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We herein report a new nitrogen-directed Rh(III)-catalyzed C(sp2)–H bond functionalization of N-nitrosoanilines and azoxybenzenes with maleimides as a coupling partner, in which the olefination/alkylation process can be finely controlled at room temperature by variation of the reaction conditions. This method shows excellent functional group tolerance, and presents a mild access to the resulting olefination/alkylation products in moderate to good yields.

Gemcitabine (GEM) is the first-line medication for pancreatic ductal adenocarcinoma (PDAC). However, over some treatment cycles, GEM sensitivity declines and chemotherapeutic resistance develops, resulting in tumor recurrence and metastasis. Therefore, it is critical to elucidate the mechanism of GEM chemoresistance. And a specific drug that is closely related to the mechanism is urgently required to sensitize GEM. Here, tissue inhibitor of matrix metalloproteinases 1 (TIMP1) and phosphorylated mammalian target of rapamycin (p-mTOR) were found to be substantially elevated in PDAC patients and were associated with worse overall survival. The TIMP1/PI3K/AKT/mTOR pathway was found in GEM-resistant PDAC cells and was revealed to be involved in epithelial-mesenchymal transition (EMT) and apoptosis. Furthermore, arsenic trioxide (ATO), a basic therapeutic drug for acute promyelocytic leukemia, mediated TIMP1 reduction by inducing reactive oxygen species generation and hampered the subsequent PI3K/AKT/mTOR axis. Moreover, the combination of ATO and GEM cooperatively suppressed the TIMP1/PI3K/AKT/mTOR pathway, synergistically inhibited EMT and promoted apoptosis. In vitro and in vivo, ATO combined with GEM has a collaborative anticancer effect, inhibiting cancer cell proliferation, migration, invasion, and suppressing tumor growth both in PDAC parental and GEM-resistant cells. Overall, the TIMP1/PI3K/AKT/mTOR pathway is present in PDAC and linked to GEM resistance. ATO suppresses the axis to sensitize GEM and reverse GEM resistance, suggesting a promising treatment for the disease.

Perineural invasion (PNI) occurs in most pancreatic ductal adenocarcinomas (PDACs). The relationship between cancer cells and peripheral nerves, however, is unknown. Therefore, we focused on the cooperation of PDAC cells and peripheral nerve astrocytes, Schwann cells (SCs), in PNI. The mutual tumor-supportive secretory cytokines between SCs (sNF96.2) and PDAC cells (PANC-1, BxPC-3) were screened by human cytokine arrays and verified. The prognostic value of selected cytokines and SC-associated markers was confirmed in PDAC patients. TIMP1 and CCL7 were found to form a paracrine feedback loop between PDAC cells and SCs. PDAC cell-derived TIMP1 promotes SCs proliferation and migration via CD63/PI3K/AKT signaling. CCL7 secreted from SCs enhances PDAC cell migration, invasion and expression of TIMP1 via CCR2/STAT3. PDAC cell-SC cooperation in PNI was blocked when TIMP1 knockdown in vitro and in vivo. Finally, TIMP1, CCL7 and SC-associated markers were correlated with PNI and prognosis in PDAC patients. In conclusion, SCs collaborate with PDAC cells through the TIMP1-CCL7 paracrine feedback loop to promote PNI. TIMP1 knockdown in PDAC cells suppresses PNI. Strategies to disrupt the TIMP1-CCL7 feedback loop might be developed to inhibit PNI in PDAC.

As a crucial part of the Terahertz microwave power module (TPM), electronic power conditioner (EPC) needs to operate with high switching frequency and provide high-voltage output. This paper proposes a power supply design to meet the needs of EPC, featuring series-resonant full-bridge converter, realizing about 22 kV voltage output. The feasibility of the design was verified by simulation. From the perspective of ripple voltage and voltage spikes, the electromagnetic compatibility (EMC) issues inside the module have also been analyzed.

Background We previously reported an inverse relationship between B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and Raf kinase inhibitory protein (RKIP), which is associated with the prognosis of gastric cancer (GC). In this study, we further explored the microRNA (miRNA) regulatory mechanism between Bmi-1 and RKIP. Methods Microarray analysis was first carried out to identify miRNA profiles that were differentially expressed in cells overexpressing Bmi-1. Then, miRNAs that could regulate RKIP were identified. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to measure the expression of Bmi-1, miR-155, miR-27a and RKIP. RKIP was confirmed as a target of miR-27a and miR-155 through luciferase reporter assays, qRT-PCR and Western blotting. The effects of the Bmi-1/miR-27a/RKIP and Bmi-1/miR-155/RKIP axes on tumor growth, proliferation, migration, invasion, colony-formation ability, metastasis and chemoresistance were investigated both in vitro and in vivo. Results The downregulation of RKIP by Bmi-1 occurred at the protein but not mRNA level. This indicates probable posttranscriptional regulation. miRNA expression profiles of cells with ectopic expression of Bmi-1 were analyzed and compared to those of control cells by microarray analysis. A total of 51 upregulated and 72 downregulated miRNAs were identified. Based on publicly available algorithms, miR-27a and miR-155 were predicted, selected and demonstrated to target RKIP. Bmi-1, miR-27a and miR-155 are elevated in human GC and associated with poor prognosis of GC, while RKIP is expressed at lower levels in GC and correlated with good prognosis. Then, in vitro tests shown that in addition to regulating RKIP expression via miR-27a and miR-155, Bmi-1 was also able to regulate the migration, invasion, proliferation, colony-formation ability and chemosensitivity of GC cells through the same pathway. Finally, the in vivo test showed similar results, whereby the knockdown of the Bmi-1 gene led to the inhibition of tumor growth, metastasis and chemoresistance through miR-27a and miR-155. Conclusions Bmi-1 was proven to induce the expression of miR-27a and miR-155 and thus promote tumor metastasis and chemoresistance by targeting RKIP in GC. Overall, miR-27a and miR-155 might be promising targets for the screening, diagnosis, prognosis, treatment and disease monitoring of GC.

The therapeutic effect of gemcitabine (GEM) in pancreatic ductal adenocarcinoma (PDAC) is limited due to low drug sensitivity and high drug resistance. Tissue inhibitor of matrix metalloprotease 1 (TIMP1) is reportedly associated with GEM resistance in PDAC. However, the effect of TIMP1 down-regulation in combination with GEM treatment is unknown. We analyzed the expression of TIMP1 in human PDAC tissue using western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry. TIMP1 was highly expressed in PDAC specimens. Kaplan-Meier survival analysis suggested that a higher level of TIMP1 was correlated with poorer overall survival in 103 PDAC patients. The mRNA and protein expression profiles of TIMP1 were explored in the HTERT-HPNE human pancreatic ductal epithelium cell line, five PDAC cell lines (MIA PaCa-2, PANC-1, BxPC-3, Capan2, and SW1990), and two GEM-resistant PDAC cell lines (MIA PaCa-2R and PANC-1R). Compared with HTERT-HPNE, TIMP1 was highly expressed in the PDAC cell lines. In addition, TIMP1 was upregulated in GEM-resistant PDAC cell lines compared with their parental cells. When TIMP1 was knocked-down using short hairpin RNA, GEM-induced cytotoxicity and apoptosis were increased, while colony formation was repressed in MIA PaCa-2, PANC-1, and their GEM-resistant cells. When Bax was activated by BAM7 or Bcl-2 was inhibited by venetoclax, CCK-8 assays demonstrated that GEM sensitivity was restored in GEM-resistant cells. When Bax was down-regulated by siRNA, CCK-8 assays verified that GEM sensitivity was decreased in PDAC cells. The observations that TIMP1 knockdown enhanced GEM sensitivity and reversed chemoresistance by inducing cells apoptosis indicated cooperative antitumor effects of shTIMP1 and GEM therapy on PDAC cells. The combination may be a potential strategy for PDAC therapy.

The interactions of tobacco shred with other tobacco-based materials, like expanded cut tobacco, cut reconstituted tobacco and expanded cut stem during co-pyrolysis and co-combustion, were investigated using thermogravimetric analyzer. The results illustrated that the interactions barely existed during the co-pyrolysis, but promoted the combustion during the co-combustion process of all binary mixtures. Oxidative decompositions of solid char for all binary mixtures were promoted by the interactions during the co-combustion process. The activation energy distributions, which were obtained by the Kissinger–Akahira–Sunose method from the TG data, well explained how the interactions influenced the combustion of the binary mixtures. For further understanding the effects of interactions on the combustion behaviors of the mixed materials, the release characteristics of heat, smoke, CO and CO2 were determined by the cone calorimeter tests. Results demonstrated that the interactions among the binary mixtures enhanced the HRR rates and THR values, but reduced the smoke production rates, the amounts of total smoke production and the CO/CO2 ratio. Thus, it could be concluded that the health harm of cigarette smoking can be reduced by blending these tobacco-based materials to some extent.

We report on the synthesis of Fe3O4@SiO2 nanoparticles incorporated poly(divinylbenzene) monolithic column via in situ polymerization. The monolith had larger specific surface area and relatively uniform porous structure and was characterized by scanning electron microscopy, nitrogen adsorption–desorption, and Fourier transform infrared spectroscopy. The monolith was then applied for the evaluation of gas chromatography separation properties. Here, an electromagnetic induction heating technique was employed to control the column temperature with the thermal effect of eddy current in ferromagnetic materials Fe3O4. The monolith offered good separation efficiency for benzene and toluene and a higher column efficiency was obtained up to 4481 and 9216 plates per meter, respectively. In addition, the injection volume and column capacity of the proposed system are as much as 5 µL and 100 ng. This makes it possible to use a UV detector. The fabricated Fe3O4@SiO2 nanoparticles incorporated poly(divinylbenzene) monolithic column has been shown to be very promising for gas chromatography separation.

The effects of exogenous potassium salts on the thermal degradation of flue-cured tobacco were investigated using thermogravimetric analysis (TGA), surface area/porosity measurements (SAPM), real-time fourier transform infrared (RT-FTIR), and thermogravimetric/Fourier transform infrared spectrometry (TG-FTIR), respectively. TGA analysis showed that potassium salts accelerated tobacco’s degradation at around 150–350 °C, but improved the thermal stability of char residue at high temperature range. The porous texture analysis displayed that potassium salts reduced the pore volume and surface area of tobacco pyrolysis residues. Further study using RT-FTIR illustrated that there was a positive catalysis of potassium salts with C O, O H and C O bonds at different temperature ranges, but a protective effect was given to C H bond, C C bond and aromatic moieties except for the accelerating degradation of C H by the oxidation effect of KNO 3 . The evolution comparison of their gaseous products manifested that potassium salts cut down the emission of CO 2 , H 2 O, CO, aldehydes and alkanes, but enhanced the release of carbonyl compounds, anhydrides and alcohols at around 150–350 °C. Above 350 °C, the potassium salt-containing samples exhibited a gentle escape process for both the oxygen-bearing molecules (CO 2 , H 2 O and CO) and oxygen-free species (alkanes, methane and unsaturated compounds) in comparison with their quick emission for the virgin samples.

In this paper, the quantitative evaluation of CO yields of flue-cured tobacco under the low-temperature heating conditions was investigated using a steady state tube furnace (SSTF) on the basis of controlled equivalence ratio method. Then the effect of temperature, ventilation condition and elemental compositions on the CO yields was studied, respectively. There was a strikingly low CO yield of heated tobacco under a fixed ventilation condition in comparison with flaming or even smouldering tobacco, and the temperature just slightly influenced the CO yield of flue-cured tobacco under the low-temperature heating states. At a fixed temperature of 450 °C, the CO yield, with reducing air velocity, first increased fast and then tended to remain unchanged. The correlation study indicates that there were no significant relationships between CO yields and the individual element except for the content of carbon and hydrogen, while the significant negative correlations of CO yields with the ratio of potassium to sulphur (K/S) at the 0.01 level appeared. Further random-Forest analysis revealed that K/S is another important factor influencing CO yields of fuel-cured tobacco under the externally heated pyrolysis conditions after hydrogen content.

The thermal decomposition of pectin was studied, and some major products were online analyzed by tunable synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV-PIMS). The principal products were furfural, methyl 2-furoate and 5-oxo-tetrahydro-furan-2-carbaldehyde. Some new high molecular weight intermediate products were firstly observed thanks to the soft ionization and MSMS structural analysis of ions. The results demonstrated the variation of the pyrolysis product pool with temperatures, dividing the thermal decomposition process into two stages: the low-temperature stage for the intramolecular pyrolysis of galacturonic acid subunit at the chain ends of polymers and the high-temperature stage for the rupture of α-(1 → 4) glycosidic bond between galacturonic acid subunit. This work reported a new application of SVUV-PIMS in pectin pyrolysis and demonstrated its good performance in product analysis. The formation mechanisms of some major products from pectin pyrolysis were discussed based on the analysis of pyrolysates, which should provide insight into the pyrolysis behavior of pectin.