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Background: Colorectal cancer (CRC) is a significant public problem and the third cause of cancer-induced death all over the world. In addition, long noncoding RNA (lncRNA) has been reported as a vital mediator in human cancer. However, the precise role of lncRNA myocardial infarction associated transcript (MIAT) in CRC is unclear. Methods: The abundance of MIAT, miR-488-3p, and the type 1 insulin-like growth factor receptor (IGF1R) was measured by real-time quantitative polymerase chain reaction assay. The western blot assay was carried out to assess the protein level in CRC samples or control group. The cell activity, abilities of migration and invasion, and glycolysis were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell, and testing glucose consumption and lactate product, correspondingly. The target association between miR-488-3p, MIAT, or IGF1R was predicted and established by bioinformatics tools, dual-luciferase reporter, and RNA pull-down assays, correspondingly. The effects of MIAT silencing in vivo were analyzed by animal experiments. Results: LncRNA MIAT was upregulated in CRC sample and that was positively correlated with IGF1R expression. Loss-of-functional assay suggested that knockdown of MIAT impeded cell activity, migration, invasion, and glycolysis of CRC cells in vivo, along with xenograft growth in vivo. Moreover, silencing of IGF1R inhibited the progression of CRC. Therefore, overexpression of IGF1R could abolish silencing of MIAT-induced effects on CRC cells. Mechanistically, MIAT was a sponge for miR-488-3p, thereby regulating IGF1R expression in CRC. Conclusion: The present study confirmed that the "MIAT/miR-488-3p/IGF1R" pathway was involved in the development of CRC, which may be the target for developing therapeutic approaches for CRC.

Background Therapeutic monoclonal antibodies targeting complement C5 have proven to be a very effective approach for the treatment of complement-associated diseases including paroxysmal nocturnal hemoglobinuria (PNH). However, C5 antibody alone often cannot sufficiently block the alternative pathway (AP) of the complement system, nor reduce the deposition of C3b on the cell surface produced by C3 activation, and even increase the deposition, which is considered to be the cause of extravascular hemolysis in PNH patients treated with C5 antibody. As a natural and powerful complement inhibitor, CR1 has potential for drug development, but shows poor druggability due to low yield, short PK etc. Here, by fusing different CR1 fragments with the C5 antibody, we tried to obtain a fusion protein with good yield, purity and activity. Methods Candidate fusion proteins were generated by transient transfection expression and purified via Protein A affinity chromatography. Their bioactivities were investigated by in vitro classical pathway (CP)- and AP-mediated hemolysis assays. C3b deposition was calculated by flow cytometry. The PK/PD characteristics of optimized fusion proteins were tested in wildtype and human C5 transgenic mice, as well as cynomolgus monkeys. The therapeutic effect of the final product for complement-associated diseases was examined in collage antibody induced arthritis (CAIA) model mice. Results By fusing the mutated short consensus repeat (SCR) 1–5 fragment of CR1 to N-terminal of the heavy chain of C5 antibody, modifying surface charge and attaching linkers, we finally obtained a bifunctional complement inhibitory fusion protein with higher yield and superior CP and AP inhibitory activities. It showed a capability to inhibit C3 fragment deposition and therapeutic potential for CAIA, with one-week in vivo sustained bioactivity. Conclusions The fusion protein has the potential to become a more comprehensive complement activity-inhibiting drug, which may overcome the inefficiency of C5 antibody therapy.

The Western Qinling orogenic belt (WQOB) is one of the most important prospective gold districts in China, with widely distributed Indosinian intermediate–acidic intrusions. The Liziyuan Au deposit is a representative orogenic deposit in the northern WQOB, hosting several sections spatially associated with igneous rocks. The Au deposit is hosted by meta-sedimentary volcanic rocks of the Cambrian–Ordovician Liziyuan Group and the Tianzishan monzogranite. Two periods, including five stages of mineralization, are recognized in this area: an early metamorphic mineralization period (PI), including quartz–pyrite (Stage I) and banded quartz–polymetallic sulfide (Stage II) veins, and a later magmatic mineralization period (PII) including quartz–K-feldspar–pyrite–molybdenite veins (Stage III), quartz–polymetallic sulfide–chlorite ± calcite veinlets and stockwork (Stage IV), and late calcite–quartz veinlets (Stage V). Geochronological studies indicate a SHRIMP zircon U-Pb age of 236.1 Ma for the Tianzishan monzogranite, and our published ages of ore-bearing diorite porphyrite of the Suishizi section and granite porphyry of the Jiancaowan section being 213 and 212 Ma, respectively. Pyrites formed in association with PI and PII mineralization have well-defined Rb–Sr ages of 220 ± 7.5, 205.8 ± 8.7, and 199 ± 15 Ma, with close temporospatial coupling between mineralization and magmatism. The δ18O and δD values of fluid inclusions in Stage IV auriferous quartz veins range from −0.03‰ to +5.24‰ and −93‰ to −75‰, respectively, suggesting that mineralizing fluid was likely of magmatic origin. Three distinct ranges of δ34S values are identified in the studied sections (i.e., 7.04‰–9.12‰, −4.95‰ to −2.44‰, and 0.10‰–3.08‰), indicating a source containing multiple sulfur isotopes derived from magmatic and metamorphic fluids. The Liziyuan Au deposit is thus likely an orogenic deposit closely related to magmatism. Geochemical characteristics indicate that Tianzishan monzogranite is adakitic and was derived from thickened lower crust during Triassic orogenesis. The ore-bearing diorite porphyrite and granite porphyry formed in a post-collision extensional setting. Together with previous geological and geochemical data, our results indicate that the Liziyuan orogenic Au deposit was formed by early collisional–compressional metamorphism and late post-collision extensional magmatic fluids related to the evolution of the WQOB.

Defective cobalt oxide hydrate nanosheets with abundant oxygen vacancies and high porosity were fabricated via room-temperature reductive treatments, and they performed well in the electrocatalytic oxidation reaction of 5-hydroxymethylfurfural.

Objective: To observe the clinical effect of modified Yu Rong San gel eye mask in the treatment of dark circles. Methods: 96 cases of patients with dark circles were randomly divided into treatment group and control group. In the control group and the treatment group, the common eye mask and the modified Yu Rong San gel eye mask were applied to the black circle area respectively. After 15min, water was used to wash the face, the application of the mask for one time a day, four weeks, one course, and three courses were observed. Results: After three courses of treatment, the total effective rate of the treatment group was higher than that of the control group (P

Active crustal deformation of the Tibetan plateau results in destructive continental earthquakes and is therefore the focus of intense research interest. Increases in the numbers of Global Navigation Satellite System (GNSS) networks and stations deployed in Tibet are allowing for the characterization of crustal deformation during different phases of the earthquake cycle. Here, we present the status of a “seismic + high-rate GNSS” network deployed in eastern Tibet, including its data streams and data processing system, with the goal of supporting quasi-real-time earthquake source determination. Furthermore, we use this network to test a prototype earthquake early warning (EEW) system using data from the 2008 Mw 7.9 Wenchuan earthquake, the 2011 Mw 9.0 Tohoku earthquake, and 2200 synthetic earthquakes with moment magnitudes ranging from 6.5 to 7.5 on the southern Longmen Shan fault and Anninghe fault. The results show that our current methodology could respond to moderate-to-large earthquakes (magnitude 7+) within tens of seconds after the origin time, with implications for EEW applications in China.

Purpose The purpose of this study is to propose an isogeometric analysis (IGA) approach for solving the Reynolds equation in textured piston ring cylinder liner (PRCL) contacts. Design/methodology/approach The texture region is accurately and conveniently expressed by non-uniform rational B-splines (NURBS) besides hydrodynamic pressure and the oil film density ratio is represented in this mathematical form. A quadratic programming method combined with a Lagrange multiplier method is developed to address the cavitation issue. Findings The comparison with the results solved by an analytical method has verified the effectiveness of the proposed approach. In the study of the PRCL contact with two-dimensional circular dimple textures, the solution of the IGA approach shows high smoothness and accuracy, and it well satisfies the complementarity condition in the case of cavitation presence. Originality/value This paper proposes an IGA approach for solving the Reynolds equation in textured PRCL contacts. Its novelty is reflected in three aspects. First, NURBS functions are simultaneously used to express the solution domain, texture shape, hydrodynamic pressure and oil density ratio. Second, the streamline upwind/Petrov–Galerkin method is adopted to create a weak form for the Reynolds equation that takes the oil density ratio as a first-order unknown variable. Third, a quadratic programming approach is developed to impose the complementarity conditions between the hydrodynamic pressure and the oil density ratio.

Aims Woody plants are widely distributed in various grassland types along the altitudinal/climatic gradients in Xinjiang, China. Considering previously reported change in carbon (C) storage following woody plant encroachment in grasslands and the mediating effect of climate on this change, we predicted that a positive effect of woody plants on plant C storage in semiarid grasslands may revert to a negative effect in arid grasslands. We first investigated the spatial variation of aboveground C (AGC) and belowground C (BGC) storage among grassland types and then tested our prediction. Methods We measured the living AGC storage, litter C (LC) and BGC storage of plants in two physiognomic types, wooded grasslands (aboveground biomass of woody plants at least 50%) and pure grasslands without woody plants in six grassland types representing a gradient form semiarid to arid conditions across Xinjiang. Important Findings Living AGC, LC, BGC and total plant C storage increased from desert to mountain meadows. These increases could also be explained by increasing mean annual precipitation (MAP) or decreasing mean annual temperature (MAT), suggesting that grassland types indeed represented an aridity gradient. Woody plants had an effect on the plant C storage both in size and in distribution relative to pure grasslands. The direction and strength of the effect of woody plants varied with grassland types due to the mediating effect of the climate, with wetter conditions promoting a positive effect of woody plants. Woody plants increased vegetation-level AGC through their high AGC relative to herbaceous plants. However, more negative effects of woody plants on herbaceous plants with increasing aridity led to a weaker increase in the living AGC in arid desert, steppe desert and desert steppe than in the less arid other grassland types. Under greater aridity (lower MAP and higher MAT), woody plants allocated less biomass to roots and had lower BGC and had a more negative impact on herbaceous plant production, thereby reducing vegetation-level BGC in the desert, steppe desert and desert steppe. In sum, this resulted in a negative effect of woody plants on total plant C storage in the most arid grasslands in Xinjiang. As a consequence, we predict that woody plant encroachment may decrease rather than increase C storage in grasslands under future drier conditions.

Colon and rectal cancers are the leading causes of cancer-related deaths in the United States and effective targeted therapies are in need for treating them. Our genomic analyses show hemizygous deletion of TP53, an important tumor suppressor gene, is highly frequent in both cancers, and the 5-year survival of patients with the more prevalent colon cancer is significantly reduced in the patients with the cancer harboring such deletion, although such reduction is not observed for rectal cancer. Unfortunately, direct targeting TP53 has been unsuccessful for cancer therapy. Interestingly, POLR2A, a gene essential for cell survival and proliferation, is almost always deleted together with TP53 in colon and rectal cancers. Therefore, RNA interference (RNAi) with small interfering RNAs (siRNAs) to precisely target/inhibit POLR2A may be an effective strategy for selectively killing cancer cells with TP53 deficiency. However, the difficulty of delivering siRNAs specifically into the cytosol where they perform their function, is a major barrier for siRNA-based therapies. Here, metformin bicarbonate (MetC) is synthesized to develop pH-responsive MetC-nanoparticles with a unique “bomb” for effective cytosolic delivery of POLR2A siRNA, which greatly facilitates its endo/lysosomal escape into the cytosol and augments its therapeutic efficacy of cancer harboring TP53 deficiency. Moreover, the MetC-based nanoparticles without functional siRNA show notable therapeutic effect with no evident toxicity or immunogenicity.

Aims We have found a positive effect of woody plants on total plant carbon (C) storage in less arid grassland was shifted to a negative effect in arid grasslands in Xinjiang, a typical arid region in China. In this study, we further assessed the effects of woody plants on aboveground primary productivity (ANPP) and soil organic C (SOC) storage and explored the mediation of climate conditions on these effects. We also aimed to elucidate the reasons for the effects on SOC storage in terms of ANPP and belowground biomass C (BGC). Methods We compared the difference in ANPP and SOC content between pure and wooded grasslands and evaluated the relation between SOC content and ANPP and BGC in six grassland types along the altitude (climatic) gradients. Results In three arid types, woody plants had a negative effect on ANPP due to their more negative impacts on herbaceous plants and lower ANPP. The negative effect on ANPP and BGC led to that on SOC storage in these types. In less arid types, there had a positive effect on ANPP because woody plants had weaker negative impacts on herbaceous plants and higher ANPP. A positive effect on ANPP combined with a neutral impact on BGC contributed to a positive effect on SOC storage in these types. Conclusions Woody plants had a negative effect on ANPP and SOC storage in most arid grasslands in Xinjiang. We predicted that increasing aridity may reduce ANPP and SOC storage with woody plant encroachment in the future.

A simple and efficient biphasic system consisting of H2O, tetrahydrofuran (THF), cyclohexane (CHX) and Al2(SO4)3 was employed to convert cellulose into 5-hydroxymethylfurfural (HMF) with high yield of 71.2%. The real volumes of organic phase (Vorg) and aqueous phase (Vaque) of the biphasic system at reaction temperature were measured to found out that over 80% of the added H2O was dissolved into the organic phase at reaction temperature, leading to high Vorg/Vaque (over 44/1) and high concentration of Al2(SO4)3 (over 0.34 g/mL) in aqueous phase. The high concentration of Al2(SO4)3 in aqueous phase could efficiently catalyze the conversion of cellulose into HMF, while the high Vorg/Vaque could protect the formed HMF from rehydration, all of which are responsible for the high efficiency of the system on conversion of cellulose into HMF. The addition of CHX into reaction mixture could decrease the solubility of Al2(SO4)3 and H2O in the organic phase, which could improve the stability of HMF in the reaction system, resulting higher yield of HMF from cellulose. Because of the high Vorg/Vaque of the reaction system, one microemulsion-like system and liquid film catalytic model are proposed for the cellulose-to-HMF process.

The association between biodiversity and belowground biomass (BGB) remains a central debate in ecology. In this study, we compared the variations in species richness (SR) and BGB as well as their interaction in the top (0–20 cm), middle (20–50 cm) and deep (50–100 cm) soil depths among 8 grassland types (lowland meadow, temperate desert, temperate desert steppe, temperate steppe desert, temperate steppe, temperate meadow steppe, mountain meadow and alpine steppe) and along environmental gradients (elevation, energy condition (annual mean temperature (AMT) and potential evapotranspiration (PET)), and mean annual precipitation (MAP)) based on a 2011–2013 survey of 379 sites in Xinjiang, Northwest China. The SR and BGB varied among the grassland types. The alpine steppe had a medium level of SR but the highest BGB in the top soil depth, whereas the lowland meadow had the lowest SR but the highest BGB in the middle and deep soil depths. The SR and BGB in the different soil depths were tightly associated with elevation, MAP and energy condition; however, the particular forms of trends in SR and BGB depended on environmental factors and soil depths. The relationship between SR and BGB was unimodal in the top soil depth, but SR was positively related with BGB in the middle soil depth. Although elevation, MAP, energy condition and SR had significant effects on BGB, the variations in BGB in the top soil depth were mostly determined by elevation, and those in the middle and deep soil depths were mainly affected by energy condition. These findings highlight the importance of environmental factors in the regulations of SR and BGB as well as their interaction in the grasslands in Xinjiang.

Phytic acid derived carbons provide an excellent dual functionality for lithium- and sodium-ion batteries under tuned pyrolysis temperature. The acquired carbon at 800 °C is suitable to lithium-ion batteries due to its high surface area (1426.75 m2 g−1) and hierarchical porous structure. Tested against Li, it delivers a high capacity of 1787 mA h g−1 and coulombic efficiency of 82%. Another obtained carbon at 950 °C is suitable to sodium-ion batteries due to its large lattice spacing (0.4115 nm), defect density and phosphorus content (1.12%). Tested against Na, it delivers the initial specific capacity of 387 mA h g−1 with coulombic efficiency of 50.6%, and maintains a high reversible capacity of 300 mA h g−1 after 300 cycles at a current rate of 100 mA g−1. High energy density and power density are also acquired in lithium- and sodium-ion batteries. The effects of pyrolysis temperature on microstructure and electrochemical behaviours of carbons are discussed detailedly. It is proved that the carbons with tuned pyrolysis temperature behave differently due to a synergistic effect among the lattice spacing, graphitization degree, defect density, phosphorus concentration and porous structure.

The design of efficient and low-cost electrocatalysts for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) remains a significant challenge for the hydrogen production. Herein, CuO nanowires encapsulated by Ni and NiFe hydroxides (CuO@Ni/NiFe hydroxides) in-situ grown on the surface of Cu plate were fabricated via chemical oxidation-calcination process and room-temperature interfacial Galvanic reaction, which were applied to the efficient overall water splitting. Thanks to the improved specific surface area and the conductivity, the optimized core-shell CuO@Ni/NiFe hydroxides nanowire array exhibit impressive OER performance as well as HER activity in 1 M KOH which delivers a current density of 10 mA cm −2 at an overpotential of 230 mV for OER and 125 mV for HER. Significantly, core-shell CuO@Ni/NiFe hydroxides used as bifunctional catalysts for an overall water splitting can achieve a low onset potential of ∼1.50 V and a relatively high specific current density of 40 mA cm −2 at ∼1.73 V. This feasible strategy provides an accumulative opportunity for fabricating low-cost, effective bifunctional catalysts for overall water splitting.

Achieving 'clinical cure' in children with chronic hepatitis B (CHB) with safe and effective antiviral treatment is an unmet medical need. Peginterferon (PegIFN) has higher hepatitis B s antigen (HBsAg) clearance than nucleoside analogs (NUC). Currently, studies on interferon (IFN) in the treatment of Chinese children with CHB are relatively rare. This study aimed to further explore the efficacy of PegIFNα-2a as an antiviral treatment in Chinese children and analyse the long-term follow-up after drug discontinuation. We enrolled 118 patients with CHB (2-16 years old, 79 cases are males) treated with PegIFNα-2a by the author in the Third People's Hospital of Kunming City from February 2009 to February 2015. The course of treatment was 52 weeks, with a follow-up period of 104 weeks. All the patients completed at least 1 dose, of which 104 completed at least 36 weeks of treatment and 104 weeks of follow-up. During treatment and follow-up, indicators such as alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA and HBV serological markers were monitored, and the efficacy and safety of PegIFNα-2a in the treatment of CHB patients were observed. Hepatitis B e antigen (HBeAg) clearance and seroconversion rates were 53.8% and 49%, respectively, when the drug was discontinued; 72.1% and 72.1%, respectively, at the end of the follow-up; and 98.2% and 98%, respectively, for sustained response. HBsAg clearance and seroconversion rates were 48.1% and 47.1%, respectively, when the drug was discontinued; 53.8% and 52.9%, respectively, at the end of the follow-up; and 94% and 95.9%, respectively, for sustained response. The HBV DNA suppression rate was 89.4% when the drug was discontinued, 90.4% at the end of the follow-up and 97.8% for sustained response. Two patients had virological relapse (2.3%) during follow-up; however, no clinical relapse occurred. Multivariate regression analysis showed that genotype B, weight < 25 kg or between 25 and 45 kg, and reduction of HBsAg by more than 1 log following 24 weeks of treatment were independent predictors of HBsAg clearance at the end of follow-up. Adverse events that occurred during treatment were similar to those reported in previous clinical studies on PegIFN. The results of this study showed that PegIFN was safe and effective in the treatment of children with CHB, and sustained response could be achieved after treatment. PegIFN treatment of children with CHB helps more achieve 'clinical cure'.

TP53 is the most frequently mutated or deleted gene in triple negative breast cancer (TNBC). Both the loss of TP53 and the lack of targeted therapy are significantly correlated with poor clinical outcomes, making TNBC the only type of breast cancer that has no approved targeted therapies. Through in silico analysis, we identified POLR2A in the TP53-neighboring region as a collateral vulnerability target in TNBC tumours, suggesting that its inhibition via small interfering RNA (siRNA) may be an amenable approach for TNBC targeted treatment. To enhance bioavailability and improve endo/lysosomal escape of siRNA, we designed pH-activated nanoparticles for augmented cytosolic delivery of POLR2A siRNA (siPol2). Suppression of POLR2A expression with the siPol2-laden nanoparticles (siPol2@NPs) leads to enhanced growth reduction of tumours characterised by hemizygous POLR2A loss. These results demonstrate the potential of the pH-responsive nanoparticle and the precise POLR2A targeted therapy in TNBC harbouring the common TP53 genomic alteration.

Asymmetric supercapacitors (ASCs) as a promising candidate to complement batteries, have been studied for decades due to the relatively high power density. The energy storage of ASCs is significantly affected by the well-designed electrode material and delicate charge balance of electrodes. With the hope to design better supercapacitor devices, we firstly synthesize C-NiO/NiCo2O4 nanocomposites with the modified nanowire structure and a small amount of carbon, effectively boosting the specific capacitance and cyclic-stability. In addition, a multi-electrode system is developed to investigate match degrees of C-NiO/NiCo2O4//AC ACSs, and the inter-restricted behavior of positive and negative electrodes. By this real-time electrochemical method, the potential contributions of electrodes in ASCs are further revealed during charge/discharge process. Therefore, ASC device with optimal match degree delivers areal capacitance up to 3482 mF cm−2, and the maximum energy and power density of 42.69 mWh cm−3 and 1.66 W cm−3. Importantly, this work throws light on the fundamental study for supercapacitors in terms of materials design and charge match degrees.