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•New polyether acidic ionic liquids (ILs) have been synthesized.•ILs/TfOH mixtures have good miscibility with isobutane and isobutene.•IL/TfOH catalytic system has high selectivity ...for C8-alkylate product.•The recycling of TfOH is easily achieved.•IL/TfOH catalytic system can afford high-quality alkylate gasoline.
A series of novel polyether-based Brønsted acidic ionic liquids (ILs) have been synthesized, which contain both a polyoxyethylene (POE) chain and a sulfonic group (SO3H). The prepared ILs can well dissolve trifluoromethanesulfonic acid (TfOH), and IL/TfOH mixture has good intermiscibility with the reactants of isobutane and isobutene. Then, a new IL/TfOH catalytic system for the preparation of alkylate gasoline has been developed. The advantages of the new catalytic system are high selectivity for C8-alkylate product and the recyclability of TfOH catalyst. Under the optimal catalytic conditions (using the IL with the polymerization degree n=75, IL/TfOH(v/v)=5, reaction temperature 60°C, reaction time 30min, and stirring rate 800rpm), the C8-selectivity can reach 80%, and above 95% of C8-alkylate product is trimethylpentane (TMP). Therefore, the new IL/TfOH catalytic system can afford high-quality alkylate gasoline. In addition, the conversion of isobutene and C8-selectivity both have gradually a little drop during 6 recycles, which should attribute to a little loss of TfOH in every recycle.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Herein, we describe a nickel-catalyzed reductive deaminative arylalkylation of tethered alkenes with pyridinium salts as C(sp3) electrophiles. This two-component dicarbofunctionalization reaction ...enables the efficient synthesis of various benzene-fused cyclic compounds bearing all-carbon quaternary centers. The approach presented in this paper proceeds under mild conditions, tolerating a wide variety of functional groups and heterocycles. It has been used to functionalize complicated molecules at a late stage.
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IJS, KILJ, NUK, PNG, UL, UM
The purpose of this study was to explore the clinical efficacy and safety of Gynostemma pentaphyllum (G. pentaphyllum) in the treatment of hyperlipidemia, and to provide systematic evaluation basis ...for clinical application. CNKI, Wanfang Data, VIP, Web of science, PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) about G. pentaphyllum in the treatment of hyperlipidemia. Review Manager 5.4 were used for statistical analysis. Through reading topics, abstracts, and full texts, 27 papers with 2311 cases involved that met the inclusion and exclusion criteria were finally included for the analysis. In terms of curative effect, the effect of G. pentaphyllum alone in increasing high density lipoprotein (HDL) index was better than that of conventional treatment, and the effect of reducing total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) was similar to that of conventional treatment. There was a synergistic effect between G. pentaphyllum and conventional drugs, and the combination of G. pentaphyllum and conventional drugs was superior to conventional treatment in reducing TG and increasing HDL. G. pentaphyllum can also decrease the levels of serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase in the treatment of hyperlipidemia, indicating a certain protective function of the liver. In terms of safety, there were fewer cases of adverse reactions in the G. pentaphyllum treatment group, and the adverse reaction events reported in the literature was mild. According to the results of meta-analysis, G. pentaphyllum was effective in the treatment of hyperlipidemia, and it has the potential to be combined with traditional drugs, has a certain liver protection function, and was superior to traditional drugs in the treatment of hyperlipidemia. KCI Citation Count: 0
Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy ...can decrease neuronal death and infiltration of inflammatory cells, exerting a neuroprotective effect. We hypothesized that the combination of mild therapeutic hypothermia and adipose-derived stem cells would be neuroprotective for treatment of stroke. A rat model of transient middle cerebral artery occlusion was established using the nylon monofilament method. Mild therapeutic hypothermia (33°C) was induced after 2 hours of ischemia. Adipose-derived stem cells were administered through the femoral vein during reperfusion. The severity of neurological dysfunction was measured by a modified Neurological Severity Score Scaling System. The area of the infarct lesion was determined by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. The regeneration of microvessels and changes in the glial scar were detected by immunofluorescence staining. The inflammatory responses after ischemic brain injury were evaluated by in situ staining using markers of inflammatory cells. The expression of inflammatory cytokines was measured by reverse transcription-polymerase chain reaction. Compared with mild therapeutic hypothermia or adipose-derived stem cell treatment alone, their combination substantially improved neurological deficits and decreased infarct size. They synergistically reduced the number of TUNEL-positive cells and glial fibrillary acidic protein expression, increased vascular endothelial growth factor levels, effectively reduced inflammatory cell infiltration and down-regulated the mRNA expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α and interleukin-6. Our findings indicate that combined treatment is a better approach for treating stroke compared with mild therapeutic hypothermia or adipose-derived stem cells alone.
Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly ...more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth and the ability to attract monocyte-derived M2 macrophages in vitro. In the tumor microenvironment, CD70 was associated with immune cell infiltrates, such as T cells; myeloid-derived suppressor cells; and monocytes/macrophages based on the RNA-sequencing profile. The CD163+ macrophages were far more abundant than T cells were. This overwhelming level of macrophages was identified only in GBM and not in low-grade gliomas and normal brain specimens, implying their tumor association. CD70 was detected only on tumor cells, not on macrophages, and was highly correlated with CD163 gene expression in primary GBM. Additionally, the co-expression of the CD70 and CD163 genes was found to correlate with decreased survival for patients with primary GBM. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation. Our current efforts to target this molecule using chimeric antigen receptor T cells hold great potential for treating patients with GBM.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
It is still a major challenge for targeted cancer chemotherapy to design a stable biocompatible micellar drug delivery system. To address this dilemma, novel responsive cross-linked micelles ...(x-micelles) based on polyurethane with photo-responsive coumarin derivatives and pH-responsive hydrazone groups were synthesized. The polymers could be self-assembled into micelles using a typical and facile way. The x-micelles were stable at physiological conditions after UV light induced cross-linking, and can be disassociated under acidic condition. The drug loading content (DLC) and the encapsulation efficiency (EE) of the obtained x-micelles (15.2% and 60.8% respectively) were higher than those of micelles (9.8% and 39.2% respectively), and the DOX release rate of x-micelles was also improved. For targeted therapy, folic acid (FA) was then conjugated to x-micelles, resulting in x-micelles-FA. Cellular viability experiments show that both x-micelles and micelles had a low cytotoxicity and good biocompatibility of up to 1000 μg mL
, and DOX-loaded x-micelles-FA and x-micelles exhibited half-maximal inhibitory concentration (IC
) values of 1.17 and 2.40 μg mL
, respectively, to HeLa cells, but have lower cytotoxicity to L929 cells. The pH-responsive x-micelles-FA exhibited superior extracellular stability but activated intracellular drug release. We have demonstrated that the polyurethane with UV- and pH-responsive properties as a novel platform for tumor-targeting drug delivery.
Ankyrin repeat and SOCS Box containing 3 (ASB3) is an E3 ubiquitin ligase. It has been reported to regulate the progression of some cancers, but no systematic pan-cancer analysis has been conducted ...to explore its function in prognosis and immune microenvironment.
In this study, mRNA expression data were downloaded from TCGA and GTEx database. Next generation sequencing data from 14 glioblastoma multiforme (GBM) samples by neurosurgical resection were used as validation dataset. Multiple bioinformatics methods (ssGSEA, Kaplan-Meier, Cox regression analysis, GSEA and online tools) were applied to explore ASB3 expression, gene activity, prognosis of patients in various cancers, and its correlation with clinical information, immune microenvironment and pertinent signal pathways in GBM. The biological function of ASB3 in tumor-infiltrating lymphocytes (TILs) was verified using an animal model.
We found that ASB3 was aberrant expressed in a variety of tumors, especially in GBM, and significantly correlated with the prognosis of cancer patients. The level of ASB3 was related to the TMB, MSI and immune cell infiltration in some cancer types. ASB3 had a negative association with immune infiltration and TME, including regulatory T cells (Tregs), cancer-associated fibroblasts, immunosuppressors and related signaling pathways in GBM. ASB3 overexpression reduced the proportion of Tregs in TILs. GSEA and PPI analysis also showed negative correlation between ASB3 expression and oncogenetic signaling pathways in GBM.
A comprehensive pan-cancer analysis of ASB3 showed its potential function as a biomarker of cancer prognosis and effective prediction of immunotherapy response. This study not only enriches the understanding of the biological function of ASB3 in pan-cancer, especially in GBM immunity, but also provides a new reference for the personalized immunotherapy of GBM.
The natural history of patients with low-grade glioma (LGG) varies widely, but most patients eventually deteriorate, leading to poor prognostic outcomes. We aim to develop biological models that can ...accurately predict the outcome of LGG prognosis.
Prognostic genes for glutamine metabolism were searched by univariate Cox regression, and molecular typing was constructed. Functional enrichment analysis was done to evaluate potential prognostic-related pathways by analyzing differential genes in different subtypes. Enrichment scores of specific gene sets in different subtypes were measured by gene set enrichment analysis. Different immune infiltration levels among subtypes were calculated using algorithms such as CIBERSORT and ESTIMATE. Gene expression levels of prognostic-related gene signatures of glutamine metabolism phenotypes were used to construct a RiskScore model. Receiver operating characteristic curve, decision curve and calibration curve analyses were used to evaluate the reliability and validity of the risk model. The decision tree model was used to determine the best predictor variable ultimately.
We found that C1 had the worst prognosis and the highest level of immune infiltration, among which the highest macrophage infiltration can be found in the M2 stage. Moreover, most of the pathways associated with tumor development, such as MYC_TARGETS_V1 and EPITHELIAL_MESENCHYMAL_TRANSITION, were significantly enriched in C1. The wild-type IDH and MGMT hypermethylation were the most abundant in C1. A five-gene risk model related to glutamine metabolism phenotype was established with good performance in both training and validation datasets. The final decision tree demonstrated the RiskScore model as the most significant predictor of prognostic outcomes in individuals with LGG.
The RiskScore model related to glutamine metabolism can be an exceedingly accurate predictor for LGG patients, providing valuable suggestions for personalized treatment.
Objective:
This study aimed to research the effect of transcranial direct current stimulation (tDCS) and functional electrical stimulation (FES) on the lower limb function of post-convalescent stroke ...patients.
Methods:
A total of 122 patients in the stroke recovery stage who suffered from leg dysfunction were randomly divided into two groups: a tDCS group (
n
= 61) and a FES group (
n
= 61). All patients received same routine rehabilitation and equal treatment quality, the tDCS group was treated with tDCS, while the FES group received FES. The lower limb Fugl-Meyer assessment (FMA), modified Barthel index (MBI), functional ambulatory category (FAC), and somatosensory evoked potential (SEP) were used to assess the patients at three different stages: prior to treatment, 4 weeks after treatment, and 8 weeks after treatment.
Results:
The assessment scores for FMA, MBI, and FAC for the lower extremities after treatment (
P
> 0.05) were compared with those before treatment. The FMA, MBI, and FAC scores of the tDCS group were significantly higher than those of the FES group in all three stages (
P
< 0.05). The FMA, MBI, and FAC assessment scores of both groups were significantly higher after 4 weeks of treatment than that before treatment, and the scores after 8 weeks of treatment were significantly higher than those after 4 weeks after treatment (
P
< 0.05). The P40, N45 latencies decreased and the P40, N45 amplitudes increased, but there was no significant difference before treatment and after treatment (
P
>0.05), and there was no significant difference of the tDCS and FES groups before treatment and after treatment.
Conclusion:
In conclusion, FMA, MBI, and FAC indicate that both tDCS and FES can significantly promote the recovery of a patient’s leg motor function and tDCS is more effective than FES in the stroke recovery stage. The application value of SEP in stroke patients remains to be further studied.
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