The embryos of lotus (Nelumbo nucifera Gaertn.) is a famous traditional Chinese medicine used to treat insomnia, memory decline, and dementia for a long time. However, the underlying material basis an Show more
The embryos of lotus (Nelumbo nucifera Gaertn.) is a famous traditional Chinese medicine used to treat insomnia, memory decline, and dementia for a long time. However, the underlying material basis and mechanisms of this medicine are still unclear. Isoliensinine (IL) is a major alkaloid derived from lotus embryos. Our previous research has demonstrated that IL can exert strong anti-inflammatory and neuroprotective effects in vitro. To reveal the underlying therapeutic effect and mechanism of IL on Alzheimer's disease (AD)-like mice induced by AlCl The AD-like mice were modeled by intragastric injection (i.g.) of AlCl IL (1, 3, and 10 mg/kg) treatment effectively ameliorated cognitive impairment in AD-like model mice. IL inhibited the decrease of brain index and body weight in AD-like mice and alleviated neuronal damage in the cortex and hippocampus (DG, CA1, and CA3). IL decreased the levels of Ca IL has a significant therapeutic effect on pathological alterations and cognitive impairment in AlCl Show less
Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to u Show more
Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to unravel causal associations between 2,940 circulating proteins and 19 CVD. We found 218 proteins that impacted risk of one or more CVDs through forward MR (106 and 182 using cis-pQTLs only and cis- + trans-pQTLs, respectively), among which 107 were previously reported as associated with CVD or CVD-related traits. There were 102 proteins replicated (FDR < 5%, 53 with cis-pQTLs only and 88 with cis- + trans-pQTLs) using the FinnGen Olink data. BTN3A2 was highlighted as a novel candidate gene for ischemic stroke, suggesting a crosstalk between immune modulation and stroke pathogenesis. Single cell integration prioritized PAM for stable angina pectoris and ventricular arrhythmia and LPL for peripheral artery disease, whose transcriptional expressions were enriched in cardiomyocytes. Forward and reverse MR found largely non-overlapping proteins (only 2 overlapped: LGALS4 and MMP12), suggesting distinct proteomic causes and consequences of CVD. Our study provides human genetics-based evidence of novel candidate genes, a foundational step towards full-scale causal human biology-based drug discovery for CVD. Show less
Given the lack of evidence, we cannot definitively determine the relationship between attachment networks and problematic mobile phone use, hindering effective intervention strategies. Therefore, a th Show more
Given the lack of evidence, we cannot definitively determine the relationship between attachment networks and problematic mobile phone use, hindering effective intervention strategies. Therefore, a three-wave longitudinal study was designed to explore the heterogeneity of parent-child attachment networks using latent profile analysis (LPA) and random intercept latent transition analysis (RI-LTA). Participants included 2116 adolescents (ages 14-21; 53.8% girls). Results identified five stable parent-child attachment network profiles, each showing moderate but decreasing stability. Notably, adolescents who were grouped into an attachment network characterized by secure maternal attachment but insecure paternal attachment, similar to those in attachment networks with both insecure maternal and paternal attachment, scored higher levels of problematic mobile phone use than those who were grouped into attachment networks with both secure maternal and paternal attachment. Our findings fill empirical gaps and provide strong evidence supporting attachment-based interventions to reduce problematic mobile phone use. Show less
The development of an immunosuppressive microenvironment is a critical factor in stomach carcinogenesis. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) serve a pivotal function in medi Show more
The development of an immunosuppressive microenvironment is a critical factor in stomach carcinogenesis. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) serve a pivotal function in mediating immune suppression. However, the precise mechanisms underlying PMN-MDSCs infiltration into the tumor immune microenvironment (TIME) and their immunosuppressive functions remain poorly understood. In this investigation, we observed that PMN-MDSCs were up-regulated during stomach carcinogenesis, with gastric cancer (GC) cells secreting CCL26 to promote the infiltration of PMN-MDSCs into the TIME via the CX3CR1 receptor. The infiltrating CX3CR1 Show less
Accumulation of amyloid-β (Aβ) peptides and hyperphosphorylated tau proteins in the hippocampus triggers cognitive memory decline in Alzheimer's disease (AD). The incidence and mortality of sporadic A Show more
Accumulation of amyloid-β (Aβ) peptides and hyperphosphorylated tau proteins in the hippocampus triggers cognitive memory decline in Alzheimer's disease (AD). The incidence and mortality of sporadic AD were tightly associated with diabetes and hyperlipidemia, while the exact linked molecular mechanism is uncertain. Here, the present investigation identified significantly elevated serum Kallistatin levels in AD patients concomitant with hyperglycemia and hypertriglyceridemia, suggesting potential crosstalk between neuroendocrine regulation and metabolic dysregulation in AD pathophysiology. In addition, the constructed Kallistatin-transgenic (KAL-TG) mice defined its cognitive memory impairment phenotype and lower long-term potentiation in hippocampal CA1 neurons accompanied by increased Aβ deposition and tau phosphorylation. Mechanistically, Kallistatin could directly bind to the Notch1 receptor and thereby upregulate BACE1 expression by inhibiting PPARγ signaling, resulting in Aβ cleavage and production. Besides, Kallistatin could promote the phosphorylation of tau by activating GSK-3β. Fenofibrate, a hypolipidemic drug, could alleviate cognitive memory impairment by downregulating Aβ and tau phosphorylation of KAL-TG mice. Collectively, the experiments clarified a novel mechanism for Aβ accumulation and tau protein hyperphosphorylation regulation by Kallistatin, which might play a crucial role in linking metabolic syndromes and cognitive memory deterioration, and suggested that fenofibrate might have the potential for treating metabolism-related AD. Show less
Animal models are used widely to study pulmonary hypertension (PH). The cell populations that respond to disease-inducing stimuli in these models and their relationship to human disease remain incompl Show more
Animal models are used widely to study pulmonary hypertension (PH). The cell populations that respond to disease-inducing stimuli in these models and their relationship to human disease remain incompletely defined. This study analyzed the relationship between several rodent models of PH and human disease at single-cell resolution. scRNA-seq was performed on lungs from mice exposed to hypoxia or Sugen/hypoxia, rats exposed to monocrotaline, and controls. A cross-species single-cell dataset was integrated with human lung cell atlas (HLCA) and single-cell dataset from idiopathic pulmonary arterial hypertension (IPAH) to identify overlapping cell subsets between experimental and human disease and species. High levels of overlap were found between species and models of PH, HLCA, and IPAH datasets. Cell subsets perturbed in rat and mouse PH were similar to those found in human disease, with macrophages and endothelial cells being most affected. A novel We established a comprehensive cross-species single-cell atlas of mainstream rodent PH models, highlighting several novel macrophage and endothelial subtypes and signaling motifs potentially contributing to human disease. Show less
To explore neurodynamic bases underlying subjective cognitive decline (SCD) based on edge-centric functional network. 211 SCD patients and 210 healthy controls (HC) were recruited from the Alzheimer's Show more
To explore neurodynamic bases underlying subjective cognitive decline (SCD) based on edge-centric functional network. 211 SCD patients and 210 healthy controls (HC) were recruited from the Alzheimer's Disease Neuroimaging Initiative. Edge time series (ETS) were obtained based on resting-state functional magnetic resonance data. The top 10% co-fluctuation signals of all time points in ETS were extracted to construct the high-amplitude frame networks, and the co-fluctuation signals from the remaining time points were used to construct the low-amplitude frame networks. In both network states, the graph theory and network-based statistics (NBS) analyses were used to compare SCD and HC. The correlation of the imaging indicators with cognitive scores and apolipoprotein E (APOE) ε4 genes was performed by Spearman correlation analysis. SCD exhibited lower peak amplitude and longer trough-to-trough duration (TTD) compared to HC. In both network states, the normalized clustering coefficient, normalized characteristic path length, small-worldness, and global efficiency of SCD were significantly reduced, and the altered nodal centralities of SCD predominantly exhibited a decreasing trend. However, the high-amplitude frame network identified more altered brain regions compared to the low-amplitude frame network. Furthermore, a SCD-related subnetwork was found in the high-amplitude frame network, which was composed of 11 brain regions and 13 edges. TTD was positively related to the number of APOE ε4 genes; the normalized characteristic path length, the betweenness centrality of right postcentral gyrus, and the connection between bilateral angular gyrus were correlated with cognitive scores. Our findings demonstrate that the edge-centric network framework reveals details of brain network alterations in SCD through different perspectives, and these alterations hold potential as novel biomarkers for SCD. Show less
Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathologic Show more
Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β-amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose-free diet or mannose transporter antagonists. Mechanistically, single-cell RNA sequencing and metabolomics suggested that mannose-mediated N-glycosylation of BACE1 and Nicastrin enhances their protein stability, promoting Aβ production. Additionally, reduced mannose intake decreased BACE1 and Nicastrin stability, ultimately lowering Aβ production and mitigating AD pathology. this results highlight that high-dose mannose consumption may exacerbate AD pathogenesis. Restricting dietary mannose may have therapeutic benefits. Show less
Bo Lin, Mengsen Li · 2025 · Frontiers in immunology · Frontiers · added 2026-04-24
Abnormalities in the Wnt/β-catenin pathway promote the development of hepatocellular carcinoma (HCC). Mutations in CTNNB1, which encodes β-catenin, are frequently found in clinical HCC samples, as are Show more
Abnormalities in the Wnt/β-catenin pathway promote the development of hepatocellular carcinoma (HCC). Mutations in CTNNB1, which encodes β-catenin, are frequently found in clinical HCC samples, as are loss-of-function mutations in signaling pathway regulators such as axis inhibition protein 1 (Axin1) and adenomatous polyposis coli (APC). The activation of the Wnt/β-catenin pathway synergizes with other oncogenic signal molecules such as c-Met or glypican-3, contributing to HCC development. Furthermore, Wnt/β-catenin pathway activation in the tumour microenvironment (TME) leads to cold tumour and resistance to immunotherapy. In this review, we discuss two models of Wnt/β-catenin signaling activation, role of Wnt/β-catenin signaling pathway in the development of HCC, the association between Wnt/β-catenin pathway and tumour angiogenesis, metastasis, and immune escape in the TME, and the targeting of this signaling pathway for HCC treatment. Show less
Arsenic (As) is a toxic metalloid widespread in the environment, and its exposure has been associated with a variety of adverse health outcomes. As exposure is demonstrated to cause nonalcoholic fatty Show more
Arsenic (As) is a toxic metalloid widespread in the environment, and its exposure has been associated with a variety of adverse health outcomes. As exposure is demonstrated to cause nonalcoholic fatty liver disease (NAFLD), and the underlying epigenetic mechanisms remain largely unknown. This study aimed to investigate the roles of histone modifications in low-level As exposure-induced NAFLD in rats. The results showed that exposure to As caused lipid accumulation and upregulated the expression of lipid metabolism-related genes Show less
Central nervous system (CNS) tumors often harbor alterations in genes regulating key cellular pathways, including fibroblast growth factor receptor (FGFR) genes. Here, we report the efficacy and safet Show more
Central nervous system (CNS) tumors often harbor alterations in genes regulating key cellular pathways, including fibroblast growth factor receptor (FGFR) genes. Here, we report the efficacy and safety of treatment with pemigatinib, an oral, potent, selective FGFR1-3 inhibitor, in patients with advanced FGFR-altered CNS tumors. FIGHT-207 was a single-arm, open-label, phase 2 study of pemigatinib in patients with advanced solid tumors harboring FGFR fusions/rearrangements or other mutations. Patients received pemigatinib 13.5 mg once daily until disease progression or unacceptable toxicity. Endpoints included tumor response and safety. Of the 13 patients with CNS tumors in FIGHT-207, 10 had glioblastoma. Fibroblast growth factor receptor alterations were FGFR3-TACC3 fusions (n = 9), FGFR1 K656E mutations (n = 2), FGFR1 N546K mutation (n = 1), and FGFR1-MITF fusion (n = 1). Three patients (23%) displayed objective responses (1 complete, 2 partial). Safety was consistent with the overall FIGHT-207 population. Pemigatinib had antitumor activity and a manageable safety profile in patients with CNS tumors. Show less
Gentidelasides A-G (1-7) seven unreported loganin derivatives and fourteen known compounds (8-21) were isolated from the flowers of Gentiana delavayi Franch. Their structures including absolute config Show more
Gentidelasides A-G (1-7) seven unreported loganin derivatives and fourteen known compounds (8-21) were isolated from the flowers of Gentiana delavayi Franch. Their structures including absolute configurations were unambiguously elucidated by analysis of extensive NMR spectroscopy, ECD, and HRESIMS, as well as enzymatic hydrolysis. In vitro bioassay, compound 7 showed obvious inhibitory effects on the production of Aβ40 and Aβ42, with IC Show less
Palmitic acid (PA), being the most prevalent free fatty acid in the human, holds significant implications as a risk factor for atherosclerosis (AS) due to its ability to induce physiological dysfuncti Show more
Palmitic acid (PA), being the most prevalent free fatty acid in the human, holds significant implications as a risk factor for atherosclerosis (AS) due to its ability to induce physiological dysfunction in endothelial cells (ECs). Endothelial cell-specific molecule 1 (ESM1), has been identified as a marker for activated ECs. Nevertheless, the mechanisms underlying ESM1-induced endothelial cell proliferation remain elusive. The expression of ESM1, ANGPTL4 and autophagy related protein were confirmed by western blot. Proliferation ability was tested by MTT and EdU. Lipids level was confirmed by Oil red staining. Autophagic flux was confirmed by Monodansylcadaverine (MDC) staining and pCMV-mCherry-GFP-LC3B fluorescence staining assay. The mouse model of AS was used to observe the effect of PA on the ESM1-ANGPTL4-autophagy signaling axis. This study elucidates ESM1-ANGPTL4 axis in maintaining proliferation of ECs and lipid reprogramming. Furthermore, it has been observed that PA has the ability to stimulate EC to autonomously increase the expression of ESM1, which in turn can counteract the detrimental effects of PA on ECs. Conversely, when ESM1 is suppressed, the damaging effects of PA on ECs are exacerbated. Mechanistically, our findings indicate that ESM1 facilitates EC proliferation and lipids homeostasis by up-regulating autophagy through ANGPTL4. This effect of ESM1 on ECs can be attenuated by ATG7 inhibiting. Additionally, the serum levels of ESM1 were found to be elevated in AS mice. ESM1 was found to enhance ECs proliferation and mitigate endothelial cell injury induced by PA through the upregulation of autophagy. This mechanism potentially serves as a protective factor against atherosclerosis progression. Show less
Yolk percentage is a critical index in the egg product industry, reflecting both nutritional value and economic benefits. To elucidate the underlying mechanisms that contribute to variations in egg yo Show more
Yolk percentage is a critical index in the egg product industry, reflecting both nutritional value and economic benefits. To elucidate the underlying mechanisms that contribute to variations in egg yolk percentage, we performed integrated transcriptome and metabolome analyses on the liver, ovary, and magnum tissues of Rhode Island Red chickens with high and low yolk percentages. A total of 322 differentially expressed genes (DEGs) and 128 significantly differential metabolites (SDMs) (VIP>1, P < 0.05) were identified in the liver, whereas 419 DEGs and 215 SDMs were detected in the ovary, and 238 DEGs along with 47 SDMs were found in the magnum. In the liver, genes such as HMGCR, DHCR7, MSMO1, and CYP7A1 were linked to cholesterol metabolism, essential for steroid hormone synthesis and yolk formation, while ACACB, ACSL1, ACSL4, LPL, and SGPP2 were involved in fatty acid biosynthesis, a key process for supplying energy and structural components of the yolk. In the ovary, COL6A6, COMP, CHAD, ITGA7, THBS2, and TNC contributed to extracellular matrix-receptor interactions, which are fundamental for follicle development and oocyte maturation. In the magnum, UGT1A1, MAOB, and ALDH3B2 participated in drug metabolism-cytochrome P450 and amino acid metabolism, ensuring a proper environment for egg white formation and potentially influencing nutrient allocation to the yolk. Metabolic pathway enrichment revealed that steroid hormone biosynthesis, glycerophospholipid metabolism, and betaine metabolism were predominant in the liver; pyruvate, taurine, and hypotaurine metabolism in the ovary; and phenylalanine metabolism in the magnum. Moreover, integrated analysis highlighted key metabolites and genes potentially regulating yolk deposition, including 7,8-dihydroneopterin and Pg 38:4 in the liver (related to immune modulation and lipid metabolism, respectively), thalsimine in the ovary, as well as DL-glutamine in the magnum, all of which may be crucial for maintaining metabolic homeostasis and supporting egg formation. Collectively, these findings deepen our understanding of how distinct molecular and metabolic pathways in the liver, ovary, and magnum orchestrate yolk proportion and deposition. Such insights may advance future strategies to improve egg quality and productivity in poultry breeding programs. Show less
The Tibetan sheep is a typical hypoxia-tolerant mammal, which lives on the plateau, at an altitude of between 2500 and 5000 m above sea level; the study of its hypoxic adaptation mechanism provides a Show more
The Tibetan sheep is a typical hypoxia-tolerant mammal, which lives on the plateau, at an altitude of between 2500 and 5000 m above sea level; the study of its hypoxic adaptation mechanism provides a reference for exploring the hypoxic adaptation mechanism of other animals. To grope for the genetic mechanism of adaptation to the hypoxic environment at the transcriptional level in Tibetan sheep testicular tissue, and to identify candidate genes and key pathways related to sheep adaptation, histological observation of testicular tissues from two sheep breeds was carried out using haematoxylin-eosin (HE) conventional staining. A total of 103 differentially expressed genes (DEGs) were authenticated in high altitude Tibetan sheep (ZYH) and low altitude Tibetan sheep (ZYM) by RNA sequencing technology (RNA-Seq), which included 50 up-regulated genes and 53 down-regulated genes. Functional analyses revealed several terms and pathways that were closely related to testis adaptation to the plateau. Several genes (including GGT5, AGTR2, EDN1, LPAR3, CYP2C19, IGFBP3, APOC3 and PKC1) were remarkably enriched in several pathways and terms, which may impact the Plateau adaptability of sheep by adjusting its reproductive activity and sexual maturation, and protecting Sertoli cells, various spermatocytes, and spermatogenesis processes. The results make a reasonable case for a better understanding of the molecular mechanisms of adaptation to altitude in sheep. Show less
Dyslipidemia exacerbates pancreatic β-cell apoptosis, heightening the risk of type 2 diabetes (T2DM). Kansuinine A (KA), a diterpene from Euphorbia roots, exhibits antiapoptotic properties, suggestive Show more
Dyslipidemia exacerbates pancreatic β-cell apoptosis, heightening the risk of type 2 diabetes (T2DM). Kansuinine A (KA), a diterpene from Euphorbia roots, exhibits antiapoptotic properties, suggestive of its therapeutic potential against T2DM. In this study, we evaluated the protective effects of KA against apolipoprotein C3 (ApoC3)-rich low-density lipoprotein (LDL) (AC3RL)-induced β-cell apoptosis and its underlying mechanism of action. ApoE Show less
Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompl Show more
Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompletely defined. Here, we found that BAF60a functions as a chromatin regulator that sustains biphasic GSIS and preserves β cell function under metabolic stress conditions. BAF60a was downregulated in β cells from obese and diabetic mice, monkeys, and humans. β cell-specific inactivation of BAF60a in adult mice impaired GSIS, leading to hyperglycemia and glucose intolerance. Conversely, restoring BAF60a expression improved β cell function and systemic glucose homeostasis. Mechanistically, BAF60a physically interacted with Nkx6.1 to selectively modulate chromatin accessibility and transcriptional activity of target genes critical for GSIS coupling in islet β cells. A BAF60a V278M mutation associated with decreased β cell GSIS function was identified in human donors. Mice carrying this mutation, which disrupted the interaction between BAF60a and Nkx6.1, displayed β cell dysfunction and impaired glucose homeostasis. In addition, GLP-1R and GIPR expression was significantly reduced in BAF60a-deficient islets, attenuating the insulinotropic effect of GLP-1R agonists. Together, these findings support a role for BAF60a as a component of the epigenetic machinery that shapes the chromatin landscape in β cells critical for glucose sensing and insulin secretion. Show less
To investigate the impact of obesity on brain structure and cognition using large neuroimaging and genetic data. Associations between body mass index (BMI), gray matter volume (GMV), whiter matter hyp Show more
To investigate the impact of obesity on brain structure and cognition using large neuroimaging and genetic data. Associations between body mass index (BMI), gray matter volume (GMV), whiter matter hyper-intensities (WMH), and fluid intelligence score (FIS) were estimated in 30283 participants from the UK Biobank. Longitudinal data analysis was conducted. Genome-wide association studies were applied to explore the genetic loci associations among BMI, GMV, WMH, and FIS. Mendelian Randomization analyses were applied to further estimate the effects of obesity on changes in the brain and cognition. The observational analysis revealed that BMI was negatively associated with GMV (r = -0.15, p < 1 The phenotypic and genetic association between obesity and aging brain and cognitive decline suggested that weight control could be a promising strategy for slowing the aging brain. Show less
Bi-allelic pathogenic variants in A two-month-old infant died from sudden-onset acute heart failure. We performed a full forensic autopsy with detailed histological examination and conducted trio-base Show more
Bi-allelic pathogenic variants in A two-month-old infant died from sudden-onset acute heart failure. We performed a full forensic autopsy with detailed histological examination and conducted trio-based whole-exome sequencing (WES) on the proband and parents to identify the genetic etiology. Postmortem examination revealed severe HCM, an atrial septal defect (ASD), and extensive myocardial necrosis and fibrosis. WES identified compound heterozygous pathogenic variants in This "molecular autopsy" established a definitive cause for the infant's death, linking a novel variant to a severe pathological phenotype. Crucially, the diagnosis guided the clinical management of the asymptomatic carrier parents, prompting long-term cardiac surveillance and enabling preimplantation genetic testing (PGT) for future family planning. This case demonstrates how integrating molecular diagnostics with forensic pathology facilitates a systems medicine approach, transforming a fatal index case into actionable preventive care for the entire family. Show less
The color of rice leaves are important agronomic traits that directly influence the proportion of sunlight energy utilization and ultimately affect the yield and quality, so it is crucial to excavate Show more
The color of rice leaves are important agronomic traits that directly influence the proportion of sunlight energy utilization and ultimately affect the yield and quality, so it is crucial to excavate the mechanism of regulating rice leave color. To investigate the molecular mechanism that triggers the purple color in rice leaf, phenotypic characterization and genome-wide transcriptome analysis were conducted using the japonica rice cultivar nipponbare (Nip) and its two purple leaf mutants, A total of 2247, 5484, 4525, 2103, 4375 and7029DEGs (differentially expressed genes) were identified in nip-a vs These results not only revealed the molecular mechanism triggering leaf purple color in the rice mutants Show less
The benefits of plant essential oils (EO) on the health of animals have been frequently reported, but their alteration of lipid metabolism in obese pigs has yet to be explored. This study aimed to ass Show more
The benefits of plant essential oils (EO) on the health of animals have been frequently reported, but their alteration of lipid metabolism in obese pigs has yet to be explored. This study aimed to assess the impact of EO blends (oregano, cinnamon and lemon oils) on growth performance, meat physicochemical parameters, intestinal health and lipid metabolism in the small intestine of weaned Bamei (a kind of obese-type pig) piglets. One hundred and forty-four male 60-day-old weaned Bamei piglets were randomly assigned to three groups of six replicates each: CON (basal diet), T1 (basal diet + 250 mg/kg EO), and T2 (basal diet + 500 mg/kg EO) over 28 days. The results showed that T1 trended to improve the average daily gain and feed intake to body gain ratio (p < 0.1), reduced water loss (p < 0.05), and increased the redness of meat (p < 0.05) compared to the CON. In addition, a significant change in the proportion of C17:0 and C20:1 was observed in the meat of T1 (p < 0.05). Improved intestinal health was evidenced by the reduced crypt depth, improved villi-to-crypt length ratio, and better superoxide dismutase activity in T1 (p < 0.05). Further study on intestinal lipid metabolism showed that duodenal lipase activity and the mRNA expression levels of lipid transport-related genes in the jejunum (FABPs, APOA1, APOB and ACSL3) were significantly reduced, alongside diminished serum lipid metabolites (Total protein and triglyceride) in the groups fed with EO (p < 0.05). In short, EO supplementation especially at 250 mg/kg improved intestinal health and inhibited lipid metabolism, which had a positive effect on the overall performance of Bamei piglets. This new evidence contributes to understanding the early regulatory role of EO in obese pigs and their potential to alleviate adolescent obesity. Show less
The Huainan pig (HN) is known for its impressive litter size and exquisite meat quality. However, it also exhibits certain drawbacks such as excessive fat deposition, a relatively low percentage of le Show more
The Huainan pig (HN) is known for its impressive litter size and exquisite meat quality. However, it also exhibits certain drawbacks such as excessive fat deposition, a relatively low percentage of lean meat percentage, and a slower growth rate. Crossbreeding with lean-type breeds, such as Large White, Landrace, and Berkshire can enhance offspring traits, and increase genetic diversity. In this study we employed RNA-seq technology to identify differentially expressed genes (DEGs) in subcutaneous adipose tissue (SAT) samples from HN pigs and their crosses with multiple breeds (with three replicates per group). In the SAT of Huainan × Berkshire pigs (BH), Huainan × Yorkshire pigs (YH), and Huainan × Landrace pigs (LH), numerous key functional genes were identified, including In conclusion, these findings offer valuable insights and provide a foundation for future research on the molecular mechanisms underlying fat deposition in pigs. Show less
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular bacterial pathogen that grows within a specialized membrane-bound compartment known as the Salmonella-containing Show more
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular bacterial pathogen that grows within a specialized membrane-bound compartment known as the Salmonella-containing vacuole (SCV). The molecular composition and regulatory mechanisms governing SCV dynamics remain incompletely understood. In this study, we employed proximity-dependent biotin identification (BioID) to analyze the SCV proteome during infection. For this, we targeted the UltraID biotin ligase to the SCV by fusing it to a type 3 secreted effector. We demonstrate that the bacteria express and translocate the effector-UltraID fusion protein directly into host cells for labeling of the cytosolic face of the SCV surface. Proteomic analysis of biotinylated proteins revealed previously undescribed proteins associated with the SCV, including regulators of vesicular trafficking, cellular metabolism and lipid transport. Among these, VPS13C, a lipid transporter and membrane contact site protein, was identified as a critical regulator of SCV morphology and fission. Functional studies revealed that VPS13C also promotes ER-SCV contact formation, controls SCV positioning in host cells, and facilitates cell-to-cell spread by the bacteria. Together, our findings highlight the utility of BioID as a tool to study host-pathogen interactions in the context of infection and characterize VPS13C as a novel modulator of the intracellular life cycle of S. Typhimurium. Show less
Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression, which limits the availability of targeted t Show more
Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression, which limits the availability of targeted therapies and results in poor prognosis. Immune checkpoint blockade (ICB) therapies have emerged as promising treatments by enhancing anti-tumor immunity; however, a substantial proportion of patients with TNBC exhibit primary or acquired resistance. This resistance is largely influenced by the tumor microenvironment (TME). This study uses integrated single-cell and spatial transcriptomics to elucidate key cellular mechanisms of resistance, with particular emphasis on lipid-mediated stromal-immune interactions within the TNBC TME. This investigation encompassed analysis of single-cell RNA sequencing (scRNA-seq) data from three TNBC datasets and spatial transcriptomic data from 43 TNBC samples. Spatial niches and cell-cell interactions were identified using the Multimodal Intersection Analysis (MIA) algorithm. Experimentally, adipose-derived mesenchymal stem cells (AD-SCs) were co-cultured with MDA-MB-231 TNBC cells to generate lipid-processing CAFs (lpCAFs) and subsequently co-cultured with THP-1 macrophages. Lipid metabolism and M2 polarization of macrophages were assessed using BODIPY staining, Oil Red O, qPCR, flow cytometry and Western blotting techniques. ABCA8 ABCA8 Show less
SLC35B4, a nucleotide sugar transporter that mediates the transport of UDP-GlcNAc and UDP-xylose, was found to be required for the replication of influenza A virus (IAV) of the H5N1 subtype in our gen Show more
SLC35B4, a nucleotide sugar transporter that mediates the transport of UDP-GlcNAc and UDP-xylose, was found to be required for the replication of influenza A virus (IAV) of the H5N1 subtype in our genome-wide siRNA library screen. We found that defective IAV replication in SLC35B4-deficient A549 cells was independent of virus strain specificity, and the virulence of IAV in Slc35b4 knockdown mice was also decreased. By examining the individual stages of the IAV replication cycle, we discovered that the amount of internalized IAV was significantly reduced in SLC35B4-knockout A549 cells. Mechanistically, SLC35B4 facilitated IAV replication by transporting UDP-xylose, which attaches to the serine residue of heparan sulfate proteoglycans (HSPGs) in the heparan sulfate (HS) biosynthesis pathway. Knockdown of associated host factors (i.e., XYLT2, B4GALT7, EXT1, and EXT2) in the HS biosynthesis pathway also impaired IAV replication. Furthermore, we revealed that AGRN, a unique HSPG family member, was important for the endocytosis of IAV in A549 cells. Moreover, we found that the homeostasis of the AGRN protein was regulated by HS modification mediated by the initial UDP-xylose transporter SLC35B4, thereby affecting the expression level of endocytic adapter AP2B1 to influence IAV internalization. Collectively, these findings establish that SLC35B4 is an important regulator of IAV replication and uncover the underlying mechanisms by which SLC35B4 employs UDP-xylose transport activity to promote IAV internalization.IMPORTANCEThe entry process of IAV represents a favorable target for drug development. In this study, we identified SLC35B4 as an important host factor for the efficient replication of different subtypes of IAV Show less
Qianzhu Jiang, Huiting Li · 2025 · Journal of bioenergetics and biomembranes · Springer · added 2026-04-24
Myocardial fibrosis (MF) is a key pathological process driving heart failure, characterized by excessive extracellular matrix (ECM) deposition and impaired cardiac function. Although myocyte-specific Show more
Myocardial fibrosis (MF) is a key pathological process driving heart failure, characterized by excessive extracellular matrix (ECM) deposition and impaired cardiac function. Although myocyte-specific enhancer factor 2 A (MEF2A) is implicated in cardiac fibroblast activation, its role in MF remains unclear. We manipulated MEF2A expression in cardiac fibroblasts (CFs) through knockdown and overexpression, and assessed fibrosis markers, migration, and RhoA signaling. Binding of MEF2A to the Snail1 promoter was predicted using JASPAR and validated by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. Rescue experiments with Snail1 overexpression and RhoA inhibition were performed. An angiotensin II (Ang II)-induced MF mouse model was used to evaluate cardiac function by echocardiography and to assess collagen deposition through picrosirius red (PSR) staining. MEF2A was significantly upregulated in Ang II-induced fibrotic hearts and CFs. MEF2A knockdown reduced α-SMA and Col1a1 expression, inhibited CF migration, and suppressed activation of the Snail1/RhoA/α-SMA pathway. ChIP and luciferase assays confirmed the direct binding of MEF2A to the Snail1 promoter. Inhibition of RhoA signaling reversed MEF2A-induced myofibroblast activation and migration. Rescue experiments showed that Snail1 overexpression restored the fibrotic phenotype suppressed by MEF2A knockdown. In vivo, MEF2A knockdown improved left ventricular function, reduced collagen deposition (PSR staining), and lowered heart weight/tibia length ratios. MEF2A promotes myocardial fibrosis by directly activating Snail1 and engages the RhoA/α-SMA pathway. Targeting MEF2A offers a promising therapeutic strategy to attenuate MF and improve heart function. Show less
The treatment and prognosis of cardiac amyloidosis (CA) depend heavily on the accurate identification of amyloid protein types. Histopathological methods are the most commonly used approach, but often Show more
The treatment and prognosis of cardiac amyloidosis (CA) depend heavily on the accurate identification of amyloid protein types. Histopathological methods are the most commonly used approach, but often produce inconclusive results. The application of mass spectrometry with laser microdissection mass spectrometry based on non-targeted proteomics in CA diagnosis is gradually being recognized, but it is expensive, time-consuming, and still in the early stages of scientific research applications. This study aims to establish a novel typing method based on targeted semi-quantitative proteomics to address the shortcomings of existing methods. Formalin-fixed, paraffin-embedded (FFPE) myocardial tissue samples from 52 CA and 52 hypertrophic cardiomyopathy (HCM) patients were analyzed. A semi-quantitative typing method was developed using triple quadrupole mass spectrometry, with laser microdissection mass spectrometry (LMD-MS) serving as the reference standard. A total of 52 peptides were analyzed. Key amyloid-associated proteins (AAPs) -apolipoprotein A-IV (apo A-IV), apolipoprotein E (apo E), and serum amyloid P component (SAP) - showed high diagnostic accuracy, with AUC values of 0.964, 0.999, and 0.923, respectively. Transthyretin (TTR), immunoglobulin light chains- κ (IGL - κ), and IGL-λ were semi-quantified using normalized scores (NS) adjusted for microdissection and peptide peak areas. An NS This targeted semi-quantitative mass spectrometry method has high consistency with non-targeted LMD-MS typing, with an accuracy higher than IHC (100 % vs. 30.8 %), while compensating for the shortcomings of non-targeted proteomics. It provides a practical method for CA typing in routine clinical laboratories and may help identify rare subtypes of amyloidosis in the future. Show less
Melatonin (MLT) can improve mitophagy, thereby ameliorating cognitive deficits in Alzheimer's disease (AD) patients. Hence, our research focused on the potential value of MLT-related genes (MRGs) in A Show more
Melatonin (MLT) can improve mitophagy, thereby ameliorating cognitive deficits in Alzheimer's disease (AD) patients. Hence, our research focused on the potential value of MLT-related genes (MRGs) in AD through bioinformatic analysis. First, the key cells in the single-cell dataset GSE138852 were screened out based on the proportion of annotated cells and Fisher's test between the AD and control groups. The differentially expressed genes (DEGs) in the key cell and GSE5281 datasets were identified, and the MRGs in GSE5281 were selected via weighted gene coexpression network analysis. After intersecting two sets of DEGs and MRGs, we performed Mendelian randomization analysis to identify the MRGs causally related to AD. Biomarkers were further ascertained through receiver operating characteristic curve (ROC) and expression analysis in GSE5281 and GSE48350. Furthermore, gene set enrichment analysis, immune infiltration analysis and correlation analysis with metabolic pathways were conducted, as well as construction of a regulator network and molecular docking. According to the Fisher test, oligodendrocytes were regarded as key cells due to their excellent abundance in the GSE138852 dataset, in which there were 281 DEGs between the AD and control groups. After overlapping with 3,490 DEGs and 550 MRGs in GSE5281, four genes were found to be causally related to AD, namely, G protein-coupled receptor, family C, group 5, member B (GPRC5B), Methyltransferase-like protein 7 A (METTL7A), NF-κB inhibitor alpha (NFKBIA) and RAS association domain family 4(RASSF4). Moreover, GPRC5B, NFKBIA and RASSF4 were deemed biomarkers, except for METTL7A, because of their indistinctive expression between the AD and control groups. Biomarkers might be involved in oxidative phosphorylation, adipogenesis and heme metabolism. Moreover, T helper type 17 cells, natural killer cells and CD56dim natural killer cells were significantly correlated with biomarkers. Transcription factors (GATA2, POU2F2, NFKB1, etc.) can regulate the expression of biomarkers. Finally, we discovered that all biomarkers could bind to MLT with a strong binding energy. Our study identified three novel biomarkers related to MLT for AD, namely, GPRC5B, NFKBIA and RASSF4, providing a novel approach for the investigation and treatment of AD patients. Show less