Swine enteric coronaviruses pose a significant challenge to the global pig industry, inflicting severe diarrhea and high mortality rates among piglets, and resulting in substantial economic losses. In Show more
Swine enteric coronaviruses pose a significant challenge to the global pig industry, inflicting severe diarrhea and high mortality rates among piglets, and resulting in substantial economic losses. In our clinical practice, we observed that the addition of potassium molybdate (PM) to the feed could dramatically reduce diarrhea and diarrhea-related mortality in piglets. However, the underlying mechanisms remain elusive and merit further investigation. In this study, we revealed that PM effectively inhibited the infection of both aminopeptidase N (APN)-dependent coronaviruses, transmissible gastroenteritis virus (TGEV), and porcine respiratory coronavirus (PRCV), both Show less
Oocyte maturation-coupled mRNA post-transcriptional regulation is essential for the establishment of developmental potential. Previously, oocyte mRNA translation efficiencies focused on the trans-regu Show more
Oocyte maturation-coupled mRNA post-transcriptional regulation is essential for the establishment of developmental potential. Previously, oocyte mRNA translation efficiencies focused on the trans-regulation of key RNA-binding protein (RBPs), rarely related to RNA structure. RNA G-quadruplexes (rG4s) are four-stranded RNA secondary structures involved in many different aspects of RNA metabolism. In this study, we have developed a low-input technique for rG4 detection (G4-LACE-seq) in mouse oocytes and found that rG4s were widely distributed in maternal transcripts, with enrichment in untranslated regions, and they underwent transcriptome-wide removal during meiotic maturation. The rG4-selective small-molecule ligand BYBX stabilized rG4s in the oocyte transcriptome and impaired spindle assembly and meiotic cell cycle progression. The proteomic spectrum results revealed that rG4 accumulation weakened the binding of a large number of RBPs to mRNAs, especially those associated with translational initiation. Ribosomal immunoprecipitation and translational reporter assays further proved that rG4s in the untranslated regions negatively affected the translational efficiency of key maternal mRNAs. Overexpression DEAH/RHA family helicase-36 partially reverses BYBX-induced oocyte developmental defects, suggesting its importance in rG4 regulation. Collectively, this study describes the distribution, dynamic changes, and regulation of rG4s in the mouse maternal transcriptome. Before meiosis resumption, a large number of rG4s in oocytes are necessary to maintain the translatome at a low level, and DHX36-mediated rG4 removal promotes a translational switch and is required for successful maternal-to-zygotic transition. Show less
Hepatoid carcinoma of the ovary (HCO) is a highly uncommon and aggressive neoplasm originating from the surface epithelial cells of the ovary, characterized by hepatocyte-like differentiation. To date Show more
Hepatoid carcinoma of the ovary (HCO) is a highly uncommon and aggressive neoplasm originating from the surface epithelial cells of the ovary, characterized by hepatocyte-like differentiation. To date, most information on HCO is derived from case reports, with fewer than 50 documented cases globally. In this case report, we present a detailed account of the diagnosis, treatment, and prognosis of a patient diagnosed as having bilateral HCO, which is even rarer. Targeted next-generation sequencing revealed somatic mutations in PIK3C3 and TP53, with no BRCA1/2 alterations, and a molecular profile consistent with microsatellite stability and low tumor mutational burden. We also review the current literature to situate our findings within the broader context of existing knowledge. Given the rarity of bilateral HCO, our objective is to contribute to the existing body of knowledge by providing a comprehensive description of its clinical features, molecular characteristics, and treatment strategies. This effort may enhance understanding of this rare malignancy and offer insights to improve patient outcomes in clinical practice. Show less
Gliomas, particularly glioblastoma, are aggressive brain tumors with poor prognosis and unmet therapeutic needs. Structural maintenance of chromosomes 4 (SMC4), a core component of the condensin compl Show more
Gliomas, particularly glioblastoma, are aggressive brain tumors with poor prognosis and unmet therapeutic needs. Structural maintenance of chromosomes 4 (SMC4), a core component of the condensin complex, is dysregulated in multiple cancers, but its role in glioma metabolism and metastasis remains unclear. Using integrated multi-omics analyses of glioma datasets, we assessed SMC4 expression and its correlation with clinical outcomes. Functional studies in U-251MG and LN229 glioma cells including CCK-8, EdU, cell cycle, Transwell, and wound-healing assays were combined with subcutaneous xenograft and tail-vein metastasis mouse models to evaluate SMC4's effects on proliferation, migration, invasion, and metastasis. ECAR/OCR and rescue experiments validated SMC4's role in glycolysis. Luciferase reporter and ChIP assays identified nuclear factor I A (NFIA) as an upstream transcriptional regulator of SMC4. A prognostic model (SRRS) was developed via LASSO regression and validated across cohorts. SMC4 was significantly overexpressed in glioma tissues, with higher expression correlating with advanced tumor grades and poorer patient survival (AUC > 0.82). Mechanistically, SMC4 promoted G1/S cell cycle transition and proliferation SMC4 drives glioma progression through dual mechanisms TGF-β/SMAD-mediated metastasis and LDHA-dependent glycolysis regulated by NFIA. This extends beyond its known role in TGF-β activation by identifying NFIA as an upstream regulator and metabolic reprogramming as a novel function. The SRRS and nomogram provide robust tools for prognosis and personalized therapy, supporting the NFIA/SMC4 axis and downstream effectors as potential therapeutic targets for glioma. Show less
The present case report presents the diagnostic challenges of pediatric diffuse low-grade glioma (pDLGG) with oligodendroglioma-like features. The patient, an 11-year-old girl, presented with refracto Show more
The present case report presents the diagnostic challenges of pediatric diffuse low-grade glioma (pDLGG) with oligodendroglioma-like features. The patient, an 11-year-old girl, presented with refractory epilepsy and brain imaging did not provide a clear diagnosis. Intraoperatively, the tumor appeared gray-yellow to gray-red, with moderate texture and unclear borders, consistent with LGG. Postoperative pathology showed diffuse infiltrative growth of the tumor, with pleomorphic cell morphology and oligodendroglioma-like gliocyte proliferation. Staining was positive for markers such as glial fibrillary acidic protein and Olig-2. Genomic analysis revealed BRAF V600E, fibroblast growth factor receptor (FGFR)1 and FGFR4 mutations, but no IDH mutations or other related mutations. The final diagnosis was pDLGG with alterations in the MAPK pathway. The present case underscores the importance of molecular and histological features in the diagnosis of pDLGG, especially when clinical and imaging characteristics are atypical, as molecular diagnostics provide key insights for disease classification. Show less
Little is known about the association between physical activity and the risk of pre-sarcopenic obesity (pre-SO) among adolescents. Hence, this study aimed to examine the association between physical a Show more
Little is known about the association between physical activity and the risk of pre-sarcopenic obesity (pre-SO) among adolescents. Hence, this study aimed to examine the association between physical activity and pre-SO in a sample of 2143 adolescents aged 12 to 18 years from Yinchuan, China. The pre-SO was defined by three criteria: low skeletal muscle mass adjusted by weight (SMM/W) combined with body mass index (BMI), fat mass percentage (FMP), and waist circumference (WC). After adjusting for age, smoking, drinking, sleep time, and high-fat food consumption, participants with high physical activity (HPA) had a lower risk of pre-SO compared to those with low physical activity (LPA) according to the obesity criteria of FMP (OR 0.63, 95% CI, 0.48-0.83, P < 0.05), and WC (OR 0.71, 95% CI, 0.52-0.96, P < 0.05). Additionally, restricted cubic spline models showed a linear dose-response association between total physical activity (TPA) and pre-SO no matter what obesity criteria were adopted (all P overall trend < 0.05, all P non-linear > 0.50). Subgroup analyses revealed that individuals with higher TPA levels exhibited a decreased risk of pre-SO in boys according to the obesity criteria of FMP, and WC. In conclusion, HPA is associated with a reduced risk of pre-SO in adolescents, especially among boys. Show less
Polygonum multiflorum Thunb., a plant rich in diverse bioactive constituents, has been widely used in East Asia in functional foods and medicine to ameliorate inflammatory disorders through its multi- Show more
Polygonum multiflorum Thunb., a plant rich in diverse bioactive constituents, has been widely used in East Asia in functional foods and medicine to ameliorate inflammatory disorders through its multi-component activity. The effectiveness of these botanical extracts is thought to involve complex interactions among diverse constituents; however, the molecular basis of such interactions remains insufficiently understood. In this study, we explored the anti-inflammatory properties of the ethanol extract of Polygonum multiflorum (PME) through a combination of chemical profiling and computational analysis. PME was found to reduce the production of nitric oxide, inducible nitric oxide synthase, and interleukin-6 in LPS-stimulated RAW 264.7 macrophages. Using HS-SPME-GC-MS in conjunction with network pharmacology, we identified 32 volatile constituents, among which five core compounds were predicted to be associated with three inflammation-related targets: ESR1, FASN, and NR1H3. Dual-ligand molecular docking and molecular dynamics simulations suggested that the sequence of ligand binding may influence the stability and interaction patterns of protein-ligand complexes, offering insights into possible mechanisms of synergy and antagonism mediated by key residues such as ARG394 in ESR1. Overall, these findings contribute to a better understanding of how binding order and structural context may shape constituent-target interactions, providing a basis for the further development of multi-component natural product strategies against inflammation. This study underscores the relevance of incorporating multi-ligand dynamics into natural product research and presents an integrated experimental-computational framework to investigate the cooperative or competitive behaviors of functional food constituents, thereby supporting the rational design of optimized multi-target formulations. Show less
In the microenvironment of atherosclerosis (AS), low-density lipoprotein (LDL) accumulates in injured endothelial areas and undergoes oxidation, thereby generating oxidized LDL (ox-LDL). The formation Show more
In the microenvironment of atherosclerosis (AS), low-density lipoprotein (LDL) accumulates in injured endothelial areas and undergoes oxidation, thereby generating oxidized LDL (ox-LDL). The formation of ox-LDL, in turn, not only amplifies endothelial cell (EC) dysfunction but also triggers macrophage polarization into the pro-inflammatory M1 phenotype. This cascade results in increased inflammatory cytokine secretion and exacerbated lipid accumulation. Therefore, a dual-targeting strategy aimed at both ECs and macrophages to inhibit the vicious circle between inflammation and lipids is a promising avenue for AS treatment. Simvastatin (SIM)-loaded nanomicelles (PLA-PEG/SIM) were prepared using the thin-film hydration method. Then, platelet membrane (PM) was coated the nanomicelles via sonication to obtain PM@PLA-PEG/SIM dual-targeting biomimetic nanoparticles. The morphological features of the nanoparticles were assessed by transmission electron microscopy (TEM). Cytotoxicity was evaluated using the CCK-8 assay and live/dead cell staining. Their targeting ability toward ECs and macrophages was assessed by flow cytometry and confocal laser scanning microscopy (CLSM). The biosafety, targeting ability, and therapeutic efficacy of PM@PLA-PEG/SIM against AS were further validated in ApoE PM@PLA-PEG/SIM effectively reduced the drug toxicity of SIM, exhibiting good biocompatibility. In vitro, cell experiment results showed that the nanoparticles inhibited foam cell formation, decreased interleukin-6 (IL-6) expression, and increased interleukin-4 (IL-4) and interleukin-10 (IL-10) expression by promoting macrophage repolarization. In vivo, results indicated that the formulation demonstrated excellent plaque-targeting ability. More importantly, the plaque area and lipid levels in the PM@PLA-PEG/SIM group were lowest, and plaques were most stable, showing its best therapeutic efficiency. PM@PLA-PEG/SIM alleviated progression of AS by co-targeting ECs and macrophages to inhibit the vicious cycle between inflammation and lipids. Our study provides a new strategy for the treatment of the disease by the co-targeting biomimetic nanoparticle. Show less
By integrating single-cell and bulk RNA-sequencing data for esophageal cancer (ESCA), we developed and validated a seven-macrophage-gene prognostic signature (FCN1, SCARB2, ATF5, PHLDA2, GLIPR1, CHORD Show more
By integrating single-cell and bulk RNA-sequencing data for esophageal cancer (ESCA), we developed and validated a seven-macrophage-gene prognostic signature (FCN1, SCARB2, ATF5, PHLDA2, GLIPR1, CHORDC1, and BCKDK). This signature effectively stratified patients into high- and low-risk groups with significantly different overall survival, achieving area under the curve (AUC) values greater than 0.7 for 1-, 2-, and 3-year survival prediction. A high-risk status correlated with an immunosuppressive tumor microenvironment, characterized by lower infiltration of B cells and CD8 + T cells, and was associated with reduced sensitivity to multiple chemotherapeutic agents, including Cisplatin and 5-Fluorouracil. Conversely, a low-risk status was linked to greater immune cell infiltration and higher predicted chemosensitivity. At the single-cell level, pseudotime analysis revealed that macrophage maturation significantly correlated with a decreasing risk score, suggesting that mature macrophages may contribute to a favorable prognosis. Furthermore, cell communication analysis identified high-risk macrophages as dominant drivers of a pro-tumorigenic microenvironment via signaling pathways, such as SPP1 and complement. In conclusion, this seven-gene signature is a robust prognostic biomarker that offers a new strategy for personalized risk assessment and treatment selection in ESCA. The online version contains supplementary material available at 10.1007/s13205-025-04452-w. Show less
The STAT3 pathway promotes epithelial-mesenchymal transition, migration, invasion and metastasis in cancer. STAT3 upregulates the transcription of the key epithelial-mesenchymal transition transcripti Show more
The STAT3 pathway promotes epithelial-mesenchymal transition, migration, invasion and metastasis in cancer. STAT3 upregulates the transcription of the key epithelial-mesenchymal transition transcription factor SNAIL in a DNA binding-independent manner. However, the mechanism by which STAT3 is recruited to the SNAIL promoter to upregulate its expression is still elusive. In our study, the lysine methylation binding protein L3MBTL3 is positively associated with metastasis and poor prognosis in female patients with breast cancer. L3MBTL3 also promotes epithelial-mesenchymal transition and metastasis in breast cancer. Mechanistic analysis reveals that L3MBTL3 interacts with STAT3 and recruits STAT3 to the SNAIL promoter to increase SNAIL transcription levels. The interaction between L3MBTL3 and STAT3 is required for SNAIL transcription upregulation and metastasis in breast cancer, while the methylated lysine binding activity of L3MBTL3 is not required for these functions. In conclusion, L3MBTL3 and STAT3 synergistically upregulate SNAIL expression to promote breast cancer metastasis. Show less
8p11 myeloproliferative syndrome (EMS) is a rare aggressive hematologic malignancy with a poor prognosis that can rapidly develop into acute leukemia. It is characterized by the translocation of fibro Show more
8p11 myeloproliferative syndrome (EMS) is a rare aggressive hematologic malignancy with a poor prognosis that can rapidly develop into acute leukemia. It is characterized by the translocation of fibroblast growth factor receptor-1 (FGFR1), and there is still a lack of effective and reliable treatment methods at present. This report provides a new therapeutic strategy for EMS patients diagnosed with BCR-FGFR1 fusion. This report describes a case of EMS patient with a positive BCR-FGFR1 fusion gene, whose manifestations are similar to those of chronic myeloid leukemia (CML). After diagnosis by fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq), olverembatinib, the third-generation tyrosinase inhibitor (TKI) developed in China, was used for treatment. After monotherapy and follow-up for more than one year, partial molecular response (PR) was achieved. During this period, hematologic remission and cytogenetic remission were achieved. The treatment safety of the entire process was excellent. In summary, olverembatinib provides more treatment options for rare diseases such as 8p11 myeloproliferative syndrome. Show less
Atherosclerosis, a leading cause of cardiovascular disease, is driven by a complex interplay of dyslipidemia, inflammation, and arterial plaque formation and progression. Animal models are indispensab Show more
Atherosclerosis, a leading cause of cardiovascular disease, is driven by a complex interplay of dyslipidemia, inflammation, and arterial plaque formation and progression. Animal models are indispensable to elucidate the pathogenesis and develop novel therapies. Rodent models are widely utilized due to their cost-effectiveness, reproducibility, and rapid disease progression. However, notable species differences exist in lipoprotein composition and lipid metabolism pathways. Mice and rats exhibit an HDL-dominant profile, whereas Syrian golden hamsters express cholesteryl ester transfer protein (CETP) and display a higher LDL fraction, but lower than that of humans, offering a model closer to human metabolically. Divergent CETP activity across species further complicates the translational relevance of the findings from these models for atherosclerosis and related metabolic disorders. This review systematically examines the key factors in rodent model selection and optimization, with consideration on the roles of sex and age. We focus on three commonly used and well-characterized rodent strains prone to atherosclerosis: C57BL/6J mice, Sprague-Dawley (SD) rats, Wistar rats, and golden hamsters. On Show less
Prior research has consistently demonstrated that higher levels of digital health literacy contribute positively to improved mental health outcomes and overall quality of life among patients. Neverthe Show more
Prior research has consistently demonstrated that higher levels of digital health literacy contribute positively to improved mental health outcomes and overall quality of life among patients. Nevertheless, the interplay between digital health literacy and the experience of perceived stigma-particularly among burn patients-remains underexplored, and the potential heterogeneity within this relationship has not been adequately addressed. This cross-sectional study, conducted from June to July 2025, recruited 534 burn patients (mean age 31.05 ± 9.52 years; 61.0% male) from three tertiary hospitals in Sichuan Province, China. Participants completed validated scales assessing digital health literacy, social support, appearance anxiety, perceived stigma, and demographics. Data were analyzed using Pearson correlations, latent profile analysis (LPA) with fit indices, univariate analyses (chi-square tests and Digital health literacy was negatively correlated with perceived stigma ( This study confirms heterogeneity in digital health literacy and perceived stigma among burn patients, with social support and appearance anxiety as key influencers. Findings support targeted interventions to enhance digital health literacy and reduce perceived stigma, advancing precision psychological care for burn survivors. Show less
Protein arginine methyltransferase 5 (PRMT5) complexes with methylosome protein 50 (MEP50) play crucial roles in tumor progress. However, the regulatory mechanism of governing the PRMT5-MEP50 hetero-o Show more
Protein arginine methyltransferase 5 (PRMT5) complexes with methylosome protein 50 (MEP50) play crucial roles in tumor progress. However, the regulatory mechanism of governing the PRMT5-MEP50 hetero-octameric complex remains unclear. Here, we demonstrate that C6orf223, to our knowledge an uncharacterized protein, facilitates PRMT5-MEP50 multiprotein complex assembling, thereby promoting colorectal cancer (CRC) growth and metastasis. C6orf223 forms dimers through disulfide bonds, with its N-terminal arginine-enriched region binding to the C-terminal negatively charged groove of PRMT5, thus stabilizing PRMT5-MEP50 multiprotein and enhancing PRMT5 methyltransferase activity. Consequently, PRMT5-mediated H4R3me2s substantially decreases the expression of the tumor suppressor GATA5, leading to the upregulation of multiple oncogenic target genes including WWTR1, FGFR1, and CLU. Targeting C6orf223 using siRNAs encapsulated in ferritin protein shells effectively suppresses CRC tumor growth and metastasis. Collectively, our findings characterize the role of C6orf223 in facilitating PRMT5-MEP50 hetero-octameric complex assembling and suggest that C6orf223 could serve as a potential therapeutic target for CRC. Show less
Alpha-enolase (ENO1), the enzyme catalyzing 2-phosphoglycerate conversion to phosphoenolpyruvate, is highly expressed in diffuse large B-cell lymphoma (DLBCL) and correlates with adverse clinical outc Show more
Alpha-enolase (ENO1), the enzyme catalyzing 2-phosphoglycerate conversion to phosphoenolpyruvate, is highly expressed in diffuse large B-cell lymphoma (DLBCL) and correlates with adverse clinical outcomes. Thus, understanding the relationship between ENO1-related gene (ERG) network and DLBCL is imperative. Here, we integrated multi-omics profiling (RIP-seq, RNA-seq, and protein interactome analysis) to identify ERGs and established a prognostic model by machine learning algorithms. We identified eleven hub genes (CHERP, SYNE2, INTS1, FAP, MMP9, LRP5, RBM8A, PRMT5, SLC25A6, PABPC4, PSTPIP2) using RNA sequencing, RNA immunoprecipitation sequencing, and protein interaction profiling. A prognostic model was constructed using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression in the GSE10846 dataset and validated in two independent cohorts. DLBCL patients were stratified into high- and low-risk groups based on the model, and clinical characteristics were compared. The tumor immune microenvironment (TIME) was analyzed using CIBERSORT and xCell algorithms to explore correlations with the ERG score. Drug sensitivity assays in DLBCL cell lines were performed to validate the model's predictive capacity for chemotherapy response. Furthermore, the functional role of PABPC4, a key gene in the scoring system, was investigated through A prognostic model including 11 hub genes was established. Patients in the high-risk group exhibited worse clinical outcomes and an immunosuppressive TIME, characterized by altered expression of immune checkpoint-related proteins. This group demonstrated increased sensitivity to vincristine, etoposide, and oxaliplatin. Knockdown of PABPC4 significantly inhibited cell proliferation, reduced colony formation, and delayed tumor growth The ERG scoring system offers a robust and precise tool for predicting survival and guiding personalized treatment in DLBCL patients. Show less
To identify latent profiles of demoralization among older adults with disabilities, analyze their influencing factors, and examine their associations with active aging. From February to July 2025, a c Show more
To identify latent profiles of demoralization among older adults with disabilities, analyze their influencing factors, and examine their associations with active aging. From February to July 2025, a convenience sample of 411 older adults with disabilities was recruited from a tertiary hospital in Anhui Province, China. Data were collected using a general information questionnaire, the Chinese version of the Demoralization Scale, and the Active Aging Scale. Latent profile analysis (LPA) was performed based on demoralization subscale scores. Univariate and multinominal analyses were employed to investigate the influencing factors, and the Kruskal-Wallis The prevalence of demoralization syndrome was 49.1%. LPA identified three distinct profiles: the Well-Adapted Group (53.3%), the Disheartened-Helpless Group (23.8%), and the Fully Demoralized Group (22.9%). The Kruskal-Wallis Nearly half of the older adults with disabilities experienced demoralization, with heterogeneous subgroups identified. The active aging status of demoralized subgroups requires urgent attention. These findings suggest the need for targeted interventions tailored to the characteristics of each profile to improve mental health and promote active aging in this population. Show less
Xiaolei Song, Chenchen Wang, Qin Ding+8 more · 2025 · Journal of controlled release : official journal of the Controlled Release Society · Elsevier · added 2026-04-24
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. The vicious circle between amyloid-β peptide (Aβ) overgeneration and microglial dysfunction is an important path Show more
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. The vicious circle between amyloid-β peptide (Aβ) overgeneration and microglial dysfunction is an important pathological event that promotes AD progression. However, therapeutic strategies toward only Aβ or microglial modulation still have many problems. Herein, inspired by the Aβ transportation, an Aβ-derived peptide (CKLVFFAED) engineered biomimetic nanodelivery system (MK@PC-R NPs) is reported for realizing BBB penetration and reprogram neuron and microglia in AD lesion sites. This hollow mesoporous Prussian blue-based MK@PC-R NPs carrying curcumin and miRNA-124 can down-regulate β secretase expression, thereby inhibiting Aβ production and reducing Aβ-induced neurotoxicity. Meanwhile, MK@PC-R NPs with excellent antioxidant and anti-inflammatory properties could normalize the microglial phenotype and promote Aβ degradation, providing neuroprotection. As expected, after treatment with MK@PC-R NPs, the Aβ burdens, neuron damages, neuroinflammation, and memory deficits of transgenic AD mice (APP/PS1 mice) are significantly attenuated. Overall, this biomimetic nanodelivery system with anti-Aβ and anti-inflammatory properties provides a promising strategy for the multi-target therapy of early AD. Show less
High-abundance serum proteins, mostly modified by N-glycans, are usually depleted from human sera to achieve in-depth analyses of serum proteome and sub-proteomes. In this study, we show that these hi Show more
High-abundance serum proteins, mostly modified by N-glycans, are usually depleted from human sera to achieve in-depth analyses of serum proteome and sub-proteomes. In this study, we show that these high-abundance glycoproteins (HAGPs) can be used as valuable standard glycopeptide resources, as long as the structural features of their glycans have been well defined at the glycosite-specific level. By directly analyzing intact glycopeptides enriched from serum, we identified 1322 unique glycopeptides at 48 N-glycosites from the top 12 HAGPs (19 subclasses). These HAGPs could be further classified into four major groups based on the structural features of their attached N-glycans. Immunoglobins including IGHG1/2/3/4, IGHA1/2 and IGHM were mostly modified by core fucosylated and bisected N-glycans with rarely sialic acids. Alpha-1-acid glycoproteins (ORM1/2) and haptoglobins (HP) were mainly modified by tri-and tetra-antennary (40 %) N-glycans with antenna-fucoses and sialic acids. Complement components C3 and C4A/B were highly modified by oligo-mannose glycans. The other HAGPs including SERPINA1, A2M, TF, FGB/G and APOB mainly contain bi-antennary complex glycans with the common core structure and (sialyl-) LacNAc branch structures. These HAGPs are easily detected by LC-MS analysis and therefore could be used as standard glycopeptides for glycoproteomic methodology studies as well as possible clinical utilities. Show less
Perioperative neurocognitive disorder (PND) is a common complication following thoracic surgery and often leading to poor outcomes. Despite ongoing research, effective treatments for late PND remain l Show more
Perioperative neurocognitive disorder (PND) is a common complication following thoracic surgery and often leading to poor outcomes. Despite ongoing research, effective treatments for late PND remain limited. Identifying reliable biomarkers for early diagnosis is, therefore, essential. A prospective cohort study was conducted with 60 elderly patients undergoing thoracic surgery. Serum samples were collected within 10 minutes prior to anesthesia and following extubation to measure adiponectin (APN), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), aquaporin-4 (AQP4) and brain-derived neurotrophic factor (BDNF). Among PND patients, serum APN, PKA, AQP4, and BDNF levels were markedly decreased compared with the normal group. While serum cAMP (HR = 1.087, p = 0.695, 95% CI [0.284-4.166]) and PKA (HR = 0.996, p = 0.09, 95% CI [0.491-0.947]) were not significantly correlated with PND, serum APN (HR = 0.307, 95% CI [0.113-0.835], p = 0.021), AQP4 (HR = 0.204, 95% CI [0.060-0.697], p = 0.011), and BDNF (HR = 0.382, 95% CI [0.177-0.823], p = 0.014) were protective factors against PND. ROC analysis demonstrated that APN (AUC = 0.68, 95% CI [0.51-0.87]), AQP4 (AUC = 0.73, 95% CI [0.59-0.87]), BDNF (AUC = 0.73, 95% CI [0.59-0.87]), and the model of combining those biomarkers (AUC = 0.91, 95% CI [0.83-0.99]) could predict PND. PND patients exhibited a lower protective stress response to surgical trauma. High serum APN, AQP4, and BDNF levels were independent protective factors for PND, and a combined model of these biomarkers showed predictive potential for PND. Show less
This study aims to identify and characterize daily activity accumulation patterns (bouts of physical activity and sedentary behavior) among adolescents and then to explore the associations between the Show more
This study aims to identify and characterize daily activity accumulation patterns (bouts of physical activity and sedentary behavior) among adolescents and then to explore the associations between these groups and depressive symptoms. A total of 521 adolescents aged 13-18 years from Wuhan and Changsha, China, were included. Bouts of physical activity (PA) and sedentary behavior (SED) were measured using accelerometers. The Center for Epidemiologic Studies Depression Scale was used to assess participants' depressive symptoms. Latent profile analysis was employed to identify distinct groups based on their activity patterns. Three distinct groups were identified: "Prolonged sitters" ( The synergistic effect of strategies to reduce total SED duration by limiting SED bouts to 30 min or less and increasing light physical activity (LPA) may also be effective in alleviating depressive symptoms in adolescents. 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
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
Yuanpeng Zhu, Di Liu, Xiangjie Yin+3 more · 2025 · The spine journal : official journal of the North American Spine Society · Elsevier · added 2026-04-24
Current clinical guidelines lack clear, quantitative recommendations on intensity-specific physical activity (PA) levels for preventing back pain. Moreover, accelerometer-based evidence regarding dose Show more
Current clinical guidelines lack clear, quantitative recommendations on intensity-specific physical activity (PA) levels for preventing back pain. Moreover, accelerometer-based evidence regarding dose-response relationships and interactions between PA and genetic susceptibility remains limited. To determine the relationships between accelerometer-measured total and intensity-specific PA and incident back pain, and to assess potential effect modification by polygenic risk scores (PRS). Prospective, large-scale, population-based study using UK Biobank data. UK Biobank participants who wore wrist accelerometers for 7 days (N=71,601). Incident back pain, defined as the first recorded ICD-10 dorsalgia code (M54). Total PA, light PA (LPA), and moderate-to-vigorous PA (MVPA) were derived using validated machine-learning algorithms from raw accelerometer data. Dose-response relationships were modeled using restricted cubic splines within Cox proportional hazards models, with adjustment for and stratification by a polygenic risk score (PRS). Point estimates for the population attributable fraction (PAF) were then calculated. Body mass index (BMI) mediation was assessed. Over a median follow-up of 7.0 years, total PA and MVPA exhibited nonlinear inverse associations with incident back pain, independent of genetic risk, with thresholds at approximately 35 milli-g (total PA) and 60 min/day (MVPA). The adjusted PAF was 15.9% for low MVPA and 9.9% for low total PA. Associations were strongest for MVPA, followed by total PA; no significant association was observed for LPA. Within both PRS strata, risk declined monotonically across PA quartiles, with similar effect sizes and no PA × PRS interaction. Notably, participants with high PRS and high PA had lower risk than those with low PRS and low PA. BMI mediated 26.2% of the total PA association and 15.5% of the MVPA association. Accelerometer-measured MVPA robustly reduces back-pain risk, independent of genetic predisposition. Future guidelines should provide clear, intensity-specific recommendations and account for the observed nonlinear dose-response to optimize prevention. Show less
Acupuncture has been proposed as a therapeutic intervention for stroke recovery, yet the underlying molecular mechanisms remain poorly understood. In this study, we used a mouse model of hemorrhagic s Show more
Acupuncture has been proposed as a therapeutic intervention for stroke recovery, yet the underlying molecular mechanisms remain poorly understood. In this study, we used a mouse model of hemorrhagic stroke induced by autologous blood injection to investigate the effects of acupuncture on post-stroke recovery at the cellular and molecular levels, utilizing single-cell RNA sequencing. Our findings revealed that acupuncture modulates the gene expression of microglia, astrocytes, and oligodendrocytes, three major glial cell types, which may contribute to the improvement of stroke-induced phenotypes. Notably, we identified a potential role of the APOE-TREM2 signaling axis, with ligand-binding interactions enhancing microglia activation and promoting their neuroprotective functions. These findings also suggested that acupuncture may promote microglia-astrocyte interactions, leading to enhanced neuroinflammation resolution and tissue repair. Our study provided new insights into the cellular mechanisms underlying acupuncture's therapeutic effects in stroke recovery and highlighted the potential of targeting glial cell-mediated pathways, including APOE-TREM2, as a strategy for improving post-stroke rehabilitation. Show less
Patients with cancer undergoing cisplatin chemotherapy frequently experience cardiotoxic side effects that significantly affect their prognosis and survival rates. Our study found that Panax ginseng r Show more
Patients with cancer undergoing cisplatin chemotherapy frequently experience cardiotoxic side effects that significantly affect their prognosis and survival rates. Our study found that Panax ginseng root extract exerted a significant protective effect against cisplatin-induced myocardial cell injury. The present study aims to elucidate the underlying mechanisms by which the bioactive components of Panax ginseng mitigate cisplatin-induced cardiotoxicity (CIC). In vitro, the candidate active components were screened by network pharmacological prediction and in neonatal rat ventricular myocytes (NRVMs), and their mechanisms of action were verified by transcriptome sequencing, western blotting, gene overexpression, immunoprecipitation, immunofluorescence, and cellular thermal shift assays. A C57BL/6 CIC mouse model was established to verify the protective effects of the candidate components and the in vivo mechanism of the candidate components. Through network pharmacology prediction and cellular activity screening of ginseng root compounds, ginsenoside Rh2(S) (Rh2) was identified as a significant active component. Transcriptomic, in vitro, and in vivo experiments demonstrated that Rh2 can activate the Pak1/Limk1/cofilin phosphorylation pathway, thereby inactivating the actin-severing protein cofilin and protecting cardiomyocytes from cisplatin-induced actin depolymerization. Additionally, Rh2 suppressed the ROS/caspase-3/GSDME pathway to inhibit cisplatin-induced pyroptosis. Furthermore, co-immunoprecipitation and overexpression experiments confirmed that Rh2 activated the FGFR1/HRAS axis, thereby simultaneously regulating the two aforementioned pathways to combat CIC. This study demonstrated for the first time that Rh2 is the main active component in Panax ginseng that maintains cytoskeletal homeostasis and inhibits pyroptosis by regulating the FGFR1/HRAS pathway to resist CIC. This study aimed to provide a theoretical basis for expanding the targets and pathways of CIC treatment, and for the development of related drugs. Show less
This study aims to investigate the roles of the EXT1 and FGFR3 genes in the development of osteochondromas, focusing specifically on their potential interactions in chondrocyte proliferation, differen Show more
This study aims to investigate the roles of the EXT1 and FGFR3 genes in the development of osteochondromas, focusing specifically on their potential interactions in chondrocyte proliferation, differentiation, and tumor formation. In vitro, the ATDC5 chondroprogenitor cell line was used to examine the effects of inactivation of both EXT1 and FGFR3. In vivo, a mouse model with dual gene knockout of Ext1 and Fgfr3 was constructed to further explore these genes' roles in tumor formation by observing the incidence and distribution patterns of osteochondromas. The in vitro experiments demonstrated that ATDC5 cells with reduced expression of EXT1 and FGFR3 genes exhibited enhanced chondrogenic differentiation. In vivo, Fgfr3 The EXT1 and FGFR3 genes play crucial regulatory roles in the development of osteochondromas. Deficiencies in Ext1 and Fgfr3 can induce the formation of osteochondromas. Show less
Postnatal cardiac function in mammals is closely associated with cardiomyocyte proliferation and hypertrophy. However, the molecular mechanisms regulating cardiomyocyte proliferation and hypertrophy h Show more
Postnatal cardiac function in mammals is closely associated with cardiomyocyte proliferation and hypertrophy. However, the molecular mechanisms regulating cardiomyocyte proliferation and hypertrophy have not yet been fully elucidated. Therefore, phenotypic measurements and transcriptomic sequencing were performed on myocardial tissues from 7-day-old (P7) and 3-month-old (3m) female C57BL/6 mice to investigate changes in cardiomyocytes during growth and development and to identify key genes regulating myocardial growth and development. In comparison to 7-day-old mice, 3-month-old mice exhibited a significant increase in heart weight ( Show less
The melanocortin system centrally regulates energy homeostasis, with key components such as melanocortin-4 receptor (MC4R) and adenylyl cyclase 3 (ADCY3) in neuronal primary cilia. Mutations in
β-Secretase (BACE1), a key enzyme to producing neurotoxic β-amyloid, is a potential biomarker of Alzheimer's disease (AD). Developing a sensitive and efficient detection method for BACE1 activity is s Show more
β-Secretase (BACE1), a key enzyme to producing neurotoxic β-amyloid, is a potential biomarker of Alzheimer's disease (AD). Developing a sensitive and efficient detection method for BACE1 activity is significant for AD progression evaluation. Due to the poor cleavage efficiency and acidic working conditions of BACE1, developing probes with high stability and strong signals is challenging for its detection. This work proposed a dual-mode BACE1 detection method based on surface-enhanced Raman scattering and dark-field microscopy. 4-Mercaptobenzoic acid (4-MBA), as the internal Raman reporter of Au@Ag nanoparticles (NPs), shows stable and enhanced Raman signals in an acidic environment. The plasmonic Au Show less