Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/β-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/β-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.

The present study evaluated effects of dietary supplementation with tryptophan (Trp) on muscle growth, protein synthesis and antioxidant capacity in hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. Fish were fed six different diets containing 2·6 (control), 3·1, 3·7, 4·2, 4·7 and 5·6 g Trp/kg diet for 56 d, respectively. Results showed that dietary Trp significantly (1) improved muscle protein content, fibre density and frequency of fibre diameter; (2) up-regulated the mRNA levels of PCNA, myf5, MyoD1, MyoG, MRF4, IGF-I, IGF-II, IGF-IR, PIK3Ca, TOR, 4EBP1 and S6K1; (3) increased phosphorylation levels of AKT, TOR and S6K1; (4) decreased contents of MDA and PC, and increased activities of CAT, GST, GR, ASA and AHR; (5) up-regulated mRNA levels of CuZnSOD, CAT, GST, GPx, GCLC and Nrf2, and decreased Keap1 mRNA level; (6) increased nuclear Nrf2 protein level and the intranuclear antioxidant response element-binding ability, and reduced Keap1 protein level. These results indicated that dietary Trp improved muscle growth, protein synthesis as well as antioxidant capacity, which might be partly related to myogenic regulatory factors, IGF/PIK3Ca/AKT/TOR and Keap1/Nrf2 signalling pathways. Finally, based on the quadratic regression analysis of muscle protein and MDA contents, the optimal Trp requirements of hybrid catfish (21·82–39·64 g) were estimated to be 3·94 and 3·93 g Trp/kg diet (9·57 and 9·54 g/kg of dietary protein), respectively.

The East Asian winter monsoon (EAWM) is one of the most dynamic components of the global climate system. Although poorly understood, knowledge of long-term spatial differences in EAWM variability during the glacial–interglacial cycles is important for understanding the dynamic processes of the EAWM. We reconstructed the spatiotemporal characteristics of the EAWM since the last glacial maximum (LGM) using a comparison of proxy records and long-term transient simulations. A loess grain-size record from northern China (a sensitive EAWM proxy) and the sea surface temperature gradient of an EAWM index in sediments of the southern South China Sea were compared. The data–model comparison indicates pronounced spatial differences in EAWM evolution, with a weakened EAWM since the LGM in northern China but a strengthened EAWM from the LGM to the early Holocene, followed by a weakening trend, in southern China. The model results suggest that variations in the EAWM in northern China were driven mainly by changes in atmospheric carbon dioxide (CO2) concentration and Northern Hemisphere ice sheets, whereas orbital insolation and ice sheets were important drivers in southern China. We propose that the relative importance of insolation, ice sheets, and atmospheric CO2 for EAWM evolution varied spatially within East Asia.

There is growing interest globally in using real-world data (RWD) and real-world evidence (RWE) for health technology assessment (HTA). Optimal collection, analysis, and use of RWD/RWE to inform HTA requires a conceptual framework to standardize processes and ensure consistency. However, such framework is currently lacking in Asia, a region that is likely to benefit from RWD/RWE for at least two reasons. First, there is often limited Asian representation in clinical trials unless specifically conducted in Asian populations, and RWD may help to fill the evidence gap. Second, in a few Asian health systems, reimbursement decisions are not made at market entry; thus, allowing RWD/RWE to be collected to give more certainty about the effectiveness of technologies in the local setting and inform their appropriate use. Furthermore, an alignment of RWD/RWE policies across Asia would equip decision makers with context-relevant evidence, and improve timely patient access to new technologies. Using data collected from eleven health systems in Asia, this paper provides a review of the current landscape of RWD/RWE in Asia to inform HTA and explores a way forward to align policies within the region. This paper concludes with a proposal to establish an international collaboration among academics and HTA agencies in the region: the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) working group, which seeks to develop a non-binding guidance document on the use of RWD/RWE to inform HTA for decision making in Asia.

The experiment was conducted to investigate the effects of dietary threonine (Thr) on growth performance and muscle growth, protein synthesis and antioxidant-related signalling pathways of hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. A total of 1200 fish (14·19 (se 0·13) g) were randomly distributed into six groups with four replicates each, fed six diets with graded level of Thr (9·5, 11·5, 13·5, 15·4, 17·4 and 19·3 g/kg diets) for 56 d. Results showed (P < 0·05) that dietary Thr (1) increased percentage weight gain, specific growth rate, feed efficiency and protein efficiency ratio; (2) up-regulated growth hormone (GH), insulin-like growth factor 1 (IGF-1), proliferating cell nuclear antigen, myogenic regulation factors (MyoD, Myf5, MyoG and Mrf4) and myosin heavy chain (MyHC) mRNA levels; (3) increased muscle protein content via regulating the protein kinase B/target of rapamycin signalling pathway and (4) decreased malondialdehyde and protein carbonyl contents, increased catalase, glutathione-S-transferase, glutathione reductase and GSH activities, up-regulated mRNA levels of antioxidant enzymes related to NFE2-related factor 2 and γ-glutamylcysteine ligase catalytic subunit. These results suggest that Thr has a potential role to improve muscle growth and protein synthesis, which might be due to the regulation of GH-IGF system, muscle growth-related gene, antioxidative capacity and protein synthesis-related signalling pathways. Based on the quadratic regression analysis of specific growth rate, the Thr requirement of hybrid catfish (14·19–25·77 g) was estimated to be 13·77 g/kg of the diet (33·40 g/kg of dietary protein).

Autonomous ships are gaining in importance and are expected to shape the future of the global shipping industry. This evolutionary shift raises serious issues about compliance with the International Regulations for Preventing Collisions at Sea 1972 (COLREGs). This paper reviews the literature on autonomous ships from the perspective of the obligations of good seamanship imposed by COLREGs. The authors conclude that to facilitate the introduction of autonomous ships, the application barriers presented by COLREGs need to be analysed. With this goal, this paper presents a perspective from navigational practice. Four nautical scientists and two deck officers were invited to give their opinions. The analysis indicates that COLREGs require further elaboration and amendments to eliminate uncertainty of interpretation. In particular, the paper highlights the need to amend the ‘look-out’ rule (COLREGs Rule 5) to permit look-out by ‘computer vision’ alone while, at the same time, preserving the distinction between vessels navigating in restricted visibility and in sight of one another.

Flow around a high-speed rotating circular cylinder for $Re\leqslant 500$ is investigated numerically. The Reynolds number is defined as $UD/\unicode[STIX]{x1D708}$ with $U$, $D$ and $\unicode[STIX]{x1D708}$ being the free-stream flow velocity, the diameter of the cylinder and the kinematic viscosity of the fluid, respectively. The aim of this study is to investigate the effect of a high rotation rate on the wake flow for a range of Reynolds numbers. Simulations are performed for Reynolds numbers of 100, 150, 200, 250 and 500 and a wide range of rotation rates from 1.6 to 6 with an increment of 0.2. Rotation rate is the ratio of the rotational speed of the cylinder surface to the incoming fluid velocity. A systematic study is performed to investigate the effect of rotation rate on the flow transition to different flow regimes. It is found that there is a transition from a two-dimensional vortex shedding mode to no vortex shedding mode when the rotation rate is increased beyond a critical value for Reynolds numbers between 100 and 200. Further increase in rotation rate results in a transition to three-dimensional flow which is characterized by the presence of finger-shaped (FV) vortices that elongate in the wake of the cylinder and very weak ring-shaped vortices (RV) that wrap the surface of the cylinder. The no vortex shedding mode is not observed at Reynolds numbers greater than or equal to 250 since the flow remains three-dimensional. As the rotation rate is increased further, the occurrence frequency and size of the ring-shaped vortices increases and the flow is dominated by RVs. The RVs become bigger in size and the flow becomes chaotic with increasing rotation rate. A detailed analysis of the flow structures shows that the vortices always exist in pairs and the strength of separated shear layers increases with the increase of rotation rate. A map of flow regimes on a plane of Reynolds number and rotation rate is presented.

Underground Nuclear Astrophysics in China (JUNA) will take the advantage of the ultra-low background in Jinping underground lab. High current accelerator with an ECR source and detectors were commissioned. JUNA plans to study directly a number of nuclear reactions important to hydrostatic stellar evolution at their relevant stellar energies. At the first period, JUNA aims at the direct measurements of 25Mg(p,γ)26 Al, 19F(p,α) 16 O, 13C(α, n) 16O and 12C(α,γ) 16O near the Gamow window. The current progress of JUNA will be given.

In high power laser facility for inertial confinement fusion research, final optics assembly (FOA) plays a critical role in the frequency conversion, beam focusing, color separation, beam sampling and debris shielding. The design and performance of FOA in SG-II Upgrade laser facility are mainly introduced here. Due to the limited space and short focal length, a coaxial aspheric wedged focus lens is designed and applied in the FOA configuration. Then the ghost image analysis, the focus characteristic analysis, the B integral control design and the optomechanical design are carried out in the FOA design phase. In order to ensure the FOA performance, two key technologies are developed including measurement and adjustment technique of the wedged focus lens and the stray light management technique based on ground glass. Experimental results show that the design specifications including laser fluence, frequency conversion efficiency and perforation efficiency of the focus spot have been achieved, which meet the requirements of physical experiments well.

The Shen-Guang II Upgrade (SG-II-U) laser facility consists of eight high-power nanosecond laser beams and one short-pulse picosecond petawatt laser. It is designed for the study of inertial confinement fusion (ICF), especially for conducting fast ignition (FI) research in China and other basic science experiments. To perform FI successfully with hohlraum targets containing a golden cone, the long-pulse beam and cylindrical hohlraum as well as the short-pulse beam and cone target alignment must satisfy tight specifications (30 and $20~\unicode[STIX]{x03BC}\text{m}$ rms for each case). To explore new ICF ignition targets with six laser entrance holes (LEHs), a rotation sensor was adapted to meet the requirements of a three-dimensional target and correct beam alignment. In this paper, the strategy for aligning the nanosecond beam based on target alignment sensor (TAS) is introduced and improved to meet requirements of the picosecond lasers and the new six LEHs hohlraum targets in the SG-II-U facility. The expected performance of the alignment system is presented, and the alignment error is also discussed.

This research was designed for the first time to investigate the photocatalytic activities of MoO3/g-C3N4 composite in converting CO2 to fuels under simulated sunlight irradiation. The composite was synthesized using a simple impregnation-heating method and MoO3 nanoparticles was in situ decorated on the g-C3N4 sheet. Characterization results indicated that the introduction of MoO3 nanoparticles into g-C3N4 fabricated a direct Z-scheme heterojunction structure. The effective interfacial charge-transfer across the heterojunction significantly promoted the separation efficiency of charge carriers. The optimal CO2 conversion rate of the composite reached 25.6 μmol/(h gcat), which was 2.7 times higher than that of g-C3N4. Additionally, the synthesized MoO3/g-C3N4 also presented excellent photoactivity in RhB degradation under visible-light irradiation.

Excavation of the Han Dynasty chambered tomb at Laoguanshan in Chengdu, south-west China, has provided the earliest known evidence of pattern loom technology. Four model looms, along with accompanying artefacts and figurines relating to the weaving process, give insight into the technique of jin silk production. The discovery is hugely significant as it provides the first direct evidence of pattern-weave textile production in ancient China. Jin silk, made using this method, was both valuable and widely distributed, and the design of the machine influenced the invention of later looms and the spread of technology throughout Eurasia and Europe, representing great technological accomplishment for the second century BC.

The objective of this study was to determine the protective effect of glutamate (Glu) in Cu-induced oxidative injury in fish intestine in vivo and enterocytes in vitro. The results indicated that exposure to 6 mg/l Cu for 72 h induced the production of reactive oxygen species, thereby increasing protein oxidation and lipid peroxidation in enterocytes of grass carp in vitro. Cells exposed to Cu alone resulted in a significant increase in lactate dehydrogenase release, which is accompanied by depletions of antioxidants, including total superoxide dismutase (T-SOD), glutathione S-transferase (GST), glutathione reductase (GR), anti-superoxide anion (ASA), anti-hydroxy radical (AHR) activities and GSH content. Pre-treatment with Glu remarkably prevented the toxic effects of Cu on the T-SOD, GST, GR, AHR, and ASA activities and GSH content in enterocytes. However, Cu induced an adaptive increase in the activities of catalase and glutathione peroxidase (GPx). Glu supplementation further increased GPx activity in enterocytes. Interestingly, the experiment in vivo showed that Glu pre-supplementation significantly elevated SOD, GPx, GST, GR, ASA and AHR activities, as well as GSH content. Further results showed that pre-treatment with Glu could alleviate Cu-induced oxidative injury by elevating antioxidant enzyme activities through regulating the expression of NF-E2-related nuclear factor 2 (Nrf2) mRNA. Together, these results indicated that Glu could attenuate Cu-induced cellular oxidative damage in fish intestine, likely mediated through Nrf2 signalling pathways regulating mRNA expressions of antioxidant enzyme genes and synthesis of GSH.

Facilitated by recent establishment of terrestrial networks and satellite constellations of Automatic Identification System (AIS) receivers, ship trajectories are becoming increasingly available and the size of recorded trajectories is getting larger. Large sets of trajectories create problems of storing, transmitting and processing data. Using appropriate methods, an accurate representation of the original trajectories can be obtained by compressing redundant information, while maintaining the main characteristic elements. In this paper, a new scheme and the implementation of the Douglas-Peucker (DP) algorithm are presented, which can simplify AIS trajectories by extracting characteristic points. As for the simplification threshold, the solo parameter of the DP algorithm, a new AIS-based minimum ship domain evaluation method is proposed and acts as criteria for simplification threshold determination. Finally, a validation is made to examine the effectiveness of the DP simplification algorithm and the rationality of the simplification threshold. The result indicates that the DP algorithm can simplify AIS trajectories effectively; the simplification threshold is scientific and reasonable.

This study investigated the effects of glycinin on the growth, intestinal oxidative status, tight junction components, cytokines and apoptosis signalling factors of fish. The results showed that an 80 g/kg diet of glycinin exposure for 42 d caused poor growth performance and depressed intestinal growth and function of juvenile Jian carp (Cyprinus carpio var. Jian). Meanwhile, dietary glycinin exposure induced increases in lipid peroxidation and protein oxidation; it caused reductions in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities; and it increased MnSOD, CuZnSOD, GPx1b and GPx4a mRNA levels, suggesting an adaptive mechanism against stress in the intestines of fish. However, dietary glycinin exposure decreased both the activity and mRNA levels of nine isoforms of glutathione-S-transferase (GST) (α, μ, π, ρ, θ, κ, mGST1, mGST2 and mGST3), indicating toxicity to this enzyme activity and corresponding isoform gene expressions. In addition, glycinin exposure caused partial disruption of intestinal cell–cell tight junction components, disturbances of cytokines and induced apoptosis signalling in the distal intestines>mid intestines>proximal intestines of fish. Glycinin exposure also disturbed the mRNA levels of intestinal-related signalling factors Nrf2, Keap1a, Keap1b, eleven isoforms of protein kinase C and target of rapamycin/4E-BP. Interestingly, glutamine was observed to partially block those negative influences. In conclusion, this study indicates that dietary glycinin exposure causes intestinal oxidative damage and disruption of intestinal physical barriers and functions and reduces fish growth, but glutamine can reverse those negative effects in fish. This study provides some information on the mechanism of glycinin-induced negative effects.