Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 8.686
1.
Ann Surg Oncol ; 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38847985

BACKGROUND: The prognostic analysis of lung invasive mucinous adenocarcinoma (IMA) is deficient due to the lack of a universally recommended histological grading system, leading to unregulated treatment approaches. OBJECTIVE: We aimed to examine the clinical trajectory of IMA and assess the viability of utilizing the existing grading system for lung invasive non-mucinous adenocarcinoma in the context of IMA. METHODS: We retrospectively collected clinicopathological data from 265 IMA patients. Each case re-evaluated the tumor grade using the following three classification systems: the 4th Edition of the World Health Organization classification system, the International Association for the Study of Lung Cancer (IASLC) grading system, and a two-tier grading system. We performed a comparative analysis of these grading systems and identified the most effective grading system for IMA. RESULTS: The study comprised a total of 214 patients with pure IMA and 51 patients with mixed IMA. The 5-year overall survival (OS) rates for pure IMA and mixed IMA were 86.7% and 57.8%, respectively. All three grading systems proved to be effective prognostic classifiers for IMA. The value of area under the curve at 1-, 3-, and 5-year OS was highest for the IASLC grading system compared with the other grade systems and the clinical stage. The IASLC classification system was an independent prognostic predictor (p = 0.009, hazard ratio 2.243, 95% confidence interval 1.219-4.127). CONCLUSION: Mixed IMA is more aggressive than pure IMA, with an OS rate on par with that of high-grade pure IMA. The IASLC grading system can better indicate prognosis and is recommended for lung IMA.

2.
Int J Impot Res ; 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38834872

Previous study has highlighted an association between cannabis use (CU) and an increased risk of erectile dysfunction (ED), potentially due to indirect effects on sex hormonal balance. However, the evidence remains controversial, and the causal relationship is unclear. This study utilized genome-wide association study (GWAS) data to investigate the causal relationships between cannabis use disorder (CUD), lifetime cannabis use (LCU), and ED, as well as levels of sex hormones including estradiol (E2), bioavailable testosterone (BT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) through Mendelian randomization (MR) analysis. The primary method of analysis was the inverse variance weighted (IVW) method. Data from the FinnGen and UK Biobank were used for replication and meta-analysis. The results indicated no causal relationship between genetically predicted CUD (OR = 0.97, 95% CI 0.87-1.10, P = 0.66) and LCU (OR = 1.13, 95% CI 0.84-1.50, P = 0.42) with the risk of ED. The meta-analysis provided consistent evidence (P > 0.05). No causal relationships were found between CUD and LCU with E2(CUD: ß = 0.00, 95% CI 0.00-0.01, P = 0.37; LCU: ß = 0.00, 95% CI -0.02-0.01, P = 0.62), BT (CUD: ß = 0.00, 95% CI -0.03-0.02, P = 0.90; LCU: ß = 0.02, 95% CI -0.04-0.09, P = 0.46), FSH (CUD: ß = 0.01, 95% CI -0.18-0.20, P = 0.92; LCU: ß = 0.01, 95% CI -0.44-0.47, P = 0.95), and LH (CUD: ß = 0.01, 95% CI -0.18-0.21, P = 0.90; LCU: ß = 0.13, 95% CI -0.22-0.49, P = 0.46). Sensitivity analyses detected no evidence of horizontal pleiotropy or heterogeneity, ensuring the robustness of the results. In conclusion, this MR analysis did not provide evidence supporting a causal relationship between CU and ED or sex hormone levels.

3.
Crit Rev Anal Chem ; : 1-28, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38836446

Fluorescent probe technology holds great promise in the fields of environmental monitoring and clinical diagnosis due to its inherent advantages, including easy operation, reliable detection signals, fast analysis speed, and in situ imaging capabilities. In recent years, a wide range of fluorescent probes based on diverse fluorophores have been developed for the analysis and detection of various analytes, yielding significant achievement. Among these fluorophores, the dicyanoisophorone-based fluorophores have garnered significant attention. Dicyanoisoporone exhibits minimal fluorescence, yet possesses a robust electron-withdrawing capability, rendering it suitable for constructing of D-π-A structured fluorophores. Leveraging the intramolecular charge transfer (ICT) effect, such fluorophores exhibit near-infrared (NIR) fluorescence emission with a large Stokes shift, thereby offering remarkable advantages in the design and development of NIR fluorescence probes. This review article primarily focus on small-molecule dicyanoisoporone-based probes from the past two years, elucidating their design strategies, detection performances, and applications. Additionally, we summarize current challenges while predicting future directions to provide valuable references for developing novel and advanced fluorescence probes based on dicyanoisoporone derivatives.

4.
iScience ; 27(6): 109946, 2024 Jun 21.
Article En | MEDLINE | ID: mdl-38827402

The clinical success of immune checkpoint inhibitors is compromised by the fact of immune-related adverse events (irAEs), especially for older patients. To identify predictive biomarkers for older patients with irAEs, we used multiplex immunoassay and flow cytometry and liquid chromatography-tandem mass spectrometry to test immune factors and plasma protein and metabolites levels in non-small cell lung cancer (NSCLC) patients. The results showed that older patients with irAEs displayed lower CD28, CD4+ T cell, and B cell and higher interleukin (IL)-10 and CCL2 levels at baseline. Besides, lower aldolase, fructose-bisphosphate B (ALDOB), higher ST6GAL1, and lower lactate/pyruvate ratio at baseline were found in older patients with irAEs. Based on metabolomic markers, predictive models were developed to distinguish patients with grade 2-4 irAEs from grade 0-1 (Area under curve, AUC = 0.831) and to distinguish patients with grade 3-4 irAEs from grade 2 (AUC = 1). Our results confirmed the predictive value of plasma metabolites for irAEs in older patients with NSCLC.

5.
Front Endocrinol (Lausanne) ; 15: 1348771, 2024.
Article En | MEDLINE | ID: mdl-38863934

Background: Ovarian stimulation (OS) for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with PCOS often results in multiple follicular development, yet some individuals experience poor or suboptimal responses. Limited data exist regarding the impact of poor/suboptimal ovarian response on pregnancy outcomes in women with PCOS. Objectives: The aim of this study was to evaluate whether the live birth rate (LBR) per fresh embryo transfer and cumulative live birth rate (CLBR) per aspiration cycle differ in women with PCOS defined by the Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria. Methods: A retrospective study involving 2,377 women with PCOS who underwent their first IVF/ICSI cycle at Sun Yat-sen Memorial Hospital from January 2011 to December 2020 was used. Patients were categorized into four groups based on age, antral follicle count, and the number of oocytes retrieved, according to the POSEIDON criteria. The LBR and CLBR were compared among these groups. Logistic regression analysis was performed to assess whether the POSEIDON criteria served as independent risk factors and identify factors associated with POSEIDON. Results: For patients <35 years old, there was no significant difference in the clinical pregnancy rate between POSEIDON and non-POSEIDON patients, whereas POSEIDON patients exhibited lower rates of implantation and live birth. POSEIDON Group 1a displayed lower rates of implantation, clinical pregnancy, and live birth. However, no significant differences were observed in the rates of clinical pregnancy and live birth between POSEIDON Group 1b and non-POSEIDON groups. For patients ≥35 years old, there were no significant differences in the rates of implantation, clinical pregnancy, and live birth between POSEIDON and non-POSEIDON patients. CLBRs were significantly lower in POSEIDON Groups 1 and 2, compared with the non-POSEIDON groups. The levels of body mass index (BMI), follicle-stimulating hormone (FSH), and antral follicle count (AFC) were associated with POSEIDON hypo-response. POSEIDON was found to be associated with lower CLBR, but not LBR per fresh embryo transfer. Conclusions: In patients with PCOS, an unexpected suboptimal response can achieve a fair LBR per fresh embryo transfer. However, CLBR per aspirated cycle in POSEIDON patients was lower than that of normal responders. BMI, basal FSH level, and AFC were independent factors associated with POSEIDON. Our study provides data for decision-making in women with PCOS after an unexpected poor/suboptimal response to OS.


Birth Rate , Embryo Transfer , Fertilization in Vitro , Live Birth , Ovulation Induction , Polycystic Ovary Syndrome , Pregnancy Rate , Humans , Female , Retrospective Studies , Adult , Pregnancy , Embryo Transfer/methods , Live Birth/epidemiology , Fertilization in Vitro/methods , Sperm Injections, Intracytoplasmic/methods , Pregnancy Outcome , Infertility, Female/therapy
6.
Bioresour Technol ; : 130977, 2024 Jun 17.
Article En | MEDLINE | ID: mdl-38897546

This study examined the combination of activated carbon and magnetite with calcium peroxide in enhancing the anaerobic digestion (AD) performance of food waste (FW). The individual mechanisms of these two approaches were also clarified. The results indicated that AC/CaO2 achieved the highest specific methane yield of 434.4 mL/g VS, followed by Fe3O4/CaO2 (416.9 mL/g VS). Both were significantly higher than other groups (control, AC, Fe3O4, and CaO2 were 330.1, 341.4, 342.8, and 373.2 mL/g VS, respectively). Additionally, compared to Fe3O4/CaO2, AC/CaO2 further increased reactive oxygen species (ROS), thereby enhancing the hydrolytic acidification process. Simultaneously, the higher ROS levels of Fe3O4/CaO2 and AC/CaO2 promoted the formation of microbial aggregates and established a more robust enzymatic defense system and unique damage repair strategy. The research comparatively analyzed the synergistic mechanism of iron-based and carbon-based conductive materials with CaO2, providing new perspectives for optimizing the AD of FW.

7.
Huan Jing Ke Xue ; 45(6): 3225-3233, 2024 Jun 08.
Article Zh | MEDLINE | ID: mdl-38897746

Soil nitrogen accumulation in cropland and groundwater nitrogen pollution can be effectively alleviated by reducing exogenous nitrogen input, and fallow is an important measure for reducing exogenous nitrogen input. To explore the effects of fallow on nitrogen accumulation in the soil profile and shallow groundwater, the soil profile and shallow groundwater in cropland around Fuxian Lake were selected as research objects. The changes in nitrogen accumulation in the 0-100 cm soil profile and nitrogen concentration in shallow groundwater before (December 2017) and after (August 2020 and April 2021) fallow and their relationships were analyzed. The results showed that the content and storage of nitrogen in soil profiles were significantly reduced by fallow, and the contents of TN, ON, DTN, NO3--N, and NH4+-N in 0-30, 30-60, and 60-100 cm soil profiles after fallow decreased by 18.4 %-36.5 %, 16.1 %-26.8 %, 54.0 %-130.2 %, 59.5 %-90.8 %, and 60.1 %-110.6 %, respectively. The storages of TN, ON, DTN, NO3--N, and NH4+-N in 0-100 cm soil profiles before fallow were (17.20 ±0.97) t·hm-2, (15.50 ±1.23) t·hm-2, (0.68 ±0.06) t·hm-2, (266.8 ±31.17) kg·hm-2, and (18.7 ±3.04) kg·hm-2, respectively. However, their storages after fallow decreased by 25.5 %, 23.3 %, 44.7 %, 80.1 %, and 59.9 %, respectively. Fallow also changed the concentration and composition of different forms of nitrogen in shallow groundwater. The concentrations of TN, ON, NO3--N, and NH4+-N in groundwater after fallow decreased by 88.4 %, 82.7 %, 92.1 %, and 65.8 %, respectively, and ON/TN and NH4+-N/TN increased from 26 % and 6 % before fallow to 39 % and 17 % after fallow, respectively, whereas NO3--N/TN decreased from 61 % before fallow to 41 % after fallow. Changes in nitrogen concentrations and their forms in groundwater were closely related to DTN, NO3--N, and NH4+-N in the soil profile and pH, ORP, and DO in groundwater before and after fallow. Our study highlights that fallow effectively reduced nitrogen accumulation in cropland soil profiles, further alleviating nitrogen pollution in shallow groundwater, and was conducive to preventing the deterioration of water quality in plateau lakes.

8.
Chem Sci ; 15(23): 8651-8663, 2024 Jun 12.
Article En | MEDLINE | ID: mdl-38873071

Na3V2(PO4)3 (NVP) cathode materials with the advantages of long cycle life and superior thermal stability have been considered promising cathode candidates for SIBs. However, the unsatisfactory energy density derived from low theoretical capacity and operating voltage (3.35 V vs. Na+/Na, based on the V3+/V4+ redox couple) inevitably limits their practical application. Therefore, the activation of the V4+/V5+ redox couple (∼4.0 V vs. Na+/Na) in NVP-based cathode materials to boost the energy density of SIBs has attracted extensive attention. Herein, we first analyze the challenges of activation of the V4+/V5+ redox couple in NVP-based cathode materials. Subsequently, the recent achievement of NVP-based cathode materials with activated V4+/V5+ redox reactions for SIBs is overviewed. Finally, further research directions of high voltage V4+/V5+ redox reactions in NVP-based cathodes are proposed. This review provides valuable guidance for developing high energy density NVP-based cathode materials for SIBs.

9.
Expert Opin Ther Pat ; : 1-17, 2024 Jun 13.
Article En | MEDLINE | ID: mdl-38849323

INTRODUCTION: Stimulator of Interferon Genes (STING) is an innate immune sensor. Activation of STING triggers a downstream response that results in the expression of proinflammatory cytokines (TNF-α, IL-1ß) via nuclear factor kappa-B (NF-κB) or the expression of type I interferons (IFNs) via an interferon regulatory factor 3 (IRF3). IFNs can eventually result in promotion of the adaptive immune response including activation of tumor-specific CD8+ T cells to abolish the tumor. Consequently, activation of STING has been considered as a potential strategy for cancer treatment. AREAS COVERED: This article provides an overview on structures and pharmacological data of CDN-like and non-nucleotide STING agonists acting as anticancer agents (January 2021 to October 2023) from a medicinal chemistry perspective. The data in this review come from EPO, WIPO, RCSB PDB, CDDI. EXPERT OPINION: In recent years, several structurally diverse STING agonists have been identified. As an immune enhancer, they are used in the treatment of tumors, which has received extensive attention from scientific community and pharmaceutical companies. Despite the multiple challenges that have appeared, STING agonists may offer opportunities for immunotherapy.

10.
Bioresour Technol ; 406: 130992, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38885726

Methane recovery and organics removal in sulfate (SO42-)-rich wastewater anaerobic digestion are hindered by electron competition between methanogenesis and sulfidogenesis. Here, intermittently electrostimulated bioelectrodes were developed to facilitate direct interspecies electron transfer (DIET)-driven syntrophic methanogenesis, increasing substrate competition among methanogenic archaea (MA). By optimising the electrochemical environment, MA was able to employ electron transfer more efficiently than sulfate-reducing bacteria (SRB), resulting in significant methane accumulation (58.1 ± 1.0 mL-CH4/m3reactor) and COD removal (90.5 ± 0.5 %) at lower COD/SO42- ratio. Intermittent electrostimulation improved the metabolic pathway for electroactive bacteria to utilize acetate and direct electrons to electrotrophic MA, decreasing SRB abundance and affecting the sulfate reduction pathway. Intermittently electrostimulated biofilms significantly increased gene levels of key enzymes in electron transport for cytochrome and e-pili biosynthesis, crucial for DIET, demonstrating enhanced DIET-driven syntrophic methanogenesis. This study provides a strategic approach to optimize methanogenesis in sulfate-rich wastewater anaerobic digestion.

11.
Langmuir ; 2024 Jun 17.
Article En | MEDLINE | ID: mdl-38887034

Single-atom catalysts (SACs) are attractive in one-carbon (C1) chemistry because of their high atom efficiency. However, it is a great challenge for understanding the dynamic roles of SACs under operating conditions. Here, isolated Pt atoms trapped on defective CeO2 surface are investigated by experiments, especially operando techniques, which offers basic understanding of the nature and dynamic evolution of the Pt-CeO2 interface in dry reforming of methane (DRM). The Pt-Olattice configuration is highly active for CH4 dissociation at the expense of the Olattice atoms, which in turn promotes the H-assisted dissociation of CO2. The transformation of Pt atoms between positive and metallic states is driven by the DRM reaction, which is essential for rendering highly efficient catalysis. The dynamic evolution of Pt atoms favors to eliminate the reactive intermediates, such as carbonates and formates. The dynamic nature of the Pt-CeO2 interface in the DRM reaction shows a similar picture to the Yin and Yang transformation in ancient Chinese Tai Ji wisdom.

12.
J Transl Med ; 22(1): 576, 2024 Jun 18.
Article En | MEDLINE | ID: mdl-38890738

INTRODUCTION: Identifying new biomarkers for predicting immune checkpoint inhibitors (ICIs) response in non-small cell lung cancer (NSCLC) is crucial. We aimed to assess the variant allele frequency (VAF)-related profile as a novel biomarker for NSCLC personalized therapy. METHODS: We utilized genomic data of 915 NSCLC patients via cBioPortal and a local cohort of 23 patients for model construction and mutational analysis. Genomic, transcriptomic data from 952 TCGA NSCLC patients, and immunofluorescence (IF) assessment with the local cohort supported mechanism analysis. RESULTS: Utilizing the random forest algorithm, a 15-gene VAF-related model was established, differentiating patients with durable clinical benefit (DCB) from no durable benefit (NDB). The model demonstrated robust performance, with ROC-AUC values of 0.905, 0.737, and 0.711 across training (n = 313), internal validation (n = 133), and external validation (n = 157) cohorts. Stratification by the model into high- and low-score groups correlated significantly with both progression-free survival (PFS) (training: P < 0.0001, internal validation: P < 0.0001, external validation: P = 0.0066) and overall survival (OS) (n = 341) (P < 0.0001). Notably, the stratification system was independent of PD-L1 (P < 0.0001) and TMB (P < 0.0001). High-score patients exhibited an increased DCB ratio and longer PFS across both PD-L1 and TMB subgroups. Additionally, the high-score group appeared influenced by tobacco exposure, with activated DNA damage response pathways. Whereas, immune/inflammation-related pathways were enriched in the low-score group. Tumor immune microenvironment analyses revealed higher proportions of exhausted/effector memory CD8 + T cells in the high-score group. CONCLUSIONS: The mutational VAF profile is a promising biomarker for ICI therapy in NSCLC, with enhanced therapeutic stratification and management as a supplement to PD-L1 or TMB.


Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung , Gene Frequency , Immune Checkpoint Inhibitors , Lung Neoplasms , Mutation , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Lung Neoplasms/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Immune Checkpoint Inhibitors/therapeutic use , Biomarkers, Tumor/genetics , Male , Female , Gene Frequency/genetics , Mutation/genetics , Middle Aged , Aged , Cohort Studies , Treatment Outcome
13.
Mitochondrial DNA B Resour ; 9(6): 787-792, 2024.
Article En | MEDLINE | ID: mdl-38903543

Bassia scoparia, an annual potherb belonging to the family Amaranthaceae, has been widely used in traditional Chinese and Japanese medicine for over 2000 years. Herein, we presented its complete chloroplast. The chloroplast genome sequence was 151,278 bp in length with a 36.6% content of GC. The genome showed the typical quadripartite structure, comprising a pair of inverted repeat (IR) regions (24,353 bp) separated by a large single-copy (LSC) region (84,067 bp) and a small single-copy (SSC) region (18,505 bp). This chloroplast genome harbored 133 predicted genes, including 88 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis indicated that B. scoparia was closely related to B. littorea. This newly sequenced chloroplast genome not only enhances our understanding of the genome of Bassia but also provides valuable insights for the evolutionary study of the family Amaranthaceae.

14.
Mucosal Immunol ; 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38844208

Mycobacterium tuberculosis- (Mtb) infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection. Using single-cell metabolic and transcriptional analyses, we found that neutrophils in the Mtb-infected lung displayed elevated mitochondrial metabolism, which was largely attributed to the induction of activated neutrophils with enhanced metabolic activities. The activated neutrophil subpopulation was also identified in the lung granulomas from Mtb-infected non-human primates. Functionally, activated neutrophils harbored more viable bacteria and displayed enhanced lipid uptake and accumulation. Surprisingly, we found that IFNγ promoted the activation of lung neutrophils during Mtb infection. Lastly, perturbation of lipid uptake pathways selectively compromised Mtb survival in activated neutrophils. These findings suggest that neutrophil heterogeneity and metabolic diversity are key to their permissiveness for Mtb, and that metabolic pathways in neutrophils represent potential host-directed therapeutics in TB.

15.
Pediatr Allergy Immunol ; 35(6): e14182, 2024 Jun.
Article En | MEDLINE | ID: mdl-38899630

BACKGROUND: Polymorphisms in susceptibility genes are a major risk factor for the development of asthma. Understanding these genetic variants helps elucidate asthma's pathogenesis, predict its onset, expedite antiasthma medication development, and achieve precise targeted individualized treatment. This study developed a test kit based on susceptibility genes for predicting asthma in Chinese children. METHODS: The present study constructed a VariantPro Targeted Library Preparation System with 72 single nucleotide polymorphism (SNP) loci associated with asthma from the ClinVar, OMIM, and SNPedia databases. These SNP loci were detected in the peripheral blood of 499 children with asthma and 500 healthy children. Significant differences were discovered for seven SNP loci. Simultaneously, whole exome sequencing of 46 children with asthma and 50 healthy children identified eight SNP loci with significant differences. The 15 SNP loci identified from Chinese children with asthma were validated in an independent population of 97 children with asthma and 93 healthy children by conducting multiplex polymerase chain reaction (PCR)-next-generation sequencing genotyping. RESULTS: Four loci (rs12422149, rs7216389, rs4065275, and rs41453444) were identified, and a single-tube multifluorescent qPCR (real-time quantitative PCR) test kit was developed using these four SNP loci. The kit was tested on 269 children with asthma and 724 children with bronchopneumonia. CONCLUSIONS: We identified four loci as susceptibility genes and developed a quantitative PCR test kit for predicting asthma development in Chinese children.


Asthma , Exome Sequencing , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Adolescent , Child , Child, Preschool , Female , Humans , Male , Asthma/genetics , Asthma/diagnosis , Case-Control Studies , China/epidemiology , Databases, Genetic , East Asian People/genetics , Exome Sequencing/methods , Genotype , High-Throughput Nucleotide Sequencing/methods
16.
Cell Metab ; 2024 Jun 13.
Article En | MEDLINE | ID: mdl-38901424

Somatic mutations in non-malignant tissues are selected for because they confer increased clonal fitness. However, it is uncertain whether these clones can benefit organ health. Here, ultra-deep targeted sequencing of 150 liver samples from 30 chronic liver disease patients revealed recurrent somatic mutations. PKD1 mutations were observed in 30% of patients, whereas they were only detected in 1.3% of hepatocellular carcinomas (HCCs). To interrogate tumor suppressor functionality, we perturbed PKD1 in two HCC cell lines and six in vivo models, in some cases showing that PKD1 loss protected against HCC, but in most cases showing no impact. However, Pkd1 haploinsufficiency accelerated regeneration after partial hepatectomy. We tested Pkd1 in fatty liver disease, showing that Pkd1 loss was protective against steatosis and glucose intolerance. Mechanistically, Pkd1 loss selectively increased mTOR signaling without SREBP-1c activation. In summary, PKD1 mutations exert adaptive functionality on the organ level without increasing transformation risk.

17.
Phytomedicine ; 131: 155773, 2024 Aug.
Article En | MEDLINE | ID: mdl-38833946

BACKGROUND: The activation of the NLRP3 inflammasome has recently been revealed as a novel pathological mechanism of coronary heart disease (CHD). The Dan-Lou tablets (DLT) is widely used in the clinical treatment of CHD and prescription characterized by multi-component and multi-target regulation. However, the anti-inflammatory mechanism of DLT in the treatment of CHD remains unclear. PURPOSE: This study aimed to evaluate the effect of DLT in the treatment of CHD on the priming and activation of the NLRP3 inflammasome and to investigate the underlying anti-inflammatory mechanisms. METHODS: First, CHD rats model were established by a high-fat diet combined with left anterior coronary artery ligation (LADCA) followed by DLT intervention. The therapeutic effect of DLT was evaluated according to cardiac function, lipid level, and cardiac histopathology. Next, data-independent acquisition (DIA) proteomics was used to identify the key differential proteins of DLT intervention in CHD rats, and bioinformatics analysis was performed. Finally, the differentially expressed proteins in the NOD-like signaling pathway were verified based on bioinformatics results, and the priming and activation steps of the NLRP3 inflammasome were detected. RESULTS: In this study, a high-fat diet combined with LADCA was utilized to generate a CHD model, and DLT alleviated myocardial ischemia injury by inhibiting lipid deposition and inflammatory response. Proteomic studies observed that the RNF31, TXN2, and GBP2 of the NOD-like receptor signaling pathway were verified as the key targets of DLT in inhibiting myocardial injury in CHD rats. Furthermore, DLT in the treatment of CHD rats may function through the downregulation of P2X7R expression, thereby interfering with the priming (TLR4/MyD88/NF-κB) and activation (NLRP3/ASC/Caspase-1) of the NLRP3 inflammasome regulated by HSP90, and may then reduce the release of the IL-1ß and IL-18 inflammatory factors to play an anti-myocardial injury effect. CONCLUSION: Our findings elucidate a novel mechanism of DLT and provide some new drug evaluation targets and therapeutic strategies for CHD. This study innovatively proposed that DLT further exerts an anti-myocardial injury effect by inhibiting P2X7R expression, thereby interfering with the priming (TLR4/MyD88/NF-κB) and activation (NLRP3/ASC/Caspase-1) of the NLRP3 inflammasome regulated by HSP90, and then downregulates the release of the IL-1ß and IL-18 inflammatory factors.


Coronary Disease , Drugs, Chinese Herbal , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Rats, Sprague-Dawley , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammasomes/metabolism , Male , Coronary Disease/drug therapy , Drugs, Chinese Herbal/pharmacology , Rats , Anti-Inflammatory Agents/pharmacology , Disease Models, Animal , Signal Transduction/drug effects , Diet, High-Fat/adverse effects , Tablets , Interleukin-1beta/metabolism , Inflammation/drug therapy , Myeloid Differentiation Factor 88/metabolism
18.
Eur J Gastroenterol Hepatol ; 36(7): 845-849, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38829942

BACKGROUND: Meckel diverticulum (MD) is an important cause of gastrointestinal bleeding in children. Small bowel capsule endoscopy (SBCE) is a first-line examination method applied to patients with obscure gastrointestinal bleeding, but there are few studies on its application in children with MD. This article aims to provide evidence in favor of the auxiliary diagnosis of MD in children by analyzing its characteristics using SBCE. METHODS: We retrospectively collected the clinical data of patients with suspected MD. RESULTS: A total of 58 children were included in this study. All 58 children presented overt gastrointestinal bleeding (bloody stool or melena). Capsule endoscopy identified protruding lesions in 2 cases, double-lumen changes in 30 cases (all considered as MD), vascular lesions in 7 cases, intestinal mucosal inflammatory lesions in 3 cases, ulcers or erosion in 3 cases, and no obvious abnormalities in SBCE in 12 cases. Both SBCE and technetium-99 scans were performed for 24 cases, 22 of which were diagnosed MD by their combined results, giving a diagnostic coincidence rate of 91.7%. Eight cases were highly suspected as MD but were negative for the technetium-99 scan and positive for SBCE. CONCLUSION: SBCE has high accuracy in the diagnosis of MD in children, especially when performed in combination with a technetium-99 scan, which can greatly improve the diagnostic rate of MD in children.


Capsule Endoscopy , Gastrointestinal Hemorrhage , Meckel Diverticulum , Humans , Meckel Diverticulum/complications , Meckel Diverticulum/diagnostic imaging , Meckel Diverticulum/diagnosis , Capsule Endoscopy/methods , Male , Female , Retrospective Studies , Child , Child, Preschool , Gastrointestinal Hemorrhage/etiology , Adolescent , Infant , Intestine, Small/diagnostic imaging , Intestine, Small/pathology , Predictive Value of Tests , Radionuclide Imaging , Radiopharmaceuticals
19.
Bioact Mater ; 39: 287-301, 2024 Sep.
Article En | MEDLINE | ID: mdl-38827170

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

20.
J Colloid Interface Sci ; 672: 152-160, 2024 May 31.
Article En | MEDLINE | ID: mdl-38833735

Optical information encryption with high encoding capacities can significantly boost the security level of anti-counterfeiting in the scenario of guaranteeing the authenticity of a wide scope of common and luxury goods. In this work, a novel counterfeiting material with high-degree complexity is fabricated by microencapsulating cholesteric liquid crystals and triplet-triplet annihilation upconversion fluorophores to integrate structural coloration with fluorescence and upconversion photoluminescence. Moreover, the multimode security ink presents tailorable optical behaviors and programmable abilities on flexible substrates by various printing techniques, which offers distinct information encryption under different optical modes. The advanced strategy provides a practical versatile platform for high-secure-level multimode optical inks with largely enhanced encoding capacities, programmability, printability, and cost-effectiveness, which manifests enormous potentials for information encryption and anti-counterfeiting technology.

...