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Biomedical subjects

Tao Yang

Publications and source records attributed to Tao Yang.

10 recordsLinked to original sources

Spatially resolved single-cell atlas reveals the macroevolutionary trajectory of animal hearts.

Animal hearts display diverse anatomical structures during adaptive evolution. Here, we present a multiomics atlas of adult hearts from 27 species across chordates, arthropods, and mollusks. Joint analysis indicates that Bilateria hearts share a core gene repertoire, taking a stepwise "add-on" approach as a universal evolutionary strategy. The "proto-heart" is populated by key cell types, including cardiomyocytes, fibroblasts, endothelial cells, and neural cells, which maintained core signatures while evolving with shifts in living environments and corresponding adaptations in the cardiovascular system. Additionally, we reveal an evolutionarily conserved cardiomyocyte state dynamic potentially linked to cardiac development and stress responses. Finally, we identify a common molecular program underpinning chamber evolution from a ventricular foundation. This work establishes a resource for understanding the intrinsic mechanisms of heart evolution.

Animals

CeOx-Induced Spatial and Electronic Modulation for General Direct Oxo Coupling in Transition Metal Hydroxides.

Electrochemical water splitting has emerged as a sustainable paradigm for hydrogen generation, where sluggish kinetics of the oxygen evolution reaction (OER) catalyzed by transition metal-based materials remain the critical bottleneck. Herein, we present a strategy that anchors CeOx nanoparticles (∼2 nm) onto two-dimensional Ni(OH)2 nanosheets, enabling dual modulation of spatial configuration and electronic states to accelerate O-O coupling. Spatially, interfacial lattice distortion between CeOx and Ni(OH)2 optimizes Ni-Ni dual-metal sites with reduced interatomic spacing. Electronically, dynamic modulation through reversible Ce3+/Ce4+ redox cycling positions Ce as an electronic regulation hub, stabilizing Ni species at the catalytically favorable +3 oxidation state through Ce─O─Ni interactions. This synergistic effect shifts the pathway from adsorbate evolution mechanism (AEM) to oxide pathway mechanism (OPM). The prepared CeOx@Ni(OH)2 achieves an overpotential of 152 mV at 10 mA cm-2 and operates continuously over 2000 h with limited performance decay. When integrated into an alkaline anion exchange membrane water electrolyzer (AEMWE), it requires 1.91 V to attain 1 A cm-2 and maintains stable operation for 450 h. This OPM activation strategy shows potential applicability across CeOx-loaded transition metal hydroxides, including Ni(OH)2, Co(OH)2, NiCo, and NiFe layered double hydroxides, offering a promising approach for alkaline OER enhancement.

alkaline water oxidation

Chromosome-level genome assembly of the small-sized Taihang donkey (Equus asinus).

China harbors a rich diversity of donkey breeds, with small-sized donkeys (<110&#x2009;cm) representing a largely underexplored group. Here, we present the first high-quality, chromosome-level genome assembly of a small-sized donkey, generated using PacBio HiFi sequencing (286.7&#x2009;Gb), Hi-C scaffolding (240.47&#x2009;Gb), and annotated with RNA-seq data. The final assembly has a total length of 2.7&#x2009;Gb and comprises 32 chromosomes (including both X and Y chromosomes), in which five chromosomes were fully assembled without gaps. It possesses a scaffold N50 of 106.70&#x2009;Mb and 84 contigs (contig N50&#x2009;=&#x2009;63.60&#x2009;Mb), and captures 99.2% of BUSCO genes. The assembly achieved a consensus quality value (QV) of 77.44, corresponding to an extremely low base-level error rate, indicating exceptional nucleotide accuracy. This high-quality genome provides a valuable resource for investigating genetic variation, adaptive evolution, and domestication processes in small-sized donkeys, and will facilitate the conservation and sustainable utilization of rich donkey genetic resources in China.

Animals

Age-stratified associations of glycemia, blood pressure, and cholesterol with mortality in diabetes: A prospective cohort study.

BACKGROUND: Optimization of HbA1c, blood pressure and cholesterol, referred to as the "ABCs", is central to the management of diabetes. However, the age-specific associations of these factors with mortality in patients with diabetes remains unclear. METHODS: In this prospective cohort study, 43,732 Chinese adults aged&#x2009;&#x2265;&#x2009;40 years with diabetes were included from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Participants were stratified by age (<&#x2009;55, 55-<65, 65-<75, &#x2265;&#x2009;75 years). Cox proportional hazards regression and Fine-Gray competing risk models were employed to estimate the associations of HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with all-cause, cardiovascular, and non-cardiovascular mortality across age groups. Relative importance and population attributable fractions (PAFs) were computed for each metabolic factor. RESULTS: During a median follow-up of 10.1 years, 3,975 deaths were documented. Age significantly modified the associations of HbA1c, SBP, and LDL-C with all mortality outcomes (all P for interaction&#x2009;<&#x2009;0.05). Among participants aged&#x2009;<&#x2009;75 years, HbA1c showed graded positive associations with all-cause, cardiovascular, and non-cardiovascular mortality. The SBP thresholds associated with increased mortality risk were 140 mmHg in those aged&#x2009;<&#x2009;65 years and 160 mmHg in those aged 65-<75 years. Among those aged&#x2009;&#x2265;&#x2009;75 years, however, the patterns of these associations differed markedly. Elevated mortality risk was observed only at HbA1c&#x2009;&#x2265;&#x2009;9%, with a hazard ratio (HR) of 1.51 (95% confidence interval [CI]: 1.19-1.91) for all-cause mortality and a subdistribution hazard ratio (SHR) of 1.70 (95% CI: 1.23-2.36) for cardiovascular mortality, while SBP showed no significant association with any mortality outcome in this age group. Moreover, LDL-C emerged as a significant risk factor for cardiovascular mortality. Compared with participants with LDL-C&#x2009;<&#x2009;1.8 mmol/L, those with LDL-C of 1.8-<2.6 mmol/L exhibited a significantly higher risk (SHR: 1.86; 95% CI: 1.11-3.11). Additionally, LDL-C had the largest PAF for cardiovascular mortality (9.6%) within this age group. CONCLUSIONS: The impacts of ABC factors on mortality risk vary substantially by age among adults with diabetes. In patients aged&#x2009;&#x2265;&#x2009;75 years, less stringent glycemic and blood pressure targets may be appropriate, whereas lipid management remains critically important for reducing cardiovascular mortality.

Humans

Development of an Efficient Regeneration and Agrobacterium-Mediated Transformation Protocol for Hosta 'Light Star' Using the RUBY Reporter Gene.

Hosta plantaginea is a perennial shade-tolerant herb of the Liliaceae family, with high ornamental and urban greening value. Hosta 'Light Star' is a newly developed ornamental cultivar with yellow-margined leaves and lilac flowers, but no efficient in vitro regeneration or genetic transformation system has been established for this cultivar to date. In this study, we established a highly efficient in vitro regeneration system for Hosta 'Light Star,' and developed an Agrobacterium-mediated genetic transformation protocol using the RUBY visual reporter gene for non-invasive screening of positive transformants. The optimal callus induction medium was MS&#x2009;+&#x2009;2&#xa0;mg/L 6-BA&#x2009;+&#x2009;0.3&#xa0;mg/L NAA&#x2009;+&#x2009;0.05&#xa0;mg/L 2, 4-D, with a callus induction rate of 53.33% for leaf explants (the optimal explant for sterile seedlings). The optimal adventitious bud proliferation medium was MS&#x2009;+&#x2009;2&#xa0;mg/L 6-BA&#x2009;+&#x2009;0.1&#xa0;mg/L NAA, with a proliferation coefficient of 5.87. The optimal rooting medium was 1/2 MS&#x2009;+&#x2009;0.5&#xa0;mg/L NAA&#x2009;+&#x2009;0.5&#xa0;mg/L IBA, with a 100% rooting rate. The optimal transplant substrate was perlite:vermiculite&#x2009;=&#x2009;2:1, with a 100% transplant survival rate after acclimatization. For Agrobacterium-mediated transformation, the optimal infection parameters were as follows: Agrobacterium suspension OD600&#x2009;=&#x2009;0.6, infection time of 10&#xa0;min, and 200&#xa0;&#x3bc;M acetosyringone; the optimal selection conditions were 300&#xa0;mg/L cefotaxime for bacteriostasis and 30&#xa0;mg/L hygromycin for transformant screening. The final stable transformation efficiency was 2.50% (95% CI 1.23-3.77%), with an escape rate of 16.13%. Transgenic plants showed distinct purplish-red coloration in roots, stems, and leaves, with significantly higher betacyanin accumulation than wild-type plants (p&#x2009;<&#x2009;0.05). Stable integration and expression of the RUBY gene were confirmed by PCR, RT-PCR, and RT-qPCR. This study establishes the first efficient regeneration and Agrobacterium-mediated transformation system for Hosta 'Light Star,' and validates the feasibility of the RUBY reporter gene as a visual marker for Hosta transformation. This system provides a solid technical platform for functional genomic studies, CRISPR/Cas9-mediated gene editing, and molecular breeding of ornamental traits in Hosta.

Transformation, Genetic

Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine.

Cardiovascular diseases are leading global causes of death and disability, often presenting as interrelated phenotypes of atherosclerotic vascular disease, heart failure and arrhythmias. Cardiovascular diseases arise from interactions between environmental factors and predisposing genotypes and include common Mendelian lipid disorders, cardiomyopathies and arrhythmia syndromes. The identification of a pathogenic variant through genetic testing can inform disease diagnosis, risk prediction, treatment and family screening. However, a major roadblock in genomic medicine is that for many variants, especially missense variants, we lack sufficient evidence to enable a definitive classification, and therefore these variants are deemed as 'variants of uncertain significance'. In this Review, we describe how multiplexed assays of variant effects can enable the functional assessment of nearly all coding variants in a target sequence, potentially offering a proactive approach to identifying the functional significance of gene variants that are observed later in a patient. We discuss validation, including the role of in silico variant effect predictors, and how multiplexed experimental methods are informing cardiovascular disease biology and ultimately resolving the problem of variants of uncertain significance at scale.

Humans

Epigenetic Histone &#x3b2;-Hydroxybutyrylation Contributes to Renoprotection by &#x3b2;-Hydroxybutyrate in the Dahl Rat.

BACKGROUND: Previously, we demonstrated that the ketone body, &#x3b2;-hydroxybutyrate, is a potent antihypertensive and reno-protective metabolite in Dahl Salt-Sensitive rats. However, the mechanism by which &#x3b2;-hydroxybutyrate confers these beneficial effects is understudied. Here we focused on determining whether the reno-protective effect of &#x3b2;-hydroxybutyrate is due to its known ability to epigenetically remodel chromatin via histone &#x3b2;-hydroxybutyrylation. METHODS: We used the same animal protocol previously used for the discovery of the reno-protective effect of &#x3b2;-hydroxybutyrate. Briefly, postweaning, male and female Dahl Salt-Sensitive rats were split into 2 groups and supplemented with or without 1,3-butanediol for 6 weeks. At euthanasia, circulating &#x3b2;-hydroxybutyrate was quantitated. Renal homogenates were examined for histone 3 lysine 9 &#x3b2;-hydroxybutyrylation, chromatin occupancy, transcriptomic and proteomic profiles with validations. RESULTS: Rats supplemented with 1,3-butanediol had higher circulating &#x3b2;-hydroxybutyrate, renal histone &#x3b2;-hydroxybutyrylation, and significant remodeling of chromatin. Notably, regions of the genome associated with lipid catabolism were predominantly in an open chromatin configuration, leading to active transcription and translation. The most highly upregulated gene actively transcribed and translated was Hmgcs2 (3-hydroxy-3-methylglutaryl CoA synthase 2), a gene responsible for the biosynthesis of &#x3b2;-hydroxybutyrate in mitochondria. In contrast, regions with more compact chromatin structures contained immune function genes, Ptprc (protein tyrosine phosphatase receptor type C) and Lcp1 (lymphocyte cytosolic protein 1), which were suppressed. CONCLUSIONS: These results reveal that renal epigenetic histone &#x3b2;-hydroxybutyrylation is a novel mechanism by which transcriptional regulation of both energy metabolism and immune function occur concomitantly and contribute to renoprotection in the hypertensive Dahl rat.

Animals

Microbiota and kidney disease: the road ahead.

More than 850 million individuals worldwide, accounting for 10-15% of the adult population, are estimated to have chronic kidney disease. Each of these individuals is host to tens of trillions of microorganisms that are collectively referred to as microbiota - a dynamic ecosystem that both influences host health and is itself influenced by changes in the host. Available evidence supports the existence of functional connections between resident microorganisms and kidney health that are altered in the context of specific kidney diseases, including acute kidney injury, chronic kidney disease and renal stone disease. Moreover, promising data from preclinical studies suggest that targeting of gut microbial pathways may provide new therapeutic opportunities for the treatment of kidney disease. This Roadmap describes current understanding of the mechanisms by which microorganisms regulate host organ function, the effects of kidney disease on the gut microbiome, and how these insights may contribute to the development of microbe-targeted therapeutics. We highlight key knowledge gaps that remain to be addressed and strategies for addressing these, outlining both the promise and the potential pitfalls of leveraging our understanding of the gut microbiota to better understand and treat kidney disease.

Humans

Chromosome-level genome assembly of starry flounder (Platichthys stellatus).

Starry flounder (Platichthys stellatus) is widely distributed along the coastlines of the North Pacific. As an euryhaline flatfish, it can adapt to a wide range of environmental salinity ranging from freshwater to seawater, and is a promising aquaculture flatfish species in Korea and North China. However, no high-quality starry flounder reference genome has been reported to date, which greatly limits the studies of genetics and functional genomics. Here, we obtained a high-quality chromosome-level starry flounder genome assembly with a&#xa0;length of 643.56&#x2009;Mb (scaffold N50: 26.19&#x2009;Mb, contig N50: 10.00&#x2009;Mb) combining short-reads sequencing, PacBio HiFi sequencing, and Hi-C sequencing. Approximately 94.02% of assembled sequences were anchored into 24 pseudochromosomes, and a total of 18 telomeres were detected. Totally 22,835 protein-coding genes and 227.87&#x2009;Mb repetitive sequences were identified. In summary, the high-quality chromosome-level genome assembly not only provides valuable resources for genetic research in starry flounder, but also advances the development of molecular breeding technology of starry flounder.

Animals

Ketone body mediated histone &#x3b2;-hydroxybutyrylation is reno-protective.

Starvation, intermittent fasting and exercise, all of which are recommended lifestyle modifiers share a common metabolic signature, ketogenesis to generate the ketone bodies, predominantly &#x3b2;-hydroxybutyrate. &#x3b2;-hydroxybutyrate exerts beneficial effects across various contexts, preventing or mitigating disease. We hypothesized that these dynamic health benefits of &#x3b2;-hydroxybutyrate might stem from its ability to regulate genome architecture through chromatin remodeling via histone &#x3b2;-hydroxybutyrylation, thereby influencing the transcriptome. Focusing on the kidney, which is an end organ protected by &#x3b2;-hydroxybutyrate, we examined histone &#x3b2;-hydroxybutyrylation-mediated chromatin remodeling. Notably, regions of the genome associated with lipid catabolism were predominantly in an open chromatin configuration, leading to active transcription and translation. Significant &#x3b2;-hydroxybutyrylation was observed in the kidneys and the most highly upregulated gene actively transcribed and translated was 3-hydroxy-3-methyglutaryl CoA Synthase 2 (Hmgcs2), a gene responsible for the biosynthesis of &#x3b2;-hydroxybutyrate in mitochondria. In contrast, regions with more compact chromatin structures were enriched with genes related to immune function such as protein tyrosine phosphatase receptor type C (Ptprc) and lymphocyte cytosolic protein 1 (Lcp1), which exhibited reduced transcription and translation. These results reveal that renal epigenetic histone &#x3b2;-hydroxybutyrylation is a novel mechanism by which transcriptional regulation of both energy metabolism and immune function occur concomitantly to protect kidneys and lower hypertension.

Blood pressure