The mediation effect of 24-hour physical activities on the association between type 2 diabetes and mortality is unclear. Additionally, Little evidence was found on the isotemporal substitution effect Show more
The mediation effect of 24-hour physical activities on the association between type 2 diabetes and mortality is unclear. Additionally, Little evidence was found on the isotemporal substitution effect of 24-hour physical activities components on changing Life expectancy among patients with type 2 diabetes diagnosed. To address the abovementioned research gap, the study has a two-fold aims: first, to examine the mediation effect of 24-hour physical activities in type 2 diabetes and mortality; and second, to address how reallocating time on different daily activities would affect life expectancy. Analysis was conducted on the accelerometer data of 103,359 participants in the UK Biobank, with a median age of 57 years (range 39 to 70). Compositional mediation cox model was conducted to analyze the mediating effects of 24-hour physical activities. Additionally, the cohort Life table method was utilized to estimate the changes of Life-years over the next 10 years resulting from the substitution effect of different physical activities. During a mean follow-up of 13.95 (range 2.95-16.28) years, 2,649 deaths were recorded. Diabetes was significantly associated with increased time spent engaging in sedentary behavior (SB), and reduced time spent on moderate-to-vigorous physical activity (MVPA) and light-intensive physical activity (LPA), thereby demonstrating an association with higher mortality risk. The indirect effect of physical activity (HR = 1.27, 95% CI 1.23-1.30) accounted for 41.9% of the total effect of diabetes on mortality. Furthermore, the Life expectancy gains with a maximum of 1.32 years over the next 10 years was found when reallocating SB time to MVPA. The results revealed that 24-hour physical activities might mediate the association between diabetes and mortality. Therefore, promoting participation in MVPA and reducing sedentary activities among diabetes patients was expected to have a positive effect on Life expectancy over the next 10 years. Show less
To investigate the mechanism of liraglutide affecting lipid metabolism by regulating lipolysis and lipogenesis in cells and ob/ob mice. 3 T3-L1 cells were treated with liraglutide in vitro, and differ Show more
To investigate the mechanism of liraglutide affecting lipid metabolism by regulating lipolysis and lipogenesis in cells and ob/ob mice. 3 T3-L1 cells were treated with liraglutide in vitro, and differentially expressed genes were screened by RNA sequencing. Gene Ontology (GO) and KEGG (Kvoto Encyclopedia of Genes and Genomes) enrichment analyses identified target genes for lipid regulation of liraglutide. 3 T3-L1 preadipocytes were induced to differentiate into adipocytes using a "cocktail method". Western blot and immunofluorescence were used to detect the expression of target genes and the lipid regulatory effect of liraglutide. 3 T3-L1 preadipocytes were transfected with lentivirus overexpressing Zbtb20 to study its role in adipogenesis, and gene expression was analyzed by RT-qPCR and Western blot. In vivo, ob/ob mice were subcutaneously injected with liraglutide or saline for 4 weeks. Blood lipids, adipose tissue volume and adipocyte size were detected. Immunohistochemical analysis and RT-qPCR were used to detect the expression of target genes in adipose tissue. Liraglutide reduced lipid droplets and TG levels and altered the expression of genes related to fatty acid metabolism, lipogenesis, fatty acid oxidation, and adipocyte browning. The results of PCR, Western blot and immunofluorescence confirmed that liraglutide could regulate the adipogenesis by downregulating the transcriptional suppressor ZBTB20, and overexpression of Zbtb20 inhibited the expression of LPL, the key enzyme for lipohydrolysis. Liraglutide regulates lipid metabolism through ZBTB20-LPL pathway to reveal its molecular mechanism. Show less
Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection te Show more
Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection techniques. Herein, a unique hydrogel incorporating extracellular matrix from fish swim bladder (FSB-ECM), which has distinct advantages over mammalian derived ECM, such as low antigenicity, bioactivity, and source safety, is developed. It consists of collagen, glycoproteins, and proteoglycans, including 13 proteins common in the myocardial matrix and three specific proteins: HSPG, Col12a1, and vWF. This hydrogel enhances cardiac cell adhesion and stretching while promoting angiogenesis and M2 macrophage polarization. In addition, its storage modulus (G') increases over time, reaching about 1000 Pa after 5 min, which facilitates transcatheter delivery and in situ gelling. Furthermore, this hydrogel provides sustained support for cardiac contractions, exhibiting superior longevity. In a rat model of ischemic heart failure, the ejection fraction significantly improves with FSB-ECM treatment, accompanied by increased angiogenesis, reduced inflammation, and decreased infarct size. Finally, RNA sequencing combined with in vitro assays identifies ANGPTL4 as a key protein involved in mediating the effects of FSB-ECM treatment. Overall, this new injectable hydrogel based on FSB-ECM is suitable for transcatheter delivery and possesses remarkable reparative capabilities for treating heart failure. Show less
Osteoglophonic Dysplasia (OGD) is an autosomal dominant skeletal dysplasia characterized by impaired bone growth resulting in short stature, severe craniofacial abnormalities, and in some patients FGF Show more
Osteoglophonic Dysplasia (OGD) is an autosomal dominant skeletal dysplasia characterized by impaired bone growth resulting in short stature, severe craniofacial abnormalities, and in some patients FGF23-mediated hypophosphatemia. It is caused by gain-of-function variants in FGFR1, particularly in or near the transmembrane domain of the receptor. We used CRISPR in mice to knock-in the FGFR1 p.N330I variant, chosen based on its association with FGF23 excess. Skeletal phenotyping of this Show less
Molecular QTL studies quantify whether genetic variants affect molecular traits, but non-linear effects including distributional patterns, variance, and interactions provide mechanistic insights beyon Show more
Molecular QTL studies quantify whether genetic variants affect molecular traits, but non-linear effects including distributional patterns, variance, and interactions provide mechanistic insights beyond mean-level associations. Methods for detecting distributional effects have been developed for eQTL analysis, yet applications have focused on method demonstrations rather than large-scale biological discovery. We comprehensively mapped quantile, variance, and interaction QTLs across 34 data-set from 22 molecular contexts in >2,300 human brain donors, revealing that 48.7% of quantile QTLs (qQTLs) exhibit context-dependent regulation invisible to linear models, with enrichment at phenotypic extremes and in cell-type-specific regulatory elements, chromatin accessibility regions, and long-range chromosomal contacts. qQTL variants explained additional trait heritability beyond linear QTLs for brain-related traits. At Alzheimer's disease (AD) risk loci, qQTL analysis revealed complex regulatory architecture including variance effects at 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
R-loop is a common chromatin feature consisting of a displaced single-stranded DNA and an RNA-DNA hybrid, and dysregulation of R-loop surveillance results in genomic and transcriptomic instability. Al Show more
R-loop is a common chromatin feature consisting of a displaced single-stranded DNA and an RNA-DNA hybrid, and dysregulation of R-loop surveillance results in genomic and transcriptomic instability. Although the RNA moiety of most R-loops originates from linear transcripts, circular RNAs (circRNAs), outputs from back-splicing, can also hybridize with the complementary strand of a DNA duplex. However, how circRNA-associated R-loops (ciR-loops) are monitored remains elusive. Here, we identify the DEAD-box RNA helicase Brr2 as an evolutionarily-conserved ciR-loop repressor with dual roles in inhibiting circRNA generation and resolving harmful ciR-loops. Accumulation of ciR-loops caused by loss-of-function of this dual-action factor induces antisense transcription and premature transcription termination for many genes and generates significant DNA damage, which further leads to a series of defects in DNA replication, cell division and cell proliferation. We propose that functional integration of multilayered regulation by a single protein can be an efficient double protection against genome instability. Show less
Pork serves as a significant meat commodity, with intramuscular fat (IMF) content being a critical determinant of its quality. However, the epigenetic mechanism of porcine IMF deposition is still uncl Show more
Pork serves as a significant meat commodity, with intramuscular fat (IMF) content being a critical determinant of its quality. However, the epigenetic mechanism of porcine IMF deposition is still unclear. This study integrated proteomics and lactylation profiles from the longissimus thoracis (LT) muscles of pigs with extremely high (IMF_H) and extremely low (IMF_L) IMF content to clarify the association between lactylation and porcine fat deposition. Furthermore, an intramuscular preadipocyte induction and differentiation model was conducted to elucidate the changes in lactylation during adipocyte differentiation. Finally, the regulatory role of lactylation in adipocyte differentiation was explored by modulating lactate production during the induction and differentiation of preadipocytes. Proteomic analysis revealed significantly increased expression of key lipid metabolism related proteins (FASN, APOA4, FABP4, ACLY, PLIN1) in IMF_H pig muscle tissues compared with IMF_L tissues, along with substantial activation of lipid metabolism pathways. Lactylation profiling identified 95 differential lysine sites across 56 proteins, with most showing lower lactylation levels in the IMF_H group. The integrative omics analysis revealed differences in lactylation profiles in porcine LT tissues with varying efficiencies of IMF deposition, highlighted PGK1, PKM, and PYGM as central lactylation-modified proteins in porcine fat deposition regulation. Further in vitro study proved that lactate-mediated lactylation inhibited adipogenic differentiation of porcine intramuscular preadipocytes through PPARγ signaling pathway. This study clarified the changes in the lactylation profile in porcine LT tissues with varying efficiencies of IMF deposition, and demonstrated that lactate-mediated lactylation inhibits the PPARγ signaling pathway and the adipogenic differentiation of porcine intramuscular preadipocyte. This study provided a new insight to understanding the epigenetic regulation mechanisms of lipid deposition in pigs. Show less
This study evaluated the protective effects of naringin (NG) against intestinal injury in 7-day-old piglets infected with porcine epidemic diarrhea virus (PEDV). Eighteen piglets (Duroc × Landrace × L Show more
This study evaluated the protective effects of naringin (NG) against intestinal injury in 7-day-old piglets infected with porcine epidemic diarrhea virus (PEDV). Eighteen piglets (Duroc × Landrace × Large, body weight = 2.58 ± 0.05 kg) were divided into three treatment groups based on similar body weights and equal numbers of males and females: the blank control group (CON group), the PEDV infection group (PEDV group), and the NG intervention + PEDV infection group (NG + PEDV group) ( Show less
This study aimed to develop and apply a novel computational pipeline combining SELFormer, a transformer architecture-based chemical language model, with advanced deep learning techniques to predict na Show more
This study aimed to develop and apply a novel computational pipeline combining SELFormer, a transformer architecture-based chemical language model, with advanced deep learning techniques to predict natural compounds (NCs) with potential in Alzheimer's disease (AD) treatment. The NCs were identified based on activity related to seven AD-specific genes, including acetylcholinesterase (AChE), amyloid precursor protein (APP), beta-secretase 1 (BACE1), and presenilin-1 (PSEN1). We implemented a computational pipeline using SELFormer and deep learning techniques, conducted optimal clustering and quantitative structure-activity relationship (QSAR) analyses, and performed a uniform manifold approximation and projection (UMAP) to categorize compounds based on bioactivity levels. Molecular docking analysis was carried out on selected compounds. To validate the computational predictions, we conducted in vitro studies using nerve growth factor (NGF)-differentiated PC12 cells. Finally, we mapped the relationships between food sources containing the identified compounds and their target proteins. Optimal clustering analysis revealed five distinct groups of NCs, while QSAR analysis highlighted variations in molecular properties across clusters. The UMAP projection identified 17 highly active NCs (pIC This integrated computational and experimental approach offers a promising framework for identifying potential NCs for AD treatment. The results contribute to exploring effective therapeutic strategies against AD. Show less
Recent researches highlight the interdependence of lipoprotein(a) [Lp(a)] and Lp(a)-associated cardiovascular risk with the background inflammatory burden. This study aimed to investigate whether syst Show more
Recent researches highlight the interdependence of lipoprotein(a) [Lp(a)] and Lp(a)-associated cardiovascular risk with the background inflammatory burden. This study aimed to investigate whether systemic inflammation modulates Lp(a)-associated coronary stenosis in chronic coronary syndromes (CCS). A total of 1513 participants undergoing angiography at a tertiary cardiology center in China were included in our retrospective, cross-sectional study. Participants were categorized into normal, mild, and severe groups based on the Gensini Scores, which quantitatively assess stenosis severity. Multinomial logistic models were calculated according to accompanying systemic inflammation concentration. Participants with elevated Lp(a) levels had a high coronary stenosis risk: fully adjusted model odds ratios (ORs) [95% confidence intervals (CIs)] for the mild vs. normal and severe vs. normal groups were 1.47 (1.11-1.96) and 1.68 (1.21-2.33). Notably, the strongest Lp(a)-coronary stenosis associations after multi-variable adjustment persisted only in low inflammation concentration [systemic inflammation response index (SIRI) < 0.64)] [mild vs. normal, OR 2.03, 95% CI 1.17-3.54, Elevated Lp(a) correlates with coronary stenosis only in low inflammation concentration. Considering systemic inflammation in personalized Lp(a)-lowering therapies is more conducive for CCS managements. Show less
The objective of this study was to assess the correlation between the ApoB/ApoA ratio and the recurrence of kidney stones in a Chinese adult population. We collected electronic records of patients wit Show more
The objective of this study was to assess the correlation between the ApoB/ApoA ratio and the recurrence of kidney stones in a Chinese adult population. We collected electronic records of patients with kidney stones who underwent surgical treatment at our hospital from March 2016 to March 2022. These patients were followed up and categorized into groups based on the recurrence of kidney stones. Parameters related to routine blood and biochemical tests, as well as the history of hypertension and diabetes mellitus, were gathered. Multiple imputation was applied for missing data. Subsequently, differences between the recurrence and non-recurrence groups were assessed using the chi-square test, independent samples t test, or Wilcoxon rank sum test. Logistic regression analysis, subgroup analysis, and propensity-matched analysis were conducted to evaluate the relationship between the ApoB/ApoA ratio and kidney stone recurrence. The study included a total of 923 participants aged > 18 years, among whom 296 experienced kidney stone recurrence during the follow-up period. An elevated ApoB/ApoA ratio was identified as a risk factor for kidney stone recurrence (adjusted OR = 2.48, 95% CI 1.04, 5.92). Propensity-matched analyses further supported the association, showing that elevated ApoB/ApoA ratios were linked to a higher risk of renal stone recurrence (OR = 3.37, 95% CI 1.24-9.17). The dose-response curve illustrated a positive linear correlation between the ApoB/ApoA ratio and the risk of kidney stone recurrence. Increased ApoB/ApoA ratios are positively correlated with the risk of kidney stone recurrence. This association remains significant, although a causal relationship cannot be definitively established. Show less
Parkinson's disease (PD) is a neurodegenerative disorder caused by complex genetic and environmental factors. Genome-edited human pluripotent stem cells (hPSCs) offer a unique experimental platform to Show more
Parkinson's disease (PD) is a neurodegenerative disorder caused by complex genetic and environmental factors. Genome-edited human pluripotent stem cells (hPSCs) offer a unique experimental platform to advance our understanding of PD etiology by enabling the generation of disease-relevant cell types carrying patient mutations along with isogenic control cells. To facilitate this approach, we generated a collection of 65 human stem cell lines genetically engineered to harbor high risk or causal variants in genes associated with PD ( Show less
Accelerated population aging and rising incidence of bone defects have intensified the need for advanced bone regeneration strategies. While tissue-engineered scaffolds fabricated via 3D printing offe Show more
Accelerated population aging and rising incidence of bone defects have intensified the need for advanced bone regeneration strategies. While tissue-engineered scaffolds fabricated via 3D printing offer promising alternatives to conventional grafts, most techniques fail to replicate the multi-scale fibrous architecture of native bone extracellular matrix, limiting their biofunctionality. To address this, we developed a hybrid manufacturing strategy integrating low-temperature thermally induced phase separation with extrusion-based 3D printing of polylactic acid (PLA) scaffolds. By optimizing solvent ratios (THF: DMF = 3:1) and freezing temperatures (-196 °C-4 °C), we produced scaffolds with tunable micro-nano fibrous surfaces and macroporous structures. Key findings revealed that scaffolds processed at -196 °C (PLA-196) exhibited the highest porosity (pore size: 6.01 ± 2.06 μm), superior hydrophilicity, and enhanced compressive modulus. These scaffolds significantly promoted BMSC adhesion, proliferation, and osteogenic differentiation via activation of Show less
The genetic foundations underlying the observed disease resistance in certain indigenous pig breeds, notably the Min pigs of China, present a compelling underexplored subject of study. Exploring the m Show more
The genetic foundations underlying the observed disease resistance in certain indigenous pig breeds, notably the Min pigs of China, present a compelling underexplored subject of study. Exploring the mechanisms of disease resistance in these breeds could lay the groundwork for genetic improvements in pig immunity, potentially augmenting overall pig productivity. In this study, whole blood samples were collected from pre- and post- swine fever vaccinated Min and Large White pigs for transcriptome sequencing. The mRNA and lncRNA in both pig breeds were analyzed, and intra-group and inter-group comparisons were also conducted. The results indicated that a greater number of immune-related pathways such as the JAK-STAT and PI3K-AKT signaling were enriched in Min pigs. Furthermore, genes involved in inflammation and antiviral responses, including IL16, IL27, USP18, and DHX58, were upregulated in post-vaccination Min pigs compared to post-vaccination Large White pigs. This heightened immune responsiveness could contribute to the observed differences in disease resistance between Min pigs and Large White pigs. Show less
Sepsis-associated acute lung injury (SA-ALI), a critical complication of sepsis, is characterized by immune dysregulation-induced pulmonary dysfunction. Shenmai Injection (SMI) is a standardized herba Show more
Sepsis-associated acute lung injury (SA-ALI), a critical complication of sepsis, is characterized by immune dysregulation-induced pulmonary dysfunction. Shenmai Injection (SMI) is a standardized herbal preparation consisting of Panax ginseng C.A.Mey (Hongshen) and Ophiopogon japonicus (Thunb.) Ker Gawl (Maidong), traditionally used for qi-replenishing, collapse-stabilizing, and lung-moistening therapy. Although clinically utilized in the management of SA-ALI, the specific mechanisms by which it acts against SA-ALI necessitate further investigation. The present study endeavors to comprehensively determine the therapeutic efficacy of SMI against SA-ALI through an integrated approach combining network pharmacology, metabolomics, metagenomic sequencing, and experimental validation. In this study, murine SA-ALI was established using lipopolysaccharide (LPS) and Poly(I:C). Results indicated that SMI administration significantly attenuated pulmonary inflammation, restored blood-gas barrier integrity, reduced serum pro-inflammatory cytokines and suppressed NF-κB pathway activation in SA-ALI mice. Network pharmacology elucidated the multi-targeted mechanism of SMI in modulating steroid hormone biosynthesis. Integrated metabolomics and target analysis revealed that ophiopogonin A/B and luteolin in SMI alleviates metabolic dysregulation by targeting key enzymes, including AKR1C3, HSD17B1/2, and SULT1E1. Metagenomic profiling demonstrated SMI-mediated gut microbiota remodeling, marked by suppression of pathogenic Chlamydiaceae (particularly Chlamydia abortus) and enrichment of commensal Lactobacillaceae. Correlation analysis showed that intestinal androstenedione and androsterone levels during SMI treatment recovery were negatively correlated with Chlamydia abortus abundance. In conclusion, SMI enhances the recovery from sepsis-associated SA-ALI by dual modulation of gut microbial ecology and host metabolic homeostasis, thereby establishing its potential as a multi-mechanistic therapeutic candidate for sepsis-related organ injury. Show less
Although light-intensity physical activity (LPA) has been suggested to be associated with a lower risk of mortality, the minimal and optimal volumes of LPA remain unclear. We aimed to examine the mini Show more
Although light-intensity physical activity (LPA) has been suggested to be associated with a lower risk of mortality, the minimal and optimal volumes of LPA remain unclear. We aimed to examine the minimal and optimal volumes of LPA associated with the risks of mortality and disease incidence (i.e., cardiovascular diseases and cancer). Data were derived from the population-based UK Biobank cohort study, including 69,492 adults aged 43-78 years. Accelerometer-measured LPA was defined using a validated, published machine learning-based Random Forest activity method, which was categorized into 4 quartile groups. All-cause and cause-specific mortality (cardiovascular disease- and cancer-specific) were determined according to the International Classification of Diseases, 10th version codes. Disease incidence was defined based on primary care, hospitalization, or death records. During a median follow-up period of 8.04 years, 2024 adults died from all causes, 539 from cardiovascular disease, and 1175 from cancer. For all-cause mortality, compared with participants in the lowest quartile of LPA (<3.9 h/day), the hazard ratios (HRs) and 95% confidence intervals (95%CIs) were 0.82 (95%CI: 0.73‒0.93) for those with 3.9 to <5.0 h/day, 0.75 (95%CI: 0.66‒0.85) for those with 5.0 to <6.1 h/day, and 0.77 (95%CI: 0.68‒0.88) for those with ≥6.1 h/day, respectively. There was an inverse non-linear dose-response association between LPA and all-cause mortality, with an optimal dose of 5.72 h/day (95%CI: 5.45‒6.41; HR = 0.63, 95%CI: 0.56‒0.71) and a minimal dose of 3.59 h/day (95%CI: 3.53-8.56; HR = 0.81, 95%CI: 0.78‒0.86), with the 5th percentile as the reference. Similar patterns were observed for cause-specific mortality and disease incidence (cardiovascular disease and cancer). Engaging in LPA for ∼3.5 h/day was conservatively associated with lower risk of mortality and disease incidence, with further risk reductions observed up to an optimal dose of ∼6.0 h/day. These findings suggest that sufficient LPA offers important health benefits, which can inform the development of future PA guidelines. Show less
Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (P Show more
Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (PZI) and trioxytriphenylamine (TOT) ligands, was synthesized. PZI-Au-TOT displays decent thermally activated delayed fluorescence (TADF) with a quantum yield of 93 % in doped film. The crystals of PZI-Au-TOT show simultaneous TADF, polymorphism, and linearly polarized luminescence (LPL). The polymorph-dependent emission properties with widely varied peaks from 560 to 655 nm are attributed to different packing modes in terms of isolated monomers, discrete π-π stacked dimers or dimer PLUS. Two well-defined microcrystals of PZI-Au-TOT exhibit linearly polarized thermally activated delayed fluorescence with a degree of polarization up to 0.64. This work demonstrates that the molecular rotational flexibility of D-M-A type complexes endows an integration of multiple functions into one complex through manipulation of supramolecular aggregation. This type of complexes is expected to serve as a versatile platform for the fabrication of crystal materials for advanced photonic applications. 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
Breast cancer (BC) is one of the most prevalent malignant diseases affecting women. Cytochrome c (Cyt c) plays a critical role in various pathological processes, however, its precise mechanism in BC r Show more
Breast cancer (BC) is one of the most prevalent malignant diseases affecting women. Cytochrome c (Cyt c) plays a critical role in various pathological processes, however, its precise mechanism in BC remains unclear. This study aimed to identify prognostic genes linked to Cyt c in BC and explore their underlying mechanisms. Transcriptome data related to BC were initially obtained from TCGA and GEO database. Prognostic genes were identified through differential expression analysis, univariate Cox regression, and LASSO analysis. A risk model was subsequently developed and validated. Additionally, enrichment analysis, immune microenvironment analysis, and the construction of a TFs-mRNA network were conducted. Finally, the expression levels of prognostic genes were examined in both tumor and normal tissue samples, with confirmation through RT-qPCR. Eight prognostic genes ( Show less
Our previous investigations identified miR-30a-3p as a differentially expressed miRNA in ovine mammary tissue across sheep breeds with distinct lactation performance and different physiological stages Show more
Our previous investigations identified miR-30a-3p as a differentially expressed miRNA in ovine mammary tissue across sheep breeds with distinct lactation performance and different physiological stages. However, its regulatory mechanisms controlling mammary gland development and lactation remain unexplored. In this study, the effect of miR-30a-3p on the proliferation of ovine mammary epithelial cells (MECs) and the target genes of miR-30a-3p were investigated. The regulatory effects of miR-30a-3p on the expression of the target genes and the content of triglycerides in ovine MECs were also analyzed. The transfection of miR-30a-3p mimic was found to promote cell viability and the number of proliferated ovine MECs using CCK8 and Edu assays. On the contrary, the miR-30a-3p inhibitor showed the opposite results with the miR-30a-3p mimic. These results suggest that miR-30a-3p promotes the proliferation of ovine MECs. The dual luciferase assay revealed that Phosphatase and Tensin Homolog ( Show less
To investigate the risk factors associated with coronary heart disease (CHD) in patients with metabolic-associated fatty liver disease (MAFLD) and develop a nomogram prediction model. This study inclu Show more
To investigate the risk factors associated with coronary heart disease (CHD) in patients with metabolic-associated fatty liver disease (MAFLD) and develop a nomogram prediction model. This study included 394 patients with MAFLD who underwent coronary angiography at The Affiliated Hospital of Qingdao University between December 2019 and December 2024. The study cohort was divided in a 7:3 ratio into training and validation sets comprising 277 and 117 cases, respectively. The training group was further divided into the MAFLD-only ( Of the 394 MAFLD cases, 313 had CHD-related complications. Of the 277 patients in the training set, 220 had CHD, and of the 117 patients in the validation set, 93 had CHD. LASSO regression analysis revealed that the following variables were associated with the risk of CHD: sex, lipoprotein(a) (Lp[a]), low-density lipoprotein cholesterol, white blood cell count (WBC), glycated triglyceride-glucose index (TyG), and atherosclerosis index (AIP). Multivariate logistic regression analysis revealed that sex, Lp(a), WBC, TyG, and AIP were independent risk factors for CHD in MAFLD cases. A nomogram was constructed and an ROC curve was plotted, based on which the optimal cutoff value was determined as 0.698. The area under the curve of the nomogram in the training and validation cohorts was 0.860 (95% CI = 0.807-0.913) and 0.843 (95% CI = 0.757-0.929), respectively. Calibration curves for CHD risk probability showed good agreement between the nomogram's predicted probabilities and the observed event rates. DCA demonstrated the net clinical benefit of the constructed nomogram. Sex, Lp(a), WBC, TyG, and AIP emerged as independent risk factors for CHD in patients with MAFLD and the nomogram prediction model constructed using these factors could effectively predict CHD occurrence. Show less
To investigate the influence of MEK5/ERK5 pathway on mitophagy in osteosarcoma (OS), as well as the involved molecular mechanisms. The overlapped genes of mitophagy-related genes from MSigDB database Show more
To investigate the influence of MEK5/ERK5 pathway on mitophagy in osteosarcoma (OS), as well as the involved molecular mechanisms. The overlapped genes of mitophagy-related genes from MSigDB database and DEGs between metastatic and primary OS groups from GSE32981 were identified. GSVA of mitophagy-related pathways between the metastatic and primary groups were analyzed. The relationships between Nur77 and mitophagy-related pathways, prognosis, immune infiltrating cells, immune response gene sets were investigated. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting were utilized to assess the expression levels of MEK5, ERK5, Nur77, PINK1, and Parkin. Cellular behaviors and mitochondrial potential were evaluated via CCK-8, Transwell assay and JC-1 staining. Total 4 overlapped genes were obtained as mitophagy-related DEGs, including GABARAPL1, HIF1A, PINK1, and RB1CC1. The activity scores of 3 mitophagy-related pathways exhibited significant differences between metastatic and primary groups. Importantly, Nur77 was significantly negatively correlated with a mitophagy-related pathway (GOBP MITOPHAGY: R = - 0.48, P = 0.02). The Nur77 expression in metastatic group was remarkedly higher than that in the primary group (P < 0.001). Patients with high Nur77 expression had poor prognosis, with AUC values all above 0.615 in predicting 1-, 3-, and 5-year survival. In addition, Nur77 was closely related to numerous immune cells, including activated dendritic cells, activated mast cells and M0 macrophages, and immune response gene sets chemokines and cytokines (all P < 0.05). In addition, MEK5/ERK5 pathway is activated in OS, and Nur77 is overexpressed in OS, and MEK5/ERK pathway promotes Nur77 expression, tumorigenesis and mitochondrial function in U2OS cells. Cytosporone B implement significantly increased the tumorigenesis of U2OS cells in sh-MEK5 group, and inhibited the weaken in mitochondrial membrane potential caused by MEK5 downregulation, and reversed the protein levels of mitophagy markers PINK1 and Parkin in sh-MEK5 group. MEK5-ERK5 pathway mediates mitophagy by regulating Nur77 to promote tumorigenesis of OS cells. These findings offered promising therapeutic targets for OS. Show less
Cattle body size measurements constitute the conformation traits that facilitate their production, fertility, and longevity status. Prioritizing functional variants and causal genes of conformation tr Show more
Cattle body size measurements constitute the conformation traits that facilitate their production, fertility, and longevity status. Prioritizing functional variants and causal genes of conformation traits is essential for understanding their genetic basis. In this study, we conducted single-trait and multitrait GWAS for 20 body conformation traits using imputed sequence data in 7,674 Chinese Holstein individuals and identified 27 QTL regions. Leveraging these QTL regions, we performed multitrait Bayesian fine-mapping to identify 30 independent credible sets of putative causal variants. Incorporating GWAS and cis-acting expression QTL data, Mendelian randomization was used to infer 153 putative causal gene-trait relationships. The previously reported genes, such as CCND2, TMTC2, and NRG3, were confirmed in our study. Of note, several novel candidate causal genes were also identified, such as C1R, RIMS1, SERPINB8, NETO2, TTYH3, TTC3, ANAPC4, and PSMD13. Our results provide new insights into the regulatory mechanisms of body conformation traits in cattle. Show less
Long noncoding RNAs (lncRNAs), non-protein-coding transcripts exceeding 200 nucleotides, are critical regulators of gene expression through chromatin remodeling, transcriptional modulation, and post-t Show more
Long noncoding RNAs (lncRNAs), non-protein-coding transcripts exceeding 200 nucleotides, are critical regulators of gene expression through chromatin remodeling, transcriptional modulation, and post-transcriptional modifications. While ionizing radiation (IR) induces cellular damage through direct DNA breaks, reactive oxygen species (ROS)-mediated oxidative stress, and bystander effects, the functional involvement of lncRNAs in the radiation response remains incompletely characterized. Here, through genome-wide CRISPR activation (CRISPRa) screening in non-small cell lung cancer (NSCLC) cells, we identified LOC401312 as a novel radiosensitizing lncRNA, the stable overexpression of which significantly enhanced IR sensitivity. Transcriptomic profiling revealed that LOC401312 transcriptionally upregulates carbamoyl-phosphate synthase 1 (CPS1), a mitochondrial enzyme involved in pyrimidine biosynthesis. Notably, CPS1 overexpression recapitulated the radiosensitization phenotype observed with LOC401312 activation. Mechanistic investigations revealed that CPS1 suppresses the phosphorylation of ATM kinase (Ser1981) protein, which is a key mediator of DNA damage checkpoint activation. This study established the LOC401312-CPS1-ATM axis as a previously unrecognized regulatory network governing radiation sensitivity, highlighting the potential of lncRNA-directed metabolic rewiring to impair DNA repair fidelity. Our findings not only expand the functional landscape of lncRNAs in DNA damage response but also provide a therapeutic rationale for targeting the LOC401312-CPS1 axis to improve radiotherapy efficacy in NSCLC. Show less
Juvenile hormone (JH) is important to maintain insect larval status; however, its cell membrane receptor has not been identified. Using the lepidopteran insect
To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatom Show more
To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatomical structures of the midfoot and Lisfranc joint complexes. A total of 100 adult lower limbs were dissected and the types of LPL were divided according to their insertions, among them, 63 were (63%) and 37 were female (37%); 50 were on the left side (50%) and 50 were on the right side (50%). The fiber bundle length, origin width, insertion width, and thickness of the LPL were measured. (1) According to the insertions of the LPL, they were divided into: ① Type I, the LPL was inserted at the base of the second metatarsal (M2) in 47 cases; ② Type II, the LPL was inserted at the base of M2 and fused with tibialis posterior tendon (TPT) in 16 cases; ③ Type III, the LPL was absent in 16 cases; ④ Type IV, the LPL was inserted at TPT in 6 cases; ⑤ Type V, the LPL was inserted at the intermediate cuneiform (IC) in 1 case; ⑥ Type VI, bifid LPL with one bundle inserted at the base of M2, and the other bundle inserted at the medial cuneiform (MC) in 4 cases; ⑦ Type VII, two bundles of LPL inserted at the base of M2 in 8 cases; ⑧ Type VIII, the LPL consisted of 3 bundles; the distal, middle and proximal bundles was inserted at the base of M2, the TPT and the lateral side of navicular bone in 2 cases, respectively. (2) There was a statistical significance in the length of LPL between male (31.62 ± 3.83) mm and female (28.07 ± 3.46) mm (t=-3.050, P = 0.003). There was no statistical significance in the types of LPL between male and female (Z=-1.721, P > 0.05), and no statistical significance in the types between left and right sides (Z=-0.026, P > 0.05). According to our research, LPL originates from M5 and is divided into 8 types according to its insertion location, of which insertion at the base of M2 is the most common. In addition, we found that LPL has fibrous fusion with the long plantar ligament and the TPT, which may be involved in maintaining arch stability. The classification of LPL in this study is a supplement to the anatomical structure of the middle foot and Lisfranc joint complex, providing a new direction for the diagnosis and treatment of middle foot and arch injury in the future. Show less