Zinc mediates control of nitrogen fixation via transcription factor filamentation.

Plants adapt to fluctuating environmental conditions by adjusting their metabolism and gene expression to maintain fitness1. In legumes, nitrogen homeostasis is maintained by balancing nitrogen acquired from soil resources with nitrogen fixation by symbiotic bacteria in root nodules2-8. Here we show that zinc, an essential plant micronutrient, acts as an intracellular second messenger that connects environmental changes to transcription factor control of metabolic activity in root nodules. We identify a transcriptional regulator, FIXATION UNDER NITRATE (FUN), which acts as a sensor, with zinc controlling the transition between an inactive filamentous megastructure and an active transcriptional regulator. Lower zinc concentrations in the nodule, which we show occur in response to higher levels of soil nitrate, dissociates the filament and activates FUN. FUN then directly targets multiple pathways to initiate breakdown of the nodule. The zinc-dependent filamentation mechanism thus establishes a concentration readout to adapt nodule function to the environmental nitrogen conditions. In a wider perspective, these results have implications for understanding the roles of metal ions in integration of environmental signals with plant development and optimizing delivery of fixed nitrogen in legume crops.

Establishing chronic models of age-related macular degeneration via long-term iron ion overload.

Age-related macular degeneration (AMD) is characterized by the degenerative senescence in the retinal pigment epithelium (RPE) and photoreceptors, which is accompanied by the accumulation of iron ions in the aging retina. However, current models of acute oxidative stress are still insufficient to simulate the gradual progression of AMD. To address this, we established chronic injury models by exposing the aRPE-19 cells, 661W cells, and mouse retina to iron ion overload over time. Investigations at the levels of cell biology and molecular biology were performed. It was demonstrated that long-term treatment of excessive iron ions induced senescence-like morphological changes, decreased cell proliferation, and impaired mitochondrial function, contributing to apoptosis. Activation of the mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were confirmed both in the aRPE-19 and 661W cells. Furthermore, iron ion overload resulted in dry AMD-like lesions and decreased visual function in the mouse retina. These findings suggest that chronic exposure to overloading iron ions plays a significant role in the pathogenesis of retinopathy and provide a potential model for future studies on AMD.NEW & NOTEWORTHY To explore the possibility of constructing reliable research carriers on age-related macular degeneration (AMD), iron ion overload was applied to establish models in vitro and in vivo. Subsequent investigations into cellular physiology and molecular biology confirmed the presence of senescence in these models. Through this study, we hope to provide a better option of feasible methods for future researches into AMD.

Immunization with a low dose of zymosan A confers resistance to depression-like behavior and neuroinflammatory responses in chronically stressed mice.

Stimulation of the innate immune system prior to stress exposure is a possible strategy to prevent depression under stressful conditions. Based on the innate immune system stimulating activities of zymosan A, we hypothesize that zymosan A may prevent the development of chronic stress-induced depression-like behavior. Our results showed that a single injection of zymosan A 1 day before stress exposure at a dose of 2 or 4 mg/kg, but not at a dose of 1 mg/kg, prevented the development of depression-like behaviors in mice treated with chronic social defeat stress (CSDS). The prophylactic effect of a single zymosan A injection (2 mg/kg) on CSDS-induced depression-like behaviors disappeared when the time interval between zymosan A and stress exposure was extended from 1 day or 5 days to 10 days, which was rescued by a second zymosan A injection 10 days after the first zymosan A injection and 4 days (4×, once daily) of zymosan A injections 10 days before stress exposure. Further analysis showed that a single zymosan A injection (2 mg/kg) 1 day before stress exposure could prevent the CSDS-induced increase in pro-inflammatory cytokines in the hippocampus and prefrontal cortex. Inhibition of the innate immune system by pretreatment with minocycline (40 mg/kg) abolished the preventive effect of zymosan A on CSDS-induced depression-like behaviors and CSDS-induced increase in pro-inflammatory cytokines in the brain. These results suggest that activation of the innate immune system triggered by zymosan A prevents the depression-like behaviors and neuroinflammatory responses in the brain induced by chronic stress.

Stacking-induced phonon transport engineering of siligene.

Tunable phonon transport properties of two-dimensional materials are desirable for effective heat management in various application scenarios. Here, we demonstrate by first-principles calculations and Boltzmann transport theory that the lattice thermal conductivity of siligene could be efficiently engineered by forming various stacking configurations. Unlike few-layer graphene, the stacked siligenes are found to be covalently bonded along the out-of-plane direction, which leads to unique dependence of the thermal conductivity on both the stacking order and layer number. Due to the restricted flexural phonon scattering induced by the horizontal reflection symmetry, the AA stacking configuration of bilayer siligene exhibits obviously higher thermal conductivity compared with the AB stacking. In addition, we observe increasing thermal conductivity with the layer number, as evidenced by the reduced phonon scattering phase space and Grüneisen parameter. Interestingly, the Fuchs-Sondheimer model works well for the thickness-dependent thermal conductivity of stacked siligenes.

Quinolone Antibiotics Inhibit the Rice Photosynthesis by Targeting Photosystem II Center Protein: Generational Differences and Mechanistic Insights.

Soil antibiotic pollution profoundly influences plant growth and photosynthetic performance, yet the main disturbed processes and the underlying mechanisms remain elusive. This study explored the photosynthetic toxicity of quinolone antibiotics across three generations on rice plants and clarified the mechanisms through experimental and computational studies. Marked variations across antibiotic generations were noted in their impact on rice photosynthesis with the level of inhibition intensifying from the second to the fourth generation. Omics analyses consistently targeted the light reaction phase of photosynthesis as the primary process impacted, emphasizing the particular vulnerability of photosystem II (PS II) to the antibiotic stress, as manifested by significant interruptions in the photon-mediated electron transport and O2 production. PS II center D2 protein (psbD) was identified as the primary target of the tested antibiotics, with the fourth-generation quinolones displaying the highest binding affinity to psbD. A predictive machine learning method was constructed to pinpoint antibiotic substructures that conferred enhanced affinity. As antibiotic generations evolve, the positive contribution of the carbonyl and carboxyl groups on the 4-quinolone core ring in the affinity interaction gradually intensified. This research illuminates the photosynthetic toxicities of antibiotics across generations, offering insights for the risk assessment of antibiotics and highlighting their potential threats to carbon fixation of agroecosystems.

Bombesin receptor-activated protein homolog deficiency altered the pattern of pathological changes of psoriasis - like skin lesion in mice.

This study investigated the potential role of the mouse homolog of bombesin receptor-activated protein (BRAP) in imiquimod (IMQ) induced psoriasis - like skin inflammation. The expression of both human BRAP, encoded by C6orf89, and its mouse homolog, encoded by BC004004, has been found to be expressed abundantly in the keratinocytes. BC004004 knockout mice (BC004004-/-) were topically treated with IMQ daily for 7 days to test whether they were more vulnerable to psoriasis - like inflammation. We found that those mice exhibited an altered pattern of inflammation process compared to isogenic wild type control mice (BC004004+/+). BC004004-/- mice developed skin lesions with earlier and more acute onset, as well as a quicker remission. The cytokines related to pathogenesis of psoriasis also exhibited different expression patterns in IMQ treated BC004004-/- mice. On day 4 of IMQ treatment, BC004004-/- mice exhibited a higher expression level of IL-17A compared to BC004004+/+ mice, suggesting a more robust activation of Th17 cells in the knockout mice. The serum level of thymic stromal lymphopoietin (TSLP), one of the keratinocyte derived cytokines, was also increased in BC004004-/- mice and reached its peak on day 4. Knockdown of BRAP in cultured human keratinocyte-derived HaCaT cells by siRNA silencing led to increased release of TSLP. Our data suggest that the elevated of level of TSLP released from keratinocytes due to BRAP deficiency might mediate the crosstalk between the epidermal cells and immune cells and thereby contributing to the altered pathological changes observed in psoriasis - like skin lesion in knockout mice.

Determination of microplastics in agricultural soil by double-shot pyrolysis-gas chromatography combined with two-step extraction.

A method for the determination of five microplastics in agricultural soil was established by double-shot pyrolysis-gas chromatography combined with two-step extraction. First, polycarbonate (PC), polystyrene (PS), polypropylene (PP), and polyethylene (PE) were extracted from soil samples using a mixed solvent of cyclohexanone and p-xylene, and then PE terephthalate was extracted with m-methylphenol. Subsequently, PC and PE terephthalate were analyzed by thermochemolysis, and PE, PP, and PS were investigated by direct pyrolysis at 600°C. The linearity of the method was satisfactory for five microplastics and the correlation coefficients were higher than 0.97 in the respective concentration range. The limits of detection and the limits of quantification were 0.2-10.0 and 0.5-20.0 µg/g, respectively. The method provided recoveries of 75.1%-141.5%, with acceptable repeatability within 20.0%. It was a supplementary method for the existing characterization of microplastics in agricultural soil.

CTNNAL1 promotes the structural integrity of bronchial epithelial cells through the RhoA/ROCK1 pathway.

Adhesion molecules play critical roles in maintaining the structural integrity of the airway epithelium in airways under stress. Previously, we reported that catenin alpha-like 1 (CTNNAL1) is downregulated in an asthma animal model and upregulated at the edge of human bronchial epithelial cells (HBECs) after ozone stress. In this work, we explore the potential role of CTNNAL1 in the structural adhesion of HBECs and its possible mechanism. We construct a CTNNAL1 ‒/‒ mouse model with CTNNAL1-RNAi recombinant adeno-associated virus (AAV) in the lung and a CTNNAL1-silencing cell line stably transfected with CTNNAL1-siRNA recombinant plasmids. Hematoxylin and eosin (HE) staining reveals that CTNNAL1 ‒/‒ mice have denuded epithelial cells and structural damage to the airway. Silencing of CTNNAL1 in HBECs inhibits cell proliferation and weakens extracellular matrix adhesion and intercellular adhesion, possibly through the action of the cytoskeleton. We also find that the expressions of the structural adhesion-related molecules E-cadherin, integrin ß1, and integrin ß4 are significantly decreased in ozone-treated cells than in vector control cells. In addition, our results show that the expression levels of RhoA/ROCK1 are decreased after CTNNAL1 silencing. Treatment with Y27632, a ROCK inhibitor, abolished the expressions of adhesion molecules induced by ozone in CTNNAL1-overexpressing HBECs. Overall, the findings of the present study suggest that CTNNAL1 plays a critical role in maintaining the structural integrity of the airway epithelium under ozone challenge, and is associated with epithelial cytoskeleton dynamics and the expressions of adhesion-related molecules via the RhoA/ROCK1 pathway.

Assessing the impact of Chlorantraniliprole (CAP) pesticide stress on oilseed rape (Brassia campestris L.): Residue dynamics, enzyme activities, and metabolite profiling.

This study investigates the effects of chlorantraniliprole (CAP) pesticide stress on oilseed rape through comprehensive pot experiments. Assessing CAP residue variations in soil and oilseed rape (Brassia campestris L.), enzyme activities (POD, CPR, GST), and differential metabolites, we unveil significant findings. The average CAP residue levels were 18.38-13.70 mg/kg in unplanted soil, 9.94-6.30 mg/kg in planted soil, and 0-4.18 mg/kg in oilseed rape samples, respectively. Soil microbial influences and systemic pesticide translocation into oilseed rape contribute to CAP residue variations. Under the influence of CAP stress, oilseed rape displays escalated enzyme activities (POD, CPR, GST) and manifests 57 differential metabolites. Among these, 32 demonstrate considerable downregulation, mainly impacting amino acids and phenolic compounds, while 25 exhibit noteworthy overexpression, primarily affecting flavonoid compounds. This impact extends to 24 metabolic pathways, notably influencing amide biosynthesis, as well as arginine and proline metabolism. These findings underscore the discernible effects of CAP pesticide stress on oilseed rape.

Airway epithelial ITGB4 deficiency induces airway remodeling in a mouse model.

BACKGROUND: Airway epithelial cells (AECs) with impaired barrier function contribute to airway remodeling through the activation of epithelial-mesenchymal trophic units (EMTUs). Although the decreased expression of ITGB4 in AECs is implicated in the pathogenesis of asthma, how ITGB4 deficiency impacts airway remodeling remains obscure. OBJECTIVE: This study aims to determine the effect of epithelial ITGB4 deficiency on the barrier function of AECs, asthma susceptibility, airway remodeling, and EMTU activation. METHODS: AEC-specific ITGB4 conditional knockout mice (ITGB4-/-) were generated and an asthma model was employed by the sensitization and challenge of house dust mite (HDM). EMTU activation-related growth factors were examined in ITGB4-silenced primary human bronchial epithelial cells of healthy subjects after HDM stimulation. Dexamethasone, the inhibitors of JNK phosphorylation or FGF2 were administered for the identification of the molecular mechanisms of airway remodeling in HDM-exposed ITGB4-/- mice. RESULTS: ITGB4 deficiency in AECs enhanced asthma susceptibility and airway remodeling by disrupting airway epithelial barrier function. Aggravated airway remodeling in HDM-exposed ITGB4-/- mice was induced through the enhanced activation of EMTU mediated by Src homology domain 2-containing protein tyrosine phosphatase 2/c-Jun N-terminal kinase/Jun N-terminal kinase-dependent transcription factor/FGF2 (SHP2/JNK/c-Jun/FGF2) signaling pathway, which was partially independent of airway inflammation. Both JNK and FGF2 inhibitors significantly inhibited the aggravated airway remodeling and EMTU activation in HDM-exposed ITGB4-/- mice. CONCLUSIONS: Airway epithelial ITGB4 deficiency induces airway remodeling in a mouse model of asthma through enhanced EMTU activation that is regulated by the SHP2/JNK/c-Jun/FGF2 pathway.

Conditional knockout of ITGB4 in bronchial epithelial cells directs bronchopulmonary dysplasia.

Neonatal respiratory system disease is closely associated with embryonic lung development. Our group found that integrin ß4 (ITGB4) is downregulated in the airway epithelium of asthma patients. Asthma is the most common chronic respiratory illness in childhood. Therefore, we suspect whether the deletion of ITGB4 would affect fetal lung development. In this study, we characterized the role of ITGB4 deficiency in bronchopulmonary dysplasia (BPD). ITGB4 was conditionally knocked out in CCSP-rtTA, Tet-O-Cre and ITGB4f/f triple transgenic mice. Lung tissues at different developmental stages were collected for experimental detection and transcriptome sequencing. The effects of ITGB4 deficiency on lung branching morphogenesis were observed by fetal mouse lung explant culture. Deleting ITGB4 from the airway epithelial cells results in enlargement of alveolar airspaces, inhibition of branching, the abnormal structure of epithelium cells and the impairment of cilia growth during lung development. Scanning electron microscopy showed that the airway epithelial cilia of the ß4ccsp.cre group appear to be sparse, shortened and lodging. Lung-development-relevant factors such as SftpC and SOX2 significantly decreased both mRNA and protein levels. KEGG pathway analysis indicated that multiple ontogenesis-regulating-relevant pathways converge to FAK. Accordingly, ITGB4 deletion decreased phospho-FAK, phospho-GSK3ß and SOX2 levels, and the correspondingly contrary consequence was detected after treatment with GSK3ß agonist (wortmannin). Airway branching defect of ß4ccsp.cre mice lung explants was also partly recovered after wortmannin treatment. Airway epithelial-specific deletion of ITGB4 contributes to lung developmental defect, which could be achieved through the FAK/GSK3ß/SOX2 signal pathway.

Oxidative stress-induced lncRNA CYLD-AS1 promotes RPE inflammation via Nrf2/miR-134-5p/NF-κB signaling pathway.

Oxidative stress-induced damage to and dysfunction of retinal pigment epithelium (RPE) cells are important pathogenetic factors of age-related macular degeneration (AMD); however, the underlying molecular mechanism is not fully understood. Long noncoding RNAs (lncRNAs) have important roles in various biological processes. In this study, using an oxidative damage model in RPE cells, we identified a novel oxidation-related lncRNA named CYLD-AS1. We further revealed that the expression of CYLD-AS1 was increased in RPEs during oxidative stress. Depletion of CYLD-AS1 promoted cell proliferation and mitochondrial function and protected RPE cells against hydrogen peroxide (H2 O2 )-induced damage. Mechanistically, CYLD-AS1 also regulated the expression of NRF2, which is related to oxidative stress, and NF-κB signaling pathway members, which are related to inflammation. Remarkably, these two signaling pathways were mediated by the CYLD-AS1 interactor miR-134-5p. Moreover, exosomes secreted by CYLD-AS1 knockdown RPE cells had a lower proinflammatory effect than those secreted by control cells. In summary, our study revealed that CYLD-AS1 affects the oxidative stress-related and inflammatory functions of RPE cells by sponging miR-134-5p to mediate NRF2/NF-κB signaling pathway activity, suggesting that targeting CYLD-AS1 could be a promising strategy for the treatment of AMD and related diseases.

Lack of bombesin receptor-activated protein homologous protein impairs hippocampal synaptic plasticity and promotes chronic unpredictable mild stress induced behavioral changes in mice.

Bombesin receptor-activated protein (BRAP) and its homologous protein in mice, which is encoded by bc004004 gene, were expressed abundantly in brain tissues with unknown functions. We treated bc004004-/- mice with chronic unpredictable mild stress (CUMS) to test whether those mice were more vulnerable to stress-related disorders. The results of forced swimming test, sucrose preference test, and open field test showed that after being treated with CUMS for 28 days or 35 days both bc004004-/- and bc004004+/+ mice exhibited behavioural changes and there was no significant difference between bc004004+/+ and bc004004-/-. However, behavioural changes were observed only in bc004004-/- mice after being exposed to CUMS for 21 days, but not in bc004004+/+ after 21-day CUMS exposure, indicating that lack of BRAP homologous protein may cause vulnerability to stress-related disorders in mice. In addition, bc004004-/- mice showed a reduction in recognition memory as revealed by novel object recognition test. Since memory changes and stress related behavioural changes are all closely related to the hippocampus function we further analyzed the changes of dendrites and synapses of hippocampal neurons as well as expression levels of some proteins closely related to synaptic function. bc004004-/- mice exhibited decreased dendritic lengths and increased amount of immature spines, as well as altered expression pattern of synaptic related proteins including GluN2A, synaptophysin and BDNF in the hippocampus. Those findings suggest that BRAP homologous protein may have a protective effect on the behavioural response to stress via regulating dendritic spine formation and synaptic plasticity in the hippocampus.

Intranasal Monophosphoryl Lipid a Administration Ameliorates depression-like Behavior in Chronically Stressed Mice Through Stimulation of Microglia.

We and others have reported that systematic stimulation of the central innate immune system by a low dose of lipopolysaccharide (LPS) can improve depression-like behavior in chronically stressed animals. However, it is unclear whether similar stimulation by intranasal administration could improve depression-like behavior in animals. We investigated this question using monophosphoryl lipid A (MPL), a derivative of LPS that lacks the adverse effects of LPS but is still immuno-stimulatory. We found that a single intranasal administration of MPL at a dose of 10 or 20 µg/mouse, but not at a dose of 5 µg/mouse, ameliorated chronic unpredictable stress (CUS)-induced depression-like behavior in mice, as evidenced by the decrease in immobility time in tail suspension test and forced swimming test and the increase in sucrose intake in sucrose preference test. In the time-dependent analysis, the antidepressant-like effect of a single intranasal MPL administration (20 µg/mouse) was observed 5 and 8 h but not 3 h after drug administration and persisted for at least 7 days. Fourteen days after the first intranasal MPL administration, a second intranasal MPL administration (20 µg/mouse) still showed an antidepressant-like effect. The innate immune response mediated by microglia might mediate the antidepressant-like effect of intranasal MPL administration, because both inhibition of microglial activation by pretreatment with minocycline and depletion of microglia by pretreatment with PLX3397 prevented the antidepressant-like effect of intranasal MPL administration. These results suggest that intranasal administration of MPL can produce significant antidepressant-like effects in animals under chronic stress conditions via stimulation of microglia.

Polarization-resolved and helicity-resolved Raman spectra of monolayer XP3 (X = Ge and In).

Monolayer XP3 (X = Ge, In) is a theoretically predicted two-dimensional (2D) material with fascinating adsorption efficiency, foreshadowing its potential applications in the photovoltaic and optoelectronic communities. To achieve a comprehensive understanding of its optical properties and to further boost quickly identifying its specific applications, in this paper we systematically investigated the polarization-resolved and helicity-resolved Raman spectra excited by two commonly used laser lines (532 nm and 633 nm) through density functional theory. The dynamical stability of monolayer XP3 is demonstrated by phonon dispersion. Monolayer GeP3 and InP3 are found to exhibit significantly different point group symmetries and thereby Raman properties due to the big difference in atomic size and electronic configurations between the Ge atom and In atom. Raman anisotropy of monolayer XP3 has been found when the wave vector of linear polarized incident light is parallel to the monolayer, and all the anisotropic Raman active phonons are categorized in terms of the locations of two (four) maxima in polarization angle dependent Raman intensities of the parallel (perpendicular) configuration. The polarization direction averaged Raman spectra have been further discussed according to the characteristics of light absorbance. The calculations of helicity-resolved Raman spectra indicate a stronger helicity selection rule under helical excitation with the wave vector normal to the monolayer. The present work paves the way for the suitable design, characterization and exploitation of the proposed 2D material with controllable surface properties for applications in electronics and optoelectronics.

How Does Migration Affect HIV Sexual Risk Behaviors Among Involuntary Bachelors? The Mediating Roles of Neighborhoods and Social Networks.

The sex ratio imbalance in China since the 1980s has resulted in a large number of involuntary bachelors in rural China. Previous studies have found an association between migration and HIV sexual risk behaviors among involuntary bachelors, but how migration affects these bachelors' HIV sexual risk behaviors remain poorly understood. Using data from a cross-sectional survey in 2017 (a sample of 740 male respondents who had rural household registration, had never been married, and were aged 28-49 years), we investigated the relationship between migration and HIV sexual risk behaviors. Logistic regressions show that migration, neighborhood characteristics, and social networks were significantly associated with commercial sex and multiple sex partners, whereas only neighborhood characteristics and social networks were positively correlated with sexual partnership concurrency. Neighborhood characteristics and social networks mediated the relationships of migration with commercial sex and migration with multiple sex partners. Social networks mediated the association between neighborhood characteristics and concurrency. Multiple-step mediation analysis showed that the indirect effect of migration on commercial sex and multiple sexual partners through neighborhood characteristics and social networks was significant. Our findings suggest that further interventions should address neighborhood characteristics and social networks together.

Chronic endometritis incidence in infertile women with and without polycystic ovary syndrome: a propensity score matched study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is known to be associated with chronic low-grade inflammation and endometrial dysfunction. Chronic endometritis (CE) is a type of local inflammation that can contribute to endometrial dysfunction in infertile women. Some clinicians recommend screening for CE in women at high risk, such as those with endometrial polyps. However, it is still uncertain whether there is a relationship between PCOS and CE, as well as whether women with PCOS require enhanced screening for CE. This study was to assess the incidence of CE among infertile women with PCOS by hysteroscopy combined with histopathology CD138 immunohistochemical staining of endometrium. METHODS: A total of 205 patients in the PCOS group and 4021 patients in the non-PCOS group from July 2017 to August 2022 were included in this retrospective study. After nearest-neighbor 1:4 propensity score matching (PSM), 189 PCOS patients were matched with 697 non-PCOS patients. Basic information was recorded. The CE incidence was compared. The risk factors affecting CE incidence were also analyzed. RESULTS: No significantly higher CE incidence in infertile women with PCOS were found either in total analysis or after PSM (P = 0.969; P = 0.697; respectively). Similar results were discovered in the subgroup of Body Mass Index (BMI) (P = 0.301; P = 0.671; P = 0.427; respectively) as well as the four PCOS phenotypes (P = 0.157). Intriguingly, the incidence of CE increased as BMI increased in the PCOS group, even though no significant differences were found (P = 0.263). Multivariate logistic regression showed that age, infertility duration, infertility type, PCOS, and obesity were not the independent risk factors affecting CE incidence. CONCLUSION: The incidence of CE in PCOS patients did not significantly increase compared to non-PCOS patients. Similarly, no significant differences in the incidence of CE were observed among different PCOS phenotypes. The current evidence does not substantiate the need for widespread CE screening among PCOS women, potentially mitigating the undue financial and emotional strain associated with such screenings.

CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway.

The downregulation of adhesion molecule catenin alpha-like 1 (CTNNAL1) in airway epithelial cells of asthma patients and house dust mite (HDM)-induced asthma animal models was illustrated in our previous study. It is assumed to contribute to airway inflammation and mucus hypersecretion. In this work, we further explore the underlying mechanism of CTNNAL1 in asthma. CTNNAL1-silenced female mice exhibit a decreased level of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated and ATP-gated Cl - channel that correlates with mucus hypersecretion. Our previous study demonstrated that ROCK1 expression decreases but ROCK2 expression increases in the lungs of a CTNNAL1-silenced mouse model. Inhibition of ROCK1 leads to a reduction in CFTR expression in CTNNAL1-overexpressing and CTNNAL1-silenced human bronchial epithelial (HBE) cells. It has been reported that ROCK1 is a downstream target of RhoA and that activation of RhoA increases CFTR expression after CTNNAL1 deficiency in vitro and in vivo. The above results indicate that CTNNAL1 regulates CFTR expression through the ROCK1 pathway. In addition, the expression of CFTR-associated ligand (CAL) is increased after CTNNAL1 silencing, and immunoprecipitation results confirm the interaction between ROCK1 and CAL. Inhibition of CAL does not influence ROCK1 expression but increases CFTR expression in CTNNAL1-silenced HBE cells. These data suggest that CTNNAL1 deficiency decreases CFTR expression in the HDM-induced asthma mouse model through the ROCK1-CAL signaling pathway.

A Structure-Aware Convolutional Neural Network for Automatic Diagnosis of Fungal Keratitis with In Vivo Confocal Microscopy Images.

Fungal keratitis (FK) is a common and severe corneal disease, which is widely spread in tropical and subtropical areas. Early diagnosis and treatment are vital for patients, with confocal microscopy cornea imaging being one of the most effective methods for the diagnosis of FK. However, most cases are currently diagnosed by the subjective judgment of ophthalmologists, which is time-consuming and heavily depends on the experience of the ophthalmologists. In this paper, we introduce a novel structure-aware automatic diagnosis algorithm based on deep convolutional neural networks for the accurate diagnosis of FK. Specifically, a two-stream convolutional network is deployed, combining GoogLeNet and VGGNet, which are two commonly used networks in computer vision architectures. The main stream is used for feature extraction of the input image, while the auxiliary stream is used for feature discrimination and enhancement of the hyphae structure. Then, the features are combined by concatenating the channel dimension to obtain the final output, i.e., normal or abnormal. The results showed that the proposed method achieved accuracy, sensitivity, and specificity of 97.73%, 97.02%, and 98.54%, respectively. These results suggest that the proposed neural network could be a promising computer-aided FK diagnosis solution.

WRKY Transcriptional Factor IlWRKY70 from Iris laevigata Enhances Drought and Salinity Tolerances in Nicotiana tabacum.

Drought and high salinity greatly affect plant growth and development. WRKY transcription factors play a key role in plant tolerance to abiotic stress, but the functions of WRKYs in the ornamental monocotyledon Iris laevigata remain largely unexplored. In this study, we cloned IlWRKY70 and found that it is a Group III WRKY localized in the nucleus. The expression of IlWRKY70 was induced by NaCl and PEG-6000, which reached peaks (4.38 and 5.65 times) after 3 h and 1 h, respectively. The exogenous overexpression of IlWRKY70 in N. tabacum significantly improved the resistance under NaCl and drought treatments, as evidenced by higher germination rates, longer root lengths, and increased fresh weights compared to those of control plants. In addition, transgenic seedlings showed significantly reduced wilting, higher photosynthetic performance, higher Fv/Fm and chlorophyll content, and lower stomatal conductance. Moreover, transgenic lines showed higher antioxidant enzymatic activities, lower reactive oxygen species (ROS), and lower malondialdehyde contents. Accordingly, we also found higher expressions of antioxidant defense genes, including SOD, CAT, and POD, in transgenic lines compared to controls under salt and drought stresses. Thus, IlWRKY70 enhances the abilities of salt and drought tolerances in plants, at least partially, via ROS regulation and can be used for breeding I. laevigata possessing enhanced salt and drought resistances.