes (cliff avoidance, air righting) and sensory functions (auditory startle, thermal reflex), movement and coordination functions and activity (pivoting, foot splay, continuous corridor activity), learning and memory performance (shock avoidance, conditioning reflex), and the density of CA1–CA4 hippocampal pyramidal neurons. Modest but significant dose-dependent neuronal death and functional impairment were seen in both 0.071 and 0.213 Gy groups. In conclusion, even prenatal low-dose β-radiation may impair murine central nervous system (CNS) development suggesting the potential importance of minimizing environmental exposure during human pregnancy.

Background Uremic pruritus is a common and intractable symptom in patients on chronic hemodialysis, but factors associated with the severity of pruritus remain unclear. This study aimed to explore the associations of metabolic factors and dialysis adequacy with the aggravation of pruritus. Methods We conducted a 5-year prospective cohort study on patients with maintenance hemodialysis. A visual analogue scale (VAS) was used to assess the intensity of pruritus. Patient demographic and clinical characteristics, laboratory parameters, dialysis adequacy (assessed by Kt/V), and pruritus intensity were recorded at baseline and follow-up. Change score analysis of the difference score of VAS between baseline and follow-up was performed using multiple linear regression models. The optimal threshold of Kt/V, which is associated with the aggravation of uremic pruritus, was determined by generalized additive models and receiver operating characteristic analysis. Results A total of 111 patients completed the study. Linear regression analysis showed that lower Kt/V and use of low-flux dialyzer were significantly associated with the aggravation of pruritus after adjusting for the baseline pruritus intensity and a variety of confounding factors. The optimal threshold value of Kt/V for pruritus was 1.5 suggested by both generalized additive models and receiver operating characteristic analysis. Conclusions Hemodialysis with the target of Kt/V ≥1.5 and use of high-flux dialyzer may reduce the intensity of pruritus in patients on chronic hemodialysis. Further clinical trials are required to determine the optimal dialysis dose and regimen for uremic pruritus.

Uremic pruritus is common and bothersome in patients receiving either peritoneal dialysis (PD) or hemodialysis (HD). To date, the preferred dialysis modality regarding the alleviation of uremic pruritus remains controversial. We conducted this cross-sectional study to compare the prevalence, intensity, and characteristics of uremic pruritus between PD and HD patients. Patients receiving maintenance dialysis at a referral medical center in Taiwan were recruited. Dialysis modality, patient demographic, clinical characteristics, and laboratory data were recorded. The intensity of uremic pruritus was measured using visual analogue scale (VAS) scores. Multivariate linear regression analysis was conducted to compare the severity of uremic pruritus between PD and HD patients. Generalized additive models were applied to detect nonlinear effects between pruritus intensity and continuous covariates. A total of 380 patients completed this study, with a mean age of 60.3 years and 49.2% being female. Uremic pruritus was presented in 24 (28.6%) of the 84 PD patients and 113 (38.2%) of the 296 HD patients (P = .12). The VAS score of pruritus intensity was significantly lower among the PD patients than the HD patients (1.32 ± 2.46 vs 2.26 ± 3.30, P = .04). Multivariate linear regression analysis showed that PD was an independent predictor for lower VAS scores of pruritus intensity compared with HD (β-value −0.88, 95% confidence interval −1.62 to −0.13). The use of active vitamin D was also an independent predictor for a lower intensity of uremic pruritus, whereas hyperphosphatemia and higher serum levels of triglyceride and aspartate transaminase were significantly associated with higher pruritus intensity. There was a trend toward a less affected body surface area of uremic pruritus in the PD patients than in the HD patients, but the difference did not reach statistical significance (P = .13). In conclusion, the severity of uremic pruritus was lower among PD patients than HD patients, and PD may provide better alleviation of pruritus symptoms. The result provides a valuable reference for clinicians and patients when choosing a dialysis modality.