Evolink: a phylogenetic approach for rapid identification of genotype-phenotype associations in large-scale microbial multispecies data.

MOTIVATION: The discovery of the genetic features that underly a phenotype is a fundamental task in microbial genomics. With the growing number of microbial genomes that are paired with phenotypic data, new challenges, and opportunities are arising for genotype-phenotype inference. Phylogenetic approaches are frequently used to adjust for the population structure of microbes but scaling them to trees with thousands of leaves representing heterogeneous populations is highly challenging. This greatly hinders the identification of prevalent genetic features that contribute to phenotypes that are observed in a wide diversity of species. RESULTS: In this study, Evolink was developed as an approach to rapidly identify genotypes associated with phenotypes in large-scale multispecies microbial datasets. Compared with other similar tools, Evolink was consistently among the top-performing methods in terms of precision and sensitivity when applied to simulated and real-world flagella datasets. In addition, Evolink significantly outperformed all other approaches in terms of computation time. Application of Evolink on flagella and gram-staining datasets revealed findings that are consistent with known markers and supported by the literature. In conclusion, Evolink can rapidly detect phenotype-associated genotypes across multiple species, demonstrating its potential to be broadly utilized to identify gene families associated with traits of interest. AVAILABILITY AND IMPLEMENTATION: The source code, docker container, and web server for Evolink are freely available at https://github.com/nlm-irp-jianglab/Evolink.

Screening and identification of miR-181a-5p in oral squamous cell carcinoma and functional verification in vivo and in vitro.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common malignant tumor associated with poor prognosis. MicroRNAs (miRNAs) play crucial regulatory roles in the cancer development. However, the role of miRNAs in OSCC development and progression is not well understood. METHODS: We sought to establish a dynamic Chinese hamster OSCC animal model, construct miRNA differential expression profiles of its occurrence and development, predict its targets, and perform functional analysis and validation in vitro. RESULTS: Using expression and functional analyses, the key candidate miRNA (miR-181a-5p) was selected for further functional research, and the expression of miR-181a-5p in OSCC tissues and cell lines was detected. Subsequently, transfection technology and a nude mouse tumorigenic model were used to explore potential molecular mechanisms. miR-181a-5p was significantly downregulated in human OSCC specimens and cell lines, and decreased miR-181a-5p expression was observed in multiple stages of the Chinese hamster OSCC animal model. Moreover, upregulated miR-181a-5p significantly inhibited OSCC cell proliferation, colony formation, invasion, and migration; blocked the cell cycle; and promoted apoptosis. BCL2 was identified as a target of miR-181a-5p. BCL2 may interact with apoptosis- (BAX), invasion- and migration- (TIMP1, MMP2, and MMP9), and cell cycle-related genes (KI67, E2F1, CYCLIND1, and CDK6) to further regulate biological behavior. Tumor xenograft analysis indicated that tumor growth was significantly inhibited in the high miR-181a-5p expression group. CONCLUSION: Our findings indicate that miR-181a-5p can be used as a potential biomarker and provide a novel animal model for mechanistic research on oral cancer.

Characterizing Transcriptional Regulatory Sequences in Coronaviruses and Their Role in Recombination.

Novel coronaviruses, including SARS-CoV-2, SARS, and MERS, often originate from recombination events. The mechanism of recombination in RNA viruses is template switching. Coronavirus transcription also involves template switching at specific regions, called transcriptional regulatory sequences (TRS). It is hypothesized but not yet verified that TRS sites are prone to recombination events. Here, we developed a tool called SuPER to systematically identify TRS in coronavirus genomes and then investigated whether recombination is more common at TRS. We ran SuPER on 506 coronavirus genomes and identified 465 TRS-L and 3,509 TRS-B. We found that the TRS-L core sequence (CS) and the secondary structure of the leader sequence are generally conserved within coronavirus genera but different between genera. By examining the location of recombination breakpoints with respect to TRS-B CS, we observed that recombination hotspots are more frequently colocated with TRS-B sites than expected.

The Evolution Pathway of Ammonia-Oxidizing Archaea Shaped by Major Geological Events.

Primordial nitrification processes have been studied extensively using geochemical approaches, but the biological origination of nitrification remains unclear. Ammonia-oxidizing archaea (AOA) are widely distributed nitrifiers and implement the rate-limiting step in nitrification. They are hypothesized to have been important players in the global nitrogen cycle in Earth's early history. We performed systematic phylogenomic and marker gene analyses to elucidate the diversification timeline of AOA evolution. Our results suggested that the AOA ancestor experienced terrestrial geothermal environments at ∼1,165 Ma (1,928-880 Ma), and gradually evolved into mesophilic soil at ∼652 Ma (767-554 Ma) before diversifying into marine settings at ∼509 Ma (629-412 Ma) and later into shallow and deep oceans, respectively. Corroborated by geochemical evidence and modeling, the timing of key diversification nodes can be linked to the global magmatism and glaciation associated with the assembly and breakup of the supercontinent Rodinia, and the later oxygenation of the deep ocean. Results of this integrated study shed light on the geological forces that may have shaped the evolutionary pathways of the AOA, which played an important role in the ancient global nitrogen cycle.

The taxonomic distribution of histamine-secreting bacteria in the human gut microbiome.

BACKGROUND: Biogenic histamine plays an important role in immune response, neurotransmission, and allergic response. Although endogenous histamine production has been extensively studied, the contributions of histamine produced by the human gut microbiota have not been explored due to the absence of a systematic annotation of histamine-secreting bacteria. RESULTS: To identify the histamine-secreting bacteria from in the human gut microbiome, we conducted a systematic search for putative histamine-secreting bacteria in 36,554 genomes from the Genome Taxonomy Database and Unified Human Gastrointestinal Genome catalog. Using bioinformatic approaches, we identified 117 putative histamine-secreting bacteria species. A new three-component decarboxylation system including two colocalized decarboxylases and one transporter was observed in histamine-secreting bacteria among three different phyla. We found significant enrichment of histamine-secreting bacteria in patients with inflammatory bowel disease but not in patients with colorectal cancer suggesting a possible association between histamine-secreting bacteria and inflammatory bowel disease. CONCLUSIONS: The findings of this study expand our knowledge of the taxonomic distribution of putative histamine-secreting bacteria in the human gut.

Cell senescence altered the miRNA expression profile in porcine angular aqueous plexus cells.

Purpose: This study investigates the impact of aging on the miRNA expression profile in porcine angular aqueous plexus (AAP) cells, which are the porcine equivalent of human Schlemm's canal endothelial cells. Methods: AAP endothelial cells were isolated and cultured in physiologic (5% O2) or hyperoxic condition (40% O2) for 14 days to induce cell senescence. miRNA and protein expression profiles of control and senescent cells were analyzed with miRNA microarray and isobaric tags for relative and absolute quantification (iTRAQ), respectively. Results: The miRNA microarray identified 33 differentially expressed miRNAs in senescent cells compared with controls (p<0.05), and quantitative real-time PCR (qRT-PCR) confirmed 12 of them (p<0.05). iTRAQ analysis identified 148 upregulated and 222 downregulated proteins (p<0.05, fold change>1.2). Bioinformatics analysis of miRNA microarray and proteomics data predicted that six out of seven miRNAs are associated with aqueous humor outflow by targeting integrin and the downstream pathways (Src/Rho kinase, focal adhesion kinase (FAK)/NO-cGMP), and one miRNA might influence gap junction by targeting the Inositol trisphosphate receptor (IP3R) /Protein kinase C (PKC) pathway. Conclusions: This study identified miRNAs in senescent AAP cells that might regulate aqueous humor outflow by targeting proteins involved in focal adhesion, cytoskeleton, NO-cGMP signaling, and gap junction.

DSab-origin: a novel IGHD sensitive VDJ mapping method and its application on antibody response after influenza vaccination.

BACKGROUND: Functional antibody genes are often assembled by VDJ recombination and then diversified by somatic hypermutation. Identifying the combination of sourcing germline genes is critical to understand the process of antibody maturation, which may facilitate the diagnostics and rapid generation of human monoclonal antibodies in therapeutics. Despite of successful efforts in V and J fragment assignment, method in D segment tracing remains weak for immunoglobulin heavy diversity (IGHD). RESULTS: In this paper, we presented a D-sensitive mapping method called DSab-origin with accuracies around 90% in human monoclonal antibody data and average 95.8% in mouse data. Besides, DSab-origin achieved the best performance in holistic prediction of VDJ segments assignment comparing with other methods commonly used in simulation data. After that, an application example was explored on the antibody response based on a time-series antibody sequencing data after influenza vaccination. The result indicated that, despite the personal response among different donors, IGHV3-7 and IGHD4-17 were likely to be dominated gene segments in these three donors. CONCLUSIONS: This work filled in a computational gap in D segment assignment for VDJ germline gene identification in antibody research. And it offered an application example of DSab-origin for studying the antibody maturation process after influenza vaccination.

The recent progress in proteochemometric modelling: focusing on target descriptors, cross-term descriptors and application scope.

As an extension of the conventional quantitative structure activity relationship models, proteochemometric (PCM) modelling is a computational method that can predict the bioactivity relations between multiple ligands and multiple targets. Traditional PCM modelling includes three essential elements: descriptors (including target descriptors, ligand descriptors and cross-term descriptors), bioactivity data and appropriate learning functions that link the descriptors to the bioactivity data. Since its appearance, PCM modelling has developed rapidly over the past decade by taking advantage of the progress of different descriptors and machine learning techniques, along with the increasing amounts of available bioactivity data. Specifically, the new emerging target descriptors and cross-term descriptors not only significantly increased the performance of PCM modelling but also expanded its application scope from traditional protein-ligand interaction to more abundant interactions, including protein-peptide, protein-DNA and even protein-protein interactions. In this review, target descriptors and cross-term descriptors, as well as the corresponding application scope, are intensively summarized. Additionally, we look forward to seeing PCM modelling extend into new application scopes, such as Target-Catalyst-Ligand systems, with the further development of descriptors, machine learning techniques and increasing amounts of available bioactivity data.

Roles of miR-200 family members in lung cancer: more than tumor suppressors.

miRNAs are a class of single-stranded noncoding RNAs, which have no coding potential, but modulate many molecular mechanisms including cancer pathogenesis. miRNAs participate in cell proliferation, differentiation, apoptosis, as well as carcinogenesis or cancer progression, and their involvement in lung cancer has been recently shown. They are suggested to have bidirectional functions on important cancer-related genes so as to enhance or attenuate tumor genesis. Epithelial-mesenchymal transition (EMT) is a fundamental process which contributes to integrity of organogenesis and tissue differentiation as well as tissue repair, organ fibrosis and the progression of carcinoma, and several miRNAs were suggested to form the network regulating EMT in lung cancer, among which, miR-200 family members (miR-200a, miR-200b, miR-200c, miR-429 and miR-141) play crucial roles in the suppression of EMT.

Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism.

Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

Effects of Tricyclazole on Cadmium Tolerance and Accumulation Characteristics of a Dark Septate Endophyte (DSE), Exophiala pisciphila.

Exophiala pisciphila is a cadmium-tolerant fungus, and produces 1,8-dihydroxynaphthalene melanin which can be inhibited by tricyclazole. Tricyclazole at higher levels (20 and 40 µg mL−1) reduced the growth and sporulation of E. pisciphila, but toxicity was not observed at a low concentration (2.5 µg mL−1). Under cadmium (Cd) stress (50, 100 and 200 mg L−1), 2.5 µg mL−1 of tricyclazole reduced fungal growth and sporulation. These reduces indicated a decrease on Cd tolerance of E. pisciphila. For both the 0 and 2.5 µg mL−1 tricyclazole treatments, Cd was associated mostly with cell walls and was extracted by 2 % acetic acid and 1 M NaCl. The FTIR spectra of the E. pisciphila mycelia were similar for both 0 and 2.5 µg mL−1 tricyclazole treatments, which showed hydroxyl, amine, carboxyl and phosphate groups. Thus inhibition of melanin synthesis by tricyclazole did not change Cd accumulation characteristics in E. pisciphila. Results suggested that melanin played a protective role for E. pisciphila against Cd stress, but inhibition of melanin synthesis did not have a remarkable impact on Cd accumulation in E. pisciphila.

Macrophage-Centric Biomaterials for Bone Regeneration in Diabetes Mellitus: Contemporary Advancements, Challenges, and Future Trajectories.

Increased susceptibility to bone fragility and the diminution of bone regenerative capacity are recognized as significant and frequent sequelae of diabetes mellitus. Research has elucidated the pivotal role of macrophages in the pathogenesis and repair of diabetic bone defects. Notwithstanding this, the therapeutic efficacy of traditional interventions remains predominantly inadequate. Concomitant with substantial advancements in tissue engineering in recent epochs, there has been an escalation in the development of biomaterials designed to modulate macrophage activity, thereby augmenting osseous tissue regeneration in the context of hyperglycemia. This review amalgamates insights from extant research and delineates recent progressions in the domain of biomaterials that target macrophages for the regeneration of diabetic bone, whilst also addressing the clinical challenges and envisaging future directions within this field.

The important role of nitrate in iron and manganese dissolution and sulfate formation in fine particles at a coastal site in Northern China.

Bioavailable transition trace elements, such as soluble iron (Fes) and soluble manganese (Mns) in aerosols, play a crucial role in atmospheric sulfate formation and marine ecosystems. In this study conducted during the spring of 2017 in Qingdao, a coastal city in Northern China, we applied a combined approach of multiple linear regression (MLR) incorporating the results of positive matrix factorization (PMF) to estimate the solubility of Fe and Mn from various sources. PMF analysis showed that dust was the largest contributor to total Fe (FeT) (45.5 %), followed by non-ferrous smelting (20.3 %) and secondary formation processes (17.8 %). However, secondary formation processes (33.2 %), vehicle exhaust (19.3 %) and aqueous-phase processes (19.0 %) were found to be the primary contributors to Fes. For total Mn (MnT) and Mns, dust (21.2 % âˆ¼ 35.0 %), secondary formation processes (20.3 % âˆ¼ 25.6 %) and industry (12.6 % âˆ¼ 16.3 %) were identified as the dominant contributors. The solubilities of Fe and Mn varied significantly depending on their sources. Interestingly, nitrate played a more pronounced role than sulfate in facilitating the dissolution of Fe and Mn during the acid processing due to the high molar ratio of NO3-/2SO42- (1.72 ± 0.54) under the average RH of 56 % ± 15 %. This phenomenon suggested that the acid processing was primarily triggered by nitrate formation due to the low deliquescence relative humidity (DRH) of nitrate. Additionally, we discovered that the catalytic oxidation of SO2 in aerosol water was primarily driven by Fe rather than Mn, serving as a more significant pathway for sulfate formation within a pH range of 2.0 to 4.4. These findings provide valuable insights into the impact of acidification on the dissolution of Fe and Mn under conditions of moderate RH in the real ambient atmosphere with the increasing of NO3-/2SO42- molar ratio.

Waste Tea-Derived Theabrownins for Solar-Driven Steam Generation.

Solar-driven seawater desalination has been considered an effective and sustainable solution to mitigate the global freshwater crisis. However, the substantial cost associated with photothermal materials for evaporator fabrication still hinders large-scale manufacturing for practical applications. Herein, we successfully obtained high yields of theabrownins (TB), which were oxidation polymerization products of polyphenols from waste and inferior tea leaves using a liquid-state fermentation strategy. Subsequently, a series of photothermal complexes were prepared based on the metal-phenolic networks assembled from TB and metal ions (Fe(III), Cu(II), Ni(II), and Zn(II)). Also, the screened TB@Fe(III) complexes were directly coated on a hydrophilic poly(vinylidene fluoride) (PVDF) membrane to construct the solar evaporation device (TB@Fe(III)@PVDF), which not only demonstrated superior light absorption property and notable hydrophilicity but also achieved a high water evaporation rate of 1.59 kg m-2 h-1 and a steam generation efficiency of 90% under 1 sun irradiation. More importantly, its long-term stability and exceptionally low production cost enabled an important step toward the possibility of large-scale practical applications. We believe that this study holds the potential to pave the way for the development of sustainable and cost-effective photothermal materials, offering new avenues for utilization of agriculture resource waste and solar-driven water remediation.

Mechanically Controlled Enzymatic Polymerization and Remodeling.

In nature, proteins possess the remarkable ability to sense and respond to mechanical forces, thereby triggering various biological events, such as bone remodeling and muscle regeneration. However, in synthetic systems, harnessing the mechanical force to induce material growth still remains a challenge. In this study, we aimed to utilize low-frequency ultrasound (US) to activate horseradish peroxidase (HRP) and catalyze free radical polymerization. Our findings demonstrate the efficacy of this mechano-enzymatic chemistry in rapidly remodeling the properties of materials through cross-linking polymerization and surface coating. The resulting samples exhibited a significant enhancement in tensile strength, elongation, and Young's modulus. Moreover, the hydrophobicity of the surface could be completely switched within just 30 min of US treatment. This work presents a novel approach for incorporating mechanical sensing and rapid remodeling capabilities into materials.

Large-scale genomic survey with deep learning-based method reveals strain-level phage specificity determinants.

BACKGROUND: Phage therapy, reemerging as a promising approach to counter antimicrobial-resistant infections, relies on a comprehensive understanding of the specificity of individual phages. Yet the significant diversity within phage populations presents a considerable challenge. Currently, there is a notable lack of tools designed for large-scale characterization of phage receptor-binding proteins, which are crucial in determining the phage host range. RESULTS: In this study, we present SpikeHunter, a deep learning method based on the ESM-2 protein language model. With SpikeHunter, we identified 231,965 diverse phage-encoded tailspike proteins, a crucial determinant of phage specificity that targets bacterial polysaccharide receptors, across 787,566 bacterial genomes from 5 virulent, antibiotic-resistant pathogens. Notably, 86.60% (143,200) of these proteins exhibited strong associations with specific bacterial polysaccharides. We discovered that phages with identical tailspike proteins can infect different bacterial species with similar polysaccharide receptors, underscoring the pivotal role of tailspike proteins in determining host range. The specificity is mainly attributed to the protein's C-terminal domain, which strictly correlates with host specificity during domain swapping in tailspike proteins. Importantly, our dataset-driven predictions of phage-host specificity closely match the phage-host pairs observed in real-world phage therapy cases we studied. CONCLUSIONS: Our research provides a rich resource, including both the method and a database derived from a large-scale genomics survey. This substantially enhances understanding of phage specificity determinants at the strain level and offers a valuable framework for guiding phage selection in therapeutic applications.

Hedgehog/Gli2 signaling triggers cell proliferation and metastasis via EMT and wnt/ß-catenin pathways in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is the most lethal oral malignant tumor, however, clinical outcomes remain unsatisfactory. The Hedgehog/Gli2 pathway plays a pivotal role in tumor progression, yet the regulatory mechanism governing its involvement in the malignant evolution process of OSCC remains elusive. Methods: OSCC animal tissue samples were used to detect the activation of the Hedgehog/Gli2 pathway in OSCC. Based on the clinical information of oral cancer patients in TCGA database, the role of this pathway in patients was analyzed, and the activation status of this pathway was verified in human OSCC cells. After activating or inhibiting the Hedgehog pathway, the effects of this pathway on the biological function of OSCC cells and its regulatory mechanism were examined. Interfering the expression of Gli2, a key transcription factor in this pathway, revealed the role of Hedgehog/Gli2 pathway in the malignant evolution of OSCC cells. Results: The Hedgehog pathway exhibits abnormal activation in animal models of OSCC. Clinical data from TCGA demonstrate a significant enrichment of the Hedgehog pathway in patients with OSCC, and Gli2, a key downstream factor of this pathway, is closely associated with the occurrence and progression of OSCC. Cellular studies have revealed aberrant activation of this pathway in human OSCC cells, which exerts its function by modulating the activation of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathways. Subsequent investigations further confirm the pivotal involvement of Gli2 in the Hedgehog pathway activation, underscoring its potential as a therapeutic target for inhibiting malignant proliferation and metastasis of OSCC cells through modulation of EMT and Wnt/ß-catenin pathways. Conclusion: The Hedgehog/Gli2 pathway induces EMT and activates Wnt/ß-catenin pathway to trigger the malignant proliferation and metastasis of OSCC cells, and Gli2 plays a key role in this process, which suggests that targeting Gli2 may be a promising therapeutic strategy for inhibiting the proliferation and metastasis of OSCC.

BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen.

Metabolism of haem by-products such as bilirubin by humans and their gut microbiota is essential to human health, as excess serum bilirubin can cause jaundice and even neurological damage. The bacterial enzymes that reduce bilirubin to urobilinogen, a key step in this pathway, have remained unidentified. Here we used biochemical analyses and comparative genomics to identify BilR as a gut-microbiota-derived bilirubin reductase that reduces bilirubin to urobilinogen. We delineated the BilR sequences from similar reductases through the identification of key residues critical for bilirubin reduction and found that BilR is predominantly encoded by Firmicutes species. Analysis of human gut metagenomes revealed that BilR is nearly ubiquitous in healthy adults, but prevalence is decreased in neonates and individuals with inflammatory bowel disease. This discovery sheds light on the role of the gut microbiome in bilirubin metabolism and highlights the significance of the gut-liver axis in maintaining bilirubin homeostasis.

Characteristics of aerosol aminiums over a coastal city in North China: Insights from the divergent impacts of marine and terrestrial influences.

Aminium ions, as crucial alkaline components within fine atmospheric particles, have a notable influence on new particle formation and haze occurrence. Their concentrations within coastal atmosphere depict considerable variation due to the interplay of distinctive marine and terrestrial sources, further complicated by dynamic meteorological conditions. This study conducted a comprehensive examination of aminiums ions concentrations, with a particular focus on methylaminium (MMAH+), dimethylaminium (DMAH+), trimethylaminium (TMAH+), and triethylaminium (TEAH+) within PM2.5, over varying seasons (summer, autumn, and winter of 2019 and summer of 2021), at an urban site in the coastal megacity of Qingdao, Northern China. The investigations revealed that the total concentration of particulate aminium ions (∑Aminium) was 21.6 ± 23.6 ng/m3, exhibiting higher values in the autumn and winter compared to the two summer periods. Considering diurnal variations during autumn and winter, concentrations of particulate aminium ions (excluding TEAH+) exhibited a slight increase during the day compared to night, with a notable peak during the morning hours. However, it was not the case for TEAH+, which was argued to be readily oxidized by ambient oxidants in the afternoon. Additionally, the ∑Aminium within the summer demonstrated markedly elevated levels during the day compared to night, potentially attributed to daytime sea fog associated with sea-land breeze interactions. Positive matrix factorization results indicate terrestrial anthropogenic emissions, including vehicle emission mixed with road dust and primary pollution, as the primary sources of MMAH+ and DMAH+. Conversely, TMAH+ was predominantly emitted from agricultural and marine sources. With the dominance of sea breeze in summer, TMAH+ was identified as a primary marine emission correlated with sea salt, while MMAH+, DMAH+, and TEAH+ were postulated to undergo secondary formation. Furthermore, a notable inverse correlation was observed between TMAH+ and methanesulfonate in PM2.5, consistent with dynamic emissions of sulfur-content and nitrogen-content gases reported in the literature.

Dependence of evolution of Cyanobacteria superiority on temperature and nutrient use efficiency in a meso-eutrophic plateau lake.

Algal blooms in lakes have been a challenging environmental issue globally under the dual influence of human activity and climate change. Considerable progress has been made in the study of phytoplankton dynamics in lakes; The long-term in situ evolution of dominant bloom-forming cyanobacteria in meso-eutrophic plateau lakes, however, lacks systematic research. Here, the monthly parameters from 12 sampling sites during the period of 1997-2022 were utilized to investigate the underlying mechanisms driving the superiority of bloom-forming cyanobacteria in Erhai, a representative meso-eutrophic plateau lake. The findings indicate that global warming will intensify the risk of cynaobacteria blooms, prolong Microcystis blooms in autumn to winter or even into the following year, and increase the superiority of filamentous Planktothrix and Cylindrospermum in summer and autumn. High RUETN (1.52 Biomass/TN, 0.95-3.04 times higher than other species) under N limitation (TN < 0.5 mg/L, TN/TP < 22.6) in the meso-eutrophic Lake Erhai facilitates the superiority of Dolichospermum. High RUETP (43.8 Biomass/TP, 2.1-10.2 times higher than others) in TP of 0.03-0.05 mg/L promotes the superiority of Planktothrix and Cylindrospermum. We provided a novel insight into the formation of Planktothrix and Cylindrospermum superiority in meso-eutrophic plateau lake with low TP (0.005-0.07 mg/L), which is mainly influenced by warming, high RUETP and their vertical migration characteristics. Therefore, we posit that although the obvious improvement of lake water quality is not directly proportional to the control efficacy of cyanobacterial blooms, the evolutionary shift in cyanobacteria population structure from Microcystis, which thrives under high nitrogen and phosphorus conditions, to filamentous cyanobacteria adapted to low nitrogen and phosphorus levels may serve as a significant indicator of water quality amelioration. Therefore, we suggest that the risk of filamentous cyanobacteria blooms in the meso-eutrophic plateau lake should be given attention, particularly in light of improving water quality and global warming, to ensure drinking water safety.