Visible-light-driven alkene dicarboxylation with formate and CO2 under mild conditions.

Low-cost formate salt was used as the reductant and part of the carboxyl source in a visible-light-driven dicarboxylation of diverse alkenes, including simple styrenes. The highly competing hydrocarboxylation side reaction was successfully overridden. Good yields of products were obtained under mild reaction conditions at ambient temperature and pressure of CO2. The dual role of formate salt may stimulate the discovery of a range of new transformations under mild and friendly conditions.

Piperlongumine conquers temozolomide chemoradiotherapy resistance to achieve immune cure in refractory glioblastoma via boosting oxidative stress-inflamation-CD8+-T cell immunity.

BACKGROUND: The failure of novel therapies effective in preclinical animal models largely reflects the fact that current models do not really mimic the pathological/therapeutic features of glioblastoma (GBM), in which the most effective temozolomide chemoradiotherapy (RT/TMZ) regimen can only slightly extend survival. How to improve RT/TMZ efficacy remains a major challenge in clinic. METHODS: Syngeneic G422TN-GBM model mice were subject to RT/TMZ, surgery, piperlongumine (PL), αPD1, glutathione. Metabolomics or transcriptomics data from G422TN-GBM and human GBM were used for gene enrichment analysis and estimation of ROS generation/scavenging balance, oxidative stress damage, inflammation and immune cell infiltration. Overall survival, bioluminescent imaging, immunohistochemistry, and immunofluorescence staining were used to examine therapeutic efficacy and mechanisms of action. RESULTS: Here we identified that glutathione metabolism was most significantly altered in metabolomics analysis upon RT/TMZ therapies in a truly refractory and reliable mouse triple-negative GBM (G422TN) preclinical model. Consistently, ROS generators/scavengers were highly dysregulated in both G422TN-tumor and human GBM. The ROS-inducer PL synergized surgery/TMZ, surgery/RT/TMZ or RT/TMZ to achieve long-term survival (LTS) in G422TN-mice, but only one LTS-mouse from RT/TMZ/PL therapy passed the rechallenging phase (immune cure). Furthermore, the immunotherapy of RT/TMZ/PL plus anti-PD-1 antibody (αPD1) doubled LTS (50%) and immune-cured (25%) mice. Glutathione completely abolished PL-synergistic effects. Mechanistically, ROS reduction was associated with RT/TMZ-resistance. PL restored ROS level (mainly via reversing Duox2/Gpx2), activated oxidative stress/inflammation/immune responses signature genes, reduced cancer cell proliferation/invasion, increased apoptosis and CD3+/CD4+/CD8+ T-lymphocytes in G422TN-tumor on the basis of RT/TMZ regimen. CONCLUSION: Our findings demonstrate that PL reverses RT/TMZ-reduced ROS and synergistically resets tumor microenvironment to cure GBM. RT/TMZ/PL or RT/TMZ/PL/αPD1 exacts effective immune cure in refractory GBM, deserving a priority for clinical trials.

Combined effects of vehicles and waste incineration on urban air halogenated and parent polycyclic aromatic hydrocarbons.

Traffic emissions and waste incineration are the main sources of PAHs in urban atmosphere, but their spatially superimposed effects are currently unclear. This study assessed the spatial distribution of PAHs and HPAHs concentrations in the atmosphere of Shenzhen by simulating the spatial and temporal dispersion of PAHs and HPAHs emissions from on-road vehicles and municipal solid waste incinerators (MSWIs). Generally, the concentrations of PAHs and HPAHs were higher on workdays than on weekends due to higher traffic volumes, while the prevailing wind direction of the northeast could cause more widespread dispersion of PAHs and HPAHs within Shenzhen's atmosphere. After superimposing the spatial distribution of pollutants emitted by vehicles and MSWIs, PAHs within 1000 m downwind of MSWIs are mainly contributed by MSWIs and beyond 1000 m by vehicles. The cancer risk values induced by exposure to PAHs and HPAHs via inhalation in Shenzhen were below the acceptable risk level for males and females in each age group, while adults faced the highest cancer risk, followed by adolescents and children. However, spatially, the cancer risk values were above the priority risk level for adult males in localized high-traffic areas in Futian and Luohu districts.

Alkene Synthesis by Photo-Wolff-Kischner Reaction of Sulfur Ylides and N-Tosylhydrazones.

A visible-light-driven and room temperature photo-Wolff-Kischner reaction of sulfur ylides and N-tosylhydrazones has been developed for the first time to provide modular access to alkene synthesis. The high functional group tolerance and broad substrate scope were demonstrated by more than 60 examples. Both E- and Z-olefinic stereochemistry in the products could be controlled with excellent stereoselectivity. A series of mechanistic studies support that the reaction should proceed through a radical-carbanion crossover pathway, specifically involving addition of photo-generated sulfur ylide radical cations to N-tosylhydrazones to form carbanions and subsequent Wolff-Kischner process.

Bioactive monoterpene phenol dimers from the fruits of Psoralea corylifolia L.

Nine undescribed monoterpene phenol dimers, bisbakuchiols D-L (1-9), were isolated from the fruits of Psoralea corylifolia L. Their structures were elucidated based on extensive spectral analysis. The absolute configurations of 1-9 were specified by experimental and quantum chemical calculations of ECD spectra, and that of 1 was further established by X-ray diffraction analysis using Cu Kα radiation. Bisbakuchiols (1-4) were composed of two bakuchiols, one of which was cyclized via a C-7'/ C-12' single bond to form a six-member ring, and connect to each other by C-4-O-C-13' bonds. Bisbakuchiols (7-9) had a pyran ring by linkage of C-8-O-C-12. In the enzyme assay, compounds 5 and 9 exhibited significant PTP1B inhibitory activities with IC50 values of 0.69 and 0.73 µM, and compounds 1 and 3 showed moderate PTP1B inhibitory activities. Furthermore, a molecular docking simulation of PTP1B and active compounds 5 and 9 showed that these active compounds possess low binding affinities ranging from -6.9 to -7.1 kcal/mol.

[Clinical Significance of Monosomal Karyotype in MDS].

OBJECTIVE: To investigate the frequency, karyotype characteristics and prognosis significance of monosomal karyotype (MK) in newly diagnosed MDS patients. METHODS: The clinical, laboratorial and follow-up data of 202 MDS patients received the chromosome karyotype test in Department of Hematology, Ningbo Hospital of Zhejiang University from 2009 to 2018 were analyzed retrospectively, the monosomal karyotype features, clinical characteristics and their effects on the prognosis of MDS patients also were analyzed. RESULTS: Among 202 cases of MDS, 25 (12.38%) confirmed to be the MK. The abnormality of chromosome 5 (60.00%), 7 (56.00%), 17 (56.00%), 15 (56.00%), 13 (40.00%) and 20（40.00%）were common in monosomal karyotype. MK+-MDS (MDS with monosomal karyotype) patients had higher bone marrow blast percentage than MK--MDS (MDS without monosomal karyotype) patients, the median are 6.25% and 3.00% (P＜0.01) respectively, but there were no difference in age, sex, hemoglobin level, white blood cell count, neutrophile granulocyte percentage, platelet count, blood blast percentage, serum ferritin, folic acid and vitaminB12 between MK+-MDS and MK--MDS. The overall survival time of MK+-MDS and MK--MDS patiens with chromosome 3, 5, 7, 13, 15, 17 abnormalities was significantly shorter than MK--MDS and AK+MK--MDS patients (MDS with abnormal karyotype but without monosomal karyotype) , the MK+-MDS patients had a median survival time of 7.33 months, but the median survival time had not been reached in MK--MDS and AK+MK--MDS patients had not been reached by the end of the follow-up, and could not be assessed (P＜0.01). CONCLUSION: The monosomal karyotype is a poor prognosis factor for newly-diagnosed MDS patients. The poor prognosis suggested by monosomal karyotype may be related with the abnormality of 3, 5, 7, 13, 15 and 17 chromosome.

Emission characteristics of parent and halogenated PAHs in simulated municipal solid waste incineration.

With a self-designed small-scale waste incinerator, emission behaviors of parent and halogenated polycyclic aromatic hydrocarbons (PAHs and HPAHs) were simulated and visualized. According to our results, the 2-3 ring PAHs have higher emission factors (EFs) than those of the 4-6 ring PAHs during waste incineration. The EFs of individual HPAHs are comparable in all incineration products. Overall, the EFs of Æ©16PAH and Æ©3ClPAH decreased in the order of gas > bottom ash > particle > fine particle while the EF order for Æ©6BrPAH is bottom ash > particle > gas > fine particle. Based on qualitative observation, the size distributions of Σ16PAH, Σ3ClPAH, and Σ6BrPAH were characterized by trimodal peaks. Coagulation of fine particles in air may lead to enrichment of target compounds in the coarse particle fraction. The gas-particle partition did not reach theoretical equilibrium and most PAHs and HPAHs were absorbed inside the organic carbon. Estimated mass emission of target compounds in Shenzhen suggests that the gaseous phase from MSW incineration is the major contributor to the urban environment. However, automotive emissions contribute more to urban air pollution than MSW incineration in Shenzhen. Generally, compared with other real waste treatment, waste incineration is a more efficient method for waste-to-energy recovery and produces fewer pollutants, although the resultant carcinogenic substances are never truly harmless.

Incidence of real-world automotive parent and halogenated PAH in urban atmosphere.

This study reports results from a tunnel experiment impact of real-world traffic-related particle and gas parent and halogenated polycyclic aromatic hydrocarbons (PAHs and HPAHs) on urban air. The traffic related emission characteristics and subsequent environmental behavior of these compounds were investigated. To understand the significance of real-world transport emissions to the urban air, traffic-related mass emissions of PAHs and HPAHs were estimated based on measured emission factors. According to our results, PAHs and HPAHs emissions via particulate phase were greater than those via gaseous phase; particles in 2.1-3.3 µm size fraction, have the major contribution to particulate PAHs and HPAHs emissions. Over all, contribution of traffic-related emission of PAHs (only ∼3% of the total PAHs emission in China) is an overstated source of PAHs pollution in China. Actually, exhaust pipe emission contributed much less than the total traffic-related emission of pollutants.

Vehicle exhaust: An overstated cause of haze in China.

Overall, total exhaust emissions of NOX, VOC and particulate matter (PM) declined, though vehicles in use continued to increase in China. This suggested that contribution of motor vehicle exhaust to haze in China may be exaggerated. A higher frequency of haze episodes in China with lower total emissions fraction from vehicle exhaust compared with those in the USA confirmed that there exists no strict causality between vehicle and haze. No significant correlation (p<0.05) between haze days and the contribution of vehicles to airborne PM2.5 (particulates that are <2.5µm in aerodynamic diameter) or car ownerships. All results revealed again that vehicle exhaust is an overstated cause for haze formation in China.