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The redox homeostasis defense mechanism of tumor cells is one of the prime reasons for the unsatisfactory effect of photodynamic therapy (PDT). So far, little attention has been paid to this obstacle. In this work, we reported a synthesizing simple yet versatile nanogel (BCPS), synthesized by cystamine dihydrochloride functionalized sodium carboxymethylcellulose (CMC-SS), bovine serum albumin, and Phycocyanobilin self-assembly. The BCPS reduced the levels of glutathione molecules by reacting with glutathione, thereby interfering with intracellular redox homeostasis and enhancing the sensitivity of tumor cells to PDT. The BCPS was shown to possess excellent serum stability, high blood compatibility, low toxic side effects, and higher reactive oxygen species (ROS) utilization. After irradiation, the BCPS could significantly increase intracellular ROS level by approximately 1.6-fold and decrease the IC 50 to HeLa cells by approximately 1.5-fold, compared to the pre-functional drugs BCP. This proposed strategy, based on increasing the utilization rate of ROS in tumor cells is promising for application potentials in tumor therapy. Scheme 1 Graphical abstract of multifunctional nanogel based on carboxymethyl cellulose interfering with cellular redox homeostasis enhances PCB photodynamic therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Phycocyanobilin (PCB), a tetrapyrrole chromophore compound of Phycocyanin (PC) from Arthrospira platensis. Previous studies have shown that it has anti-inflammatory and immunomodulatory biological activities. In this work, we found that it can be used as a new anticancer photosensitizer, which is almost non-toxic readily available and less costly. A rapid production process of PCB was developed, with a yield of 19.2 ± 1.1 mg/g. By using semi-preparative liquid chromatography and silica gel column chromatography, PCB was refined to a purity of 99.97 ± 0.02%. Nuclear magnetic resonance spectroscopy and mass spectrometry were used to determine the PCB structure. The optimized wavelength of the light source that caused PCB to produce reactive oxygen species (ROS) was 660 nm. PCB had an estimated active oxygen quantum yield of 0.1595, 14.5 times that of PC (0.0110). Meanwhile, PCB produced ROS in MCF-7 cells under light conditions. After the protein of PC was partially removed, the quantum yield of active oxygen in PCB is greatly improved, which was helpful to enhance its anticancer activity. The photodynamic anticancer activity of PCB (IC 50 :8.26 ± 1.19 μM) was significantly enhanced compared with PC (IC 50 :255.29 ± 1.72 μM). PCB (without light) had no significant anticancer activity in vitro , but it showed strong anticancer activity in vivo , which was equivalent to the activity of the positive drug group: Zinc-Phthalocyanine (ZnPc) with light. This may be because PCB had the effect of eliminating inflammation and improving immunity. PCB significantly enhanced its anticancer activity under light conditions due to the production of reactive oxygen species. The experimental results showed that PCB had dual anticancer effects of chemotherapy and phototherapy in vivo , and had potential to become a new anticancer photosensitizer. [Display omitted] • High purity Phycocyanobilin is purified and characterized from Arthrospira Platensis. • It is reported for the first time that Phycocyanobilin is used for photodynamic anticancer therapy. • We find that Phycocyanobilin possesses good anticancer effects both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

As a ground treatment method, geosynthetic-reinforced pile foundation (GRPF) is widely applied in the railway construction, especially in high-speed railway (HSR), due to the strict restrictions on post-construction settlement. The post-construction settlement is commonly considered induced by the weight of railway structure as well as the moving train load. Therefore, the dynamic stress developed in the GRPF induced by HSR is important for the post-construction settlement study. However, most studies focus on the dynamic stress on the track and subgrade, studies concerning dynamic stress in GRPF are few. In this paper, a three-dimensional time-domain viscoelastic finite element method (FEM) model is developed to study the dynamic response of GRPF under the high-speed rail load. The simulation model is verified by a comparison with the results of analytical solution. And based on this model, parameter study is conducted. The investigation of train speed and the pile group layout has shown that the dynamic stress amplitude significantly increases after the train speed reaches the Rayleigh wave velocity of the subgrade, while the pile-soil stress acts reversely. For the influence of the pile group layout, three variables: pile cap size, longitudinal pile spacing, and lateral pile spacing are studied respectively. A parametric study of pile cap size, longitudinal pile spacing and lateral pile spacing have suggested that the amplitude of dynamic stress developed in the soil is more susceptible to the pile spacing rather than pile cap size. Besides, increasing replacement ratio results in the decrease of dynamic pile-soil stress ratio. • Three types of critical speed are proposed with high speed studied in the model. • Dynamic response in the pile foundation is the focus in this paper. • Replacement ratio is studied as a variable to discuss dynamic pile-soil stress ratio. [ABSTRACT FROM AUTHOR]

Altruistic preference (AP) and government subsidies are both crucial for manufacturing-recycling systems to stimulate eco-design and recycling. This paper discusses the impacts of AP and two government subsidies (an eco-design subsidy and a recycling subsidy) on a manufacturing-recycling system with eco-design, and explores rational AP coefficient and subsidy strategies from the perspective of the economy, environment, and social welfare. The principal results are 1) AP will improve the eco-design level and recycling rate, but the AP coefficient should be set below a certain threshold; 2) recycling subsidy is always conductive to both eco-design and recovery, while eco-design subsidy only has this effect when manufacturers develop recycling-biased eco-design; 3) eco-design subsidy has more negative spillover effects and sometimes conflicts with the effect of AP; and 4) subsidies are crucial in manufacturing-recycling systems with AP but governments should implement an appropriate subsidy strategy based on the specific goals and types of the eco-design. [Display omitted] • Altruistic preference and subsidies in manufacturing-recycling system are considered. • Altruistic preference helps to improve eco-design level and recycling rate. • The effects of subsidies might conflict with the impact of altruistic preference. • Manufacturers should control the degree of altruistic preference below a threshold. • Governments should devise appropriate subsidy schemes according to specific goals. [ABSTRACT FROM AUTHOR]

Upon sustained loading, colloidal gels tend to feature delayed viscoplastic creep deformations. However, the relationship, if any, between the structure and creep dynamics of gels remains elusive. Here, based on accelerated molecular dynamics simulations and the recently developed softness approach (i.e., classification-based machine learning), we reveal that the propensity of a gel to exhibit long-time creep is encoded in its static, unloaded structure. By taking the example of a calcium–silicate–hydrate gel (the binding phase of concrete), we extract a local, non-intuitive structural descriptor (a revised version of the "softness" metric proposed by the pioneering work from Cubuk et al.) that is strongly correlated with the dynamics of the particles. Notably, the macroscopic creep rate exhibits an exponential dependence on the average softness. We find that creep results in a decrease in softness in the gel structure, which, in turn, explains the gradual decay of the creep rate over time. Finally, we demonstrate that the softness metric is strongly correlated with the average energy barrier that is accessible to the particles. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • In the Early–Middle Jurassic, the Tethyan Himalayas was located at 18.9° ± 4.3°S. • The paleolatitude of the Tethyan Himalayas is consistent with cratonic India. • The Neo-Tethys Ocean expanded by 2300–4200 km during the Early–Middle Jurassic. The latitudinal changes of Greater India and the paleogeographic evolution of the Tethys Ocean are controversial and depend strongly on determining the paleogeographic locations of the Tethyan Himalayas as a function of geological time. However, the lack of reliable paleomagnetic results from the Jurassic in the Tethyan Himalayas has cast a shadow on the above research. We conducted detailed paleomagnetic research on the Ningri Formation strata (Early–Middle Jurassic) of the Zanda area, Tethyan Himalayas. Positive fold and reversal tests and microscopic observations indicate that the characteristic remanent magnetization component (ChRM) is primary. Elongation/Inclination analysis of the ChRM of the Ningri Formation yields a best-estimated value of 35.8° for the mean inclination with a 95 % confidence interval between 29.2° and 42.3°. Our results constrain the Early–Middle Jurassic paleolatitude of the Tethyan Himalayas to 18.9 ± 4.3°S. The calculated paleopole is at 30.9°N, 277.1°E (A 95 = 4.3°, K = 12.6). The Neo-Tethys Ocean had an N-S width of approximately 2300 km during the Early Jurassic and 4200 km during the Middle Jurassic by combining published paleolatitudes of the Lhasa Terrane and the Tethyan Himalayas. [ABSTRACT FROM AUTHOR]

• The Chuburi pluton has an emplacement age of 73 Ma. • The Chuburi pluton is composed of highly fractionated I-type granites. • The Chuburi pluton was generated by magmatic mixing of mantle and lower crust. • The generation of the Chuburi pluton was associated with lithospheric delamination. The tectonic evolution of the Lhasa and Qiangtang collision zone is poorly understood due to a lack of pivotal magmatic records and complex geology in central Tibet. In this study, we present zircon U–Pb ages, whole-rock major and trace elements, and Sr–Nd–Pb isotopic data for the newly discovered Chuburi pluton in the southern Qiangtang block. Zircon U–Pb data reveal that the Chuburi pluton was emplaced during the Late Cretaceous (ca. 73 Ma). Bulk-rock analyses show that this intrusion is characterized by high SiO 2 , Na 2 O and K 2 O, but low MgO, CaO and P 2 O 5. The granites are enriched with large-ion lithophile elements and light rare earth elements, with marked Eu anomalies, and there are few heavy rare earth elements and high field strength elements. These geochemical features indicate that the Chuburi pluton is a highly fractionated I-type granite. The nine granitic samples show high (87Sr/86Sr) i ratios (0.7064–0.7089), negative εNd(t) values (−1.94 to −5.59) and have Nd isotopic model ages ranging from 0.76 to 0.97 Ga. The initial Pb isotopic ratios of the Chuburi pluton is uniform: (206Pb/204Pb) t = 18.774–18.884; (207Pb/204Pb) t = 15.695–15.713; (208Pb/204Pb) t = 39.362–39.613. Based on geochemical characteristics of the Chuburi pluton, and consideration of the region geological setting, we suggest that the parent magma was generated by magmatic mixing of mantle and lower crust, and then undergoing extensive fractional crystallization with removal of K-feldspar, plagioclase, mafic mineral and minor accessory mineral. The crust beneath the central Tibet may have been significantly thickened following the final Lhasa-Qiangtang amalgamation. We argue the generation of the Chuburi pluton can be interpreted as a result of regional lithospheric delamination. [ABSTRACT FROM AUTHOR]