ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

Optical imaging is highly valued for its superior temporal and spatial resolution. This is particularly important in near-infrared II (NIR-II, 1 000-3 000 nm) imaging, which offers advantages such as reduced tissue absorption, minimal scattering, and low autofluorescence. These characteristics make NIR-II imaging especially suitable for deep tissue visualization, where high contrast and minimal background interference are critical for accurate diagnosis and monitoring. Currently, inorganic fluorescent probes—such as carbon nanotubes, rare earth nanoparticles, and quantum dots—offer high brightness and stability. However, they are hindered by ambiguous structures, larger sizes, and potential accumulation toxicity in vivo. In contrast, organic fluorescent probes, including small molecules and polymers, demonstrate higher biocompatibility but are limited by shorter emission wavelengths, lower quantum yields, and reduced stability. Recently, gold clusters have emerged as a promising class of nanomaterials with potential applications in biocatalysis, fluorescence sensing, biological imaging, and more. Water-soluble gold clusters are particularly attractive as fluorescent probes due to their remarkable optical properties, including strong photoluminescence, large Stokes shifts, and excellent photostability. Furthermore, their outstanding biocompatibility—attributed to good aqueous stability, ultra-small hydrodynamic size, and high renal clearance efficiency—makes them especially suitable for biomedical applications. Gold clusters hold significant potential for NIR-II fluorescence imaging. Atomic-precision gold clusters, typically composed of tens to hundreds of gold atoms and measuring only a few nanometers in diameter, possess well-defined three-dimensional structures and clear spatial coordination. This atomic-level precision enables fine-tuned structural regulation, further enhancing their fluorescence properties. Variations in cluster size, surface ligands, and alloying elements can result in distinct physicochemical characteristics. The incorporation of different atoms can modulate the atomic and electronic structures of gold clusters, while diverse ligands can influence surface polarity and steric hindrance. As such, strategies like alloying and ligand engineering are effective in enhancing both fluorescence and catalytic performance, thereby meeting a broader range of clinical needs. In recent years, gold clusters have attracted growing attention in the biomedical field. Their application in NIR-II imaging has led to significant progress in vascular, organ, and tumor imaging. The resulting high-resolution, high signal-to-noise imaging provides powerful tools for clinical diagnostics. Moreover, biologically active gold clusters can aid in drug delivery and disease diagnosis and treatment, offering new opportunities for clinical therapeutics. Despite the notable achievements in fundamental research and clinical translation, further studies are required to address challenges related to the standardized synthesis and complex metabolic behavior of gold clusters. Resolving these issues will help accelerate their clinical adoption and broaden their biomedical applications.

Intelligence encompasses various abilities, including logical reasoning, comprehension, self-awareness, learning, planning, creativity, and problem-solving. Extensive research and practical experience suggest that there are sex differences in intellectual development, with females typically maturing earlier than males. However, the key genes and molecular network mechanisms underlying these sex differences in intellectual development remain unclear. To date, Genome-Wide Association Studies (GWAS) have identified 507 genes that are significantly associated with intelligence. This study first analyzed RNA sequencing data from different stages of brain development (from BrainSpan), revealing that during the late embryonic stage, the average expression levels of intelligence-related genes are higher in males than in females, while the opposite is observed during puberty. This study further constructed interaction networks of intelligence-related genes with sex-differential expression in the brain, including the prenatal male network (HELP-M: intelligence genes with higher expression levels in prenatal males) and the pubertal female network (HELP-F: intelligence genes with higher expression levels in pubertal females). The findings indicate that the key genes in both networks are Ep300 and Ctnnb1. Specifically, Ep300 regulates the transcription of 53 genes in both HELP-M and HELP-F, while Ctnnb1 regulates the transcription of 45 genes. Ctnnb1 plays a more prominent role in HELP-M, while Ep300 is more crucial in HELP-F. Finally, this study conducted sequencing validation on rats at different developmental stages, and the results indicated that in the prefrontal cortex of female rats during adolescence, the expression levels of the intelligence genes in HELP-F, as well as key genes Ep300 and Ctnnb1, were higher than those in male rats. These genes were also involved in neurodevelopment-related biological processes. The findings reveal a sex-differentiated intelligence gene network and its key genes, which exhibit varying expression levels during the neurodevelopmental process.
Female ; Intelligence/physiology* ; Male ; Sex Characteristics ; Animals ; Brain/growth & development* ; E1A-Associated p300 Protein/physiology* ; beta Catenin/physiology* ; Transcriptome ; Rats ; Gene Expression Profiling ; Genome-Wide Association Study

The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals ; MAP Kinase Kinase Kinases/physiology* ; Rats ; Myocytes, Cardiac/pathology* ; Disulfiram/pharmacology* ; Cardiomegaly ; Apoptosis/drug effects* ; Cell Line ; Angiotensin II ; Necroptosis/drug effects* ; Interleukin-1beta/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Lactones ; Resorcinols ; Zearalenone/administration & dosage*

The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal

This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*

This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Male ; Humans ; Capsules ; Female ; Disease Models, Animal