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1.
Discov Oncol ; 15(1): 212, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836972

ABSTRACT

BACKGROUND: Liquid biopsies, for example, exosomal circular RNA (circRNA) can be used to assess potential predictive markers for hepatocellular carcinoma (HCC) in patients after curative resection. This study aimed to search for effective prognostic biomarkers for HCC in patients after surgical resection based on exosomal circRNA expression profiles. We developed two nomograms incorporating circRNAs to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) of HCC patients. METHOD: Plasma exosomes isolated from HCC patients and healthy individuals were used for circRNA microarray analysis to explore differentially expressed circRNAs. Pearson correlation analysis was used to evaluate the correlation between circRNAs and clinicopathological features. Cox regression analysis was used to explore the correlation between circRNA and postoperative survival time as well as recurrence time. A nomogram based on circRNA and clinicopathological characteristics was established and further evaluated to predict prognosis and recurrence. RESULT: Among 60 significantly upregulated circRNAs and 25 downregulated circRNAs, hsa_circ_0029325 was selected to verify its power for predicting HCC outcomes. The high expression level of exosomal hsa_circ_0029325 was significantly correlated with OS (P = 0.001, HR = 2.04, 95% CI 1.41-3.32) and RFS (P = 0.009, HR = 1.62, 95% CI 1.14-2.30). Among 273 HCC patients, multivariate regression analysis showed that hsa_circ_0029325 (HR = 1.96, 95% CI 1.21-3.18), tumor size (HR = 2.11, 95% CI 1.33-3.32), clinical staging (HR = 2.31, 95% CI 1.54-3.48), and tumor thrombus (HR = 1.74, 95% CI 1.12-2.7) were independent risk factors for poor prognosis in HCC patients after radical resection. These independent predictors of prognosis were incorporated into the two nomograms. The AUCs under the 1-year, 3-year, and 5-year survival and recurrence curves of the OS and RFS nomograms were 0.755, 0.749, and 0.742 and 0.702, 0.685, and 0.642, respectively. The C-index, calibration curves, and clinical decision curves showed that the two prediction models had good predictive performance. These results were verified in the validation cohort with 90 HCC patients. CONCLUSION: Our study established two reliable nomograms for predicting recurrence and prognosis in HCC patients. We also show that it is feasible to screen potential predictive markers for HCC after curative resection through exosomal circRNA expression profile analysis.

2.
Infect Dis Poverty ; 13(1): 28, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38610035

ABSTRACT

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.


Subject(s)
One Health , Animals , Asia , Capacity Building , Policy , Zoonoses/prevention & control
3.
Anal Chem ; 96(16): 6301-6310, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38597061

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) is a transformative technology that unravels the intricate cellular state heterogeneity. However, the Poisson-dependent cell capture and low sensitivity in scRNA-seq methods pose challenges for throughput and samples with a low RNA-content. Herein, to address these challenges, we present Well-Paired-Seq2 (WPS2), harnessing size-exclusion and quasi-static hydrodynamics for efficient cell capture. WPS2 exploits molecular crowding effect, tailing activity enhancement in reverse transcription, and homogeneous enzymatic reaction in the initial bead-based amplification to achieve 3116 genes and 8447 transcripts with an average of ∼20000 reads per cell. WPS2 detected 1420 more genes and 4864 more transcripts than our previous Well-Paired-Seq. It sensitively characterizes transcriptomes of low RNA-content single cells and nuclei, overcoming the Poisson limit for cell and barcoded bead capture. WPS2 also profiles transcriptomes from frozen clinical samples, revealing heterogeneous tumor copy number variations and intercellular crosstalk in clear cell renal cell carcinomas. Additionally, we provide the first single-cell-level characterization of rare metanephric adenoma (MA) and uncover potential specific markers. With the advantages of high sensitivity and high throughput, WPS2 holds promise for diverse basic and clinical research.


Subject(s)
Single-Cell Analysis , Transcriptome , Humans , Cell Nucleus/metabolism , Cell Nucleus/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , RNA/genetics , Sequence Analysis, RNA , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , High-Throughput Nucleotide Sequencing
4.
Brain Behav Immun ; 119: 394-407, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38608743

ABSTRACT

Chronic infection with Toxoplasma gondii (T. gondii) emerges as a risk factor for neurodegenerative diseases in animals and humans. However, the underlying mechanisms are largely unknown. We aimed to investigate whether gut microbiota and its metabolites play a role in T. gondii-induced cognitive deficits. We found that T. gondii infection induced cognitive deficits in mice, which was characterized by synaptic ultrastructure impairment and neuroinflammation in the hippocampus. Moreover, the infection led to gut microbiota dysbiosis, barrier integrity impairment, and inflammation in the colon. Interestingly, broad-spectrum antibiotic ablation of gut microbiota attenuated the adverse effects of the parasitic infection on the cognitive function in mice; cognitive deficits and hippocampal pathological changes were transferred from the infected mice to control mice by fecal microbiota transplantation. In addition, the abundance of butyrate-producing bacteria and the production of serum butyrate were decreased in infected mice. Interestingly, dietary supplementation of butyrate ameliorated T. gondii-induced cognitive impairment in mice. Notably, compared to the healthy controls, decreased butyrate production was observed in the serum of human subjects with high levels of anti-T. gondii IgG. Overall, this study demonstrates that gut microbiota is a key regulator of T. gondii-induced cognitive impairment.


Subject(s)
Cognitive Dysfunction , Dysbiosis , Gastrointestinal Microbiome , Hippocampus , Toxoplasma , Toxoplasmosis , Animals , Mice , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/microbiology , Toxoplasmosis/metabolism , Toxoplasmosis/complications , Dysbiosis/metabolism , Humans , Male , Hippocampus/metabolism , Mice, Inbred C57BL , Fecal Microbiota Transplantation/methods , Butyrates/metabolism , Female , Cognition/physiology
5.
J Org Chem ; 89(9): 6106-6116, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38632856

ABSTRACT

An electrochemical oxidative cross-coupling strategy for the synthesis of N-sulfenylsulfoximines from sulfoximines and thiols was accomplished, giving diverse N-sulfenylsulfoximines in moderate to good yields. Moreover, this strategy can be extended to construct the N-P bond of N-phosphinylated sulfoximines. With electrons as reagents, the oxidative dehydrogenation cross-coupling reaction proceeds smoothly in the absence of traditional redox reagents.

6.
J Clin Transl Hepatol ; 12(3): 287-297, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38426194

ABSTRACT

The roles of γδ T cells in liver cancer, especially in the potential function of immunotherapy due to their direct cytotoxic effects on tumor cells and secretion of important cytokines and chemokines, have aroused research interest. This review briefly describes the basic characteristics of γδ T cells, focusing on their diverse effects on liver cancer. In particular, different subtypes of γδ T cells have diverse or even opposite effects on liver cancer. We provide a detailed description of the immune regulatory network of γδ T cells in liver cancer from two aspects: immune components and nonimmune components. The interactions between various components in this immune regulatory network are dynamic and pluralistic, ultimately determining the biological effects of γδ T cells in liver cancer. We also integrate the current knowledge of γδ T-cell immunotherapy for liver cancer treatment, emphasizing the potential of these cells in liver cancer immunotherapy.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 312: 124058, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38387411

ABSTRACT

A series fluorescent probes (TBM-Cx (x = 1, 4, 8)) were designed based on embedding various alkoxy chains on the electron donor of triphenylamine (TPA)-based dicyanovinyl (MT) compound with an electron-deficient benzothiadiazole (BTD) for sensitive, selective, and visualizing detection of cyanide in aqueous solution. Due to the nucleophilic addition of CN-, the intramolecular charge transfer (ICT) of these probes was inhibited by the destroyed conjugated structure, exhibiting excellent "turn-on" fluorescence response toward cyanide anion (CN-) in tetrahydrofuran (THF). However, the alkoxy chains with different lengths embedded in TPA not only enhance the sensitivity and solubility, but also regulate the emission behavior from ICT to aggregation-induced emission (AIE) characteristics. The binding mechanism and AIE sensing performances between the probes and CN- have been investigated and compared in THF/water mixture by spectral tools and theoretical calculations. The results showed that the ICT-based TBM-C1 probe with methoxy chain showed significantly turn-on fluorescence response to CN- as low as 0.077 µM in THF/water solution at high water fraction (90 %). Due to the AIE sensing process, TBM-C1 was successfully employed to determine CN- in food and water samples, image CN- in living cells and BALB/c mice, and prepare test kits for visualizing cyanide.

8.
Radiat Res ; 201(4): 310-316, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38355101

ABSTRACT

The increased expression of Copine 1 (CPNE1) has been observed in various cancers, which promotes cell proliferation, apoptosis, and radio resistance. However, the potential mechanism of CPNE1 in nasopharyngeal carcinoma (NPC) remains elusive. Consequently, our objective was to investigate the role of CPNE1 in regulating proliferation and radio resistance of NPC. CPNE1 expression in NPC and normal patients were obtained from Cancer Genome Atlas (TCGA) database. An elevated CPNE1 was observed in NPC patients and cells (C666-1, SUNE-1, and HNE-1). Then, C666-1 and SUNE-1 cells were subjected to si-CPNE1 under different radiations (0-8 Gy). Cell growth and proliferation were measured by CCK8 and EDU assays, which demonstrated si-CPNE1 suppressed proliferation. Colony formation was performed to detect cell viability under different radiation therapy and survival curve of cell was plotted, which indicated that CPNE1 knockdown improved cell radiosensitivity. Additionally, flow cytometry showed silence of CPNE1 enhanced apoptosis rate in radiated cells. To further investigate the mechanisms of CPNE1 regulating NPC, the expression of activated phosphate Akt (p-Akt) was assessed through western blotting. We observed elevated p-Akt in si-CPNE1 transfected C666-1 and SUNE-1 cells. In conclusion, these results demonstrated that CPNE1 expression is elevated in nasopharyngeal carcinoma cells, and its silencing could attenuate nasopharyngeal carcinoma advancement and improve radiosensitivity to radiation therapy by controlling Akt activation.


Subject(s)
Nasopharyngeal Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Nasopharyngeal Carcinoma/radiotherapy , Proto-Oncogene Proteins c-akt/genetics , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/pathology , Cell Line, Tumor , Apoptosis/genetics , Cell Proliferation/genetics
9.
J Am Chem Soc ; 146(4): 2339-2344, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38237055

ABSTRACT

Li-O2 batteries (LOBs) are considered as one of the most promising energy storage devices due to their ultrahigh theoretical energy density, yet they face the critical issues of sluggish cathode redox kinetics during the discharge and charge processes. Here we report a direct synthetic strategy to fabricate a single-atom alloy catalyst in which single-atom Pt is precisely dispersed in ultrathin Pd hexagonal nanoplates (Pt1Pd). The LOB with the Pt1Pd cathode demonstrates an ultralow overpotential of 0.69 V at 0.5 A g-1 and negligible activity loss over 600 h. Density functional theory calculations show that Pt1Pd can promote the activation of the O2/Li2O2 redox couple due to the electron localization caused by the single Pt atom, thereby lowering the energy barriers for the oxygen reduction and oxygen evolution reactions. Our strategy for designing single-atom alloy cathodic catalysts can address the sluggish oxygen redox kinetics in LOBs and other energy storage/conversion devices.

11.
Microb Pathog ; 186: 106484, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38052278

ABSTRACT

Sexual reproduction plays a crucial role in the transmission and life cycle of toxoplasmosis. The merozoites are the only developmental stage capable of differentiation into male and female gametes, thereby initiating sexual reproduction to form oocysts that are excreted into the environment. Hence, our study aimed to perform proteomic analyses of T. gondii Pru strain merozoites, a pre-sexual developmental stage in cat IECs, and tachyzoites, an asexual developmental stage, using the tandem mass tag (TMT) method in order to identify the differentially expressed proteins (DEPs) of merozoites. Proteins functions were subjected to cluster analysis, and DEPs were validated through the qPCR method. The results showed that a total of 106 proteins were identified, out of which 85 proteins had quantitative data. Among these, 15 proteins were differentially expressed within merozoites, with four exhibiting up-regulation and being closely associated with the material and energy metabolism as well as the cell division of T. gondii. Two novel DEPs, namely S8GHL5 and A0A125YP41, were identified, and their homologous family members have been demonstrated to play regulatory roles in oocyte maturation and spermatogenesis in other species. Therefore, they may potentially exhibit regulatory functions during the differentiation of micro- and macro-gametophytes at the initiation stage of sexual reproduction in T. gondii. In conclusion, our results showed that the metabolic and divisional activities in the merozoites surpass those in the tachyzoites, thereby providing structural, material, and energetic support for gametophytes development. The discovery of two novel DEPs associated with sexual reproduction represents a significant advancement in understanding Toxoplasma sexual reproduction initiation and oocyst formation.


Subject(s)
Parasites , Toxoplasma , Animals , Male , Female , Toxoplasma/genetics , Toxoplasma/chemistry , Merozoites/chemistry , Merozoites/metabolism , Proteomics/methods , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Oocysts , Reproduction , Transcription Factors/metabolism
12.
Adv Sci (Weinh) ; 11(9): e2306612, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38126673

ABSTRACT

Human norovirus (HuNoV) is the leading cause of nonbacterial acute gastroenteritis, which is highly infectious, rapidly evolving, and easily transmitted through feces. The accurate and early detection of HuNoV subtypes is essential for effective treatment, early surveillance, risk assessment, and disease prevention. In this study, a portable multiplex HuNoV detection platform that combines integrated microfluidics and cascade isothermal amplification, using a streamlined protocol for clinical fecal-based diagnosis is presented. To overcome the problems of carryover contamination and the incompatibility between recombinase polymerase amplification (RPA) and loop-mediated isothermal amplification (LAMP), a Dynamic confined-space-implemented One-pot RPA-LAMP colorimetric detection system (DORLA) is developed by creating a hydrogen bond network. The DORLA system exhibits excellent sensitivity, with detection limits of 10 copies µL-1 and 1 copy µL-1 for HuNoV GI and GII, respectively. In addition, a portable diagnostic platform consisting of a thermostatic control module and an integrated 3D-printed microfluidic chip for specific HuNoV capture, nucleic acid pretreatment, and DORLA detection, which enables simultaneous diagnosis of HuNoV GI and GII is developed. A DORLA-based microfluidic platform exhibits satisfactory performance with high sensitivity and portability, and has high potential for the rapid point-of-care detection of HuNoV in clinical fecal samples, particularly in resource-limited settings.


Subject(s)
Communicable Diseases , Nucleic Acids , Humans , Microfluidics , Point-of-Care Systems
13.
Sci Total Environ ; 913: 169625, 2024 Feb 25.
Article in English | MEDLINE | ID: mdl-38157892

ABSTRACT

The prevalence of shared bicycles has raised concerns over their potential to transmit pathogens and microbes harboring antibiotic resistance genes (ARGs), which pose significant human health risks. This study investigated the impact of anthropogenic activities on the composition of ARGs and microbial communities on shared bicycles during the COVID-19 pandemic and subsequent lockdown when shared bicycle usage was altered. A total of 600 swab samples from shared bicycle surfaces were collected in Shanghai before and during COVID-19 lockdown periods. Even during lockdown, 12 out of 14 initially detected ARG subtypes persisted, indicating their tenacity in the face of reduced anthropogenic activities. These ARGs displayed significantly higher absolute and relative abundance levels before the lockdown. In addition, the percentage of potential pathogens in the total microbial abundance remained at 0.029 % during the lockdown, which was lower than the pre-lockdown percentage of 0.035 % and suggested that these risks persist within shared bicycle systems. Interestingly, although microbial abundance decreased without the consecutive use of shared bicycles during lockdown, the microbial diversity increased under the impact of restricted anthropogenic activities (p < 0.001). This emphasizes the need for continuous monitoring and research to comprehend microbial community behaviors in various environments. This study uncovered the underlying impacts of the COVID-19 lockdown on the microbial and ARG communities of shared bicycles, providing comprehensive insights into the health management of shared transportation. Although lockdown can decrease the abundance of ARGs and potential pathogens, additional interventions are needed to prevent their continued spread.


Subject(s)
COVID-19 , Microbiota , Humans , Anti-Bacterial Agents/pharmacology , Pandemics , Bicycling , Genes, Bacterial , China/epidemiology , Drug Resistance, Microbial/genetics , COVID-19/epidemiology
14.
Sci Adv ; 9(49): eadj2660, 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38055828

ABSTRACT

Knowledge of high-pressure melting curves of silicate minerals is critical for modeling the thermal-chemical evolution of rocky planets. However, the melting temperature of davemaoite, the third most abundant mineral in Earth's lower mantle, is still controversial. Here, we investigate the melting curves of two minerals, MgSiO3 bridgmanite and CaSiO3 davemaoite, under their stability field in the mantle by performing first-principles molecular dynamics simulations based on the density functional theory. The melting curve of bridgmanite is in excellent agreement with previous studies, confirming a general consensus on its melting temperature. However, we predict a much higher melting curve of davemaoite than almost all previous estimates. Melting temperature of davemaoite at the pressure of core-mantle boundary (~136 gigapascals) is about 7700(150) K, which is approximately 2000 K higher than that of bridgmanite. The ultrarefractory nature of davemaoite is critical to reconsider many models in the deep planetary interior, for instance, solidification of early magma ocean and geodynamical behavior of mantle rocks.

15.
EBioMedicine ; 98: 104898, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38029461

ABSTRACT

BACKGROUND: Malaria, a widespread parasitic disease caused by Plasmodium species, remains a significant global health concern. Rapid and accurate detection, as well as species genotyping, are critical for effective malaria control. METHODS: We have developed a Flexible, Robust, Equipment-free Microfluidic (FREM) platform, which integrates recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR)-based detection, enabling simultaneous malaria infection screening and Plasmodium species genotyping. The microfluidic chip enabled the parallel detection of multiple Plasmodium species, each amplified by universal RPA primers and genotyped by specific crRNAs. The inclusion of a sucrose solution effectively created spatial separation between the RPA and CRISPR assays within a one-pot system, effectively resolving compatibility issues. FINDINGS: Clinical assessment of DNA extracts from patients with suspected malaria demonstrates the FREM platform's superior sensitivity (98.41%) and specificity (92.86%), yielding consistent results with PCR-sequencing for malaria detection, which achieved a positive predictive agreement of 98.41% and a negative predictive agreement of 92.86%. Additionally, the accuracy of species genotyping was validated through concordance rates of 90.91% between the FREM platform and PCR-sequencing. INTERPRETATION: The FREM platform offers a promising solution for point-of-care malaria screening and Plasmodium species genotyping. It highlights the possibility of improving malaria control efforts and expanding its applicability to address other infectious diseases. FUNDING: This work was financially supported by International Joint Laboratory on Tropical Diseases Control in Greater Mekong Subregion, National Natural Science Foundation of China, the Natural Science Foundation of Shanghai, Bill & Melinda Gates Foundation and National Research and Development Plan of China.


Subject(s)
Malaria , Plasmodium , Humans , Microfluidics , Genotype , China , Plasmodium/genetics , Malaria/diagnosis , Malaria/parasitology , Sensitivity and Specificity
16.
Trends Analyt Chem ; 1682023 Nov.
Article in English | MEDLINE | ID: mdl-37840598

ABSTRACT

Infectious diseases (such as sepsis, influenza, and malaria), caused by various pathogenic bacteria and viruses, are widespread across the world. Early and rapid detection of disease-related pathogens is necessary to reduce their spread in the world and prevent their potential global pandemics. The clustered regularly interspaced short palindromic repeats (CRISPR) technology, as the next-generation molecular diagnosis technique, holds immense promise in the detection of infectious diseases because of its remarkable advantages, including supreme flexibility, sensitivity, and specificity. While numerous CRISPR-based biosensors have been developed for application in environmental monitoring, food safety, and point-of-care diagnosis, there remains a critical need to summarize and explore their potential in human health. This review aims to address this gap by focusing on the latest advancements in CRISPR-based biosensors for infectious disease detection. We provide an overview of the current status, pre-amplification methods, the unique feature of each CRISPR system, and the design of CRISPR-based biosensing strategies to detect disease-associated nucleic acids. Last but not least, the review analyzes the current challenges and provides future perspectives, which will contribute to developing more effective CRISPR-based biosensors for human health.

17.
Proc Natl Acad Sci U S A ; 120(39): e2307722120, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37725654

ABSTRACT

Single-cell RNA-seq (scRNA-seq) analysis of multiple samples separately can be costly and lead to batch effects. Exogenous barcodes or genome-wide RNA mutations can be used to demultiplex pooled scRNA-seq data, but they are experimentally or computationally challenging and limited in scope. Mitochondrial genomes are small but diverse, providing concise genotype information. We developed "mitoSplitter," an algorithm that demultiplexes samples using mitochondrial RNA (mtRNA) variants, and demonstrated that mtRNA variants can be used to demultiplex large-scale scRNA-seq data. Using affordable computational resources, mitoSplitter can accurately analyze 10 samples and 60,000 cells in 6 h. To avoid the batch effects from separated experiments, we applied mitoSplitter to analyze the responses of five non-small cell lung cancer cell lines to BET (Bromodomain and extraterminal) chemical degradation in a multiplexed fashion. We found the synthetic lethality of TOP2A inhibition and BET chemical degradation in BET inhibitor-resistant cells. The result indicates that mitoSplitter can accelerate the application of scRNA-seq assays in biomedical research.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , RNA, Mitochondrial , Single-Cell Gene Expression Analysis , Mitochondria/genetics
18.
PLoS Negl Trop Dis ; 17(9): e0011102, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37721957

ABSTRACT

Toxoplasma gondii (T. gondii) is an opportunistic parasite that can infect the central nervous system (CNS), causing severe toxoplasmosis and behavioral cognitive impairment. Mortality is high in immunocompromised individuals with toxoplasmosis, most commonly due to reactivation of infection in the CNS. There are still no effective vaccines and drugs for the prevention and treatment of toxoplasmosis. There are five developmental stages for T. gondii to complete life cycle, of which the tachyzoite and bradyzoite stages are the key to the acute and chronic infection. In this study, to better understanding of how T. gondii interacts with the host CNS at different stages of infection, we constructed acute and chronic infection models of T. gondii in astrocytes, and used label-free proteomics to detect the proteome changes before and after infection, respectively. A total of 4676 proteins were identified, among which 163 differentially expressed proteins (fold change ≥ 1.5 or ≤ 0.67 and p-value ≤ 0.05) including 109 up-regulated proteins and 54 down-regulated proteins in C8-TA vs C8 group, and 719 differentially expressed proteins including 495 up-regulated proteins and 224 down-regulated proteins in C8-BR vs C8-TA group. After T. gondii tachyzoites infected astrocytes, differentially expressed proteins were enriched in immune-related biological processes to promote the formation of bradyzoites and maintain the balance of T. gondii, CNS and brain. After T. gondii bradyzoites infected astrocytes, the differentially expressed proteins up-regulated the host's glucose metabolism, and some up-regulated proteins were strongly associated with neurodegenerative diseases. These findings not only provide new insights into the psychiatric pathogenesis of T. gondii, but also provide potential targets for the treatment of acute and chronic Toxoplasmosis.

19.
Infect Dis Poverty ; 12(1): 70, 2023 Aug 03.
Article in English | MEDLINE | ID: mdl-37537637

ABSTRACT

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.


Subject(s)
Global Health , One Health , Animals , Humans , Zoonoses/prevention & control , Public Health , Capacity Building
20.
One Health ; 17: 100607, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37588422

ABSTRACT

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.

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