UV Light-Mediated Hydrolytic Reaction to Develop Magnetic Hydrogel Actuators with Spatially Distributed Ferriferous Oxide Microparticles.

Magnetic hydrogel actuators are developed by incorporating magnetic fillers into the hydrogel matrix. Regulating the distribution of these fillers is key to the exhibited functionalities but is still challenging. Here a facile way to spatially synthesize ferrosoferric oxide (Fe3O4) microparticles in situ in a thermal-responsive hydrogel is reported. This method involves the photo-reduction of Fe3+ ions coordinated with carboxylate groups in polymer chains, and the hydrolytic reaction of the reduced Fe2+ ions with residual Fe3+ ions. By controlling the irradiation time and position, the concentration of Fe3O4 microparticles can be spatially controlled, and the resulting Fe3O4 pattern enables the hydrogel to exhibit complex locomotion driven by magnet, temperature, and NIR light. This method is convenient and extendable to other hydrogel systems to realize more complicated magneto-responsive functionalities.

PD-L1 upregulation promotes drug-induced pulmonary fibrosis by inhibiting vimentin degradation.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality and limited therapeutic options. The immune checkpoint PD1/PD-L1 axis is related to the pathogenesis of pulmonary fibrosis, and upregulated expression levels of PD-L1 have been demonstrated in IPF patients. However, the mechanism of PD-L1 in pulmonary fibrosis is not fully understood. Here, we demonstrated upregulated expression of PD-L1 in fibrotic lung tissues and sera of IPF patients. Bleomycin (BLM) treatment induced PD-L1 upregulation, EMT (Epithelial-Mesenchymal Transition) and fibrosis-like morphology changes in human pulmonary alveolar epithelial cells (HPAEpiCs). Silencing PD-L1 attenuated BLM-induced EMT and fibrosis-like morphology changes in HPAEpiCs. In addition, we identified that PD-L1 directly binds to vimentin and inhibits vimentin ubiquitination, thereby increasing vimentin levels in HPAEpiCs. Silencing of vimentin inhibited BLM- and PD-L1-induced fibrosis in HPAEpiCs. The correlation between PD-L1 and EMT or vimentin expression was further confirmed in clinical samples and animal models. Finally, we used BLM- and paraquat-induced pulmonary fibrosis animal models to confirm the anti-pulmonary fibrosis effects of PD-L1 silencing. Taken together, our findings suggest that upregulated PD-L1 stimulates EMT of alveolar epithelial cells by increasing vimentin levels by inhibiting vimentin ubiquitination, thereby contributing to pulmonary fibrosis.

Programmable Thermo-Responsive Actuation of Hydrogels via Light-Guided Surface Growth of Active Layers on Shape Memory Substrates.

Hydrogel shape memory and actuating functionalities are heavily pursued and have found great potential in various application fields. However, their combination for more flexible and complicated morphing behaviors is still challenging. Herein, it is reported that by controlling the light-initiated polymerization of active hydrogel layers on shape memory hydrogel substrates, advanced morphing behaviors based on programmable hydrogel shapes and actuating trajectories are realized. The formation and photo-reduction-induced dissociation of Fe3+ -carboxylate coordination endow the hydrogel substrates with the shape memory functionality. The photo-reduced Fe2+ ions can diffuse from the substrates into the monomer solutions to initiate the polymerization of the thermally responsive active layers, whose actuating temperatures and amplitudes can be facially tuned by controlling their thicknesses and compositions. One potential application, a shape-programmable 3D hook that can lift an object with a specific shape, is also unveiled. The demonstrated strategy is extendable to other hydrogel systems to realize more versatile and complicated actuating behaviors.

Low blood carotenoid status in dementia and mild cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: Given their potent antioxidation properties, carotenoids play a role in delaying and preventing dementia and mild cognitive impairment (MCI). However, observational studies have found inconsistent results regarding the associations between blood carotenoid levels and the risk of dementia and MCI. We conducted this systematic review and meta-analysis to investigate the relationship between blood carotenoid levels and the risk of dementia and MCI. METHODS: A systematic search was performed in the Web of Science, PubMed, Embase, and Cochrane Library electronic databases to retrieve relevant English articles published from their inception until February 23, 2023. Study quality was assessed by the Newcastle-Ottawa scale. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were pooled using random-effect meta-analyses. Ultimately, 23 studies (n = 6610) involving 1422 patients with dementia, 435 patients with MCI, and 4753 controls were included. RESULTS: Our meta-analysis showed that patients with dementia had lower blood lycopene (SMD: -0.521; 95%CI: -0.741, -0.301), α-carotene (SMD: -0.489; 95%CI: -0.697, -0.281), ß-carotene (SMD: -0.476; 95%CI: -0.784, -0.168), lutein (SMD: -0.516; 95%CI: -0.753, -0.279), zeaxanthin (SMD: -0.571; 95%CI: -0.910, -0.232) and ß-cryptoxanthin (SMD: -0.617; 95%CI: -0.953, -0.281) than the controls. Our results indicated that blood carotenoid levels were significantly lower in patients with dementia than in controls, despite high heterogeneity across the studies. Owing to insufficient data, we did not observe a similar and stable relationship between blood carotenoid levels and MCI. CONCLUSIONS: Our meta-analysis indicated that lower blood carotenoid levels may be a risk factor for dementia and MCI.

[Research progress of the regulation of orphan nuclear receptors on chronic liver diseases].

The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.

N6-methyladenosine-related lncRNAs identified as potential biomarkers for predicting the overall survival of Asian gastric cancer patients.

OBJECTIVE: Gastric cancer (GC) is one of the most prevalent malignant tumors in Asian countries. Studies have proposed that lncRNAs can be used as diagnostic and prognostic indicators of GC due to the high specificity of lncRNAs expression involvement in GC. Recently, N6-methyladenosine (m6A) has also emerged as an important modulator of the expression of lncRNAs in GC. This study aimed at establishing a novel m6A-related lncRNAs prognostic signature that can be used to construct accurate models for predicting the prognosis of GC in the Asian population. METHODS: First, the levels of m6A modification and m6A methyltransferases expression in GC samples were determined using dot blot and western blot analyses. Next, we evaluated the lncRNAs expression profiles and the corresponding clinical data of 88 Asian GC patients retrieved from The Cancer Genome Atlas (TCGA) database. Differential expression of m6A-related lncRNAs between GC and normal tissues was investigated. The relationship between these target lncRNAs and potential immunotherapeutic signatures was also analyzed. Gene set enrichment analysis (GSEA) was performed to identify the malignancy-associated pathways. Univariate Cox regression, LASSO regression, and multivariate Cox regression analyses were performed to establish a novel prognostic m6A-related lncRNAs prognostic signature. Moreover, we constructed a predictive nomogram and determined the expression levels of nine m6A-related lncRNAs in 12 pairs of clinical samples. RESULTS: We found that m6A methylation levels were significantly increased in GC tumor samples compared to adjacent normal tissues, and the increase was positively correlated with tumor stage. Patients were then divided into two clusters (cluster 1 and cluster 2) based on the differential expression of the m6A-related lncRNAs. Results showed that there was a significant difference in survival probability between the two clusters (p = 0.018). Notably, the low survival rate in cluster 2 may be associated with high expression of immune cells (resting memory CD4+ T cells, p = 0.027; regulatory T cells, p = 0.0018; monocytes, p = 0.00095; and resting dendritic cells, p = 0.015), and low expression of immune cells (resting NK cells, p = 0.033; and macrophages M1, p = 0.045). Enrichment analysis indicated that malignancy-associated biological processes were more common in the cluster 2 subgroup. Finally, the risk model comprising of six m6A-related lncRNAs was identified as an independent predictor of prognoses, which could divide patients into high- or low-risk groups. Time-dependent ROC analysis suggested that the risk score could accurately predict the prognosis of GC patients. Patients in the high-risk group had worse outcomes compared to patients in the low-risk group, and the risk score showed a positive correlation with immune cells (resting memory CD4+ T cells, R = 0.31, P = 0.038; regulatory T cells, R = 0.42, P = 0.0042; monocytes, R = 0.42, P = 0.0043). However, M1 macrophages (R = -0.37, P = 0.012) and resting NK cells (R = -0.31, P = 0.043) had a negative correlation with risk scores. Furthermore, analysis of clinical samples validated the weak positive correlation between the risk score and tumor stage. CONCLUSIONS: The risk model described here, based on the six m6A-related lncRNAs signature, and may predict the clinical prognoses and immunotherapeutic response in Asian GC patients.

In Situ Anodic Oxidation Tuning of NiFeV Diselenide to the Core-Shell Heterojunction for Boosting Oxygen Evolution.

Developing non-noble metal-based core-shell heterojunction electrocatalysts with high catalytic activity and long-lasting stability is crucial for the oxygen evolution reaction (OER). Here, we prepared novel core-shell Fe,V-NiSe2@NiFe(OH)x heterostructured nanoparticles on hydrophilic-treated carbon paper with high electronic transport and large surface area for accelerating the oxygen evolution rate via high-temperature selenization and electrochemical anodic oxidation procedures. Performance testing shows that Fe,V-NiSe2@NiFe(OH)x possesses the highest performance for OER compared to as-prepared diselenide core-derived heterojunctions, which only require an overpotential of 243 mV at 10 mA cm-2 and a low Tafel slope of 91.6 mV decade-1 under basic conditions. Furthermore, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) confirm the morphology and elementary stabilities of Fe,V-NiSe2@NiFe(OH)x after long-term chronopotentiometric testing. These advantages are largely because of the strong synergistic effect between the Fe,V-NiSe2 core with high conductivity and the amorphous NiFe(OH)x shell with enriched defects and vacancies. This study also presents a general approach to designing and synthesizing more active core-shell heterojunction electrocatalysts for OER.

Possible effects of Treponema pallidum infection on human vascular endothelial cells.

Pathogens can affect host cells in various ways, and the same effect can be found in the Treponema pallidum acting on the endothelium of host vessels, and the mechanism is often complex and multiple. Based on the existing T. pallidum of a cognitive framework, the first concerns involving T. pallidum or the bacteria protein directly acted on vascular endothelial cells of the host, the second concerns mainly involved in the process of T. pallidum infection in vivo blood lipid change, secretion of cytokines and the interactions between immune cells indirectly. Through both direct and indirect influence, this study explores the role of host by T. pallidum infect in the process of the vascular endothelium.

Research progress of CO2 oxidative dehydrogenation of propane to propylene over Cr-free metal catalysts.

CO2-assisted oxidative dehydrogenation of propane (CO2-ODHP) is an attractive strategy to offset the demand gap of propylene due to its potentiality of reducing CO2 emissions, especially under the demands of peaking CO2 emissions and carbon neutrality. The introduction of CO2 as a soft oxidant into the reaction not only averts the over-oxidation of products, but also maintains the high oxidation state of the redox-active sites. Furthermore, the presence of CO2 increases the conversion of propane by coupling the dehydrogenation of propane (DHP) with the reverse water gas reaction (RWGS) and inhibits the coking formation to prolong the lifetime of catalysts via the reverse Boudouard reaction. An effective catalyst should selectively activate the C-H bond but suppress the C-C cleavage. However, to prepare such a catalyst remains challenging. Chromium-based catalysts are always applied in industrial application of DHP; however, their toxic properties are harmful to the environment. In this aspect, exploring environment-friendly and sustainable catalytic systems with Cr-free is an important issue. In this review, we outline the development of the CO2-ODHP especially in the last ten years, including the structural information, catalytic performances, and mechanisms of chromium-free metal-based catalyst systems, and the role of CO2 in the reaction. We also present perspectives for future progress in the CO2-ODHP.

[Research progress on role of traditional Chinese medicine in hepatic fibrosis based on miRNA-mediated activation of NLRP3 inflammasome].

In recent years, liver fibrosis has become a hotspot in the field of liver diseases. MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3) inflammasome activation is pivotal in the pathogenesis of liver fibrosis. The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis. Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation, including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway, miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway, miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1), miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factor κB(NF-κB) inflammatory pathway, miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-α inducible protein 3(A20), and miR-20 b-promoted expression of IL-1ß and IL-18 by activating NLRP3 signaling pathway. Additionally, the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma, Glycyrrhizae Radix et Rhizoma, Aurantii Fructus, Polygoni Cuspidati Rhizoma et Radix, Moutan Cortex, Paeoniae Radix Alba, Epimedii Folium, and Cinnamomi Cortex) was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.

[Study on mechanism of curcumol against liver fibrosis based on autophagy and apoptosis of hepatic stellate cells].

The present study clarified the molecular mechanism of curcumol against liver fibrosis based on its effects on the autopha-gy and apoptosis of hepatic stellate cells. The hepatic stellate cells were divided into a blank control group, a transforming growth factor-ß1(TGF-ß1)(10 ng·mL~(-1)) group, and low-(12.5 mg·L~(-1)), medium-(25 mg·L~(-1)), and high-dose(50 mg·L~(-1)) curcumol groups. The effect of curcumol on the viability of hepatic stellate cells induced by TGF-ß1 was detected by the MTT assay kit. The apo-ptosis in each group was determined by flow cytometry. Real-time fluorescence-based quantitative PCR(RT-PCR) was employed for the detection of mRNA expression of α-smooth muscle actin(α-SMA), type Ⅰ collagen(collagen Ⅰ), and type Ⅲ collagen(collagen Ⅲ). Western blot was used to detect the protein expression of p62, microtubule-associated protein 1 light chain 3(LC3), beclin1, B cell lymphoma 2(Bcl-2), and Bcl-2-associated X protein(Bax). Transmission electron microscopy(TEM) was used to observe cell morphology and autophagosome formation in each group. The autophagic flux was observed after cell infection with adenovirus under double fluorescence labeling. The cell viability assay revealed that compared with the TGF-ß1 group, the curcumol groups showed significantly decreased cell viability. The apoptosis assay showed that the apoptosis rates of the curcumol groups were significantly higher than that of the TGF-ß1 group. RT-PCR indicated that the mRNA expression of α-SMA, collagenⅠ, and collagen Ⅲ in the curcumol groups was significantly lower than that of the TGF-ß1 group. Western blot showed that the expression of p62, LC3, beclin1, Bcl-2, and Bax in the curcumol groups was significantly different from that in the TGF-ß1 group. As demonstrated by TEM, compared with the TGF-ß1 group, the curcumol groups showed significantly increased autophagosomes. The detection of autophagic flow by the adenovirus under double fluorescence labeling showed that autolysosomes in the curcumol groups were significantly increased compared with those in the TGF-ß1 group. Curcumol can induce the autophagy and apoptosis of hepatic stellate cells, which may be one of its anti-liver fibrosis mechanisms.

HIV-induced cancer--all paths leading to Rome.

BACKGROUND: Although several viruses have been proved to induce host specific microRNAs (miRNAs, miRs), the expression of functional miRNAs induced by Human Immunodeficiency Virus 1 (HIV-1) infection is still unknown. The variation of the expression of HIV-1 inducing miRNAs both in vitro and in vivo (in all types of infected patient groups) implies that these specific miRNAs have potential roles in the development of diseases. However, few researches have noticed the roles of these serum miRNAs. In this study, we attempted to establish a macrocontrol regulation system and simulate the influence of HIV-1 inducing miRNAs during the development of cancer. METHODS: The miRbase, FunRich software, miRtarbase, STRING, TargetScanhuman, Cytoscape plugin ClueGO/Cluepedia/STRING, DAVID Bioinformatics Resources and GEO database were comprehensively employed in this bioinformatics study. RESULTS: The miRNAs in the serum of AIDS patients and its target genes have different expression levels in serum, an array of which are associated with cancer and metabolism signaling pathways. Moreover, the emerging role of miRNAs in HIV-1 infection is also involved in human cancer, using TCGA data integrative analysis. CONCLUSIONS: Therefore, we infer that serum miRNAs in HIV-1 infection may play important roles in HIV-induced cancer and could be used as a potential biomarker for HIV-cancers detection.

The outer membrane protein Tp92 of Treponema pallidum induces human mononuclear cell death and IL-8 secretion.

Treponema pallidum is the pathogen that causes syphilis, a sexually transmitted disease; however, the pathogenic mechanism of this organism remains unclear. Tp92 is the only T. pallidum outer membrane protein that has structural features similar to the outer membrane proteins of other Gram-negative bacteria, but the exact functions of this protein remain unknown. In the present study, we demonstrated that the recombinant Tp92 protein can induce human mononuclear cell death. Tp92 mediated the human monocytic cell line derived from an acute monicytic leukemia patient (THP-1) cell death by recognizing CD14 and/or TLR2 on cell surfaces. After the stimulation of THP-1 cells by the Tp92 protein, Tp92 may induce atypical pyroptosis of THP-1 cells via the pro-caspase-1 pathway. Meanwhile, this protein caused the apoptosis of THP-1 cells via the receptor-interacting protein kinase 1/caspase-8/aspase-3 pathway. Tp92 reduced the number of monocytes among peripheral blood mononuclear cells. Interestingly, further research showed that Tp92 failed to increase the tumour necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-10, IL-18 and monocyte chemotactic protein 1 (MCP)-1 levels but slightly elevated the IL-8 levels via the Nuclear Factor (NF)-κB pathway in THP-1 cells. The data suggest that Tp92 recognizes CD14 and TLR2, transfers the signal to a downstream pathway, and activates NF-κB to mediate the production of IL-8. This mechanism may help T. pallidum escape recognition and elimination by the host innate immune system.

A preliminary study on the proinflammatory mechanisms of Treponema pallidum outer membrane protein Tp92 in human macrophages and HMEC-1 cells.

AIMS: To determine proinflammatory mechanisms of Treponema pallidum outer membrane protein Tp92 in the early syphilis infection in human macrophages and HMEC-1 cells. METHODS: Recombinant Tp92 protein was used to stimulate target human macrophages and HMEC-1 cells. PDTC (Pyrrolidinedithiocarbamic acid), SB202190 and Z-YVAD-FMK were used to block the MyD88/NF-κB, MAPKs/p38 and NLRP3/Caspase-1 pathway, respectively. TNF-α, IL-1ß, IL-6, IL-8,NLRP3, casepase-1 were detected by ELISA or Western blot. Lactate dehydrogenase (LDH) activity was measured. RESULTS: Tp92 protein could significantly induced the secretion of proinflammatory cytokines TNF-α, IL-1ß, IL-6 and IL-8 in HMEC-1 cells, but not in macrophages except IL-8. When MyD88/NF-κB pathway was blocked, differences in the secretion of TNF-α, IL-6 and IL-1ß levels and LDH enzyme activity between Tp92 group and Tp92 + PDTC group were not significant (P > 0.05) in HMEC-1 cells and macrophages except IL-8(P < 0.05). When MAPKs/p38 pathway was blocked, differences in the secretion of TNF-α, IL-1ß, IL-6 and IL-8 and LDH enzyme activity both Tp92 group and Tp92 + SB2010190 group were not significant (P > 0.05) in HMEC-1 cells and macrophages. In contrast, when NLRP3/Caspase-1 pathway was blocked with Z-YVAD-FMK, TNF-α, IL-6 and IL-1ß levels, LDH enzyme activity, and Caspase-1 and NLRP3 protein levels were significantly declined (P < 0.05) in HMEC-1 cells except IL-8(P > 0.05). The LDH enzyme activity in macrophages was decreased before and after Z-YVAD-FMK blocking (P < 0.05),however, differences in the secretion of TNF-α, IL-1ß, IL-6 and IL-8 between Tp92 group and Tp92+Z-YVAD-FMK group in macrophages were not significant (P > 0.05). CONCLUSIONS: Tp92 protein may promote proinflammatory cytokines TNF-α, IL-1ß, IL-6 secretion of HMEC-1 cells, but not in macrophages, and increase the LDH enzyme activity of HMEC-1 cells and macrophages through NLRP3/Caspase-1 pathway. However, Tp92 protein may promote IL-8 secretion of HMEC-1 cells and macrophages through MyD88/NF-κB pathway.

Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway.

Nowadays, although chemotherapy is an established therapy for breast cancer, the molecular mechanisms of chemotherapy resistance in breast cancer remain poorly understood. This study aims to explore the effects of endoplasmic reticulum stress on autophagy, apoptosis, and chemotherapy resistance in human breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the cell viability of six human breast cancer cell lines (MCF-7, ZR-75-30, T47D, MDA-MB-435s, MDA-MB-453, and MDA-MB-231) treated with tunicamycin (5 µM), after which MCF-7 cells were selected for further experiment. Then, MCF-7 cells were divided into the control (without any treatment), tunicamycin (8 µ), BEZ235 (5 µ), and tunicamycin + BEZ235 groups. Cell viability of each group was testified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Western blotting was applied to determine the expressions of endoplasmic reticulum stress and PI3K/AKT/mTOR pathway-related proteins and autophagy- and apoptosis-related proteins. Monodansylcadaverine and Annexin V-fluorescein isothiocyanate/propidium iodide staining were used for determination of cell autophagy and apoptosis. Furthermore, MCF-7 cells were divided into the control (without any treatment), tunicamycin (5 µM), cisplatin (16 µM), cisplatin (16 µM) + BEZ235 (5 µM), tunicamycin (5 µM) + cisplatin (16 µM), and tunicamycin (5 µM) + cisplatin (16 µM) + BEZ235 groups. Cell viability and apoptosis were also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Annexin V-fluorescein isothiocyanate/propidium iodide staining. In MCF-7 cells treated with tunicamycin, cell viability decreased significantly, but PEAK, eIF2, and CHOP were upregulated markedly and p-PI3K, p-AKT, and p-MTOR were downregulated in dose- and time-dependent manners. In the tunicamycin + BEZ235 group, the cell viability was lower and the apoptosis rate was higher than those of the control and monotherapy groups. Compared with the cisplatin group, the tunicamycin + cisplatin group showed a relatively higher growth inhibition rate; the growth inhibition rate substantially increased in the tunicamycin + cisplatin + BEZ235 group than the tunicamycin + cisplatin group. The apoptosis rate was highest in tunicamycin + cisplatin + BEZ235 group, followed by tunicamycin + cisplatin group and then cisplatin group. Our study provide evidence that endoplasmic reticulum stress activated by tunicamycin could promote breast cancer cell autophagy and apoptosis and enhance chemosensitivity of MCF-7 cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

Construction of ß-Trifluoromethyl Enol Ether via Base-Promoted C-O Coupling and Rearrangement of Hydrogen Atom.

A novel, high-efficiency and high-selectivity construction of ß-trifluoromethyl enol ether via base-induced/promoted C-O coupling of trifluoromethylated vinyl chloride and phenols is presented with a broad substrate scope. The reaction mechanism, especially the significantly high selectivity, was excavated and understood via DFT calculation and is well supported by the experimental observation.

Palladium-Catalyzed Direct Cross-Coupling of Carboranyllithium with (Hetero)Aryl Halides.

A palladium-catalyzed direct C-arylation reaction of readily available cage carboranyllithium reagents with aryl halides has been developed for the first time. This method is applicable to a wide range of aryl halide substrates including aryl iodides, aryl bromides, and heteroaromatic halides.