Aplastic anemia (AA) is a bone marrow failure disease characterized by immune-mediated destruction of hematopoietic stem and progenitor cells. Bone marrow adiposity represents a typical pathological m Show more
Aplastic anemia (AA) is a bone marrow failure disease characterized by immune-mediated destruction of hematopoietic stem and progenitor cells. Bone marrow adiposity represents a typical pathological manifestation observed in AA. The aim of this study was to establish a murine model of AA using immune-mediated methods and assess the impact of rapamycin (Rapa) and cyclosporin A (CsA) on bone marrow adiposity. The AA murine model was induced by 137Cs γ-ray irradiation and allogeneic lymphocyte infusion. Rapamycin and cyclosporine were administered intraperitoneally. Hematological parameters, bone marrow adiposity, and lipidomic profiles were evaluated. Gene and protein expression related to adipogenesis were analyzed. The Hematoxylin and Eosin (HE) and BODIPY staining results revealed an increase in adipocyte area and a decrease in hematopoietic area in AA murine. Relative expression levels of PPAR-γ, LPL, and Ap2 mRNA were significantly elevated in bone marrow mononuclear cells (BMMNCs) from the AA group. Lipidomics analysis indicated notable differences between the AA group and the normal group regarding lipid metabolism, particularly concerning glycerolphospholipids. Following treatment with Rapa and CsA, not only did the hematological profile of AA murine recover, but there was also a reduction in bone marrow adiposity in HE and BODIPY staining and a decrease in the gene and protein expression of PPAR-γ, LPL, and Ap2. The lipidomic analysis revealed a reduction in the lipid metabolism of AA murine following Rapa and CsA treatment in AA murine, particularly acylcarnitin (ACar), phosphatidylserine (PS) and phosphatidylethanolamine (PE). The enrichment results of the KEGG pathway analysis demonstrated a statistically significant role of C42H82N010P in glycerophospholipid metabolism. Our study used lipidomics for the first time to investigate lipid metabolism in AA murine, revealing that Rapa and CsA primarily downregulate glycerophospholipid metabolism as a means to alleviate bone marrow adiposity in AA murine. Show less
Subcutaneous fat deposition critically impacts duck meat quality and feed efficiency. We monitored growth and fat deposition in ducks from 30 to 70 days, performed transcriptomics on adipose tissue, a Show more
Subcutaneous fat deposition critically impacts duck meat quality and feed efficiency. We monitored growth and fat deposition in ducks from 30 to 70 days, performed transcriptomics on adipose tissue, and established an in vitro duck preadipocyte model to assess Fat deposition peaked at 50 days. Show less
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on Show more
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on the molecular mechanisms underlying differences in lipid droplet accumulation in avian adipocytes remains limited. This study confirmed a significant positive correlation (R Show less
This study investigated the synergistic effects of combining ferulic acid esterase (FAE)-producing lactobacillus with homofermentative and heterofermentative lactic acid bacteria (LAB) on the fermenta Show more
This study investigated the synergistic effects of combining ferulic acid esterase (FAE)-producing lactobacillus with homofermentative and heterofermentative lactic acid bacteria (LAB) on the fermentation quality, nutrient composition, and aerobic stability of corn stover silage. In this study, five LAB strains were isolated and identified from various silages. Among them, strain AR1 was identified as The results showed that the co-fermentation of homofermentative and heterofermentative strains improved silage fermentation quality. The addition of AR1 to the combination of homofermentative and heterofermentative LAB further enhanced lactic acid and acetic acid production, decreased neutral and acid detergent fiber contents, and improved aerobic stability. Principal component analysis and membership function analysis identified the LPLR group (an equal mixture of AR1, R10, JF2, and R3 at 1 × 10 Show less
Acetyl-CoA synthetase 2 (ACSS2) is the obligatory gatekeeper for converting rumen-derived acetate into acetyl-CoA in ruminants. However, whether ACSS2 actively regulates the transcriptional networks g Show more
Acetyl-CoA synthetase 2 (ACSS2) is the obligatory gatekeeper for converting rumen-derived acetate into acetyl-CoA in ruminants. However, whether ACSS2 actively regulates the transcriptional networks governing lactation, beyond its catalytic role, remains unclear. This study aimed to elucidate the molecular characteristics of buffalo ACSS2 and investigate its function as a central node in the metabolic-transcriptional circuitry of buffalo mammary epithelial cells (BuMECs). The complete coding sequence of buffalo ACSS2 was characterized, and its expression was analyzed across lactation stages. Subcellular localization was determined via high-resolution confocal microscopy. We utilized siRNA-mediated knockdown in BuMECs to assess cell viability, triglyceride (TAG) content, and the expression of core metabolic and regulatory genes to dissect the underlying molecular mechanisms. ACSS2 expression was highly enriched in lactating mammary tissue, and the protein exhibited a dual nucleocytoplasmic distribution. ACSS2 knockdown induced a "dual collapse" of cellular function: it severely impaired lipogenesis (significantly reducing intracellular TAG and downregulating FASN, ACACA, SCD, CD36, LPL, FABP3, DGAT1, DGAT2 and AGPAT6) and arrested cell proliferation (downregulating the G1/S phase regulators CCND1, CCNE1, CDK2 and CDK4). Mechanistically, ACSS2 depletion dismantled the transcriptional machinery itself, suppressing the mRNA levels of master regulators SREBF1 and PPARG. Crucially, this collapse was accompanied by the paradoxical upregulation of the SREBP1-inhibitor INSIG1, suggesting that metabolic stress triggers an INSIG1-mediated blockade of the feedback loop. This study establishes ACSS2 as a critical metabolic checkpoint in the buffalo mammary gland, rather than a passive enzyme. We propose a model where ACSS2 maintains a reciprocal positive feedback loop with SREBP1 and PPARG. By ensuring sufficient acetyl-CoA to suppress INSIG1 and support histone acetylation (implied by nuclear localization), ACSS2 couples substrate availability to the stability of the lipogenic program and cell cycle progression. These findings reveal an evolutionarily conserved metabolic-epigenetic axis essential for high-efficiency lactation in ruminants. Show less
Diabetes affects over half a billion people worldwide, with cardiovascular disease being its leading cause of death, either occurring secondary to atherosclerosis or due to an intrinsic defect in hear Show more
Diabetes affects over half a billion people worldwide, with cardiovascular disease being its leading cause of death, either occurring secondary to atherosclerosis or due to an intrinsic defect in heart muscle (diabetic cardiomyopathy, DbCM). One instigator for DbCM is impaired cardiac metabolism characterized by excessive fatty acid (FA) delivery and utilization by the heart, causing oxidative stress and toxic lipid accumulation. Inhibition of vascular endothelial growth factor B (VEGFB) has been shown to counter these factors associated with abnormal cardiac metabolism by inducing metabolic flexibility and preventing cardiac lipid accumulation in Type 2 diabetes. However, its impact on lipoprotein lipase (LPL) and the sources of FA for cardiac use in Type 1 diabetes is unknown. Global Show less
This article presents a case of a rare lymphoplasmacytic lymphoma (LPL) complicated by spherocytosis in a 74-year-old male. The patient reported progressive fatigue and anemia and had a medical histor Show more
This article presents a case of a rare lymphoplasmacytic lymphoma (LPL) complicated by spherocytosis in a 74-year-old male. The patient reported progressive fatigue and anemia and had a medical history of type 2 diabetes, hypertension, and cerebral infarction. Laboratory tests indicated moderate anemia (hemoglobin 80 g/L) and a monoclonal increase in serum IgG. A bone marrow biopsy combined with immunohistochemistry confirmed the diagnosis of lymphoplasmacytic lymphoma (IgG-κ type, MYD88 L265P negative). A peripheral blood smear revealed an increase in spherocytes, a positive acidified glycerolysis test (AGLT50), abnormal erythrocyte osmotic fragility, and a negative direct antiglobulin test. Genetic screening for hereditary erythrocyte diseases showed no pathogenic variations. The patient's condition stabilized following targeted therapy with zanubrutinib and rituximab (ZR regimen). This case underscores the complexity of diagnosing dual hematological anomalies, highlights the importance of multidisciplinary collaboration, and seeks to explore the potential pathophysiological link between LPL and spherocytosis, offering a reference for diagnosis and treatment in similar clinical scenarios. Show less
Intramuscular fat (IMF) is a key determinant of meat quality, influencing tenderness, juiciness, and flavor. Previous studies have reported that the deposition of IMF is controlled by various factors. Show more
Intramuscular fat (IMF) is a key determinant of meat quality, influencing tenderness, juiciness, and flavor. Previous studies have reported that the deposition of IMF is controlled by various factors. However, there is a shortage of research exploring the variations in IMF deposition across age groups from a microbial perspective. This study evaluated the differences in IMF deposition between yearling (1-year-old) and mature (4-year-old) Longdong Cashmere goats and analyzed its association with gut microbiota. The results revealed that the IMF content in shoulder meat and blood lipid levels increased with age (p < 0.05). Conversely, the contents of lipoprotein lipase (LPL) in the liver and duodenum significantly decreased with age. Microbial diversity differed between the two age groups, with specific microbiota identified from the gut of goats involved in the lipid metabolism pathway. The concentrations of valeric and isovaleric acids in the rumen, as well as acetic, propionic and isovaleric acids in the colon, were higher in yearling goats than in mature goats (p < 0.05). Spearman correlation analysis of IMF deposition indicators with gut microbiota revealed that, within the rumen, the abundances of CAG-791 and Sodaliphilus were positively correlated with IMF content in shoulder meat and TG levels, while exhibiting a negative correlation with the contents of valeric acids. Furthermore, the abundance of Clostridium_R showed a positive association with IMF content in shoulder meat and with the abundances of CAG-791and Sodaliphilus. In contrast, the abundance of Bact₁₁ was negatively correlated with IMF content in shoulder meat, TG levels, and the abundances of CAG-791, Sodaliphilus and Clostridium_R. Within the abomasum, the abundances of UMGS and Hylemonella₅₈₂₃₀₈ were correlated with IMF content in the shoulder meat, as well as serum LDL and VLDL levels. This study provides significant insights into the age-dependent gut microbiota associated with intramuscular fat deposition in goats and identifies several potential gut microbiota for further research on their impacts on IMF deposition. Show less
Organic afterglow materials are garnering increasing attention due to their great potential in practical applications. To date, most organic afterglow materials can achieve only millisecond- or second Show more
Organic afterglow materials are garnering increasing attention due to their great potential in practical applications. To date, most organic afterglow materials can achieve only millisecond- or second-scale afterglow lifetimes, while realizing long persistent luminescence (LPL) lasting for hours or even days remains a significant challenge. Since 2017, when Adachi and Kabe first achieved LPL lasting over an hour in a purely organic system, LPL materials have undergone a decade of development, with polymer-based LPL materials exhibiting rapid progress in recent years. The energy level alignment in exciplex polymers and the resulting charge separation characteristics are closely associated with their unique LPL functional properties, primarily stemming from the well-designed donor and acceptor organic structures. This article provides a systematic review of the design strategies for LPL polymers and summarizes their current application advances in optical anti-counterfeiting, night-time illumination, smart textiles, and other related fields. Show less
The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, usi Show more
The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, using a CRISPR/Cas9-mediated Show less
Backfat thickness, a key selection trait in pig-breeding programmes, has traditionally been measured as a homogeneous layer. However, backfat is anatomically structured into three distinct layers, and Show more
Backfat thickness, a key selection trait in pig-breeding programmes, has traditionally been measured as a homogeneous layer. However, backfat is anatomically structured into three distinct layers, and each layer likely contributes differently to carcass quality. In addition, previous studies have shown that the deposition of the third layer of backfat is phenotypically correlated with intramuscular fat (IMF). Therefore, targeted selection for specific backfat layers, particularly the third layer, represents a potential strategy to increase IMF content while maintaining a high lean meat percentage. However, the genetic architecture of these distinct porcine backfat layers remains poorly understood. The aim of this study was to estimate the genetic parameters and identify key candidate genes underlying the three backfat layers. We collected B-mode ultrasound images from 561 Landrace pigs to measure individual layer thickness, followed by DNA extraction, genotyping, genetic parameter estimation, and a genome-wide association study (GWAS). Our measurements showed that the first layer of backfat (FBF) is the thickest, followed by the second (SBF) and the third (TBF) layers. Genetic parameter estimation yielded heritability estimates of 0.37, 0.42, 0.38, 0.34, 0.32, 0.24, and 0.21 for total backfat (BF), FBF, FBF/BF, SBF, SBF/BF, TBF, and TBF/BF, respectively. Through integrated analysis of GWAS, Bayesian fine-mapping, and gene annotation, we identified 15 non-redundant candidate genes associated with different backfat layers. These included two genes (SOAT1 and ACBD6) shared by BF and SBF, LPL for BF and FBF, and CAND1 for TBF and TBF/BF. Additionally, SERPINA12 and SERPINA6 were associated with BF; PRKAG1 and PRDM16 with FBF; EPRS1 and SLC39A10 with FBF/BF; PTGES and CRAT with SBF; and ACLY, CAVIN1, and PDZRN3 with SBF/BF. Our results indicate that each layer is governed by a distinct set of genes, which advances our understanding of the genetic basis of backfat layers in pigs. Show less
Tail fat deposition constitutes a distinctive adaptive phenotype in sheep. The Large-tailed Han (LTH) and Small-tailed Han (STH) breeds display pronounced divergence in tail fat storage, offering an i Show more
Tail fat deposition constitutes a distinctive adaptive phenotype in sheep. The Large-tailed Han (LTH) and Small-tailed Han (STH) breeds display pronounced divergence in tail fat storage, offering an ideal model for elucidating lipid metabolism regulation. Integrated sRNA-Seq and RNA-Seq analysis identified 521 differentially expressed genes and 144 miRNAs, which were significantly enriched in lipid metabolism pathways, including fatty acid metabolism and PPAR signaling. Key candidate genes ( Show less
The primary renal complication of diabetes mellitus is diabetic kidney disease (DKD). The precise pathogenic mechanisms of DKD remain poorly elucidated. The aim of this study was to identify potential Show more
The primary renal complication of diabetes mellitus is diabetic kidney disease (DKD). The precise pathogenic mechanisms of DKD remain poorly elucidated. The aim of this study was to identify potential energy metabolism-related genes associated with DKD. The GSE30529 and GSE30528 datasets were retrieved from the Gene Expression Omnibus, and energy metabolism-related genes were obtained from the GeneCards database. Differentially expressed genes (DEGs) between DKD and control groups were analyzed. The biological functions and signaling pathways of these DEGs were evaluated using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). The diagnostic performance of hub genes for DKD was assessed using receiver operating characteristic (ROC) curve analysis. Expression levels of five significant energy metabolism-related genes were validated through immunohistochemistry. The Nephroseq V5 tool was used to evaluate gene expression in DKD and to determine correlations between gene expression and renal function in patients with DKD. A total of 17 energy metabolism-related DEGs were identified. Five hub genes-ALB, IGF1, CD36, LPL, and UCP2-were identified. Among these, CD36 and LPL demonstrated relatively high diagnostic accuracy for DKD. The findings suggest that CD36, IGF1, LPL, and UCP2 may serve as potential biomarkers for DKD. The genes CD36, IGF1, LPL, and UCP2 represent potential energy metabolism-related biomarkers with possible applications in the diagnosis and treatment of DKD. Show less
Suhua Wu, Juan Peng, Xiaodong Wang+11 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Obesity has become a global epidemic and a major contributor to the development of Type 2 diabetes (T2D) through the promotion of insulin resistance. Emerging evidence has shown that GPX4 expression i Show more
Obesity has become a global epidemic and a major contributor to the development of Type 2 diabetes (T2D) through the promotion of insulin resistance. Emerging evidence has shown that GPX4 expression is reduced in macrophages under hyperglycemic conditions; however, the involvement of macrophage-specific GPX4 in obesity-associated insulin resistance remains unclear. We generated macrophage-specific Gpx4 knockout (Gpx4 Show less
Reading acquisition requires linking visual symbols with speech sounds, leading to the development of neural sensitivity to print. While prior studies have shown the importance of cross-modal integrat Show more
Reading acquisition requires linking visual symbols with speech sounds, leading to the development of neural sensitivity to print. While prior studies have shown the importance of cross-modal integration in spoken language areas, the higher-level visual area (lvOT) processing printed words remained more context-dependent. This longitudinal study investigated whether the lvOT undergoes cross-modal reorganization to facilitate print-speech integration during reading development and how these changes relate to reading skills. We followed children over two years, beginning at the onset of formal reading instruction. We examine lvOT responses to print-specific, speech-specific, and its convergence at whole-brain, region of interest, and voxel-based levels. Results showed that with reading experience, the initial print-specific responses in the lvOT are transformed into responses to both print and speech input. This transformation positively correlates with reading skills, especially in early stages of reading acquisition. These findings suggest that reading acquisition drives cross-modal reorganization within the lvOT, enabling the area to integrate print and speech. They shed light on the broader neural mechanisms supporting reading development. Show less
To investigate the toxic effects of PFNA on aquatic organisms, this study used large yellow croaker (L. crocea) as a model and examined the impacts of 1000 ng/L PFNA exposure for 3, 7, and 14 days on Show more
To investigate the toxic effects of PFNA on aquatic organisms, this study used large yellow croaker (L. crocea) as a model and examined the impacts of 1000 ng/L PFNA exposure for 3, 7, and 14 days on the hepatic and intestinal systems. Histopathological examination, transcriptomic profiling, and 16S rRNA gene sequencing were employed to evaluate tissue damage, gene expression changes, and gut microbial alterations. The results revealed that PFNA exposure induced progressive histopathological changes in the liver, including nuclear enlargement and vacuolization, with increasing severity over time. In the intestine, PFNA caused structural damage to villi, characterized initially by vacuolization and subsequently by erosion, swelling, and dissolution as exposure duration increased. Transcriptomic analysis of liver showed early activation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway, followed by the predominant enrichment of the phosphatidylinositol-3-kinase/protein kinase B (PI3K-Akt) pathway at later stages. These findings suggest a "two-phase" mechanism by which PFNA disrupted lipid and carbohydrate metabolism. Gut microbiota analysis showed that PFNA exposure significantly reduced α-diversity, increased the abundance of Proteobacteria, enriched opportunistic pathogens such as Vibrio spp., and altered functional profiles related to amino acid and carbohydrate metabolism. Correlation analysis identified significant associations between specific gut microbial taxa (e.g., Deferribacterota, Dependentiae) and the expression levels of key hepatic metabolic genes (lpl, foxo3), suggesting a potential mediating role of the gut-liver axis in PFNA-induced hepatotoxicity. From the perspective of aquaculture, this study provided a view of metabolic disruption and host-microbe interaction caused by PFNA. It contributes critical scientific evidence for assessing the ecological risks of per- and polyfluoroalkyl substances (PFAS) in aquatic environments. Show less
Organic and organic-inorganic hybrid materials exhibiting room-temperature phosphorescence (RTP) and long persistent luminescence (LPL) materials have attracted growing attention for various time-reso Show more
Organic and organic-inorganic hybrid materials exhibiting room-temperature phosphorescence (RTP) and long persistent luminescence (LPL) materials have attracted growing attention for various time-resolved optoelectronic applications. To date, realizing intrinsically distinct RTP and LPL emissions within a single material system remains elusive, yet it is crucial for unlocking multifunctional applications such as multilevel optical encryption. Here, a Mn Show less
Xinjiang Province possesses several local sheep breeds which are well known for their tender meat, delicious taste, and lack of odor. At present, the microbial composition in the gastrointestinal trac Show more
Organic room-temperature phosphorescence (RTP) materials have attracted significant interest due to their potential in optoelectronics and anti-counterfeiting. However, achieving multicolor-tunable an Show more
Organic room-temperature phosphorescence (RTP) materials have attracted significant interest due to their potential in optoelectronics and anti-counterfeiting. However, achieving multicolor-tunable and long-lived RTP with simple, low-cost systems remains challenging. Herein, a facile host-guest doping strategy is developed to realize efficient and color-tunable RTP by embedding butterfly-shaped triphenylamine-based guest molecules (TPA, DBD, and DBDBD) into various host matrices (e.g., TPP, BPP, or CA). The doped crystals exhibit distinct afterglow colors (green to yellow) and prolonged long-persistent luminescence (LPL) (from 1 to 6 s of afterglow time) and phosphorescence lifetimes up to 763.33 ms, governed by host-guest energy transfer and intersystem crossing enhancement. Density functional theory (DFT) calculations reveal that the guest's electron-donating ability and the host's heavy-atom effect (e.g., P in TPP) synergistically promote charge separation and suppress non-radiative decay. Notably, DBDBD:TPP shows the longest LPL (6 s of afterglow time) due to optimal energy level alignment and strong intermolecular interactions. By leveraging the time- and color-dependent afterglow, applications in multilevel information encryption and anti-counterfeiting are demonstrated, where encrypted messages are dynamically revealed under UV excitation. This work provides a simple yet versatile approach to designing low-cost, multicolor RTP materials for advanced photonic applications. Show less
Embryos produced in vitro exhibit heightened cryosensitivity due to excessive lipid accumulation. Previous studies demonstrated that cyclic guanosine monophosphate (cGMP) modulates intracellular lipid Show more
Embryos produced in vitro exhibit heightened cryosensitivity due to excessive lipid accumulation. Previous studies demonstrated that cyclic guanosine monophosphate (cGMP) modulates intracellular lipid metabolism through cGMP-dependent protein kinase (PKG) signaling in various cell types. This study investigated the effects of cGMP on (i) cryosurvival in sheep embryos, (ii) embryonic quality, and (iii)lipolysis-related parameters. Specifically, we quantified lipid droplet content, free fatty acid levels, and hormone-sensitive lipase (HSL) phosphorylation status as key indicators of lipolytic activity. The results showed that cGMP pretreatment (0.5 mM) for 10 min prior to slow freezing significantly improved post-thaw embryo recovery rates and upregulated the mRNA expression of key developmental genes (POU5F1, SOX2, CDX2, and NANOG). cGMP pretreatment significantly upregulated the expression of multiple lipid catabolism genes (ACSL4, HMGCR, HMGCS1, LIPE, LPL, LIPF, and PLIN2), with LIPE (encoding HSL) exhibiting the most pronounced induction (27.10-fold increase vs. control). Following cGMP pretreatment, PKG activation triggered significant increases in the intracellular Ca Show less
We aimed to investigate whether maternal and fetal genetic predispositions to insulin deficiency and resistance affect offspring fetal growth through distinct pathways in multi-ethnic populations. In Show more
We aimed to investigate whether maternal and fetal genetic predispositions to insulin deficiency and resistance affect offspring fetal growth through distinct pathways in multi-ethnic populations. In 5065 multi-ethnic mother-infant pairs, we examined the conditional associations of maternal and fetal partitioned polygenic risk scores (pPRSs) for type 2 diabetes-related pathways with fetal growth outcomes, including birthweight, sum of skinfold thicknesses (SSF), large-for-gestational-age (LGA) births and small-for-gestational-age (SGA) births. Two-sample Mendelian randomisation (2SMR) in Europeans was performed for triangulation. Exposures were eight type 2 diabetes-related pathways (n=1,812,017), eight beta cell function indices (n=26,356) and two insulin sensitivity indices (n=53,657). Outcomes were maternal and fetal genetically determined birthweight (n=406,063). Mediation analysis was used to assess the mediation effects of maternal glucose levels and BMI on maternal genetic effects and of cord blood C-peptide on fetal genetic effects. Co-localisation analyses were performed to test for shared causal variants. Fetal type 2 diabetes polygenic risk score (PRS) and pPRSs for lipodystrophy-related insulin resistance and impaired fasting glucose (IFG)-related insulin deficiency were associated with lower birthweight and SSF, while maternal type 2 diabetes PRS and pPRSs for IFG-related insulin deficiency and obesity-related insulin resistance were associated with higher offspring birthweight, SSF and LGA. These associations were consistent across five ethnic groups. Maternal post-load hyperglycaemia mediated 44.2% and 34.2% of the effects of type 2 diabetes PRS and IFG pPRS, respectively, while maternal BMI mediated 43.4% of the effect of Obesity pPRS. 2SMR found consistent results in Europeans and further revealed that fetal insulin sensitivity index and corrected insulin response were associated with higher birthweight. Some loci with shared causal variants acted through multiple pathways, including CDKAL1, TCF7L2, ADCY5 and MACF1. Reduced fetal growth may be driven by lipodystrophy-related insulin resistance and IFG-related insulin deficiency pathways. Targeting pregnant women with high type 2 diabetes PRS/pPRS and prescribing interventions to reduce their post-load hyperglycaemia and BMI may help reduce offspring risk of LGA. Show less
Yuanyuan Wang, Shuzhen Fu, Yong Shen+1 more · 2026 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · added 2026-04-24
To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. The clinical data of 10 patients with KMT2A fusion ge Show more
To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival. Show less
In this study, we used optical genome mapping (OGM), conventional karyotyping, and next-generation sequencing to analyze cytogenomic alterations in 91 cases of T-cell acute lymphoblastic leukemia/lymp Show more
In this study, we used optical genome mapping (OGM), conventional karyotyping, and next-generation sequencing to analyze cytogenomic alterations in 91 cases of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Whereas karyotyping detected abnormal karyotypes in 55% of cases, OGM identified cytogenetic abnormalities in 97.8% of the cases and provided clinically relevant information beyond karyotyping in ∼70% of cases. OGM detected gene rearrangements in 80% of cases, including 24 recurrent gene fusions and 21 previously unreported putative gene fusions in T-ALL. Copy number variants were detected in 93% of cases, with interstitial deletions the most common. Gene mutations were detected in 93% of cases, with NOTCH1 being most frequent (in 57% of cases). Combining all data, most T-ALL cases harbored 3 or more cytogenomic aberrations. Specific cytogenomic alterations differed among T-ALL subtypes as follows: rearrangements of BCL11B and PICALM::MLLT10, deletions of 7p, and mutations involving DNMT3A, WT1, TET2, IDH2, and FLT3 were common in early T-precursor and near-early T-precursor subtypes. Rearrangements of TLX1, KMT2A, STIL::TAL1, and NUP214::ABL1, deletions of 9p, and FBXW7 mutations were frequently associated with the cortical subtype. We conclude that integration of OGM and next-generation sequencing with karyotyping enables comprehensive cytogenomic profiling of T-ALL that improves detection of clinically relevant genomic alterations and may inform disease classification and future studies of risk stratification. Show less
In this retrospective study, a total of 3468 adolescent and adult AML patients were screened, and 181 patients harboring The incidence of Our study revealed the heterogeneous outcomes of
PICALM∶∶MLLT10 fusion gene-positive precursor B-cell acute lymphoblastic leukemia(pro-B-ALL)is clinically rare.This article reports the case of a 29-year-old female patient who presented a mediastinal Show more
PICALM∶∶MLLT10 fusion gene-positive precursor B-cell acute lymphoblastic leukemia(pro-B-ALL)is clinically rare.This article reports the case of a 29-year-old female patient who presented a mediastinal mass.Diagnostic investigations confirmed PICALM∶∶MLLT10 fusion gene-positive pro-B-ALL.The patient sequentially received radiotherapy and multiple lines of chemotherapy but developed short-term drug resistance and lineage change,progressing to mixed-phenotype acute leukemia.A review of relevant literature was conducted to analyze its pathogenesis and molecular characteristics,aiming to provide references for clinical diagnosis and treatment. Show less
Ting Fang, Xinyu Yang, Xiaoqing Deng+5 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Excessive fructose intake is strongly associated with metabolic diseases, with the carbohydrate response element-binding protein (ChREBP) playing a key role in its metabolism, particularly in renal tu Show more
Excessive fructose intake is strongly associated with metabolic diseases, with the carbohydrate response element-binding protein (ChREBP) playing a key role in its metabolism, particularly in renal tubules. However, the role of its active form, ChREBP-β, was previously unclear. In this study, ChREBP-β overexpression and ChREBP knockout mouse models were utilized to investigate the effects of excessive fructose intake in vivo. In addition, primary renal tubular epithelial cells from mice and human kidney-2 (HK2) cells were applied for further validation in vitro. We found that ChREBP-β leads to increased transcription to mediate endoplasmic reticulum stress and mitochondrial dysfunction, which ultimately impairs renal function. Our findings underscore the critical role of ChREBP-β in fructose-related renal disorders. Show less
High-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummin Show more
High-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummingbirds, parrots, honeyeaters, and sunbirds by generating nine new genomes and 90 tissue-specific transcriptomes. Comparative screens revealed an excess of repeated selection in both protein-coding and regulatory sequences in sugar-feeding birds, suggesting reuse of genetic elements. Sequence or expression changes in sugar-feeders affect genes involved in blood pressure regulation and lipid, amino acid, and carbohydrate metabolism, with experiments showing functional changes in honeyeater hexokinase 3. Show less
Renal tubulointerstitial fibrosis (TIF) is a hallmark pathological feature of diabetic kidney disease (DKD). This study investigates the role and molecular mechanisms of retinol saturase (RetSat) in D Show more
Renal tubulointerstitial fibrosis (TIF) is a hallmark pathological feature of diabetic kidney disease (DKD). This study investigates the role and molecular mechanisms of retinol saturase (RetSat) in DKD-associated TIF. RetSat expression was assessed in renal tissues from DKD patients and mice and correlated with the severity of TIF. Functional experiments were conducted RetSat expression was significantly up regulated in the renal tissues of both DKD patients and mice, correlating with the deterioration of TIF. These findings indicate that RetSat promotes TIF in DKD by disrupting the Smurf2-ChREBP ubiquitination axis, highlighting RetSat as a promising therapeutic target for DKD. Show less
Neuropathic pain (NP), a chronic disorder caused by somatosensory nervous system lesions, severely impairs the quality of life. Microglial metabolic reprogramming and neuroinflammation drive NP progre Show more
Neuropathic pain (NP), a chronic disorder caused by somatosensory nervous system lesions, severely impairs the quality of life. Microglial metabolic reprogramming and neuroinflammation drive NP progression. Although ChREBP (key metabolic regulator) protects against NP, its specific mechanisms remain unclear. NP rat model was established via spared nerve injury (SNI) surgery, and mechanical allodynia was evaluated using Von Frey tests. ChREBP expression in microglia was detected through immunofluorescence, RT-qPCR, and western blot. Functional studies involved ChREBP knockdown/overexpression to assess effects on microglial polarization, neuroinflammation, neuronal excitability, pain behaviors, and fatty acid metabolism. Mechanisms were explored via dual-luciferase reporter and chromatin immunoprecipitation assays. Mechanical pain thresholds were significantly decreased on the ipsilateral side after SNI. ChREBP was upregulated in SDH microglia after SNI and in LPS-stimulated microglia in vitro. ChREBP knockdown inhibited anti-inflammatory microglial polarization, exacerbated neuroinflammation, and aggravated pain. Conversely, ChREBP overexpression promoted the anti-inflammatory phenotype, suppressed neuroinflammation, and alleviated pain. ChREBP enhanced microglial fatty acid oxidation and energy metabolism. Mechanistically, ChREBP bound to the TFBS1 site on the PGC-1α promoter to activate its transcription. PGC-1α overexpression rescued the impairments caused by ChREBP knockdown, including reduced fatty acid oxidation, suppressed anti-inflammatory polarization, elevated inflammatory factors, and increased neuronal excitability. The protective effects of ChREBP were attenuated by the fatty acid oxidation inhibitor Etomoxir. ChREBP alleviates NP by enhancing microglial fatty acid oxidation and anti-inflammatory phenotype via PGC-1α transcriptional activation, revealing a novel metabolic-immune axis for potential NP therapy. Show less