Antibiotic misuse has been a severe problem in animal husbandry. It is meaningful to replace antibiotics with Bacillus, as feed additives are indeed a research hotspot. Bacillus pumilus plays a certai Show more
Antibiotic misuse has been a severe problem in animal husbandry. It is meaningful to replace antibiotics with Bacillus, as feed additives are indeed a research hotspot. Bacillus pumilus plays a certain role in promoting the growth performance and immunological indicators of animals. There are few reports about the function of goat-derived B. pumilus in animals until now. This study aimed to investigate the effects of B. pumilus fsznc-09 on growth performance and immune function of Jintang black goats. B. pumilus-treated group was fed with 1 ml freeze-dried agent of B. pumilus fsznc-09 at a concentration of 109 cfu/ml every 2 days. The growth performance, serum biochemical indexes, the expressions of muscle development and metabolism related genes of Jintang black goats were measured after 30 days. The results showed that the average daily gain and average daily feed intake were significantly increased, and feed conversion ratio was significantly decreased. The activities of total superoxide dismutase, alkaline phosphatase, immunoglobulin G and interferon-γ in serum of goats were significantly increased. However, the activity of malondialdehyde in serum was significantly decreased. The diameters and areas in longissimus dorsi fibre and gluteus fibre of goats were significantly decreased, while the densities in gluteus fibre of goats were significantly increased. The expressions of FAS, LPL, PPAR-γ, CAT, MYOD1, MYOG, MYF5 and MyHCI in longissimus dorsi and gluteus of goats were significantly improved. The expressions of TGFβ1, SREBP-1, MyHCIIb and MyHCIIx in longissimus dorsi and gluteus of goats were significantly increased. The expressions of FN1 in longissimus dorsi and MyHCIIa in gluteus of goats were significantly decreased. In conclusion, B. pumilus fsznc-09 can effectively improve the growth performance, immunological indicators and the expressions of muscle development and metabolism related genes of Jintang black goat. Show less
Transient receptor potential channel 6 (TRPC6) is reported to be involved in the pathogenesis of diabetic complications, but its role in diabetic retinopathy (DR) remains unknown. The aim of our study Show more
Transient receptor potential channel 6 (TRPC6) is reported to be involved in the pathogenesis of diabetic complications, but its role in diabetic retinopathy (DR) remains unknown. The aim of our study was to determine the role and mechanism of TRPC6 in DR. High glucose was used to construct a DR cell model using rat retinal Müller cells (rMC-1). Intracellular Ca The knockdown of TRPC6 reduced inflammation and cell pyroptosis in HG induced rMC-1 cells, whereas overexpression of TRPC6 had the opposite effects. The inhibition of ROS and NLRP3 reversed TRPC6-mediated cell pyroptosis in the DR cell model. In addition, EP300 increased the expression of H3K27ac and TRPC6 to promote cell pyroptosis, which was suppressed by the knockdown of TRPC6. Our study revealed a novel EP300/H3K27ac/TRPC6 signaling pathway that may contribute to HG induced Müller cell pyroptosis. TRPC6 played a novel role in Müller cell pyroptosis triggered by HG, and may be a potential target for DR treatment in the future. Show less
Jie Li, Lijuan Zhang, Yun Tao+3 more · 2023 · European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · Elsevier · added 2026-04-24
Hepatocellular carcinoma (HCC) is a serious life-threatened tumor with high morbidity and mortality. This study aimed to study the effects of combination TACE and anti-PD-L1 liposome drug in treating Show more
Hepatocellular carcinoma (HCC) is a serious life-threatened tumor with high morbidity and mortality. This study aimed to study the effects of combination TACE and anti-PD-L1 liposome drug in treating HCC in mice models. We constructed the liposome drug with phosphatidylcholine and cholesterol and mannitol, etc. Besides, the HCC mice model was established through abdominal subcutaneous injection HepG2 cancer cells in mice, then the PE-10 polyethylene catheter was used for TACE therapy. The mice were separately received transcatheter arterial chemoembolization treatment, avelumab liposome drug therapy, and TACE combined with avelumab liposome drug therapy. Flow cytometry was used to analyze cell apoptosis. Western blot, Immunofluorescence staining, real-time PCR were performed to detect protein and gene expressions. The liposomes drug was successfully constructed with a diameter of (125.5 ± 15.3) nm. After the mice received TACE and (or) immunotherapy, the combined liposome drug therapy significantly reduced the volume of hepatic carcinoma tissues, besides, the apoptotic rate of hepatic carcinoma cells in the combined liposome drug treatment group was increased obviously compared with other groups. Moreover, the protein TGFβR2 located in the cellular membrane was obviously down-regulated in the combined liposome drug therapy, while the expression of SMAD7 and PTPN14 was up-regulated in the treatment groups compared with the mice without treatment, besides, the protein PTPN14 was mainly located in the nucleus. Additionally, the mRNA expression of genes SNAI1 and Vimentin was significantly down-regulated in the combined liposome drug therapy. Combination of transcatheter arterial chemoembolization and anti-PD-L1 liposome drug therapy significantly suppressed hepatocellular carcinoma proliferation and metastasis in mice models. Show less
Mulberry (Morus alba L.) leaf, as a medicinal and food homologous traditional Chinese medicine, has a clear therapeutic effect on type 2 diabetes mellitus (T2DM), yet its underlying mechanisms have no Show more
Mulberry (Morus alba L.) leaf, as a medicinal and food homologous traditional Chinese medicine, has a clear therapeutic effect on type 2 diabetes mellitus (T2DM), yet its underlying mechanisms have not been totally clarified. The study aimed to explore the mechanism of mulberry leaf in the treatment of T2DM through tandem mass tag (TMT)-based quantitative proteomics analysis of skeletal muscle. The anti-diabetic activity of mulberry leaf extract (MLE) was evaluated by using streptozotocin-induced diabetic rats at a dose of 4.0 g crude drug /kg p.o. daily for 8 weeks. Fasting blood glucose, body weight, food and water intake were monitored at specific intervals, and oral glucose tolerance test and insulin tolerance test were conducted at the 7th and 8th week respectively. At the end of the experiment, levels of glycated hemoglobin A1c, insulin, free fat acid, leptin, adiponectin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were assessed and the pathological changes of rat skeletal muscle were observed by HE staining. TMT-based quantitative proteomic analysis of skeletal muscle and bioinformatics analysis were performed and differentially expressed proteins (DEPs) were validated by western blot. The interactions between the components of MLE and DEPs were further assessed using molecular docking. After 8 weeks of MLE intervention, the clinical indications of T2DM such as body weight, food and water intake of rats were improved to a certain extent, while insulin sensitivity was increased and glycemic control was improved. Serum lipid profiles were significantly reduced, and the skeletal muscle fiber gap and atrophy were alleviated. Proteomic analysis of skeletal muscle showed that MLE treatment reversed 19 DEPs in T2DM rats, regulated cholesterol metabolism, fat digestion and absorption, vitamin digestion and absorption and ferroptosis signaling pathways. Key differential proteins Apolipoprotein A-1 (ApoA1) and ApoA4 were successfully validated by western blot and exhibited strong binding activity to the MLE's ingredients. This study first provided skeletal muscle proteomic changes in T2DM rats before and after MLE treatment, which may help us understand the molecular mechanisms, and provide a foundation for developing potential therapeutic targets of anti-T2DM of MLE. Show less
Qiqing Sun, Fangjie Wang, Linbo Su+5 more · 2023 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · added 2026-04-24
To explore the clinical and genetic characteristics of eight children with Primary hypertrophic cardiomyopathy (HCM). Eight children with HCM admitted to the Department of Cardiology of Henan Children Show more
To explore the clinical and genetic characteristics of eight children with Primary hypertrophic cardiomyopathy (HCM). Eight children with HCM admitted to the Department of Cardiology of Henan Children's Hospital from January 2018 to December 2021 were selected as the study subjects. Clinical data of the children were collected. Whole exome sequencing was carried out on two children, and trio whole exome sequencing was carried out on the remainder 6 children. Sanger sequencing was used to verify the candidate variants in the children and their parents, and the pathogenicity of the variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had included 5 males and 3 females, with their ages ranging from 5 to 13 years old. The average age of diagnosis was (7.87 ± 4.8) years old, and the cardiac phenotype showed non-obstructive HCM in all of the patients. WES has identified variants of the MYH7 gene in 4 children, including c.2155C>T (p.Arg719Trp), c.1208G>A (p.Arg403Gln), c.1358G>A (p.Arg453His), and c.1498G>A (p.Glu500Lys). Based on the guidelines from the ACMG, the first 3 variants were classified as pathogenic, while c.1498G>A (p.Glu500Lys) was classified as likely pathogenic (PM1+PM2_Supporting+PM6+PP3), which was also unreported previously. The remaining four children had all harbored maternal variants, including MYL2: c.173G>A (p.Arg58Gln; classified as pathogenic), TPM1: c.574G>A (p.Glu192Lys) and ACTC1: c.301G>A (p.Glu101Lys)(both were classified as likely pathogenic), and MYBPC3: c.146T>G (p.Ile49Ser; classified as variant of uncertain significance). Seven children were treated with 0.5 ~ 3 mg/(kg·d) propranolol, and their symptoms had improved significantly. They were followed up until September 30, 2022 without further cardiac event. Genetic testing can clarify the molecular basis for unexplained cardiomyopathy and provide a basis for clinical diagnosis and genetic counseling. Discovery of the c.1498G>A (p.Glu500Lys) variant has also expanded the spectrum of MYH7 gene mutations underlying HCM. Show less
Ischemic stroke (IS) is a fatal neurological disease that occurs when the blood flow to the brain is disrupted, leading to brain tissue damage and functional impairment. Cellular senescence, a vital c Show more
Ischemic stroke (IS) is a fatal neurological disease that occurs when the blood flow to the brain is disrupted, leading to brain tissue damage and functional impairment. Cellular senescence, a vital characteristic of aging, is associated with a poor prognosis for IS. This study explores the potential role of cellular senescence in the pathological process following IS by analyzing transcriptome data from multiple datasets (GSE163654, GSE16561, GSE119121, and GSE174574). By using bioinformatics methods, we identified hub-senescence-related genes such as Show less
Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not in individuals with metabolic syndrome, with the underlying mechanisms still being unc Show more
Short-chain fatty acids, including butyrate, have multiple metabolic benefits in individuals who are lean but not in individuals with metabolic syndrome, with the underlying mechanisms still being unclear. We aimed to investigate the role of gut microbiota in the induction of metabolic benefits of dietary butyrate. We performed antibiotic-induced microbiota depletion of the gut and fecal microbiota transplantation (FMT) in APOE*3-Leiden.CETP mice, a well-established translational model for developing human-like metabolic syndrome, and revealed that dietary butyrate reduced appetite and ameliorated high-fat diet-induced (HFD-induced) weight gain dependent on the presence of gut microbiota. FMT from butyrate-treated lean donor mice, but not butyrate-treated obese donor mice, into gut microbiota-depleted recipient mice reduced food intake, attenuated HFD-induced weight gain, and improved insulin resistance. 16S rRNA and metagenomic sequencing on cecal bacterial DNA of recipient mice implied that these effects were accompanied by the selective proliferation of Lachnospiraceae bacterium 28-4 in the gut as induced by butyrate. Collectively, our findings reveal a crucial role of gut microbiota in the beneficial metabolic effects of dietary butyrate as strongly associated with the abundance of Lachnospiraceae bacterium 28-4. Show less
Parallel to major changes in fatty acid and glucose metabolism, defect in branched-chain amino acid (BCAA) catabolism has also been recognized as a metabolic hallmark and potential therapeutic target Show more
Parallel to major changes in fatty acid and glucose metabolism, defect in branched-chain amino acid (BCAA) catabolism has also been recognized as a metabolic hallmark and potential therapeutic target for heart failure. However, BCAA catabolic enzymes are ubiquitously expressed in all cell types and a systemic BCAA catabolic defect is also manifested in metabolic disorder associated with obesity and diabetes. Therefore, it remains to be determined the cell-autonomous impact of BCAA catabolic defect in cardiomyocytes in intact hearts independent from its potential global effects. In this study, we developed two mouse models. One is cardiomyocyte and temporal-specific inactivation of the E1α subunit (BCKDHA-cKO) of the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, which blocks BCAA catabolism. Another model is cardiomyocyte specific inactivation of the BCKDH kinase (BCKDK-cKO), which promotes BCAA catabolism by constitutively activating BCKDH activity in adult cardiomyocytes. Functional and molecular characterizations showed E1α inactivation in cardiomyocytes was sufficient to induce loss of cardiac function, systolic chamber dilation and pathological transcriptome reprogramming. On the other hand, inactivation of BCKDK in intact heart does not have an impact on baseline cardiac function or cardiac dysfunction under pressure overload. Our results for the first time established the cardiomyocyte cell autonomous role of BCAA catabolism in cardiac physiology. These mouse lines will serve as valuable model systems to investigate the underlying mechanisms of BCAA catabolic defect induced heart failure and to provide potential insights for BCAA targeted therapy. Show less
Despite the increasing prevalence rate of nonalcoholic fatty liver disease (NAFLD) worldwide, efficient pharmacotherapeutic regimens against NAFLD still need to be explored. Previous studies found tha Show more
Despite the increasing prevalence rate of nonalcoholic fatty liver disease (NAFLD) worldwide, efficient pharmacotherapeutic regimens against NAFLD still need to be explored. Previous studies found that pioglitazone and metformin therapy could partly ameliorate NAFLD, but their combination therapy effects have not been researched. In the present study, we assessed the protective effects of metformin and pioglitazone combination therapy on liver lipid metabolism in high-fat diet (HFD)-fed mice and investigated the molecular mechanism. Male C57BL/6 mice were divided into five groups: normal control; HFD control; metformin monotherapy; pioglitazone monotherapy and combined therapy. After 8 weeks of pharmacological intervention, glucose and lipid metabolism characteristics, hepatic histology, lipidomics profiling and RNA-seq analysis were performed. The combination of pioglitazone and metformin significantly ameliorated HFD-induced metabolic disturbance and the hepatic oil red O area. A lipidomics analysis showed that combined therapy could significantly reduce the high levels of free fatty acids (FFA), diacylglycerol and triglycerides, while a set of glycerophospholipids and sphingolipids were increased in the combined therapy group. Consistently, an RNA-seq analysis also showed a remarkable reduction in genes associated with FFA uptake and de novo lipogenesis, including Pioglitazone and metformin might have a synergistic protective effect on NAFLD by improving hepatic lipid profiles in HFD-induced mice. Further studies are needed to verify the clinical effects. Show less
BACE1 is the rate-limiting enzyme for β-amyloid (Aβ) production and therefore is considered a prime drug target for treating Alzheimer's disease (AD). Nevertheless, the BACE1 inhibitors failed in clin Show more
BACE1 is the rate-limiting enzyme for β-amyloid (Aβ) production and therefore is considered a prime drug target for treating Alzheimer's disease (AD). Nevertheless, the BACE1 inhibitors failed in clinical trials, even exhibiting cognitive worsening, implying that BACE1 may function in regulating cognition-relevant neural circuits. Here, we found that parvalbumin-positive inhibitory interneurons (PV INs) in hippocampal CA1 express BACE1 at a high level. We designed and developed a mouse strain with conditional knockout of BACE1 in PV neurons. The CA1 fast-spiking PV INs with BACE1 deletion exhibited an enhanced response of postsynaptic N-methyl-D-aspartate (NMDA) receptors to local stimulation on CA1 oriens, with average intrinsic electrical properties and fidelity in synaptic integration. Intriguingly, the BACE1 deletion reorganized the CA1 recurrent inhibitory motif assembled by the heterogeneous pyramidal neurons (PNs) and the adjacent fast-spiking PV INs from the superficial to the deep layer. Moreover, the conditional BACE1 deletion impaired the AMPARs-mediated excitatory transmission of deep CA1 PNs. Further rescue experiments confirmed that these phenotypes require the enzymatic activity of BACE1. Above all, the BACE1 deletion resets the priming of the fear memory extinction. Our findings suggest a neuron-specific working model of BACE1 in regulating learning and memory circuits. The study may provide a potential path of targeting BACE1 and NMDAR together to circumvent cognitive worsening due to a single application of BACE1 inhibitor in AD patients. Show less
Isoxazole 9 (ISX9) is a neurogenesis-promoting small molecule compound that can up-regulate the expression of NeuroD1 and induce differentiation of neuronal, cardiac and islet endocrine progenitors. S Show more
Isoxazole 9 (ISX9) is a neurogenesis-promoting small molecule compound that can up-regulate the expression of NeuroD1 and induce differentiation of neuronal, cardiac and islet endocrine progenitors. So far, the molecular mechanisms underlying the action of ISX9 still remain elusive. To identify a novel agonist of the Wnt/β-catenin, a cell-based SuperTOPFlash reporter system was used to screen known-compound libraries. An activation effect of ISX9 on the Wnt/β-catenin pathway was analysed with the SuperTOPFlash or SuperFOPFlash reporter system. Effects of ISX9 on Axin1/LRP6 interaction were examined using a mammalian two-hybrid system, co-immunoprecipitation, microscale thermophoresis, emission spectra and mass spectrometry assays. The expression of Wnt target and stemmness marker genes were evaluated with real-time PCR and immunoblotting. In vivo hair regeneration abilities of ISX9 were analysed by immunohistochemical staining, real-time PCR and immunoblotting in hair regrowth model using C57BL/6J mice. In this study, ISX9 was identified as a novel agonist of the Wnt/β-catenin pathway. ISX9 targeted Axin1 by covalently binding to its N-terminal region and potentiated the LRP6-Axin1 interaction, thereby resulting in the stabilization of β-catenin and up-regulation of Wnt target genes and stemmness marker genes. Moreover, the topical application of ISX9 markedly promoted hair regrowth in C57BL/6J mice and induced hair follicle transition from telogen to anagen via enhancing Wnt/β-catenin pathway. Taken together, our study unravelled that ISX9 could activate Wnt/β-catenin signalling by potentiating the association between LRP6 and Axin1, and may be a promising therapeutic agent for alopecia treatment. Show less
Several studies have confirmed that the pathophysiological progression of Alzheimer's disease (AD) is closely related to changes in the intestinal microbiota; thus, modifying the intestinal microbiota Show more
Several studies have confirmed that the pathophysiological progression of Alzheimer's disease (AD) is closely related to changes in the intestinal microbiota; thus, modifying the intestinal microbiota has emerged as a new way to treat AD. Effective interventions for gut microbiota include the application of probiotics and other measures such as fecal microbiota transplantation (FMT). However, the application of probiotics ignores that the intestine is a complete microecosystem with competition among microorganisms. FMT also has issues when applied to patient treatment. In a previous study, we found that eight species of bacteria that are isolated with high frequency in the normal intestinal microbiota (i.e., intestinal dominant microbiota) have biological activities consistent with the effects of FMT. In this article, we confirmed that the treatment of intestinal dominant microbiota significantly restored intestinal microbiota abundance and composition to normal levels in APP/PS1 mice; downregulated brain tissue pro-inflammatory cytokines (IL-1β and IL-6) and amyloid precursor protein (APP) and β-site APP cleavage enzyme 1 (BACE1) expression levels; and reduced the area of Aβ plaque deposition in the brain hippocampus. Our study provides a new therapeutic concept for the treatment of AD, adjusting the intestinal microecological balance through dominant intestinal microbiota may be an alternative to FMT. Show less
Angiopoietin-like 4 (ANGPTL4) is a secreted metabolism-modulating glycoprotein involved in the progression of tumours, cardiovascular diseases, metabolic syndrome and infectious diseases. In this stud Show more
Angiopoietin-like 4 (ANGPTL4) is a secreted metabolism-modulating glycoprotein involved in the progression of tumours, cardiovascular diseases, metabolic syndrome and infectious diseases. In this study, more CD8 Show less
The poor prognosis of serous ovarian cancer (SOC) is due to its high invasive capacity and cisplatin resistance of SOC cells, whereas the molecular mechanisms remain poorly understood. In the present Show more
The poor prognosis of serous ovarian cancer (SOC) is due to its high invasive capacity and cisplatin resistance of SOC cells, whereas the molecular mechanisms remain poorly understood. In the present study, the expression and function of non-muscle myosin heavy chain IIB (MYH10) in SOC are identified by immunohistochemistry, in vitro, and in vivo studies, respectively. The mechanism of MYH10 is demonstrated by co-immunoprecipitation, GST pull-down, confocal laser assays, and so on. The results show that the knockdown of MYH10 suppressed SOC cell proliferation, migration, invasion, metastasis, and cisplatin resistance both in vivo and in vitro. Further studies confirm that the MYH10 protein functional domain combines with non-muscle myosin heavy chain IIA (MYH9) to recruit the deubiquitinating enzyme Ubiquitin-specific proteases 45 and deubiquitinates snail to inhibit snail degradation, eventually promoting tumorigenesis, progression, and cisplatin resistance in SOC. In clinical samples, MYH10 expression is significantly elevated in SOC samples compared to the paratumor samples. And the expression of MYH10 is positively correlated with MYH9 expression. MYH10+/MYH9+ co-expression is an independent prognostic factor for predicting SOC patient survival. These findings uncover a key role of the MYH10-MYH9-snail axis in SOC carcinogenesis, progression, and cisplatin resistance, and provide potential novel therapeutic targets for SOC intervention. Show less
The melanocortin pathway is well established to be critical for body-weight regulation in both rodents and humans. Despite extensive studies focusing on this pathway, the downstream brain sites that m Show more
The melanocortin pathway is well established to be critical for body-weight regulation in both rodents and humans. Despite extensive studies focusing on this pathway, the downstream brain sites that mediate its action are not clear. Here, we found that, among the known paraventricular hypothalamic (PVH) neuron groups, those expressing melanocortin receptors 4 (PVH Show less
Background Sarcomere gene mutation and myocardial fibrosis are both associated with poorer clinical outcomes in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to determine Show more
Background Sarcomere gene mutation and myocardial fibrosis are both associated with poorer clinical outcomes in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to determine the relationship between sarcomere gene mutation and myocardial fibrosis measured by both histopathology and cardiac magnetic resonance (CMR). Methods and Results Two hundred twenty-seven patients with HCM who underwent surgical treatment, genetic testing, and CMR were enrolled. We retrospectively analyzed basic characteristics, sarcomere gene mutation, and myocardial fibrosis measured by CMR and histopathology. In our study, the mean age was 43 years, and 152 patients (67.0%) were men. A total of 107 patients (47.1%) carried a positive sarcomere gene mutation. The myocardial fibrosis ratio was significantly higher in the late gadolinium enhancement (LGE)+ group (LGE+ 14.3±7.5% versus LGE- 9.0±4.3%; Show less
Reactive gliosis of Müller cells plays an important role in the pathogenesis of diabetic retinopathy (DR). Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been shown to improve D Show more
Reactive gliosis of Müller cells plays an important role in the pathogenesis of diabetic retinopathy (DR). Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been shown to improve DR by inhibiting reactive gliosis. However, the mechanism of inhibition has yet to be elucidated. This study investigated the effects of liraglutide on Müller glia reactivity in the early stages of DR and the underlying mechanisms. Proteomics combined with bioinformatics analysis, HE staining, and immunofluorescence staining revealed ganglion cell loss, reactive gliosis of Müller cells, and extracellular matrix (ECM) imbalance in rats with early stages of DR. High glucose (HG) exposure up-regulated GFAP and TNF-α expression and down-regulated ITGB1 expression and FN1 content in extracellular fluid in rMC1 cells, thereby promoting reactive gliosis. GLP-1R knockdown and HG+DAPT inhibition experiments show that liraglutide balances ECM levels by inhibiting activation of the Notch1/Hes1 pathway and ameliorates high-glucose-induced Müller glia reactivity. Thus, the study provides new targets and ideas for improvement of DR in early stages. Show less
The promotion of intersystem crossing (ISC) is critical for achieving a high-efficiency long-persistent luminescence (LPL) from organic materials. However, the use of a transition-metal complex for LP Show more
The promotion of intersystem crossing (ISC) is critical for achieving a high-efficiency long-persistent luminescence (LPL) from organic materials. However, the use of a transition-metal complex for LPL materials has not been explored because it can also shorten the emission lifetime by accelerating the phosphorescence decay. Here, we report a new class of LPL materials by doping a monovalent Au-carbene complex into a boron-embedded molecular host. The donor-acceptor systems exhibit photoluminescence with both high efficiencies (>57 %) and long lifetimes (ca. 40 ms) at room temperature. It is revealed that the Au atom promotes the population of low-lying triplet excited states of the host aggregate (T Show less
Analysis of circulating tumor DNA (ctDNA) in patients with metastatic prostate cancer (mPC) provides an opportunity to identify and monitor genomic alterations during a patient's treatment course. We Show more
Analysis of circulating tumor DNA (ctDNA) in patients with metastatic prostate cancer (mPC) provides an opportunity to identify and monitor genomic alterations during a patient's treatment course. We evaluated whether the presence of specific gene amplifications (GAs) and plasma copy number (PCN) alterations are associated with disease features. This is a single-institution retrospective study of patients with mPC who underwent ctDNA profiling using Guardant360 The presence of liver and/or lung metastases was associated with GAs of The association of select GAs with survival provides an additional tool for assessing mCRPC prognosis and informing management. Serial monitoring of ctDNA GAs is also useful to guide prognosis and therapeutic response. Show less
Wen Zheng, Wenjun Li, Yini Zeng+7 more · 2023 · Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · added 2026-04-24
Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke. Previous studies revealed that delayed recanalization might cause serious ische Show more
Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke. Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury. However, plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke. This study aims to explore the role of delayed recanalization on blood-brain barrier (BBB) in the penumbra (surrounding ischemic core) and neurological outcomes after middle cerebral artery occlusion (MCAO). Recanalization was performed on the 3rd day after MCAO. BBB disruption was tested by Western blotting, Evans blue dye, and immunofluorescence staining. Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO. The expression of fibroblast growth factor 21 (FGF21), fibroblast growth factor receptor 1 (FGFR1), phosphatidylinositol-3-kinase (PI3K), and serine/threonine kinase (Akt) in the penumbra were observed by immunofluorescence staining and/or Western blotting. The extraversion of Evans blue, IgG, and albumin increased surrounding ischemic core after MCAO, but significantly decreased after recanalization. The expression of Claudin-5, Occludin, and zona occludens 1 (ZO-1) decreased surrounding ischemic core after MCAO, but significantly increased after recanalization. Infarct volume reduced and neurological outcomes improved following recanalization (on the 7th day after MCAO). The expressions of Claudin-5, Occludin, and ZO-1 decreased surrounding ischemic core following MCAO, which were up-regulated corresponding to the increases of FGF21, p-FGFR1, PI3K, and p-Akt after recanalization. Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K, p-Akt, Occludin, Claudin-5, and ZO-1 in the penumbra, which weakened the beneficial effects of recanalization on neurological outcomes after MCAO. Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway, which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats. Show less
Hypertension is a progressive metabolic disease characterized by circadian regulation of lipid metabolism disorder. Identifying specific lipid components and maintaining circadian homeostasis of lipid Show more
Hypertension is a progressive metabolic disease characterized by circadian regulation of lipid metabolism disorder. Identifying specific lipid components and maintaining circadian homeostasis of lipid metabolism might be a promising therapeutic strategy for hypertension. Isorhynchophylline (IRP) can regulate lipid metabolism; however, the underlying mechanism of IRP in improving lipid metabolism rhythm disorder is still unclear. The lipid circadian biomarkers and abnormal metabolic pathways intervened by IRP were investigated using diurnal lipidomic research methods. The 24-h circadian changes in mRNA and protein expression levels of circadian genes, including Bmal1, Clock, Cry1, Cry2, Per1, and Per2, and lipid metabolism-related factors (PPARα and LPL) were determined using RT-PCR and western blot analyses, respectively. The underlying mechanisms were intensively investigated by inhibiting Bmal1. Molecular docking and drug affinity responsive target stability analyses were performed to assess the binding affinity of IRP and Bmal1. IRP treatment could effectively improve 24-h blood pressure, ameliorate the lipid metabolic rhythm disorder, reverse the expression levels of circadian rhythm genes, and regulate lipid metabolism-related genes (PPARα and LPL) by mediating Bmal1. This study highlighted the potential effects of IRP in maintaining the circadian homeostasis of lipid metabolism and the treatment of hypertension. Show less
The epithelial-mesenchymal transition (EMT) is an important process during metastasis in various tumors, including colorectal cancer (CRC). Thus, the study of its characteristics and related genes is Show more
The epithelial-mesenchymal transition (EMT) is an important process during metastasis in various tumors, including colorectal cancer (CRC). Thus, the study of its characteristics and related genes is of great significance for CRC treatment. In this study, 26 EMT-related gene sets were used to score each sample from The Cancer Genome Atlas program (TCGA) colon adenocarcinoma (COAD) database. Based on the 26 EMT enrichment scores for each sample, we performed unsupervised cluster analysis and classified the TCGA-COAD samples into three EMT clusters. Then, weighted gene co-expression network analysis (WGCNA) was used to investigate the gene modules that were significantly associated with these three EMT clusters. Two gene modules that were strongly positively correlated with the EMT cluster 2 (worst prognosis) were subjected to Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. Then, a prognosis-related risk model composed of three hub genes Show less
In this work, a simple and sensitive electrochemical sensor was proposed for the detection of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) activity. Firstly, the BACE1 specific peptide w Show more
In this work, a simple and sensitive electrochemical sensor was proposed for the detection of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) activity. Firstly, the BACE1 specific peptide was modified onto the Au electrode to graft a single-strand DNA with polycytosine DNA sequence (dC Show less
Guillain-Barre syndrome (GBS) is an immune-mediated inflammatory peripheral neuropathy. This study aimed to conduct a systematic analysis of the serum lipids profile in GBS. We measured the serum lipi Show more
Guillain-Barre syndrome (GBS) is an immune-mediated inflammatory peripheral neuropathy. This study aimed to conduct a systematic analysis of the serum lipids profile in GBS. We measured the serum lipids profile in 85 GBS patients and compared it with that of 85 healthy controls matched for age and sex. Additionally, we analyzed the correlation between lipids and the severity, subtypes, precursor infections, clinical outcomes, clinical symptoms, immunotherapy, and other laboratory markers of GBS. Compared to the healthy controls, GBS exhibited significantly elevated levels of Apolipoprotein B (APOB), Apolipoprotein C2 (APOC2), Apolipoprotein C3 (APOC3), Apolipoprotein E (APOE), triglycerides (TG), and residual cholesterol (RC). Conversely, Apolipoprotein A1 (APOA1), Apolipoprotein A2 (APOA2), and high-density lipoprotein (HDL) were substantially lower in GBS. Severe GBS displayed noticeably higher levels of APOC3 and total cholesterol (TC) compared to those with mild disease. Regarding different clinical outcomes, readmitted GBS demonstrated higher RC expression than those who were not readmitted. Moreover, GBS who tested positive for neuro-virus antibody IGG in cerebrospinal fluid (CSF) exhibited heightened expression of APOC3 in comparison to those who tested negative. GBS with cranial nerve damage showed significantly reduced expression of HDL and APOA1 than those without such damage. Additionally, GBS experiencing limb pain demonstrated markedly decreased HDL expression. Patients showed a significant reduction in TC after intravenous immunoglobulin therapy. We observed a significant positive correlation between lipids and inflammatory markers, including TNF-α, IL-1β, erythrocyte sedimentation rate (ESR), white blood cells, monocytes, and neutrophils in GBS. Notably, APOA1 exhibited a negative correlation with ESR. Furthermore, our findings suggest a potential association between lipids and the immune status of GBS. The research demonstrated a strong connection between lipids and the severity, subtypes, clinical outcomes, precursor infections, clinical symptoms, immunotherapy, inflammation, and immune status of GBS. This implies that a low-fat diet or the use of lipid-lowering medications may potentially serve as an approach for managing GBS, offering a fresh viewpoint for clinical treatment of this condition. Show less
Hematoma-induced neuroinflammation is the cause of poor prognosis in intracerebral hemorrhage (ICH); therefore, promoting blood clearance and blocking overactivated inflammation are rational approache Show more
Hematoma-induced neuroinflammation is the cause of poor prognosis in intracerebral hemorrhage (ICH); therefore, promoting blood clearance and blocking overactivated inflammation are rational approaches for ICH treatment. β-site amyloid precursor protein (APP) lyase-1 (BACE1) is a key molecule regulating the microglial phenotype transition in neurodegenerative diseases. Therefore, the aim of this study was to investigate the role of BACE1 in microglial phagocytosis and inflammatory features in ICH. Here, we demonstrated the unique advantages of targeting BACE1 in microglia using an autologous blood model and primary microglia hemoglobin stimulation. When BACE1 was inhibited early in ICH, fewer residual hematomas remained, consistent with an increase in genetic features that favor phagocytosis and anti-inflammation. In addition, inhibition of BACE1 enhanced the secretion of anti-inflammatory cytokines and substantially reduced the expression of proinflammatory genes, which was regulated by signal transduction and phosphorylation of activator of transcription 3 (STAT3). Further pharmacological inhibition of STAT3 phosphorylation effectively blocked the proinflammatory and weak phagocytic phenotype of microglia due to BACE1 induction. In summary, BACE1 is the critical molecule regulating the inflammatory and phagocytic phenotypes of microglia after ICH, and targeted inhibition of the BACE1/STAT3 pathway is an important strategy for the future treatment of ICH-induced neurological injury. Show less
Alzheimer's disease (AD) is a critical neurodegenerative disease that manifests as progressive intellectual decline and is pathologically characterized by a progressive loss of neurons in the brain. D Show more
Alzheimer's disease (AD) is a critical neurodegenerative disease that manifests as progressive intellectual decline and is pathologically characterized by a progressive loss of neurons in the brain. Despite extensive research on this topic, the pathogenesis of AD is not fully understood, while the beta-amyloid (A Show less