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Biomedical subjects

Tao Li

Publications and source records attributed to Tao Li.

15 recordsLinked to original sources

Genotype II Live-Attenuated ASFV Vaccine Bearing 24 Genes Deletion in 3 Independent Regions Is Able to Provide Complete Protection Against Homologous Lethal Challenge.

African swine fever (ASF) is an acute, febrile, and highly contagious infectious disease of swine with the etiological agent of African swine fever virus (ASFV). The mortality rate of virulent strains is as high as 100%. Strengthening biosafety is so far the most effective way to prevent and control ASF. Therefore, it is urgent to develop a safe and effective vaccine. In this study, a Genotype II live-attenuated ASF vaccine bearing 24 genes deletion in 3 independent regions was constructed based on the highly virulent Eurasian strain ASFV CN/GS 2018 backbone. The resulting mutant ASFV-Δ24 is characterized by complete deletion of 24 genes distributed in 3 genomic positions of 852 to 11 468, 19 732 to 22 929, and 179 519 to 180 617, among which MGF100 and whole MGF300 families are pioneeringly removed. The ASFV-Δ24 displayed a delayed and reduced replication kinetics as well as aberrant icosahedral empty particles devoid of a nucleoid when compared to the parental virus. Animal experiments showed that ASFV-Δ24 was completely attenuated in animals as evidenced by stable body temperature and no ASF-compatible clinical signs in vaccinated pigs. The ASFV-Δ24 could provide complete homologous protection against lethal challenge, as vaccinated pigs demonstrated boosted antibody response, transient but low levels of viremia in blood and virus titers in organs as well as almost undetectable viral shedding. Gene deletions in multiple regions are helpful for prevention of virulence reversion. These results indicate that ASFV-Δ24 can be used as an effective and promising candidate vaccine to control the spread of ASFV.

Animals

Assessing the accuracy and efficiency of an electronic platform for managing childhood illnesses in rural China: A cluster randomized controlled trial.

OBJECTIVES: The Integrated Management of Childhood Illness (IMCI) faces challenges in capacity building and quality control. This trial aims to assess an electronic IMCI (eIMCI) platform in improving the effectiveness and efficiency in disease classification and management by community health workers (CHWs). DESIGN: Cluster randomized controlled trial. SETTING: Rural western China. PARTICIPANTS: 24 CHWs and 72 ill children aged 2 months to 5 years (3 children per CHW). CHWs were randomly assigned to intervention or control groups. INTERVENTIONS: The intervention CHWs received online training and performed disease management using the eIMCI platform featuring integrated training modules and decision-support tools. The control group received traditional face-to-face training and used paper-based IMCI protocols. MAIN OUTCOME MEASURES: Proportion of children correctly diagnosed or classified by CHWs, as determined by a pediatric specialist. Relative risk (RR) between groups was estimated using Poisson Generalized Linear Mixed Models incorporating a random intercept for CHW to account for clustering of children within individual CHWs and adjusting for key covariates at both the CHW and child levels. RESULTS: The intervention group (13 CHWs, 39 children) had a higher rate of correct classification (64.1%) compared to the control group (11 CHWs, 33 children) (39.4%, P&#x2009;=&#x2009;.056). Multivariable regression analysis confirmed this (RR&#x2009;=&#x2009;2.1, 95% CI: 1.5-3.1; P&#x2009;<&#x2009;.001). No significant difference was found in correct treatment rates (38.5% vs. 27.3%, P&#x2009;=&#x2009;.316). Online training reduced time and costs by approximately 80%, though with a slight decrease in post-training evaluation scores. CONCLUSIONS: The eIMCI platform shows potential in enhancing IMCI implementation and significantly reducing the training burden in resource-limited settings. Trial registration: Chinese Clinical Trial Registry: ChiCTR2100042533, https://www.chictr.org.cn/showproj.html?proj=119995.

Humans

Balancing growth and immunity of potato by humidity-dependent expression of a late blight resistance gene.

Inducible expression of resistance genes is an effective approach to balance plant growth and immunity, thus facilitating the development of disease-resistant crop cultivars. While pathogen-responsive and immunity-related promoters have been adopted for this purpose, alternative design strategies remain to be explored. High relative humidity (RH) has been recognized as a crucial permissive environmental condition for the occurrence of devastating plant diseases including tomato and potato late blight. Here, we identified humidity-activated cis-regulatory elements (HAEs) in Solanum lycopersicum through an integrative analysis of transcriptomics and chromatin accessibility data. Sequence homology-inferred HAEs in S. tuberosum can predict humidity-elicited changes in downstream gene expression. Transgenic S. tuberosum lines expressing a late blight resistance gene driven by an artificial humidity-inducible promoter containing a natural S. tuberosum HAE were generated. These transgenic lines exhibited comparable late blight resistance levels to the lines overexpressing the same resistance gene in controlled zoospore inoculation bioassays, while avoiding growth suppression and tuber yield penalties in common garden experiments. Our findings highlight the importance of plant cis-regulatory elements in the transcriptional responses to high RH and provide a proof-of-concept for a humidity-inducible environment-responsive resistance gene deployment strategy to engineer disease-resistant crop cultivars without compromising growth and yield.

Phytophthora infestans

Differentiated extraction strategies for selenium speciation in hyperaccumulator and non-hyperaccumulator plants via orthogonal LC-AFS.

The growing demand for selenium (Se)-enriched products highlights the need for accurate and accessible Se speciation analysis. In this study, a cost-effective orthogonal liquid chromatography-atomic fluorescence spectrometry (LC-AFS) method was developed for the determination of seven Se species (SeO3 2-, SeO4 2-, SeLan, SeMet, SeCys2, MeSeCys, and &#x3b3;-GluMeSeCys), providing an alternative to ICP-MS-based approaches. Differences in Se accumulation mechanisms between hyperaccumulator Cardamine hupingshanensis and non-hyperaccumulator wheat significantly affected extraction efficiency. The sequential aqueous-enzymatic extraction increased SeLan recovery in C. hupingshanensis from 5.06 to 143.74&#xa0;&#x3bc;g Se g-1, a 28.41-fold increase, while anaerobic extraction enhanced SeMet recovery in wheat from 98.73 to 112.17&#xa0;&#x3bc;g Se g-1. Consequently, matrix-specific strategies improved Se recoveries from 20.82% to 80.65% in C. hupingshanensis and from 34.11% to 90.02% in wheat. These findings highlight the importance of matrix-specific extraction for accurate Se speciation analysis.

Cardamine hupingshanensis

Impact of oxidative stress on malignant tumor progression and emerging therapeutic strategies.

Oxidative stress, driven by an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a pivotal role in cancer biology. While persistent, moderately elevated ROS levels can promote genomic instability, tumor progression, and immune evasion, excessive ROS accumulation can overwhelm antioxidant defenses and trigger cancer cell death. Despite promising preclinical findings, clinical translation remains a challenge because of the context-dependent effects of ROS. A deeper understanding of oxidative stress regulation may lead to the development of novel precision medicine strategies, optimizing cancer therapies while minimizing adverse effects. This review highlights the concentration-dependent effects of oxidative stress in tumorigenesis, focusing on its impact on DNA damage, metabolic reprogramming, and immune modulation. We discuss recent advancements in ROS-targeting strategies, including pro-oxidant therapies that exploit redox vulnerabilities in cancer cells and antioxidant-based approaches aimed at mitigating oxidative stress-driven resistance to treatment. Moreover, we examine the interplay between oxidative stress and the tumor microen-vironment, emphasizing its influence on immune surveillance and therapeutic responses. This re-view provides insights into ROS-targeting interventions and their potential in oncologic treatment paradigms.

malignant tumors

Redox cycling of viral RNA polymerase controls picornavirus replication.

Picornaviruses, including foot-and-mouth disease virus (FMDV), enterovirus 71 (EV71) and encephalomyocarditis virus (EMCV), are important pathogens that cause fever, herpes, and myocarditis in humans and animals. The interplay between picornaviruses and their hosts remains enigmatic. Here we perform porcine genome-wide CRISPR/Cas9 screens and identify methionine sulfoxide reductase B3 (MSRB3) as an essential factor for FMDV. MSRB3 deficiency inhibits FMDV replication. Mechanistically, MSRB3 eliminates methionine oxidation of FMDV 3D polymerase and stabilizes its expression. Further studies show that radical SAM domain-containing protein 1 (RSAD1) catalyzes methionine oxidation of FMDV 3D polymerase and promotes its aggregation and subsequent degradation through the autophagy-lysosome pathway. Importantly, RSAD1-MSRB3-mediated redox modification also affects the stability of 3D polymerases of EV71 and EMCV, and regulates their infectivity and pathogenesis both in vitro and in vivo. Collectively, this study corroborates that RSAD1-MSRB3-mediated redox cycling of 3D polymerase plays a conserved function in modulating picornavirus infection, providing insights into viral pathogenesis and broad-spectrum antiviral development.

Animals

Microbial aerobic degradation of 4-isopropylnitrobenzene by Sphingobium yanoikuyae strain SG1.

4-Isopropylnitrobenzene (4-IPNB) is a nitroaromatic compound commonly employed as an intermediate in pesticide synthesis and chemical manufacturing. Despite its potential environmental persistence and ecological risks, the microbial degradation pathway of 4-IPNB remains largely unknown. In this study, a Gram-negative bacterium, designated Sphingobium yanoikuyae strain SG1, was isolated from a pesticide manufacturing site in Brazil for its ability to utilize 4-IPNB as the sole added source of carbon, nitrogen, and energy. Aerobic degradation of 4-IPNB by strain SG1 was accompanied by nitrite release, and intermediate-trapping experiments revealed the transient accumulation of 4-isopropylcatechol (4-IPC). Together, these findings support the initial conversion of 4-IPNB to 4-IPC through oxidative denitration and dihydroxylation. Genomic and transcriptomic analyses further inferred several candidate nitroarene dioxygenases that may catalyze this initial reaction. Furthermore, the downstream metabolism of 4-IPC proceeded via both meta- and ortho-cleavage pathways, with cell-extract enzyme assays demonstrating predominant meta-cleavage activity under the tested conditions. Strain SG1 also degraded 4-IPNB in nonsterile soil slurry microcosms, extending its degradation capability beyond defined liquid culture. This study provides the first comprehensive insight into the microbial aerobic degradation of 4-IPNB, advances our understanding of the environmental fate of emerging nitroaromatic contaminants, and supports the potential of strain SG1 in 4-IPNB biodegradation and removal.

Sphingomonadaceae

Schizophrenia and bipolar disorder: a comparative analysis of genetic and brain network connectivity.

BACKGROUND: Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric conditions with overlapping clinical presentations, genetic risk factors, and brain network dysfunction. Whether alterations in large-scale intrinsic brain networks reflect shared or disorder-specific genetic influences remains poorly understood. Clarifying this distinction is essential for refining etiological models and improving diagnostic precision. METHODS: Genome-wide inferred statistics (GWIS) were applied to decompose the genetic architecture of SCZ and BD into shared and unique components. Using resting-state network (RSN) data from the UK Biobank, functional connectivity (FC) and structural connectivity (SC) were extracted as neuroimaging phenotypes. Causal inference approaches were subsequently employed to infer potential directional relationships between brain network connectivity and each disorder. RESULTS: Analyses revealed both common and distinct patterns of brain network connectivity associated with SCZ and BD. Notably, SC within the default mode network (DMN) exhibited opposing effects across the two disorders, suggesting divergent structural underpinnings despite clinical overlap. Additionally, SC within the limbic network (LN) and frontotemporal control network demonstrated potential causal relationships with both conditions, implicating these circuits astransdiagnostic neural substrates. CONCLUSION: These findings illuminate the shared and disorder-specific genetic and neural architecture underlying SCZ and BD. Integrating genome-wide genetic methods with large-scale neuroimaging data offers a powerful framework for disentangling psychiatric comorbidity and may inform more targeted diagnostic criteria and individualized treatment strategies.

Humans

Multi-omics profiling of cerebrospinal fluid in autoimmune encephalitis: insights into pathogenesis and therapeutic targets.

BACKGROUND: Autoimmune encephalitis (AIE) is a rare, severe inflammatory brain disease, with its pathogenesis not yet fully elucidated. This study aimed to characterize proteomic and metabolomic alterations in the cerebrospinal fluid (CSF) of AIE patients and identify potential therapeutic targets. METHODS: 65 consecutive AIE patients and age-matched concurrent controls were enrolled, respectively. Clinical characteristics, including blood and CSF laboratory findings, were compared between the two groups, and CSF samples were collected for multi-omics analysis. Differentially expressed proteins (DEPs) and metabolites (DEMs) between AIE patients and controls were identified using data-independent acquisition-based proteomics and targeted liquid chromatography-mass spectrometry-based metabolomics, followed by integrated multi-omics analysis. RESULTS: Compared with controls, AIE patients had lower levels of triglyceride and C1q, but higher HDL-CH levels, neutrophil counts, and eosinophil counts in blood. CSF leukocyte, erythrocyte, lymphocyte, and mononuclear cell counts were also elevated in AIE patients. Proteomic analysis identified 163 DEPs, with enrichment of 87 canonical pathways primarily associated with immune-inflammatory responses, neuronal-synaptic dysfunction, and cell signaling and metabolic pathways. Metabolomic analysis recognized 21 DEMs, predominantly amino acids, lipids, and carbohydrates, which were involved in lipid-carbohydrate metabolism and immune regulation. Integrated multi-omics analysis validated these findings and identified several potential therapeutic targets for AIE, including the IL6-STAT3 axis. CONCLUSIONS: Integrated multi-omics analysis systematically delineates cellular and molecular alterations underlying AIE. Immune-inflammatory response and lipid metabolism are pivotal in AIE progression and the IL6-STAT3 axis holds promise as a potential therapeutic target.

Humans

PRDM16 Regulates Prostate Cancer Cell Dormancy and Prevents Bone Metastatic Outgrowth.

UNLABELLED: Understanding dormancy in prostate cancer is challenging because of model availability. In this study, using murine and human prostate cancer cell lines, we generated a stress-induced model of dormancy in vitro and demonstrated that the phenotype could be sustained upon intrailiac artery delivery into the bone marrow microenvironment. RNA sequencing analysis revealed that the transcription factor positive regulatory domain-containing 16 (PRDM16) was commonly upregulated in dormant prostate cancer cells compared with controls. Furthermore, bone marrow-disseminated prostate cancer cells from primary orthotopic tumors were largely positive for PRDM16. Genetic ablation and forced ectopic expression supported a role for PRDM16 in maintaining prostate cancer dormancy in vitro and in vivo. Clinically, PRDM16 negatively correlated with disease recurrence and with the E2F cell-cycle program in disseminated tumor cells derived from the bone marrow of patients with prostate cancer. Gene enrichment and characterization studies implicated PRDM16 as a regulator of metabolic and cell-cycle pathways. Chromatin immunoprecipitation-qPCR further revealed that PRDM16 binds upstream of the promoter of RB1, a potent repressor of E2F activity. Overall, this study developed a straightforward method for inducing cancer cell dormancy and applied this approach to find that PRDM16 governs an intrinsic dormancy program in prostate cancer. SIGNIFICANCE: PRDM16 initiates a dormancy program in prostate cancer cells that is sustained in the bone marrow microenvironment, highlighting PRDM16 as a potential biomarker for relapse and target for eliminating dormant cancer cells.

Male

Genomic insights into karyotype evolution and adaptive mechanisms in Polygonaceae species.

Polygonaceae, with ecological versatility and global distribution, is an ideal system for investigating plant adaptation. However, the genomic mechanisms underlying its karyotype evolution and environmental resilience remain unclear. We herein present chromosome-level genomes of 11 species from 10 Polygonaceae genera. Our analyses reveal that Gypsy retrotransposons are key drivers of genome size variations in Polygonaceae. We reconstructed a Polygonaceae ancestral karyotype comprising 28 proto-chromosomes and elucidated evolutionary trajectories via extensive chromosomal rearrangements. Furthermore, we constructed a cross-genus super pan-genome for Polygonaceae, identifying 80,055 gene families, of which 9,845 (12.30%) are core gene families. Private genes are found to contribute significantly to interspecific differences in adaptability. Notably, gene copy number variations are identified as a critical factor influencing adaptations to diverse niches involving species-specific increases in metabolic pathways. This study provides a genomic framework for Polygonaceae karyotype plasticity and adaptive innovation, offering insights into plant evolution under environmental challenges.

Karyotype

Discovery of Respiratory Pathogens in People Living With HIV in the African Cohort Study.

INTRODUCTION: Respiratory infection outbreaks pose a threat to the readiness of the United States and allied armed forces. Predicting and preventing such outbreaks requires understanding of the epidemiology of potential respiratory pathogens in communities where service members live and work. We conducted pan-viral surveillance of respiratory specimens from people living with HIV or without HIV but under the risk enrolled in the U.S. Military HIV Research Program's African Cohort Study to determine the prevalence and possible clinical presentation of viruses in this population. METHODS: The African Cohort Study is an open-ended prospective cohort study that enrolls people with and without HIV aged &#x2265;15&#x2009;years at 12 clinical sites in Kenya, Tanzania, Uganda, and Nigeria. The study follows participants every 6 months and collects social, demographic, clinical, and laboratory data. A total of 131 respiratory samples, collected from March 2022 to February 2023 from participants in South Rift Valley Province, Kenya, who had symptoms of respiratory illness or a positive COVID-19 test, were analyzed using a pan-viral hybridization metagenomic next-generation sequencing approach. Libraries were sequenced on the Illumina Next-generation Sequencing System NovaSeq 6000. Sample data were run through several pathogen discovery pipelines. RESULTS: Full genome and partial genome sequences were assembled for several respiratory viruses including SARS-CoV-2, human coronavirus HKU1, human adenovirus 62, human metapneumovirus, human mastadenovirus B (coinfection with SARS-CoV-2), human mastadenovirus C (coinfection with SARS-CoV-2), and human parechovirus 3 (coinfection with adenovirus 62). The results showed that SARS-CoV-2 lineages correspond with lineages circulating during March 2022 to February 2023 and revealed additional viral respiratory pathogens and viruses known to be associated with HIV. CONCLUSIONS: These preliminary results suggest that continued genomic surveillance efforts are needed for data-driven decisions on force health protection, prevention of emerging respiratory infections, and mitigation of impacts on military readiness caused by infectious diseases.

Humans

Multi-Omics Analyses Reveal the Red and Far-Red Light Combination Enhancing Heterologous Protein and Metabolite Production in Nicotiana benthamiana.

Transient expression of exogenous protein in Nicotiana benthamiana leaves via agroinfiltration offers a rapid and efficient platform for functional gene discovery and heterologous production of valuable eukaryotic proteins and metabolites. Though light quality is an important factor for plant photomorphogenesis, its impact on the efficiency of transient expression remains unexplored. In this study, we examined the influence of five representative light qualities with varying wavelength mix on the N. benthamiana growth and recombinant green fluorescent protein (GFP) production. Plants with red and far-red light treatment (LED-red) showed the highest GFP expression, 57.4% higher than white light. Further study showed that a higher dosage of post-infiltration Agrobacterium and the resulting increase in the number of transcripts contribute to the expression rate enhancement. Moreover, as for exogenous metabolites, a 76.5% increase of accumulated taxadiene was also observed in LED-red group. Integrated transcriptomic, proteomic and metabolomic revealed that LED-red plants reduced the resistance pathways before infiltration, inducing a higher dosage of post-agroinfiltration Agrobacterium. Our results suggest that N. benthamiana grown under LED-red creates a more favorable environment for Agrobacterium growth, enhancing heterologous protein and metabolite production. This study highlights the potential utilization of light quality as an implementable tool in plant synthetic biology.

Nicotiana

Effects of different temperatures on chondrocyte growth: a transcriptomic analysis.

BACKGROUND: Our previous study demonstrated that temperature-related microwave ablation (MWA) can safely modulate growth plates of piglets' vertebrae. Therefore, this study is designed to investigate the effects of different temperatures on chondrocyte viability and the underlying molecular mechanisms in vitro. METHODS: Following a 10-minute treatment at different temperatures (37&#xa0;&#xb0;C, 40&#xa0;&#xb0;C, 42&#xa0;&#xb0;C, 44&#xa0;&#xb0;C, 46&#xa0;&#xb0;C, 48&#xa0;&#xb0;C, and 50&#xa0;&#xb0;C), CCK-8 assay was used to examine the viability of ATDC5 cells at 12&#xa0;h. Differentially expressed genes (DEGs) and the hub genes in ATDC5 cells treated at 37&#xa0;&#xb0;C, 40&#xa0;&#xb0;C and 44&#xa0;&#xb0;C were identified using RNA-seq.&#xa0;The expression of hub genes in ATDC5 cells was validated using RT-qPCR. RESULTS: Compared with 37&#xa0;&#xb0;C, exposure to 40&#xa0;&#xb0;C significantly increased the viability of ATDC5 cells, while 42&#xa0;&#xb0;C had no significant effect. Additionally, exposure to 44&#xa0;&#xb0;C, 46&#xa0;&#xb0;C, 48&#xa0;&#xb0;C, and 50&#xa0;&#xb0;C exhibited the opposite pattern, with ATDC5 cells being particularly less than 50% active after treatment at 46&#xa0;&#xb0;C, 48&#xa0;&#xb0;C, and 50&#xa0;&#xb0;C. Differential expression analysis identified 179, 374 and 221 DEGs in the comparisons of 40&#xa0;&#xb0;C vs. 37&#xa0;&#xb0;C, 44&#xa0;&#xb0;C vs. 37&#xa0;&#xb0;C, and 44&#xa0;&#xb0;C vs. 40&#xa0;&#xb0;C, respectively. These DEGs predominantly regulated proliferation, differentiation, necrosis, inflammatory and immune responses, and ECM synthesis/degradation. Furthermore, they were associated with the Ras, PI3K/AKT, mTOR, cAMP, and MAPK pathways. Agt, Hspa1a, Hspb1, and Nlrc4 were identified as hub genes in DEGs, and RT-qPCR confirmed that the mRNA expression patterns of these hub genes in ATDC5 cells were largely consistent with the RNA-seq results. CONCLUSION: The regulation of chondrocyte viability by temperature is associated with Ras, PI3K/AKT, mTOR, cAMP, and MAPK pathways. Additionally, Agt, Hspa1a, Hspb1, and Nlrc4 may be the key regulatory genes in this process.

Chondrocytes

Phase Transition of Wax Enabling CRISPR Diagnostics for Automatic At-Home Testing of Multiple Sexually Transmitted Infection Pathogens.

Sexually transmitted infections (STIs) significantly impact women's reproductive health. Rapid, sensitive, and affordable detection of these pathogens is essential, especially for home-based self-testing, which is crucial for individuals who prioritize privacy or live in areas with limited access to healthcare services. Herein, an automated diagnostic system called Wax-CRISPR has been designed specifically for at-home testing of multiple STIs. This system employs a unique strategy by using the solid-to-liquid phase transition of wax to sequentially isolate and mix recombinase polymerase amplification (RPA) and CRISPR assays in a microfluidic chip. By incorporating a home-built controlling system, Wax-CRISPR achieves true one-pot multiplexed detection. The system can simultaneously detect six common critical gynecological pathogens (CT, MG, UU, NG, HPV 16, and HPV 18) within 30&#xa0;min, with a detection limit reaching 10-18 M. Clinical evaluation demonstrates that the system achieves a sensitivity of 96.8% and a specificity of 97.3% across 100 clinical samples. Importantly, eight randomly recruited untrained operators performe a double-blinded test and successfully identified the STI targets in 33 clinical samples. This wax-transition-based one-pot CRISPR assay offers advantages such as low-cost, high-stability, and user-friendliness, making it a useful platform for at-home or field-based testing of multiple pathogen infections.

Sexually Transmitted Diseases