Profile and Determinants for Complications of Imported Malaria in 5 Chinese Provinces From 2014 to 2021: Retrospective Analysis.

Background: In 2021, the World Health Organization officially declared the People's Republic of China as malaria-free. However, despite this milestone achievement, the continued occurrence of severe and fatal cases of imported malaria in China, due to globalization and increased international communication, remains a significant public health concern. Objective: The aim of this study was to elucidate the epidemiological characteristics of imported malaria in 5 Chinese provinces from 2014 to 2021 and to identify the factors that influence complications in imported malaria cases. The findings will provide a basis for enhancing prevention and control measures, thereby consolidating China's achievements in malaria elimination. Methods: A case-based retrospective study was performed, using surveillance data collected from the representative provinces of China from 2014 to 2021. Epidemiological characteristics were analyzed using descriptive statistics. Logistic regression was used to identify the factors influencing the occurrence of complications. Results: A total of 5559 malaria cases were included during the study period. The predominant species was Plasmodium falciparum (3940/5559, 70.9%), followed by Plasmodium ovale (1054/5559, 19%), Plasmodium vivax (407/5559, 7.3%), Plasmodium malariae (157/5559, 2.8%), and 1 case of Plasmodium knowlesi. Most of the cases were male (5343/5559, 96.1%). The complication rates for P falciparum and P ovale were 11.4% and 3.3%, respectively. Multivariate logistic regression analysis of the relevant factors of malaria complications revealed potential protective factors, including a previous infection by Plasmodium (P<.001; odds ratio [OR] 0.512, 95% CI 0.422-0.621), and risk factors, including increased age (P=.004; OR 1.014, 95% CI 1.004-1.024), misdiagnosis at the first clinical visit (P<.001; OR 3.553, 95% CI 2.886-4.375), and the time interval from onset to treatment (P=.001; OR 1.026, 95% CI 1.011-1.042). Subgroup analyses identified risk factors associated with P falciparum, which include advanced age (P=.004; OR 1.015, 95% CI 1.005-1.026), initial misdiagnosis during the first clinical visit (P<.001; OR 3.549, 95% CI 2.827-4.455), the time interval from onset to treatment (P<.001; OR 1.043, 95% CI 1.022-1.063), and a delay of more than 3 days from the first treatment to diagnosis (P<.001; OR 2.403, 95% CI 1.823-3.164). Additionally, the risk factors pertaining to P ovale involve misdiagnosis at the initial clinical visit (P=.01; OR 2.901, 95% CI 1.336-6.298), the time interval from onset to treatment (P=.002; OR 1.095, 95% CI 1.033-1.160), and the duration from the initial treatment to diagnosis (P=.43; OR 1.032, 95% CI 0.953-1.118). Previous infections can prevent the progression of both P falciparum and P ovale. Conclusions: This study showed that the increasing proportion of P ovale in recent years should not be ignored. Furthermore, there is a need to improve diagnostic awareness, enhance the capacity of medical institutions, and provide health education for high-risk groups.

Integrating bioinformatics and multiple machine learning to identify mitophagy-related targets for the diagnosis and treatment of diabetic foot ulcers: evidence from transcriptome analysis and drug docking.

Background: Diabetic foot ulcers are the most common and serious complication of diabetes mellitus, the high morbidity, mortality, and disability of which greatly diminish the quality of life of patients and impose a heavy socioeconomic burden. Thus, it is urgent to identify potential biomarkers and targeted drugs for diabetic foot ulcers. Methods: In this study, we downloaded datasets related to diabetic foot ulcers from gene expression omnibus. Dysregulation of mitophagy-related genes was identified by differential analysis and weighted gene co-expression network analysis. Multiple machine algorithms were utilized to identify hub mitophagy-related genes, and a novel artificial neural network model for assisting in the diagnosis of diabetic foot ulcers was constructed based on their transcriptome expression patterns. Finally, potential drugs that can target hub mitophagy-related genes were identified using the Enrichr platform and molecular docking methods. Results: In this study, we identified 702 differentially expressed genes related to diabetic foot ulcers, and enrichment analysis showed that these genes were associated with mitochondria and energy metabolism. Subsequently, we identified hexokinase-2, small ribosomal subunit protein us3, and l-lactate dehydrogenase A chain as hub mitophagy-related genes of diabetic foot ulcers using multiple machine learning algorithms and validated their diagnostic performance in a validation cohort independent of the present study (The areas under roc curve of hexokinase-2, small ribosomal subunit protein us3, and l-lactate dehydrogenase A chain are 0.671, 0.870, and 0.739, respectively). Next, we constructed a novel artificial neural network model for the molecular diagnosis of diabetic foot ulcers, and the diagnostic performance of the training cohort and validation cohort was good, with areas under roc curve of 0.924 and 0.840, respectively. Finally, we identified retinoic acid and estradiol as promising anti-diabetic foot ulcers by targeting hexokinase-2 (-6.6 and -7.2 kcal/mol), small ribosomal subunit protein us3 (-7.5 and -8.3 kcal/mol), and l-lactate dehydrogenase A chain (-7.6 and -8.5 kcal/mol). Conclusion: The present study identified hexokinase-2, small ribosomal subunit protein us3 and l-lactate dehydrogenase A chain, and emphasized their critical roles in the diagnosis and treatment of diabetic foot ulcers through multiple dimensions, providing promising diagnostic biomarkers and targeted drugs for diabetic foot ulcers.

Identification of novel immune-related signatures for keloid diagnosis and treatment: insights from integrated bulk RNA-seq and scRNA-seq analysis.

BACKGROUND: Keloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids. METHOD: Bulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids. RESULTS: In the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion. CONCLUSION: In summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment.

Identification of habitat suitability for the dominant zoonotic tick species Haemaphysalis flava on Chongming Island, China.

Haemaphysalis ticks are pathogenic vectors that threaten human and animal health and were identified in Chongming, the third largest island in China. To understand the distribution of these ticks and determine their potential invasion risk, this study aimed to identify the habitat suitability of the dominant tick H. flava based on natural environmental factors. Geographic information system (GIS) images were combined with sample points from tick investigations to map the spatial distribution of H. flava. Data on 19 bioclimatic variables, environmental variables, and satellite-based landscapes of Chongming Island were retrieved to create a landcover map related to natural environmental determinants of H. flava. These data included 38 sites associated with the vectors to construct species distribution models with MaxEnt, a model based on the maximum entropy principle, and to predict habitat suitability for H. flava on Chongming Island in 2050 and 2070 under different climate scenarios. The model performed well in predicting the H. flava distribution, with a training area under the curve of 0.84 and a test area under the curve of 0.73. A habitat suitability map of the whole study area was created for H. flava. The resulting map and natural environment analysis highlighted the importance of the normalized difference vegetation index and precipitation in the driest month for the bioecology of H. flava, with 141.61 km2 (11.77%), 282.94 km2 (23.35%), and 405.30 km2 (33.69%) of highly, moderately, and poorly suitable habitats, respectively. The distribution decreased by 135.55 km2 and 138.82 km2 in 2050 and 2070, respectively, under the shared socioeconomic pathway (SSP) 1.2.6 climate change scenario. However, under SSP 5.8.5, the total area will decrease by 128.5 km2 in 2050 and increase by 151.64 km2 in 2070. From a One Health perspective, this study provides good knowledge that will guide tick control efforts to prevent the spread of Haemaphysalis ticks or transmission risk of Haemaphysalis-borne infections at the human-animal-environment interface on the island.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

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.

Towards an actionable One Health approach.

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.

Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

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.

Assessing food security performance from the One Health concept: an evaluation tool based on the Global One Health Index.

BACKGROUND: Food systems instantiate the complex interdependencies across humans, physical environments, and other organisms. Applying One Health approaches for agri-food system transformation, which adopts integrated and unifying approaches to optimize the overall health of humans, animals, plants, and environments, is crucial to enhance the sustainability of food systems. This study develops a potential assessment tool, named the global One Health index-Food Security (GOHI-FS), aiming to evaluate food security performance across countries/territories from One Health perspective and identify relevant gaps that need to be improved for sustainable food systems. METHODS: We comprehensively reviewed existing frameworks and elements of food security. The indicator framework of GOHI-FS was conceptualized following the structure-process-outcome model and confirmed by expert advisory. Publicly available data in 2020 was collected for each indicator. The weighting strategy was determined by the Fuzzy Analytical Hierarchy Process. The data for each indicator was normalized and aggregated by weighted arithmetic mean. Linear regressions were performed to evaluate the associations of GOHI-FS with health and social-economic indicators. RESULTS: The GOHI-FS includes 5 first-level indicators, 19 second-level indicators and 45 third-level indicators. There were 146 countries/territories enrolled for evaluation. The highest average score of first-level indicators was Nutrition (69.8) and the lowest was Government Support and Response (31.3). There was regional heterogeneity of GOHI-FS scores. Higher median scores with interquartile range (IQR) were shown in North America (median: 76.1, IQR: 75.5-76.7), followed by Europe and Central Asia (median: 66.9, IQR: 60.1-74.3), East Asia and the Pacific (median: 60.6, IQR: 55.5-68.7), Latin America and the Caribbean (median: 60.2, IQR: 57.8-65.0), Middle East and North Africa (median: 56.6, IQR: 52.0-62.8), South Asia (median: 51.1, IQR: 46.7-53.8), and sub-Saharan Africa (median: 41.4, IQR: 37.2-46.5). We also found significant associations between GOHI-FS and GDP per capita, socio-demographic index, health expenditure and life expectancy. CONCLUSIONS: GOHI-FS is a potential assessment tool to understand the gaps in food security across countries/territories under the One Health concept. The pilot findings suggest notable gaps for sub-Saharan Africa in numerous aspects. Broad actions are needed globally to promote government support and response for food security.

China's application of the One Health approach in addressing public health threats at the human-animal-environment interface: Advances and challenges.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

Tackling global health security by building an academic community for One Health action.

BACKGROUND: One Health approach is crucial to tackling complex global public health threats at the interface of humans, animals, and the environment. As outlined in the One Health Joint Plan of Action, the international One Health community includes stakeholders from different sectors. Supported by the Bill & Melinda Gates Foundation, an academic community for One Health action has been proposed with the aim of promoting the understanding and real-world implementation of One Health approach and contribution towards the Sustainable Development Goals for a healthy planet. MAIN TEXT: The proposed academic community would contribute to generating high-quality scientific evidence, distilling local experiences as well as fostering an interconnected One Health culture and mindset, among various stakeholders on different levels and in all sectors. The major scope of the community covers One Health governance, zoonotic diseases, food security, antimicrobial resistance, and climate change along with the research agenda to be developed. The academic community will be supported by two committees, including a strategic consultancy committee and a scientific steering committee, composed of influential scientists selected from the One Health information database. A workplan containing activities under six objectives is proposed to provide research support, strengthen local capacity, and enhance global participation. CONCLUSIONS: The proposed academic community for One Health action is a crucial step towards enhancing communication, coordination, collaboration, and capacity building for the implementation of One Health. By bringing eminent global experts together, the academic community possesses the potential to generate scientific evidence and provide advice to local governments and international organizations, enabling the pursuit of common goals, collaborative policies, and solutions to misaligned interests.

Analysis of risk factors of prolonged mechanical ventilation in patients with severe burn injury.

BACKGROUND: Mechanical ventilation is an essential means of life support for patients with severe burns. However, prolonged mechanical ventilation (PMV) increases the incidence of complications and length of hospital stay. Therefore, studying the risk factors of mechanical ventilation duration is of great significance for reducing the duration of mechanical ventilation, reducing related complications, and improving the success rate of severe burn treatment. METHOD: This study was a retrospective study of patients with burns ≥30% of the area admitted to the BICU of Guangzhou Red Cross Hospital affiliated with Jinan University from January 2016 to January 2023 who were mechanically ventilated. Patients were classified into the prolonged mechanical ventilation group if they were mechanically ventilated for ≥21 days. Then, independent risk factors for prolonged mechanical ventilation were determined by logistic regression analysis of the collected data. RESULT: Of all the 112 enrolled patients, 79 had prolonged mechanical ventilation, with an incidence of 70.5%. Logistic regression analysis revealed that including abbreviated burn severity index (ABSI%) (P < 0.001), moderate and severe inhalation injury (P = 0.005, P = 0.044), albumin (P = 0.032), lactic acid (P < 0.001) were independent risk factors for prolonged mechanical ventilation. In addition, ventilator-related complications were 44% in the PMV group and 21% in the non-PMV group. CONCLUSION: ABSI%, inhalation injury, albumin, and lactic acid on admission are the risk factors for PMV in severe burn patients. In addition, ventilator-related complications were higher in group PMV than in group non-PMV in our study.

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.

Acceleration of Stepwise Carbon-Polygold Bonding Cleavage in Hypercoordinated Carbon-Centered Gold(I) Clusters.

Hypercoordinated carbon-centered organometallic clusters extensively exist in polymetallic and metal surface catalysis. The investigation on their electronic structures and transformations is crucial for mechanistic studies. Herein, we try to clarify the reactivity difference between a hypercoordinated tetrametalated species [PA-C-Au4]+ and a classical trimetalated one [(PA-C-Au3) + H]+ based on experimental and theoretical studies. Under a protonolysis condition, the hypercoordinated carbon species [PA-C-Au4]+ experiences a sequential cleavage process of carbon-polymetal bonding through the trinuclear [(PA-C-Au3) + H]+ intermediate to end up with a methyl group. Theoretical studies indicate that the high symmetry of five-center bonding in [PA-C-Au4]+ promotes the delocalization of negative charges, finally resulting in less nucleophilicity of the central hypercarbon atom. In contrast, the low C3V triangular arrangement of gold atoms in the [(PA-C-Au3) + H]+ structure causes the decrease in orbital interaction between the Aun moiety and the central carbon atom and the increase in the negative charge on the central carbon atom. Along with the gradual cleavage of the carbon-polymetal bonding, the accumulation of negative charges and the reduction of steric hindrance around the central carbon atom jointly contribute to the synergistic multi-step protodeauration process. This work not only illustrates the reactivity difference of RC-Mn species in different degrees of metalation but also provides an essential structural basis for the design of synergistic polymetallic catalysts.

Macrophage Inactivation by Small Molecule Wedelolactone via Targeting sEH for the Treatment of LPS-Induced Acute Lung Injury.

Soluble epoxide hydrolase (sEH) plays a critical role in inflammation by modulating levels of epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids (EpFAs). Here, we investigate the possible role of sEH in lipopolysaccharide (LPS)-mediated macrophage activation and acute lung injury (ALI). In this study, we found that a small molecule, wedelolactone (WED), targeted sEH and led to macrophage inactivation. Through the molecular interaction with amino acids Phe362 and Gln384, WED suppressed sEH activity to enhance levels of EETs, thus attenuating inflammation and oxidative stress by regulating glycogen synthase kinase 3beta (GSK3ß)-mediated nuclear factor-kappa B (NF-κB) and nuclear factor E2-related factor 2 (Nrf2) pathways in vitro. In an LPS-stimulated ALI animal model, pharmacological sEH inhibition by WED or sEH knockout (KO) alleviated pulmonary damage, such as the increase in the alveolar wall thickness and collapse. Additionally, WED or sEH genetic KO both suppressed macrophage activation and attenuated inflammation and oxidative stress in vivo. These findings provided the broader prospects for ALI treatment by targeting sEH to alleviate inflammation and oxidative stress and suggested WED as a natural lead candidate for the development of novel synthetic sEH inhibitors.

Direct targeting of sEH with alisol B alleviated the apoptosis, inflammation, and oxidative stress in cisplatin-induced acute kidney injury.

Acute kidney injury (AKI) is a pathological condition characterized by a rapid decrease in glomerular filtration rate and nitrogenous waste accumulation during hemodynamic regulation. Alisol B, from Alisma orientale, displays anti-tumor, anti-complement, and anti-inflammatory effects. However, its effect and action mechanism on AKI is still unclear. Herein, alisol B significantly attenuated cisplatin (Cis)-induced renal tubular apoptosis through decreasing expressions levels of cleaved-caspase 3 and cleaved-PARP and the ratio of Bax/Bcl-2 depended on the p53 pathway. Alisol B also alleviated Cis-induced inflammatory response (e.g. the increase of ICAM-1, MCP-1, COX-2, iNOS, IL-6, and TNF-α) and oxidative stress (e.g. the decrease of SOD and GSH, the decrease of HO-1, GCLC, GCLM, and NQO-1) through the NF-κB and Nrf2 pathways. In a target fishing experiment, alisol B bound to soluble epoxide hydrolase (sEH) as a direct cellular target through the hydrogen bond with Gln384, which was further supported by inhibition kinetics and surface plasmon resonance (equilibrium dissociation constant, K D = 1.32 µM). Notably, alisol B enhanced levels of epoxyeicosatrienoic acids and decreased levels of dihydroxyeicosatrienoic acids, indicating that alisol B reduced the sEH activity in vivo. In addition, sEH genetic deletion alleviated Cis-induced AKI and abolished the protective effect of alisol B in Cis-induced AKI as well. These findings indicated that alisol B targeted sEH to alleviate Cis-induced AKI via GSK3ß-mediated p53, NF-κB, and Nrf2 signaling pathways and could be used as a potential therapeutic agent in the treatment of AKI.

Inula japonica ameliorated the inflammation and oxidative stress in LPS-induced acute lung injury through the MAPK/NF-κB and Keap1/Nrf2 signalling pathways.

OBJECTIVES: To investigate the protective effect and underlying mechanism of Inula japonica (TEIJ) in the treatment of acute lung injury (ALI). METHODS: Protective effects of TEIJ in the inflammation and oxidative stress were studied in lipopolysaccharide (LPS)-induced ALI mice. Meanwhile, Western blot and real-time qPCR were carried out to investigate the underlying mechanism of TEIJ for ALI as well as immunohistochemistry. KEY FINDINGS: TEIJ significantly alleviated the course of ALI via suppressing the interstitial infiltrated inflammatory cells, the increase of inflammatory factors and the decrease of anti-oxidative factors. TEIJ inactivated the MAPK/NF-κB signalling pathway to suppress the transcription of its downstream target genes, such as TNF-α, IL-6, etc. Meanwhile, TEIJ activated the Keap1/Nrf2 signalling pathway to regulate expression levels of Nrf2 and its target proteins. The results of LC-QTOF-MS/MS indicated potential active constituents of I. japonica, terpenoids and flavonoids. Additionally, terpenoids and flavonoids synergistically alleviated LPS-induced ALI depending on MAPK/NF-κB and Keap1/Nrf2 signalling pathways. CONCLUSION: I. japonica could be considered a potential agent to treat ALI via regulating the MAPK/NF-κB and Keap1/Nrf2 signalling pathways.

The application of aromaticity and antiaromaticity to reaction mechanisms.

Aromaticity, in general, can promote a given reaction by stabilizing a transition state or a product via a mobility of π electrons in a cyclic structure. Similarly, such a promotion could be also achieved by destabilizing an antiaromatic reactant. However, both aromaticity and transition states cannot be directly measured in experiment. Thus, computational chemistry has been becoming a key tool to understand the aromaticity-driven reaction mechanisms. In this review, we will analyze the relationship between aromaticity and reaction mechanism to highlight the importance of density functional theory calculations and present it according to an approach via either aromatizing a transition state/product or destabilizing a reactant by antiaromaticity. Specifically, we will start with a particularly challenging example of dinitrogen activation followed by other small-molecule activation, C-F bond activation, rearrangement, as well as metathesis reactions. In addition, antiaromaticity-promoted dihydrogen activation, CO2 capture, and oxygen reduction reactions will be also briefly discussed. Finally, caution must be cast as the magnitude of the aromaticity in the transition states is not particularly high in most cases. Thus, a proof of an adequate electron delocalization rather than a complete ring current is recommended to support the relatively weak aromaticity in these transition states.

Biotransformation of 18ß-Glycyrrhetinic Acid by Human Intestinal Fungus Aspergillus niger RG13B1 and the Potential Anti-Inflammatory Mechanism of Its Metabolites.

18ß-Glycyrrhetinic acid (GA) is a triterpenoid possessing an anti-inflammatory activity in vivo, while the low bioavailability limits its application due to its intestinal accumulation. In order to investigate the metabolism of GA in intestinal microbes, it was incubated with human intestinal fungus Aspergillus niger RG13B1, finally leading to the isolation and identification of three new metabolites (1-3) and three known metabolites (4-6) based on 1D and 2D NMR and high-resolution electrospray ionization mass spectroscopy spectra. Metabolite 6 could target myeloid differentiation protein 2 (MD2) to suppress the activation of nuclear factor-kappa B (NF-κB) signaling pathway via inhibiting the nuclear translocation of p65 to downregulate its target proteins and genes in lipopolysaccharide (LPS)-mediated RAW264.7 cells. Molecular dynamics suggested that metabolite 6 interacted with MD2 through the hydrogen bond of amino acid residue Arg90. These findings demonstrated that metabolite 6 could serve as a potential candidate to develop the new inhibitors of MD2.

Assessment of performance for a key indicator of One Health: evidence based on One Health index for zoonoses in Sub-Saharan Africa.

BACKGROUND: Zoonoses are public health threats that cause severe damage worldwide. Zoonoses constitute a key indicator of One Health (OH) and the OH approach is being applied for zoonosis control programmes of zoonotic diseases. In a very recent study, we developed an evaluation system for OH performance through the global OH index (GOHI). This study applied the GOHI to evaluate OH performance for zoonoses in sub-Saharan Africa. METHODS: The framework for the OH index on zoonoses (OHIZ) was constructed including five indicators, 15 subindicators and 28 datasets. Publicly available data were referenced to generate the OHIZ database which included both qualitative and quantitative indicators for all sub-Sahara African countries (n = 48). The GOHI algorithm was used to estimate scores for OHIZ. Indicator weights were calculated by adopting the fuzzy analytical hierarchy process. RESULTS: Overall, five indicators associated with weights were generated as follows: source of infection (23.70%), route of transmission (25.31%), targeted population (19.09%), capacity building (16.77%), and outcomes/case studies (15.13%). Following the indicators, a total of 37 sub-Sahara African countries aligned with OHIZ validation, while 11 territories were excluded for unfit or missing data. The OHIZ average score of sub-Saharan Africa was estimated at 53.67/100. The highest score was 71.99 from South Africa, while the lowest score was 40.51 from Benin. It is also worth mentioning that Sub-Sahara African countries had high performance in many subindicators associated with zoonoses, e.g., surveillance and response, vector and reservoir interventions, and natural protected areas, which suggests that this region had a certain capacity in control and prevention or responses to zoonotic events. CONCLUSIONS: This study reveals that it is possible to perform OH evaluation for zoonoses in sub-Saharan Africa by OHIZ. Findings from this study provide preliminary research information in advancing knowledge of the evidenced risks to strengthen strategies for effective control of zoonoses and to support the prevention of zoonotic events.