Tumor initiation and growth depend on its microenvironment in which cancer-associated fibroblasts （CAFs） in tumor stroma play an important role. Prostaglandin E2 （PGE2） and interleukin （IL）-6 signal ...pathways are involved in the crosstalk between tumor and stromal cells. However, how PGE2-mediated signaling modulates this crosstalk remains unclear. Here, we show that microRNA （miR）-149 links PGE2 and IL-6 signaling in mediating the crosstalk between tumor cells and CAFs in gastric cancer （GC）. miR-149 inhibited fibroblast activation by targeting IL-6 and miR-149 expression was substantially suppressed in the CAFs of GC. miR-149 negatively regulated CAFs and their effect on GC development both in vitro and in vivo. CAFs enhanced epithelial-to-mesenchymal transition （EMT） and the stem-like properties of GC cells in a miR-149-1L-6-dependent manner. In addition to IL-6, PGE2 receptor 2 （PTGER2/EP2） was revealed as another potential target of miR-149 in fibroblasts. Furthermore, H. pylori infection, a leading cause of human GC, was able to induce cyclooxygenase-2 （COX-2）/PGE2 signaling and to enhance PGE2 production, resulting in the hypermethylation of miR-149 in CAFs and increased IL-6 secretion. Our findings indicate that miR-149 mediates the crosstalk between tumor cells and CAFs in GC and highlight the potential of interfering miRNAs in stromal cells to improve cancer therapy.
AbstractObjectiveTo investigate whether vitamin D supplementation is associated with lower mortality in adults.DesignSystematic review and meta-analysis of randomised controlled trials.Data ...sourcesMedline, Embase, and the Cochrane Central Register from their inception to 26 December 2018.Eligibility criteria for selecting studiesRandomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group.Main outcome measuresAll cause mortality.Results50 trials with a total of 74 655 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I2=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.85, 0.74 to 0.97, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation (P for interaction=0.04); neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality.ConclusionsVitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 15%. Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality.Study registrationPROSPERO registration number CRD42018117823.
We propose a novel approach to generate distributed fiber sensing system based on phase-sensitive optical time domain reflectometer (Φ-OTDR) and phase-generated carrier demodulation algorithm. An ...unbalanced Michelson interferometer is introduced at the receiving end of the system. The back Rayleigh scattering light from a certain position along the sensing fiber would interfere to generate interference light signal versus time, whose phase carries the sensing information. Phase-generated carrier demodulation algorithm is proposed and carried out to recover the phase information. A single frequency vibration event is applied to a certain position along the sensing fiber and we realize to demodulate it correctly. The noise level of the phase sensitive OTDR system is about 3 × 10 -3 rad/VHz and a signal to noise ratio about 30.45 dB is achieved. The maximum sensing length and the spatial resolution of the Φ-OTDR system are 10 km and 6 m with pulse repetition rate at 10 kHz and 6 m fiber delay in MI with interrogating pulse width of 30 ns.
Ag-Based nanocomposites, including supported Ag nanocomposites and bimetallic Ag nanocomposites, have been intensively investigated as highly efficient catalysts because of their high activity and ...stability, easy preparation, low cost, and low toxicity. Herein, we systematically summarize and comprehensively evaluate versatile synthetic strategies for the preparation of Ag-based nanocomposites, and outline their recent advances in catalytic oxidation, catalytic reduction, photocatalysis and electrocatalysis. In addition, the challenges and prospects related to Ag-based nanocomposites for various catalytic applications are also discussed. In light of the most recent advances in Ag-based nanocomposites for catalysis applications, this review provides a comprehensive assessment on the material selection, synthesis and catalytic characteristics of these catalysts, which offers a strategic guide to build a close connection between Ag nanocomposites and catalysis applications.
Developing Type‐I photosensitizers is considered as an efficient approach to overcome the deficiency of traditional photodynamic therapy (PDT) for hypoxic tumors. However, it remains a challenge to ...design photosensitizers for generating reactive oxygen species by the Type‐I process. Herein, we report a series of α,β‐linked BODIPY dimers and a trimer that exclusively generate superoxide radical (O2−.) by the Type‐I process upon light irradiation. The triplet formation originates from an effective excited‐state relaxation from the initially populated singlet (S1) to triplet (T1) states via an intermediate triplet (T2) state. The low reduction potential and ultralong lifetime of the T1 state facilitate the efficient generation of O2−. by inter‐molecular charge transfer to molecular oxygen. The energy gap of T1‐S0 is smaller than that between 3O2 and 1O2 thereby precluding the generation of singlet oxygen by the Type‐II process. The trimer exhibits superior PDT performance under the hypoxic environment.
Heavy‐atom‐free boron dipyrromethene (BODIPY)‐based photosensitizers generate ROS exclusively by the Type‐I process upon near‐infrared light illumination for tumor ablation.
Autophagy is an important mechanism for cellular self‐digestion and basal homeostasis. This gene‐ and modulator‐regulated pathway is conserved in cells. Recently, several studies have shown that ...autophagic dysfunction is associated with pulmonary hypertension (PH). However, the relationship between autophagy and PH remains controversial. In this review, we mainly introduce the effects of autophagy‐related genes and some regulatory molecules on PH and the relationship between autophagy and PH under the conditions of hypoxia, monocrotaline injection, thromboembolic stress, oxidative stress, and other drugs and toxins. The effects of other autophagy‐related drugs, such as chloroquine, 3‐methyladenine, rapamycin, and other potential therapeutic drugs and targets, in PH are also described.
Autophagic dysfunction is associated with pulmonary hypertension (PH). However, the relationship between autophagy and PH remains controversial. In this review, we mainly introduce the effects of autophagy‐related genes and some regulatory molecules on PH and the relationship between autophagy and PH under the conditions of hypoxia, monocrotaline injection, thromboembolic stress, oxidative stress, and other drugs and toxins.
Although urine‐based human papillomavirus (HPV) detection is promising in cervical cancer screening, it has not yet been well‐developed. Women aged 30–65 were invited to participate in the current ...study to provide one urine and two paired vaginal samples. Urine was detected by polymerase chain reaction (PCR)‐based HPV test (urine‐based HPV test). Two vaginal samples were tested by careHPV and GenPlex® HPV genotyping assay, respectively. Women with vaginal HPV positive were called back for colposcopy and biopsied if clinically indicated. The consistency was 79.0% (κ = 0.563) and 80.5% (κ = 0.605) between the urine‐based HPV test, careHPV test, and GenPlex® HPV genotyping assay. Against CIN2 detection, the careHPV test showed 77.4% sensitivity, and 71.0% specificity, while the GenPlex® HPV genotyping assay had a sensitivity of 100% and a specificity of 58.7%. For urine‐based HPV test, the corresponding rates were 96.8% and 58.7%. Moreover, no significant differences were observed between the urine‐based HPV test and careHPV test (p = 0.3395) and GenPlex® HPV genotyping assay (p = 0.338). The newly developed urine‐based HPV test demonstrated acceptable consistency and comparable clinical performance with referenced HPV tests for vaginal samples. Therefore, urine‐based HPV detection could be a useful alternative for women with difficulties to access cervical cancer screening.
Implementing selective-area p-type doping through ion implantation is the most attractive choice for the fabrication of GaN-based bipolar power and related devices. However, the low activation ...efficiency of magnesium (Mg) ions and the inevitable surface decomposition during high-temperature activation annealing process still limit the use of this technology for GaN-based devices. In this work, we demonstrate successful p-type doping of GaN using protective coatings during a Mg ion implantation and thermal activation process. The p-type conduction of GaN is evidenced by the positive Seebeck coefficient obtained during thermopower characterization. On this basis, a GaN p-i-n diode is fabricated, exhibiting distinct rectifying characteristics with a turn-on voltage of 3 V with an acceptable reverse breakdown voltage of 300 V. Electron beam induced current (EBIC) and electroluminescent (EL) results further confirm the formation of p-type region due to Mg ion implantation and subsequent thermal activation. This repeatable and uniform manufacturing process can be implemented in mass production of GaN devices for versatile power and optoelectronic applications.
The construction of host–guest-binding-induced phosphorescent supramolecular assemblies has become one of increasingly significant topics in biomaterial research. Herein, we demonstrate that the ...cucurbit8uril host can induce the anthracene-conjugated bromophenylpyridinium guest to form a linear supramolecular assembly, thus facilitating the enhancement of red fluorescence emission by the host-stabilized charge-transfer interactions. When the anthryl group is photo-oxidized to anthraquinone, the obtained linear nanoconstructs can be readily converted into the homoternary inclusion complex, accompanied by the emergence of strong green phosphorescence in aqueous solution. More intriguingly, dual organelle-targeted imaging abilities have been also distinctively achieved in nuclei and lysosomes after undergoing photochemical reaction upon UV irradiation. This photooxidation-driven purely organic room-temperature phosphorescence provides a convenient and feasible strategy for supramolecular organelle identification to track specific biospecies and physiological events in the living cells.
Cadmium (Cd) is highly toxic to most organisms, but some rare plant species can hyperaccumulate Cd in aboveground tissues without suffering from toxicity. The mechanism underlying Cd detoxification ...by hyperaccumulators is interesting but unclear.
Here, the heavy metal ATPase 3 (SpHMA3) gene responsible for Cd detoxification was isolated from the Cd/zinc (Zn) hyperaccumulator Sedum plumbizincicola. RNA interference (RNAi)-mediated silencing and overexpression of SpHMA3 were induced to investigate its physiological functions in S. plumbizincicola and a nonhyperaccumulating ecotype of Sedum alfredii.
Heterologous expression of SpHMA3 in Saccharomyces cerevisiae showed Cd-specific transport activity. SpHMA3 was highly expressed in the shoots and the protein was localized to the tonoplast. The SpHMA3-RNAi lines were hypersensitive to Cd but not to Zn, with the growth of shoots and young leaves being severely inhibited by Cd. Overexpressing SpHMA3 in the nonhyperaccumulating ecotype of S. alfredii greatly increased its tolerance to and accumulation of Cd, but not Zn.
These results indicate that elevated expression of the tonoplast-localized SpHMA3 in the shoots plays an essential role in Cd detoxification, which contributes to the maintenance of the normal growth of young leaves of S. plumbizincicola in Cd-contaminated soils.
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