To achieve high charge density for the triboelectric polymer is a crucial task for fabricating triboelectric nanogenerators (TENGs). This work has developed a quenching polarization (QP) method to ...create ultrahigh and long‐persistent triboelectric charge on the triboelectric polymer with weak dipole polarity. The Ethylene chlorotrifluoroethylene copolymer (ECTFE) film can reach a charge density of 391 µC m−2 in the vertical contact mode by using this QP treatment, which is 200% higher than the result achieved by the most widely used method of corona polarization. The mechanism of the improvement through QP on the triboelectric properties is studied on the basis of the polarization induced grain refinement and interfacial trapping. The QP‐treated ECTFE can maintain ultra‐high charge density for both solid‐solid and solid‐liquid TENG. More interestingly, the charge induced by QP treatment is so persistent that it produces a recoverable discharging phenomenon for solid‐liquid TENG, which has never been observed before. This QP method provides a different approach for fabricating high‐performance triboelectric materials, while the QP‐induced changes in crystallization and tribo‐charge density can help to complete the physical understanding of the electrification mechanism of triboelectric polymer.
A quenching polarization method is developed to create ultrahigh and long‐persistent triboelectric charge on weak polar triboelectric polymer. This method refines the grains of ECTFE through the drastic change of temperature under the externally applied electric field and increases interfaces between the crystalline and amorphous regions, which induce a large amount of interfacial deep traps for charges storage.
Novel light-driven and electro-driven polyethylene glycol (PEG)/two-dimensional MXene composite (PEG@MXene) with enhanced thermal conductivity and electrical conductivity as form-stable phase change ...material (FSPCM) is first obtained via the simple vacuum impregnation by employing MXene as the supporting skeleton as well as thermally conductive and electrically conductive filler and PEG as the phase change working substance. Fourier transform infrared spectroscopy (FT-IR) indicates that no chemical reaction occurred between PEG and MXene during adsorption process, but X-ray diffraction (XRD) results show the crystalline regions of PEG was decreased by the incorporation of MXene. The differential scanning calorimetry (DSC), polarizing microscope (POM), as well as XRD results demonstrate that the MXene nanosheets act as heterogeneous crystal nuclei and promote the crystallization of PEG. The melting and freezing latent heats of PEG@MXene are as high as 131.2 and 129.5 J/g, respectively, the relative enthalpy efficiency is 80.3%, and the thermal conductivity and electrical conductivity are 2.052 W/mK and 10.41 S/m, respectively. The obtained PEG@MXene has excellent light-to-thermal conversion, electro-to-thermal conversion and thermal energy storage performance. All these results demonstrate that the obtained PEG@MXene will have a great potential application for thermal energy storage.
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•A novel light-driven and electro-driven PEG@MXene FSPCM is first obtained.•The thermal conductivity and electrical conductivity of PEG@MXene are significantly improved.•The obtained PEG@MXene will have a great potential application for thermal energy storage.
ObjectiveAntidepressant use during gestation has been associated with risk of major congenital malformations but estimates can lack statistical power or be confounded by maternal depression. We aimed ...to determine the association between first-trimester exposure to antidepressants and the risk of major congenital malformations in a cohort of depressed/anxious women.Setting and participantsData were obtained from the Quebec Pregnancy Cohort (QPC). All pregnancies with a diagnosis of depression or anxiety, or exposed to antidepressants in the 12 months before pregnancy, and ending with a live-born singleton were included.Outcome measuresAntidepressant classes (selective serotonin reuptake inhibitors (SSRI), serotonin–norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA) and other antidepressants) and types were individually compared with non-exposure during the first trimester (depressed untreated). Major congenital malformations overall and organ-specific malformations in the first year of life were identified.Results18 487 pregnant women were included. When looking at the specific types of antidepressant used during the first trimester, only citalopram was increasing the risk of major congenital malformations (adjusted OR, (aOR) 1.36, 95% CI 1.08 to 1.73; 88 exposed cases), although there was a trend towards increased risk for the most frequently used antidepressants. Antidepressants with serotonin reuptake inhibition effect (SSRI, SNRI, amitriptyline (the most used TCA)) increased the risk of certain organ-specific defects: paroxetine increased the risk of cardiac defects (aOR 1.45, 95% CI 1.12 to 1.88), and ventricular/atrial septal defects (aOR 1.39, 95% CI 1.00 to 1.93); citalopram increased the risk of musculoskeletal defects (aOR 1.92, 95% CI 1.40 to 2.62), and craniosynostosis (aOR 3.95, 95% CI 2.08 to 7.52); TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95% CI 1.05 to 5.72), and digestive defects (aOR 2.55, 95% CI 1.40 to 4.66); and venlafaxine was associated with respiratory defects (aOR 2.17, 95% CI 1.07 to 4.38).ConclusionsAntidepressants with effects on serotonin reuptake during embryogenesis increased the risk of some organ-specific malformations in a cohort of pregnant women with depression.
On March 11, 2020, the World Health Organization declared its assessment of coronavirus disease 2019 (COVID‐19) as a global pandemic. However, specific anti‐severe acute respiratory ...syndrome‐coronavirus 2 (SARS‐CoV‐2) drugs are still under development, and patients are managed by multiple complementary treatments. We performed a retrospective analysis to compare and evaluate the effect of low molecular weight heparin (LMWH) treatment on disease progression. For this purpose, the clinical records and laboratory indicators were extracted from electronic medical records of 42 patients with COVID‐19 (21 of whom were treated with LMWH, and 21 without LMWH) hospitalized (Union Hospital of Huazhong University of Science and Technology) from February 1 to March 15, 2020. Changes in the percentage of lymphocytes before and after LMWH treatment were significantly different from those in the control group (P = 0.011). Likewise, changes in the levels of D‐dimer and fibrinogen degradation products in the LMWH group before and after treatment were significantly different from those in the control group (P = 0.035). Remarkably, IL‐6 levels were significantly reduced after LMWH treatment (P = 0.006), indicating that, besides other beneficial properties, LMWH may exert an anti‐inflammatory effect and attenuate in part the “cytokine storm” induced by the virus. Our results support the use of LMWH as a potential therapeutic drug for the treatment of COVID‐19, paving the way for a subsequent well‐controlled clinical study.
Heparan sulfate proteoglycans (HSPG) are macromolecular glyco-conjugates expressed ubiquitously on the cell surface and in the extracellular matrix where they interact with a wide range of ligands to ...regulate many aspects of cellular function. The capacity of the side glycosaminoglycan chain heparan sulfate (HS) being able to interact with diverse protein ligands relies on its complex structure that is generated by a controlled biosynthesis process, involving the actions of glycosyl-transferases, sulfotransferases and the glucuronyl C5-epimerase. It is believed that activities of the modification enzymes control the HS structures that are designed to serve the biological functions in a given cell or biological status. In this review, we briefly discuss recent understandings on the roles of HSPG in cytokine stimulated cellular signaling, focusing on FGF, TGF-β, Wnt, Hh, HGF and VEGF.
•Heparan sulfate proteoglycans play important roles in cytokine stimulated cell signalling•The complicated structure of heparan sulfate enables it interacting with diverse cytokines and their receptors•Heparin may interfere the functions of heparan sulfate
Extracellular vesicle (EV)-mediated intercellular transfer of signaling proteins and nucleic acids has recently been implicated in the development of cancer and other pathological conditions; ...however, the mechanism of EV uptake and how this may be targeted remain as important questions. Here, we provide evidence that heparan sulfate (HS) proteoglycans (PGs; HSPGs) function as internalizing receptors of cancer cell-derived EVs with exosome-like characteristics. Internalized exosomes colocalized with cell-surface HSPGs of the syndecan and glypican type, and exosome uptake was specifically inhibited by free HS chains, whereas closely related chondroitin sulfate had no effect. By using several cell mutants, we provide genetic evidence of a receptor function of HSPG in exosome uptake, which was dependent on intact HS, specifically on the 2-O and N-sulfation groups. Further, enzymatic depletion of cell-surface HSPG or pharmacological inhibition of endogenous PG biosynthesis by xyloside significantly attenuated exosome uptake. We provide biochemical evidence that HSPGs are sorted to and associate with exosomes; however, exosome-associated HSPGs appear to have no direct role in exosome internalization. On a functional level, exosome-induced ERK1/2 signaling activation was attenuated in PG-deficient mutant cells as well as in WT cells treated with xyloside. Importantly, exosome-mediated stimulation of cancer cell migration was significantly reduced in PG-deficient mutant cells, or by treatment of WT cells with heparin or xyloside. We conclude that cancer cell-derived exosomes use HSPGs for their internalization and functional activity, which significantly extends the emerging role of HSPGs as key receptors of macromolecular cargo.
Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in ...our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.
Ophthalmic manifestations have recently been observed in acute and post-acute complications of COVID-19 caused by SARS-CoV-2 infection. Our precious study has shown that host RNA editing is linked to ...RNA viral infection, yet ocular adenosine to inosine (A-to-I) RNA editing during SARS-CoV-2 infection remains uninvestigated in COVID-19. Herein we used an epitranscriptomic pipeline to analyze 37 samples and investigate A-to-I editing associated with SARS-CoV-2 infection, in five ocular tissue types including the conjunctiva, limbus, cornea, sclera, and retinal organoids. Our results revealed dramatically altered A-to-I RNA editing across the five ocular tissues. Notably, the transcriptome-wide average level of RNA editing was increased in the cornea but generally decreased in the other four ocular tissues. Functional enrichment analysis showed that differential RNA editing (DRE) was mainly in genes related to ubiquitin-dependent protein catabolic process, transcriptional regulation, and RNA splicing. In addition to tissue-specific RNA editing found in each tissue, common RNA editing was observed across different tissues, especially in the innate antiviral immune gene MAVS and the E3 ubiquitin-protein ligase MDM2. Analysis in retinal organoids further revealed highly dynamic RNA editing alterations over time during SARS-CoV-2 infection. Our study thus suggested the potential role played by RNA editing in ophthalmic manifestations of COVID-19, and highlighted its potential transcriptome impact, especially on innate immunity.
Proteoglycan (PG) coreceptors carry heparan sulfate (HS) chains that mediate interactions with growth factors, morphogens, and receptors. Thus, PGs modulate fundamental processes such as cell ...survival, division, adhesion, migration, and differentiation. This review summarizes recent biochemical and genetic information that sheds new light on the nature of HS-protein binding. Unexpectedly, many interactions appear to depend more on the overall organization of HS domains than on their fine structure.
Esophageal squamous dysplasia is believed to be the precursor lesion of esophageal squamous cell carcinoma (ESCC); however, the genetic evolution from dysplasia to ESCC remains poorly understood. ...Here, we applied multi-region whole-exome sequencing to samples from two cohorts, 45 ESCC patients with matched dysplasia and carcinoma samples, and 13 tumor-free patients with only dysplasia samples. Our analysis reveals that dysplasia is heavily mutated and harbors most of the driver events reported in ESCC. Moreover, dysplasia is polyclonal, and remarkable heterogeneity is often observed between tumors and their neighboring dysplasia samples. Notably, copy number alterations are prevalent in dysplasia and persist during the ESCC progression, which is distinct from the development of esophageal adenocarcinoma. The sharp contrast in the prevalence of the 'two-hit' event on TP53 between the two cohorts suggests that the complete inactivation of TP53 is essential in promoting the development of ESCC.The pathogenesis of oesophageal squamous cell carcinoma is a multi-step process but the genetic determinants behind this progression are unknown. Here the authors use multi-region exome sequencing to comprehensively investigate the genetic evolution of precursor dysplastic lesions and untransformed oesophagus.
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