Cirrhosis and hepatocellular carcinoma (HCC) are long-term complications of chronic liver disease (CLD). In this large multi-ancestry genome-wide association study of all-cause cirrhosis (35,481 cases Show more
Cirrhosis and hepatocellular carcinoma (HCC) are long-term complications of chronic liver disease (CLD). In this large multi-ancestry genome-wide association study of all-cause cirrhosis (35,481 cases, 2.36M controls) and HCC (6,680 cases, 1.76M controls), we identified 27 loci associated with cirrhosis (10 novel) and 11 with HCC (three novel). Three novel cirrhosis loci were replicated in independent cohorts (e.g. Show less
Traumatic brain injury (TBI) represents a major cause of mortality and disability worldwide, particularly affecting young adults and elderly populations. This study investigates the neuroprotective po Show more
Traumatic brain injury (TBI) represents a major cause of mortality and disability worldwide, particularly affecting young adults and elderly populations. This study investigates the neuroprotective potential of orlistat (ORL), a gastrointestinal lipase inhibitor, in a murine TBI model. Behavioral, histological, and molecular analyses demonstrated that ORL significantly attenuated TBI-induced neurological damage. Microglial depletion experiments revealed that ORL's neuroprotective effects were largely mediated through microglial modulation. In vitro and in vivo studies showed that ORL suppressed microglial activation, phagocytosis, and migration. Single-cell RNA sequencing identified upregulation of lipoprotein lipase (LPL) in a TBI-induced microglial subpopulation. Molecular docking predicted ORL-LPL binding, suggesting direct enzymatic inhibition. Transcriptomic and metabolomic analyses further revealed ORL's modulation of microglial metabolic pathways and inflammatory responses. Our findings position ORL as a promising repurposed therapeutic for TBI through its novel mechanism of targeting microglial LPL-mediated neuroinflammation. Show less
Mammalian scent glands mediate species-specific chemical communication, yet the mechanistic basis for convergent musk production remain incompletely understood. Forest musk deer and muskrat have indep Show more
Mammalian scent glands mediate species-specific chemical communication, yet the mechanistic basis for convergent musk production remain incompletely understood. Forest musk deer and muskrat have independently evolved specialized musk-secreting glands, representing a striking case of convergent evolution. Through an integrated multi-omics approach, this study identified cyclopentadecanone as a shared key metabolic precursor in musk from both forest musk deer and muskrat, although downstream metabolite profiles diverged between the two lineages. Single-cell RNA sequencing revealed that these specialized apocrine glands possessed unique secretory architecture and exhibited transcriptional profiles associated with periodic musk production, distinct from those in conventional apocrine glands. Convergent features were evident at the cellular level, where acinar, ductal, and basal epithelial subtypes showed parallel molecular signatures across both taxa. Notably, acinar cells in both species expressed common genes involved in fatty acid and glycerolipid metabolism (e.g., Show less
The chimeric cytokine IC7Fc conveys the metabolic signaling properties of the glycoprotein 130 receptor cytokines interleukin-6 and ciliary neurotrophic factor via membrane-bound signaling. IC7Fc was Show more
The chimeric cytokine IC7Fc conveys the metabolic signaling properties of the glycoprotein 130 receptor cytokines interleukin-6 and ciliary neurotrophic factor via membrane-bound signaling. IC7Fc was previously shown to slow the progression of type 2 diabetes mellitus, and here, we demonstrate its effect on atherosclerotic development. In APOE*3-Leiden.CETP mice, an atherosclerosis-prone model with a humanized lipoprotein metabolism, IC7Fc markedly lowered plasma triglyceride and total cholesterol levels. This was mechanistically explained by an inhibition of de novo lipogenesis in the liver, increased synthesis of bile acids from cholesterol, and down-regulated apolipoprotein B synthesis, which resulted in decreased cholesterol secretion in very low-density lipoprotein particles. As a consequence, IC7Fc treatment considerably reduced atherosclerotic lesion formation and vascular inflammation compared with current antihyperlipidemic therapy. In conclusion, IC7Fc is a promising pharmacological treatment for cardiometabolic diseases targeting hyperlipidemia and inflammation. Show less
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined r Show more
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined receptor signals, and assessed their regulatory capacities and specificities through in silico analysis of ligand-receptor interactions. Consequently, we identified a B cell subset that expressed cytokine interleukin-27 (IL-27) and chemokine CXCL10. Through the IL-27-IL-27 receptor interaction, these IL-27/CXCL10-producing B cells targeted CD40-activated B cells in vitro and, upon induction by immunization and viral infection, optimized antibody responses and antiviral immunity in vivo. Also present in breast cancer tumors and retained there through CXCL10-CXCR3 interaction-mediated self-targeting, these cells promoted B cell PD-L1 expression and immune evasion. Mechanistically, Show less
With the development of optical anti-counterfeiting and the increasing demand for high-level information encryption, multimodal luminescence (MML) materials attract much attention. However, the discov Show more
With the development of optical anti-counterfeiting and the increasing demand for high-level information encryption, multimodal luminescence (MML) materials attract much attention. However, the discovery of these multifunctional materials is very accidental, and the versatile host suitable for developing such materials remains unclear. Here, a grossite-type fast ionic conductor CaGa Show less
Brain metastasis occurs in up to 40% of patients with non-small cell lung cancer (NSCLC). Considerable genomic heterogeneity exists between the primary lung tumor and respective brain metastasis; howe Show more
Brain metastasis occurs in up to 40% of patients with non-small cell lung cancer (NSCLC). Considerable genomic heterogeneity exists between the primary lung tumor and respective brain metastasis; however, the identity of the genes capable of driving brain metastasis is incompletely understood. Here, we carried out an in vivo genome-wide CRISPR activation screen to identify molecular drivers of brain metastasis from an orthotopic xenograft model derived from a patient with NSCLC. We found that activating expression of the Alzheimer's disease-associated beta-secretase 1 (BACE1) led to a substantial increase in brain metastases. Furthermore, genetic and pharmacological inhibition of BACE1 blocked NSCLC brain metastasis. Mechanistically, we identified that BACE1 acts through epidermal growth factor receptor to drive this metastatic phenotype. Together, our data highlight the power of in vivo CRISPR activation screening to unveil molecular drivers and potential therapeutic targets of NSCLC brain metastasis. Show less
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with no effective pharmacological treatments. The causal role of triglycerides (TGs) in AAA development remains unclear and contr Show more
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with no effective pharmacological treatments. The causal role of triglycerides (TGs) in AAA development remains unclear and controversial. Mendelian randomization was applied to assess causal relationships between lipoproteins, circulating proteins, metabolites, and the risk of AAA. To test the hypothesis that elevated plasma TG levels accelerate AAA development, we used Mendelian randomization analyses integrating genetic, proteomic, and metabolomic data identified causal relationships between elevated TG-rich lipoproteins, TG metabolism-related proteins/metabolites, and AAA risk. In the angiotensin II infusion AAA model, most These findings identify hypertriglyceridemia as a key contributor to AAA pathogenesis and suggest that targeting TG-rich lipoproteins may be a promising therapeutic strategy for AAA. Show less
The integration of serum biomarkers and gene polymorphisms may enhance early prognostic assessment in sepsis. Early and accurate prediction of outcomes is crucial for optimizing treatment strategies a Show more
The integration of serum biomarkers and gene polymorphisms may enhance early prognostic assessment in sepsis. Early and accurate prediction of outcomes is crucial for optimizing treatment strategies and improving survival. However, the clinical utility of combining genetic markers with conventional inflammatory indicators remains insufficiently validated. In this retrospective cohort ( 6 predictors were retained - PCT, CRP, lactate (LAC), lactate clearance rate (LCR), TLR4 rs4986790, and PPARγ rs1801282. The nomogram achieved AUC 0.885 (95% CI 0.812-0.943) with sensitivity 88.6% and specificity 73.9%; calibration was good (H - L χ This integrative biomarker-genotype model demonstrated strong internal performance and potential clinical utility for individualized risk stratification in sepsis. The results support combining genetic susceptibility and inflammatory biomarkers for enhanced prognostic precision, although external and multi-ethnic validation remains warranted before widespread adoption. Show less
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a substantial global threat. SARS-CoV-2 nonstructural proteins (NSPs) are essential for impeding the host replication mechanism while Show more
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a substantial global threat. SARS-CoV-2 nonstructural proteins (NSPs) are essential for impeding the host replication mechanism while also assisting in the production and organization of new viral components. However, NSPs are not incorporated into viral particles, and their subsequent fate within host cells remains poorly understood. Additionally, their role in viral pathogenesis requires further investigation. This study aimed to discover the ultimate fate of NSP6 in host cells and to elucidate its role in viral pathogenesis. We investigated the effects of NSP6 on cell death and explored the underlying mechanism; moreover, we examined the degradation mechanism of NSP6 in human cells, along with analysing its correlation with coronavirus disease 2019 (COVID-19) severity in patient peripheral blood mononuclear cells (PBMCs). NSP6 was demonstrated to induce cell death. Specifically, NSP6 interacted with EI24 autophagy-associated transmembrane protein (EI24) to increase intracellular Ca This study reveals that KLHL22-mediated ubiquitination controls NSP6 stability and that NSP6 induces autophagic cell death via calcium overload, highlighting its cytotoxic role and suggesting therapeutic strategies that target calcium signaling or promote NSP6 degradation as potential interventions against COVID-19. Show less
Studying the molecular properties of drugs and their interactions with human targets aids in better understanding the clinical performance of drugs and guides drug development. In computer-aided drug Show more
Studying the molecular properties of drugs and their interactions with human targets aids in better understanding the clinical performance of drugs and guides drug development. In computer-aided drug discovery, it is crucial to utilize effective molecular feature representations for predicting molecular properties and designing ligands with high binding affinity to targets. However, designing an effective multi-task and self-supervised strategy remains a significant challenge for the pretraining framework. In this study, a multi-task self-supervised deep learning framework is proposed, MTSSMol, which utilizes ≈10 million unlabeled drug-like molecules for pretraining to identify potential inhibitors of fibroblast growth factor receptor 1 (FGFR1). During the pretraining of MTSSMol, molecular representations are learned through a graph neural networks (GNNs) encoder. A multi-task self-supervised pretraining strategy is proposed to fully capture the structural and chemical knowledge of molecules. Extensive computational tests on 27 datasets demonstrate that MTSSMol exhibits exceptional performance in predicting molecular properties across different domains. Moreover, MTSSMol's capability is validated to identify potential inhibitors of FGFR1 through molecular docking using RoseTTAFold All-Atom (RFAA) and molecular dynamics simulations. Overall, MTSSMol provides an effective algorithmic framework for enhancing molecular representation learning and identifying potential drug candidates, offering a valuable tool to accelerate drug discovery processes. All of the codes are freely available online at https:// github.com/zhaoqi106/MTSSMol. Show less
Zhigancao Decoction (ZGCD) is derived from "Treatise on Febrile Diseases" and is traditionally prescribed for treating a variety of cardiovascular conditions. As of now, there are no data to support i Show more
Zhigancao Decoction (ZGCD) is derived from "Treatise on Febrile Diseases" and is traditionally prescribed for treating a variety of cardiovascular conditions. As of now, there are no data to support its use as a treatment for diabetic cardiomyopathy (DCM) and the mechanism behind the effect is unclear as well. In the present study, clinical evidence for the efficacy of ZGCD in patients with DCM was examined using a meta-analysis and its underlying anti-DCM molecular mechanisms were explored via network pharmacology. The current study utilized an extensive search strategy encompassing various domestic and foreign databases databases to retrieve pertinent articles published up to June 2024. In light of this, a thorough evaluation of the benefits and safety of Zhigancao decoction (ZGCD) was conducted in this study using RevMan and Stata. Subsequently, a number of active compounds and target genes for ZGCD were gathered from the TCMSP and BATMAN-TCM databases, while the main targets for DCM were obtained from databases such as GenCards, OMIM, TTD, and DrugBank. To select core genes, protein-protein interaction networks were generated using the STRING platform, and enrichment analyses were completed using the Metascape platform. Meta-analysis results were ultimately derived from 9 studies involving 661 patients in total. In comparison with WM therapy alone, the pooled results showed that ZGCD significantly enhanced overall effectiveness. Additionally, the utilization of ZGCD was leading to a reduction in LVEDV, LVESV and LVDD, also a greater increase in LVEF. Meanwhile, the utilization of ZGCD during intervention was more effective in reducing SBP, and DBP. In addition, the ZGCD showed potential in reducing the occurrence of adverse events. In the context of network pharmacology, five constituents of ZGCD-namely lysine, quercetin, gamma-aminobutyric acid, stigmasterol, and beta-sitosterol-are posited to exert anti-diabetic cardiomyopathy (anti-DCM) effects through interactions with the molecular targets ASS1, SERPINE1, CACNA2D1, AVP, APOB, ICAM1, EGFR, TNNC1, F2, F10, IGF1, TNNI2, CAV1, INSR, and INS. The primary mechanisms by which ZGCD may achieve its anti-DCM effects are likely mediated via the AGEs/RAGE signaling pathway, as well as through pathways related to lipid metabolism and atherosclerosis. In comparison to WM therapy alone, ZGCD demonstrates greater efficacy and safety in the management of DCM. ZGCD not only significantly reduces blood pressure, but also enhances cardiac function while producing fewer adverse effects. The therapeutic effects of ZGCD on DCM can likely be ascribed to its capacity to modulate the AGEs-RAGE signaling pathway, as well as its efficacy in enhancing lipid metabolism and mitigating atherosclerosis. identifier (INPLASY202430133). Show less
The competency of specialist nurse clinical educators is crucial for the effectiveness of specialist nurse training programmes. However, variability in teaching competency and training needs among edu Show more
The competency of specialist nurse clinical educators is crucial for the effectiveness of specialist nurse training programmes. However, variability in teaching competency and training needs among educators remains insufficiently studied, especially in the context of rapidly evolving healthcare education in China. This study aimed to identify distinct core competency profiles among clinical educators for specialist nurses, examine associated socio-demographic factors, and explore differences in training needs across profiles. A cross-sectional online survey was conducted with 3,945 specialist nurse clinical educators from 30 Chinese regions. The Chinese version of the Nurse Educator Core Competency Scale (NECCS) and a self-developed training needs questionnaire were used. Latent Profile Analysis (LPA) identified competency subgroups, while multinomial logistic regression and Kruskal-Wallis tests examined associated variables and training needs. Latent Profile Analysis identified three competency profiles: foundational (8.6%), intermediate (43.0%), and advanced (48.4%), with mean scores of 43.89, 68.24, and 91.68, respectively. Educators without prior training were significantly more likely to belong to the foundational (OR = 3.195, p < 0.001) and intermediate (OR = 1.676, p < 0.001) groups compared to those with training experience. Advanced-competency educators showed the highest demand for curriculum design training, with 75% rating it as highly necessary. In contrast, educators in the intermediate group identified clinical teaching methods and techniques as their top training need (58.7%). Those in the foundational group prioritised common pedagogical methods and instructional technologies (54.7%). Clinical educator competencies vary by background characteristics and training exposure. Tailored, competency-based training is needed to address these gaps and enhance the quality of specialist nursing education. Show less
As a chronic lipid driven arterial disease, dyslipidemia is one of the most critical risk factors for atherosclerosis (AS). The gut microbiota plays an important role in regulating host lipid metaboli Show more
As a chronic lipid driven arterial disease, dyslipidemia is one of the most critical risk factors for atherosclerosis (AS). The gut microbiota plays an important role in regulating host lipid metabolism disorders. Studies have shown that the herb "Gualou-Xiebai" (GLXB) can effectively regulate the blood lipid levels of ApoE Show less
Interleukin-27 (IL-27) is a cytokine that is reported to be highly expressed in the peripheral blood of patients with pulmonary tuberculosis (PTB). IL-27-mediated signaling pathways, which exhibit ant Show more
Interleukin-27 (IL-27) is a cytokine that is reported to be highly expressed in the peripheral blood of patients with pulmonary tuberculosis (PTB). IL-27-mediated signaling pathways, which exhibit anti- Mycobacterium tuberculosis (Mtb) properties, have also been demonstrated in macrophages infected with Mtb. However, the exact mechanism remains unclear. This study aimed to clarify the potential molecular mechanisms through which IL-27 enhances macrophage resistance to Mtb infection. Both normal and PTB patients provided bronchoalveolar lavage fluid (BALF). Peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals and stimulated with 50 ng/mL macrophage-colony stimulating factor (M-CSF) to obtain monocyte-derived macrophages (MDMs). Using 100 ng/mL phorbol 12-myristate 13-acetate (PMA), THP-1 cells were induced to differentiate into THP-1-derived macrophage-like cells (TDMs). Both MDMs and TDMs were subsequently infected with the Mtb strain H37Rv and treated with 50 ng/mL IL-27 prior to infection. The damage and inflammation of macrophages were examined using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Patients with PTB had elevated levels of IL-27 in their BALF. Preconditioning with IL-27 was shown to reduce H37Rv-induced MDMs and TDMs apoptosis while also decreasing the levels of Cleaved Caspase-3, Bax and the proinflammatory cytokines TNF-α, IL-1β, and IL-6, promoting the expression of Bcl-2 and the anti-inflammatory factors IL-10 and IL-4. Silencing of the IL-27 receptor IL-27Ra increased macrophage damage and inflammation triggered by H37Rv. Mechanistically, IL-27 activates autophagy by inhibiting TLR4/NF-κB signaling and activating the PI3K/AKT signaling pathway, thereby inhibiting H37Rv-induced macrophage apoptosis and the inflammatory response. Our study suggests that IL-27 alleviates H37Rv-induced macrophage injury and the inflammatory response by activating autophagy and that IL-27 may be a new target for the treatment of PTB. Show less
Time-restricted feeding (TRF) is a dietary intervention that has been shown to have numerous health benefits. However, it is important to further investigate the potential effectiveness of TRF in addr Show more
Time-restricted feeding (TRF) is a dietary intervention that has been shown to have numerous health benefits. However, it is important to further investigate the potential effectiveness of TRF in addressing sarcopenic obesity (SO), which is characterized by a combination of age-related obesity and sarcopenia. In this study, 14-month-old C57BL/6J male mice were fed either regular chow diet or high-fat diet (HFD), and had either ad libitum or restricted access to food for 8 hours daily (Intervention for 7 months). For the human trial (ChiCTR2100052876), obese individuals (n=21) with a Body Mass Index ≥28 were recruited and instructed to adopt an 8-hour eating window and a 16-hour fasting period. Here, we found that the TRF intervention significantly reduced global fat mass (P < .001) and volume (P < .05), and increase lean mass compared to mice fed with HFD. Furthermore, TRF improved overall metabolic mobility (8h TRF+HFD vs. AL+HFD). This intervention also enhanced liver FGF21 protein levels (P < .01) and the expression of FGFR1 and FGF21 target genes in adipose and muscle tissues, thus improving mitochondrial quality control in these tissues. Notably, TRF interventions led to a significant decrease in serum FGF21 levels (P < .05). In the human trial, TRF intervention resulted in a significant reduction in weight (P < .001) and body fat levels (P < .001) among obese individuals, as well as a decrease in serum GLU (P < .001), insulin (P < .001), and TC levels (P < .05). Overall, the findings indicate that TRF intervention improves SO by regulating liver FGF21 expression, thereby enhancing FGF21 sensitivity in adipose and muscle tissues. Show less
Left-behind adolescents in China may face heightened risks of involvement in cyberbullying due to their psychological vulnerability and complex social circumstances. Considering the potential heteroge Show more
Left-behind adolescents in China may face heightened risks of involvement in cyberbullying due to their psychological vulnerability and complex social circumstances. Considering the potential heterogeneity within this population, this study aimed to identify distinct patterns of cyberbullying and cybervictimization among left-behind adolescents and to explore how reactive anger, left-behind patterns, gender, and grade level predict membership in these subgroups. A total of 1,351 junior high school students (752 left-behind, 599 non-left-behind) were recruited from five schools. Latent profile analysis (LPA) was used to identify distinct patterns, and multinomial logistic regression was used to examine the relationships between predictors and various profiles. (1) Three distinct profiles of cyberbullying and cybervictimization were identified among left-behind adolescents. (2) Left-behind adolescents were more likely to experience cybervictimization compared to their non-left-behind peers. (3) Reactive anger, left-behind patterns, gender, and grade level significantly predicted subgroup membership. These findings underscore the importance of developing targeted interventions and considering the specific psychosocial vulnerabilities of left-behind youth. Show less
Goose foie gras production requires force-feeding with high-energy feed, disrupting hepatic lipid homeostasis and causing excessive lipid accumulation. To investigate the formation mechanism, we colle Show more
Goose foie gras production requires force-feeding with high-energy feed, disrupting hepatic lipid homeostasis and causing excessive lipid accumulation. To investigate the formation mechanism, we collected liver samples from Landes geese at pre-force-feeding (D0), mid-force-feeding (D16), and terminal-force-feeding (D25) stages. Overfeeding shifted liver color from reddish-brown to yellow, significantly increasing size and weight. Histological analysis revealed pronounced lipid droplet accumulation in hepatocytes. Biochemical analysis indicated force-feeding groups (D16, D25) exhibited continuous and significant decreases in liver moisture, crude ash, and crude protein content compared to D0, while crude fat increased substantially. Integrated transcriptomic and lipidomic analyses identified 497 differentially expressed genes (DEGs) and 368 differential lipid molecules (DLMs) between D16 and D0, and 303 DEGs and 172 DLMs between D25 and D16. KEGG enrichment highlighted four pathways associated with fatty liver formation: glycerolipid metabolism, adipocytokine signaling pathway, ErbB signaling pathway, and MAPK signaling pathway. Within these, key genes ( Show less
Jinyu Bai, Xueli Qiu, Huajian Shan+10 more · 2025 · Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · Oxford University Press · added 2026-04-24
The Wnt/β-catenin signaling pathway is a classical pathway that regulates bone metabolism. The G protein inhibitory α subunits 1 and 3 (Gαi1/3) can couple with multiple growth factor/cytokine receptor Show more
The Wnt/β-catenin signaling pathway is a classical pathway that regulates bone metabolism. The G protein inhibitory α subunits 1 and 3 (Gαi1/3) can couple with multiple growth factor/cytokine receptors and act as universal adaptor proteins to mediate the activation of key downstream signaling pathways. However, it remains unclear whether and how Gαi1/3 proteins mediate Wnt/β-catenin signal transduction. In this study, we utilized single-cell sequencing analysis and employed viral transfection and gene editing techniques to alter the expression of Gαi1/3 in mouse embryonic osteoblast precursor cells. We examined the relationship between Gαi1/3 expression and the Wnt/β-catenin signaling pathway. Immunoprecipitation and confocal experiments were conducted to further explore the mechanisms by which Gαi1/3 exerts its functions. Osteogenic-related protein levels were detected by Western blotting, and the effects of Gαi1/3 proteins on osteogenic function were examined through alkaline phosphatase and Alizarin red staining. Additionally, micro-CT was used to compare bone mass in mice with different levels of Gαi1/3 expression, showing the relationship between Gαi1/3 and bone formation. Our findings indicate that Gαi1/3 proteins are significantly inversely correlated with age. Gαi1/3, rather than Gαi2, mediates the Wnt/β-catenin signaling pathway and promotes osteogenesis. Mechanistically, Gαi1/3 interacts with Axin1 and recruits it to the cell membrane, leading to inactivation of the β-catenin degradation complex. This results in β-catenin accumulation and nuclear translocation, where it activates the transcription of osteogenic genes. In vivo experiments further confirm that knockdown of Gαi1/3 significantly inhibits bone formation in mice. Our study identified Gαi1/3 as key regulatory proteins in Wnt/β-catenin signaling-mediated osteogenesis, and further elucidated its molecular mechanism in bone formation, which may provide a new therapeutic target for osteoporosis. Show less
The aim of this review is to systematically explore the critical role of dual-specific phosphatases (DUSPs) in CKD-associated cognitive impairment and their therapeutic potential. Chronic kidney disea Show more
The aim of this review is to systematically explore the critical role of dual-specific phosphatases (DUSPs) in CKD-associated cognitive impairment and their therapeutic potential. Chronic kidney disease (CKD) is a global health burden, and the cognitive impairment it induces seriously affects patients' quality of life. Studies have shown that DUSPs are involved in pathological processes such as inflammation, oxidative stress, fibrosis, and neuronal apoptosis through the regulation of signaling pathways such as MAPK, which in turn affects the cognitive function of CKD patients. Specifically, downregulation of DUSP1 and DUSP6 expression in brain tissues of CKD patients is associated with cognitive impairment, whereas upregulation of DUSP8 and DUSP16 exacerbates cognitive deficits by promoting neuroinflammation. In addition, uremic toxins (e.g., indolephenol sulfate) can further deteriorate cognitive function by altering the activity of DUSPs and interfering with central nervous system signaling. Although there are currently no clinical drugs targeting DUSPs, small molecule inhibitors, gene modulation techniques, and natural compounds have demonstrated the potential to improve cognitive function by modulating DUSPs. Future studies need to focus on optimizing the specificity and selectivity of DUSPs inhibitors and conducting rigorous clinical validation. In-depth elucidation of the mechanism of action of DUSPs in the renal-brain axis will provide an important theoretical basis for the development of novel intervention strategies for CKD-associated cognitive impairment. Show less
The co-occurrence of plasma cell neoplasm (PCN) and lymphoplasmacytic lymphoma (LPL) is rare, and their clonal relationship remains unclear. To evaluate the clinicopathologic characteristics of concom Show more
The co-occurrence of plasma cell neoplasm (PCN) and lymphoplasmacytic lymphoma (LPL) is rare, and their clonal relationship remains unclear. To evaluate the clinicopathologic characteristics of concomitant LPL/PCN. Retrospectively analyzed clinical and laboratory data of 14 cases. Three patients initially presented with immunoglobulin (Ig) M paraprotein, 1 with IgG paraprotein, and 10 had simultaneous diagnoses of PCN and LPL. In 13 cases, flow cytometry detected both LPL and PCN in marrow biopsies. Furthermore, immunohistochemistry highlighted the 2 neoplastic populations, demonstrating an increased proportion of plasma cells and their expression of cyclin D1, CD56, and/or a non-IgM isotype restriction. All cases exhibited discordant heavy-chain isotypes between LPL and PCN. Thirteen of the 14 cases (92.9%) had concordant light-chain restrictions between the 2 neoplasms, and the remaining case (7.1%) showed discordant light-chain restrictions. Of the 12 patients with follow-up, 5 were treated with myeloma regimens, 2 with LPL regimens, 3 with combined therapy, and 2 with observation alone. Follow-up ranged from 2 to 146 months (median, 12.5 months). One patient died of PCN progression, one died of comorbidity, and 10 patients were alive with or without disease. Survival analysis showed no significant difference from the control. The discordant heavy-chain isotype restrictions between PCN and LPL suggest biclonal B-cell neoplasms, which is supported by PCN's phenotypic distinction, such as the expression of cyclin D1 and/or CD56. However, our series exhibited a tendency toward concordant light-chain restrictions between the 2 neoplasms, raising the possibility that PCN may evolve from LPL through class switching. Show less
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) ameliorate motor deficits in cerebral palsy (CP), but the effect of injection frequency remains unclear. Moreover, most studies have focu Show more
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) ameliorate motor deficits in cerebral palsy (CP), but the effect of injection frequency remains unclear. Moreover, most studies have focused on mild CP models (unilateral carotid artery occlusion [UCAO] model). This study explored the effect and mechanism of hUC-MSCs in a rat model of moderate-to-severe CP (bilateral carotid artery occlusion [BCAO] model). On postnatal Day 4 (P4), Wistar rat pups underwent BCAO induction. Subsequently, they received either a single intrathecal injection of hUC-MSCs on P21 or repeated injections on P21, P28, P35, and P42. Motor performance was assessed using the rotarod and front-limb suspension tests, while neuronal regeneration and inflammation were evaluated via biomarkers including neuronal nuclear antigen (NeuN), ionized calcium-binding adapter molecule-1 (Iba-1), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and brain-derived neurotrophic factor (BDNF). P18 model screening confirmed that the BCAO model resulted in more severe brain damage and motor impairment than the UCAO model. After injection of lentivirally transfected hUC-MSCs, it was found that hUC-MSCs could nest in the damaged area and survive for at least 3 days. Administration of hUC-MSCs following BCAO modeling led to notable improvements in both behavioral performance and histological outcomes. Furthermore, repeated injections offered greater therapeutic benefits compared to single injection. It indicated that the efficacy of repeated injections of hUC-MSCs in the treatment of moderate-to-severe CP was superior to that of single injection. Its mechanism was related to the improvement of damaged myelin structure, reduced immunoinflammatory responses, and increased neurotrophic support. Show less
The current trial sought to assess the impact of fermented chicory root waste (FCRW) dietary administration on growth, lipid metabolism, chemical composition, and intestinal barrier pathway in common Show more
The current trial sought to assess the impact of fermented chicory root waste (FCRW) dietary administration on growth, lipid metabolism, chemical composition, and intestinal barrier pathway in common carp ( Show less
This study integrated the the effects of dietary Lys/Met ratio in a low protein diet on the meat quality in Tibetan sheep. A total of 90 weaned Tibetan sheep, 2 months old with initial weight of 15.37 Show more
This study integrated the the effects of dietary Lys/Met ratio in a low protein diet on the meat quality in Tibetan sheep. A total of 90 weaned Tibetan sheep, 2 months old with initial weight of 15.37 ± 0.92 kg were randomly divided into 3 treatments, which were supplemented with Lys/Met ratio at 3 (LP-H), 2 (LP-M), and 1 (LP-L) in the basal diet (10 % crude protein), respectively. After slaughter (150 days of age), the growth performances and meat quality of longissimus dorsi muscle were evaluated. The LP-L group showed significantly higher final body weight compared to the LP-M group (P < 0.05). Serum albumin and total protein levels were significantly higher in the LP-L group than in the LP-H group (P < 0.05). Furthermore, meat from the LP-L group had significantly higher protein, calcium, and vitamin E content compared to the LP-M group (P < 0.05). Transcriptomic analysis revealed 3,479 differentially expressed genes enriched in pathways related to muscle growth, energy metabolism, and signaling transduction. Metabolomic analysis identified 771 differential metabolites, significantly enriched in ABC transporters, beta-alanine metabolism, and taste transduction pathways. Integrated analysis highlighted the upregulation of the ABCD4 gene and L-valine metabolite in the LP-L group, contributing to improved phenotypic traits. These findings provide molecular insights into the regulatory mechanisms underlying the effects of dietary Lys/Met ratios on Tibetan sheep meat quality and offer a basis for developing nutritional strategies to enhance premium meat production. Show less
This study aimed to compare the diagnostic value of [ A prospective study was conducted between March 2023 and July 2023. Patients with high clinical suspicion of lung cancer were recruited. Each part Show more
This study aimed to compare the diagnostic value of [ A prospective study was conducted between March 2023 and July 2023. Patients with high clinical suspicion of lung cancer were recruited. Each participant underwent PET/CT scanning using [ A total of 101 participants were included (mean age 63.267 ± 9.344 [range 39-86 years]). In benign lung lesions, [ [ Show less
Fatty acids serve as a crucial energy source for tumor cells during the progression of chronic lymphocytic leukemia (CLL). The present study aims to elucidate the characteristics of fatty acid metabol Show more
Fatty acids serve as a crucial energy source for tumor cells during the progression of chronic lymphocytic leukemia (CLL). The present study aims to elucidate the characteristics of fatty acid metabolism (FAM) in CLL, construct a related prognostic score, and investigate the regulatory role and mechanisms of FAM in CLL development. Bulk RNA sequencing data from CLL patients and healthy controls were analyzed to identify differentially expressed fatty acid metabolic genes. FAM-score was constructed using Cox-LASSO regression and validated. Single-cell RNA sequencing was used to analyze the expression of key FAM genes in CLL immune cell subsets and investigate cellular communication. Functional assays, including cell viability, drug sensitivity, and oxygen consumption assays, were performed to assess the impact of fatty acid oxidation (FAO) inhibition on CLL cells. Three FAM-related genes (LPL, SOCS3, CNR1) were identified with independent prognostic significance to construct the risk score. The FAM-score demonstrated superior prognostic performance compared to the Binet stage and was associated with established clinical prognostic markers. Single-cell analysis revealed distinct expression patterns of LPL, SOCS3, and CNR1 across CLL immune cell subsets. Cellular communication analysis highlighted the regulatory role of distinct B cell and Treg subsets in the CLL microenvironment. CLL patients with high FAM-score displayed distinct immune infiltration patterns, with increased FAO pathway activity. Inhibition of FAO reduced CLL cell viability, synergistically enhanced the efficacy of the PI3K inhibitor idelalisib. The present study constructed a prognostic risk score based on FAM gene expression, revealing related immune phenotypic differences and exploring the regulatory role of FAO in CLL development. Targeting fatty acid metabolism potentially modulates the CLL immune microenvironment and synergistically enhances the efficacy of PI3K inhibitors. Show less
Dominant follicular development and atresia are governed by the proliferation of granulosa cells (GCs), a process influenced by the delicate balance between apoptosis and autophagy. Oxidative stress, Show more
Dominant follicular development and atresia are governed by the proliferation of granulosa cells (GCs), a process influenced by the delicate balance between apoptosis and autophagy. Oxidative stress, a pivotal catalyst of GCs apoptosis, modulates gene expression through epigenetic mechanisms, including chromatin remodeling. Nevertheless, the regulatory mechanisms underpinning GCs functionality in relation to prolificacy remain inadequately elucidated. In this study, we discovered that the chromatin accessibility of nuclear receptor subfamily 1 group D member 1 (NR1D1) was markedly enhanced in dominant follicular GCs from low-prolificacy sheep, as evidenced by Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq), which correlated with elevated NR1D1 transcript levels. Remarkably, NR1D1 emerged as a novel regulator of follicular development, exhibiting heightened expression in dominant follicles. The overexpression of NR1D1 induced cell cycle arrest, autophagy activation, and mitochondrial dysfunction via the AMPK pathway, while its knockdown fostered GCs survival and functionality. Furthermore, NR1D1 inhibits the transcription of HSD17B12, thereby contributing to oxidative stress (ROS)-induced apoptosis, as demonstrated by CUT&Tag-qPCR and dual luciferase assays. The downregulation of HSD17B12 partially alleviated the effects of NR1D1 knockdown on GCs functionality. These findings indicate that NR1D1 orchestrates GCs proliferation and apoptosis through the suppression of HSD17B12 and the activation of the AMPK pathway, establishing NR1D1 as a novel transcription factor implicated in follicular development and ovarian function, with significant implications for prolificacy. Show less
This study aimed to comprehensively evaluate the clinical effectiveness and safety of acupuncture combined with repetitive transcranial magnetic stimulation (rTMS) in treating post-stroke cognitive im Show more
This study aimed to comprehensively evaluate the clinical effectiveness and safety of acupuncture combined with repetitive transcranial magnetic stimulation (rTMS) in treating post-stroke cognitive impairment (PSCI) through meta-analysis and trial sequential analysis (TSA), moreover to provide an evidence-based basis for the treatment of PSCI in clinical practice. The study conducted a comprehensive search of eight major domestic and international databases, including PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP and China Biology Medicine (CBM). Four English and four Chinese databases of randomized controlled trials of acupuncture combined with rTMS for the treatment of PSCI from inception until July 2025. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using RevMan5.4 and Stata/MP 18.0, and trial sequential analyses were performed by TSA 0.9. Sixteen RCTs involving 1,058 patients were included, including 532 patients in the experimental group and 526 patients in the control group. Meta-analysis results showed that the experimental group had a higher clinical effectiveness rate in treating patients with PSCI compared to the control group [RR = 1.29, 95% CI (1.08, 1.55), Acupuncture combined with rTMS can improve cognitive function, regulate daily living ability, and regulate neurotransmitter levels in patients with PSCI, which is worthy recommended in the clinic. However, due to limitations in sample size, inclusion quality and incomplete reporting, it is worth noting that more rigorously designed and high-quality studies are needed to further validate these conclusions. Show less
The maternal-to-zygotic transition (MZT) is a reprograming process encompassing zygotic genome activation (ZGA) and the clearance of maternally-provided mRNAs. While some factors regulating MZT have b Show more
The maternal-to-zygotic transition (MZT) is a reprograming process encompassing zygotic genome activation (ZGA) and the clearance of maternally-provided mRNAs. While some factors regulating MZT have been identified, there are thousands of maternal RNAs whose function has not been ascribed yet. Here, we have performed a proof-of-principle CRISPR-RfxCas13d maternal screen, in which we targeted mRNAs encoding kinases and phosphatases or proteins regulating them in zebrafish. This screen identified branched-chain ketoacid dehydrogenase kinase, Bckdk, as a novel post-translational regulator of MZT. Bckdk mRNA knockdown caused epiboly defects, ZGA deregulation, H3K27ac reduction and a partial impairment of miR-430 processing. Phospho-proteomic analysis revealed that Phf10/Baf45a, a chromatin remodeling factor, is less phosphorylated upon Bckdk depletion. Further, phf10 mRNA knockdown also altered ZGA, and expression of a phospho-mimetic mutant of Phf10 rescued the developmental defects observed after bckdk mRNA depletion, as well as restored H3K27ac levels. Altogether, our results demonstrate the competence of CRISPR-RfxCas13d screenings to uncover new regulators of early vertebrate development and shed light on the post-translational control of MZT mediated by protein phosphorylation. Show less