Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease (IBD) characterized by complicated and relapsing inflammation in the gastrointestinal tract. SM934 is a water-soluble ...artemisinin analogue that shows anti-inflammatory and immuno-regulatory effects. In this study, we investigated the effects of SM934 on UC both in vivo and in vitro. A mouse model of colitis was established in mice by oral administration of 5% dextran sulfate sodium (DSS). SM934 (3, 10 mg/kg per day, ig) was administered to the mice for 10 days. After the mice were sacrificed, colons, spleens and mesenteric lymph nodes (MLNs) were collected for analyses. We showed that SM934 administration restored DSS-induced body weight loss, colon shortening, injury and inflammation scores. Furthermore, SM934 administration significantly decreased the disease activity index (DAI), histopathological scores, and myeloperoxidase (MPO) activities in colonic tissues. Moreover, SM934 administration dose-dependently decreased the mRNA and protein levels of DSS-induced pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), and the percentage of macrophages and neutrophils in colon tissues. The effects of SM934 on LPS-stimulated RAW 264.7 cells and THP-1-derived macrophages were examined in vitro. Treatment with SM934 (0.8, 8, 80 μmol/L) dose-dependently decreased the production of pro-inflammatory mediators in LPS-stimulated RAW264.7 cells and THP-1-derived macrophages via inhibiting activation of the NF-κB signaling. Our results reveal the protective effects of SM934 on DSS-induced colitis can be attributed to its suppressing effects on neutrophils and macrophages and its inhibitory role in the NF-κB signaling, suggests that SM934 might be a potential effective drug for ulcerative colitis.
Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving ...standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options.
This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18–65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III–IVA, excluding T3–4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12–16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111.
Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33–42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% 95% CI 80·4–90·6) than in the standard therapy group (75·7% 69·9–81·9), with a stratified hazard ratio of 0·50 (95% CI 0·32–0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 9% patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group.
The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.
The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation.
For the Chinese translation of the abstract see Supplementary Materials section.
The aberrant expression of myotubularin-related protein 2 (MTMR2) has been found in some cancers, but little is known about the roles and clinical relevance. The present study aimed to investigate ...the roles and clinical relevance of MTMR2 as well as the underlying mechanisms in gastric cancer (GC).
MTMR2 expression was examined in 295 GC samples by using immunohistochemistry (IHC). The correlation between MTMR2 expression and clinicopathological features and outcomes of the patients was analyzed. The roles of MTMR2 in regulating the invasive and metastatic capabilities of GC cells were observed using gain-and loss-of-function assays both in vitro and in vivo. The pathways involved in MTMR2-regulating invasion and metastasis were selected and identified by using mRNA expression profiling. Functions and underlying mechanisms of MTMR2-mediated invasion and metastasis were further investigated in a series of in vitro studies.
MTMR2 was highly expressed in human GC tissues compared to adjacent normal tissues and its expression levels were significantly correlated with depth of invasion, lymph node metastasis, and TNM stage. Patients with MTMR2
had significantly shorter lifespan than those with MTMR2
. Cox regression analysis showed that MTMR2 was an independent prognostic indicator for GC patients. Knockdown of MTMR2 significantly reduced migratory and invasive capabilities in vitro and metastases in vivo in GC cells, while overexpressing MTMR2 achieved the opposite results. MTMR2 knockdown and overexpression markedly inhibited and promoted the epithelial-mesenchymal transition (EMT), respectively. MTMR2 mediated EMT through the IFNγ/STAT1/IRF1 pathway to promote GC invasion and metastasis. Phosphorylation of STAT1 and IRF1 was increased by MTMR2 knockdown and decreased by MTMR2 overexpression accompanying with ZEB1 down-regulation and up-regulation, respectively. Silencing IRF1 upregulated ZEB1, which induced EMT and consequently enhanced invasion and metastasis in GC cells.
Our findings suggest that MTMR2 is an important promoter in GC invasion and metastasis by inactivating IFNγ/STAT1 signaling and may act as a new prognostic indicator and a potential therapeutic target for GC.
Solid‐oxide Li+ electrolytes of a rechargeable cell are generally sensitive to moisture in the air as H+ exchanges for the mobile Li+ of the electrolyte and forms insulating surface phases at the ...electrolyte interfaces and in the grain boundaries of a polycrystalline membrane. These surface phases dominate the total interfacial resistance of a conventional rechargeable cell with a solid–electrolyte separator. We report a new perovskite Li+ solid electrolyte, Li0.38Sr0.44Ta0.7Hf0.3O2.95F0.05, with a lithium‐ion conductivity of σLi=4.8×10−4 S cm−1 at 25 °C that does not react with water having 3≤pH≤14. The solid electrolyte with a thin Li+‐conducting polymer on its surface to prevent reduction of Ta5+ is wet by metallic lithium and provides low‐impedance dendrite‐free plating/stripping of a lithium anode. It is also stable upon contact with a composite polymer cathode. With this solid electrolyte, we demonstrate excellent cycling performance of an all‐solid‐state Li/LiFePO4 cell, a Li‐S cell with a polymer‐gel cathode, and a supercapacitor.
A perovskite that is stable in water with 3≤pH≤14 shows small interfacial resistance and excellent cycling performance in an all‐solid‐state Li/LiFePO4 cell, a Li‐S cell, and a supercapacitor.
The unclear Li+ local environment and Li+ conduction mechanism in solid polymer electrolytes, especially in a ceramic/polymer composite electrolyte, hinder the design and development of a new ...composite electrolyte. Moreover, both the low room-temperature Li+ conductivity and large interfacial resistance with a metallic lithium anode of a polymer membrane limit its application below a relatively high temperature. Here we have identified the Li+ distribution and Li+ transport mechanism in a composite polymer electrolyte by investigating a new solid poly(ethylene oxide) (PEO)-based NASICON–LiZr2(PO4)3 composite with 7Li relaxation time and 6Li → 7Li trace-exchange NMR measurements. The Li+ population of the two local environments in the composite electrolytes depends on the Li-salt concentration and the amount of ceramic filler. A composite electrolyte with a EO/Li+ ratio n = 10 and 25 wt % LZP filler has a high Li+ conductivity of 1.2 × 10–4 S cm–1 at 30 °C and a low activation energy owing to the additional Li+ in the mobile A2 environment. Moreover, an in situ formed solid electrolyte interphase layer from the reaction between LiZr2(PO4)3 and a metallic lithium anode stabilized the Li/composite-electrolyte interface and reduced the interfacial resistance, which provided a symmetric Li/Li cell and all-solid-state Li/LiFePO4 and Li/LiNi0.8Co0.1Mn0.1O2 cells a good cycling performance at 40 °C.
Infrared nonlinear optical (IR-NLO) materials are the key components in solid-state lasers for military and civilian applications. The development of IR-NLO materials remains urgent because the ...existing commercial materials AgGaS2 (AGS), AgGaSe2, and ZnGeP2 are limited for their own intrinsic shortcomings, for example, the lower laser damage thresholds (LDTs), the non-phase-matchable feature, and the strong two-photon absorption, respectively, exhibited in AgGaSe2 and ZnGeP2 at a conventional laser of 1 μm. Chalcogenides, halides, and iodates are known to be common sources of potential IR-NLO materials with good properties, of which the most in-depth studied is usually constructed by single anions. Recently, mixed-anion inorganic compounds are thought to be promising IR-NLO materials which can optimize comprehensive performances, especially balance the incompatibility between a large NLO coefficient and a high LDT in one material. This review focuses on the syntheses and crystal structures of mixed-anion inorganic IR-NLO materials, as well as the relationships of structure–property. Examples include four kinds of such compounds, i.e., mixed-anion chalcogenides, mixed-anion halides, mixed-anion chalcohalides, and other miscellaneous mixed-anion compounds including adducts, oxychalcogenides, oxyhalides, iodate fluorides, selenite fluorides, and halide borates. This work gives some exploring directions for novel IR-NLO materials, including how to optimize the NLO performances of the existing materials, from the inferred structure–property relationships of the potential mixed-anion inorganic NLO compounds.
Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic ...effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 μL exosomes via the tail vein (200 μg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1β release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.
Instead of carbon, Mo2C is used to modify the MoO2 material for the first time. The presence of highly conductive and electrochemical inactive Mo2C decreases the resistance of the charge transport ...and enhances the structural stability of MoO2 nanoparticles upon lithiation and delithiation, ensuring the superior cycling stability and high rate capability of the heteronanotubes. Cycled at 200 and 1000 mA g−1 for 140 cycles, the discharge capacities of the MoO2/Mo2C heteronanotubes remain to be 790 and 510 mAh g−1, respectively. This work demonstrates the potential of the novel heteronanotubes for application as an electrode material for high‐performance Li‐ion batteries.
Hierarchical porous MoO2/Mo2C heteronanotubes are obtained by using a mesoporous carbon CMK‐3 as both the template and the reactant. Taking advantage of the incorporation of high electronic conductive Mo2C and the hierarchical porous structure, the cycling and rate performance of the heteronanotubes is markedly enhanced.
The Advanced Space-based Solar Observatory (ASO-S) is a mission proposed for the 25th solar maximum by the Chinese solar community. The scientific objectives are to study the relationships between ...the solar magnetic field, solar flares and coronal mass ejections (CMEs). Three payloads are deployed: the Full-disk vector MagnetoGraph (FMG), the Lyman-α Solar Telescope (LST) and the Hard X-ray Imager (HXI). ASO-S will perform the first simultaneous observations of the photospheric vector magnetic field, non-thermal imaging of solar flares, and the initiation and early propagation of CMEs on a single platform. ASO-S is scheduled to be launched into a 720 km Sun-synchronous orbit in 2022. This paper presents an overview of the mission till the end of Phase-B and the beginning of Phase-C.
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