1.Development and validation of PhenoRAG: A visualization tool for automated human phenotype ontology term annotation based on large language models and retrieval-augmented generation technology.
Wei ZHONG ; Yousheng YAN ; Kai YANG ; Yan LIU ; Xinyu FU ; Zhengyang YAO ; Chenghong YIN
Chinese Journal of Medical Genetics 2026;43(1):36-43
OBJECTIVE:
To develop a user-friendly visualization application for the automatic annotation of Human Phenotype Ontology (HPO) terms based on large language models and retrieval-augmented generation (RAG) technology, and to validate its performance in an authoritative case dataset.
METHODS:
By integrating the domestic open-source large language model DeepSeek-V3 with RAG technology, an interactive web application was deployed on the Streamlit cloud platform. Using only the latest official HPO dataset as the data source, the lightweight sentence-embedding model BAAI/bge-small-en-v1.5 was employed to construct a FAISS vector index. During the online phase, a four-step closed-loop process is automatically completed: multilingual translation, phenotype phrase extraction, RAG candidate retrieval, term mapping, and official database validation. 121 English case reports publicly released by BMJ Case Reports and Oxford Medical Case Reports (with a gold-standard HPO set of 1 794 terms) were selected for application validation. Precision, recall, and F1 score were calculated and compared horizontally with traditional dictionary tools, standalone large language models, and the similar application "RAG-HPO". Finally, replace the model with the more advanced ChatGPT-5 and evaluate its performance on the newly extracted dataset.
RESULTS:
An HPO term automatic annotation visualization application named PhenoRAG, based on large language models and RAG technology, was successfully developed. Users can access it directly via a web link. Across the 112 cases, a total of 2 150 HPO terms were generated; 2,064 (96.0%) were fully validated by the official database, with a hallucination rate of 1.3% and an HPO ID-name mismatch rate of 2.7%. After deduplication, 1,906 terms remained for testing. The overall precision was 63.65%, recall was 67.34%, and F1 was 65.44%, significantly outperforming traditional annotation tools (F1: 0.45-0.49, P < 0.001). Although PhenoRAG's F1 was lower than that of RAG-HPO (F1 = 0.78, P < 0.001), which relies on a manually constructed synonym database of 54 000 entries plus the HPO dataset, it requires no additional dictionary maintenance and can be used without any background in computer programming. Moreover, after switching to the GPT-5 model, PhenoRAG exhibited no hallucination rate on the new dataset, and its F1 score significantly increased (P = 0.038).
CONCLUSION
Without constructing a synonym database, the PhenoRAG achieved high-accuracy automatic mapping from clinical text to standard HPO terms. It features a low usage threshold, free access, and a Chinese-language interface, and can directly serve rare disease diagnosis, genetic counseling, and research scenarios in China and worldwide, warranting further clinical promotion and multicenter validation.
Humans
;
Phenotype
;
Biological Ontologies
;
Language
;
Software
;
Large Language Models
2.External ocular manifestations among patients diagnosed with Coronavirus disease 2019 in a referral center in the Philippines.
Alyssa Louise B. Pejana-Paulino ; Aramis B. Torrefranca Jr. ; Nilo Vincent DG. Florcruz ; Ma. Dominga B. Padilla
Acta Medica Philippina 2026;60(1):69-77
BACKGROUND AND OBJECTIVES
data-mce-style="text-align: justify;">The global pandemic caused by Coronavirus Disease 2019 (COVID-19) has affected millions, with growing evidence of the potential role of ocular tissues in viral transmission. At the time of writing, local data regarding the phenomenon was limited. This study investigated external ocular manifestations in patients with COVID-19 at a referral center in the Philippines, examined correlations between demographics, systemic manifestations, and laboratory results with ocular manifestations, and determined their timing relative to systemic symptoms.
METHODSdata-mce-style="text-align: justify;">This single-center, descriptive cross-sectional study was carried out from December 8 to 18, 2020 at the adult COVID-19 wards of the Philippine General Hospital involving 72 participants. Data collection involved relevant clinical history taking and performing gross eye examination. The prevalence of ocular manifestations was described with 95% confidence intervals. Correlations between ocular manifestations and quantitative variables were analyzed with point-biserial correlation, and associations with qualitative variables were tested using chi-square or Fisher’s exact tests.
RESULTSdata-mce-style="text-align: justify;">Among participants, 31.9% presented with ocular manifestations with foreign body sensation as the most prevalent ocular symptom (11.1%) and conjunctival hyperemia as the most prevalent ocular finding (19.4%). The median age of patients with ocular manifestations was 41 years old with a higher prevalence in the male population (73.9%, CI=95%, p=0.001). No significant correlation was observed between presence of external ocular manifestations and the different systemic and ocular co-morbidities as well as with COVID-19 clinical classification. Among those who experienced symptoms, majority (29.2%) of the patients experienced systemic symptoms prior to the onset of ocular symptoms. Ocular complaints may present as the sole manifestation (13.9%). Several laboratory parameters were measured and only temperature and AST levels showed a low positive correlation with the presence of ocular manifestations.
CONCLUSIONdata-mce-style="text-align: justify;">Ocular manifestations occur in roughly one third of patients with COVID-19 based on this study population. With some individuals presenting with ocular signs or symptoms as the initial and sole manifestation, healthcare practitioners must exercise caution and remain vigilant in managing patients who present as such. At the time of writing, this is the first local study investigating the different external ocular manifestations in patients with COVID-19. There is a need to pursue more robust studies and conduct more local investigations which will guide both ophthalmologists and other practitioners in strengthening existing guidelines regarding precautionary practices, clinical diagnosis, and management of COVID-19 patients.
Human ; Sars-cov-2 ; Covid-19 ; Philippines ; Adult ; Association ; Classification ; Collection ; Confidence Intervals ; Coronavirus ; Cross-sectional Studies ; Data Collection ; Demography ; Diagnosis ; Disease ; Exercise ; Eye ; Foreign Bodies ; History ; Hospitals ; Hospitals, General ; Hyperemia ; Laboratories ; Male ; Morbidity ; Ophthalmologists ; Pandemics ; Patients ; Population ; Prevalence ; Referral And Consultation ; Role ; Sensation ; Temperature ; Time ; Tissues ; Volition ; World Health Organization ; Writing
3.Pseudomonas monteilii ZMU-T06 produces 2-substituted quinolines by oxidative dehydroaromatization.
Min YANG ; Lan ZOU ; Huimin RAN ; Lei QIN
Chinese Journal of Biotechnology 2025;41(1):288-295
2-substituted quinolines are the building blocks for the synthesis of natural products and pharmaceuticals. In comparison with classical methods, dehydroaromatization of 2-substituted-1,2,3,4-tetrahydroquinolines has emerged in recent years as an efficient and straightforward method to synthesize quinolines due to its high atom economy and sustainability. However, existing chemical methods need transition metal catalysts and harsh reaction conditions. Biocatalysis with high efficiency, high selectivity, and mild reaction conditions has become an important method of organic synthesis. We mined a strain Pseudomonas monteilii ZMU-T06 capable of producing monoamine oxidase for the dehydroaromatization of 2-substituted-1,2,3,4-tetrahydroquinolines to synthesize 2-substituted quinolines (8 substrates, yields of 45.7%-48.4%) and then hypothesized the catalytic mechanism, providing a new method for green synthesis of 2-substituted quinolines.
Quinolines/chemistry*
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Pseudomonas/classification*
;
Oxidation-Reduction
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Monoamine Oxidase/biosynthesis*
;
Biocatalysis
4.Functions and mechanisms of Zn2+-dependent histone deacetylase in plant responses to abiotic stress.
Ming WEI ; Meng ZHAO ; Xinrui WU ; Guoqiang WU
Chinese Journal of Biotechnology 2025;41(2):491-509
The HDAs (a subfamily of histone deacetylases), a class of Zn2+-dependent histone deacetylases, are highly homologous to the reduced potassium dependency 3 (RPD3) in yeast. HDAs extensively regulate chromosome stability, gene transcription, and protein activity by catalyzing the removal of acetyl group from histone and non-histone lysine residues. HDA-mediated deacetylation is essential for plant growth, development, and responses to abiotic stress. We review the research progress in HDAs regarding the discovery, structures, classification, deacetylation process, and roles in regulating plant responses to abiotic stress. Furthermore, this paper prospects the future research on HDAs, aiming to provide theoretical support for the research on epigenetic regulation mediated by HDAs.
Histone Deacetylases/classification*
;
Zinc/metabolism*
;
Stress, Physiological/physiology*
;
Plants/genetics*
5.Genetic diversity and molecular identity of Prunus mume with both ornamental and edible values based on fluorescence-labeled simple sequence repeat (SSR) markers.
Zixu WANG ; Dan ZHOU ; Yanbei ZHAO ; Yuhang TONG ; Weijun ZHENG ; Qingwei LI
Chinese Journal of Biotechnology 2025;41(2):639-656
We studied the genetic diversity and established the DNA molecular identify for Prunus mume with both ornamental and edible values, aiming to collect, identify, evaluate, and breed new varities of this plant and promote the upgrading of the P. mume industry chain in northern China. We employed 13 pairs of primers with good polymorphism, clear bands, and good repeatability to analyze the genetic diversity and establish the molecular identify of 68 germplasm accessions of P. mume with both ornamental and edible values from Xingtai, Hebei Province. We then employed the unweighted pair-group method with arithmetic means (UPGMA) to perform the cluster analysis based on genetic distance. After that, we analyzed the genetic structure of the 68 germplasm accessions based on a Bayesian model. The 13 pairs of SSR primers amplified a total of 124 alleles from 68 P. mume germplasm accessions, with the mean number of alleles (Na) of 9.538 5, the minor allele frequency (MAF) of 0.369 3, the mean number of effective alleles (Ne) of 4.483 5, and the mean Shannon genetic diversity index (I) of 1.712 4. The mean Nei's gene diversity index (H) of 0.763 7, the mean observed heterozygosity (Ho) of 0.719 5, the mean expected heterozygosity (He) of 0.769 3, the mean polymorphism information content (PIC) of 0.733 6, and the mean genetic similarity (GS) of 0.772 9 suggested that there were significant genetic differences and rich genetic diversity among the studied P. mume germplasm accessions. The cluster analysis revealed that the 68 accessions were classified into three groups, with the mean genetic distance of 0.622 6. The population structure analysis classified the germplasm accessions into two populations. According to the PIC of primers, we selected primers for combination and constructed the combination with the fewest primers required for germplasm differentiation of P. mume with both ornamental and edible values. This study provides a theoretical basis for the innovation and industrial upgrading of P. mume with both ornamental and edible values in gardening and the improvement of breeding efficiency.
Prunus/classification*
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Microsatellite Repeats/genetics*
;
Genetic Variation
;
China
;
Phylogeny
;
Polymorphism, Genetic
;
DNA, Plant/genetics*
;
Alleles
6.Identification of the MYB transcription factor family involved in response to salt stress in Picea mongolica.
Mingming SUI ; Fuman ZHANG ; Tian TIAN ; Yanqiu YAN ; Le GENG ; Hui LI ; Yu'e BAI
Chinese Journal of Biotechnology 2025;41(2):825-844
Picea mongolica, known for its remarkable tolerance to cold, drought, and salinity, is a key species for ecological restoration and urban greening in the "Three Norths" region of China. MYB transcription factors are involved in plant responses to abiotic stress and synthesis of secondary metabolites. However, studies are limited regarding the MYB transcription factors in P. mongolica and their roles in salt stress tolerance. In this study, 196 MYBs were identified based on the genome of Picea abies and the transcriptome of P. mongolica. Phylogenetic analysis classified the MYB transcription factors into seven subclasses. The R2R3-MYB subclass contained the maximum number of genes (84.77%), while the R-R and R1R2R3 subclasses each represented the smallest proportion, at about 0.51%. The MYB transcription factors within the same subclass were highly conserved, exhibiting similar motifs and gene structures. Experiments with varying salt stress gradients revealed that P. mongolica could tolerate the salt concentration up to 1 000 mmol/L. From the transcriptome data of P. mongolica exposed to salt stress (1 000 mmol/L) for 0, 3, 6, 12, and 24 h, a total of 34 differentially expressed MYBs were identified, which suggested that these MYBs played a key role in regulating the response to salt stress. The proteins encoded by these differentially expressed genes varied in length from 89 aa to 731 aa, with molecular weights ranging from 10.19 kDa to 79.73 kDa, isoelectric points between 4.80 and 9.91, and instability coefficients from 41.20 to 70.99. Subcellular localization analysis indicated that most proteins were localized in the nucleus, while three were found in the chloroplasts. Twelve MYBs were selected for quantitative real-time PCR (qRT-PCR), which showed that their expression patterns were consistent with the RNA-seq data. This study provides valuable data for further investigation into the functions and mechanisms of MYB family members in response to salt stress in P. mongolica.
Picea/physiology*
;
Transcription Factors/classification*
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Salt Stress/genetics*
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Phylogeny
;
Plant Proteins/genetics*
;
Salt Tolerance/genetics*
;
Gene Expression Regulation, Plant
7.Cloning, prokaryotic expression, and functional validation of flavonoid 3-O-glycosyltransferase gene (Rh3GT) from Rhododendron hybridum Hort.
Yicheng YAN ; Zehang WU ; Yuhang JIANG ; Gaoyuan HU ; Yujie YANG ; Xiaohong XIE ; Yueyan WU ; Yonghong JIA
Chinese Journal of Biotechnology 2025;41(2):881-895
Flavonoid 3-O-glucosyltransferase (3GT) is a key enzyme in the glucosidation of anthocyanins. To investigate the 3GT gene in rhododendron, we cloned an open reading frame (ORF) of 3GT gene (named Rh3GT) from Rhododendron hybridum Hort (Red cultivar) and then characterized this gene and the deduced protein in terms of the biochemical characteristics, expression level, and enzymatic function. The results showed that Rh3GT had a full length of 993 bp and encoded 330 amino acid residues. The deduced protein was hydrophilic, stable, weak acid, belonging to the glycosyltransferase family (GT-B type), with glutamine (Q) at position 44 in the PSPG box. The phylogenetic analysis showed that Rh3GT was most closely related to Vc3GT from Vaccinium corymbosum and Vm3GT from Vaccinium myrtillus. Rh3GT was expressed in the stems, leaves, and flowers and almost not expressed in the roots, with the highest expression level in petals during full blooming stage. Introduction of pCAMBIAL1302-Rh3GT into petals significantly up-regulated the expression level of Rh3GT and increased the total anthocyanin accumulation. Rh3GT was successfully expressed in Escherichia coli BL21 in the form of inclusion bodies with a size of about 36 kDa. The results of HPLC showed that the recombinant Rh3GT after denaturation, purification, and dilution could catalyze the synthesis of cyanidin and UDP-glucose to synthesize cyanidin 3-O-glucoside, indicating that the expressed protein had 3GT activity. This study provides basic data for further studying the molecular regulation mechanism of anthocyanin biosynthesis and theoretical support for molecular breeding of rhododendron.
Rhododendron/classification*
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Glucosyltransferases/metabolism*
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Cloning, Molecular
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Escherichia coli/metabolism*
;
Recombinant Proteins/biosynthesis*
;
Anthocyanins/biosynthesis*
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Phylogeny
;
Plant Proteins/metabolism*
;
Amino Acid Sequence
8.Acyl homoserine lactones facilitate the isolation and cultivation of Gram-negative bacteria from mouse intestine.
Changyu WANG ; Qinghua ZHAO ; Chang LIU ; Shuangjiang LIU
Chinese Journal of Biotechnology 2025;41(6):2349-2359
N-dodecanoyl-l-homoserine lactone (C12-HSL) is a signaling molecule that mediates bacterial quorum sensing, regulating bacterial population behaviors. This study investigated the effects of C12-HSL on the isolation and cultivation of gut microbiota, with the goal of enriching the diversity and number of cultivable bacterial strains from the mouse gut microbiota. Using a culture medium supplemented with C12-HSL, we isolated and cultivated bacterial strains from mouse intestinal contents, obtaining a total of 235 isolates. Preliminary identification based on the 16S rRNA gene revealed 54 bacterial species, including 4 potential new species, 4 potential new genera and 1 potential new family. Compared with the previously established mouse gut microbial biobank (mGMB), this study newly identified 42 bacterial species, enhancing the diversity of the strain library. Statistical analysis showed that the proportion of Gram-negative bacteria, particularly those belonging to Proteobacteria, isolated by this method was significantly higher than that obtained by conventional isolation and cultivation methods without the addition of C12-HSL. Subsequent cultivation experiments with one of the newly discovered bacterial species indicated that exogenous C12-HSL at 20-200 μmol/L significantly promoted the growth of this species, while higher concentrations of C12-HSL significantly reduced the cell density of this bacterium. This work confirms that quorum sensing molecules, such as C12-HSL, can enhance the growth, isolation, and cultivation of Gram-negative bacteria in the gut within a specific concentration range. Although the mechanism by which C12-HSL promotes the growth of gut bacterial strains requires further investigation, the findings of this study provide new insights into the targeted isolation, cultivation, and regulation of gut microbiota using bacterial quorum sensing signal molecules.
Animals
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Mice
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Acyl-Butyrolactones/pharmacology*
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Gastrointestinal Microbiome/drug effects*
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Quorum Sensing
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Gram-Negative Bacteria/classification*
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Intestines/microbiology*
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RNA, Ribosomal, 16S/genetics*
;
Culture Media
9.Isolation, identification, and degradation characterization of a polyethylene plastic-degrading bacterial strain.
Yuwei WANG ; Liting ZHANG ; Min XU ; Zhongli CUI ; Hui CAO
Chinese Journal of Biotechnology 2025;41(6):2405-2414
Polyethylene (PE) is widely used due to its excellent properties. However, the improper disposal of PE waste has led to serious environmental pollution. Microbial degradation of PE is a low-carbon, environmentally friendly, and highly efficient method of homogeneous recycling. The use of microbial degradation technology to treat polyethylene waste has become one of the current research hotspots. As a result, employing microbial degradation technology to address polyethylene waste has become a key focus of current research. A PE-degrading strain ETX1 was screened from waste plastics in a landfill by the enrichment culture method. The strain was identified as Lysinibacillus sp.. After incubating PE powder with the strain for 20 days, a weight loss of 29.41% was observed. Fourier transform infrared spectroscopy (FTIR) showed that special absorption peaks such as carbonyl and hydroxyl groups appeared, proving that ETX1 had the effect of degrading PE. The degradation effect of this strain was characterized by the weight loss of PE film, FTIR, scanning electron microscopy, and contact angle. The results showed that ETX1 reduced the PE film weight by up to 5.23% within 120 days. The film structure was damaged, with holes formed by erosion on the film surface, and the hydrophilicity was enhanced. Additionally, a stronger carbonyl absorption peak appeared. The discovery of the PE-degrading strain ETX1 not only enriches the resources of PE plastic-degrading strains but also lays a foundation for mining efficient PE-degrading elements, obtaining degrading enzymes, and deciphering related degradation pathways.
Polyethylene/chemistry*
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Biodegradation, Environmental
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Spectroscopy, Fourier Transform Infrared
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Bacillaceae/classification*
;
Plastics/metabolism*
10.Microbiome and its genetic potential for carbon fixation in small urban wetlands.
Minghai LIN ; Lianxin HU ; Liping HAO ; Zefeng WANG
Chinese Journal of Biotechnology 2025;41(6):2415-2431
Small urban wetlands are widely distributed and susceptible to human activities, serving as important sources and sinks of carbon. Microorganisms play a crucial role in carbon cycle, while limited studies have been conducted on the microbial diversity in small urban wetlands and the functions of microbiome in carbon fixation and metabolism. To probe into the microbiome-driven carbon cycling in small urban wetlands and dissect the composition and functional groups of microbiome, we analyzed the relationships between the microbiome structure, element metabolism pathways, and habitat physicochemical properties in sediment samples across three small wetlands in Huzhou City, and compared them with natural wetlands in the Zoige wetland. High-throughput sequencing of 16S rRNA gene amplicons and metagenomics was employed to determine the species and functional groups. Sixty medium to high-quality metagenome-assembled genomes (MAGs) were constructed, including 55 bacterial and 5 archaeal taxa, and their potential in driving elemental cycles were analyzed, with a focus on carbon fixation. Several bacterial species were found to encode a nearly complete carbon fixation pathway, including the Calvin cycle, the reductive tricarboxylic acid cycle, the Wood-Ljungdahl pathway, and the reductive glycine pathway. There were several potential novel carbon-fixing bacterial members, such as those belonging to Syntrophorhabdus (Desulfobacterota) and UBA4417 (Bacteroidetes), which had high relative abundance in the wetland microbiome. Unveiling the genetic potential of these functional groups to facilitate element cycling is of great scientific importance for enhancing the carbon sequestration capacity of small urban wetlands.
Wetlands
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Microbiota/genetics*
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Carbon Cycle/genetics*
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Bacteria/classification*
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RNA, Ribosomal, 16S/genetics*
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China
;
Cities
;
Geologic Sediments/microbiology*
;
Archaea/classification*
;
Metagenomics
;
Metagenome


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