How denitrifiers defense ciprofloxacin: Insights from intracellular and extracellular stress response.

Overuse of antibiotics has led to their existence in nitrogen-containing water. The impacts of antibiotics on bio-denitrification and the metabolic response of denitrifiers to antibiotics are unclear. We systematically analyzed the effect of ciprofloxacin (CIP) on bio-denitrification and found that 5 mg/L CIP greatly inhibited denitrification with a model denitrifier (Paracoccus denitrificans). Nitrate reduction decreased by 32.89 % and nitrous oxide emission increased by 75.53 %. The balance analysis of carbon and nitrogen metabolism during denitrification showed that CIP exposure blocked electron transfer and reduced the flow of substrate metabolism used for denitrification. Proteomics results showed that CIP exposure induced denitrifiers to use the pentose phosphate pathway more for substrate metabolism. This caused a substrate preference to generate NADPH to prevent cellular damage rather than NADH for denitrification. Notably, despite denitrifiers having antioxidant defenses, they could not completely prevent oxidative damage caused by CIP exposure. The effect of CIP exposure on denitrifiers after removal of extracellular polymeric substances (EPS) demonstrated that EPS around denitrifiers formed a barrier against CIP. Fluorescence and infrared spectroscopy revealed that the binding effect of proteins in EPS to CIP prevented damage. This study shows that denitrifiers resist antibiotic stress through different intracellular and extracellular defense strategies.

Long-Term Effectiveness of Cognitive Behavioral Therapy in Routine Outpatient Care for Youth with Anxiety Disorders.

INTRODUCTION: This study examined the long-term effectiveness of cognitive behavioral therapy (CBT) (≥ 2 years after the end of therapy) in the routine care of youth (mean 11.95 years; SD = 3.04 years) with primary anxiety disorder (AD). METHODS: Two hundred and ten children with any AD as a primary diagnosis and with any comorbidity were included in the "Kids Beating Anxiety (KibA)" clinical trial and received evidence-based CBT. Diagnoses, severity of diagnoses, and further dimensional outcome variables of symptoms and functioning were assessed before (baseline), after the last treatment session (POST), and at two follow-up (FU) assessments in the child and caregiver report: 6 months (6MONTHS-FU) and >2 years (mean 4.31; SD = 1.07 years) after the last treatment session (long-term FU). RESULTS: At POST, 61.38% showed total remission of all and any ADs. At long-term FU, the remission rate was 63.64%. Compared to baseline, ratings of severity, anxiety, impairment/burden, and life quality improved significantly after CBT in child and caregiver report. All pre-post/FU improvements and global success ratings were stable in child (Pre-Post: Hedges' g = 3.57; Pre-6MONTHS-FU: Hedges' g = 3.43; Pre-LT-FU: Hedges' g = 2.34) and caregiver report (Pre-Post: Hedges' g = 2.00; Pre-6MONTHS-FU: Hedges' g = 2.31; Pre-LT-FU: Hedges' g = 2.31) across all POST- and FU-assessment points. Some outcomes showed further significant improvement, and no deterioration was found over the course of time. Effect sizes calculated in the present study correspond to, or even exceed, effect sizes reported in previous meta-analysis. CONCLUSIONS: Stable long-term effects of "KibA" CBT for youth with ADs, comparable to those results from efficacy studies, were achieved in a routine practice setting by applying treatment manuals tested in randomized controlled trials. These findings are remarkable, as the patient group studied here consisted of an age group within the main risk phase of developing further mental disorders, and therefore an increase in new-onset anxiety and further mental disorders would be expected over the long time span studied here.

Water-soluble 4-(dimethylaminomethyl)heliomycin exerts greater antitumor effects than parental heliomycin by targeting the tNOX-SIRT1 axis and apoptosis in oral cancer cells.

The antibiotic heliomycin (resistomycin), which is generated from Streptomyces resistomycificus, has multiple activities, including anticancer effects. Heliomycin was first described in the 1960s, but its clinical applications have been hindered by extremely low solubility. A series of 4-aminomethyl derivatives of heliomycin were synthesized to increase water solubility; studies showed that they had anti-proliferative effects, but the drug targets remained unknown. In this study, we conducted cellular thermal shift assays (CETSA) and molecular docking simulations to identify and validate that heliomycin and its water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged and targeted with sirtuin-1 (SIRT1) in p53-functional SAS and p53-mutated HSC-3 oral cancer cells. We further addressed the cellular outcome of SIRT1 inhibition by these compounds and found that, in addition to SIRT1, the water-soluble 4-dmH preferentially targeted a tumor-associated NADH oxidase (tNOX, ENOX2). The direct binding of 4-dmH to tNOX decreased the oxidation of NADH to NAD+ which diminished NAD+-dependent SIRT1 deacetylase activity, ultimately inducing apoptosis and significant cytotoxicity in both cell types, as opposed to the parental heliomycin-induced autophagy. We also observed that tNOX and SIRT1 were both upregulated in tumor tissues of oral cancer patients compared to adjacent normal tissues, suggesting their clinical relevance. Finally, the better therapeutic efficacy of 4-dmH was confirmed in tumor-bearing mice, which showed greater tNOX and SIRT1 downregulation and tumor volume reduction when treated with 4-dmH compared to heliomycin. Taken together, our in vitro and in vivo findings suggest that the multifaceted properties of water-soluble 4-dmH enable it to offer superior antitumor value compared to parental heliomycin, and indicated that it functions through targeting the tNOX-NAD+-SIRT1 axis to induce apoptosis in oral cancer cells.

Cerebral Perfusion Characteristics and Dynamic Brain Structural Changes in Stroke-Prone Renovascular Hypertensive Rats: A Preclinical Model for Cerebral Small Vessel Disease.

Hypertension is a leading cause of cerebral small vessel disease (CSVD) and vascular dementia in elderly individuals. We aimed to assess cerebral perfusion and dynamic changes in brain structure in stroke-prone renovascular hypertensive rats (RHRSPs) with different durations of hypertension and to investigate whether they have pathophysiological features similar to those of humans with CSVD. The RHRSP model was established using the two-kidney, two-clip (2k2c) method, and the Morris water maze (MWM) test, MRI, immunohistochemistry, and biochemical analysis were performed at multiple time points for up to six months following the 2k2c operation. Systolic blood pressure was significantly greater in the RHRSP group than in the sham-operated group at week 4 post-surgery and continued to increase over time, leading to cognitive decline by week 20. Arterial spin labeling revealed cerebral hypoperfusion in the RHRSP group at 8 weeks, accompanied by vascular remodeling and decreased vessel density. Diffusion tensor imaging and Luxol fast blue staining indicated that white matter disintegration and demyelination gradually progressed in the corpus callosum and that myelin basic protein levels decreased. Eight weeks after surgery, blood-brain barrier (BBB) leakage into the corpus callosum was observed. The albumin leakage area was negatively correlated with the myelin sheath area (r=-0.88, p<0.001). RNA-seq analysis revealed downregulation of most angiogenic genes and upregulation of antiangiogenic genes in the corpus callosum of RHRSPs 24 weeks after surgery. RHRSPs developed cerebral hypoperfusion, BBB disruption, spontaneous white matter damage, and cognitive impairment as the duration of hypertension increased. RHRSPs share behavioral and neuropathological characteristics with CSVD patients, making them suitable animal models for preclinical trials related to CSVD.

Direct in Situ Fabrication of Multicolor Afterglow Carbon Dot Patterns with Transparent and Traceless Features via Laser Direct Writing.

Multicolor afterglow patterns with transparent and traceless features are important for the exploration of new functionalities and applications. Herein, we report a direct in situ patterning technique for fabricating afterglow carbon dots (CDs) based on laser direct writing (LDW) for the first time. We explore a facile step-scanning method that reduces the heat-affected zone and avoids uneven heating, thus producing a fine-resolution afterglow CD pattern with a minimum line width of 80 µm. Unlike previous LDW-induced luminescence patterns, the patterned CD films are traceless and transparent, which is mainly attributed to a uniform heat distribution and gentle temperature rise process. Interestingly, by regulating the laser parameters and CD precursors, an increased carbonization and oxidation degree of CDs could be obtained, thus enabling time-dependent, tunable afterglow colors from blue to red. In addition, we demonstrate their potential applications in the in situ fabrication of flexible and stretchable optoelectronics.

Cross comparison representation learning for semi-supervised segmentation of cellular nuclei in immunofluorescence staining.

The morphological analysis of cells from optical images is vital for interpreting brain function in disease states. Extracting comprehensive cell morphology from intricate backgrounds, common in neural and some medical images, poses a significant challenge. Due to the huge workload of manual recognition, automated neuron cell segmentation using deep learning algorithms with labeled data is integral to neural image analysis tools. To combat the high cost of acquiring labeled data, we propose a novel semi-supervised cell segmentation algorithm for immunofluorescence-stained cell image datasets (ISC), utilizing a mean-teacher semi-supervised learning framework. We include a "cross comparison representation learning block" to enhance the teacher-student model comparison on high-dimensional channels, thereby improving feature compactness and separability, which results in the extraction of higher-dimensional features from unlabeled data. We also suggest a new network, the Multi Pooling Layer Attention Dense Network (MPAD-Net), serving as the backbone of the student model to augment segmentation accuracy. Evaluations on the immunofluorescence staining datasets and the public CRAG dataset illustrate our method surpasses other top semi-supervised learning methods, achieving average Jaccard, Dice and Normalized Surface Dice (NSD) indicators of 83.22%, 90.95% and 81.90% with only 20% labeled data. The datasets and code are available on the website at https://github.com/Brainsmatics/CCRL.

Microglia regulate sleep through calcium-dependent modulation of norepinephrine transmission.

Sleep interacts reciprocally with immune system activity, but its specific relationship with microglia-the resident immune cells in the brain-remains poorly understood. Here, we show in mice that microglia can regulate sleep through a mechanism involving Gi-coupled GPCRs, intracellular Ca2+ signaling and suppression of norepinephrine transmission. Chemogenetic activation of microglia Gi signaling strongly promoted sleep, whereas pharmacological blockade of Gi-coupled P2Y12 receptors decreased sleep. Two-photon imaging in the cortex showed that P2Y12-Gi activation elevated microglia intracellular Ca2+, and blockade of this Ca2+ elevation largely abolished the Gi-induced sleep increase. Microglia Ca2+ level also increased at natural wake-to-sleep transitions, caused partly by reduced norepinephrine levels. Furthermore, imaging of norepinephrine with its biosensor in the cortex showed that microglia P2Y12-Gi activation significantly reduced norepinephrine levels, partly by increasing the adenosine concentration. These findings indicate that microglia can regulate sleep through reciprocal interactions with norepinephrine transmission.

A high-affinity fluorescent probe for human uridine-disphosphate glucuronosyltransferase 1A9 function monitoring under environmental pollutant exposure.

Uridine-disphosphate glucuronosyltransferase 1A9 (UGT1A9), an important detoxification and inactivation enzyme for toxicants, regulates the exposure level of environmental pollutants in the human body and induces various toxicological consequences. However, an effective tool for high-throughput monitoring of UGT1A9 function under exposure to environmental pollutants is still lacking. In this study, 1,3-dichloro-7-hydroxy-9,9-dimethylacridin-2(9H)-one (DDAO) was found to exhibit excellent specificity and high affinity towards human UGT1A9. Remarkable changes in absorption and fluorescence signals after reacting with UGT1A9 were observed, due to the intramolecular charge transfer (ICT) mechanism. Importantly, DDAO was successfully applied to monitor the biological functions of UGT1A9 in response to environmental pollutant exposure not only in microsome samples, but also in living cells by using a high-throughput screening method. Meanwhile, the identified pollutants that disturb UGT1A9 functions were found to significantly influence the exposure level and retention time of bisphenol S/bisphenol A in living cells. Furthermore, the molecular mechanism underlying the inhibition of UGT1A9 by these pollutant-derived disruptors was elucidated by molecular docking and molecular dynamics simulations. Collectively, a fluorescent probe to characterize the responses of UGT1A9 towards environmental pollutants was developed, which was beneficial for elucidating the health hazards of environmental pollutants from a new perspective.

How Do Adherence to COVID-19 Mitigation Measures and Its Predictors Change between 2020 and 2021? An Explorative Investigation in Eight European Union and Non-European Union Countries.

INTRODUCTION: Adherence to COVID-19 mitigation measures is an important vehicle that has contributed to the fight against the pandemic. The present study investigated potential changes of the level of adherence and its predictors between 2020 and 2021 in eight countries. METHODS: Adherence to COVID-19 measures and its potential predictors (perception of usefulness of the measures, rating of the governmental COVID-19 communication, mental health variables, COVID-19 burden) were compared between representative population samples from European Union countries (France, Germany, Poland, Spain, Sweden) and non-European Union countries (Russia, UK, USA) assessed in 2020 (N = 7,658) and 2021 (N = 8,244). RESULTS: In the overall sample, multiple analyses of variance revealed significantly higher levels of adherence to the measures, their perception as useful, positive mental health, and feelings of being well supported and well informed by governments in 2020 than in 2021. In contrast, feelings of being left alone and symptoms of depression, anxiety, and stress were significantly higher in 2021 than in 2020. In France, Poland, Spain, and the UK, the adherence level was significantly higher in 2020 than in 2021. In European Union countries, ratings of governmental communication were less positive, and levels of mental health were lower in 2021 than in 2020. In non-European countries, an opposite result pattern was found. CONCLUSION: The current results indicate a decrease in adherence to the mitigation measures and factors that could foster it. Potential ways how governments and authorities could enhance the population's trust in COVID-19 mitigation measures are discussed.

Constructing mesoporous biochar derived from waste carton: Improving multi-site adsorption of dye wastewater and investigating mechanism.

The development of cost-efficient biochar adsorbent with a simple preparation method is essential to constructing efficient wastewater treatment system. Here, a low-cost waste carton biochar (WCB) prepared by a simple two-step carbonization was applied in efficiently removing Rhodamine B (RhB) in aqueous environment. The maximum ability of WCB for RhB adsorption was 222 mg/g, 6 and 10 times higher than both of rice straw biochar (RSB) and broadbean shell biochar (BSB), respectively. It was mainly ascribed to the mesopore structure (3.0-20.4 nm) of WCB possessing more spatial sites compared to RSB (2.2 nm) and BSB (2.4 nm) for RhB (1.4 nm✕1.1 nm✕0.6 nm) adsorption. Furthermore, external mass transfer (EMT) controlled mass transfer resistance (MTR) of the RhB sorption process by WCB which was fitted with the Langmuir model well. Meanwhile, the adsorption process was dominated by physisorption through van der Waals forces and π-π interactions. A mixture of three dyes in river water was well removed by using WCB. This work provides a straightforward method of preparing mesoporous biochar derived from waste carton with high-adsorption capacity for dye wastewater treatment.

Targeting Keap1 with Inulae Herba activated the Nrf2 receptor to alleviate LPS-mediated acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Inulae Herba (IH) is known as Jinfeicao recorded in Chinese Pharmacopoeia with effects of lowering qi and eliminating phlegm, and used for the treatment of pulmonary diseases. However, its protective mechanism on pulmonary diseases, especially acute lung injury (ALI), is still undefined. AIM OF THE STUDY: This study aimed to explore anti-inflammatory and anti-oxidation effects of IH and its underlying mechanism for treating ALI. MATERIALS AND METHODS: We constructed a lipopolysaccharide (LPS)-ALI mouse model to reveal the therapeutical effect of IH. Western blot, real-time quantitative PCR, flow cytometry, small RNA interference, immunohistochemical staining, and the dual-luciferase experiment were performed to study the mechanism of IH for treating ALI. RESULTS: IH attenuated LPS-mediated pathological changes (e.g. pneumonedema and pulmonary congestion) through inactivation of macrophages in an ALI mouse model. The result of flow cytometry demonstrated that IH regulated the homeostasis of M1 (CD80+CD206-) and M2 (CD80+CD206+) phenotype macrophages. Furthermore, IH suppressed mRNA expressions of M1 phenotype markers, such as iNOS and IL-6, whereas promoted mRNA expressions of M2 phenotype markers, such as ARG1 and RETNLA in LPS-mediated mice. Notably, IH targeted Keap1 to activate the Nrf2 receptor, exerting its anti-inflammatory and anti-oxidation effects proved by using immunohistochemical staining, dual-luciferase, and Keap1 knockdown technologies. CONCLUSION: These findings suggested that targeting Keap1 with IH alleviated LPS-mediated ALI, and it could serve as a herbal agent for developing anti-ALI drugs.

Three-wave longitudinal prediction of positive mental health in Germany and China.

The present study is a follow-up of a prior study examining a broad range of longitudinal predictors of dimensional positive mental health (PMH) and negative mental health (NMH), using cross-cultural data from the Bochum Optimism and Mental Health (BOOM) study. The present study sought to expand prior findings on positive mental health predictors to a longer longitudinal timeframe. The analysis, specifically, tests our prior model using a third time point, The following positive constructs were examined in relation to later positive mental health: resilience, social support, social rhythm, family affluence, physical health and expectations for fertility. Negative predictors depression, anxiety, and stress were also examined in relation to time 3 positive mental health. Participants included university student samples from Germany (N = 591) and China (N = 8,831). Structural equation modeling was used to examine the effects of predictors on mental health. In China, three of the six salutogenic predictors (social rhythm regularity, positive mental health, resilience) at baseline were predictive of positive mental health at both follow-ups with generally small, but significant effects. Social support at baseline predicted more, and stress and anxiety predicted less positive mental health at follow-up 1, with generally small effects. Depression at baseline predicted less positive mental health at follow-up 2. In Germany, two of the six salutogenic predictors (positive mental health, social support) at baseline were predictive of positive mental health at both follow-ups, with generally small effects. Pathogenic predictors were not predictive of positive mental health at either follow-up. According to multi group analysis, the paths from positive mental health baseline to positive mental health follow-up 1 (FU1) as well as the path positive mental health FU1 to positive mental health follow-up 2 (FU2) were found to differ between Germany and China. All other paths could be seen as equivalent in Germany and China. Results indicate prediction of positive mental health over an extended period of time, and in particular by salutogenic predictors. Pathogenic predictors were also (negatively) predictive of PMH, but with more mixed results, underscoring the differential prediction of PMH from salutogenic and pathogenic factors.

VISN: virus instance segmentation network for TEM images using deep attention transformer.

The identification of viruses from negative staining transmission electron microscopy (TEM) images has mainly depended on experienced experts. Recent advances in artificial intelligence have enabled virus recognition using deep learning techniques. However, most of the existing methods only perform virus classification or semantic segmentation, and few studies have addressed the challenge of virus instance segmentation in TEM images. In this paper, we focus on the instance segmentation of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and other respiratory viruses and provide experts with more effective information about viruses. We propose an effective virus instance segmentation network based on the You Only Look At CoefficienTs backbone, which integrates the Swin Transformer, dense connections and the coordinate-spatial attention mechanism, to identify SARS-CoV-2, H1N1 influenza virus, respiratory syncytial virus, Herpes simplex virus-1, Human adenovirus type 5 and Vaccinia virus. We also provide a public TEM virus dataset and conduct extensive comparative experiments. Our method achieves a mean average precision score of 83.8 and F1 score of 0.920, outperforming other state-of-the-art instance segmentation algorithms. The proposed automated method provides virologists with an effective approach for recognizing and identifying SARS-CoV-2 and assisting in the diagnosis of viruses. Our dataset and code are accessible at https://github.com/xiaochiHNU/Virus-Instance-Segmentation-Transformer-Network.

IκB kinase ß (IKKß): Structure, transduction mechanism, biological function, and discovery of its inhibitors.

The effective approach to discover innovative drugs will ask natural products for answers because of their complex and changeable structures and multiple biological activities. Inhibitory kappa B kinase beta (IKKß), known as IKK2, is a key regulatory kinase responsible for the activation of NF-κB through its phosphorylation at Ser177 and Ser181 to promote the phosphorylation of inhibitors of kappa B (IκBs), triggering their ubiquitination and degradation to active the nuclear factor kappa-B (NF-κB) cascade. Chemical inhibition of IKKß or its genetic knockout has become an effective method to block NF-κB-mediated proliferation and migration of tumor cells and inflammatory response. In this review, we summarized the structural feature and transduction mechanism of IKKß and the discovery of inhibitors from natural resources (e.g. sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, and alkaloids) and chemical synthesis (e.g. pyrimidines, pyridines, pyrazines, quinoxalines, thiophenes, and thiazolidines). In addition, the biosynthetic pathway of novel natural IKKß inhibitors and their biological potentials were discussed. This review will provide inspiration for the structural modification of IKKß inhibitors based on the skeleton of natural products or chemical synthesis and further phytochemistry investigations.

The relationships between leader emotional intelligence, transformational leadership, and transactional leadership and job performance: A mediator model of trust.

This study utilized the hierarchical linear model and trust as a mediator; designated leader emotional intelligence as a team-level dimension; and designated transformational leadership, transactional leadership, and trust in supervisor as individual-level dimensions. An analysis was performed to explore the relationships between these individual- and team-level variables and the job performance of real estate brokers, as well as the potential role of trust-oriented leadership as a mediator for the relationships between leader emotional intelligence, transformational leadership, and transactional leadership and individual job performance. The empirical results revealed that leader emotional intelligence, transformational leadership, and transactional leadership had direct, significant, and positive relationships with individual job performance. Furthermore, it was also discovered that, with trust in supervisor serving as a mediator, these three variables also had indirect, significant, and positive relationships with employee job performance.

Positive Emotions Training (PoET) as an online intervention to improve mental health: a feasibility study.

BACKGROUND: Positive psychology interventions are known to have an impact on mental health as well as on a number of beneficial characteristics like optimism, gratitude and self-efficacy. The Positive Emotions Training (PoET) is one of the first holistic training programs covering eleven positive psychology constructs. The goal of this study was to test PoET's feasibility in the general population and to assess possible effects on positive and negative mental health factors. Additionally, possible effects on optimism, gratitude, happiness, resilience, and self-efficacy were examined. METHODS: The sample (n = 101) was not randomized. Participants were allocated to PoET (n = 55) or control group (n = 46) that did not receive treatment initially. The PoET group completed two training sessions (3.5 h each) that were conducted in an online format with groups of about 30 people. All participants completed positive and negative mental health measures at the beginning of the first training session and at the beginning of the second one as well as 30 days after the second session. Two-factorial repeated measures ANOVAs were conducted to test for possible effects of PoET on mental health. RESULTS: The results showed that the contents were comprehensible and that the conduction of the training was feasible overall. In addition, a significant decrease of depression and anxiety symptoms as well as a significant increase of optimism were found in the PoET group. No significant changes were found in the control group. CONCLUSIONS: Results indicate that PoET is an applicable intervention for improving mental health in the general population. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov on 21/02/2023 (Identifier/Trial registration number: NCT05737251).

Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase attenuated particulate matter 2.5 exposure mediated lung injury.

Air pollution represented by particulate matter 2.5 (PM2.5) is closely related to diseases of the respiratory system. Although the understanding of its mechanism is limited, pulmonary inflammation is closely correlated with PM2.5-mediated lung injury. Soluble epoxide hydrolase (sEH) and epoxy fatty acids play a vital role in the inflammation. Herein, we attempted to use the metabolomics of oxidized lipids for analyzing the relationship of oxylipins with lung injury in a PM2.5-mediated mouse model, and found that the cytochrome P450 oxidases/sEH mediated metabolic pathway was involved in lung injury. Furthermore, the sEH overexpression was revealed in lung injury mice. Interestingly, sEH genetic deletion or the selective sEH inhibitor TPPU increased levels of epoxyeicosatrienoic acids (EETs) in lung injury mice, and inactivated pulmonary macrophages based on the MAPK/NF-κB pathway, resulting in protection against PM2.5-mediated lung injury. Additionally, a natural sEH inhibitor luteolin from Inula japonica displayed a pulmonary protective effect towards lung injury mediated by PM2.5 as well. Our results are consistent with the sEH message and protein being both a marker and mechanism for PM2.5-induced inflammation, which suggest its potential as a pharmaceutical target for treating diseases of the respiratory system.

Predicting and Visualizing Citrus Color Transformation Using a Deep Mask-Guided Generative Network.

Citrus rind color is a good indicator of fruit development, and methods to monitor and predict color transformation therefore help the decisions of crop management practices and harvest schedules. This work presents the complete workflow to predict and visualize citrus color transformation in the orchard featuring high accuracy and fidelity. A total of 107 sample Navel oranges were observed during the color transformation period, resulting in a dataset containing 7,535 citrus images. A framework is proposed that integrates visual saliency into deep learning, and it consists of a segmentation network, a deep mask-guided generative network, and a loss network with manually designed loss functions. Moreover, the fusion of image features and temporal information enables one single model to predict the rind color at different time intervals, thus effectively shrinking the number of model parameters. The semantic segmentation network of the framework achieves the mean intersection over a union score of 0.9694, and the generative network obtains a peak signal-to-noise ratio of 30.01 and a mean local style loss score of 2.710, which indicate both high quality and similarity of the generated images and are also consistent with human perception. To ease the applications in the real world, the model is ported to an Android-based application for mobile devices. The methods can be readily expanded to other fruit crops with a color transformation period. The dataset and the source code are publicly available at GitHub.

TAK1 Improves Cognitive Function via Suppressing RIPK1-Driven Neuronal Apoptosis and Necroptosis in Rats with Chronic Hypertension.

Chronic hypertension is a major risk factor for cognitive impairment, which can promote neuroinflammation and neuronal loss in the central nervous system. Transforming growth factor ß-activated kinase 1 (TAK1) is a key molecular component in determining cell fate and can be activated by inflammatory cytokines. This study aimed to investigate the role of TAK1 in mediating neuronal survival in the cerebral cortex and hippocampus under chronic hypertensive conditions. To that end, we used stroke-prone renovascular hypertension rats (RHRSP) as chronic hypertension models. Adeno-associated virus (AAV) designed to overexpress or knock down TAK1 expression were injected into the lateral ventricles of rats and the subsequent effects on cognitive function and neuronal survival under chronic hypertensive conditions were assessed. We found that, TAK1 knockdown in RHRSP markedly increased neuronal apoptosis and necroptosis and induced cognitive impairment, which could be reversed by Nec-1s, an inhibitor of receptor interacting protein kinase 1 (RIPK1). In contrast, overexpression of TAK1 in RHRSP significantly suppressed neuronal apoptosis and necroptosis and improved cognitive function. Further knockdown of TAK1 in sham-operated rats received similar phenotype with RHRSP. The results have been verified in vitro. In this study, we provide in vivo and in vitro evidence that TAK1 improves cognitive function by suppressing RIPK1-driven neuronal apoptosis and necroptosis in rats with chronic hypertension.