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Recent studies revealed that MALT1 is a promising therapeutic target for the treatment of ABC-DLBCL. Among several reported MALT1 inhibitors, MI-2 as an irreversible inhibitor represents a new class of ABC-DLBCL therapeutics. Due to its inherent potential cross-reactivity, further structure–activity relationship (SAR) study is imperative. In this work, five focused compound libraries based on the chemical structure of MI-2 are designed and synthesized. The systematic SARs revealed that the side chain of 2-methoxyethoxy has little impact on the activity and can be replaced by other functionalized groups, providing new MI-2 analogues with retained or enhanced potency. Compounds 81 – 83 with terminal hydroxyl group as side chain displayed enhanced activities against MALT1. Replacement of triazole core with pyrazole is also tolerant, while structural modifications on other sites are detrimental. These findings will facilitate further development of small-molecule MALT1 inhibitors. [ABSTRACT FROM AUTHOR]

Objectives: To enhance the accurate prediction of the response to neoadjuvant chemotherapy (NAC) in breast cancer patients by using a quantitative analysis of dynamic enhancement magnetic resonance imaging (DCE-MRI).Materials and Methods: A dataset of 57 cancer patients with breast DCE-MR images acquired before NAC was used. Among them, 47 patients were Responders, and 10 patients were non-Responders based on the RECIST criteria. The breast regions were segmented on the MR images, and a total of 158 radiomic features were computed to represent the morphologic, dynamic, and the texture of the tumors as well as the background parenchymal features. The optimal subset of features was selected using evolutionary based Wrapper Subset Evaluator. The classifier was trained and tested using a leave-one-out cross-validation (LOOCV) method to classify Responder and non-Responder cases. The area under a receiver operating characteristic curve (AUC) was computed to assess the classifier performance. An additional independent dataset with 46 patients was also included to validate the results.Results: The evolutionary algorithm (EA)-based method identified optimal subsets comprising 12 image features that were fit for classification for the main cohort. Following the same feature selection procedure, the independent validation dataset produced 11 image features, 7 of which were identical to those from the main cohort. The classifier based on the features yield a LOOCV AUC of 0.910 and 0.874 for the main and the reproducibility study cohort, respectively. If the optimal features in the main cohort were utilized to test performance on the reproducibility cohort, the classifier generated an AUC of 0.713. While the features developed in the reproducibility cohort were applied to test the main cohort, the classifier achieved an AUC of 0.683. The AUC of the averaged receiver operating characteristic (ROC) curve for the two data cohort was 0.703.Conclusions: This study demonstrated that quantitative analyses of radiomic features from pretreatment breast DCE-MRI data could be used as valuable image markers that are associated with tumor response to NAC. [ABSTRACT FROM AUTHOR]

A facile one-pot synthesis of tricyclo-1,4-benzoxazines has been developed via metal-free intramolecular cyclization of indole derivates. These reactions were efficiently achieved at ambient temperature by using visible-light photoredox catalysis in continuous flow. This directed intramolecular cyclization could be easily handled and scaled up in an open flask, enabling construction of a focused compound library for further pharmacological evaluation. [ABSTRACT FROM AUTHOR]

Highlights: [•] N–Si codoped TiO2 fibers modified with aminosilane coupling agents were prepared. [•] N–Si codoping is responsible for a mesostructure and wide spectral response. [•] γ-Aminopropyltriethoxysilane modified TiO2 fibers exhibit a higher photoactivity. [•] The regenerated TiO2 fibers can be reused maintaining high photoactivity. [Copyright &y& Elsevier]

Abstract: The alkenylation of indoles with α,β-unsaturated ketones through a tandem addition and oxidative dehydrogenation strategy has been developed. This method provides an alternative approach for C3 alkenylation of indoles with α,β-unsaturated ketones. Using inexpensive and readily available BF3·Et2O and an ammonium salt as the efficient cocatalyst constitutes the attractive advantage of this reaction. [Copyright &y& Elsevier]

Chemotherapy is currently one of the promising therapeutic methods for non-small-cell lung cancer (NSCLC), but the emergence of multidrug resistance (MDR) is the greatest obstacle to efficient drug delivery for successful chemotherapy. Nanotechnology-based drug delivery holds great promise to promote intracellular drug delivery to reverse MDR. In this work, we used our previously synthesized ursolic acid (UA) derivative, FZU-03,010 (F3), to prepare nanodrugs of F3 with different architectures and study the role of the structure on the physiochemical properties and the biological effects against A549 and its PTX-resistant A549/PTX lung cancer cells. Using different preparation methods, amphiphilic F3 could self-assemble into different structures such as nanoaggregates (F3-NA), vesicles (F3-VC), or nanoparticles (F3-NP) with different physiochemical properties. The self-assembled nanodrugs could be utilized for the entrapment of fluorophores and showed different cellular uptake efficiencies. The cytotoxicity results demonstrated that compared with UA, F3-NA and F3-NP could suppress A549 and A549/PTX cells viability more potently at lower concentration. In addition, F3-NA and F3-NP could induce G1 cell cycle arrest, cell apoptosis and caspase-3 activation more efficiently than that of UA. Furthermore, F3-NA and F3-NP could effectively inhibit PI3K/Akt pathway and decrease the expression of Bcl-2 and the cell cycle-dependent kinase inhibitors p-ERK1/2 and Cyclin D1 in both A549 and A549/PTX cells. In conclusion, our results suggest that the UA derivative F3 is more potent in inhibiting cancer cell proliferation, and F3-NA and F3-NP have the potential to be developed as a therapeutic agent for resistant NSCLC cells. [ABSTRACT FROM AUTHOR]

• Two series chalcohalide glass varying on different cations and anions content was fabricated successfully. • The results show that the physics optics properties alter regularly with ion mole percentage. • A mono-index fiber loss of 1.91 dB/m, supercontinuum spectrum covering 1.01 ∼ 8.32 μm. Two series of novel chalcohalide glasses varying on different molar percentages of cations and anions were prepared successfully. We experimentally investigated the physical optics properties of the chalcohalide hybrid glass (Ge-As-S-Se-I) system. The results show that the short-wavelength cut-off edge (λ vis), linear refractive index (n 0), and zero-dispersion-wavelength (ZDW) regularly decrease with the increase of anionic iodine mole percentage. And the addition of cationic germanium enhances the glass transition temperature (T g), softening temperature (T p) and crystallization temperature (T x). Besides, a mono-index optical fiber was drawn successfully using the high temperature polymer as the protective layer, with a minimum loss of 1.91 dB/m at 2.6 μm. Supercontinuum (SC) covering 1.01 ∼ 8.32 μm was generated by pumping the 10-cm-long fiber at a femtosecond laser of 3.78 μm (∼150 fs, 1 kHz, 20 mW). This novel infrared (IR) glass shows great potential in many applications, such as defense military, spectroscopy, long-distance remote sensing. [ABSTRACT FROM AUTHOR]

Abstract: To develop biodegradable polymers with temperature-sensitivity, a series of polyurethanes consisting of poly (ethylene glycol) (PEG) and l-lysine ester diisocyanate (LDI) were synthesized, and the structure and molecule weight of the polymers were examined by 1H NMR, FT-IR, gel permeation chromatography (GPC). The solution properties of the copolymers were studied by turbidity measurement and size measurement. Polyurethanes could form nanoparticles by sonication in water. No temperature-sensitivity was observed with the polyurethane nanoparticles composed of PEG1000 and PEG1500. On the contrary, LDI-PEG600 exhibited a reversible temperature-responsive behavior in aqueous solution. The transition temperature (T c) of LDI-PEG600 with methyl ester of LDI was higher than that of LDI-PEG600 with butyl ester side chain. The polymers were then used to encapsulate adriamycin (ADR) by the dialyzing method from dimethylformamide solution against water. ADR could be successfully encapsulated into the polyurethane nanoparticles. The ratio of ADR release from polymeric nanoparticles increased sharply above the T c, while the release was suppressed below the T c. [Copyright &y& Elsevier]

Abstract: The comonomer effect on the structures of poly(vinylidene fluoride–hexafluoropropylene) P(VDF–HFP) copolymers was analyzed by Raman spectroscopy. The HFP content of these copolymers varies from 5% to 15%. Because of steric interactions involving the bulky HFP comonomers, the predominant chain conformation has extensively more gauche conformers in comparison to the neat PVDF. Based on both experimental and simulation studies, specific spectroscopic features in the 400–900cm−1 region have been identified that are characteristic of irregular chain conformations elucidating the perturbing effect of HFP on the equilibrium chain statistics of PVDF in the amorphous phase. In addition, these spectroscopic features were revealed to be extremely sensitive to the relative placements of the CF3 units with respect to other fluorine atoms along the chain. [Copyright &y& Elsevier]

• Arsenic-free low-loss fiber was fabricated by a process of peeled-off extrusion. • The fiber exhibits a minimum optical loss of 0.87 dB/m at 5.1 μm. • The broadest spectrum from 1.56 to 7.59 μm at −30 dB was achieved successfully. A low-loss and Arsenic-free sulfur-based chalcogenide fiber(Ge-Sb-S) was fabricated by a novel process of peeled-off extrusion. The fiber has an optical loss of <2 dB/m in a range from 5 to 6 μm with a minimum loss of 0.87 dB/m at 5.1 μm. A mid-infrared (MIR) supercontinuum (SC) spectrum covering 1.56–7.59 μm was generated from a 22-cm long fiber pumped with a femtosecond laser at 4 μm (−150 fs, 1 kHz). Simultaneously, we demonstrated that the optical fiber has a transmission efficiency of 53% at 4 μm, which is the key significance for applications such as IR night vision, bio-photonics, military defense and environmentally friendly industry. [ABSTRACT FROM AUTHOR]

• A conductive, tough multifunctional hydrogel. • Excellent adhesiveness and high photothermal conversion properties. • Dual thermo- and light-responsive deformation. • Good cell affinity and excellent conductivity. Conducting hydrogels have attracted attention as a special functional class of smart soft materials and have found applications in various advanced fields. However, acquiring all the characteristics such as conductivity, adequate adhesiveness, self-healing ability, stretchability, biocompatibility, and stimulating deformation responsiveness still remains a challenge. Inspired by the mechanism of bioadhesion in marine mussels, a multifunctional nanocomposite hydrogel with excellent adhesiveness to a broad range of substrates including human skin was developed with the help of synergistic multiple coordination bonds between clay, poly(N-isopropylacrylamide) (PNIPAM), and polydopamine nanoparticles (PDA-NPs). The prepared hydrogel showed controllable near-infrared (NIR) responsive deformation after incorporation of PDA-NPs as highly effective photothermal agents in the thermo-sensitive PNIPAM network. Meanwhile, the fabricated nanocomposite hydrogels showed excellent stretchability and conductivity, which make them attractive material candidates for application in various fields, such as electronic skin, wearable devices, and so on. [ABSTRACT FROM AUTHOR]

• The mechanism of impurity absorption and heterophase inclusion in Ge-As-S glass was investigated. • Heterophase inclusions in Ge-As-S glass can be effectively suppressed by dynamic distillation and melting at the optimized melting temperature. • The average loss of purified fiber and unpurified one is 1.86 dB/m and 2.87 dB/m, respectively. About 1 dB/m decrease in the loss is due to the absence of the visible heterophase inclusion particles in the glass. Strong absorption from the impurities and background scattering induced by heterophase inclusions are major issue in the applications of Ge-As-S glass in mid-infrared (MIR). Here, we report that, the absorption of impurities sourced from raw materials can be removed effectively by oxygen getters and hydrogen getters under static vacuum distillation, leading to almost disappearance of the absorption at 3.11 μm due to S H, <4.08 ppm at 4.01 μm due to S H and < 11.03 ppm at 7.5 μm due to As-O, respectively, in Ge 10 As 28 S 62. The impurities of H 2 O and CO 2 can be further eliminated to near zero by dynamic distillation. On the other hand, the heterophase inclusions, originating from raw materials of sulfur, arsenic and germanium, the silica-container and deoxidizer of Mg, can be eliminated thoroughly by dynamic distillation and optimized melting temperature. We draw the fibers using unpurified and purified glasses and found that, comparing with the fiber loss of 2.87 dB/m at unpurified glass, the optical loss can be decreased to about 1.86 dB/m in purified glass without any visible particles or heterophase inclusions. All the results pave the way of developing low loss Ge-As-S glass fiber for high power laser delivery. [ABSTRACT FROM AUTHOR]

A simple two-step/one-pot and highly efficient strategy for the synthesis of negletein from naturally abundant and inexpensive baicalin has been developed. In this one-pot sequence, esterification of baicalin catalyzed by concentrated H 2 SO 4 in methanol followed by the treatment with excess NaBH 4 afforded negletein in moderate yield. This method provides an additional approach for the synthesis of negletein. [ABSTRACT FROM AUTHOR]

Microtubule targeting agents (MTAs) are among the most successful chemotherapeutic drugs, but their efficacy is often limited by the development of multidrug resistance (MDR). Therefore, the development of novel MTAs with the ability to overcome MDR is urgently needed. In this contribution, through modification of the unsymmetric biaryl compounds, we discovered a novel compound dxy-1-175 with potent anti-proliferative activity against cancer cells. Mechanistic study revealed that dxy-1-175 inhibited tubulin polymerization by interacting with the colchicine-binding site of tubulin, which caused cell cycle arrest at G 2 /M phase. Based on the predicted binding model of dxy-1-175 with tubulin, a series of new 4-benzoylbiphenyl analogues were designed and synthesized. Among them, the hydrochloride compound 12e with improved solubility and good stability in human liver microsome, exhibited the most potent anti-proliferative activity with IC 50 value in the low nanomolar range, and markedly inhibited the growth of breast cancer 4T1 xenograft in vivo. Notably, 12e effectively overcame P-gp-mediated MDR and our preliminary data suggested that 12e may not be a substrate of P-glycoprotein (P-gp). Taken together, our study reveals a novel MTA 12e targeting the colchicine-binding site with potent anticancer activity and the ability to circumvent MDR. [Display omitted] • A novel tubulin inhibitor dxy-1-175 with anti-cancer activity was discovered. • By rational design, a series of new dxy-1-175 analogues were prepared. • 12e selectively and potently inhibited tumor growth both in vitro and in vivo. • 12e overcame P-gp-mediated multidrug resistance. [ABSTRACT FROM AUTHOR]

Abstract: A series of temperature- and pH-responsive polyurethanes based on hexamethylene diisocyanate (HDI) and 4,4′-diphenylmethane diisocyanate (MDI) were synthesized by a coupling reaction with bis-1,4-(hydroxyethyl) piperazine (HEP), N-methyldiethanolamine (MDEA) and N-butyldiethanolamine (BDEA), respectively. The chemical structure, molecular weight, thermal property and crystallization properties were characterized by Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) spectroscopy. The resulting polyurethanes were then used to prepare nanoparticles either by direct dispersion method or dialysis method. Their pH and temperature responsibilities were evaluated by optical transmittance and size measurement in aqueous media. Interestingly, HDI-based and MDI-based polyurethanes exhibited different pH and temperature responsive properties. Nanoparticles based on HDI-HEP and HDI-MDEA were temperature-responsive, while MDI-based biomaterials were not. All of them showed pH-sensitive behavior. The possible responsive mechanism was investigated by 1H NMR spectroscopy. The cytotoxicity of the polyurethanes was evaluated using methylthiazoletetrazolium (MTT) assay in vitro. It was shown that the HDI-based polyurethanes were non-toxic, and could be applied to doxorubicin (DOX) encapsulation. The experimental results indicated that DOX could be efficiently encapsulated into polyurethane nanoparticles and uptaken by Huh-7 cells. The loaded DOX molecules could be released from the drug-loaded polyurethane nanoparticles upon pH and temperature changes, responsively. [Copyright &y& Elsevier]

Abstract: Amino poly(glycerol methacrylate)s (PGOHMAs) were synthesized from linear or star-shaped poly(glycidyl methacrylate)s (PGMA)s via ring opening reactions with 1,2-ethanediamine, 1,4-butanediamine and diethylenetriamine, respectively. The resulting cationic polymers were employed to form polyelectrolyte complexes (PECs) with insulin. Parameters influencing complex formation were investigated by dynamic light scattering (DLS). PECs in the size range of 100–200nm were obtained under optimal conditions, i.e., the pH value of PECs was 5.58–6.27, the concentration of NaCl was 0.02mol/L, and insulin–polymer weight ratio was 0.8. The insulin association efficiency (AE) of current system increased with zeta potentials of PECs. Circular dichroism (CD) analysis corroborated that the structure of insulin in the PEC nanoparticles was preserved after lyophilization. Fourier transform infrared (FT-IR) and X-ray diffraction (XRD) experiments demonstrated that weak physical interactions between insulin and amino PGOHMAs play an important role in the formation of PECs. The release of insulin depends on both structure and architecture of amino PGOHMAs. These PECs would be potentially useful for mucosal administration. [Copyright &y& Elsevier]

Chalcogenide glass fiber usually possesses a single zero-dispersion wavelength (ZDW) that is more than 5 µm. Here, a novel W-typed double cladding chalcogenide glass fiber was designed and fabricated with optimized dispersion properties based on As 2 Se 3 -Ge 7 As 23 S 70 -Ge 10 As 23 Se 67 glasses. The results show that there are two ZDWs locating at near-infrared 2.95 µm and far-infrared 11.77 µm, and the dispersion less than 8 ps/km/nm at this range. Based on numerical simulation and viscosity analysis, a novel W-typed double-cladding fiber is fabricated via extrusion method, and the lowest loss of 1.15 dB/m is obtained at 5.68 µm. The optimized structure and dispersion distribution of the fiber ensure the excellent supercontinuum generation. When pumping at 3 µm near the first ZDW, a bandwidth supercontinuum (SC) spanning from 1 to 10.9 µm can be obtained. By pumping at 5 µm, a broad bandwidth of SC output from 1.3 to 13 µm can be obtained. This kind of low ZDW fiber has great potential for the generation of supercontinuum in the future. [ABSTRACT FROM AUTHOR]