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Oligocellulose (OC) with low polydispersity indices has been produced in large quantities using an improved method of acid-assisted hydrolysis, in which long cellulose chains disintegrate in concentrated phosphoric acid at moderately elevated temperatures. The hydrolysis time has been reduced by three orders of magnitude without compromising the overall yield of the process or the quality of OC products. The efficient production of high-quality OCs in large quantities allows for developing OC-derived elastomeric materials. A series of OC- graft -poly(isobornyl methacrylate- random - n -butyl acrylate) [OC- g -P(IBOMA- r -BA)] elastomers have been synthesized via activators regenerated by electron transfer for atom transfer radical polymerization (ARGET ATRP). OC- g -P(IBOMA- r -BA) elastomers have tunable molecular architectures and phase morphologies toward desirable mechanical properties and thermal stability suitable for various applications. The methodologies of the OC production and the graft -polymers synthesis in this study would help advance technologies for broader applications of bio-based elastomers. [Display omitted] [ABSTRACT FROM AUTHOR]

Psoralen and isopsoralen are the major components responsible for Psoraleae Fructus-induced hepatotoxicity. This study explored the role of metabolic activation by cytochrome P450 (CYP) enzymes in psoralen- and isopsoralen-induced cytotoxicity and its potential mechanisms. Inhibitors of CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 were used to screen specific CYP enzymes responsible for the metabolic activation of psoralen and isopsoralen in mouse primary hepatocytes, which was verified using the corresponding transfected cell lines. Network toxicology and transcriptome analyses were performed to explore the mechanisms underlying toxicity. Psoralen and isopsoralen decreased the viability of mouse primary hepatocytes, whereas the inhibition of CYP2C9, 2C19, 2D6, and 2E1 significantly increased their viability. Psoralen-induced cytotoxicity was significantly enhanced by the overexpression of CYP2C19 in Chinese hamster ovary cells, whereas the overexpression of the above CYP enzymes did not affect the cytotoxicity of isopsoralen. Psoralen- and isopsoralen-induced cytotoxic effects were associated with putative core targets (i.e., Fn1, Thbs1, and Tlr2) and multiple signaling pathways (e.g., PI3K-Akt, MAPK, and TNF pathways). Our results demonstrate that the metabolic activation of psoralen and isopsoralen is mediated by CYP enzymes, thereby regulating multiple core targets and signaling pathways and resulting in cytotoxicity. [Display omitted] • Psoralen and isopsoralen metabolized by CYPs exhibit clear cytotoxicity. • CYP2C19 is the primary CYP enzyme involved in the metabolic activation of psoralen. • Specific CYPs that mediated cytotoxicity of isopsoralen further need more studies. • Psoralen and isopsoralen metabolized by CYPs may act on targets (Fn1, Thbs1, etc.). [ABSTRACT FROM AUTHOR]

Background Nutrition and coagulation play important roles in cancer progression. This study was aimed to investigate the value of the albumin/fibrinogen ratio (AFR) in non-small cell lung cancer (NSCLC) patients, through a propensity score matching (PSM) method. Methods We retrospectively analyzed 529 NSCLC patients underwent surgical resection from 2010 to 2015. PSM was used to eliminate possible biases. A Cox proportional hazards regression model was performed to evaluate the prognostic value of AFR in NSCLC. Results The optimal value was 9.67 for the AFR by ROC (receiver operating characteristic) curve. The AFR was statistically significantly associated with age, sex, smoking history, histological subtype, tumor size, pathological stage and adjuvant therapy ( p  < 0.05). Multivariate analysis indicated that the pathological stage and pre-resection AFR were independent prognostic factors for patients with NSCLC. Additionally, elevated AFR indicated a better outcome, and patients with higher AFR had lower risk for overall death (OS) (HR 0.512, 95% CI 0.316–0.829, p  = 0.006) as well as disease-free death (DFS) (HR 0.561, 95% CI 0.399–0.787, p =  0.001). The propensity score model identified 120 patients from each group that were balanced for age, sex, smoking history, histological subtype, tumor size, stage distribution and adjuvant therapy. In multivariable regression analysis of PSM groups, the result indicated that the AFR was predictive for OS (HR 0.392, 95% CI 0.225–0.683, p  < 0.001) and DFS (HR 0.526, 95% CI 0.344–0.805, p  = 0.003). Conclusions Pre-resection AFR can be considered as an independent prognostic factor in NSCLC patients, and higher AFR may enhance OS and DFS of NSCLC patients. [ABSTRACT FROM AUTHOR]

In this study, the shape memory effect of novel iron-alloyed Cu–Al-Ga shape memory single crystals were reported for the first time. The microstructure, crystal structure, martensitic transformation and shape memory effect of Cu–10Al-6Ga (master alloy), Cu–10Al-6Ga-3Fe, Cu–12Al-4Ga-3Fe and Cu–14Al-4Ga-3Fe (wt.%) were investigated. All studied alloys consist of dominant martensite and fine bcc nanoparticles with richer Fe content and poorer Cu content except master alloy. The martensitic transformation start temperatures are 241.3 °C, 251.3 °C and 71.9 °C for Cu–10Al-6Ga-3Fe, Cu–12Al-4Ga-3Fe and for Cu–14Al-4Ga-3Fe alloys, respectively. For master alloy, the martensitic transformation disappears resulted from the precipitation of a large amount of α-Cu during heating. In addition, the shape memory effects clearly increase as a result of increase of the pre-strains. The Cu–14Al-4Ga-3Fe single crystal obtains a maximum shape memory effect of 6.8% with 100% strain recovery when 10% pre-strain is applied. • Iron-alloyed Cu–Al-Ga shape memory alloys were reported for the first time. • Bulk single crystals over cm-scale were prepared through only one-step annealing cast alloys. • The Cu–14Al-4Ga-3Fe single crystal possesses maximum shape memory effect of 6.8% with a 100% strain recovery. [ABSTRACT FROM AUTHOR]

• Dual-beam laser is used to solve Ti/Cu interface layer structure is difficult to be controlled by a single continuous laser. • Pulse laser is added to solve raised heat input by single continuous laser increases the thickness of Ti/Cu interface layer. • Precise control of the heat input of dual-beam laser and the use of Cu-Si wire together avoid the formation of Ti-Fe IMCs. Continuous-pulse coaxial dual-beam laser technology was used to join titanium alloy TC4 and steel Q235 successfully. The formation of Ti-Fe IMCs was inhibited by adding Cu-Si wire and using dual-beam laser heat sources to precisely control the heat input. A Ti / Cu interface layer composed of Ti 2 Cu, TiCu and AlCu 2 Ti was formed between the weld and TC4 substrate. All joints fractured at the Ti / Cu interface layer. The mechanical properties of the joints were optimized by controlling laser offset (D O) and dual-beam laser power. The effects of different power combinations of continuous and pulse laser on the properties of the joints were studied. Compared to the combination of high continuous laser power (P C) and low pulse laser power (P P), the joint strength was found to be higher with the combination of low P C and high P P. The continuous laser mainly acts on the melting of the base metal and increasing the penetration depth. The pulse laser mainly acts on the stirring molten pool and promoting the flow of the molten pool. By using the combination of high P P and low P C , it is possible to prevent the combination of Ti and Fe due to less melting of the base metal, resulting in a joint with a lower thickness and a higher width of the Ti / Cu interface layer. The joint exhibits excellent mechanical properties. [ABSTRACT FROM AUTHOR]

With the dramatically increased environmental problems, the rational design of sustainable polymers from renewable feedstocks opens new avenues to reduce the huge pollution impact. The major challenge for sustainable polymers is the decreased mechanical performance compared to that of petroleum-based materials. In this work, fully biobased sustainable elastomers were developed by integrating renewable chitin, lignin, and plant oil into one macromolecule, in which chitin was chosen as the rigid backbone, while a lignin-derived monomer vanillin acrylate (VA) and a plant oil-based monomer lauryl acrylate (LA) were selected as the hard and soft segments for the grafted side chains. A series of Chitin- graft -poly(vanillin acrylate- co -lauryl acrylate) (Chitin- g -P(VA- co -LA)) copolymers with varied feed ratios and chitin contents were synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization as an effective grafting strategy. In addition, a dynamic cross-linked network was incorporated via Schiff-base reaction to improve the macroscopic behavior of such kind of chitin graft elastomers. These sustainable elastomers are mechanically strong and show excellent reprocessablity, as well as outstanding UV-blocking property. This strategy is versatile and can inspire the further development of fully biobased sustainable materials from natural resources. [Display omitted] [ABSTRACT FROM AUTHOR]

Graphical abstract The water layer brings about more uniform Cu-Zn distribution in co-precipitates, resulting in high catalytic performance. Highlights • Co-precipitation carried out in a three-channel microreactor brought about high activity Cu-ZnO catalyst. • Complementary features of Cu2+ and Zn2+ in reaction and diffusion made the precipitate uniform. • The uniform Cu-Zn distribution in precipitates persistently acts on the evolution of catalyst microstructures. • The intensified Cu-Zn interaction resulted in high catalytic performance. Abstract A tri-inlet micro-channel reactor was used to obtain initial precipitates with uniform Cu-Zn distribution by introducing the water layer to regulate the co-precipitation process based on the inverse relation between intrinsic reaction rates and diffusion rates of Cu2+ and Zn2+, and the catalysts with high activities were obtained. High-resolution transmission electron microscope and energy dispersive spectrometer, X-ray diffraction, thermal gravimetric analysis, hydrogen temperature-programmed reduction, and N 2 O reactive frontal chromatography method were employed to analyze the evolving microstructures of the catalysts. The synthesis of methanol from syngas was utilized to measure the performance of the obtained catalysts. The results showed, as the ratio of water layer increased, better uniformity of Cu-Zn distribution in co-precipitates was achieved, thus incorporating more Zn into precursors and diminishing the ratio of aurichalcite, resulting in more intimate contact, better dispersion and stronger interaction between CuO and ZnO. All results denote clearly that the effect from the original co-precipitation impacts eventually on the Cu-Zn interfaces of catalysts and changes the catalytic performance significantly. [ABSTRACT FROM AUTHOR]

Embryonic stem cell pathways such as hedgehog and Wnt pathways are central to the tumorigenic properties of cancer stem cells (CSC). Since CSCs are characterized by their ability to self-renew, form differentiated progeny, and develop resistance to anticancer therapies, targeting the Wnt and hedgehog signaling pathways has been an important strategy for cancer treatment. Although molecules targeting either Wnt or hedgehog are common, to the best of our knowledge, those targeting both pathways have not been documented. Here we report a small molecule (compound 1 ) that inhibits both Wnt (IC 50  = 0.5 nM) and hedgehog (IC 50  = 71 nM) pathways based on reporter gene assays. We further identified that the molecular target of 1 for Wnt pathway inhibition was porcupine (a member of the membrane-bound O-acyltransferase family of proteins), a post-translational modification node in Wnt signaling; while the target of 1 mitigating hedgehog pathway was Smoothened, a key G protein coupled receptor (GPCR) mediating hedgehog signal transduction. Preliminary analysis of structure-activity-relationship identified key functional elements for hedgehog/Wnt inhibition. In in vivo studies, compound 1 demonstrated good oral exposure and bioavailability while eliciting no overt toxicity in mice. An important consideration in cancer treatment is the potential therapeutic escape through compensatory activation of an interconnected pathway when only one signaling pathway is inhibited. Toward this end, compound 1 may not only lead to the development of new therapeutics for Wnt and hedgehog related cancers, but may also help to develop potential cancer treatment which needs to target Wnt and hedgehog signaling simultaneously. [ABSTRACT FROM AUTHOR]

Sustainable diblock copolymers of poly (isobornyl acrylate)- block -poly (methyl acrylate) (PIBOA- b -PMA) were rationally designed and synthesized with terpenoid-derived monomer IBOA as the rigid segment. These PIBOA- b -PMA diblock copolymers show excellent mechanical performance comparable to traditional triblock copolymer elastomers. They can be successfully utilized as strong sustainable adhesives with good adhesion performance and high adhesive strength. Moreover, stretchable liquid-free ionic conductive materials can be successfully fabricated by incorporating lithium bis(trifluoromethane sulfonyl) imide (LiTFSI) into PIBOA- b -PMA diblock copolymers without leakage or evaporation risks. Intriguingly, these ionic conductive materials show decreased tensile strength compared to that of pristine PIBOA- b -PMA diblock copolymer due to the plasticizing effect while still maintaining excellent extensibility. The resultant stretchable ionic conductive materials show accurate and dramatic resistance change in response to intermittent stretching-retraction deformations, finger joint bending/straightening curvatures, and elbow joint bending/straightening movements, demonstrating exceptional performance. This convenient and facile strategy can offer new opportunities for the development of novel bio-based diblock copolymers toward strong adhesives and stretchable ionic conductive materials. [Display omitted] • Sustainable diblock copolymer with excellent mechanical properties were designed via RAFT polymerization. • The diblock copolymer adhesive shows strong adhesive behavior. • Ionic conductive elastomer can be successfully fabricated by incorporating lithium salt into the diblock copolymer. • These self-healable ionic conductive materials exhibit extraordinary sensing performance. [ABSTRACT FROM AUTHOR]

The Wnt signaling pathway is an essential signal transduction pathway which leads to the regulation of cellular processes such as proliferation, differentiation and migration. Aberrant Wnt signaling is known to have an association with multiple cancers. Porcupine is an enzyme that catalyses the addition of palmitoleate to a serine residue in Wnt proteins, a process which is required for the secretion of Wnt proteins. Here we report the synthesis and structure–activity-relationship of the novel porcupine inhibitors based on a ‘reversed’ amide scaffold. The leading compound 53 was as potent as the clinical compound LGK974 in a cell based STF reporter gene assay. Compound 53 potently inhibited the secretion of Wnt3A, therefore was confirmed to be a porcupine inhibitor. Furthermore, compound 53 showed excellent chemical and plasma stabilities. However, the clearance of compound 53 in liver microsomal tests was moderate to high, and the solubility of compound 53 was suboptimal. Collective efforts toward further optimization of this novel tricyclic template to develop better porcupine inhibitors will be subsequently undertaken and reported in due course. [ABSTRACT FROM AUTHOR]

In this work, a chitin-based macromolecular chain transfer agent (Chitin-CTA) was designed to graft polymers from chitin at the molecular level. Homogeneous reversible addition-fragmentation chain transfer (RAFT) polymerization was performed to prepare branched MA elastomers, chitin- graft -poly(methyl acrylate) (Chitin- g -PMA) copolymers, which were thermally stable and showed tunable glass transition temperatures. These ultra-stretchable branched MA elastomers exhibit unique strain-hardening behavior and significantly enhanced mechanical properties. Mechanical tests indicate that the chitin backbones in branched MA elastomers can act as cross-linking points to improve the tensile strength, toughness, and elasticity simultaneously. The macroscopic performance of branched MA elastomers c be further promoted by introducing hydrogen bonding as non-covalent interaction to form an additional reversible physical network. This robust and versatile grafting strategy can provide new opportunities to prepare chitin-based branched MA elastomers with extraordinary mechanical properties. [Display omitted] • Chitin-based macromolecular chain transfer agent was designed. • Chitin branched elastomers were prepared via RAFT polymerization. • These branched elastomers show significantly enhanced mechanical properties. • Chitin backbones promote the strain-hardening behavior. [ABSTRACT FROM AUTHOR]