Search PubMed⌕ Search

Biomedical subjects

Lin Chen

Publications and source records attributed to Lin Chen.

At least 19 recordsLinked to original sources
PubMed2026

Transposable Element Dynamics Drive the Genomic Evolution and Phenotypic Diversification of Allotetraploid Common Carp.

An important question in evolutionary biology is how polyploidization generates raw material for phenotypic diversification. Transposable elements (TEs) represent an underestimated source of genetic variation in eukaryotic genomes. By integrating 516 whole-genome resequencing datasets and 236 transcriptomes from common carp (Cyprinus carpio), a representative allotetraploid fish, we constructed the first population-scale landscape of TE insertions in teleosts. TE insertions are widespread in the carp genome and preferentially associated with stress-responsive genes, with DNA transposons as major contributors. Relaxed purifying selection and TE burst events coexist, generating abundant variation for subsequent subspecies differentiation. Compared with a closely related diploid species, carp exhibits more exonic TE insertions and shorter TE-gene distances, and multiple TE superfamilies expanded during tetraploidization. Genome-wide association analyses uncovered intragenic TE variants underlying domesticated traits missed by SNPs, including DNA transposon deletions associated with scale reduction and altered body shape. Notably, lighter-colored individuals harbor homozygous deletions of LTR and DNA transposons within mdfic2, whose knockout in zebrafish reduces pigmentation. Most trait-associated variants reflect lineage-specific loss of ancient TE insertions rather than recent transposition. Overall, these findings highlight the distinct role of TEs in polyploid genome evolution and phenotypic diversification, providing new insights into TE dynamics in vertebrates.

allotetraploidization↗
PubMed2026

Diosmetin Inhibits Bladder Cancer through Suppression of the PI3K-AKT Signaling Pathway and Activation of the p53 Signal Pathway Revealed by Network Pharmacology and In Vitro Experimental Verification.

INTRODUCTION: Diosmetin, a naturally occurring flavonoid abundant in plants such as chrysanthemums, lemons, and oranges, has been reported to exhibit diverse antitumor properties. However, its potential efficacy against bladder cancer remains unexplored. This study aims to investigate the anti-bladder cancer effects of Diosmetin and elucidate the underlying mechanisms using network pharmacology combined with in vitro experiments. METHODS: Public databases were employed to identify shared targets between Diosmetin and bladder cancer. A Protein-Protein Interaction (PPI) network was constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to predict core targets and signaling pathways. The predicted mechanisms were subsequently validated through in vitro assays. RESULTS: A total of 48 common targets were identified. PPI network analysis revealed 22 hub genes, including AKT1 and MDM2. GO analysis indicated enrichment in 208 biological processes, 23 cellular components, and 38 molecular functions. KEGG analysis suggested that Diosmetin exerts anti-bladder cancer effects primarily through pathways such as Pathways in cancer, PI3K-AKT signaling, and Proteoglycans in cancer. Notably, the PI3K-AKT pathway showed the highest gene enrichment, indicating its potential prominence. In vitro experiments demonstrated that Diosmetin suppresses bladder cancer cell proliferation and induces apoptosis. Additionally, Diosmetin reduced the expression of p-PI3K, p-AKT, and MDM2, while upregulating p53 expression, suggesting involvement of both the PI3K-AKT and p53 pathways. DISCUSSION: These findings align with network pharmacology predictions and highlight the potential of Diosmetin as a multi-target agent against bladder cancer, warranting further in vivo investigation. CONCLUSION: Diosmetin inhibits bladder cancer cell proliferation and promotes apoptosis by suppressing the PI3K-AKT pathway and activating the p53 pathway.

Diosmetin↗
PubMed2026

A novel phage vB_VhaM_HVS-1 inhibits host cell associated Vibrio harveyi.

INTRODUCTION: Vibrio harveyi is a major pathogen causing skin ulceration syndrome and mass mortality in sea cucumber Apostichopus japonicus aquaculture. METHODS: In this study, a pathogenic strain NB-3 was isolated from diseased A. japonicus and identified as V. harveyi based on morphological, physiological, and genomic analyses. A novel lytic phage vB_VhaM_HVS-1 belonging to the family Straboviridae (class Caudoviricetes) was isolated from A. japonicus breeding pond silt. RESULTS: The phage exhibited a latent period of 50 min and a burst size of approximately 168 PFU/cell, and its genome lacked lysogeny-related genes, suggesting a lytic nature. Phage treatment significantly reduced the number of cell-associated bacteria, decreasing the association rate from 2.3% to nearly 0. Flow cytometry revealed that phage infection protected coelomocytes from V. harveyi-induced damage, increasing the proportion of viable cells from 78.17% to 88.54%. CONCLUSION: These findings demonstrate that phage vB_VhaM_HVS-1 effectively reduces V. harveyi association with coelomocytes and alleviates host cell apoptosis. The phage shows strong potential as an alternative biocontrol agent against V. harveyi infection in sea cucumber aquaculture.

aquaculture disease↗
PubMed2026

In vivo epigenome editing reduces circulating lipids and attenuates atherosclerosis in mice.

Atherosclerotic cardiovascular disease remains the leading cause of global mortality, with hypercholesterolemia serving as a critical driver of atherogenesis. Although current lipid-lowering therapies substantially improve circulating lipid profiles, strategies that provide more durable, safe, and efficient control of lipid metabolism are still needed. Epigenome editing offers a promising approach for long-lasting repression of disease-modifying genes without altering the underlying DNA sequence. Here, we develop CRISPRoff platforms delivered by adeno-associated virus or lipid nanoparticle to epigenetically silence hepatic Hmgcr or Pcsk9 in vivo. In both C57BL/6J wild-type and ApoE-/- mice, CRISPRoff mediates robust and durable repression of these targets, leading to marked reductions in circulating total cholesterol, low-density lipoprotein cholesterol, and triglycerides. In the ApoE-/- context, epigenetic silencing of Pcsk9 confers pronounced vascular protection, including decreased lipid accumulation in the liver and aortic root, reduced necrotic core formation, diminished macrophage infiltration, and enhanced plaque stability. Together, these results provide proof of principle that CRISPRoff-based epigenome editing enables stable repression of clinically relevant targets and ameliorates key features of atherosclerotic disease. This work lays the foundation for broader therapeutic applications of epigenetic modulation in cardiovascular disorders.

Animals↗
PubMed2026

The effect of dexmedetomidine in mechanically ventilated patients with sepsis and septic shock: a meta-analysis of randomized controlled trials.

PURPOSE: Dexmedetomidine (DEX) is a central sympatholytic with sedative properties widely used in critically ill patients. However, its effects in patients with sepsis and septic shock remain controversial. This meta-analysis evaluated the efficacy and safety of DEX compared to other sedatives in mechanically ventilated patients with sepsis and septic shock. METHODS: A systematic search was conducted across PubMed, Embase, Scopus, and Cochrane Library from inception through May 1, 2025 for randomized controlled trials comparing DEX with other sedatives or placebo in mechanically ventilated patients with sepsis and septic shock. Primary outcomes included overall mortality and Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes encompassed duration of mechanical ventilation (MV), length of stay in Intensive Care Unit (ICU), incidence of hypotension and bradycardia. RESULTS: Fifteen studies involving 3,882 patients (1,945 in the DEX group, 1,937 in the control group) were included. DEX was demonstrated no significant differences compared to other sedatives or placebo in overall mortality (Risk Ratio [RR] 0.98, 95% Confidence Interval [CI] 0.90 to 1.07, p = 0.71, I2 = 0%), SOFA scores (Mean Difference [MD] - 0.14, 95% CI -0.81 to 0.52, p = 0.67, I2 = 0%), length of stay in ICU (MD -0.32, 95% CI -1.69 to 1.06, p = 0.65, I2 = 77%), or incidence of hypotension (RR 1.15, 95% CI 0.81 to 1.62, p = 0.44, I2 = 14%). However, DEX significantly reduced the duration of MV (MD -0.54, 95% CI -0.98 to -0.10, p = 0.02, I2 = 25%) but was associated with an increased incidence of bradycardia (RR 1.67, 95% CI 1.22 to 2.28, p = 0.001, I2 = 0%). CONCLUSIONS: In mechanically ventilated patients with sepsis and septic shock, DEX shortened duration of MV but was associated increased bradycardia risk. No mortality or organ dysfunction benefits were observed. These findings suggest DEX is a reasonable therapeutic option to facilitate earlier ventilator weaning in selected patients (particularly those without shock), but careful monitoring for cardiovascular adverse effects is warranted.

Humans↗
PubMed2026

Hidden Diversity in the Sands: Genomic Footprints of Pleistocene Refugia and Fragile Futures of the Turkestan Ground-Jay (Podoces panderi) in Central Asia.

The Turkestan ground-jay (Podoces panderi), a corvid endemic to Central Asia's deserts and steppes, exemplifies how extreme environments drive speciation. Our study provides the first comprehensive high-resolution genomic analysis of this species, using complete mitochondrial genomes (49 individuals) to decode its population structure and demographic past. Our analyses revealed three highly divergent genetic clusters with strong geographic structure. The P. p. iliensis population (Cluster_3) showed particularly pronounced genetic distinctiveness, with significant differentiation from P. p. panderi (Cluster_2 and Cluster_1) populations. This clear genetic separation supports the taxonomic validity of P. p. iliensis as a distinct evolutionary lineage. Demographic reconstruction indicated that Cluster_2 likely represents the ancestral group, with subsequent southward expansion into the Karakum region. The isolated P. p. iliensis population exhibited signatures of long-term isolation, including reduced genetic diversity and absence of recent gene flow with other clusters. These results provide strong evidence that P. p. iliensis represents a distinct evolutionary unit. The genetic structuring into three clusters reflects historical isolation in desert refugia during Pleistocene climatic fluctuations. Notably, we detected asymmetric gene flow among three clusters. These findings redefine P. panderi as a model for desert adaptation, where climatic extremes forged genetic fragmentation amid limited dispersal. Beyond taxonomy, our work highlights how aridification sculpted biodiversity in Asia's interior, urging conservation attention for these evolutionarily distinct lineages.

Animals↗
PubMed2025

Hematological diseases-related mucormycosis: A retrospective single center study.

BACKGROUND AND AIM: Mucormycosis is a life-threatening invasive fungal infection. This study aimed to analyze the clinical characteristics of patients with hematologic malignancies complicated with mucormycosis. METHODS: This retrospective study investigated the clinical characteristics, epidemiological features, treatment, and prognosis of 46 patients with hematological diseases and Mucor infection as indicated by mNGS from August 28, 2020 to September 11, 2023. Metagenomic next-generation sequencing (mNGS) refers to the application of high-throughput sequencing technology for the comprehensive analysis of nucleic acid content in patient samples, facilitating the detection and characterization of microbial DNA and/or RNA, and then comparing and analyzing the results with an information database to determine the types of pathogenic microorganisms present in the sample. RESULTS: The median age of admission for the included patients was 49 years (9-78). Multivariate analysis identified age over 60 years (p&#x2009;=&#x2009;0.006&#x2009;<&#x2009;0.05), high-dose corticosteroids (p&#x2009;=&#x2009;0.001&#x2009;<&#x2009;0.05), neutropenia lasting more than 10 days (p&#x2009;=&#x2009;0.041&#x2009;<&#x2009;0.05), and two or more Mucor infections (p&#x2009;=&#x2009;0.004&#x2009;<&#x2009;0.05) were independent risk factors for OS in patients with hematological diseases. Moreover, differences between groups were analyzed using the Fisher exact probability method, and no significant difference was observed in the efficacy of various types of antifungal therapies. CONCLUSION: Patients with hematologic malignancies benefit greatly from early diagnosis and treatment when suspected of Mucor infection. mNGS is an important supplementary method for early diagnosis of Mucor infection. Moderated use of corticosteroids, reducing the duration of neutropenia, and enhancing autologous immune function are important measures to reduce patient mortality rate.

Retrospective Studies↗
PubMed2025

Platelets sequester extracellular DNA, capturing tumor-derived and free fetal DNA.

Platelets are anucleate blood cells vital for hemostasis and immunity. During cell death and aberrant mitosis, nucleated cells release DNA, resulting in "cell-free" DNA in plasma (cfDNA). An excess of cfDNA is deleterious. Given their ability to internalize pathogen-derived nucleic acids, we hypothesized that platelets may also clear endogenous cfDNA. We found that, despite lacking a nucleus, platelets contained a repertoire of DNA fragments mapping across the nuclear genome. We detected fetal DNA in maternal platelets and cancer-derived DNA in platelets from patients with premalignant and cancerous lesions. As current liquid biopsy approaches utilize platelet-depleted plasma, important genetic information contained within platelets is being missed. This study establishes a physiological role for platelets that has not previously been highlighted, with broad translational relevance.

Female↗
PubMed2025

Habitat radiomics predicts occult lymph node metastasis and uncovers immune microenvironment of head and neck cancer.

BACKGROUND: Occult lymph node metastasis (LNM) is a key prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). This study was to establish radiomics models derived from intratumoral, peritumoral, and habitat regions for identifying occult LNM in HNSCC. METHODS: Patients with pathologically confirmed HNSCC from three medical Centers (from March 2014 to April 2024) and The Cancer Genome Atlas (TCGA) were enrolled. Center 1 was split into training (n&#x2009;=&#x2009;330) and internal test sets (n&#x2009;=&#x2009;154), while Center 2 and Center 3 served as the external test set (n&#x2009;=&#x2009;183). Genomic set (n&#x2009;=&#x2009;50) from TCGA and single-cell RNA sequencing set (n&#x2009;=&#x2009;6) from Center 1 were used for biological analysis. We used the intratumoral, peritumoral, and habitat volumes of interest (VOIs) to extract radiomics features, respectively. Based on Logistic Regression (LR), Support Vector Machine (SVM), and Random Forest (RF) classifiers, nine radiomics models were built to confirm the optimal predictive performance. The best-performing model, along with clinical-radiologic data, was combined to develop a hybrid model. The log-rank test was used to evaluate the model's prognostic performance. Additionally, bulk and single-cell RNA sequencing were applied for investigating the biological mechanisms underlying the optimal model. RESULTS: The RF-habitat radiomics model showed the best performance, achieving AUCs of 0.835-0.919 across all datasets. Survival analysis further confirmed the prognostic value of the RF-habitat radiomics model. The RF-habitat radiomics model and the hybrid model notably surpassed the clinical model in predictive performance. Moreover, the RF-habitat radiomics model was associated with the abundance level of exhaustion-associated CD8&#x2009;+&#x2009;T cells, uncovering the immune microenvironment characteristics contributing to occult LNM in HNSCC. CONCLUSIONS: The RF-habitat radiomics model demonstrated excellent performance for predicting occult LNM in HNSCC across three cohorts, providing a non-invasive solution for occult LNM. Furthermore, radiogenomic analysis further revealed the biological associations of the model, primarily related to T cell dysfunction.

Humans↗
PubMed2025

Rice transcription factor bHLH25 confers resistance to multiple diseases by sensing H2O2.

Hydrogen peroxide (H2O2) is a ubiquitous signal regulating many biological processes, including innate immunity, in all eukaryotes. However, it remains largely unknown that how transcription factors directly sense H2O2 in eukaryotes. Here, we report that rice basic/helix-loop-helix transcription factor bHLH25 directly senses H2O2 to confer resistance to multiple diseases caused by fungi or bacteria. Upon pathogen attack, rice plants increase the production of H2O2, which directly oxidizes bHLH25 at methionine 256 in the nucleus. Oxidized bHLH25 represses miR397b expression to activate lignin biosynthesis for plant cell wall reinforcement, preventing pathogens from penetrating plant cells. Lignin biosynthesis consumes H2O2 causing accumulation of non-oxidized bHLH25. Non-oxidized bHLH25 switches to promote the expression of Copalyl Diphosphate Synthase 2 (CPS2), which increases phytoalexin biosynthesis to inhibit expansion of pathogens that escape into plants. This oxidization/non-oxidation status change of bHLH25 allows plants to maintain H2O2, lignin and phytoalexin at optimized levels to effectively fight against pathogens and prevents these three molecules from over-accumulation that harms plants. Thus, our discovery reveals a novel mechanism by which a single protein promotes two independent defense pathways against pathogens. Importantly, the bHLH25 orthologues from available plant genomes all contain a conserved M256-like methionine suggesting the broad existence of this mechanism in the plant kingdom. Moreover, this Met-oxidation mechanism may also be employed by other eukaryotic transcription factors to sense H2O2 to change functions.

Hydrogen Peroxide↗
PubMed2007

Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells.

Islet cell replacement is considered as the optimal treatment for type I diabetes. However, the availability of human pancreatic islets for transplantation is limited. Here, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin-producing cells by introduction of the pancreatic duodenal homeobox-1 (PDX-1). Recombinant adenoviral vector was used to deliver PDX-1 gene into hMSCs. After being infected with Ad-PDX-1, hMSCs were successfully induced to differentiate into insulin-secreting cells. The differentiated PDX-1+ hMSCs expressed multiple islet-cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C-peptide in a weak glucose-regulated manner. After the differentiated PDX-1+ hMSCs were transplanted into STZ-induced diabetic mice, euglycemia can be obtained within 2 weeks and maintained for at least 42 days. These findings validate the hMSCs model system as a potential basis for enrichment of human beta cells or their precursors, and a possible source for cell replacement therapy in diabetes.

Adenoviridae↗
PubMed2007

[Effect of p53 on the variation of renal tubular epithelial cells after kidney ischemia/reperfusion injury].

AIM: To observe the variation of renal tubular epithelial cells in p53(+/+) and p53(-/-) mice with young or old age at different time after kidney ischemia/reperfusion injury (IRI), and to investigate the contribution of p53 gene in the variation. METHODS: p53(+/+) and p53(-/-) male mice at age of 2 and 12 months were made ischemic by clamping left renal hila for 45 min. At 0, 1, 3 and 7 d, 1, 3 and 6 month after reflow, renal tissues were processed for morphometric observation and proliferating cell nuclear antigen(PCNA), apoptosis and senescence-associated beta-galactosidase (SA-beta-gal) analysis, using hematoxylin and eosin stain, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick-end labeling (TUNEL) and histochemical staining, respectively. RESULTS: Renal tubule necrosis was more severely in p53(-/-) mice and aged mice compared to p53(+/+) mice and young mice (P<0.05), respectively. Apoptotic cells in p53(+/+) mice increased obviously compared to p53(-/-) mice (P<0.05) at 7 d after IRI. In young wild-type mice, occasionally faint staining for SA-beta-gal activity began to appear at 1 month, and obviously significantly increased at 3 and 6 months after IRI (P<0.05), but in contralateral kidney at any time as mentioned above, and in the IRI kidneys in p53(-/-) mice at 1 and 3 months, there was almost no positive staining for SA-beta-gal; occasionally positive staining for SA-beta-gal was observed in the IRI kidney in p53(-/-) mice at 6 months after IRI. In p53 (-/-) and p53(+/+) aged mice, both kindeys had positive staining for SA-beta-gal activity at 0 d after IRI, but the level of the activity in p53(-/-) mice was much more lower than that in p53(+/+) mice (P<0.05), then the level of the activity decreased notably at 1 d in the IRI kidney (P<0.05). Positive stain of nuclear PCNA in p53(+/+) young mice had no statistical significance compared to p53(+/+) aged mice (P>0.05). But in p53(-/-) mice, significant positive staining for PCNA was tested, especially in young mice and in IRI kidneys (P>0.05). Correlation analysis between senescent and apoptotic cells in aged mice was made at 1 d after IRI, then striking negative correlation was found between both of them in p53(+/+) mice (r=-0.82, P<0.05), but no statistical correlation in p53(-/-) mice (r=0.26, P>0.05). CONCLUSION: IRI can accelerate renal tubular cell senescence and cellular death(both necrosis and apoptosis)after that. p53 gene may play an important role in the variation of tubular epithelial cells after kidney IRI.

Animals↗
PubMed2006

Opposite patterns of hemisphere dominance for early auditory processing of lexical tones and consonants.

In tonal languages such as Mandarin Chinese, a lexical tone carries semantic information and is preferentially processed in the left brain hemisphere of native speakers as revealed by the functional MRI or positron emission tomography studies, which likely measure the temporally aggregated neural events including those at an attentive stage of auditory processing. Here, we demonstrate that early auditory processing of a lexical tone at a preattentive stage is actually lateralized to the right hemisphere. We frequently presented to native Mandarin Chinese speakers a meaningful auditory word with a consonant-vowel structure and infrequently varied either its lexical tone or initial consonant using an odd-ball paradigm to create a contrast resulting in a change in word meaning. The lexical tone contrast evoked a stronger preattentive response, as revealed by whole-head electric recordings of the mismatch negativity, in the right hemisphere than in the left hemisphere, whereas the consonant contrast produced an opposite pattern. Given the distinct acoustic features between a lexical tone and a consonant, this opposite lateralization pattern suggests the dependence of hemisphere dominance mainly on acoustic cues before speech input is mapped into a semantic representation in the processing stream.

Acoustic Stimulation↗
PubMed2006

Expression of semaphorin 6D in gastric carcinoma and its significance.

AIM: To investigate the protein and mRNA expression of semaphorin 6D in gastric carcinoma and its significance. METHODS: The protein and mRNA expression of semaphorin 6D was detected by semi-quantitative reverse transcription PCR and Western blotting respectively in 30 cases of gastric carcinoma and normal gastric mucosa. RESULTS: The protein and mRNA expression of semaphorin 6D in gastric carcinoma was significantly higher than that in normal gastric mucosa (0.24 +/- 0.06 vs 0.19 +/- 0.07, 0.26 +/- 0.09 vs 0.20 +/- 0.10, P < 0.05). CONCLUSION: Semaphorin 6D may play an important role in the occurrence and development of gastric carcinoma, and is related to tumor angiogenesis.

Adult↗
PubMed2006

Genome-wide atlas of gene expression in the adult mouse brain.

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

Animals↗
PubMed2006

Forced running enhances neurogenesis in the hippocampal dentate gyrus of adult rats and improves learning ability.

To investigate the effect of forced running in motor-driven wheel on neurogenesis in the hippocampal dentate gyrus (DG) of adult rats, 5-bromo-2-deoxyuridine (BrdU), a thymidine analog was applied to mark cell proliferation. Neuroepthelial stem cell protein (nestin) expression was used to identify neural stem/precursor cells. The BrdU- and nestin-positive cells were examined by immunohistochemical technique. The ability of learning was evaluated by Y-maze test to explore the functional role of the newborn cells in the DG after forced running. It was found that the number of BrdU- and nestin-positive cells in the DG in running groups was significantly increased compared to that in the control group (P<0.05). The effect of forced running on neurogenesis was intensity-dependent. In addition, an improvement of learning ability in Y-maze test was observed after forced running. These findings suggest that forced running in motor-driven wheel could enhance neurogenesis in the hippocampal DG of adult rats and improve learning ability.

Animals↗