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A base-catalyzed divergent synthesis of 1,4,5-trisubstituted or 1,4-disubstituted imidazoles through TosMIC-based [3 + 2] cyclization reaction has been developed.

Patients treated with immune checkpoint inhibitors (ICIs) often experience unique immune-related adverse events (irAEs), and the previous studies demonstrated an association between irAEs and better outcomes in patients with ICI treatment for advanced non-small cell lung cancer (NSCLC). However, the correlation between the occurrence of mild and severe irAEs and prognosis remains unclear. Additionally, little is known regarding the association between the timing of mild and severe irAEs and clinical outcomes. We retrospectively conducted a multicenter study of advanced NSCLC patients treated with ICI monotherapy. Of the 222 patients, 79 patients (35.6%) experienced at least one irAE, and most were of grade 1 or 2 (mild) (26.6%). The most common irAEs were pneumonitis (n = 21, 9.5%) and skin-related adverse reactions (n = 19, 8.6%). The median progression-free survival of all patients treated with ICIs was 3.2 months. Patients experiencing irAEs had a better prognosis than those without such events (6.5 vs. 2.6 months, p = 0.004), and mild irAEs were associated with the best prognosis. The difference in overall survival between mild and severe irAEs was significant (34.3 vs. 17.3 months, p = 0.021). We further analyzed differences between patients with irAEs occurring at 3 or 6 weeks, and found that the earlier the occurrence of mild irAEs, the better the prognosis; however, the opposite was true for severe irAEs. In summary, patients with early occurring mild irAEs showed better clinical outcomes, whereas those with early severe irAEs tended to show poorer clinical outcomes.

An interesting β-isoquinidine catalyzed divergent reaction was developed to produce either spirocyclopentene oxindoles, spirocyclopentadiene oxindoles or bisoxindoles in a high enantioselective fashion. The utility of this protocol was demonstrated by the versatile transformations of the products. This work not only represents the first highly stereoselective intermolecular catalytic asymmetric allylic alkylation reaction between two isatin-derived MBH carbonate molecules but also constitutes a rare example of isatin-derived MBH carbonate-based enantioselective and α-regioselective [3+2] cycloaddition reactions.

Yi-Bing Xu,1,2 Yiping Zhang,1,2 Zhengbo Song,1,2 Wenxian Wang,1,2 Lan Shao1,2 1Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310022, People’s Republic of China; 2Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, 310022, People’s Republic of ChinaCorrespondence: Lan ShaoZhejiang Cancer Hospital, No. 1 East Banshan Road, Hangzhou, 310022, Zhejiang Province, People’s Republic of ChinaTel +86 1 782 686 6632Email shaolan1677@163.comBackground: Brain metastasis (BM) is an important factor shortening the lives of patients with lung cancer. Patients with cystic BM have seldom been reported. Here, we compared the efficacy and prognosis of different therapeutic schedules for solid BM and cystic BM in patients with non-small cell lung cancer (NSCLC).Methods: A retrospective study was conducted of 355 patients with pathologically confirmed stage IV NSCLC, all of whom had BM. We analyzed the clinical characteristics of these patients and the efficacy of targeted drugs and chemotherapy regimens.Results: A total of 255 patients with solid BM (cohort 1) and 33 patients with cystic BM (cohort 2) had evaluable efficacy. We evaluated these 33 patients in cohort 2. The median progression-free survival (PFS) and overall survival (OS) were 8.4 months and 23.0 months, respectively. A significant difference was observed between targeted regimens and chemotherapy treatment in terms of the PFS (12.6 months vs 6.3 months, P = 0.001) and OS (47.9 months vs 17.0 months, P = 0.007). Multivariate analyses showed that treatment regimen (chemotherapy) was a poor prognostic factor for PFS (P < 0.05). Cystic BM may be more likely to occur in patients with NSCLC with genetic mutations. A difference in prognosis was observed between patients who underwent targeted treatment and chemotherapy. A significant difference in intracranial PFS was observed between cohorts (cohort 1 vs cohort 2: 15.4 months vs 9.9 months, P = 0.015), and this advantage was clear in patients who did not receive targeted therapies (11.7 months vs 6.5 months, P = 0.003). However, the OS in patients with targeted therapies in cohort 2 was significantly longer than that in cohort 1 (23.4 months vs 47.9 months, P = 0.013).Conclusion: Patients with NSCLC, particularly those who develop cystic BM, should be genetically tested as much as possible to find out more suitable drug therapies.Keywords: cystic brain metastases, tyrosine kinase inhibitors, chemotherapy, radiation therapy, lung cancer

A novel Tin-functionalized integrated rubber of styrene-isoprene-butadiene (St-Ip-Bd) tri-copolymer (Sn-SIBR) was prepared by anionic polymerization using self-made tin-containing organolithium (SnLi) as initiator, tetrahydrofuran (THF) as polar modifier, and cyclohexane as solvent. The microstructure and the glass-transition temperature (Tg) of tri-copolymers were characterized by 1H NMR and differential scanning calorimetry (DSC), respectively. The result shows that the non-1,4-structure content and the Tg of tri-copolymers increased with the increase of THF dosage and the initiator concentration or the decrease of polymerization temperature. We also obtained the relationships between the ln(T/Li)( THF/ SnLi, mole ratio) and the non-1,4-structure content, the non-1,4-structure content and the Tg of copolymers, respectively.

In this paper a modified JPDA algorithm to avoid track coalescence is proposed. An exclusive measurement is defined for every target in the new algorithm, and with other targets will be pruned, which resists two or more targets share the same measurement as a key measurement and avoids track coalescence. The simulation results show that the new algorithm can effectively solve track coalescence problem in all kinds of scenarios, while keeping a high tracking performance.

For the problem of tracking multiple targets, the Joint Probabilistic Data Association approach has shown to be very effective in handling clutter and missed detections. However, it tends to coalesce neighboring tracks and ignores the coupling between those tracks. To avoid track coalescence,a K Nearest Neighbor Joint Probabilistic Data Association algorithm is proposed in this paper. Like the Joint Probabilistic Data Association algorithm, the association possibilities of target with every measurement will be computed in the new algorithm, but only the first K measurements whose association probabilities with the target are larger than others' are used to estimate target's state. Finally, through Monte Carlo simulations, it is shown that the new algorithm is able to avoid track coalescence and keeps good tracking performance in heavy clutter and missed detections.

A novel Tin-functionalized integrated rubber of styrene-isoprene-butadiene tri-copolymer (SIBR) was prepared in the styrene (St)/isoprene (Ip) /butadiene (Bd) system with self-made tin-containing organolithium (simplified as SnLi) as initiator via living anionic polymerization. By means of several measures such as TEM, SEM and dynamic viscoelastometer, morphology, static mechanical properties, wear ability, dynamic heat build-up and dynamic viscoelasticity of Tin-functionalized SIBR (Sn-SIBR) were studied and compared with non-functionalized SIBR and NR/S-SBR (40/60) blend. The result shows that with improving antiskid properties and wear resistance, Sn-SIBR reduces the rolling resistance over 30%, which has excellent mechanic properties and dynamic properties. Sn-SIBR satisfies the overall property requirements of high-performance tire tread, and it is an ideal new style tread material for high-property environmental green tire.

For the problem of tracking multiple targets, the Joint Probabilistic Data Association approach has shown to be very effective in handling clutter and missed detections. However, it tends to coalesce neighboring tracks and ignores the coupling between those tracks. To avoid track coalescence，a K Nearest Neighbor Joint Probabilistic Data Association algorithm is proposed in this paper. Like the Joint Probabilistic Data Association algorithm, the association possibilities of target with every measurement will be computed in the new algorithm, but only the first K measurements whose association probabilities with the target are larger than others' are used to estimate target's state. Finally, through Monte Carlo simulations, it is shown that the new algorithm is able to aviod track coalescence and keeps good tracking performance in heavy clutter and missed detections.

On cherche toujours l’esthetique ; meme si on ne sait pas vraiment ce que c’est et pourquoi on la recherche. L’esthetique traditionnelle chinoise considere que la symetrie est la beaute, et la cle de cette beaute consiste dans le troisieme element pouvant determiner la symetrie, c’est-a-dire ce que l’on appelle « determinant », « delimitant » ou « reliant ». L’essence du troisieme element reside dans le sens. Dans la vie quotidienne, on utilise d’une part le sens pour organiser sa vie et d’autre part, par l’« elaboration » du sens, on veut agir sur l’autre.