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Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer's disease. The middle temporal gyrus region of the brain is susceptible to pronounced impairment in Alzheimer's disease. Identification of the molecules involved in vascular aberrance of the middle temporal gyrus would support elucidation of the mechanisms underlying Alzheimer's disease and discovery of novel targets for intervention. We carried out single-cell transcriptomic analysis of the middle temporal gyrus in the brains of patients with Alzheimer's disease and healthy controls, revealing obvious changes in vascular function. CellChat analysis of intercellular communication in the middle temporal gyrus showed that the number of cell interactions in this region was decreased in Alzheimer's disease patients, with altered intercellular communication of endothelial cells and pericytes being the most prominent. Differentially expressed genes were also identified. Using the CellChat results, AUCell evaluation of the pathway activity of specific cells showed that the obvious changes in vascular function in the middle temporal gyrus in Alzheimer's disease were directly related to changes in the vascular endothelial growth factor (VEGF)A-VEGF receptor (VEGFR) 2 pathway. AUCell analysis identified subtypes of endothelial cells and pericytes directly related to VEGFA-VEGFR2 pathway activity. Two subtypes of middle temporal gyrus cells showed significant alteration in AD: endothelial cells with high expression of Erb-B2 receptor tyrosine kinase 4 (ERBB4high) and pericytes with high expression of angiopoietin-like 4 (ANGPTL4high). Finally, combining bulk RNA sequencing data and two machine learning algorithms (least absolute shrinkage and selection operator and random forest), four characteristic Alzheimer's disease feature genes were identified: somatostatin (SST), protein tyrosine phosphatase non-receptor type 3 (PTPN3), glutinase (GL3), and tropomyosin 3 (PTM3). These genes were downregulated in the middle temporal gyrus of patients with Alzheimer's disease and may be used to target the VEGF pathway. Alzheimer's disease mouse models demonstrated consistent altered expression of these genes in the middle temporal gyrus. In conclusion, this study detected changes in intercellular communication between endothelial cells and pericytes in the middle temporal gyrus and identified four novel feature genes related to middle temporal gyrus and vascular functioning in patients with Alzheimer's disease. These findings contribute to a deeper understanding of the molecular mechanisms underlying Alzheimer's disease and present novel treatment targets.
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The inhibition of amino acids on the formation of protein-bound HAs was assessed in both model systems and roast beef patties, and the synergism between these amino acids was also investigated. The amino acids can promote the formation of protein-bound HAs at low addition amount, and the total content of protein-bound HAs increased from 444.05 ± 4.98 ng/g of the control group to 517.36 ± 16.51 ng/g when 0.05 % cysteine was added. Amino acid combinations exhibited stable inhibitory effects, with the maximum inhibitory rate of 64 % in the treatment with histidine-proline combination (1:4). The synergistic inhibition may be caused by simultaneously scavenging intermediates and competing for the binding sites of muscle proteins, and the reaction with protein-bound HAs to form adduct can serve as supporting factors to co-mitigate the promotion in protein-bound HAs from increased protein solubility. These findings proposed the potential mitigation strategies against protein-bound HAs formation.
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Ainsliaea fragrans Champ, a strong heat-clearing and detoxifying traditional Chinese medicine, has been effectively used for treating chronic cervicitis, endometritis, pelvic inflammatory diseases, and other conditions caused by damp heat. It shows a good effect in the treatment of cervicitis and has broad clinical application prospects. Nevertheless, there is no comprehensive study on its in vivo and in vitro chemical analysis. UHPLC-QTOF-MS/MS combined with the non-targeted characteristic filter analysis were used to conjecture and characterize the chemical components and in vivo metabolites of rats following oral administration of Ainsliaea fragrans Champ. In this study, A total of 85 compounds were identified in Ainsliaea fragrans Champ, including 29 flavonoids, 14 sesquiterpenoids, 25 chlorogenic acids, and 17 other compounds. In the plasma of rats after administration of Ainsliaea fragrans Champ, 160 compounds were deduced (19 prototype compounds and 141 metabolites). The 141 metabolites consist of 50 flavonoids, 80 phenolic acids and 11 Chlorogenic acids. The related metabolic pathways mainly involved demethylation, reduction, sulfonation, decarboxylation, hydroxylation, methylation, and glucuronide conjunction. In summary, the chemical components and metabolites of Ainsliaea fragrans Champ were comprehensively identified by using a rapid and accurate analysis method, which laid a foundation for dissecting its bioactive substances. In addition, it provides a scientific basis for the in-depth study of the material basis of Ainsliaea fragrans Champ efficacy and theoretical support for illustrating the mechanism of medical action and its clinical application.
Subject(s)
Drugs, Chinese Herbal , Flavonoids , Rats, Sprague-Dawley , Tandem Mass Spectrometry , Animals , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Rats , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/metabolism , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Administration, Oral , Flavonoids/blood , Flavonoids/chemistry , Female , Chlorogenic Acid/blood , Chlorogenic Acid/chemistry , Chlorogenic Acid/administration & dosage , Chlorogenic Acid/metabolism , Asteraceae/chemistry , Hydroxybenzoates/blood , Hydroxybenzoates/analysis , Hydroxybenzoates/metabolismABSTRACT
Sarcopenia is a condition characterized by age-related loss of muscle mass and strength. Increasing evidence suggests that patients with sarcopenia have higher rates of coronavirus 2019 (COVID-19) infection and poorer post-infection outcomes. However, the exact mechanism and connections between the two is unknown. In this study, we used high-throughput data from the GEO database for sarcopenia (GSE111016) and COVID-19 (GSE171110) to identify common differentially expressed genes (DEGs). We conducted GO and KEGG pathway analyses, as well as PPI network analysis on these DEGs. Using seven algorithms from the Cytoscape plug-in cytoHubba, we identified 15 common hub genes. Further analyses included enrichment, PPI interaction, TF-gene and miRNA-gene regulatory networks, gene-disease associations, and drug prediction. Additionally, we evaluated immune cell infiltration with CIBERSORT and assessed the diagnostic accuracy of hub genes for sarcopenia and COVID-19 using ROC curves. In total, we identified 66 DEGs (34 up-regulated and 32 down-regulated) and 15 hub genes associated with sarcopenia and COVID-19. GO and KEGG analyses revealed functions and pathways between the two diseases. TF-genes and TF-miRNA regulatory network suggest that FOXOC1 and hsa-mir-155-5p may be identified as key regulators, while gene-disease analysis showed strong correlations with hub genes in schizophrenia and bipolar disorder. Immune infiltration showed a correlation between the degree of immune infiltration and the level of infiltration of different immune cell subpopulations of hub genes in different datasets. The ROC curves for ALDH1L2 and KLF5 genes demonstrated their potential as diagnostic markers for both sarcopenia and COVID-19. This study suggests that sarcopenia and COVID-19 may share pathogenic pathways, and these pathways and hub genes offer new targets and strategies for early diagnosis, effective treatment, and tailored therapies for sarcopenia patients with COVID-19.
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PURPOSE: This study aimed to evaluate the clinical and radiological outcomes of modified suture-bridge technique fixation for anterior cruciate ligament (ACL) tibial avulsion fracture. METHOD: Minors who underwent arthroscopic reduction and modified suture bridge fixation of ACL tibial avulsion fracture between January 2018 and January 2022 were retrospectively analyzed. Postoperative MRI and X-ray examinations were performed to evaluate the presence of epiphyseal plate injury and fracture healing. Moreover, KT-1000 side-to-side difference, Lachman test, range of motion (ROM), the subjective Knee score of the International Knee Documentation Committee (IKDC), Lysholm Knee score, and Tegner activity grade score were evaluated preoperatively and at the minimum 1-year follow-up visit. RESULTS: A total of 16 participants met the inclusion criteria. They had a mean age of 12.6 years (range, 9-16 years); mean time to surgery, 6.9 days (range, 2-13 days) and had a minimum of 12 months clinical follow-up (mean, 25.4 months; range, 12-36 months) after surgery. Postoperative radiographs and MRI showed no injury to the epiphyseal plate, optimal reduction immediately after the operation, and bone union within three months in all patients. All of the following showed significant improvements (pre- vs. postoperatively): mean KT-1000 side-to-side difference (8.6 vs. 1.5; p < 0.05), Lachman tests (2 grade 9 and 3 grade 7 vs. 0 grade 12 and 1 grade 4; p < 0.05), IKDC subjective score (48.3 vs. 95.0; p < 0.05), mean Lysholm score (53.9 vs. 92.2; p < 0.05), mean Tegner activity score (3.2 vs. 8.3; p < 0.05) and mean ROM (42.9°vs 133.1°; p < 0.05). CONCLUSION: Arthroscopic reduction and modified suture bridge fixation for ACL tibial avulsion fracture is a dependable and recommended treatment that can effectively restore the stability and function of the knee and is worthy of clinical promotion.
Subject(s)
Anterior Cruciate Ligament Injuries , Fractures, Avulsion , Suture Techniques , Tibial Fractures , Humans , Retrospective Studies , Adolescent , Male , Child , Female , Fractures, Avulsion/surgery , Fractures, Avulsion/diagnostic imaging , Tibial Fractures/surgery , Tibial Fractures/diagnostic imaging , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Injuries/diagnostic imaging , Arthroscopy/methods , Treatment Outcome , Anterior Cruciate Ligament/surgery , Anterior Cruciate Ligament/diagnostic imaging , Range of Motion, Articular , Follow-Up StudiesABSTRACT
INTRODUCTION: Our previous work reveals a critical role of activation of neuronal Alox5 in exacerbating brain injury post seizures. However, whether neuronal Alox5 impacts the pathological process of epilepsy remains unknown. OBJECTIVES: To prove the feasibility of neuron-specific deletion of Alox5 via CRISPR-Cas9 in the blockade of seizure onset and epileptic progression. METHODS: Here, we employed a Clustered regularly interspaced short-palindromic repeat-associated proteins 9 system (CRISPR/Cas9) system delivered by adeno-associated virus (AAV) to specifically delete neuronal Alox5 gene in the hippocampus to explore its therapeutic potential in various epilepsy mouse models and possible mechanisms. RESULTS: Neuronal depletion of Alox5 was successfully achieved in the brain. AAV delivery of single guide RNA of Alox5 in hippocampus resulted in reducing seizure severity, delaying epileptic progression and improving epilepsy-associated neuropsychiatric comorbidities especially anxiety, cognitive deficit and autistic-like behaviors in pilocarpine- and kainic acid-induced temporal lobe epilepsy (TLE) models. In addition, neuronal Alox5 deletion also reversed neuron loss, neurodegeneration, astrogliosis and mossy fiber sprouting in TLE model. Moreover, a battery of tests including analysis of routine blood test, hepatic function, renal function, routine urine test and inflammatory factors demonstrated no noticeable toxic effect, suggesting that Alox5 deletion possesses the satisfactory biosafety. Mechanistically, the anti-epileptic effect of Alox5 deletion might be associated with reduction of glutamate level to restore excitatory/inhibitory balance by reducing CAMKII-mediated phosphorylation of Syn ISer603. CONCLUSION: Our findings showed the translational potential of AAV-mediated delivery of CRISPR-Cas9 system including neuronal Alox5 gene for an alternative promising therapeutic approach to treat epilepsy.
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BACKGROUND: This study aimed to investigate risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) based on baseline high-resolution computed tomography (HRCT). METHODS: This prospective observational study enrolled patients with IPF treated at the General Hospital of Ningxia Medical University between January 2019 and January 2021. HRCT-derived quantitative parameters at baseline were analyzed. RESULTS: A total of 102 patients [92 (90.2%) males with a mean age of 67 years] with IPF were included, with a median follow-up of 32 (24-40.5) months. AE occurred in 30 (29.4%) IPF patients. Multivariable logistic regression analysis identified Doppler transthoracic echocardiography suggestive of pulmonary hypertension (PH) (13.43; 95% CI: 4.18-41.09; P < 0.001), honeycombing (OR 1.08; 95% CI: 1.02-1.14; P = 0.013), and whole lung volume (OR 0.99; 95% CI: 0.99-1.00; P = 0.037) as independent risk factors for AE-IPF. The combination of PH, honeycombing, whole lung volume, and the percentage of predicted forced vital capacity (FVC% pred) showed a high area under the curve from receiver operating characteristic curves of 0.888, with a sensitivity of 90% and specificity of 78%. CONCLUSIONS: This study emphasizes that quantitative CT parameters (honeycombing, whole lung volume) may serve as risk factors for AE-IPF. The combination of honeycombing, whole lung volume, FVC% pred, and PH may aid in predicting AE-IPF.
Subject(s)
Idiopathic Pulmonary Fibrosis , Tomography, X-Ray Computed , Humans , Male , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/physiopathology , Aged , Prospective Studies , Female , Risk Factors , Middle Aged , Disease Progression , Lung/diagnostic imaging , Lung/physiopathology , Logistic Models , Hypertension, Pulmonary/diagnostic imaging , ROC CurveABSTRACT
Background: In the 21st century, as globalization accelerates and global public health crises occur, the One Health approach, guided by the holistic thinking of human-animal-environment and emphasizing interdisciplinary collaboration to address global health issues, has been strongly advocated by the international community. An immediate requirement exists for the creation of an assessment tool to foster One Health initiatives on both global and national scales. Methods: Built upon extensive expert consultations and dialogues, this follow-up study enhances the 2022 global One Health index (GOHI) indicator system. The GOHI framework is enriched by covering three indices, e.g. external drivers index (EDI), intrinsic drivers index (IDI), and core drivers index (CDI). The comprehensive indicator system incorporates 13 key indicators, 50 indicators, and 170 sub I-indicators, utilizing a fuzzy analytic hierarchy process to ascertain the weight for each indicator. Weighted and summed, the EDI, IDI, and CDI scores contribute to the computation of the overall GOHI 2022 score. By comparing the ranking and the overall scores among the seven regions and across 160 countries/territories, we have not only derived an overall profile of the GOHI 2022 scores, but also assessed the GOHI framework. We also compared rankings of indicators and sub I-indicators to provide greater clarity on the strengths and weaknesses of each region within the One Health domains. Results: The GOHI 2022 performance reveals significant disparities between countries/territories ranged from 39.03 to 70.61. The global average score of the GOHI 2022 is 54.82. The average score for EDI, IDI, and CDI are 46.57, 58.01, and 57.25, respectively. In terms of global rankings, countries from North America, Europe and Central Asia, East Asia and Pacific present higher scores. In terms of One Health domains of CDI, the lowest scores are observed in antimicrobial resistance (median: 43.09), followed by food security (median: 53.78), governance (median: 54.77), climate change (median: 64.12) and zoonotic diseases (median: 69.23). Globally, the scores of GOHI vary spatially, with the highest score in North America while lowest in sub-Saharan Africa. In addition, evidence shows associations between the socio-demographic profile of countries/territories and their GOHI performance in certain One Health scenarios. Conclusion: The objective of GOHI is to guide impactful strategies for enhancing capacity building in One Health. With advanced technology and an annually updated database, intensifying efforts to refine GOHI's data-mining methodologies become imperative. The goal is to offer profound insights into disparities and progressions in practical One Health implementation, particularly in anticipation of future pandemics.
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Nogo-B, a ubiquitously expressed member of the reticulon family, plays an important role in maintaining endoplasmic reticulum (ER) structure, regulating protein folding, and calcium homeostasis. In this study, we demonstrate that Nogo-B expression and secretion are upregulated in lung cancer and correlate to overall survival. Nogo-B is secreted by various cells, particularly lung cancer cells. ER stress and phosphorylation at serine 107 can induce Nogo-B secretion. Secretory Nogo-B suppresses the differentiation of Th2 cells and the release of type 2 cytokines, thus influencing the anti-tumor effects of Th2-related immune cells, including IgE+B cell class switching and eosinophil activation.
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Loop dynamics redesign is an important strategy to manipulate protein function. Cellobiose 2-epimerase (CE) and other members of its superfamily are widely used for diverse industrial applications. The structural feature of the loops connecting barrel helices contributes greatly to the differences in their functional characteristics. Inspired by the in-silico mutation with molecular dynamics (MD) simulation analysis, we propose a strategy for identifying disulfide bond mutation candidates based on the prediction of protein flexibility and residue-residue interaction. The most beneficial mutant with the newly introduced disulfide bond would simultaneously improve both its thermostability and its reaction propensity to the targeting isomerization product. The ratio of the isomerization/epimerization catalytic rate was improved from 4:103 to 9:22. MD simulation and binding free energy calculations were applied to provide insights into molecular recognition upon mutations. The comparative analysis of enzyme/substrate binding modes indicates that the altered catalytic reaction pathway is due to less efficient binding of the native product. The key residue responsible for the observed phenotype was identified by energy decomposition and was further confirmed by the mutation experiment. The rational design of the key loop region might be a promising strategy to alter the catalytic behavior of all (α/α)6-barrel-like proteins.
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The complex global context, including globalization, rapid urbanization, and climate change, poses significant challenges to urban stability and development. Balancing urban land use efficiency and resilience is crucial for sustainable progress. Focusing on the vulnerable Yellow River Basin (YRB), this study examines the interplay between urban resilience and land use efficiency. Panel data from 2013 to 2020 for 54 cities in the YRB were used, it quantifies the Coupling Coordination Degree of Urban Resilience and Urban Land Use Efficiency (CCDUU), explores its spatiotemporal evolution and influencing factors. Key findings include: The CCDUU exhibits a sustained and discernible growth trend. Notably, CCDUU is higher in downstream areas in comparison to the middle reaches, reaching its lowest point in the upstream areas; however, the increase in CCDUU in the upstream areas surpasses that observed in other regions. Concurrently, regional disparities in CCDUU are diminishing. Despite the presence of a notable positive spatial correlation in CCDUU within the YRB, the strength of this spatial association is not sufficiently robust. Of paramount importance factor is the role of regional innovation, which significantly influences the enhancement of CCDUU. Following closely is the degree of openness, whereas the positive effects of government support and population density are concentrated predominantly in the upper YRB region. In contrast, urban-rural disparity exerts an adverse impact on CCDUU in most regions. Policy recommendations for enhancing CCDUU in YRB cities include strengthening government support and planning control, particularly in upstream regions, to achieve efficient resource utilization and environmental protection. Implementing population density management policies, encouraging rational movement, and promoting population migration to upstream areas can alleviate pressure in downstream cities. Enhancing openness, attracting foreign investment, and promoting innovation and industrial upgrading will drive economic structural upgrades and improve CCDUU.
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Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied by emotional disturbance, especially anxiety and depression. More and more evidence shows that the imbalance of mitochondrial Ca2+ (mCa2+) homeostasis has a close connection with the pathogenesis of anxiety and depression. The Mitochondrial Calcium Uniporter (MCU), a key channel of mCa2+ uptake, induces the imbalance of mCa2+ homeostasis and may be a therapeutic target for anxiety and depression of AD. In the present study, we revealed for the first time that MCU knockdown in hippocampal neurons alleviated anxious and depressive behaviors of APP/PS1/tau mice through elevated plus-maze (EPM), elevated zero maze (EZM), sucrose preference test (SPT) and tail suspension test (TST). Western blot analysis results demonstrated that MCU knockdown in hippocampal neurons increased levels of glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (vGAT) and GABAA receptor α1 (GABRA1) and activated the PKA-CREB-BDNF signaling pathway. This study indicates that MCU inhibition has the potential to be developed as a novel therapy for anxiety and depression in AD.
Subject(s)
Alzheimer Disease , Anxiety , Calcium Channels , Depression , Disease Models, Animal , Hippocampus , Mice, Transgenic , Neurons , Animals , Alzheimer Disease/metabolism , Hippocampus/metabolism , Neurons/metabolism , Depression/metabolism , Calcium Channels/metabolism , Calcium Channels/genetics , Anxiety/metabolism , Mice , Male , Mitochondria/metabolism , Glutamate Decarboxylase/metabolism , Gene Knockdown Techniques/methods , Behavior, Animal/physiologyABSTRACT
BACKGROUND: This study aimed to analyze the trends and burden of occupational exposure to asbestos in the United States (U.S.) from 1990 to 2019, focusing on mortality rates, geographic distribution, age and sex patterns, and causes of death. METHODS: Data on the number of deaths attributable to occupational exposure to asbestos were collected from 1990 to 2019 in the U.S. Joinpoint analysis was conducted to assess trends over time, and regression models were applied to calculate annual percentage changes (APC) and annual average percentage changes (AAPC). Geographic distribution was examined using mapping techniques. Age and sex patterns were analyzed, and causes of death were identified based on available data. RESULTS: From 1990 to 2019, the overall number of deaths due to occupational exposure to asbestos in the U.S. increased by 20.2%. However, age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALYs) rates (ASDR) exhibited a decline over the same period. Geographic analysis revealed differences in the number of deaths across states in 2019, with California reporting the highest number of fatalities. Age-specific mortality and DALYs showed an increase with age, peaking in older age groups. Tracheal, bronchus, and lung cancer were the leading causes of death attributed to asbestos exposure, with increasing trends observed over the past five years. CONCLUSION: The study highlights significant trends and burden in occupational exposure to asbestos in the U.S., including overall increases in mortality rates, declining ASMR and ASDR, geographic disparities, age and sex patterns, and shifts in causes of death. These findings underscore the importance of continued monitoring and preventive measures to mitigate the burden of asbestos-related diseases.
Subject(s)
Asbestos , Cause of Death , Occupational Exposure , Humans , United States/epidemiology , Male , Occupational Exposure/adverse effects , Occupational Exposure/statistics & numerical data , Female , Cause of Death/trends , Middle Aged , Aged , Adult , Disability-Adjusted Life Years/trendsABSTRACT
Mercury (Hg), as a global pollutant, is persistent, migratory, insidious, highly biotoxic and highly enriched, and is widely distributed in the atmosphere, hydrosphere, biosphere and lithosphere. Wetland ecosystems, as active mercury reservoirs, have become the most important sources and sinks of heavy metal mercury. Distinguished from natural wetlands, artificial wetlands located in urban sections of rivers face problems such as diverse urban pollution sources and complex spatial and temporal changes. Therefore, in this study, five intermittently distributed artificial wetlands were selected from the upstream to the downstream of the Changchun section of the Yitong River, a tributary of the Songhua River basin in the old industrial base of Northeast China. The mercury levels in the water bodies, sediments and plants of the artificial wetlands were collected and tested in four quarters from April 2023 to analyse the spatial and temporal distribution characteristics of total mercury. The results showed that the mercury levels in the water bodies, sediments and plants of the five wetlands showed a fluctuating trend with the river flow direction and had certain spatial and temporal distribution characteristics. This phenomenon was attributed to the sinking of external mercury pollution sources. In general, the wetland ecosystems showed a decreasing trend in the total Hg output of the downstream watershed. This may be due to the retention of particulate matter by aquatic plants in artificial wetlands to regular salvage of dead aquatic plants. At the same time urbanization and industrialization affect mercury levels in aquatic environments, so the risk of residential exposure needs to be looked at.
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The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.
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Heavy metal cadmium (Cd) is widespread in contaminated soil and an important factor limiting plant growth. NO3- (nitrate) affects Cd uptake and thus changes Cd tolerance in plants; however, the underlying molecular regulatory mechanisms have not yet been elucidated. Here, we analyzed a novel gene, NtARF11 (auxin response factor), which regulates Cd tolerance in tobacco via the NO3- uptake pathway, through experiments with NtARF11-knockout and NtARF11-overexpression transgenic tobacco lines. NtARF11 was highly expressed under Cd stress in tobacco plants. Under Cd stress, overexpression of NtARF11 enhanced Cd tolerance in tobacco compared to that in wild-type tobacco, as shown by the low Cd concentration, high chlorophyll concentration, and low accumulation of reactive oxygen species in NtARF11-overexpressing tobacco. Moreover, low NO3- concentrations were observed in NtARF11-overexpressing tobacco plants. Further analyses revealed direct binding of NtARF11 to the promoter of the nitrate transporter NtNRT1.1, thereby negatively regulating its expression in tobacco. Notably, NtNRT1.1 knockout reduced NO3- uptake, which resulted in low Cd concentrations in tobacco. Altogether, these results demonstrate that the NtARF11-NtNRT1.1 module functions as a positive regulator of Cd tolerance by reducing the Cd uptake in tobacco, providing new insights for improving Cd tolerance of plants through genetic engineering.
Subject(s)
Cadmium , Gene Expression Regulation, Plant , Nicotiana , Plant Proteins , Plants, Genetically Modified , Nicotiana/metabolism , Nicotiana/genetics , Nicotiana/drug effects , Cadmium/toxicity , Cadmium/metabolism , Gene Expression Regulation, Plant/drug effects , Plant Proteins/genetics , Plant Proteins/metabolism , Nitrates/metabolism , Anion Transport Proteins/genetics , Anion Transport Proteins/metabolism , Promoter Regions, GeneticABSTRACT
Salt stress is one of the main abiotic factor affecting plant growth. We have previously identified a key gene (NtHD9) in Nicotiana tabacum L. that positively regulates the formation of long glandular trichomes (LGTs). Here, we verified that both abiotic stress (aphids, drought and salt stress) could restore the phenotype lacking LGTs in NtHD9-knockout (NtHD9-KO) plants. The abiotic stress response assays indicated that NtHD9 is highly sensitive to salt stress. Compared with cultivated tobacco "K326" (CK) plants, NtHD9-overexpressing (NtHD9-OE) plants with more LGTs exhibited stronger salt tolerance, whereas NtHD9-KO with no LGTs showed weaker tolerance to salt. The densities and sizes of the glandular heads gradually increased with increasing NaCl concentrations in NtHD9-KO plants. Mineral element determination showed that leaves and trichomes of NtHD9-OE plants accumulated less Na+ but had higher K+ contents under salt stress, thus maintaining ion homeostasis in plants, which could contribute to a robust photosynthetic and antioxidant system under salt stress. Therefore, NtHD9-OE plants maintained a larger leaf area and root length under high-salt conditions than CK and NtHD9-KO plants. We verified that NtHD9 could individually interact with NtHD5, NtHD7, NtHD12, and NtJAZ10 proteins. Salt stress led to an increase in jasmonic acid (JA) levels and activated the expression of NtHDs while inhibiting the expression of NtJAZ. This study suggests that the glandular heads play an important role in plant resistance to salt stress. The activation of JA signaling leading to JAZ protein degradation may be key factors regulating the glandular heads development under salt stress.
Subject(s)
Nicotiana , Plant Proteins , Salt Tolerance , Trichomes , Nicotiana/genetics , Nicotiana/metabolism , Nicotiana/physiology , Trichomes/metabolism , Trichomes/growth & development , Plant Proteins/metabolism , Plant Proteins/genetics , Salt Tolerance/genetics , Gene Expression Regulation, Plant , Oxylipins/metabolism , Cyclopentanes/metabolism , Plant Leaves/metabolism , Plant Leaves/genetics , Plants, Genetically ModifiedABSTRACT
Electrical stimulation (ES) has a remarkable capacity to regulate neuronal differentiation and neurogenesis in the treatment of various neurological diseases. However, wired devices connected to the stimulating electrode and the mechanical mismatch between conventional rigid electrodes and soft tissues restrict their motion and cause possible infections, thereby limiting their clinical utility. An approach integrating the advantages of wireless techniques and soft hydrogels provides new insights into ES-induced nerve regeneration. Herein, a flexible and implantable wireless ES-responsive electrode based on an annular gelatin methacrylate-polyaniline (Gel/Pani) hydrogel is fabricated and used as a secondary coil to achieve wireless ES via electromagnetic induction in the presence of a primary coil. The Gel/Pani hydrogels exhibit favorable biocompatibility, biodegradability, conductivity, and compression resistance. The annular electrode of the Gel/Pani conductive hydrogel (AECH) supports neural stem cell growth, while the applied wireless ES facilitates neuronal differentiation and the formation of functional neural networks in vitro. Furthermore, AECH is implanted in vivo in rats with ischemic stroke and the results reveal that AECH-mediated wireless ES significantly ameliorates brain impairment and neurological function by activating endogenous neurogenesis. This novel flexible hydrogel system addresses wireless stimulation and implantable technical challenges, holding great potential for the treatment of neurodegenerative diseases.
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BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.