Life Sciences[JOURNAL]
Sun
200 papers
ACAT3 controls hepatic cholesterol metabolism and modulates systemic energy homeostasis of male mice.
Ma Z, Chen Q, Zhang J … +11 more , Huang Z, Wu Q, Shi T, Liu X, Shu H, Ma Y, Cheng K, Zhang C, Jia Z, Feng Y, Jiang C
Life Sci · 2026 Sep · PMID 42264322 · Publisher ↗
AIMS: Acetyl coenzyme A acetyltransferase (ACAT) family enzymes catalyses the conversion of acetyl-CoA into acetoacetyl-CoA that provides the substrate for ketone and cholesterol biosynthesis. In the present study, we ai...
AIMS: Acetyl coenzyme A acetyltransferase (ACAT) family enzymes catalyses the conversion of acetyl-CoA into acetoacetyl-CoA that provides the substrate for ketone and cholesterol biosynthesis. In the present study, we aimed to assess the function of hepatic ACAT3 in cholesterol and bile acid homeostasis, and its effects on systemic energy metabolism. MATERIALS AND METHODS: We used genetic overexpression and knockout (KO) mouse models to liver-targeted access the function of ACAT3 in mouse liver. We then applied multiple analysis to investigate the changes in morphology, physiology, histology and molecular levels of the mice. KEY FINDINGS: Acat3 is highly expressed in liver tissue of mice and its expression levels are downregulated during obesity, diabetes and aging. Hepatic Acat3 overexpression reduces body weight, fat mass and promotes glucose metabolism in mice. Mice with Acat3 overexpression have reduced serum lipid concentrations and adipose tissue weight. While Acat3 overexpression changed hepatic Cholesterol metabolic signaling and bile acid composition. Global and liver-specific (Acat3) Acat3 KO mice have reduced lean mass and energy expenditure. Liver-specific Acat3 KO reduces body weight, disrupts the gut microbiota and hepatic bile acid composition. SIGNIFICANCE: Both overexpression and knockout of Acat3 lead to changes in hepatic cholesterol metabolic pathway, which alters bile acid synthesis and composition. These alterations in bile acid profiles subsequently influence intestinal microbiota, thereby modulating systemic energy homeostasis of mice. Modulation of ACAT3 or its downstream mechanisms alters bile acid profiles to improve glucose and lipid metabolism and develop new therapeutic strategies for clinical applications.
Pharmacological effects of nebivolol on endothelial response in a preeclampsia in vitro model.
Bueno-Pereira TO, de Andrade AD, Zampieri GM … +2 more , Nunes PR, Sandrim VC
Life Sci · 2026 Sep · PMID 42264321 · Publisher ↗
UNLABELLED: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by systemic endothelial dysfunction and a profound anti-angiogenic state driven by elevated soluble fms-like tyrosine kinase-1 (sF...
UNLABELLED: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by systemic endothelial dysfunction and a profound anti-angiogenic state driven by elevated soluble fms-like tyrosine kinase-1 (sFlt-1). While the third-generation β-AR nebivolol promotes vasodilation partially via receptor β-AR activation, whether its protective effects can reverse the complex anti-angiogenic and hypoxic stress of PE remains unclear. AIMS: This study aimed to determine the functional and molecular effects of nebivolol in a PE-like endothelial microenvironment and to understand the specific contribution of β-AR. MATERIAL AND METHODS: Endothelial cells exposed to chemical hypoxia and 10% plasma from women with early-onset PE were treated with nebivolol, the selective β-AR agonist CL316,243, or the β-AR antagonist L-748,337. We quantified sFlt-1 secretion, evaluated the transcription of key angiogenic, vasoactive, and cytoprotective genes, and assessed cell migration using migration and transwell assays. KEY FINDINGS: Nebivolol selectively modulated specific components of the PE phenotype, reducing sFlt-1 secretion, downregulating VEGFR2 and EDN1, and upregulating HMOX1. Conversely, it significantly inhibited endothelial cell migration. Crucially, selective β-AR activation via CL316,243 failed to mirror these integrated responses, and β-AR antagonism did not reverse nebivolol's actions. SIGNIFICANCE: We conclude that nebivolol's protective effects in a PE-like environment do not depend primarily on β-AR activation, but rather reflect a broader, pleiotropic vascular pharmacological profile. Translating these results clinically suggests that targeting single-receptor pathways may be insufficient in the complex environment of PE, positioning multi-target agents like nebivolol as candidates for modulating endothelial dysfunction in gestational hypertensive disorders.
Trimethylamine N-oxide drives cardiac aging by activating NLRP3-mediated pyroptosis.
Qiu Z, Zhang H, Tan B … +12 more , Chen Q, Gao H, Yao Y, Peng Y, Xue H, Guo Q, Tian D, Xiao L, Teng X, Ma Y, Wu Y, Jin S
Life Sci · 2026 Sep · PMID 42264141 · Publisher ↗
AIMS: The present study was aimed to investigate whether trimethylamine N-oxide (TMAO) contributed to cardiac aging and to explore the underlying mechanism. MATERIALS AND METHODS: Male C57BL/6 J mice were randomly divide...
AIMS: The present study was aimed to investigate whether trimethylamine N-oxide (TMAO) contributed to cardiac aging and to explore the underlying mechanism. MATERIALS AND METHODS: Male C57BL/6 J mice were randomly divided into four age groups (3, 12, 18, and 24 months) to assess the cardiac function. Markers of senescence, oxidative stress, and the protein expression of pyroptosis were also measured. To test the hypothesis that TMAO promoted cardiac aging, 8-week-old mice were intraperitoneally injected with TMAO for 1-3 months and 3,3-dimethyl-1-butanol was administered in drinking water starting from 15 months of age for three months to inhibit TMAO production. Gasdermin D (GSDMD) knockout mice were also used. KEY FINDINGS: Plasma TMAO levels increased with age and correlated with upregulation of cardiac senescence markers, diastolic dysfunction, cardiac fibrosis, and elevated plasma brain natriuretic peptide levels. Starting from 2 months of TMAO treatment, impairment of cardiac diastolic function and progression of cardiac fibrosis were observed alongside the upregulation of senescence marker proteins expression. Mechanistically, TMAO promoted cardiac oxidative stress and activated the NLRP3-mediated pyroptosis pathway. Genetic ablation of GSDMD abolished TMAO-associated cardiac aging. Furthermore, pharmacological inhibition of TMAO production in aged mice attenuated oxidative stress, suppressed NLRP3-mediated pyroptosis activation, and alleviated cardiac aging. SIGNIFICANCE: This study revealed that plasma TMAO levels progressively increase with age in mice and TMAO contributed to cardiac aging in a time-dependent manner through NLRP3-mediated pyroptosis driven by oxidative stress. Moreover, the inhibition of TMAO generation might offer a basis for future therapeutic strategies.
CAD drives Angiotensin II-induced vascular smooth muscle cell activation via upregulation of pyrimidine biosynthesis and rRNA synthesis.
Park MJ, Kim D, Park KG … +3 more , Jeong GH, Byun JK, Choi YK
Life Sci · 2026 Sep · PMID 42264140 · Publisher ↗
AIMS: Vascular smooth muscle cell (VSMC) phenotypic switching is a hallmark of vascular remodeling in diseases such as restenosis and atherosclerosis. Although Angiotensin II (Ang II) promotes VSMC proliferation and migr...
AIMS: Vascular smooth muscle cell (VSMC) phenotypic switching is a hallmark of vascular remodeling in diseases such as restenosis and atherosclerosis. Although Angiotensin II (Ang II) promotes VSMC proliferation and migration through various signaling pathways, the role of nucleotide metabolism remains poorly understood. This study investigates the functional significance of CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase), a rate-limiting enzyme in de novo pyrimidine biosynthesis, in Ang II-induced VSMC activation and pathological vascular remodeling. MATERIALS AND METHODS: Primary VSMCs were stimulated with Ang II to induce phenotypic switching. A mouse carotid artery ligation model was used to study neointimal hyperplasia in vivo. VSMC proliferation and migration were assessed via EdU incorporation and Transwell assays, respectively. The functional role of CAD expression was interrogated through pharmacological inhibition and gene silencing. Molecular mechanisms, including ribosomal RNA (rRNA) synthesis and protein translation, were analyzed using Western blotting and qPCR. KEY FINDINGS: Ang II stimulation and vascular injury significantly increased CAD expression and phosphorylation. This activation enhanced rRNA synthesis and translation of remodeling-associated proteins, including intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9). Uridine supplementation rescued phenotypic defects caused by CAD silencing, confirming that pyrimidine biosynthesis sustains the pathological VSMC phenotype. Furthermore, CAD inhibition attenuated Ang II-induced VSMC proliferation and migration in vitro and reduced neointimal hyperplasia in vivo. SIGNIFICANCE: Our findings identify nucleotide metabolism as a central determinant of VSMC pathology. By linking biosynthetic signaling to translational control, CAD represents a promising therapeutic target for proliferative vascular diseases.
HDAC2-mediated H3K27ac Governs ZFP42 transcription and autophagy in granulosa cells of pigs.
Liao W, Li N, Jiang Y … +5 more , Huang E, Mao K, Ma B, Zhao J, Yuan X
Life Sci · 2026 Sep · PMID 42264139 · Publisher ↗
AIMS: Histone deacetylation regulates mammalian follicular development via ovarian granulosa cells (GCs) autophagy, but the underlying mechanisms remain largely unknown. This study aimed to elucidate the epigenetic role...
AIMS: Histone deacetylation regulates mammalian follicular development via ovarian granulosa cells (GCs) autophagy, but the underlying mechanisms remain largely unknown. This study aimed to elucidate the epigenetic role of HDAC2 in GC autophagy and follicular development through ZFP42. MATERIALS AND METHODS: HDAC2 knockdown combined with autophagy detection were performed to identify the effect of HDAC2 on autophagy and ZFP42 in GCs. Subsequently, chromatin accessibility assay and CRISPR/dCas9-P300 epigenetic editing were used to explore the molecular mechanism that HDAC2 regulates the expression of ZFP42. Finally, In vitro and in vivo methods were applied to evaluate the functional effects of ZFP42 on autophagy and follicular development. KEY FINDINGS: Knockdown of HDAC2 Induces autophagy in GCs. ZFP42 protein level dynamically decreased during follicular development. Chromatin accessibility assay and CRISPR/dCas9-P300 editing revealed that HDAC2 dynamically altered H3K27ac occupancy at the promoter of ZFP42 to activating transcriptional activation of ZFP42. Functionally, ZFP42 protein interacted with the autophagic marker Beclin1 to modulate autophagy. Moreover, ZFP42 promoted GC autophagy and apoptosis to decrease serum estradiol (E2) levels and block follicular development in vivo. SIGNIFICANCE: These results provided mechanistic insights into ovarian follicle development, and proposed ZFP42 as a potential therapeutic target for autophagy-related reproductive disorders.
STELLA: a spatial transcriptomics framework for microenvironment decoding using dynamic graph neural networks.
Wang M, Zhang Z, Zhang X … +6 more , Wang Z, Dai R, Chen Z, Lei L, Li Z, Guo Q
Sci China Life Sci · 2026 Jun · PMID 42258138 · Publisher ↗
Spatial transcriptomics technology can analyze gene expression while retaining spatial information, but it is still challenging to accurately identify spatial domains and decode intercellular communication networks. This...
Spatial transcriptomics technology can analyze gene expression while retaining spatial information, but it is still challenging to accurately identify spatial domains and decode intercellular communication networks. This study proposes the STELLA framework, which integrates dynamic graph neural networks and self-supervised learning strategies to analyze spatial transcriptome data. STELLA constructs a complementary space-feature dual-graph structure, optimizes connection weights through dynamic adjacency matrix learning, and independently encodes spatial and expression information through a dual-channel graph convolutional network. The multi-head attention mechanism adaptively integrates different information sources, and feature permutation contrast learning improves representation discrimination capabilities. In a systematic evaluation across multi-platform datasets, STELLA accurately identified the tumor-muscle interface region in zebrafish melanoma, suggesting a potential association between the MT-CO1-mediated mitochondrial electron transport pathway and invasion front processes. It also identified immune aggregation areas in intestinal tissues and implicated the cyclosporin A signaling pathway in the FDCSP S4 stromal cell microenvironment. Additionally, STELLA detected that PERIOSTIN and MHC-II form a central-peripheral bidirectional regulatory network with complementary directionality in the mouse striatum. Finally, it analyzed the transition from WSN-mediated early stress response to reaEGC-mediated tissue reconstruction during axolotl brain regeneration.
The DNA-binding protein PfAP2-V regulates erythrocyte invasion and pathogenesis of the human malaria parasite Plasmodium falciparum.
Zhang Y, Wang C, Li Q … +14 more , Li A, Zhang Y, Su Z, Yu L, Zheng K, Liu T, Jiang N, Zhang Y, Sang X, Feng Y, Chen R, Wei G, Zhang Q, Chen Q
Sci China Life Sci · 2026 Mar · PMID 42258137 · Publisher ↗
The pathogenesis of Plasmodium falciparum malaria involves coordinated molecular events, including host cell invasion, intraerythrocytic replication cycles, and antigenic variation, which are critically dependent on the...
The pathogenesis of Plasmodium falciparum malaria involves coordinated molecular events, including host cell invasion, intraerythrocytic replication cycles, and antigenic variation, which are critically dependent on the stage-specific regulation of parasite proteins. Despite their biological significance, the molecular governance of these pathogenic mechanisms remains inadequately characterized. Our investigation reveals that the expression dynamics of an ApiAP2 family transcription factor, PfAP2-V (PF3D7_1239200), exhibit strong temporal coordination with the transcriptional activation of virulence-associated genes during the blood-stage development of P. falciparum parasites. These genes encompass those coding for merozoite surface antigens and the inner membrane complex families and the var gene clusters encoding P. falciparum erythrocyte membrane protein 1 (PfEMP1) cytoadherence proteins. Conditional knockdown of pfap2-v expression significantly decreased parasite intraerythrocytic proliferation, resulted in structural abnormalities in infected erythrocyte surface topology, and markedly reduced the cytoadhesion capacity of infected erythrocytes to human endothelial receptors, such as CD36, ICAM-1, and PECAM-1/CD31. Mechanistic analyses revealed that PfAP2-V directly associates with specific chromosomal regions, where it is involved in chromatin interactions and facilitates transcriptional activation. These findings establish PfAP2-V as a master transcriptional regulator that governs both parasite proliferation and the expression of the virulence factors critical for P. falciparum malaria pathogenesis.
Apicidin is a key virulence determinant of Fusarium asiaticum in wheat-rice cropping systems.
Liu X, Li K, Qiu J … +14 more , Gao T, Shi Y, Shen G, Zhou Y, Hu S, Ruan X, Wan J, Lee YW, Gu Q, Lim JY, Seo JA, Shi J, Ye W, Xu J
Sci China Life Sci · 2026 Jun · PMID 42258136 · Publisher ↗
Apicidin, an emerging mycotoxin with potent histone deacetylase inhibitory and cytotoxic activities, is increasingly detected in wheat and rice in Jiangsu Province, China. Through a population-level screening, we identif...
Apicidin, an emerging mycotoxin with potent histone deacetylase inhibitory and cytotoxic activities, is increasingly detected in wheat and rice in Jiangsu Province, China. Through a population-level screening, we identified a subset of Fusarium asiaticum strains, the dominant pathogen in wheat-rice rotation regions, as the primary producers of apicidin. Using telomere-to-telomere genome assemblies, we identified a biosynthetic gene cluster of 12 genes (FaAps-BGC) essential for apicidin production. Comparative genomic and phylogenomic analyses revealed a complex evolutionary history of FaAps-BGC, characterized by a discontinuous distribution across Fusarium species and extensive structural variation. Large-scale population genome sequencing further showed that loss of apicidin production was associated with either deletion of the entire FaAps-BGC or pseudogenization of the non-ribosomal peptide synthetase (NRPS) backbone gene, and correlated with reduced virulence in both wheat and rice. Functional analyses showed that deletion of the pathway-specific transcription factor gene FaAps2 led to coordinated silencing of other Aps genes within the FaAps-BGC, abolished apicidin biosynthesis, and significantly reduced virulence on both wheat and rice. Mechanistically, apicidin promotes infection by disrupting host plasma membrane integrity, inducing reactive oxygen species (ROS) accumulation, and compromising host defense response in a host-dependent manner. Together, these findings establish apicidin as a key virulence determinant in F. asiaticum and highlight how genomic variation in secondary metabolite biosynthetic pathways shapes fungal virulence in cereal cropping systems.
Structure-driven RNA remodeling underlies broad substrate recognition by NSUN2.
Hu Q, Yang W, Yu Y … +7 more , Yi R, Zhang Y, Duan L, Li F, Zhang K, Gong Q, Li S
Sci China Life Sci · 2026 May · PMID 42258135 · Publisher ↗
The human RNA mC methyltransferase NSUN2 catalyzes site-specific cytosine methylation across diverse RNA substrates and thereby regulates a wide range of biological and physiological processes. However, the molecular bas...
The human RNA mC methyltransferase NSUN2 catalyzes site-specific cytosine methylation across diverse RNA substrates and thereby regulates a wide range of biological and physiological processes. However, the molecular basis by which NSUN2 achieves broad substrate recognition while maintaining catalytic specificity has remained unclear. Here, we determine structures of human NSUN2 in both substrate-free and substrate-bound states using X-ray crystallography and cryo-electron microscopy. Structures of NSUN2 in complex with multiple tRNA substrates reveal a structure-first, sequence-tolerant strategy in which NSUN2 actively remodels tRNA architecture, exposing the buried target cytosine and positioning it within the catalytic pocket for methyl transfer. This recognition strategy enables NSUN2 to accommodate diverse tRNA substrates through a largely conserved interaction interface. Together, our findings define the molecular principles underlying NSUN2-mediated RNA mC modification.
Histone chaperone HIRA restrains ferroptosis susceptibility through epigenetic control of iron metabolism in prostate cancer.
Wang E, Sun Q, Xu Z … +9 more , Huang C, Chen Y, Wang Q, Liu S, Wang X, Ren X, Sun F, Tai S, Xu M
Sci China Life Sci · 2026 Jun · PMID 42258134 · Publisher ↗
Ferroptosis, an iron-dependent form of immunogenic cell death (ICD), represents a promising anti-tumor therapeutic strategy via effectively activating immune responses. However, the regulatory mechanisms governing ferrop...
Ferroptosis, an iron-dependent form of immunogenic cell death (ICD), represents a promising anti-tumor therapeutic strategy via effectively activating immune responses. However, the regulatory mechanisms governing ferroptosis in prostate cancer remain poorly understood, significantly impeding the development of targeted therapeutic approaches. Through genome-wide CRISPR/Cas9 screening, we identified the histone chaperone HIRA as a novel ferroptosis suppressor in prostate cancer. Integrated analysis of public datasets and immunohistochemical validation demonstrated significant HIRA overexpression in prostate tumors, which was associated with diminished cytotoxic T lymphocyte infiltration and adverse clinical outcomes. Moreover, depletion of HIRA substantially enhanced ferroptosis susceptibility in vitro and in vivo, resulting in marked tumor growth inhibition. Mechanistic investigations revealed that HIRA orchestrates iron homeostasis through coordinated epigenetic regulation. While traditionally known to mediate H3.3 deposition in actively transcribed regions, we unexpectedly observed that HIRA depletion induced a widespread redistribution of H3.3 occupancy, with more regions gained than lost, suggesting compensatory H3.3 deposition dynamics. This redistribution coincided with increased chromatin accessibility and transcriptional regulation of iron metabolism genes, ultimately attenuating intracellular Fe accumulation and ferroptosis resistance. Notably, HIRA depletion augmented CD4 and CD8 T cell infiltration and demonstrated synergistic efficacy with PD-1 immune checkpoint blockade in PCa models. Thus, our study establishes HIRA as an important epigenetic regulator of ferroptosis through iron metabolism modulation and nominates it as a promising therapeutic target for combination therapy in advanced prostate cancer.
High-density lipoprotein antioxidant function is associated with lipid profiles and lipid-lowering therapy.
Cao HY, Mo ZW, Ma ZS … +7 more , Liu YF, Wang C, Peng YM, Kang YT, Li Y, Ou ZJ, Ou JS
Sci China Life Sci · 2026 Jun · PMID 42258133 · Publisher ↗
Dyslipidemia is an important risk factor for coronary artery disease (CAD). However, the relationship between high-density lipoprotein (HDL) antioxidant function and plasma lipid profile has not been fully investigated....
Dyslipidemia is an important risk factor for coronary artery disease (CAD). However, the relationship between high-density lipoprotein (HDL) antioxidant function and plasma lipid profile has not been fully investigated. Lipid-lowering therapy is recommended in patients with CAD. The relationship between HDL antioxidant function and lipid-lowering therapy remains unclear. This study aimed to analyze the association between HDL antioxidant function, lipid profiles, and lipid-lowering therapy in patients with CAD. To investigate this, we recruited 1,000 patients with CAD and 200 healthy subjects. HDL lipid peroxide content was measured and normalized by HDL cholesterol (HDL-C) levels to represent HDL antioxidant function (nHDLox). nHDLox levels were compared across different CAD severities. The association between nHDLox and lipid profiles was also analyzed. The difference in nHDLox between patients who received lipid-lowering therapy and those who did not was analyzed. A correlation analysis was performed to investigate the association between nHDLox and fasting blood glucose and inflammatory markers. Results demonstrated that nHDLox levels were elevated in patients with CAD compared to healthy subjects, and were also higher in patients with acute coronary syndrome and CAD combined with three-vessel disease. Receiver operating characteristic curve analysis showed that nHDLox was better than triglyceride-glucose index and HDL-C levels in predicting CAD. nHDLox positively correlated with total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels. Further analysis showed an approximately "L"-shaped relationship between nHDLox and HDL-C levels. Moreover, among CAD patients with LDL-C < 3.0 mmol/L, nHDLox was significantly reduced in the lipid-lowering therapy group compared to that in the group without lipid-lowering therapy. Furthermore, nHDLox positively correlated with fasting blood glucose levels and inflammatory markers. In conclusion, HDL antioxidant function is associated with lipid profiles. Lipid-lowering therapy improves HDL antioxidant function in patients with CAD, and nHDLox may serve as an indicator for the efficacy of such treatment.
Ciliates: a window into the diversity and complexity of unicellular eukaryotic life.
Gao F, Miao W, Song X … +4 more , Tian M, Wang W, Xiong J, Song W
Sci China Life Sci · 2026 Jul · PMID 42258132 · Publisher ↗
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KLF6 regulates osteoclastogenesis through DUSP16 in OVX-induced bone loss.
Yang C, Zhang W, Liu X … +9 more , Li W, Qin Y, Li W, Wu Z, Jiang K, Wang C, Qian Z, Wang L, Geng D
Sci China Life Sci · 2026 Mar · PMID 42258131 · Publisher ↗
Estrogen deficiency results in enhanced bone resorption by osteoclasts, a critical factor in the development of postmenopausal osteoporosis. This study investigates the regulatory role of KLF6 in osteoclast differentiati...
Estrogen deficiency results in enhanced bone resorption by osteoclasts, a critical factor in the development of postmenopausal osteoporosis. This study investigates the regulatory role of KLF6 in osteoclast differentiation and evaluates its potential in reducing bone loss in ovariectomized (OVX) mice. The results show that the expression of KLF6 gradually decreases during osteoclast differentiation, and this decrease is more pronounced in the OVX model. Reducing the expression level of KLF6 can promote the differentiation of osteoclasts. Through RNA sequencing and ChIP analysis, we found that KLF6 inhibits the activity of the MAPK signaling pathway by upregulating the expression of DUSP16, thereby suppressing osteoclast differentiation. In vivo experiments demonstrate that overexpression of KLF6 via adeno-associated virus can reduce OVX-induced bone loss, suggesting that KLF6 may serve as a potential therapeutic target for bone loss caused by estrogen deficiency.
E-Syt1 recruits PI4KA to endoplasmic reticulum-plasma membrane junctions to enhance PI4P synthesis.
Tong C, Mao R, Wang D … +5 more , Xi J, Su M, Fu W, Li D, Liu JJ
Sci China Life Sci · 2026 Jun · PMID 42258130 · Publisher ↗
Phosphatidylinositol-4-phosphate (PI4P) is a low-abundance membrane lipid that plays crucial roles in lipid exchange and homeostasis, signal transduction, and vesicle trafficking. PI4KA, a type III phosphatidylinositol 4...
Phosphatidylinositol-4-phosphate (PI4P) is a low-abundance membrane lipid that plays crucial roles in lipid exchange and homeostasis, signal transduction, and vesicle trafficking. PI4KA, a type III phosphatidylinositol 4-kinase, catalyzes PI4P synthesis at the plasma membrane (PM). However, the mechanism by which cytoplasmic PI4KA is recruited to the PM to regulate PI4P levels in response to extracellular and intracellular signals remains unclear. We found that PI4KA is tightly associated with membranous organelles, including the endoplasmic reticulum (ER). In response to Ca, the membrane tethering protein extended synaptotagmin 1 (E-Syt1) recruits ER-localized PI4KA to ER-PM junctions, facilitating its PM recruitment and the assembly of the enzyme complex. In hippocampal neurons undergoing synaptic potentiation, neuronal activity-induced PM localization of PI4KA and PM PI4P synthesis also rely on E-Syt1 function. Thus, E-Syt1-mediated PI4KA localization to ER-PM junctions serves as a critical mechanism by which Ca signaling regulates lipid metabolism at the PM.
The nucleosome assembly protein Nap1 regulates chromatin stability and nuclear division in Tetrahymena thermophila.
Yang S, Mi J, Xu J … +1 more , Wang W
Sci China Life Sci · 2026 Jul · PMID 42258129 · Publisher ↗
Chromatin stability is essential for maintaining genome integrity and gene regulation in eukaryotic cells. Nucleosome assembly protein 1 (Nap1) is a key regulator of chromatin dynamics across different organisms. The cil...
Chromatin stability is essential for maintaining genome integrity and gene regulation in eukaryotic cells. Nucleosome assembly protein 1 (Nap1) is a key regulator of chromatin dynamics across different organisms. The ciliate Tetrahymena thermophila contains two functionally distinct nuclei within a single cell: the diploid germline micronucleus (MIC), which undergoes mitosis and meiosis, and the polyploid somatic macronucleus (MAC), which divides amitotically. However, the function of Nap1 in this evolutionarily distant protist remains unclear. Here, we show that Nap1 localizes predominantly to the perinuclear region of the MAC during vegetative growth and is also detectable in the MAC, MIC, and cytoplasm. Truncation of the nuclear export signal (NES) increases accumulation of Nap1 in the MAC. During sexual development, Nap1 localizes to the cytoplasm, parental MAC, and developing new MAC, while Nap1 shows enhanced enrichment in the new MAC. Nap1 also partially colocalizes with the nuclear pore protein Nup98 at the MAC envelope. Knockdown of NAP1 impairs proliferation, disrupts amitotic MAC division, and induces nuclear extrusion bodies. Moreover, NAP1 deficiency causes abnormal meiotic progression. Co-immunoprecipitation coupled with mass spectrometry showed that Nap1 associates with nuclear pore complex proteins, histones, and DNA replication/repair factors. Direct binding of Nap1 to H2A-H2B and the ribosomal protein Rps6 was confirmed by pull-down assays. These findings establish Nap1 as a multifunctional protein required for nuclear envelope integrity, nuclear division, and chromatin stability in Tetrahymena.
Endurance exercise improves age- and obesity-related cardiac dysfunction and locomotor impairment through muscle Gγ1 gene in Drosophila.
Sun J, Wen D, Lin Y … +3 more , Tianshuo Y, Deyu Z, Yin X
Life Sci · 2026 Sep · PMID 42250789 · Publisher ↗
Gγ1, a member of the G protein γ subunit family, participates in regulating diverse physiological processes such as energy metabolism and actomyosin dynamics. However, it remains unclear whether muscle Gγ1 is involved in...
Gγ1, a member of the G protein γ subunit family, participates in regulating diverse physiological processes such as energy metabolism and actomyosin dynamics. However, it remains unclear whether muscle Gγ1 is involved in regulating lipid metabolism and obesity-related complications during the aging process, as well as the effects of exercise intervention on these outcomes. In this study, Gγ1 gene was knocked down and overexpressed in Drosophila muscles using the Gγ1 and Gγ1 systems. Following a 4-week endurance exercise regimen. Results showed that muscle-specific knockdown of Gγ1 accelerated age-related lipid accumulation and toxicity, as evidenced by elevated triglyceride and malondialdehyde levels, and induced mitochondrial dysfunction involving suppression of the Sir2/PGC-1α/MRCC-I pathway. These changes were accompanied by aggravated aging-related phenotypes in Drosophila, including declines in motor performance (climbing speed) and cardiac function (heart rate and fractional shortening), as well as a significant reduction in lifespan. Conversely, overexpression of Gγ1 produced opposite effects. Endurance exercise training alleviated obesity-related cardiac dysfunction and locomotor impairment by upregulating muscle Gγ1 expression in aging Drosophila, and this effect resembled an additive enhancement under conditions of muscle-specific Gγ1 overexpression. These findings suggest that muscle Gγ1 may serve as a potential therapeutic target for obesity and aging-related interventions, and exercise represents an effective strategy for mitigating metabolic and aging defects associated with muscle Gγ1 deficiency.
Chikusetsu saponin IVa mitigates septic cardiac injury by targeting DRP1 to suppress mitochondrial damage and NLRP3 inflammasome activation.
Tian W, Yu ZY, Li Z … +8 more , Zheng XY, Ding YD, Yu DH, Hu F, Li MY, Yang XF, Shen HJ, Lian JQ
Life Sci · 2026 Sep · PMID 42235794 · Publisher ↗
AIMS: Sepsis-induced myocardial injury represents a serious complication with limited treatment options. Chikusetsu saponin IVa (CHS), a triterpenoid saponin derived from Rhizoma Panacis japonica, exhibits potent anti-in...
AIMS: Sepsis-induced myocardial injury represents a serious complication with limited treatment options. Chikusetsu saponin IVa (CHS), a triterpenoid saponin derived from Rhizoma Panacis japonica, exhibits potent anti-inflammatory and cardioprotective properties, positioning it as a promising candidate. MATERIALS AND METHODS: To elucidate the therapeutic potential and mechanism of CHS in septic cardiac dysfunction, the effects of CHS administration on lipopolysaccharide (LPS, 40 mg/kg, i.p.) and cecal ligation and puncture (CLP)-induced septic murine models were evaluated through echocardiography and histological analyses. Network pharmacology and limited proteolysis-mass spectrometry (LiP-MS) were exploited to dissect the specific mechanisms and targets of CHS. Immunofluorescence, co-immunoprecipitation, and electron microscopy were performed to validate the effects of CHS on mitochondrial integrity, inflammasome assembly, and pyroptotic injury in LPS-ATP-stimulated cardiomyocytes. KEY FINDINGS: CHS administration significantly mitigated LPS-induced cardiac injury and dysfunction of mice. CHS effectively inhibited NLRP3 upregulation, Caspase-1 activation, GSDMD cleavage, and subsequent pyroptosis both in vivo and in vitro. LiP-MS and microscale thermophoresis identified DRP1 as the direct binding protein of CHS. Cellular thermal shift assay and drug affinity responsive target stability assays further indicated that CHS improved the proteolytic and thermal stability of DRP1. CHS or DRP1 inhibitor (Mdivi1) blocked LPS-ATP-stimulated DRP1 phosphorylation, reduced mitochondrial fragmentation, and ROS overproduction. Consistently, CHS diminished LPS-ATP-induced NLRP3-TXNIP interaction and inflammasome assembly, thereby reducing cellular membrane rupture and pyroptotic cell death, whereas DRP1 overexpression exerted the opposite effect. SIGNIFICANCE: CHS represents a promising therapeutic candidate for septic cardiomyopathy by targeting DRP1-mediated mitochondrial dynamics and the NLRP3 inflammasome.
BMP and ERK signaling modulate AML-stroma interactions and contextually alter cytarabine sensitivity in AML cells.
Sharma A, Anand T, Bhattacharyya J … +2 more , Das D, Jaganathan BG
Life Sci · 2026 Sep · PMID 42235793 · Publisher ↗
AIMS: Relapse in acute myeloid leukemia (AML) frequently arises from therapy-resistant cells persisting within the bone marrow microenvironment. This study investigated stromal interactions and signaling pathway dependen...
AIMS: Relapse in acute myeloid leukemia (AML) frequently arises from therapy-resistant cells persisting within the bone marrow microenvironment. This study investigated stromal interactions and signaling pathway dependencies regulating cytarabine (AraC) response during AML progression and resistance acquisition. MATERIALS AND METHODS: AML cell lines representing FAB-M1 (KG1a), FAB-M5 (THP1), and an Ara-C-resistant THP1 derivative (CR-THP1) were cultured alone or with bone marrow-derived mesenchymal stromal cells (BMSCs). Cell viability, clonogenicity, signaling pathway activation, and gene expression were analyzed following Ara-C treatment with or without BMP and ERK pathway inhibition. Primary AML mononuclear cells and publicly available transcriptomic datasets were used for validation. KEY FINDINGS: Stromal coculture protected THP1 from Ara-C-induced apoptosis but sensitized KG1a to AraC. Despite reduced stromal adhesion, CR-THP1 cells exhibited increased Ara-C sensitivity under coculture, indicating altered microenvironmental signaling during resistance acquisition. BMP pathway inhibition enhanced Ara-C cytotoxicity in parental THP1 through suppression of stromal-induced β-catenin upregulation but failed to sensitize CR-THP1 cells. In contrast, ERK inhibition restored Ara-C sensitivity in CR-THP1, downregulated ABCB1 and ABCG2 expression, and prevented leukemia regrowth in an in vitro relapse model. Transcriptomic analyses identified alterations in drug efflux, apoptosis imbalance, BMP, ERK, and Wnt/β-catenin networks during resistance acquisition. SIGNIFICANCE: These findings identify BMP and ERK signaling as context-dependent regulators of Ara-C response in AML and demonstrate that stromal interactions evolve during resistance acquisition. Targeting BMP and ERK pathways, together with modulators of DNA repair or drug efflux, may provide therapeutic strategies to reduce relapse and improve AML outcomes.
Erratum to: Fungal oxalic acid inhibits the deamidation of CERK1 ectodomain to dampen chitin-triggered plant immunity.
Gong BQ, Liu JJ, Xu J … +2 more , Cheng J, Li JF
Sci China Life Sci · 2026 Jul · PMID 42234367 · Publisher ↗
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Nitrogen fertilization increases soil organic carbon through distinct pathways in contrasting cropland soils.
Zhou R, Xue Y, Kumar A … +14 more , Ma J, Ling J, Hartley IP, Kuzyakov Y, Zhang W, Yue S, Gao Q, Chen Y, Wang M, Liu H, Cui Z, Chen X, Zhang F, Tian J
Sci China Life Sci · 2026 May · PMID 42228254 · Publisher ↗
Nitrogen (N) fertilization influences soil organic carbon (SOC) formation by regulating plant inputs and microbial activity; however, the relative contributions of plant- versus microbial-derived carbon (C) to SOC accumu...
Nitrogen (N) fertilization influences soil organic carbon (SOC) formation by regulating plant inputs and microbial activity; however, the relative contributions of plant- versus microbial-derived carbon (C) to SOC accumulation remain unclear, largely due to site-specific variations in soil properties and the complex transformation pathways governing C stabilization. Here, we used amino sugars and lignin phenols as molecular tracers to quantify microbial necromass- and lignin-derived C contributions to SOC under N fertilization across four long-term maize field experiments in Quzhou and Changwu (alkaline, low-fertility soils) and Lishu and Yaan (acidic, high-fertility soils). Although N fertilization increased SOC across all sites, the dominant pathways for C accumulation differed in contrasting soils. In alkaline, low-fertility soils, SOC accumulation was primarily associated with greater lignin-derived C, regulated by soil geochemical properties and aggregate protection rather than increased plant inputs. In acidic, high-fertility soils, microbial necromass contributed more to SOC accumulation and was associated with greater lignin oxidation, reduced oxidase activity, and elevated oxalate-extractable Fe/Al oxides. These divergent mechanisms explain variability in SOC responses to N fertilization and emphasize the need for soil-specific nutrient management strategies to maximize C retention in croplands.
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