Genetic Susceptibility Modifies Relationships Between Air Pollutants and Stroke Risk: A Large Cohort Study.

BACKGROUND: The extent to which genetic susceptibility modifies the associations between air pollutants and the risk of incident stroke is still unclear. This study was designed to investigate the separate and joint associations of long-term exposure to air pollutants and genetic susceptibility on stroke risk. METHODS: The participants of this study were recruited by the UK Biobank between 2006 and 2010. These participants were followed up from the enrollment until the occurrence of stroke events or censoring of data. Hazard ratios (HRs) and 95% CIs for stroke events associated with long-term exposure to air pollutants were estimated by fitting both crude and adjusted Cox proportional hazards models. Additionally, the polygenic risk score was calculated to estimate whether the polygenic risk score modifies the associations between exposure to air pollutants and incident stroke. RESULTS: A total of 502 480 subjects were included in this study. After exclusion, 452 196 participants were taken into the final analysis. During a median follow-up time of 11.7 years, 11 334 stroke events were observed, with a mean age of 61.60 years, and men accounted for 56.2% of the total cases. Long-term exposures to particulate matter with an aerodynamic diameter smaller than 2.5 µm (adjusted HR, 1.70 [95% CI, 1.43-2.03]) or particulate matter with an aerodynamic diameter smaller than 10 µm (adjusted HR, 1.50 [95% CI, 1.36-1.66]), nitrogen dioxide (adjusted HR, 1.10 [95% CI, 1.07-1.12]), and nitrogen oxide (adjusted HR, 1.04 [95% CI, 1.02-1.05]) were pronouncedly associated with increased risk of stroke. Meanwhile, participants with high genetic risk and exposure to high air pollutants had ≈45% (31%, 61%; particulate matter with an aerodynamic diameter smaller than 2.5 µm), 48% (33%, 65%; particulate matter with an aerodynamic diameter smaller than 10 µm), 51% (35%, 69%; nitrogen dioxide), and 39% (25%, 55%; nitrogen oxide) higher risk of stroke compared with those with low genetic risk and exposure to low air pollutants, respectively. Of note, we observed additive and multiplicative interactions between genetic susceptibility and air pollutants on stroke events. CONCLUSIONS: Chronic exposure to air pollutants was associated with an increased risk of stroke, especially in populations at high genetic risk.

Regulating Hetero-Nucleation Enabling Over 14% Efficient Kesterite Solar Cells.

Developing well-crystallized light-absorbing layers remains a formidable challenge in the progression of kesterite Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. A critical aspect of optimizing CZTSSe lies in accurately governing the high-temperature selenization reaction. This process is intricate and demanding, with underlying mechanisms requiring further comprehension. This study introduces a precursor microstructure-guided hetero-nucleation regulation strategy for high-quality CZTSSe absorbers and well-performing solar cells. The alcoholysis of 2-methoxyethanol (MOE) and the generation of high gas-producing micelles by adding hydrogen chloride (HCl) as a proton additive into the precursor solution are successfully suppressed. This tailored modification of solution components reduces the emission of volatiles during baking, yielding a compact and dense precursor microstructure. The reduced-roughness surface nurtures the formation of larger CZTSSe nuclei, accelerating the ensuing Ostwald ripening process. Ultimately, CZTSSe absorbers with enhanced crystallinity and diminished defects are fabricated, attaining an impressive 14.01% active-area power conversion efficiency. The findings elucidate the influence of precursor microstructure on the selenization reaction process, paving a route for fabricating high-quality kesterite CZTSSe films and high-efficiency solar cells.

In Situ Observation of Field-Induced Nanoprotrusion Growth on a Carbon-Coated Tungsten Nanotip.

Nanoprotrusion (NP) on metal surface and its inevitable contamination layer under high electric field is often considered as the primary precursor that leads to vacuum breakdown, which plays an extremely detrimental effect for high energy physics equipment and many other devices. Yet, the NP growth has never been experimentally observed. Here, we conduct field emission (FE) measurements along with in situ transmission electron microscopy (TEM) imaging of an amorphous-carbon (a-C) coated tungsten nanotip at various nanoscale vacuum gap distances. We find that under certain conditions, the FE current-voltage (I-V) curves switch abruptly into an enhanced-current state, implying the growth of an NP. We then run field emission simulations, demonstrating that the temporary enhanced-current I-V is perfectly consistent with the hypothesis that a NP has grown at the apex of the tip. This hypothesis is also confirmed by the repeatable in situ observation of such a nanoprotrusion and its continued growth during successive FE measurements in TEM. We tentatively attribute this phenomenon to field-induced biased diffusion of surface a-C atoms, after performing a finite element analysis that excludes the alternative possibility of field-induced plastic deformation.

Deconvolution at the single-cell level reveals ovarian cell-type-specific transcriptomic changes in PCOS.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders in females of childbearing age. Various types of ovarian cells work together to maintain normal reproductive function, whose discordance often takes part in the development and progression of PCOS. Understanding the cellular heterogeneity and compositions of ovarian cells would provide insight into PCOS pathogenesis, but are, however, not well understood. Transcriptomic characterization of cells isolated from PCOS cases have been assessed using bulk RNA-seq but cells isolated contain a mixture of many ovarian cell types. METHODS: Here we utilized the reference scRNA-seq data from human adult ovaries to deconvolute and estimate cell proportions and dysfunction of ovarian cells in PCOS, by integrating various granulosa cells(GCs) transcriptomic data. RESULTS: We successfully defined 22 distinct cell clusters of human ovarian cells. Then after transcriptome integration, we obtained a gene expression matrix with 13,904 genes within 30 samples (15 control vs. 15 PCOS). Subsequent deconvolution analysis revealed decreased proportion of small antral GCs and increased proportion of KRT8high mural GCs, HTRA1high cumulus cells in PCOS, especially increased differentiation from small antral GCs to KRT8high mural GCs. For theca cells, the abundance of internal theca cells (TCs) and external TCs was both increased. Less TCF21high stroma cells (SCs) and more STARhigh SCs were observed. The proportions of NK cells and monocytes were decreased, and T cells occupied more in PCOS and communicated stronger with inTCs and exTCs. In the end, we predicted the candidate drugs which could be used to correct the proportion of ovarian cells in patients with PCOS. CONCLUSIONS: Taken together, this study provides insights into the molecular alterations and cellular compositions in PCOS ovarian tissue. The findings might contribute to our understanding of PCOS pathophysiology and offer resource for PCOS basic research.

ATP-binding cassette protein ABCA7 deficiency impairs sphingomyelin synthesis, cognitive discrimination, and synaptic plasticity in the entorhinal cortex.

Sphingomyelin (SM) is an abundant plasma membrane and plasma lipoprotein sphingolipid. We previously reported that ATP-binding cassette family A protein 1 (ABCA1) deficiency in humans and mice decreases plasma SM levels. However, overexpression, induction, downregulation, inhibition, and knockdown of ABCA1 in human hepatoma Huh7 cells did not decrease SM efflux. Using unbiased siRNA screening, here, we identified that ABCA7 plays a role in the biosynthesis and efflux of SM without affecting cellular uptake and metabolism. Since loss of function mutations in the ABCA7 gene exhibit strong associations with late-onset Alzheimer's disease across racial groups, we also studied the effects of ABCA7 deficiency in the mouse brain. Brains of ABCA7-deficient (KO) mice, compared with WT, had significantly lower levels of several SM species with long chain fatty acids. In addition, we observed that older KO mice exhibited behavioral deficits in cognitive discrimination in the active place avoidance task. Next, we performed synaptic transmission studies in brain slices obtained from older mice. We found anomalies in synaptic plasticity at the intracortical synapse in layer II/III of the lateral entorhinal cortex but not in the hippocampal CA3-CA1 synapses in KO mice. These synaptic abnormalities in KO brain slices were rescued with extracellular SM supplementation but not by supplementation with phosphatidylcholine. Taken together, these studies identify a role of ABCA7 in brain SM metabolism and the importance of SM in synaptic plasticity and cognition, as well as provide a possible explanation for the association between ABCA7 and late-onset Alzheimer's disease.

Flavonoids are involved in salt tolerance through ROS scavenging in the halophyte Atriplex canescens.

KEY MESSAGE: The content of flavonoids could increase in A. canescens under saline conditions. Overexpression of AcCHI in transgenic A. thaliana promotes flavonoid biosynthesis, thereby functioning in the tolerance of transgenic plants to salt and osmotic stress by maintaining ROS homeostasis. Atriplex canescens is a halophytic forage shrub with excellent adaptation to saline environment. Our previous study showed that a large number of genes related to the biosynthesis of flavonoids in A. canescens were significantly up-regulated by NaCl treatments. However, it remains unclear whether flavonoids are involved in A. canescens response to salinity. In this study, we found that the accumulation of flavonoids significantly increased in either the leaves or roots of A. canescens seedling under 100 and 300 mM NaCl treatments. Correspondingly, AcCHS, AcCHI and AcF3H, which encode three key enzymes (chalcone synthases (CHS), chalcone isomerase (CHI), and flavanone 3-hydroxylase (F3H), respectively) of flavonoids biosynthesis, were significantly induced in the roots or leaves of A. canescens by 100 or 300 mM NaCl. Then, we generated the transgenic Arabidopsis thaliana overexpressing AcCHI and found that transgenic plants accumulated more flavonoids through enhancing the pathway of flavonoids biosynthesis. Furthermore, overexpression of AcCHI conferred salt and osmotic stress tolerance in transgenic A. thaliana. Contrasted with wild-type A. thaliana, transgenic lines grew better with greater biomass, less H2O2 content as well as lower relative plasma permeability in either salt or osmotic stress conditions. In conclusion, our results indicate that flavonoids play an important role in A. canescens response to salt stress through reactive oxygen species (ROS) scavenging and the key enzyme gene AcCHI in flavonoids biosynthesis pathway of A. canescens has the potential to improve the stress tolerance of forages and crops.

Turning waste into valuables: In situ deposition of polypyrrole on the obsolete mask for Cr(VI) removal and desalination.

The global mask consumption has been exacerbated because of the coronavirus disease 2019 (COVID-19) pandemic. Simultaneously, the traditional mask disposal methods (incineration and landfill) have caused serious environmental pollution and waste of resources. Herein, a simple and green mass-production method has been proposed to recycle carbon protective mask (CPM) into the carbon protective mask/polydopamine/polypyrrole (CPM/PDA/PPy) composite by in situ polymerization of PPy. The CPM/PDA/PPy composite was used for the removal of Cr(VI) and salt ions to produce clean water. The synergistic effect of PPy and the CPM improved the removal capability of Cr(VI). The CPM/PDA/PPy composite provided high adsorption capacity (358.68 mg g-1) and economic value (811.42 mg $-1). Consequently, the CPM/PDA/PPy (cathode) was combined with MnO2 (anode) for desalination in CDI cells, demonstrated excellent desalination capacity (26.65 mg g-1) and ultrafast salt adsorption rate (6.96 mg g-1 min-1), which was higher than conventional CDI cells. Our work proposes a new low-carbon strategy to recycle discarded masks and demonstrates their utilization in Cr(VI) removal and seawater desalination.

Fault Identification and Localization of a Time-Frequency Domain Joint Impedance Spectrum of Cables Based on Deep Belief Networks.

To improve the accuracy of shallow neural networks in processing complex signals and cable fault diagnosis, and to overcome the shortage of manual dependency and cable fault feature extraction, a deep learning method is introduced, and a time-frequency domain joint impedance spectrum is proposed for cable fault identification and localization based on a deep belief network (DBN). Firstly, based on the distribution parameter model of power cables, we model and analyze the cables under normal operation and different fault types, and we obtain the headend input impedance spectrum and the headend input time-frequency domain impedance spectrum of cables under various operating conditions. The headend input impedance amplitude and phase of normal operation and different fault cables are extracted as the original input samples of the cable fault type identification model; the real part of the headend input time-frequency domain impedance of the fault cables is extracted as the original input samples of the cable fault location model. Then, the unsupervised pre-training and supervised inverse fine-tuning methods are used for automatically learning, training, and extracting the cable fault state features from the original input samples, and the DBN-based cable fault type recognition model and location model are constructed and used to realize the type recognition and location of cable faults. Finally, the proposed method is validated by simulation, and the results show that the method has good fault feature extraction capability and high fault type recognition and localization accuracy.

Ginsentide-like Coffeetides Isolated from Coffee Waste Are Cell-Penetrating and Metal-Binding Microproteins.

Coffee processing generates a huge amount of waste that contains many natural products. Here, we report the discovery of a panel of novel cell-penetrating and metal ion-binding microproteins designated coffeetide cC1a-c and cL1-6 from the husk of two popular coffee plants, Coffea canephora and Coffea liberica, respectively. Combining sequence determination and a database search, we show that the prototypic coffeetide cC1a is a 37-residue, eight-cysteine microprotein with a hevein-like cysteine motif, but without a chitin-binding domain. NMR determination of cC1a reveals a compact structure that confers its resistance to heat and proteolytic degradation. Disulfide mapping together with chemical synthesis reveals that cC1a has a ginsentide-like, and not a hevein-like, disulfide connectivity. In addition, transcriptomic analysis showed that the 98-residue micrcoproten-like coffeetide precursor contains a three-domain arrangement, like ginsentide precursors. Molecular modeling, together with experimental validation, revealed a Mg2+ and Fe3+ binding pocket at the N-terminus formed by three glutamic acids. Importantly, cC1a is amphipathic with a continuous stretch of 19 apolar amino acids, which enables its cell penetration to target intracellular proteins, despite being highly negatively charged. Our findings suggest that coffee by-products could provide a source of ginsentide-like bioactive peptides that have the potential to target intracellular proteins.

A Multifunctional Polymer as an Interfacial Layer for Efficient and Stable Perovskite Solar Cells.

Metal-cation defects and halogen-anion defects in perovskite films are critical to the efficiency and stability of perovskite solar cells (PSCs). In this work, a random polymer, poly(methyl methacrylate-co-acrylamide) (PMMA-AM), was synthesized to serve as an interfacial passivation layer for synergistically passivating the under-coordinated Pb2+ and anchor the I- of the [PbI6 ]4- octahedron. Additionally, the interfacial PMMA-AM passivation layer cannot be destroyed during the hole transport layer deposition because of its low solubility in chlorobenzene. This passivation leads to an enhancement in the open-circuit voltage from 1.12 to 1.22 V and improved stability in solar cell devices, with the device maintaining 95 % of the initial power conversion efficiency (PCE) over 1000 h of maximum power point tracking. Additionally, a large-area solar cell module was fabricated using this approach, achieving a PCE of 20.64 %.

DNA Zipper Mediated Membrane Fusion for Rapid Exosomal MiRNA Detection.

Accurate and reliable detection of exosomal miRNA can serve as a promising method for early diagnosis of disease and evaluation of therapeutic effects. However, current exosomal miRNA detection methods commonly involve exosome enrichment, containing RNA extraction, and qRT-PCR based quantification, which are expensive and time-consuming. Herein, we develop a DNA zipper-mediated membrane fusion approach for rapid exosomal miRNA detection and cancer diagnosis. First, a lipid vesicle probe containing miR21-targeting molecular beacons (MBs) is constructed and further loaded with zipper DNA constructs (ZDCs) on its surface. Meanwhile, complementary zipper DNA constructs (cZDCs) are introduced on the exosome of interest. Upon mixing them together, zipping between ZDC and cZDC induces the membrane fusion of exosomes and vesicle probes, triggering the recognition of exosomal miR21 by contained MBs and fluorescence emission that can be conveniently detected within 30 min. Importantly, with the assistance of flow cytometry, miR21-overexpressed tumor exosomes derived from either cell culture medium or clinical patient serums can be distinguished from exosomes secreted from normal cells. This approach provides a convenient way to accurately detect the exosomal miRNA, which may hold great potential in liquid biopsy for early cancer diagnosis and monitoring the therapeutic effects during the treatments.

High Power Figure-of-Merit, 10.6-kV AlGaN/GaN Lateral Schottky Barrier Diode with Single Channel and Sub-100-µm Anode-to-Cathode Spacing.

GaN-based lateral Schottky barrier diodes (SBDs) have attracted great attention for high-power applications due to its combined high electron mobility and large critical breakdown field. However, the breakdown voltage (BV) of the SBDs are far from exploiting the material advantages of GaN at present, limiting the desire to use GaN for ultra-high voltage (UHV) applications. Then, a golden question is whether the excellent properties of GaN-based materials can be practically used in the UHV field? Here, UHV AlGaN/GaN SBDs are demonstrated on sapphire with a BV of 10.6 kV, a specific on-resistance (RON,SP ) of 25.8 mΩ cm2 , yielding a power figure-of-merit (P-FOM = BV2 /RON,SP ) of 4.35 GW cm-2 . These devices are designed with single channel and 85-µm anode-to-cathode spacing, without other additional electric field management, demonstrating its great potential for the UHV application in power electronics.

Lipid metabolism-related gene prognostic index (LMRGPI) reveals distinct prognosis and treatment patterns for patients with early-stage pulmonary adenocarcinoma.

Background: Lipid metabolism plays a pivotal role in cancer progression and metastasis. This study aimed to investigate the prognostic value of lipid metabolism-related genes (LMRGs) in early-stage lung adenocarcinoma (LUAD) and develop a lipid metabolism-related gene prognostic index (LMRGPI) to predict their overall survival (OS) and treatment response. Methods: A total of 774 early-stage LUAD patients were identified from The Cancer Genome Atlas (TCGA, 403 patients) database and Gene Expression Omnibus (GEO, 371 patients) database. The non-negative Matrix Factorization (NMF) algorithm was used to identify different population subtypes based on LMRGs. The Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used to develop the LMRGPI, with receiver operating characteristic (ROC) curves and concordance index being used to evaluate its performance. The characteristics of mutation landscape, enriched pathways, tumor microenvironment (TME), and treatment response between different LMRGPI groups were also investigated. Results: We identified two population subtypes based on LMRGs in the TCGA-LUAD cohort, with distinct prognosis, TME, and immune status being observed. LMRGPI was developed based on the expression levels of six LMRGs, including ANGPTL4, NPAS2, SLCO1B3, ACOXL, ALOX15, and B3GALNT1. Higher LMRGPI was correlated with poor OS both in TCGA and GSE68465 cohorts. Two nomograms were established to predict the survival probability of early-stage LUAD, with higher consistencies being observed between the predicted and actual OS. Higher LMRGPI was significantly correlated with more frequent TP53 mutation, higher tumor mutation burden (TMB), and up-regulation of CD274. Besides, patients with higher LMRGPI presented unremarkable responses for gefitinib, erlotinib, cisplatin, and vinorelbine, while they tend to have a favorable response for immune checkpoint inhibitors (ICIs). The opposite results were observed in the low-LMRGPI group. Conclusions: We comprehensively investigated the prognostic value of LMRGs in early-stage LUAD. Given its good prognostic ability, LMRGPI could serve as a promising biomarker to predict the OS and treatment response of these patients.

Nitrogen-doped graphene quantum dots induce ferroptosis through disrupting calcium homeostasis in microglia.

BACKGROUND: Along with the wild applications of nitrogen-doped graphene quantum dots (N-GQDs) in the fields of biomedicine and neuroscience, their increasing exposure to the public and potential biosafety problem has gained more and more attention. Unfortunately, the understanding of adverse effects of N-GQDs in the central nervous system (CNS), considered as an important target of nanomaterials, is still limited. RESULTS: After we found that N-GQDs caused cell death, neuroinflammation and microglial activation in the hippocampus of mice through the ferroptosis pathway, microglia was used to assess the molecular mechanisms of N-GQDs inducing ferroptosis because it could be the primary target damaged by N-GQDs in the CNS. The microarray data suggested the participation of calcium signaling pathway in the ferroptosis induced by N-GQDs. In microglial BV2 cells, when the calcium content above the homeostatic level caused by N-GQDs was reversed, the number of cell death, ferroptosis alternations and excessive inflammatory cytokines release were all alleviated. Two calcium channels of L-type voltage-gated calcium channels (L-VGCCs) in plasma membrane and ryanodine receptor (RyR) in endoplasmic reticulum (ER) took part in N-GQDs inducing cytosolic calcium overload. L-VGCCs and RyR calcium channels were also involved in promoting the excess iron influx and triggering ER stress response, respectively, which both exert excessive ROS generation and result in the ferroptosis and inflammation in BV2 cells. CONCLUSION: N-GQDs exposure caused ferroptosis and inflammatory responses in hippocampus of mice and cultured microglia through activating two calcium channels to disrupt intracellular calcium homeostasis. The findings not only posted an alert for biomedical applications of N-GQDs, but also highlighted an insight into mechanism researches of GQDs inducing multiple types of cell death in brain tumor therapy in the future.

Proportion and risk factors of diabetic retinopathy by stage in less-developed rural areas of Hunan province of China: A multi-site cross-sectional study.

AIMS: To investigate the proportion and risk factors of diabetic retinopathy (DR) by stages in less-developed rural areas in Hunan Province of China. BACKGROUND: DR is common among people with diabetes but not well recognized in less-developed rural areas. There is insufficient evidence on the risk factors of DR by stages, making it challenging to develop targeted prevention and intervention programs for DR in primary care settings. METHODS: A multi-site cross-sectional survey was conducted among people with type 2 diabetes mellitus (T2DM) from four less-developed counties in Hunan Province of China. All participants underwent the screening of DR via digital fundus photography and completed self-reported questionnaires on their socio-demographic and clinical characteristics, diabetes self-efficacy, diabetes self-care behaviors, social support, family function, and health service accessibility. The multinomial logistic regression models were employed to explore the risk factors of DR by stage, which were selected based on the socio-ecological model, literature, and clinical experience. RESULTS: A total of 196 participants were included in this study with an average age of 57.43 ± 10.26. 59.6% (117/196) of the participants were identified as DR, including 37.2% (73/196) non-proliferative DR and 22.4% (44/196) proliferative DR. Compared to the non-DR group, the risk factors of non-proliferative DR and proliferative DR were diabetes duration (OR: 1.10, 95 CI%: 1.04-1.17; OR: 1.14, 95 CI% 1.06-1.22) and self-monitoring of blood glucose (OR: 1.09, 95 CI% 1.01-1.17; OR: 1.11, 95 CI%: 1.02-1.20); the protective factors of non-proliferative DR was accessible complication prevention and management education (OR: 0.37, 95 CI% 0.14-0.94) while the protective factors of proliferative DR were physical activities (OR: 0.89, 95 CI%: 0.80-0.98). Compared to the non-proliferative DR group, the protective factors of proliferative DR were physical activities (OR: 0.89, 95 CI% 0.02-0.89) and family function (OR: 0.84, 95 CI%: 0.04-0.84). CONCLUSION: DR was prevalent among people with T2DM in less-developed rural areas, indicating the need of strengthening DR screening. Risk factors of DR varied by stage while sharing some common factors. Future DR prevention and intervention programs may benefit from improving these factors to reduce the risk of DR by stage.

Exploring the Q-markers of Angelica sinensis (Oliv.) Diels of anti-platelet aggregation activity based on spectrum-effect relationships.

The radix of Angelica sinensis (Oliv.) Diels (RAS) is widely used in medicinal and dietary applications in China, and has the function for replenishing and invigorating the blood, stopping pain and moistening the intestines. In this study, RAS from the main geoherb regions showed better efficacy in inhibiting Adenosine diphosphate- or arachidonic acid-induced platelet aggregation than those from non-geoherb regions. In addition, the HPLC fingerprints of 30 batches of RAS, as part of the comprehensive evaluation of RAS, were established and used for spectral efficiency to screen the quality markers for anti-platelet aggregation activities. Five compounds in RAS-senkyunolide I, uridine, guanine, ferulic acid and adenosine-were demonstrated to contribute significantly to the anti-platelet aggregation activity. These bioactive compounds, especially senkyunolide I and ferulic acid with stronger activities, could be used as quality markers of RAS for quality control of RAS.

The cytochrome P450 CYP77A4 is involved in auxin-mediated patterning of the Arabidopsis thaliana embryo.

Metabolism often plays an important role in developmental control, in addition to supporting basal physiological requirements. However, our understanding of this interaction remains limited. Here, we performed quantitative phenome analysis of Arabidopsis thaliana cytochrome P450 mutants to identify a novel interaction between development and metabolism. We found that cyp77a4 mutants exhibit specific defects in cotyledon development, including asymmetric positioning and cup-shaped morphology, which could be rescued by introducing the CYP77A4 gene. Microscopy revealed that the abnormal patterning was detected at least from the 8-cell stage of the cyp77a4 embryos. We next analysed auxin distribution in mutant embryos, as the phenotypes resembled those of auxin-related mutants. We found that the auxin response pattern was severely perturbed in the cyp77a4 embryos owing to an aberrant distribution of the auxin efflux carrier PIN1. CYP77A4 intracellularly localised to the endoplasmic reticulum, which is consistent with the notion that this enzyme acts as an epoxidase of unsaturated fatty acids in the microsomal fraction. We propose that the CYP77A4-dependent metabolic pathway is an essential element for the establishment of polarity in plant embryos.

Host AAA+ ATPase TER94 Plays Critical Roles in Building the Baculovirus Viral Replication Factory and Virion Morphogenesis.

TER94 is a multifunctional AAA+ ATPase crucial for diverse cellular processes, especially protein quality control and chromatin dynamics in eukaryotic organisms. Many viruses, including coronavirus, herpesvirus, and retrovirus, coopt host cellular TER94 for optimal viral invasion and replication. Previous proteomics analysis identified the association of TER94 with the budded virions (BVs) of baculovirus, an enveloped insect large DNA virus. Here, the role of TER94 in the prototypic baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) life cycle was investigated. In virus-infected cells, TER94 accumulated in virogenic stroma (VS) at the early stage of infection and subsequently partially rearranged in the ring zone region. In the virions, TER94 was associated with the nucleocapsids of both BV and occlusion-derived virus (ODV). Inhibition of TER94 ATPase activity significantly reduced viral DNA replication and BV production. Electron/immunoelectron microscopy revealed that inhibition of TER94 resulted in the trapping of nucleocapsids within cytoplasmic vacuoles at the nuclear periphery for BV formation and blockage of ODV envelopment at a premature stage within infected nuclei, which appeared highly consistent with its pivotal function in membrane biogenesis. Further analyses showed that TER94 was recruited to the VS or subnuclear structures through interaction with viral early proteins LEF3 and helicase, whereas inhibition of TER94 activity blocked the proper localization of replication-related viral proteins and morphogenesis of VS, providing an explanation for its role in viral DNA replication. Taken together, these data indicated the crucial functions of TER94 at multiple steps of the baculovirus life cycle, including genome replication, BV formation, and ODV morphogenesis.IMPORTANCE TER94 constitutes an important AAA+ ATPase that associates with diverse cellular processes, including protein quality control, membrane fusion of the Golgi apparatus and endoplasmic reticulum network, nuclear envelope reformation, and DNA replication. To date, little is known regarding the role(s) of TER94 in the baculovirus life cycle. In this study, TER94 was found to play a crucial role in multiple steps of baculovirus infection, including viral DNA replication and BV and ODV formation. Further evidence showed that the membrane fission/fusion function of TER94 is likely to be exploited by baculovirus for virion morphogenesis. Moreover, TER94 could interact with the viral early proteins LEF3 and helicase to transport and further recruit viral replication-related proteins to establish viral replication factories. This study highlights the critical roles of TER94 as an energy-supplying chaperon in the baculovirus life cycle and enriches our knowledge regarding the biological function of this important host factor.

A Porphyrin-Based Covalent Organic Framework for Metal-Free Photocatalytic Aerobic Oxidative Coupling of Amines.

Imines are important intermediates in drug synthesis. Photocatalytic aerobic oxidative coupling of amines has been considered as a clean and promising way to produce imines and has attracted great attention. Herein, we designed and synthesized a novel two-dimensional porphyrin-based covalent organic framework (Por-BC-COF) which adopts an AA stacking mode with excellent crystallinity, high Brunauer-Emmett-Teller surface areas (1200 m2 g-1 ), wide light absorption range (200-1300 nm) and good stability in a variety of organic solvents. Por-BC-COF can be used as a metal-free heterogeneous photocatalyst for the photocatalytic oxidation of amines to imines under visible light and red light with a high yield (97 %). This work presents a novel and efficient COF photocatalyst in the application of light-driven organic synthesis.

Craniodental and Postcranial Characters of Non-Avian Dinosauria Often Imply Different Trees.

Despite the increasing importance of molecular sequence data, morphology still makes an important contribution to resolving the phylogeny of many groups, and is the only source of data for most fossils. Most systematists sample morphological characters as broadly as possible on the principle of total evidence. However, it is not uncommon for sampling to be focused on particular aspects of anatomy, either because characters therein are believed to be more informative, or because preservation biases restrict what is available. Empirically, the optimal trees from partitions of morphological data sets often represent significantly different hypotheses of relationships. Previous work on hard-part versus soft-part characters across animal phyla revealed significant differences in about a half of sampled studies. Similarly, studies of the craniodental versus postcranial characters of vertebrates revealed significantly different trees in about one-third of cases, with the highest rates observed in non-avian dinosaurs. We test whether this is a generality here with a much larger sample of 81 published data matrices across all major dinosaur groups. Using the incongruence length difference test and two variants of the incongruence relationship difference test, we found significant incongruence in about 50% of cases. Incongruence is not uniformly distributed across major dinosaur clades, being highest (63%) in Theropoda and lowest (25%) in Thyreophora. As in previous studies, our partition tests show some sensitivity to matrix dimensions and the amount and distribution of missing entries. Levels of homoplasy and retained synapomorphy are similar between partitions, such that incongruence must partly reflect differences in patterns of homoplasy between partitions, which may itself be a function of modularity and mosaic evolution. Finally, we implement new tests to determine which partition yields trees most similar to those from the entire matrix. Despite no bias across dinosaurs overall, there are striking differences between major groups. The craniodental characters of Ornithischia and the postcranial characters of Saurischia yield trees most similar to the "total evidence" trees derived from the entire matrix. Trees from these same character partitions also tend to be most stratigraphically congruent: a mutual consilience suggesting that those partitions yield more accurate trees. [Dinosauria; homoplasy; partition homogeneity.].