In this work, a sulfur (S) vacancy passivated monolayer MoS2 piezoelectric nanogenerator (PNG) is demonstrated, and its properties before and after S treatment are compared to investigate the effect ...of passivating S vacancy. The S vacancies are effectively passivated by using the S treatment process on the pristine MoS2 surface. The S vacancy site has a tendency to covalently bond with S functional groups; therefore, by capturing free electrons, a S atom will form a chemisorbed bond with the S vacancy site of MoS2. S treatment reduces the charge‐carrier density of the monolayer MoS2 surface, thus the screening effect of piezoelectric polarization charges by free carrier is significantly prevented. As a result, the output peak current and voltage of the S‐treated monolayer MoS2 nanosheet PNG are increased by more than 3 times (100 pA) and 2 times (22 mV), respectively. Further, the S treatment increases the maximum power by almost 10 times. The results suggest that S treatment can reduce free‐charge carrier by sulfur S passivation and efficiently prevent the screening effect. Thus, the piezoelectric output peaks of current, voltage, and maximum power are dramatically increased, as compared with the pristine MoS2.
Piezoelectricity of sulfur vacancy passivated MoS2 nanosheets is much higher than that of pristine MoS2 nanosheets. Sulfur vacancies can be filled through a sulfur treatment and the resulting output power of the device generates a 10‐times higher power. This result offers a new approach to realize a MoS2 nanosheet‐based high‐performance piezoelectric nanogenerator for self‐powered wearable electronics.
A hydrogel microcapsule with an intermediate thin oil layer is presented to achieve smart release of a broad range of cargoes triggered via diverse stimuli. A microfluidic technique is used to ...produce triple emulsion droplets with a thin oil layer that separates the innermost aqueous phase from the hydrogel prepolymer phase, which transforms into a hydrogel shell via photopolymerization. The intermediate oil layer within the hydrogel microcapsule acts as an effective diffusion barrier, allowing encapsulation of various small cargoes within a porous hydrogel shell until a stimulus is applied to destabilize the oil layer. It is demonstrated that diverse stimuli including chemical dissolution, mechanical stress, and osmotic pressure can be utilized to release the encapsulated cargo on‐demand. In addition, osmotic pressure and the hydrogel shell thickness can be independently tuned to control the onset time of release as well as the release behavior of multi‐cargo encapsulated hydrogel microcapsule. The release can be either simultaneous or selective.
A hydrogel microcapsule with an intermediate thin oil layer enables smart release of a broad range of cargoes via diverse stimuli. The oil layer in the microcapsules acts as an effective diffusion barrier until only when the oil layer is destabilized. The osmotic pressure and the overall stiffness of the microcapsule can be fine‐tuned to control the release behavior of the multi‐cargo encapsulated microcapsule.
Fibroblastic reticular cells (FRCs) are immunologically specialized myofibroblasts of lymphoid organ, and FRC maturation is essential for structural and functional properties of lymph nodes (LNs). ...Here we show that YAP and TAZ (YAP/TAZ), the final effectors of Hippo signaling, regulate FRC commitment and maturation. Selective depletion of YAP/TAZ in FRCs impairs FRC growth and differentiation and compromises the structural organization of LNs, whereas hyperactivation of YAP/TAZ enhances myofibroblastic characteristics of FRCs and aggravates LN fibrosis. Mechanistically, the interaction between YAP/TAZ and p52 promotes chemokine expression that is required for commitment of FRC lineage prior to lymphotoxin-β receptor (LTβR) engagement, whereas LTβR activation suppresses YAP/TAZ activity for FRC maturation. Our findings thus present YAP/TAZ as critical regulators of commitment and maturation of FRCs, and hold promise for better understanding of FRC-mediated pathophysiologic processes.
Development of localized inflammatory environments by M1 macrophages in the cardiac infarction region exacerbates heart failure after myocardial infarction (MI). Therefore, the regulation of ...inflammation by M1 macrophages and their timely polarization toward regenerative M2 macrophages suggest an immunotherapy. Particularly, controlling cellular generation of reactive oxygen species (ROS), which cause M1 differentiation, and developing M2 macrophage phenotypes in macrophages propose a therapeutic approach. Previously, stem or dendritic cells were used in MI for their anti-inflammatory and cardioprotective potentials and showed inflammation modulation and M2 macrophage progression for cardiac repair. However, cell-based therapeutics are limited due to invasive cell isolation, time-consuming cell expansion, labor-intensive and costly ex vivo cell manipulation, and low grafting efficiency. Here, we report that graphene oxide (GO) can serve as an antioxidant and attenuate inflammation and inflammatory polarization of macrophages via reduction in intracellular ROS. In addition, GO functions as a carrier for interleukin-4 plasmid DNA (IL-4 pDNA) that propagates M2 macrophages. We synthesized a macrophage-targeting/polarizing GO complex (MGC) and demonstrated that MGC decreased ROS in immune-stimulated macrophages. Furthermore, DNA-functionalized MGC (MGC/IL-4 pDNA) polarized M1 to M2 macrophages and enhanced the secretion of cardiac repair-favorable cytokines. Accordingly, injection of MGC/IL-4 pDNA into mouse MI models attenuated inflammation, elicited early polarization toward M2 macrophages, mitigated fibrosis, and improved heart function. Taken together, the present study highlights a biological application of GO in timely modulation of the immune environment in MI for cardiac repair. Current therapy using off-the-shelf material GO may overcome the shortcomings of cell therapies for MI.
When expression of more than one gene is required in cells, bicistronic or multicistronic expression vectors have been used. Among various strategies employed to construct bicistronic or ...multicistronic vectors, an internal ribosomal entry site (IRES) has been widely used. Due to the large size and difference in expression levels between genes before and after IRES, however, a new strategy was required to replace IRES. A self-cleaving 2A peptide could be a good candidate to replace IRES because of its small size and high cleavage efficiency between genes upstream and downstream of the 2A peptide. Despite the advantages of the 2A peptides, its use is not widespread because (i) there are no publicly available cloning vectors harboring a 2A peptide gene and (ii) comprehensive comparison of cleavage efficiency among various 2A peptides reported to date has not been performed in different contexts. Here, we generated four expression plasmids each harboring different 2A peptides derived from the foot-and-mouth disease virus, equine rhinitis A virus, Thosea asigna virus and porcine teschovirus-1, respectively, and evaluated their cleavage efficiency in three commonly used human cell lines, zebrafish embryos and adult mice. Western blotting and confocal microscopic analyses revealed that among the four 2As, the one derived from porcine teschovirus-1 (P2A) has the highest cleavage efficiency in all the contexts examined. We anticipate that the 2A-harboring cloning vectors we generated and the highest efficiency of the P2A peptide we demonstrated would help biomedical researchers easily adopt the 2A technology when bicistronic or multicistronic expression is required.
Heart failure remains a major public health concern with a 5-year mortality rate higher than that of most cancers. Myocardial disease in heart failure is frequently accompanied by impairment of the ...specialized electrical conduction system and myocardium. We introduce an epicardial mesh made of electrically conductive and mechanically elastic material, to resemble the innate cardiac tissue and confer cardiac conduction system function, to enable electromechanical cardioplasty. Our epicardium-like substrate mechanically integrated with the heart and acted as a structural element of cardiac chambers. The epicardial device was designed with elastic properties nearly identical to the epicardial tissue itself and was able to detect electrical signals reliably on the moving rat heart without impeding diastolic function 8 weeks after induced myocardial infarction. Synchronized electrical stimulation over the ventricles by the epicardial mesh with the high conductivity of 11,210 S/cm shortened total ventricular activation time, reduced inherent wall stress, and improved several measures of systolic function including increases of 51% in fractional shortening, ~90% in radial strain, and 42% in contractility. The epicardial mesh was also capable of delivering an electrical shock to terminate a ventricular tachyarrhythmia in rodents. Electromechanical cardioplasty using an epicardial mesh is a new pathway toward reconstruction of the cardiac tissue and its specialized functions.
The present study aimed to investigate whether the Janus‑activated kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is a critical mechanism underlying the ...cancer‑associated fibroblast (CAF)‑induced chemoresistance of gastric cancer (GC). In addition, the present study tried to suggest a natural product to compromise the effects of CAF on the chemoresistance of GC. The results of cell proliferation assay revealed that the conditioned medium (CM) collected from CAFs further increased resistance to 5‑fluorouracil (5‑FU) in GC cell lines. Secretome analysis revealed that the levels of several secreted proteins, including C‑C motif chemokine ligand 2, C‑X‑C motif chemokine ligand 1, interleukin (IL)‑6 and IL‑8, were increased in the CM from CAFs co‑cultured with cancer cells compared to CM from cancer cells. Western blot analysis revealed that CAFs activated the JAK/STAT3 signaling pathway in cancer cells. The experimental models revealed that curcumin abrogated the CAF‑mediated activation of the JAK/STAT3 signaling pathway in GC cells.
data revealed the synergistic effects of curcumin with 5‑FU treatment in xenograft GC tumors. These data strongly suggest that the suppression of the JAK/STAT3 signaling pathway counteracts the CAF‑induced chemoresistance of GC cells. It is suggested that curcumin may be a suitable natural product which may be used to overcome chemoresistance by inhibiting the CAF‑induced activation of the JAK/STAT3 signaling pathway in GC.
Background
Antisecretory drugs are commonly prescribed with clopidogrel‐based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high‐risk patients after percutaneous coronary ...intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors PPIs) may increase cardiovascular event rates on co‐administration with clopidogrel.
This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel‐based DAPT and the concomitant use of clopidogrel and inhibiting PPIs.
Methods
We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel‐based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran–Armitage trend test.
Results
From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P‐CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users.
Conclusions
Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel‐based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.
Zero-dimensional–two-dimensional (0D–2D) hybrid optoelectronic devices have demonstrated high sensitivity and high performance due to the high absorption coefficient of 0D materials with a tunable ...detection range and a high carrier transport property of 2D materials. However, the reported 0D–2D hybrid devices employ toxic nanomaterials as sensitizing layers, which can limit the practical applications. In this study, we first fabricated the 0D–2D hybrid photodetector using nontoxic InP quantum dots (QDs) as a light-absorbing layer and black phosphorus (BP) as a transport layer. The surface treatment using 1,2-ethanedithiol and thermal treatment were carried out to remove the surface long ligands of colloidal QDs, which can accelerate the charge injection of the photogenerated carriers through the interfaces between InP QDs and BP. The InP QDs/BP hybrid photodetector demonstrates a high responsivity of 1 × 109 A/W and detectivity of 4.5 × 1016 Jones at 0.05 μW cm–2 under 405 nm illumination. The results show that 0D–2D hybrid photodetectors based on III–V semiconducting QD materials can be optimized for high-performance photodetectors.
Recent evidence suggests that animal microRNAs (miRNAs) can target coding sequences (CDSs); however, the pathophysiological importance of such targeting remains unknown. Here, we show that a somatic ...heterozygous missense mutation (c.402C>G; p.C134W) in FOXL2, a feature shared by virtually all adult‐type granulosa cell tumors (AGCTs), introduces a target site for miR‐1236, which causes haploinsufficiency of the tumor‐suppressor FOXL2. This miR‐1236‐mediated selective degradation of the variant FOXL2 mRNA is preferentially conducted by a distinct miRNA‐loaded RNA‐induced silencing complex (miRISC) directed by the Argonaute3 (AGO3) and DHX9 proteins. In both patients and a mouse model of AGCT, abundance of the inversely regulated variant FOXL2 with miR‐1236 levels is highly correlated with malignant features of AGCT. Our study provides a molecular basis for understanding the conserved FOXL2 CDS mutation‐mediated etiology of AGCT, revealing the existence of a previously unidentified mechanism of miRNA‐targeting disease‐associated mutations in the CDS by forming a non‐canonical miRISC.
SYNOPSIS
An alternative miRNA‐loaded RNA‐induced silencing complex (miRISC) comprising AGO3, DHX9 and miR‐1236 targets a conserved coding sequence mutation site in the tumor suppressor FOXL2, which is found in nearly all patients that have adult‐type granulosa cell tumors. This leads to specific decay of the mutated FOXL2 mRNA.
Patients with an adult‐type granulosa cell tumor that contains a somatic missense mutation of FOXL2 (c.402C> G; p.C134W) exhibit an allelic imbalance of heterozygous FOXL2 mRNAs.
miR‐1236 causes the decay of the mutated variant FOXL2 mRNA, but not the wild‐type FOXL2 mRNA, by targeting the 402C> G mutation site in the coding sequence.
A non‐canonical miRISC complex comprising AGO3 and DHX9 preferentially targets mutated FOXL2 mRNA variant in the coding region.
miR‐1236 acts as an oncomiR for adult‐type granulosa cell tumor development by causing haploinsufficiency of the tumor suppressor FOXL2.
A cancer mutation introduces a novel miR‐1236 target site in FOXL2 mRNA, causing its miRNA‐mediated decay and leading to FOXL2 tumor suppressor haploinsufficiency.
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