Biomedical subjects

Min Liu

Publications and source records attributed to Min Liu.

9 recordsLinked to original sources

PubMed2026

Comparison of Keverprazan-based versus esomeprazole-based dual therapy for initial treatment of Helicobacter pylori infection: a prospective, multicenter, randomized controlled trial.

BACKGROUND: Keverprazan offers a new perspective for Helicobacter pylori eradication. This study compared 14-day keverprazan-amoxicillin therapy with esomeprazole-amoxicillin therapy to explore a superior treatment strategy. METHODS: This was a prospective, open-label, multicenter, randomized controlled trial in adult patients with treatment-naive H. pylori infection. Participants were randomly assigned to receive either 14-day of KA therapy (Keverprazan 20 mg b.i.d plus amoxicillin 1 g t.i.d) or 14-day of EA therapy (Esomeprazole 40 mg b.i.d plus amoxicillin 1 g t.i.d). The primary outcome was the H. pylori eradication rate. Secondary outcomes were the incidence of adverse events and patient adherence. RESULTS: A total of 264 patients were enrolled in the study. In the intention-to-treat (ITT) analysis, the eradication rates for the 14-day KA group and the 14-day EA group were 87.9% and 80.3%, respectively (p = 0.092); in the modified intention-to-treat (mITT) analysis, the eradication rates were 92.1% and 86.2%, respectively (p = 0.135); and in the per-protocol (PP) analysis, the eradication rates were 93.5% and 88.3%, respectively (p = 0.155). Non-inferiority was confirmed between the two groups (all p < 0.001). Adverse events and patient adherence were similar between the two groups. CONCLUSION: For treatment-naive H. pylori infection, the 14-day KA therapy is non-inferior to EA therapy. Given its good tolerability, pharmacogenomic independence, and potent acid suppression, KA is a rational first-line alternative to EA in the Chinese population.

Humans↗

PubMed2026

Sex- and development-specific transcriptomic profiling of venom and silk genes in the wolf spider Pardosa astrigera provides insights into ecological adaptation and predatory strategies.

Spider venom and silk glands are two major secretory systems that contribute to prey capture, defense, and reproduction, but their sex- and development-specific molecular regulation in wandering wolf spiders remains poorly understood. Here, the transcriptome of Pardosa astrigera, an important agricultural natural enemy in China, revealed significant sex- and development-associated molecular differentiation among adult females, adult males, and spiderlings. A total of 100,025 unigenes were obtained, of which 23,852 were functionally annotated, providing a comprehensive transcriptomic resource for this species. Differential expression patterns showed marked variation among groups, with 531, 1792, and 832 DEGs detected in PAF vs PAS, PAM vs PAS, and PAF vs PAM, respectively. These genes were mainly associated with metabolic, oxidation-reduction, cuticle development, MAPK signaling, and lysosome pathways. Fifteen co-expression modules revealed distinct expression patterns. The turquoise, pink, yellow, and red modules were development-related, whereas the blue module was male-biased. Venom- and spidroin-related genes were distributed across multiple modules, suggesting coordinated regulation. Overall, 42 venom peptides, 21 venom proteins, and 11 spidroins were identified. Representative genes showed strongly biased expression, including spiderling-biased U3_Pp1a and U5_Pp1e, female-biased U4_Pp1a, and male-biased SMase D_108750 and PaTuSp_108466. These findings reveal sex- and development-biased expression patterns of venom- and silk-related candidate genes in P. astrigera and may provide molecular insights into ecological adaptation and predatory strategies in wandering wolf spiders.

Animals↗

PubMed2026

Comparison of short-term clinical outcomes and patient satisfaction between intraoral scanning and conventional impressions for complete-arch implant prostheses: a pilot RCT.

OBJECTIVE: To compare framework passive fit, subjective evaluations, and short-term clinical outcomes between conventional impressions (CI) and intraoral scanning (IOS) for complete-arch implant-supported fixed dental prostheses (CIFDPs). METHODS: In this randomized controlled trial, 22 patients were allocated to the CI or IOS groups. All participants received a definitive one-piece CIFDP. The primary outcome was framework passive fit, assessed using the Vision and Tactile Score (V&T score), which included framework lift-off, the single-screw test, the full-screw test, smoothness of screw insertion, and radiographic gap assessment. Secondary outcomes included operator evaluation, patient satisfaction using a visual analog scale (VAS), early implant survival, marginal bone loss (MBL), modified Plaque Index (mPII), and complications at the 6-month follow-up. RESULTS: Twenty-two patients were enrolled (CI: n = 11; IOS: n = 11), and one patient in the CI group was lost to follow-up. No statistically significant difference in the V&T score was observed between the CI and IOS groups (4.66 ± 0.17 vs. 4.65 ± 0.28; P = 0.93). The operator reported greater nervousness during the CI procedure than during IOS (21.82 ± 15.69 vs. 8.64 ± 7.47; P < 0.05). Patients in the CI group reported significantly greater discomfort, including nausea and anxiety, than those in the IOS group (P < 0.05). At the 6-month follow-up, the early implant survival rate was 100% in both groups. No significant differences were found between the groups in MBL (0.09 ± 0.09 vs. 0.06 ± 0.10 mm; P = 0.43) or mPII (0.10 ± 0.12 vs. 0.10 ± 0.28; P = 0.99). CONCLUSION: IOS and CI achieved comparable short-term clinical outcomes in patients who met the predefined inclusion criteria, including controlled implant number, spacing, and angulation. IOS provided a more favorable experience for both operators and patients. CLINICAL SIGNIFICANCE: In complete-arch implant restorations, intraoral scanning may provide clinical outcomes comparable to those of conventional impressions while improving patient comfort.

Humans↗

PubMed2026

Mycobacterium tuberculosis MEM39 (Rv1977) hijacks host aldolase A (ALDOA) to subvert immunometabolism to facilitate bacterial intracellular survival.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is the leading cause of infectious disease-related death. As a major intracellular pathogen, Mtb can escape clearance by the immune system, but the underlying molecular mechanisms remain incompletely elucidated. Specific genomic regions of deletion (RD)-encoded proteins in virulent Mtb H37Rv have been implicated in modulating pathogenicity and immunity. Here, we report a novel RD15-encoding protein, Rv1977 (a mycobacterial cell wall protein with a size of 39 kDa, named MEM39), which facilitates Mtb survival in macrophages. The survival of the Mtb H37Rv MEM39-deficient strain is reduced in both macrophage and murine infection models. Furthermore, the mycobacterial MEM39 protein binds fructose-diphosphate aldolase A (ALDOA), a key enzyme of glycolysis, thereby impairing ALDOA enzyme activity, disrupting macrophage metabolite flux, and reducing lactate production. The MEM39-ALDOA interaction also suppresses lysosomal acidification; reduces NLRP3 inflammasome activation and the production of proinflammatory cytokines (TNF-α, IL-6 and IL-1β); and thereby promotes bacterial survival within macrophages. Disruption of the interaction between MEM39-ALDOA and a cell-penetrating synthetic peptide (VLARYASICQ) significantly suppressed Mtb survival by restoring lactate production, lysosome acidification and proinflammatory cytokine production in both macrophage and mouse infection models. These findings revealed that mycobacterial MEM39 negatively regulates host immune defense through reprogramming ALDOA-mediated glycolysis in macrophages, thereby forming a "mycobacterial MEM39 virulence factor-glycolysis metabolism-immunity" regulatory axis. Targeting MEM39 or the MEM39-ALDOA interaction interface holds promise as a new therapeutic strategy against tuberculosis.

Mycobacterium tuberculosis↗

PubMed2026

A CRISPR-Cas9 screen identifies LAPTM4A (lysosomal protein transmembrane 4 alpha) as a key host barrier against PRRSV infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) manipulates host intracellular processes, particularly macroautophagy/autophagy and lysosomal function, to facilitate its replication and spread. However, the precise host factors and molecular mechanisms by which PRRSV remodels the autophagy-lysosome axis remain poorly defined. Here, we performed a CRISPR-Cas9 knockout screen targeting 1,332 genes involved in protein degradation, metabolism, and vesicular trafficking, and identified LAPTM4A (lysosomal protein transmembrane 4 alpha) as a critical antiviral factor involved in the lysosomal pathway. A yeast two-hybrid screen identified LAPTM4A as an interactor of PRRSV GP5 (glycoprotein 5). Mechanistically, GP5 recruits the E3 ubiquitin ligase NEDD4 and the autophagy receptor SQSTM1/p62 to promote K63-linked polyubiquitination of LAPTM4A, leading to its autophagic degradation. This selective degradation activates the AMPK-ULK1-MAP1LC3/LC3 signaling cascade, initiating autophagy while facilitating MTOR-lysosome colocalization, thereby suppressing TFEB nuclear translocation and transcription of lysosome-related genes. The resulting incomplete autophagic flux enhances viral replication. Additionally, in terms of host defense, LAPTM4A maintains lysosomal homeostasis by restraining excessive autophagy through AMPK-ULK1-LC3 signaling and promoting TFEB-dependent lysosomal gene expression by impairing the binding of RPTOR/raptor to MTOR, thus providing broad antiviral protection against multiple RNA viruses. Collectively, our findings identify LAPTM4A as a central regulator of lysosome-autophagy homeostasis and reveal a viral strategy that dismantles this defense axis to facilitate infection.Abbreviations: ATG5: autophagy related 5; AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; Baf A1: bafilomycin A1; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DMVT library: protein degradation, metabolism, and vesicular trafficking library; LAPTM4A: lysosomal protein transmembrane 4 alpha; MAGeCK: model-based analysis of genome-wide CRISPR-Cas9 knockout; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; NC: negative control; PAMs: porcine alveolar macrophages; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PRRSV: porcine reproductive and respiratory syndrome virus; qRT-PCR: quantitative real-time PCR; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID50: 50% tissue culture infective dose; TFEB: transcription factor EB; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; WT: wild type.

Animals↗

PubMed2026

A single-nucleus and spatial transcriptomic atlas of poplar leaves reveals the regulation of leaf polarity and cuticle deposition.

Leaf adaxial-abaxial polarity is fundamental for plant morphogenesis and environmental adaptation through asymmetric cell differentiation. Emerging evidence reveals dorsoventral metabolic gradients act downstream of transcriptional networks to fine-tune cellular specialization. While conserved transcription factors (e.g., HD-ZIP III and KANADI) establish initial polarity, the molecular networks driving position-specific cellular differentiation and their integration with metabolic adaptation remain unclear. Leveraging single-nucleus and spatial transcriptomics, we resolve major cell classes (mesophyll, epidermal, and vascular-associated) and their adaxial-abaxial subtypes, revealing dorsoventral polarity in transcriptional profiles and metabolic pathways. Adaxial cells are enriched in phenylpropanoid/flavonoid biosynthesis, while abaxial cells show preferential activation of stress and hormone signaling. Notably, we identify MYC2 as a key regulator of adaxial cuticle biosynthesis, binding to promoters of lipid biosynthetic and transport genes (e.g., CER10 and LTPG1) and promoting cuticle thickening. Our study uncovers how positional identity shapes transcriptional and metabolic polarity in leaves, with MYC2 emerging as a central regulator coordinating organ-specific adaptations. These findings provide insights into the spatial regulation of plant development and stress resilience, offering potential strategies for engineering stress-tolerant woody crops.

Plant Leaves↗

PubMed2025

Engineering TME-activated CD47-specific CAR macrophage via Arg1 promoter for safe and effective solid tumor immunotherapy.

BACKGROUND: Chimeric antigen receptor macrophage (CAR-Mφ) therapy has promising therapeutic potential in solid tumors, yet challenges remain in target compatibility and systemic toxicity. METHODS: In this study, we screened the CD47-scFv sequence of CAR-Mφ as the extracellular structure. We then constructed a classical CD47 CAR-Mφ incorporated the costimulatory domain of the α1β1 integrin-mediated Fc-gamma receptor I (FcγRI) signaling component. Subsequently, we developed a tumor microenvironment (TME)-responsive CAR macrophage platform by the arginase 1 (Arg1) promoter to target CD47, a highly expressed but clinically challenging immune checkpoint in solid tumors. RESULTS: We found that anti-CD47-scFv-mediated macrophages can effectively kill tumor cells both in vivo and in vitro. Furthermore, by integrating an α1β1 integrin-mediated FcγRI signaling domain, CD47 CAR-Mφ exhibited superior antitumor activity in hCD47+4T1 and SGC-7901 cells in vitro, which demonstrated that the CD47 CAR-Mφ was effective against solid tumors. Subsequently, Arg1-mediated activated pArg1 CD47 CAR-Mφ exhibited strong cytotoxicity against target cancer cells. We further demonstrated TME-controllable CAR gene expression in situ and induced a significant regression of established tumors in vivo. Besides, TME-dependent activation of CD47 CAR Mφ reduced the cytotoxic killing effect on erythrocytes. CONCLUSIONS: Our findings confirmed that the TME-specific activation mechanism of pArg1 CD47 CAR-Mφ based on intrinsic Arg1 promoter reprogramming endowed CAR-Mφ to effectively mitigate erythrocyte toxicity while enabling safe multidose administration regimens. This Trojan horse-like CAR-Mφ system achieves tumor-specific activation while minimizing systemic toxicity, offering a novel strategy to expand CAR-Mφ applications for solid tumors.

Animals↗

PubMed2025

Proteomic insights into platelet dysregulation and pathogenic mechanisms of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Undissolved thrombus blocks the pulmonary arteries in chronic thromboembolic pulmonary hypertension (CTEPH), a potentially fatal illness that raises pulmonary resistance, causes right heart failure, and even results in death. Although platelets are linked to vascular dysfunction and thrombus formation, it is yet unknown what precise proteome alterations and mechanistic roles they play in CTEPH. METHODS: We extracted platelet-rich plasma from peripheral blood and separated the plasma to obtain enriched platelet pellet (EPP). Quantitative proteomics was used to examine EPP from CTEPH patients and healthy controls using mass spectrometry. The relationship between protein levels and clinical markers of right heart function was examined. Platelet activity, morphology, and interactions with other blood components were evaluated using transmission electron microscopy, immunofluorescence, and flow cytometry. RESULTS: The proteomic investigation found that 179 proteins were differentially expressed in CTEPH patients. The analysis revealed that these proteins were involved in crucial processes such as complement and coagulation cascades, phagosome, and neutrophil extracellular trap (NET) formation. Elevated proteins, specifically NOX2, PAD4, ITGB2, and HMGB1, have been associated to platelet-neutrophil aggregates and NET formation. In addition, enhanced P-selectin expression in platelets and plasma confirmed greater platelet activation in CTEPH patients. Notably, PAD4 and NOX2 levels showed a substantial correlation with hemodynamic parameters and right heart dysfunction. MPO-DNA, a NET marker associated with P-selectin and ITGB2 expression, was discovered in higher concentrations in CTEPH patients' plasmas. CONCLUSION: Platelet aggregation and activation in CTEPH encourage the formation of NETs, which advances the disease and prolongs thrombus. Right heart insufficiency and hemodynamic markers had a strong correlation with PAD4 and NOX2 levels, indicating that these biomarkers may be employed to assess the severity and prognosis of CTEPH disease and offer a fresh approach to targeted treatment. The results highlight the need for additional study to elucidate platelet-mediated pathways and create therapies for CTEPH that target platelets.

Humans↗

PubMed2025

Tandem gene duplication facilitates intertidal adaptation in atypical mangrove plants.

Mangrove plants, originating from inland ancestors, have independently adapted to extreme intertidal zones characterized by salt and hypoxia stress. While typical mangroves exhibit specialized phenotypes, like viviparous seeds and salt secretion, atypical clades that have thrived without such traits are particularly suitable for exploring the molecular and physiological basis underlying plant adaptation to intertidal zones. We assembled a chromosome-level genome of an atypical mangrove, Scyphiphora hydrophylacea, the only mangrove species in Gentianales. Similar to other mangroves, S. hydrophylacea colonized intertidal zones during climatic optimum periods of sea-level rise. Despite lacking recent whole-genome duplications (WGDs), its genome acquired extensive tandem gene duplications (TDs), leading to the rapid expansion of key salt- and hypoxia-related genes. Transcriptome data further corroborated that TD-driven gene expansions contribute to stress tolerance. Specifically, the expansion of genes involved in cation transmembrane transport, osmotic regulation, and oxidative stress response may enhance salinity tolerance, and the expansion of signal transduction and energy metabolism genes in hypoxia-response pathways may confer waterlogging tolerance. Therefore, in the absence of large-scale gene duplication, the rapid expansion of core genes involved in salt and hypoxia tolerance through tandem duplication may represent a key force driving the adaptation of atypical mangroves. These findings also provide valuable insights for crop improvement strategies aimed at enhancing environmental resilience while maintaining phenotypic stability.

Gene Duplication↗