Display omitted
•Irradiation stents were significantly associated with a decrease in the rate of stent restenosis.•Patients in the irradiation stent group obtained longer survival time.•Placement of ...irradiation stent did not add to the difficulty of technique.•The use of irradiation stent did not increase the incidence of treatment related complications.
Placement of an irradiation stent has been demonstrated to offer longer patency and survival than an uncovered self-expandable metallic stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO). We aim to further assess the efficacy of an irradiation stent compared to an uncovered SEMS in those patients.
We performed a randomized, open-label trial of participants with unresectable MBO at 20 centers in China. A total of 328 participants were allocated in parallel to the irradiation stent group (ISG) or the uncovered SEMS group (USG). Endpoints included stent patency (primary), technical success, relief of jaundice, overall survival, and complications.
The first quartile stent patency time (when 25% of the patients experienced stent restenosis) was 212 days for the ISG and 104 days for the USG. Irradiation stents were significantly associated with a decrease in the rate of stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at 360 days; p = 0.010). Patients in the ISG obtained longer survival time (median 202 days vs. 140 days; p = 0.020). No significant results were observed in technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%; p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p = 0.841).
Insertion of irradiation stents instead of uncovered SEMS could improve patency and overall survival in patients with unresectable MBO.
For patients with unresectable malignant biliary obstruction (MBO), placement of a self-expandable metallic stent (SEMS) is a recommended palliative modality to relieve pruritus, cholangitis, pain, and jaundice. However, restenosis is a main pitfall after stent placement. Data from this first multicenter randomized controlled trial showed that insertion of an irradiation stent provided longer patency and better survival than a conventional metal stent.
ClinicalTrials.gov ID: NCT02001779.
T cells are critical mediators of antigen‐specific immune responses and are common targets for immunotherapy. Biomaterial scaffolds have previously been used to stimulate antigen‐presenting cells to ...elicit antigen‐specific immune responses; however, structural and molecular features that directly stimulate and expand naïve, endogenous, tumor‐specific T cells in vivo have not been defined. Here, an artificial lymph node (aLN) matrix is created, which consists of an extracellular matrix hydrogel conjugated with peptide‐loaded‐MHC complex (Signal 1), the co‐stimulatory signal anti‐CD28 (Signal 2), and a tethered IL‐2 (Signal 3), that can bypass challenges faced by other approaches to activate T cells in situ such as vaccines. This dynamic immune‐stimulating platform enables direct, in vivo antigen‐specific CD8+ T cell stimulation, as well as recruitment and coordination of host immune cells, providing an immuno‐stimulatory microenvironment for antigen‐specific T cell activation and expansion. Co‐injecting the aLN with naïve, wild‐type CD8+ T cells results in robust activation and expansion of tumor‐targeted T cells that kill target cells and slow tumor growth in several distal tumor models. The aLN platform induces potent in vivo antigen‐specific CD8+ T cell stimulation without the need for ex vivo priming or expansion and enables in situ manipulation of antigen‐specific responses for immunotherapies.
Here, an injectable T cell‐stimulating scaffold, the artificial lymph node (aLN), is developed that works with the host immune system to create an immunostimulatory niche. The aLN can activate and expand rare, antigen‐specific CD8+ T cells from fully naïve, endogenous populations. aLN stimulated cells are fully functional and synergize with immune checkpoint blockade to reduce tumor burden and prolong survival.
Display omitted
In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed ...that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ± 13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications.
Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.
Summary
Dysfunction of endothelial progenitor cells (EPC) contribute to diabetic vascular disease. MicroRNAs (miRNAs) are key regulators of diverse cellular processes, including angiogenesis. We ...recently reported that downregulated miR‐130a in patients with Type 2 diabetes mellitus (DM) results in EPC dysfunction, including increased apoptosis, likely via its target runt‐related transcription factor 3 (Runx3). However, whether miR‐130a affects the autophagy of EPC is unknown. The aim of the present study was to explore the effects of miR‐130a on the autophagy and cell death of EPC, as well as their expression of Beclin 1 (BECN1; an initiator of autophagosome formation) and the anti‐apoptotic protein Bcl2 (which binds to and inactivates BECN1), and the role of Runx3 in mediating these effects. The EPC were cultured from peripheral blood mononuclear cells of diabetic patients and non‐diabetic controls. Cells were transfected with an miR‐130a inhibitor, or mimic‐miR‐130a or mimic‐miR‐130a plus lentiviral vector expressing Runx3 to manipulate miR‐130a and/or Runx3 levels. The number of autophagosomes was counted under transmission electron microscopy and cell death was examined by flow cytometry. The mRNA expression of Beclin1 was measured by real‐time polymerase chain reaction and the protein expression of Beclin1 and Bcl2 was determined by western blotting. Both the number of autophagosomes and Beclin1 expression were increased in EPC from patients with DM. Inhibition of miR‐130a increased the number of autophagosomes and Beclin1 expression, but attenuated Bcl2 expression. Overexpression of miR‐130a decreased the number of autophagosomes, cell death and Beclin1 expression, but promoted Bcl2 expression; these effects were mediated by Runx3. In conclusion, miR‐130a is important for maintaining normal autophagy levels and promoting the survival of EPC via regulation of Bcl‐2 and Beclin1 expression, via Runx3. MiR‐130a may be a regulator linking apoptosis and the autophagy of EPC.
Stabilizing water‐sensitive reaction intermediates is challenging but desirable for guiding reactions to desired products in water. Herein, we report that labile imine and hemiaminal functional ...groups can be stabilized inside a synthetic container compound, a water‐soluble naphthotube. The naphthotube features a primary amine group anchored in a cavity with both hydrogen bonding sites and hydrophobic surfaces. Aldehydes in bulk aqueous solution are trapped in the cavity by the amine to form hemiaminals stabilized through hydrogen bonding and hydrophobic effects. Dehydration of the hemiaminal to the imine is favored by the release of water from the hydrophobic microenvironment. Both the hemiaminals and imines can be detected at room temperature by NMR spectroscopy and mass spectrometry.
An amine‐functionalized naphthotube featuring a cavity with both hydrogen bonding sites and hydrophobic surfaces has been developed that traps aldehydes in bulk aqueous solution through the formation of hemiaminals. Dehydration of the hemiaminal to the imine is favored by the release of water from the hydrophobic microenvironment. Both the hemiaminals and imines could be detected by NMR spectroscopy and mass spectrometry at room temperature.
The injection process of powder fuel directly affects the scramjet operating performance. This study analyzes gas-particle two-phase flow during powder fuel injection. The macroscopic behavior of ...powder fuel jets under different injection pressure conditions is characterized using the high-speed shadow imaging technology. Simultaneously, the coupled model of computational fluid dynamics-discrete element method is employed to determine the experimental conditions, and the flow field structure and gas-particle interactions are analyzed. The results show that the development of powder fuel jets mainly occurs in three stages: the low-speed development stage, the high-speed development stage, and the stable stages. A long transition period exists between different stages, and the transition time decreases with increasing injection pressure. In the low-speed development stage, the powder fuel jet initially develops slowly and then develops rapidly. In the high-speed development stage, the jet initially develops rapidly and then develops slowly. The jet in the stable stage is classified into the powder particle, fluidized gas, and free flow regions. The distribution range of the particles decreases with increasing injection pressure. The fluidized gas velocity and drag force curve on the axis experience many fluctuations, and the particle velocity is almost always accelerated. Fluidized gas velocity, drag force, particle velocity, and particle acceleration distance increase with the injection pressure.
Display omitted
•The macroscopic behavior of the powder fuel jets was characterized by high-speed shadow imaging technology.•Three stages of the development of powder fuel jets were discovered.•It is found that the jet shows obvious stratification in the stable stage.•The flow process of the gas-particle two-phase jet was studied in detail.
Metal oxide‐based resistive random access memory (RRAM) has attracted a lot of attention for its scalability, temperature robustness, and potential to achieve machine learning. However, a thick oxide ...layer results in relatively high program voltage while a thin one causes large leakage current and a small window. Owing to these fundamental limitations, by optimizing the oxide layer itself a novel interface engineering idea is proposed to reduce the programming voltage, increase the uniformity and on/off ratio. According to this idea, a molybdenum disulfide (MoS2)–palladium nanoparticles hybrid structure is used to engineer the oxide/electrode interface of hafnium oxide (HfOx)‐based RRAM. Through its interface engineering, the set voltage can be greatly lowered (from −3.5 to −0.8 V) with better uniformity under a relatively thick HfOx layer (≈15 nm), and a 30 times improvement of the memory window can be obtained. Moreover, due to the atomic thickness of MoS2 film and high transmittance of ITO, the proposed RRAM exhibits high transparency in visible light. As the proposed interface‐engineering RRAM exhibits good transparency, low SET voltage, and a large resistive switching window, it has huge potential in data storage in transparent circuits and wearable electronics with relatively low supply voltage.
Based on the idea of 2D–0D interface engineering, indium–tin–oxide (ITO)/HfOx/MoS2–Pd NPs/ITO resistive random access memory (RRAM) is fabricated. Compared to conventional ITO/HfOx/ITO RRAM, the SET voltage is reduced and the memory window is enhanced. Also, this RRAM exhibits good stability and long retention time with high transparency, making it a promising candidate in the field of data storage for transparent circuits.
T cell Ig and mucin domain (Tim)-3 is well known to interact with its natural ligand, Galectin-9 (Gal-9), to regulate T cell function. However, little is known about the function of Tim-3/Gal-9 ...signaling in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) mediated by hepatic NKT cells that also express Tim-3. In the current study, we define the role and the mechanism of Tim-3/Gal-9 signaling in hepatic NKT cell regulation in a mouse model of diet-induced NAFLD. Adult male wild-type or CD1d knockout C57BL/6 mice were fed a high-fat diet to induce steatosis. Some of the mice also received one or a combination of Gal-9, anti-IL-15R/IL-15 mAb, rIL-15, α-galactosylceramide, and multilamellar liposomes containing Cl(2)MDP. The expression of Tim-3 and various markers reflecting cell proliferation, activation, cytokine production, and apoptosis was analyzed. Liver histology, steatosis grade, and hepatic triglyceride content were also evaluated. In the liver, Tim-3(+) NKT cells are in an activated state, and Gal-9 directly induces Tim-3(+) NKT cell apoptosis and contributes to the depletion of NKT cells in diet-induced steatosis. However, Gal-9 also interacts with Tim-3-expressing Kupffer cells to induce secretion of IL-15, thus promoting NKT cell proliferation. Exogenous administration of Gal-9 significantly ameliorates diet-induced steatosis by modulating hepatic NKT cell function. In summary, the Tim-3/Gal-9-signaling pathway plays a critical role in the homeostasis of hepatic NKT cells through activation-induced apoptosis and secondary proliferation and, thus, contributes to the pathogenesis of NAFLD.
It is challenging to recognize neutral hydrophilic molecules in water. Effective use of hydrogen bonds in water is generally accepted to be the key to success. In contrast, hydrophobic cavity is ...usually considered to play an insignificant role or only to provide a nonpolar microenvironment for hydrogen bonds. Herein, we report that hydrophobic cavity alone can also strongly bind neutral, highly hydrophilic molecules in water. We found that cucurbit
n
urils (
n
= 7, 8) bind 1,4-dioxane, crown ethers and monosaccharides in water with remarkable affinities. The best binding constant reaches 10
7
M
−1
for cucurbit8uril, which is higher than its binding affinities to common organic cations. Density functional theory (DFT) calculations and control experiments reveal that the hydrophobic effect is the major contributor to the binding through releasing the cavity water and/or properly occupying the weakly hydrated cavity. However, hydrophobic cavity still prefers nonpolar guests over polar guests with similar size and shape.
PDF
![Cucurbit[n]urils (n = 7, 8)...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1674-7291/small "Cucurbit[n]urils (n = 7, 8) can strongly bind neutral hydrophilic molecules in water")