Traditionally viewed as an autodigestive pathway, autophagy also facilitates cellular secretion; however, the mechanisms underlying these processes remain unclear. Here, we demonstrate that ...components of the autophagy machinery specify secretion within extracellular vesicles (EVs). Using a proximity-dependent biotinylation proteomics strategy, we identify 200 putative targets of LC3-dependent secretion. This secretome consists of a highly interconnected network enriched in RNA-binding proteins (RBPs) and EV cargoes. Proteomic and RNA profiling of EVs identifies diverse RBPs and small non-coding RNAs requiring the LC3-conjugation machinery for packaging and secretion. Focusing on two RBPs, heterogeneous nuclear ribonucleoprotein K (HNRNPK) and scaffold-attachment factor B (SAFB), we demonstrate that these proteins interact with LC3 and are secreted within EVs enriched with lipidated LC3. Furthermore, their secretion requires the LC3-conjugation machinery, neutral sphingomyelinase 2 (nSMase2) and LC3-dependent recruitment of factor associated with nSMase2 activity (FAN). Hence, the LC3-conjugation pathway controls EV cargo loading and secretion.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The development of red thermally activated delayed fluorescence (TADF) emitters having excellent optoelectronic properties and satisfactory electroluminescence efficiency is full of challenges due to ...strict molecular design principles. Two red TADF molecules, 3‐(9,9‐dimethylacridin‐10(9H)‐yl)acenaphtho1,2‐bquinoxaline‐9,10‐dicarbonitrile and 3‐(2,7‐dimethyl‐10H‐spiroacridine‐9,9′‐fluoren‐10‐yl)acenaphtho1,2‐bquinoxaline‐9,10‐dicarbonitrile, are developed by adopting a donor–acceptor molecular architecture bearing an electron‐accepting acenaphtho1,2‐bquinoxaline‐9,10‐dicarbonitrile (ANQDC) moiety and a 9,9‐dimethyl‐9,10‐dihydroacridine or 2,7‐dimethyl‐10H‐spiroacridine‐9,9′‐fluorene electron donor. The combined effects of rigid and planar D/A moieties and highly steric hindrance between D and A groups endow both molecules with high rigidity to suppress nonradiative decay processes, resulting in high photoluminescence quantum efficiencies (ΦPLs) of up to 95%. Attributed to the linear and planar acceptor motif and rod‐like molecular configuration, both emitters achieve high horizontal ratios of emitting dipole orientation of ≈80%. The organic light‐emitting diodes (OLEDs) based on both emitters exhibit red emissions peaking at ≈615 nm and successfully afford ultrahigh electroluminescence performance with an external quantum efficiency of nearly 28% and a power efficiency of above 50 lm W−1, on par with the state‐of‐the‐art device efficiency for red TADF OLEDs. This presents a feasible design strategy for excellent TADF emitters simultaneously possessing high ΦPLs and horizontally aligned emitting dipoles.
An ultrahigh‐efficiency red thermally activated delayed fluorescence (TADF) OLED with an external quantum efficiency of nearly 28% and a power efficiency of exceeding 50 lm W−1 is realized. The OLEDs incorporate excellent red TADF emitters, simultaneously exhibiting 95% photoluminescence quantum efficiency and preferentially horizontal emitting dipole orientation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aberrant aggregation of the RNA-binding protein TDP-43 in neurons is a hallmark of frontotemporal lobar degeneration caused by haploinsufficiency in the gene encoding progranulin
. However, the ...mechanism leading to TDP-43 proteinopathy remains unclear. Here we use single-nucleus RNA sequencing to show that progranulin deficiency promotes microglial transition from a homeostatic to a disease-specific state that causes endolysosomal dysfunction and neurodegeneration in mice. These defects persist even when Grn
microglia are cultured ex vivo. In addition, single-nucleus RNA sequencing reveals selective loss of excitatory neurons at disease end-stage, which is characterized by prominent nuclear and cytoplasmic TDP-43 granules and nuclear pore defects. Remarkably, conditioned media from Grn
microglia are sufficient to promote TDP-43 granule formation, nuclear pore defects and cell death in excitatory neurons via the complement activation pathway. Consistent with these results, deletion of the genes encoding C1qa and C3 mitigates microglial toxicity and rescues TDP-43 proteinopathy and neurodegeneration. These results uncover previously unappreciated contributions of chronic microglial toxicity to TDP-43 proteinopathy during neurodegeneration.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Younger generations comprise an essential segment for the mobile payment market to prosper. However, empirical evidence of the drivers/barriers of the young generation’s adoption of mobile payment ...has been inconclusive. This study intends to advance the body of knowledge on this subject based on the extended Unified Theory of Acceptance and Use of Technology (UTAUT), incorporating the young generation’s risk perception and bonus/rewards provided by the mobile-pay firms. To this end, 295 samples with the majority being more tech-savvy, namely generation Y and generation Z, were collected from an online survey in Taiwan. The empirical results in this study demonstrate the uniquely positive effect of social influence on the young generations’ behavioral intention to adopt mobile payment. While behavioral intention and promotional activities are the drivers of the young generation’s actual usage of mobile payment, perceived risks are found to exert a negative impact, reflecting the risk-averse preferences of the young generation in Taiwan. The ignorable moderation effect of gender, on the other hand, suggests the absence of a gender gap in the use of mobile payment among the young generations. The findings in this research have important implications for the development of promotion programs motivating the young generation’s adoption of mobile payment.
This study used
LUC 247 to ferment black rice sourdough, made into Type III black rice sourdough powder to produce black rice sourdough bread. The composition analysis, antioxidant capacity, and ...storage stability of the black rice sourdough bread with different proportions of black rice powder (0-60%) and fermented for different lengths of time (0-48 h) were discussed. The results showed that the black rice sourdough had the maximum lactic acid bacteria count (9 Log CFU/g) during 12 to 36 h of fermentation. The titratable acid, lactic acid, and acetic acid yields increased with the fermentation time and the proportion of black rice powder. The total anthocyanin content and antioxidant capacity increased with the fermentation time. The hardness and chewiness of the black rice sourdough bread were positively correlated with the black rice sourdough powder content and increased with storage time. In addition, the growth of fungi was significantly slowed as the additional level of black rice sourdough powder increased.
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•Benzothiophene-fused spiro-acridine donors for constructing red TADF emitters.•Satisfactory red emissions, high ΦPL of up to 72%, and high horizontal ratio of emitting dipole ...orientation of ≈ 85%.•Red TADF OLEDs with EQE of up to 24.7%.
Red thermally activated delayed fluorescence (TADF) emitters underperform their blue and green counterparts, largely due to their low photoluminescence quantum efficiency and isotropic orientation. Here, we designed two rigid and strong electron-rich donor moieties, 3-methyl-13H-spirobenzo4,5thieno3,2-cacridine-5,9′-fluorene (MSTA) and 3-phenyl-13H-spirobenzo4,5thieno3,2-cacridine-5,9′-fluorene (PSTA), by fusing benzothiophene unit on a spiro-acridine framework. Combined with a rigid, linear, and planar acenaphtho1,2-bquinoxaline-9,10-dicarbonitrile (ANQDC) acceptor, two red emitters, ANQDC-MSTA and ANQDC-PSTA, were synthesized and characterized. In virtue of high rigidity and linear donor–acceptor (D-A) molecular skeleton, both emitters showed distinct TADF nature, high photoluminescence quantum efficiencies and high horizontal ratios of emitting dipole orientation of ≈85%. Consequently, the ANQDC-PSTA-based OLEDs realized high external quantum efficiency (EQE) of 24.7% at an electroluminescence peak (ELpeak) of 622 nm, together with Commission Internationale de l’Eclairage 1931 (CIE1931) coordinates of (0.61, 0.38). Furthermore, with the modulation of the microcavity effect on the device architecture, we delivered a 19.1% EQE in a deep-red EL region, with an ELpeak of 646 nm and favorable CIE1931 coordinates of (0.64, 0.36). These efficiencies are on par with the highest EL performance for red TADF OLEDs in the similar color gamut.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is a limitation in ...the self-repair ability of the cartilage. Therefore, developing strategies for cartilage repair is very important. Here, we report on a new liquid resin preparation process of water-based polyurethane based photosensitive materials with hyaluronic acid with application of the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton's jelly mesenchymal stem cells (hWJMSCs) and the cells in this case showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and also facilitate the development of cartilage tissue engineering.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of this study was to determine the reliability and validity of a Chinese version of the Patient Health Questionnaire-9 item (PHQ-9) and its 2 subscales (1 item and 2 items) for the screening ...of major depressive disorder (MDD) among adolescents in Taiwan.
A total of 2257 adolescents were recruited from high schools in Taipei. The participants completed assessments including demographic information, the Chinese version of the PHQ-9, and the Rosenberg Self-Esteem Scale, and data on the number of physical illnesses and mental health service utilizations were recorded. Among them, 430 were retested using the PHQ-9 within 2 weeks. Child psychiatrists interviewed a subsample of the adolescents (n = 165) using the Kiddie-Schedule for Affective Disorder and Schizophrenia Epidemiological Version as the criterion standard.
The PHQ-9 had good internal consistency (α = 0.84) and acceptable test-retest reliability (0.80). The participants with higher PHQ-9 scores were more likely to have MDD. Principal component factor analysis of the PHQ-9 yielded a 1-factor structure, which accounted for 45.3% of the variance. A PHQ-9 score ≥15 had a sensitivity of 0.72 and a specificity of 0.95 for recognizing MDD. The area under the receiver operating characteristic curve was 0.90. The screening accuracy of the 2 subscales was also satisfactory, with a Patient Health Questionnaire-2 item cutoff of ≥3 being 94.4% sensitive and 82.5% specific and a Patient Health Questionnaire-1 item cutoff of ≥2 being 61.1% sensitive and 87.7% specific.
The PHQ-9 and its 2 subscales appear to be reliable and valid for detecting MDD among ethnic Chinese adolescents in Taiwan.
An autosomal recessive disease is caused by biallelic loss‐of‐function mutations. However, when more than two disease‐causing variants are found in a patient's gene, it is challenging to determine ...which two of the variants are responsible for the disease phenotype. Here, to decipher the pathogenic variants by precise haplotyping, we applied nanopore Cas9‐targeted sequencing (nCATS) to three truncation COL7A1 variants detected in a patient with recessive dystrophic epidermolysis bullosa (EB). The distance between the most 5′ and 3′ variants was approximately 19 kb at the level of genomic DNA. nCATS successfully demonstrated that the most 5′ and 3′ variants were located in one allele while the variant in between was located in the other allele. Interestingly, the proband's mother, who was phenotypically intact, was heterozygous for the allele that harbored the two truncation variants, which could otherwise be misinterpreted as those of typical recessive dystrophic EB. Our study highlights the usefulness of nCATS as a tool to determine haplotypes of complicated genetic cases. Haplotyping of multiple variants in a gene can determine which variant should be therapeutically targeted when nucleotide‐specific gene therapy is applied.
Although rare, detecting three or more disease‐causing variants in a patient's gene can be puzzling. Nanopore Cas9‐targeted sequencing deciphers the pathogenic variants by precise haplotyping in such cases.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare type of epidermal nevus involving the eccrine acrosyringia. It typically presents as asymptomatic linear keratotic papules and ...plaques along the lines of Blaschko and predominantly affects the extremities. This disease has recently been linked to somatic mutations within the GJB2 locus. Only four GJB2 mutations have been previously documented for PEODDN, and the underlying genetic basis remains inconclusive. Herein, we report an 18‐year‐old female with a hyperkeratotic plaque on the dorsa of the proximal interphalangeal joint of her right ring finger, as well as multiple small hyperkeratotic papules linearly distributed on the lateral sides of her fingers occurring since birth. Histopathological results revealed prominent parakeratotic cornoid lamella‐like tiers at the opening of the eccrine secretory ducts. Whole‐exome sequencing of the affected skin tissue revealed a heterozygous germline mutation and a postzygotic somatic mutation in GJB2. In summary, this study presents a case of PEODDN with compound heterozygous mutations in GJB2, which broadens the genetic spectrum of this disease entity and implies a possible role for second‐hit mutations in the pathogenesis of PEODDN.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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