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Four precast concrete composite walls with embedded extruded polystyrene insulation layer were designed, and the seismic performance was systematically investigated. The failure mode, hysteretic curve, skeleton curve, stiffness degradation, displacement ductility and energy dissipation capacity were explored by quasi-static tests. Moreover, the strain variation of reinforcements at the key positions of the specimens was analyzed and discussed. The test results indicated that the failure mode of the specimen with extruded polystyrene insulation layer thickness of 200 mm was flexural failure, accompanied by the concrete crushing and spalling at the wall toes; while the specimen with extruded polystyrene insulation layer thickness of 100 and 120 mm showed better cooperative working performance. The precast composite concrete wall adding diagonal braces possessed better bearing capacity, deformation capacity and cumulative energy dissipation capacity. Furthermore, the connecting reinforcements at the horizontal joint can effectively transfer stress. Finally, a simplified calculation model of bearing capacity of the precast concrete composite walls with embedded extruded polystyrene insulation layer connected by tooth groove and grouted sleeve was proposed. • An innovative precast concrete composite wall with embedded XPS insulation layer was proposed. • An innovative tooth groove and grouted sleeve connection method was proposed. • The seismic performance of precast concrete composite wall was investigated by quasi-static test. • A simplified calculation model of bearing capacity of precast concrete composite wall was established. [ABSTRACT FROM AUTHOR]

This paper proposes an innovative assembly technique using large-diameter bars anchored in several single-row, widely spaced grouted sleeves at the keyway-type horizontal joint to realize an indirect vertical connection between adjacent precast concrete (PC) walls, which has the advantages of high efficiency and ease of construction. To examine the effect of vertical connection strength (rebars' diameter at horizontal joints) on the seismic performance of PC shear walls, quasi-static cyclic loading tests on five full-size wall specimens, including one cast-in-place specimen and four PC specimens with grouted sleeve connections, are carried out. Seismic performance indicators in terms of failure modes, hysteresis characteristics, energy dissipation, ductility, and stiffness degradation of PC walls are investigated and compared with those of the cast-in-situ wall. Meanwhile, the method for predicting the bearing capacity of PC walls with large-diameter rebars is developed. The results show that the failure modes of cast-in-situ and precast walls are controlled by bending instead of shear, but there is an obvious difference in the crack propagation between the two types of walls. Carrying capacity, ductility factor, stiffness, and energy dissipation of PC walls are significantly enhanced by increasing the connection strength, by 44.1%, 23.9%, 72.1%, and 24.0%, respectively, when the connection strength reaches around 90%. Particularly, the PC wall's seismic performance is comparable to that of the cast-in-situ wall when the connection strength is 90%. The calculated results are well-matched with the experimental results, the proposed calculation method reliably predicts the bearing capacity of PC walls with large-diameter rebars. The assembly technique can be safely applied to multi-story PC wall panel structures in seismic zones. • A novel assembly method using large-diameter bars and single-row grouted sleeve connections was proposed. • Quasi-static tests on five PC walls examined how the vertical connection strength affected PC walls' seismic performance. • Relationship curves of connection strength and the ductility factor, and the lateral capacity of PC walls, were obtained. • A method for predicting the lateral capacity of PC walls with large-diameter rebar connections was developed. [ABSTRACT FROM AUTHOR]

Autophagy plays a key role in supporting cell survival against chemotherapy-induced apoptosis. In this study, we found the chemotherapy agent SN-38 induced autophagy in colorectal cancer (CRC) cells. However, inhibition of autophagy using a small molecular inhibitor 3-methyladenine (3-MA) and ATG5 siRNA did not increase SN-38-induced cytotoxicity in CRC cells. Notably, another autophagy inhibitor chloroquine (CQ) synergistically enhanced the anti-tumor activity of SN-38 in CRC cells with wild type (WT) p53. Subsequently, we identified a potential mechanism of this cooperative interaction by showing that CQ and SN-38 acted together to trigger reactive oxygen species (ROS) burst, upregulate p53 expression, elicit the loss of lysosomal membrane potential (LMP) and mitochondrial membrane potential (∆ψm). In addition, ROS induced by CQ plus SN-38 upregulated p53 levels by activating p38, conversely, p53 stimulated ROS. These results suggested that ROS and p53 reciprocally promoted each other's production and cooperated to induce CRC cell death. Moreover, we showed induction of ROS and p53 by the two agents provoked the loss of LMP and ∆ψm. Altogether, all results suggested that CQ synergistically sensitized human CRC cells with WT p53 to SN-38 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk. Lastly, we showed that CQ could enhance CRC cells response to CPT-11 (a prodrug of SN-38) in xenograft models. Thus the combined treatment might represent an attractive therapeutic strategy for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Two model compounds, 3-Phenyl-3,4-dihydro-2H-1,3-benzoxazine (PA) and 6,8-dimethyl-3-(2,4,6-trimethyl-phenyl)-3,4-dihydro-2H-1,3-benzoxazine (s-PA), were successfully synthesized and purificated. Compared with PA, s-PA also catalyzed the polymerization of BADCy even though there was no phenolic hydroxyl in its final ring-opened structures. It was confirmed that the real mechanism of benzoxazine catalyzing the polymerization of cyanate ester is the nucleophilic addition reaction of the oxygen anion on ring-opened benzoxazine to the positively charged carbon atom on cyano group. The catalytic effect also contains the contribution from the phenolic hydroxyl, but it is a secondary factor. [ABSTRACT FROM AUTHOR]

Abstract: Life Cycle Assessment was used to evaluate the environmental impacts associated with the treatment of wastewater in a wastewater treatment plant (WWTP) in Kunshan, China. CMLBaseline 2000 method was used for life cycle impact assessment using SimaPro 7.0 software. The goal of this Life Cycle Assessment study was to assess the environmental benefits and drawbacks of this WWTP in comparison with other WWTPs using different advanced treatment processes. Construction phase, operation and maintenance phase, sludge landfilling, and the transportation of chemicals to the WWTP were all taken into consideration. The LCA results of Kunshan WWTP taking renewable energy (wind power) as the energy source proposed that enhancing the effluent quality will decrease the environmental. Environmental impacts in terms of green taxes were also represented. The study revealed very different impacts for the three plants, drawing attention to the importance of the choice of the treatment process. [Copyright &y& Elsevier]

• FCN-411 had a manageable safety profile. • FCN-411 showed antitumor activity in EGFR TKI-treated, EGFR -mutated advanced NSCLC. • Patients without EGFR T790M achieved a greater ORR than those with this mutation. There are no approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR -mutated non-small cell lung cancer (NSCLC) without EGFR T790M mutation after progression on first- or second-generation EGFR-TKIs. We conducted this phase I, open-label, multicenter, dose-escalation/dose-expansion study to evaluate the safety, tolerability, antitumor activity, and pharmacokinetics of FCN-411, a TKI targeting EGFR, HER2, and HER4 , in patients with EGFR -mutated advanced NSCLC whose disease had progressed during treatment of EGFR-TKIs. Adult patients with stage IIIB–IV NSCLC harboring EGFR mutations (exon 18/19/20/21) who had progressed on prior EGFR-TKIs were enrolled. In the dose-escalation phase, patients received 4 mg, 8 mg, 12 mg, and 16 mg FCN-411 once daily until the maximum tolerated dose (MTD). In the dose-expansion phase, patients received FCN-411 at the recommended phase II dose (RP2D) continuously in 21-day cycles. The primary endpoints were safety, tolerability, MTD, and RP2D. From July 23, 2018 to September 29, 2020, 77 patients were enrolled, including 30 with EGFR T790M mutation in tumor tissues. The cut-off date was February 1, 2021. No dose-limiting toxicities were observed. The most common grade ≥ 3 treatment-emergent adverse events among all patients were diarrhea (8; 10.4%) and dermatitis acneiform (7; 9.1%). Ten of 67 evaluable patients achieved confirmed partial response, with an objective response rate (ORR) of 14.9% (95% confidence interval [CI], 8.3–24.0); the ORR was 33.3%, 14.0%, 0, and 25.0% at 4 mg, 8 mg, 12 mg, and 16 mg, respectively. Besides, the ORR in patients without and with EGFR T790M mutation was 20.5% and 7.4%, respectively. Moreover, 39 patients achieved stable disease across all doses, and the disease control rate was 73.1% (95% CI, 60.9–83.2). Median progression-free survival was 4.1 (95% CI, 2.9–5.3) months. Median duration of response and overall survival have not been reached. FCN-411 was well tolerated and demonstrated preliminary antitumor activity in patients with EGFR -mutated NSCLC after progression on EGFR-TKIs, especially in those without EGFR T790M mutation. The RP2D was defined as 8 mg once daily. Future studies are warranted. Trial registration: ClinicalTrials.gov, NCT03420079. [ABSTRACT FROM AUTHOR]

In order to find a proper treatment method for a sewage sludge disposal pit, field and laboratory investigation were conducted on the geotechnical properties of the sludge at the Changan landfill in Chengdu, China. The field investigation included borehole sampling, cone penetration tests and vane shear tests. The laboratory study involved the measurements of volume–mass relation, hydraulic conductivity, compressibility, coefficient of consolidation and shear strength for the borehole samples taken from the field. The field investigation revealed that the sludge in the disposal pit could be subdivided into three layers, i.e., top crust layer, middle fluid-like layer and deep soft plastic layer. The vane shear strength for the sludge was less than 1kPa at the fluid-like layer, and 1 and 3kPa at the deep soft plastic layer, being significantly lower than that of soft clay. Laboratory test results demonstrated that the sludge was high in organic content (18.5% to 51.8%) and water content (from 210% to 790%), and both of them exhibited a decreasing trend with depth. The variation in the organic content indicated a difference in the degree of biodegradation for the sludge at locations. The consolidation property and shear strength of the sludge exhibited a non-linear relationship to the applied consolidation pressure. The coefficient of consolidation of sewage sludge, decreasing with increasing consolidation pressure, was in an order of 10−5 cm2/s to 10−6 cm2/s, being 1–2 order lower than that of soft clay. The friction angle for the sludge increased from 10° for the pressure range from 0 to 100kPa to 15° for the pressure range from 100 to 400kPa. [ABSTRACT FROM AUTHOR]

Background Chemoradiotherapy with fluorouracil and cisplatin (PF) has shown greater clinical efficacy for local advanced oesophageal cancer but with high rate of acute toxicities. We designed the CRTCOESC study to evaluate the effect and safety of capecitabine with or without oxaliplatin versus PF with chemoradiotherapy in Chinese patients with oesophageal cancer. Methods We this randomised, open-label, multicentre trial in nine cancer centres in Henan province, China, in Chinese patients with biopsy-proven squamous oesophageal cancer (T2-4N0-2M0). We randomly assigned patients (1:1:1) to receive single capecitabine, capecitabine plus oxaliplatin, or PF, and every patient received daily radiation of 50 Gy in 2 Gy dose per fraction. Patients were stratified by different regimens cycles. Both grade 3–5 acute toxicities and 2-year overall survival were the primary endpoint, with a planned accrual of 249 patients to detect a decrease in grade 3–5 acute toxicities from 40% to 20%. Interim analysis of acute toxicities and overall response was planned for the first 120 patients. This study is registered with ClinicalTrials, number NCT02025036 . Findings Between October, 2014, and December, 2016, we accrued 128 patients, of whom 118 were eligible. 86 patients finished at least 16 weeks' follow-up and were included in the interim report (n=24 capecitabine group, n=37 capecitabine plus oxaliplatin group, and n=25 PF group). Pretreatment characters (age, gender, weight, performance status, clinical stage, lymphonodus status, and pathology grade) did not differ between the groups. Incidence of grade 3–5 acute toxicities was 25% in the capecitabine group, 32% in the capecitabine plus oxaliplatin group, and 64% in the PF group (p=0·03); the incidence was significantly lower in the capectitabine groups than the PF group (capectitabine vs PF p=0·041; capecitabine plus oxaliplatin vs PF p=0·022) and did not differ between capectitabine and capecitabine plus oxaliplatin (p=0·738). 56 patients had finished 1-year follow-up (n=12 capecitabine group, n=26 capecitabine plus oxaliplatin group, and n=18 PF group). The 1-year overall survival was 75% in the capecitabine group, 92% in the capecitabine plus oxaliplatin group, and 76% in the PF group (p=0·166). Nine patients died in total: three patients in the capecitabine group, two patients in the capecitabine plus oxaliplatin group, and four patients in the PF group. Interpretation Compared with PF, chemoradiotherapy with single capecitabine with or without oxaliplatin showed lower incidence of acute toxicities and similar 1-year overall survival. Funding National Natural Science Foundation of China. [ABSTRACT FROM AUTHOR]