A review of modification methods, joints and self-healing methods of adhesive for aerospace.

In recent years, the adhesive technology has been widely used in the production of high-strength joins and precise positioning of various materials, such as metals, glass and composite materials. The adhesive technology has become a promising assembly process in the aerospace field due to its versatility, low creep and high damage tolerance. However, the reliability and predictability of adhesive bonding still require further development due to the complex operating conditions involved. Therefore, this article reviews and discusses the latest advances in aerospace adhesive technology, such as methods for improving bonding performance, bonding techniques (including joints structure and failure modes) and self-healing adhesive layers. Additionally, the current research results are summarised, and possible development trends and research directions in the field of adhesive bonding are prospected.

Hydrogen bonding-induced high-performance stretchable organic semiconductors: a Review.

Semiconductors are widely used in electron devices. With the development of wearable soft-electron devices, conventional inorganic semiconductors are unable to meet the demand because of their high rigidity and high cost. Thus, scientists construct organic semiconductors with high charge mobility, low cost, eco-friendly, stretchable, etc. Due to the excellent performance of stretchable organic semiconductors, they can be widely used as wearable soft-electron devices, such as stretchable organic field-effect transistors (OFETs), organic solar cells (OSCs), etc. Contains flexible display devices and flexible power sources, which are of great interest for applications of future electron devices. However, there are still some challenges that need to be solved. Commonly, enhancing the stretchability may cause the degradation of charge mobility, because of the destruction of the conjugated system. Currently, scientists find that hydrogen bonding can enhance the stretchability of organic semiconductors with high charge mobility. Thus in this review, based on the structure and design strategies of hydrogen bonding, various hydrogen bonding induced stretchable organic semiconductors are introduced. In addition, the applications of the hydrogen bonding induced stretchable organic semiconductors are reviewed. Finally, the stretchable organic semiconductors design concept and potential evolution trends are discussed. The final goal is to outline a theoretical scaffold for the design of high-performance wearable soft-electron devices, which can also further advance the development of stretchable organic semiconductors for applications.

The development of stretchable and self-repairing materials applied to electronic skin.

Flexible electronic devices play a key role in the fields of flexible batteries, electronic skins, and flexible displays, which have attracted more and more attention in the past few years. Among them, the application areas of electronic skin in new energy, artificial intelligence, and other high-tech applications are increasing. Semiconductors are an indispensable part of electronic skin components. The design of semiconductor structure not only needs to maintain good carrier mobility, but also considers extensibility and self-healing capability, which is always a challenging work. Though flexible electronic devices are important for our daily life, the research on this topic is quite rare in the past few years. In this work, the recently published work regarding to stretchable semiconductors as well as self-healing conductors are reviewed. In addition, the current shortcomings, future challenges as well as an outlook of this technology are discussed. The final goal is to outline a theoretical framework for the design of high-performance flexible electronic devices that can at the same time address their commercialization challenges.

Editorial: New Advances in Nanomaterials.

In the past few years, people have been committed to a variety of properties and functional materials, among which are nanomaterials, which have been gradually developed in-depth [...].

iPSC-sEVs alleviate microglia senescence to protect against ischemic stroke in aged mice.

The polarization of microglia plays an important role in the outcome of ischemic stroke (IS). In the aged population, senescent microglia show a predominant pro-inflammatory phenotype, which leads to worse outcomes in aged ischemic stroke compared to young ischemic stroke. Recent research demonstrated that inducible pluripotent stem cell-derived small extracellular vesicles (iPSC-sEVs) possess the significant anti-ageing ability. We hypothesized that iPSC-sEVs could alleviate microglia senescence to regulate microglia polarization in aged ischemic stroke. In this study, we showed that treatment with iPSC-sEVs significantly alleviated microglia senescence as indicated by the decreased senescence-associated proteins including P16, P21, P53, and γ-H2AX as well as the activity of SA-ß-gal, and inhibited pro-inflammatory activation of microglia both in vivo and in vitro. Furthermore, iPSC-sEVs shifted microglia from pro-inflammatory phenotype to anti-inflammatory phenotype, which reduced the apoptosis of neurons, and improved the outcome of aged stroke mice. Mechanism studies showed that iPSC-sEVs reversed the loss of Rictor and downstream p-AKT (s473) in senescent microglia, which was involved in the senescence and pro-inflammatory phenotype regulation of microglia. Inhibition of Rictor abolished the iPSC-sEVs-afforded phosphorylation of AKT and alleviation of inflammation of senescent microglia. Proteomics results indicated that iPSC-sEVs carried transforming growth factor-ß1 (TGF-ß1) to upregulate Rictor and p-AKT in senescent microglia, which could be hindered by blocking TGF-ß1. Taken together, our work demonstrates iPSC-sEVs reverse the senescent characteristic of microglia in aged brains and therefore improve the outcome after stroke, at least, via delivering TGF-ß1 to upregulate Rictor and p-AKT. Our data suggest that iPSC-sEVs might be a novelty therapeutic method for aged ischemic stroke and other diseases involving senescent microglia.

High sensitivity for detecting trace Sn2+ in canned food using novel covalent organic frameworks.

Tin (Sn) element plays a vital role in the human body, and its detection is a mandatory inspection item for canned food. The application of covalent organic frameworks (COFs) in fluorescence detection has received extensive attentions. In this work, we designed a kind of novel COFs (COF-ETTA-DMTA) with high specific surface area (353.13 m2/g) by solvothermal synthesis using 2,5-dimethoxy-1,4-dialdehyde and tetra (4-aminophenyl) ethylene as precursors. It shows fast response time (about 50 s), low detection limit (228 nM) and good linearity (R2 = 0.9968) for the detection of Sn2+. Via coordination behavior, the recognition mechanism of COFs toward Sn2+ was simulated and verified by the small molecule with the same functional unit. More importantly, this COFs was successfully applied to identify Sn2+ in solid canned food (luncheon pork, canned fish, canned red kidney beans) with satisfactory results. This work provides a new approach for determining metal ions with COFs taking the advantage of their natural rich reaction set and specific surface area, improving the detection sensitivity and capacity.

Inducible Pluripotent Stem Cell-Derived Small Extracellular Vesicles Rejuvenate Senescent Blood-Brain Barrier to Protect against Ischemic Stroke in Aged Mice.

Blood-brain barrier (BBB) breakdown after ischemic stroke exacerbates brain injury and BBB senescence can cause severe neurological deficits in aged ischemic stroke population. Recent evidence reveals that inducible pluripotent stem cell-derived small extracellular vesicles (iPSC-sEVs) possess phenomenal antisenescence capability. However, whether iPSC-sEVs can rejuvenate BBB senescence to improve stroke outcomes in aged mice remains unknown. Here, we showed that long-term treatment with iPSC-sEVs alleviated aging-induced BBB senescence in aged mice. In aged stroke mice, iPSC-sEVs significantly mitigated BBB integrity damage, reduced the following infiltration of peripheral leukocytes, and decreased the release of pro-inflammatory factors from the leukocytes, which ultimately inhibited neuronal death and improved neurofunctional recovery. Mechanism studies showed that iPSC-sEVs could activate the endothelial nitric oxide synthase (eNOS) and up-regulate sirtuin 1 (Sirt1) in senescent endothelial cells. Blocking the activation of eNOS abolished iPSC-sEV-mediated rejuvenation of BBB senescence and the protection of BBB integrity. Proteomics results demonstrated that iPSC-sEVs were enriched with bioactive factors including AKT serine/threonine kinase 1 (AKT1) and calmodulin (CALM) to activate the eNOS-Sirt1 axis. Further investigation showed that AKT1 and CALM inhibitors blocked iPSC-sEV-afforded activation of the eNOS-Sirt1 axis in senescent endothelial cells. Taken together, iPSC-sEVs can protect against ischemic stroke in aged mice by rejuvenating BBB senescence, partially, through delivering AKT1 and CALM to activate eNOS-Sirt1 axis, which indicates that iPSC-sEVs treatment is an effective alternative to treat ischemic stroke in the aged population.

Membrane protein trafficking in the anti-tumor immune response: work of endosomal-lysosomal system.

Immunotherapy has changed the treatment landscape for multiple cancer types. In the recent decade, great progress has been made in immunotherapy, including immune checkpoint inhibitors, adoptive T-cell therapy, and cancer vaccines. ICIs work by reversing tumor-induced immunosuppression, resulting in robust activation of the immune system and lasting immune responses. Whereas, their clinical use faces several challenges, especially the low response rate in most patients. As an increasing number of studies have focused on membrane immune checkpoint protein trafficking and degradation, which interferes with response to immunotherapy, it is necessary to summarize the mechanism regulating those transmembrane domain proteins translocated into the cytoplasm and degraded via lysosome. In addition, other immune-related transmembrane domain proteins such as T-cell receptor and major histocompatibility are associated with neoantigen presentation. The endosomal-lysosomal system can also regulate TCR and neoantigen-MHC complexes on the membrane to affect the efficacy of adoptive T-cell therapy and cancer vaccines. In conclusion, we discuss the process of surface delivery, internalization, recycling, and degradation of immune checkpoint proteins, TCR, and neoantigen-MHC complexes on the endosomal-lysosomal system in biology for optimizing cancer immunotherapy.

Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.

To further describe the effect of the "fragile population" and their "higher-risk" comorbidities on prognosis among hospitalized Omicron patients, this observational cohort study enrolled hospitalized patients confirmed with SARS-CoV-2 during the 2022 Omicron wave in Shanghai, China. The primary outcome was progression to severe or critical cases. The secondary outcome was viral shedding time from the first positive SARS-CoV-2 detection. A total of 847 participants were enrolled, most of whom featured as advanced age (>70 years old: 30.34%), not fully vaccinated (55.84%), combined with at least 1 comorbidity (65.41%). Multivariate cox regression suggested age >70 years old (aHR[95%CI] 0.78[0.61-0.99]), chronic kidney disease (CKD) stage 4-5 (aHR[95%CI] 0.61[0.46-0.80]), heart conditions (aHR[95%CI] 0.76[0.60-0.97]) would elongate viral shedding time and fully/booster vaccination (aHR[95%CI] 1.4 [1.14-1.72]) would shorten this duration. Multivariate logistic regression suggested CKD stage 4-5 (aHR[95%CI] 3.21[1.45-7.27]), cancer (aHR[95%CI] 9.52[4.19-22.61]), and long-term bedridden status (aHR[95%CI] 4.94[2.36-10.44]) were the "higher" risk factor compared with the elderly, heart conditions, metabolic disorders, isolated hypertension, etc. for severity while female (aHR[95%CI] 0.34[0.16-0.68]) and fully/booster Vaccination (aHR[95%CI] 0.35[0.12-0.87]) could provide protection from illness progression. CKD stage 4-5, cancer and long-term bedridden history were "higher-risk" factors among hospitalized Omicron patients for severity progression while full vaccination could provide protection from illness progression.

Eliminating the original cargos of glioblastoma cell-derived small extracellular vesicles for efficient drug delivery to glioblastoma with improved biosafety.

Tumor derived small extracellular vesicles (TsEVs) display a great potential as efficient nanocarriers for chemotherapy because of their intrinsic targeting ability. However, the inherited risks of their original cargos (like loaded proteins or RNAs) from parent cancer cells in tumor progression severely hinder the practical application. In this study, a saponin-mediated cargo elimination strategy was established and practiced in glioblastoma (GBM) cell-derived small extracellular vesicles (GBM-sEVs). A high eliminating efficacy of the cargo molecules was confirmed by systematic analysis of the original proteins and RNAs in GBM-sEVs. In addition, the inherited functions of GBM-sEVs to promote GBM progression vanished after saponin treatment. Moreover, the results of cellular uptake analysis and in vivo imaging analysis demonstrated that saponin treatment preserved the homotypic targeting ability of GBM-sEVs. Thus, we developed an efficient nanocarrier with improved biosafety for GBM suppression. Furthermore, doxorubicin (DOX) transported by the saponin-treated GBM-sEVs (sa-GBM-sEVs) displayed an effective tumor suppression in both subcutaneous and orthotopic GBM models of mouse. Collectively, this study provides a feasible way to avoid the potential protumoral risks of TsEVs and can advance the clinical application of TsEVs in chemotherapy.

Efficient Colorimetric Fluoride Anion Sensor Based on π-Conjugated Carbazole Small Molecule.

The ability to detect fluoride anions with high selectivity and sensitivity by using the naked eye is crucial yet challenging. In this study, a novel, simple conjugated organic dye, N-tert-butyldimethylsilyl-3,6-diiodocarbazole (CA-TBMDS) was developed and used for the first time as a colorimetric sensor for fluoride. CA-TBMDS was found to be a highly sensitive fluoride chemosensor, with a detection limit as low as 3 × 10-5 M. The reaction of CA-TBMDS with fluoride anions in a tetrahydrofuran solution resulted in a color change from colorless to yellow under ambient light, which can be discriminated by the naked eye. The sensor operated via intermolecular proton transfer between the amide units and the fluoride anion, as confirmed by proton nuclear magnetic resonance titration. CA-TBMDS is not only highly sensitive to fluoride anions, but also exhibits high sensitivity in the presence of various ions. This work demonstrates that N-butyldimethylchlorosilane-based organic dyes have prospective utility as a type of fluoride anion chemosensor.

Hydrogen-Bonded Colorimetric and Fluorescence Chemosensor for Fluoride Anion With High Selectivity and Sensitivity: A Review.

In recent years, the wide application of fluoride materials has grown rapidly, therefore excessive discharge in the surrounding environment, especially in drinking water and organic effluent, has become a potential hazard to humans, and has even resulted in fluorosis disease. The development of a highly effective and convenient method to recognize fluoride anions in surrounding environments seems necessary and urgent. Among which, the development of a colorimetric and fluorescence fluoride chemosensor with obvious color changing allowing for naked-eye detection with high sensitivity and selectivity is more interesting and challenging. In this minireview, current novel colorimetric and fluorescence chemosensors for fluoride anions by hydrogen-bond interaction are introduced, including obvious color changing by naked-eye detection, high sensitivity and selectivity, non-pollution and fluoride extraction ability, aqueous detection, and other additional functions. Finally, the perspective of the fluoride chemosensor design concept and potential evolution trends are pointed out.

High-Resolution Multi-Channel Frequency Standard Comparator Using Digital Frequency Measurement.

The rapid improvement accuracy of the atomic frequency standard puts forward higher requirements for the measurement resolution of the atomic frequency standard comparison system. To overcome the defect that the single zero-crossing point detection is sensitive to noise in the traditional dual mixer time difference measurement method, a digital frequency measurement method is proposed. This method combines sinusoidal beat technology, multi-channel synchronous acquisition technology, and digital frequency measurement technology, and uses differential compensation of system error to realize the precision measurement of atomic frequency standard. The frequency measurement accuracy is less than 2.5 × 10-14 and the noise floor is better than 6.5 × 10-15/τ = 1 s. The system has a high frequency measurement accuracy and a low noise floor, which can realize the precise measurement of a highly stable frequency source.

Microstructure and Properties of Ag-Doped ZnO Grown Hydrothermally on a Graphene-Coated Polyethylene Terephthalate Bilayer Flexible Substrate.

Ag-doped ZnO nanorods growth on a PET-graphene substrate (Ag-ZnO/PET-GR) with different Ag-doped content were synthesized by low-temperature ion-sputtering-assisted hydrothermal synthesis method. The phase composition, morphologies of ZnO, and electrical properties were analyzed. Ag-doping affects the initially perpendicular growth of ZnO nanorods, resulting in oblique growth of ZnO nanorods becoming more obvious as the Ag-doped content increases, and the diameter of the nanorods decreasing gradually. The width of the forbidden band gap of the ZnO films decreases with increasing Ag-doped content. For the Ag-ZnO/PET-GR composite structure, the Ag-ZnO thin film with 5% Ag-doped content has the largest carrier concentration (8.1 × 1018 cm-3), the highest mobility (67 cm2 · V-1 · s-1), a small resistivity (0.09 Ω·cm), and impressive electrical properties.

Dopant-Free π-Conjugated Hole Transport Materials for Highly Stable and Efficient Perovskite Solar Cells.

Current high-efficiency hybrid perovskite solar cells (PSCs) have been fabricated with doped hole transfer material (HTM), which has shown short-term stability. Doping applied in HTMs for PSCs can enhance the hole mobility and PSCs' power conversion efficiency, while the stability of PSCs will be significantly decreased due to inherent hygroscopic properties and chemical incompatibility. Development of dopant-free HTM with high hole mobility is a challenge and of utmost importance. In this review, a series of selected and typical π-conjugated dopant-free hole transport materials, mainly regarding small molecules, are reviewed, which could consequently help to further design high-performance dopant-free HTMs. In addition, an outline of the molecular design concept and also the perspective of ideal dopant-free HTMs were explored.

Embryonic Stem Cell Derived Small Extracellular Vesicles Modulate Regulatory T Cells to Protect against Ischemic Stroke.

Stem cell derived small extracellular vesicles (sEVs) have been proved to promote neurological recovery after stroke. Recent studies demonstrate a phenomenal tissue repair ability in embryonic stem cell derived sEVs (ESC-sEVs). However, whether ESC-sEVs could protect against ischemic stroke remains unknown. Immune responses play an essential role in the pathogenesis of ischemic stroke, and modulating post-stroke immune responses ameliorates ischemia-induced brain damage. In this study, we aim to determine the therapeutic function of ESC-sEVs, specifically focusing on their role in immunomodulation after ischemic stroke. ESC-sEVs are intravenously administered after transient middle cerebral artery occlusion. ESC-sEVs significantly decrease leukocyte infiltration, inflammatory cytokine expression, neuronal death, and infarct volume and alleviate long-term neurological deficits and tissue loss after ischemic stroke. Interestingly, ESC-sEVs induce a marked increase in regulatory T cells (Tregs) after stroke. Further, ESC-sEV-afforded immunomodulatory function and neuroprotection against stroke are dependent on Tregs, as the depletion of Tregs almost completely abrogates the protective effects. Mechanistically, proteomic analysis reveals the enrichment of TGF-ß, Smad2, and Smad4 proteins in ESC-sEVs, which could be delivered to activate the TGF-ß/Smad pathway in CD4+ T cells and therefore induce Treg expansion. ESC-sEVs modulate neuroinflammation and protect against ischemic stroke through the expansion of Tregs, a process that is partially dependent on the activation of the TGF-ß/Smad signaling pathway by the transfer of TGF-ß, Smad2, and Smad4. The results suggest ESC-sEVs might be a candidate for immune modulation.

Benzo/Naphthodifuranone-Based Polymers: Effect of Perpendicular-Extended Main Chain π-Conjugation on Organic Field-Effect Transistor Performances.

For polymer semiconductors, the backbone structure plays an essential role in determining their physicochemical properties and charge transport behaviors. In this work, two donor-acceptor-type polymers (P-BDF and P-NDF) based on benzodifuranone (BDF) and naphthodifunarone (NDF) as electron-deficient moieties and indaceno-dithiophene as electron-rich groups are designed, synthesized and, for the first time, applied in organic field-effect transistor. P-BDF and P-NDF differ from their backbone structures while P-BDF has a more planar backbone conformation due to its smaller conjugated core size and P-NDF features a perpendicular-extended main chain structure. As a result, P-BDF polymer exhibits bathochromic optical absorption, deeper molecular orbital energy levels, and more importantly, closer π-stacking and stronger aggregation in the solid state and thus affords a more promising hole mobility of up to 0.85 cm2 V-1 s-1 in OFET devices, while that of the P-NDF-based devices is only 0.55 cm2 V-1 s-1 . The results suggest the great potential of BDF/NDF-type chromophores in constructing novel organic semiconductors and also indicate that the main chain coplanarity of polymer semiconductors is more essential than the sole extension of π-conjugations (especially at the perpendicular direction of polymer main chains) for the design of high-performance OFET materials.

ESC-sEVs Rejuvenate Aging Hippocampal NSCs by Transferring SMADs to Regulate the MYT1-Egln3-Sirt1 Axis.

Tissue stem cell senescence leads to stem cell exhaustion, which results in tissue homeostasis imbalance and a decline in regeneration capacity. However, whether neural stem cell (NSC) senescence occurs and causes neurogenesis reduction during aging is unknown. In this study, mice at different ages were used to detect age-related hippocampal NSC (H-NSC) senescence, as well as the function and mechanism of embryonic stem cell-derived small extracellular vesicles (ESC-sEVs) in rejuvenating H-NSC senescence. We found a progressive cognitive impairment, as well as age-related H-NSC senescence, in mice. ESC-sEV treatment significantly alleviated H-NSC senescence, recovered compromised self-renewal and neurogenesis capacities, and reversed cognitive impairment. Transcriptome analysis revealed that myelin transcription factor 1 (MYT1) is downregulated in senescent H-NSCs but upregulated by ESC-sEV treatment. In addition, knockdown of MYT1 in young H-NSCs accelerated age-related phenotypes and impaired proliferation and differentiation capacities. Mechanistically, ESC-sEVs rejuvenated senescent H-NSCs partly by transferring SMAD family members 4 (SMAD4) and 5 (SMAD5) to activate MYT1, which downregulated egl-9 family hypoxia inducible factor 3 (Egln3), followed by activation of hypoxia inducible factor 2 subunit α (HIF-2α), nicotinamide phosphoribosyl transferase (NAMPT), and sirtuin 1 (Sirt1) successively. Taken together, our results indicated that H-NSC senescence caused cellular exhaustion, neurogenesis reduction, and cognitive impairment during aging, which can be reversed by ESC-sEVs. Thus, ESC-sEVs may be promising therapeutic candidates for age-related diseases.

Prevalence and recovery time of olfactory and gustatory dysfunction in hospitalized patients with COVID­19 in Wuhan, China.

OBJECTIVE: To investigate olfactory and gustatory dysfunction in patients with coronavirus disease 2019 (COVID-19) in Wuhan using a telephone interview. METHODS: This retrospective telephone survey investigated 196 consecutive patients with COVID-19 at 3 months after discharge from two hospitals in Wuhan, China. The characteristics of the patient's disease course and time to recovery from olfactory and/or gustatory dysfunction (OD and/or GD) were collected by telephone interview. Demographic data were collected from the patient medical records. RESULTS: A total of 196 patients with COVID-19 completed the study. The most prevalent general symptoms were fever, cough, and fatigue. Overall, 19.9% of the patients reported OD and/or GD. In 87.2% of these cases, OD or GD appeared after the general symptoms. The time to recovery from OD and/or GD was more than 4 weeks in 51.4% of the patients. Patients with COVID-19 and OD and/or GD had significantly higher rates of cardiovascular disease than patients without OD and/or GD (p = 0.002). CONCLUSIONS: Recovery from chemosensory dysfunction (OD and/or GD) was slow, with over half of the patients taking more than 4 weeks to recover. Cardiovascular disease might be related to the development of olfactory or taste disorders in patients with COVID-19.