Leber's hereditary optic neuropathy-associated ND6 14484T > C mutation caused pleiotropic effects on the complex I, RNA homeostasis, apoptosis and mitophagy.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited eye disease due to mitochondrial DNA (mtDNA) mutations. LHON-linked ND6 14484T > C (p.M64V) mutation affected structural components of complex I but its pathophysiology is poorly understood. The structural analysis of complex I revealed that the M64 forms a nonpolar interaction Y59 in the ND6, Y59 in the ND6 interacts with E34 of ND4L, and L60 of ND6 interacts with the Y114 of ND1. These suggested that the m.14484T > C mutation may perturb the structure and function of complex I. Mutant cybrids constructed by transferring mitochondria from lymphoblastoid cell lines of one Chinese LHON family into mtDNA-less (ρo) cells revealed decreases in the levels of ND6, ND1 and ND4L. The m.14484T > C mutation may affect mitochondrial mRNA homeostasis, supported by reduced levels of SLIRP and SUPV3L1 involved in mRNA degradation and increasing expression of ND6, ND1 and ND4L genes. These alterations yielded decreased activity of complex I, respiratory deficiency, diminished mitochondrial ATP production and reduced membrane potential, and increased production of reactive oxygen species in the mutant cybrids. Furthermore, the m.14484T > C mutation promoted apoptosis, evidenced by elevating Annexin V-positive cells, release of cytochrome c into cytosol, levels in apoptotic proteins BAX, caspases 3, 7, 9 and decreasing levels in anti-apoptotic protein Bcl-xL in the mutant cybrids. Moreover, the cybrids bearing the m.14484T > C mutation exhibited the reduced levels of autophagy protein LC3, increased levels of substrate P62 and impaired PINK1/Parkin-dependent mitophagy. Our findings highlighted the critical role of m.14484T > C mutation in the pathogenesis of LHON.

Human TRUB1 is a highly conserved pseudouridine synthase responsible for the formation of Ψ55 in mitochondrial tRNAAsn, tRNAGln, tRNAGlu and tRNAPro.

Pseudouridine (Ψ) at position 55 in tRNAs plays an important role in their structure and function. This modification is catalyzed by TruB/Pus4/Cbf5 family of pseudouridine synthases in bacteria and yeast. However, the mechanism of TRUB family underlying the formation of Ψ55 in the mammalian tRNAs is largely unknown. In this report, the CMC/reverse transcription assays demonstrated the presence of Ψ55 in the human mitochondrial tRNAAsn, tRNAGln, tRNAGlu, tRNAPro, tRNAMet, tRNALeu(UUR) and tRNASer(UCN). TRUB1 knockout (KO) cell lines generated by CRISPR/Cas9 technology exhibited the loss of Ψ55 modification in mitochondrial tRNAAsn, tRNAGln, tRNAGlu and tRNAPro but did not affect other 18 mitochondrial tRNAs. An in vitro assay revealed that recombinant TRUB1 protein can catalyze the efficient formation of Ψ55 in tRNAAsn and tRNAGln, but not in tRNAMet and tRNAArg. Notably, the overexpression of TRUB1 cDNA reversed the deficient Ψ55 modifications in these tRNAs in TRUB1KO HeLa cells. TRUB1 deficiency affected the base-pairing (18A/G-Ψ55), conformation and stability but not aminoacylation capacity of these tRNAs. Furthermore, TRUB1 deficiency impacted mitochondrial translation and biogenesis of oxidative phosphorylation system. Our findings demonstrated that human TRUB1 is a highly conserved mitochondrial pseudouridine synthase responsible for the Ψ55 modification in the mitochondrial tRNAAsn, tRNAGln, tRNAGlu and tRNAPro.

The female germ unit is essential for pollen tube funicular guidance in Arabidopsis thaliana.

In angiosperm, two immotile sperm cells are delivered to the female gametes for fertilization by a pollen tube, which perceives guidance cues from ovules at least at two critical sites, micropyle for short-distance guidance and funiculus for comparably longer distance guidance. Compared with the great progress in understanding pollen tube micropylar guidance, little is known about the signaling for funicular guidance. Here, we show that funiculus plays an important role in pollen tube guidance and report that female gametophyte (FG) plays a critical role in funicular guidance by analysis of a 3-dehydroquinate synthase (DHQS) mutant. Loss function of DHQS in FG interrupts pollen tube funicular guidance, suggesting that the guiding signal is generated from FG. We show the evidence that the capacity of funicular guidance is established during FG functional specification after the establishment of cell identity. Specific expression of DHQS in the synergid cells, central cells, or egg cells can rescue funicular guidance defect in dhqs/+, indicating all the female germ unit cells are involved in the funicular guidance. The finding reveals that the attracting signal of pollen tube funicular guidance was generated at a site and stage manner and provides novel clue to locate and search for the signal.

The Antimicrobial Peptide Esculentin-1a(1-21)NH2 Stimulates Wound Healing by Promoting Angiogenesis through the PI3K/AKT Pathway.

Delayed wound healing is a persistent medical problem mainly caused by decreased angiogenesis. Esculentin-1a(1-21)NH2 [Esc-1a(1-21)NH2], has broad-spectrum antibacterial properties which comes from frog skins. It has shown promise as a treatment for wound healing. However, its effects on angiogenesis as well as the mechanism by which esc-1a(1-21)NH2 enhanced wound healing remained unclear. In this study, we analyzed the structural properties and biocompatibility of esc-1a(1-21)NH2 and evaluated its effect on wound closure using a full-thickness excision model in mice. Our results showed that esc-1a(1-21)NH2 significantly accelerated wound healing by increasing collagen deposition and angiogenesis, characterized by elevated expression levels of platelet, endothelial cell adhesion molecule-1 (CD31) and proliferating cell nuclear antigen (PCNA). Furthermore, the angiogenic activity of esc-1a(1-21)NH2 was confirmed in vitro by various assays. Esc-1a(1-21)NH2 significantly promoted cell migration and cell proliferation in human umbilical vein vascular endothelial cells (HUVECs) via activation of the phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (AKT) pathway, and upregulated the expression of CD31 at both mRNA and protein levels. The effect of esc-1a(1-21)NH2 on angiogenesis was diminished by LY294002, a PI3K pathway inhibitor. Taken together, this study demonstrates that esc-1a(1-21)NH2 accelerates wound closure in mice by promoting angiogenesis via the PI3K/AKT signaling pathway, suggesting its effective application in the treatment of wound healing.

High-Efficient Flame-Retardant Finishing of Cotton Fabrics Based on Phytic Acid.

In this study, an efficient phosphorus-containing flame retardant, PAPBTCA, was synthesized from phytic acid, pentaerythritol, and 1,2,3,4-butane tetracarboxylic acid, and its structure was characterized. PAPBTCA was finished on cotton fabrics by the pad-dry-curing process, and the flame retardancy, flame-retardant durability, and wrinkle resistance of the obtained flame-retardant fabrics were investigated. It should be noted that the heat release rate value of the flame-retardant cotton fabrics treated with 200 g/L PAPBTCA decreased by 90% and its excellent flame retardancy was maintained after 5 washing cycles. Meanwhile, the wrinkle resistance of flame-retardant cotton fabrics has been significantly improved. In addition, compared with the control, the breaking force loss of PAPBTCA-200 in the warp and weft directions was 24% and 21%, respectively. This study provides a new way to utilize natural phosphorus-based flame retardants to establish multifunctional finishing for cotton fabrics.

Purely Organic Fluorescence Afterglow: Visible-Light-Excitation, Inherent Mechanism, Tunable Color, and Practical Applications with Very Low Cost.

Purely organic materials with visible light excitable fluorescence afterglow are promising for applications. Herein, fluorescence afterglow with various intensity and duration was observed on fluorescent dyes once being dispersed in polymer matrix, thanks to the slow reverse intersystem crossing rate (kRISC ) and long delayed fluorescence lifetime (τDF ) derived from the coplanar and rigid chemical structure of the dyes. To verify the mechanism, different polymers were used to tune singlet-triplet splitting energy based on solvent effect. And commercial acriflavine (Acf) film showed blue shifted fluorescence compared to purified one, with slower kRISC (≈100  s-1 ) and longer τDF (0.6 s). Via energy transfer from Acf to rhodamine B, the afterglow color was further regulated, with the largest fluorescence quantum yield of 42.4 %. It was demonstrated that the materials worked on color tunable light sources, and low-cost ($2 for 50 000 labels) anti-counterfeit labels recognized by white light.

Fault Diagnosis of Power Transformer Based on Time-Shift Multiscale Bubble Entropy and Stochastic Configuration Network.

In order to accurately diagnose the fault type of power transformer, this paper proposes a transformer fault diagnosis method based on the combination of time-shift multiscale bubble entropy (TSMBE) and stochastic configuration network (SCN). Firstly, bubble entropy is introduced to overcome the shortcomings of traditional entropy models that rely too heavily on hyperparameters. Secondly, on the basis of bubble entropy, a tool for measuring signal complexity, TSMBE, is proposed. Then, the TSMBE of the transformer vibration signal is extracted as a fault feature. Finally, the fault feature is inputted into the stochastic configuration network model to achieve an accurate identification of different transformer state signals. The proposed method was applied to real power transformer fault cases, and the research results showed that TSMBE-SCN achieved 99.01%, 99.1%, 99.11%, 99.11%, 99.14% and 99.02% of the diagnostic rates under different folding numbers, respectively, compared with conventional diagnostic models MBE-SCN, TSMSE-SCN, MSE-SCN, TSMDE-SCN and MDE-SCN. This comparison shows that TSMBE-SCN has a strong competitive advantage, which verifies that the proposed method has a good diagnostic effect. This study provides a new method for power transformer fault diagnosis, which has good reference value.

Substantia nigra neuromelanin magnetic resonance imaging in patients with different subtypes of Parkinson disease.

Neuromelanin (NM) is a dark pigment that mainly exists in neurons of the substantia nigra pars compacta (SNc). In Parkinson disease (PD) patients, NM concentration decreases gradually with degeneration and necrosis of dopamine neurons, suggesting potential use as a PD biomarker. We aimed to evaluate associations between NM concentration in in vivo SN and PD progression and different motor subtypes using NM magnetic resonance imaging (NM-MRI). Fifty-four patients with idiopathic PD were enrolled. Patients were divided into groups by subtypes with different clinical symptoms: tremor dominant (TD) group and postural instability and gait difficulty (PIGD) group. Fifteen healthy age-matched volunteers were enrolled as controls. All subjects underwent clinical assessment and NM-MRI examination. PD patients showed significantly decreased contrast-to-noise ratio (CNR) values in medial and lateral SN (P < 0.05) compared to controls. CNR values in lateral SN region decreased linearly with PD progression (P = 0.001). PIGD patients showed significant decreases in CNR mean values in lateral SN compared to TD patients (P = 0.004). Diagnostic accuracy of using lateral substantia nigra (SN) in TD and PIGD groups was 79% (sensitivity 76.5%, specificity 78.6%). NM concentration in PD patients decreases gradually during disease progression and differs significantly between PD subtypes. NM may be a reliable biomarker for PD severity and subtype identification.

GaAs-Based InPBi Quantum Dots for High Efficiency Super-Luminescence Diodes.

InPBi exhibits broad and strong photoluminescence at room temperature, and is a potential candidate for fabricating super-luminescence diodes applied in optical coherence tomography. In this paper, the strained InPBi quantum dot (QD) embedded in the AlGaAs barrier on a GaAs platform is proposed to enhance the light emission efficiency and further broaden the photoluminescence spectrum. The finite element method is used to calculate the strain distribution, band alignment and confined levels of InPBi QDs. The carrier recombinations between the ground states and the deep levels are systematically investigated. A high Bi content and a flat QD shape are found preferable for fabricating super-luminescence diodes with high efficiency and a broad emission spectrum.

Direct evidence that suspensor cells have embryogenic potential that is suppressed by the embryo proper during normal embryogenesis.

The suspensor is a temporary supporting structure of proembryos. It has been proposed that suspensor cells also possess embryogenic potential, which is suppressed by the embryo as an effect of the embryo-suspensor interaction. However, data to support this hypothesis are not yet available. In this report, using an in vivo living cell laser ablation technique, we show that Arabidopsis suspensor cells can develop into embryos after removing the embryo proper. The embryo proper plays a critical role in maintaining suspensor cell identity. However, this depends on the developmental stage; after the globular embryo stage, the suspensors no longer possess the potential to develop into embryos. We also reveal that hypophysis formation may be essential for embryo differentiation. Furthermore, we show that, after removing the embryo, auxin gradually accumulates in the top suspensor cell where cell division occurs to produce an embryo. Auxin redistribution likely reprograms the fate of the suspensor cell and triggers embryogenesis in suspensor cells. Thus, we provide direct evidence that the embryo suppresses the embryogenic potential of suspensor cells.

RPL18aB helps maintain suspensor identity during early embryogenesis.

During embryogenesis, plants are thought to use a mechanism that allows the suspensor to maintain its identity. Here, we reported that RPL18aB is involved in this mechanism in Arabidopsis thaliana. The suspensor cells proliferated in rpl18aB and formed a multicellular structure rather than undergo programmed cell death, as in wild type. Suspensors of rpl18aB expressed the embryo proper marker, DRN::GFP, but not the suspensor marker, WOX8::GFP. In addition, auxin accumulated throughout the suspensors of rpl18aB proembryos. Suspensor-specific expression of RPL18aB could rescue the cell proliferation defects in rpl18aB suspensors. These findings supported a role for RPL18aB in maintaining suspensor identity.

Acetylglutamate kinase is required for both gametophyte function and embryo development in Arabidopsis thaliana.

The specific functions of the genes encoding arginine biosynthesis enzymes in plants are not well characterized. We report the isolation and characterization of Arabidopsis thaliana N-acetylglutamate kinase (NAGK), which catalyzes the second step of arginine biosynthesis. NAGK is a plastid-localized protein and is expressed during most developmental processes in Arabidopsis. Heterologous expression of the Arabidopsis NAGK gene in a NAGK-deficient Escherichia coli strain fully restores bacterial growth on arginine-deficient medium. nagk mutant pollen tubes grow more slowly than wild type pollen tubes and the phenotype is restored by either specifically through complementation by NAGK in pollen, or exogenous supplementation of arginine. nagk female gametophytes are defective in micropylar pollen tube guidance due to the fact that female gametophyte cell fate specification was specifically affected. Expression of NAGK in synergid cells rescues the defect of nagk female gametophytes. Loss-of-function of NAGK results in Arabidopsis embryos not developing beyond the four-celled embryo stage. The embryo-defective phenotype in nagk/NAGK plants cannot be rescued by watering nagk/NAGK plants with arginine or ornithine supplementation. In conclusion, our results reveal a novel role of NAGK and arginine in regulating gametophyte function and embryo development, and provide valuable insights into arginine transport during embryo development.

Active Intervention Can Decrease Burnout In Ed Nurses.

The aim of this study was to evaluate whether active intervention can decrease job burnout and improve performance among ED nurses. METHODS: This study was carried out in the emergency departments of 3 hospitals randomly selected from 8 comprehensive high-level hospitals in Jinan, China. A total of 102 nurses were enrolled and randomly divided into control and intervention groups. For 6 months, nurses in intervention groups were treated with ordinary treatment plus comprehensive management, whereas nurses in the control group were treated with ordinary management, respectively. Questionnaires were sent and collected at baseline and at the end of the study. The Student t test was used to evaluate the effect of comprehensive management in decreasing burnout. RESULTS: All ED nurses showed symptoms of job burnout at different levels. Our data indicated that comprehensive management significantly decreased emotional exhaustion and depersonalization (P < .01). DISCUSSION: The findings suggest that active intervention with comprehensive management may effectively reduce job burnout in ED nurses and contribute to relieving work-related stress and may further protect against potential mental health problems.

A bipartite molecular module controls cell death activation in the Basal cell lineage of plant embryos.

Plant zygote divides asymmetrically into an apical cell that develops into the embryo proper and a basal cell that generates the suspensor, a vital organ functioning as a conduit of nutrients and growth factors to the embryo proper. After the suspensor has fulfilled its function, it is removed by programmed cell death (PCD) at the late stages of embryogenesis. The molecular trigger of this PCD is unknown. Here we use tobacco (Nicotiana tabacum) embryogenesis as a model system to demonstrate that the mechanism triggering suspensor PCD is based on the antagonistic action of two proteins: a protease inhibitor, cystatin NtCYS, and its target, cathepsin H-like protease NtCP14. NtCYS is expressed in the basal cell of the proembryo, where encoded cystatin binds to and inhibits NtCP14, thereby preventing precocious onset of PCD. The anti-cell death effect of NtCYS is transcriptionally regulated and is repressed at the 32-celled embryo stage, leading to increased NtCP14 activity and initiation of PCD. Silencing of NtCYS or overexpression of NtCP14 induces precocious cell death in the basal cell lineage causing embryonic arrest and seed abortion. Conversely, overexpression of NtCYS or silencing of NtCP14 leads to profound delay of suspensor PCD. Our results demonstrate that NtCYS-mediated inhibition of NtCP14 protease acts as a bipartite molecular module to control initiation of PCD in the basal cell lineage of plant embryos.

The Arabidopsis Exine Formation Defect (EFD) gene is required for primexine patterning and is critical for pollen fertility.

Exine, the outermost layer of a pollen grain, has important roles in protecting microspore cytoplasm and determining species-specific interactions between pollen and stigma. The molecular mechanism underlying pollen exine formation, however, remains largely unknown. Here, we report the characterization of an Arabidopsis male-sterile mutant, efd, which exhibits male sterility in first-forming flowers. The Exine Formation Defect (EFD) gene is strongly expressed in microsporocytes, tetrads and the tapetum, and encodes a nuclear-localized de novo DNA methyltransferase. Detailed observations revealed that EFD is involved in both callose wall and primexine formation during microsporogenesis. Microspores in tetrads are not well separated in efd due to an abnormal callose wall. Its plasma membrane undulation appears normal, but primexine patterning is impaired. Primexine matrix establishment and sporopollenin accumulation at specific positions are disturbed, and thus exine formation is totally blocked in efd. We confirmed that EFD is required for pollen exine formation and male fertility via the regulation of callose wall and primexine formation. We also found that positional sporopollenin accumulation is not involved in regulating membrane undulation, but is related to the complete separation of tetrad microspores during primary exine patterning.

NtProRP1, a novel proline-rich protein, is an osmotic stress-responsive factor and specifically functions in pollen tube growth and early embryogenesis in Nicotiana tabacum.

Proline-rich proteins (PRPs) are known to play important roles in sexual plant reproduction. Most of the known proteins in the family were found in styles or pollen and modulate pollen tube growth. Here, we identified a novel member of the gene family, NtProRP1, which is preferentially expressed in tobacco pollen grains, pollen tubes and zygotes. NtProRP1 could be secreted into the extracellular space including the cell wall, and the predicted N-terminal signal peptide is crucial for its secretion. In NtProRP1-RNAi plants, pollen germination and pollen tube growth were significantly slower and showed zigzag or swell morphology in vitro. Early embryogenesis also exhibited aberrant development, indicative of its critical role in both pollen tube growth and early embryogenesis. Further investigation revealed that NtProRP1 plays a crucial role in osmotic stress response during pollen tube growth and is likely regulated by Tsi, a stress-responsive gene, suggesting that the regulatory mechanism is also involved in the stress response during sexual plant reproduction. These data provide evidence that NtProRP1 functions as a downstream factor of Tsi1 in the stress response and converges the stress signal into the modulation of pollen tube growth and early embryogenesis.

Alkaline amino acid modification based on biological phytic acid for preparing flame-retardant and antibacterial cellulose-based fabrics.

Cellulose-based fabrics have significant advantages, but their application scenarios are limited due to their flammability. This work used biomass phytic acid and protein decomposition products, alkaline amino acids (arginine, lysine, histidine) to prepare alkaline amino acid flame retardants (PALA, PALL, PALH), and they were utilized to endow Lyocell fabrics with flame-retardant and antibacterial properties. When the weight gain was about 16.0 wt%, PALA exhibited better flame-retardant effect, and the limited oxygen index value of PALA-Lyocell reached 47.1 %. In the cone calorimetry test, PALA showed the best flame-retardant efficiency in reducing flame growth index with a 92.0 % decrease in peak heat release rate. The results of thermogravimetric analysis coupled with Fourier Transform Infrared spectroscopy (TG-FTIR) and char residues indicated that the flame-retardant property of alkaline amino acid flame retardants was formed through the combined action of gas and condensed phases. In the antibacterial test, PALA had the highest antibacterial rate against Staphylococcus aureus at 97.2 %. Mechanical property, handle feeling, and whiteness results had indicated that alkaline amino acid based flame retardants had little effect on the physical properties of Lyocell fabrics. This work confirms alkaline amino acid based flame retardants have functions of flame-retardant and antibacterial properties, providing reference for the practical value of biomass in cellulose-based fabrics.

A P/N flame retardant for polyester-cotton fabrics: Flame retardancy, mechanical properties and antibacterial property.

A phosphorus­nitrogen synergistic flame retardant (named POI) was obtained by the chemical reaction between phenylphosphonic acid (PPOA) and polyethyleneimine (PEI), and used to give the flame retardancy of PTCO. The effects of PPOA and POI on various properties of PTCO were investigated. PPOA obviously improved the flame retardancy of PTCO/PPOA, while the breaking force of PTCO/PPOA was greatly reduced. However, the introduction of PEI made the surface of fabrics smoother. PTCO/POI had better flame retardancy than PTCO/PPOA did, and the limiting oxygen index value of PTCO/POI reached to 29.8 %. POI had a good effect on reducing the Rmax of both cotton and polyester components. The phosphoric acid groups in POI can promote the dehydration and carbonization reactions of PTCO, which protects the inner fabrics, and POI can release incombustible gases such as NH3 and N2 during burning, which can dilute the oxygen concentration. The flame-retardant mechanism of PTCO/POI was mainly the condensed phase. At the same time, there were no changes in whiteness and mechanical properties compared with those of PTCO, and it also had antibacterial property. This work provides a simple and effective method to prepare flame-retardant and antibacterial PTCO.

Management of triplet excitons transition: fine regulation of Förster and dexter energy transfer simultaneously.

Understanding and management of triplet excitons transition in the same molecule remain a great challenge. Hence, for the first time, by host engineering, manageable transitions of triplet excitons in a naphthalimide derivative NDOH were achieved, and monitored through the intensity ratio (ITADF/IRTP) between thermally activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP). Energy differences between lowest triplet excited states of host and guest were changed from 0.03 to 0.17 eV, and ITADF/IRTP of NDOH decreased by 200 times, thus red shifting the afterglow color. It was proposed that shorter conjugation length led to larger band gaps of host materials, thus contributing to efficient Dexter and inefficient Förster energy transfer. Interestingly, no transition to singlet state and only strongest RTP with quantum yield of 13.9% could be observed, when PBNC with loosest stacking and largest band gap acted as host. This work provides novel insight for the management and prediction of triplet exciton transitions and the development of smart afterglow materials.

The fabrication of flame-retardant viscose fabrics with phytic acid-based flame retardants: Balancing efficient flame retardancy and tensile strength.

Viscose fabrics have been widely used in various applications, but their potential fire hazard has been a concern. To address this issue, improving the flame retardancy of viscose fabrics has become a significant priority. Phytic acid (PA) and xylitol were used to create a novel flame retardant, PAXY. PAXY was finished on viscose fabrics by pad-dry-curing process, and the performance of coated viscose fabrics was investigated. The results showed that the limiting oxygen index value of PAXY13-100 (fabrics finished with a 100 g/L flame-retardant solution and the flame retardant synthesized by a 1: 3 M ratio of PA to xylitol) reached 32.8 % and the heat release rate value was decreased by 77 %. Based on the findings from the analysis of both the gas phase and condensed phase products, PAXY promoted the dehydration of viscose fabrics to produce a denser char layer, which inhibited the production of flammable gases. Surprisingly, the breaking force retention of PAXY13-100 reached 90 % in warp and 114 % in weft. Compared with that of 100 g/L PA-treated fabrics, the breaking force of PAXY13-100 increased by nearly 400 %. This work provides a new strategy for PA-based flame-retardant finishing with the synergy of flame retardancy and breaking force retention.