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1.
Heliyon ; 10(9): e30061, 2024 May 15.
Article En | MEDLINE | ID: mdl-38720696

Extensive studies have been conducted on the impact of foreign language reading anxiety on reading, primarily focusing on pedagogy and behavior but lacking electrophysiological evidence. The current study aimed to investigate the influence of foreign language reading anxiety on reading and its underlying mechanisms. The results revealed a negative correlation between foreign language reading anxiety and foreign language reading performance, irrespective of the native language. Adults with low levels of foreign language reading anxiety (LFLRA) demonstrated a significant difference in early lexical component N170 amplitude between foreign and native languages. However, this effect was not observed in adults with high levels of foreign language reading anxiety (HFLRA). In terms of N170 latency, HFLRA showed a longer N170 for the foreign language compared to the native language. Furthermore, the N170 effects were predominantly localized over the left occipitotemporal electrodes. Regarding N400 latency, a significant difference was found in LFLRA individuals between foreign and native language processing, while HFLRA individuals did not exhibit this difference. These findings suggest that HFLRA individuals experience inefficient lexical processing (such as orthography or semantics) during reading in foreign language.

2.
Article En | MEDLINE | ID: mdl-38757680

Human moral reactions to artificial intelligence (AI) agents' behavior constitute an important aspect of modern-day human-AI relationships. Although previous studies have mainly focused on autonomy ethics, this study investigates how individuals judge AI agents' violations of community ethics (including betrayals and subversions) compared with human violations. Participants' behavioral responses, event-related potentials (ERPs), and individual differences were assessed. Behavioral findings reveal that participants rated AI agents' community-violating actions less morally negative than human transgressions, possibly because AI agents are commonly perceived as having less agency than human adults. The ERP N1 component showed the same pattern with moral rating scores, indicating the modulation effect of human-AI differences on initial moral intuitions. Moreover, the level of social withdrawal correlated with a smaller N1 in the human condition but not in the AI condition. The N2 and P2 components were sensitive to the difference between the loyalty/betrayal and authority/subversion domains but not human/AI differences. Individual levels of moral sense and autistic traits also influenced behavioral data, especially on the loyalty/betrayal domain. In our opinion, these findings offer insights for predicting moral responses to AI agents and guiding ethical AI development aligned with human moral values.

3.
J Agric Food Chem ; 72(19): 11153-11163, 2024 May 15.
Article En | MEDLINE | ID: mdl-38695891

Maillard reaction (MR) plays a pivotal role in the food flavor industry, including a cascade of reactions starting with the reaction between amino compounds and reducing sugars, and thus provides various colors and flavors. A new group of volatile compounds called pyrazinones found in MR are now getting more attention. In this study, eight volatile pyrazinones were found in the asparagine MR systems, in which 3,5-dimethyl- and 3,6-dimethyl-2(1H)-pyrazinones were reported for the first time. The major formation pathways were the reactions between asparagine and α-dicarbonyls, with decarboxylation as a critical step. Besides, novel alternative pathways involving alanine amidation and successive reactions with α-dicarbonyls were explored and successfully formed eight pyrazinones. The major differences between alanine-amidated pathways and decarboxylation pathways are the amidation step and absence of the decarboxylation step. For the alanine-amidated pathways, the higher the temperature, the better the amidation effect. The optimal amidation temperature was 200 °C in this study. The reaction between the alanine amide and α-dicarbonyls after amidation can happen at low temperatures, such as 35 and 50 °C, proposing the possibility of pyrazinone formation in real food systems. Further investigations should be conducted to investigate volatile pyrazinones in various food systems as well as the biological effects and kinetic formation differences of the volatile pyrazinones.


Alanine , Asparagine , Maillard Reaction , Pyrazines , Volatile Organic Compounds , Pyrazines/chemistry , Alanine/chemistry , Asparagine/chemistry , Volatile Organic Compounds/chemistry , Flavoring Agents/chemistry
4.
J Chem Inf Model ; 2024 May 14.
Article En | MEDLINE | ID: mdl-38745420

Accumulating evidence has indicated that the expression of circular RNAs (circRNAs) can affect the cellular sensitivity to drugs and significantly influence drug efficacy. However, traditional experimental approaches for validating these associations are resource-intensive and time-consuming. To address this challenge, we propose a computational framework termed DPMGCDA leveraging dual perspective learning and path-masked graph autoencoder to predict circRNA-drug sensitivity associations. Initially, we construct circRNA-circRNA fusion similarity networks and drug-drug fusion similarity networks using similarity network fusion, ensuring a comprehensive integration of information. Based on the above, we built the circRNA homogeneous graph, the drug homogeneous graph, and the circRNA-drug heterogeneous graph. Next, we form the initial node features in the circRNA-drug heterogeneous graph from the homogeneous graph-level perspective and the combined feature-level perspective and complete the prediction of potential associations using the path-masked graph autoencoder in both perspectives. The predictions under both perspectives are finally combined to obtain the final prediction score. Transductive setting experiments and inductive setting experiments all demonstrate that our method, DPMGCDA, outperforms state-of-the-art approaches. Additionally, we verify the necessity of employing dual perspective learning through ablation tests and analyze the effective encoding capability of the path-masked graph autoencoder for features through embedding visualization. Moreover, case studies on four drugs corroborate DPMGCDA's ability to identify potential circRNAs associated with new drugs.

5.
Small Methods ; : e2400158, 2024 May 15.
Article En | MEDLINE | ID: mdl-38745530

Water electrolysis, a key enabler of hydrogen energy production, presents significant potential as a strategy for achieving net-zero emissions. However, the widespread deployment of water electrolysis is currently limited by the high-cost and scarce noble metal electrocatalysts in hydrogen evolution reaction (HER). Given this challenge, design and synthesis of cost-effective and high-performance alternative catalysts have become a research focus, which necessitates insightful understandings of HER fundamentals and material engineering strategies. Distinct from typical reviews that concentrate only on the summary of recent catalyst materials, this review article shifts focus to material engineering strategies for developing efficient HER catalysts. In-depth analysis of key material design approaches for HER catalysts, such as doping, vacancy defect creation, phase engineering, and metal-support engineering, are illustrated along with typical research cases. A special emphasis is placed on designing noble metal-free catalysts with a brief discussion on recent advancements in electrocatalytic water-splitting technology. The article also delves into important descriptors, reliable evaluation parameters and characterization techniques, aiming to link the fundamental mechanisms of HER with its catalytic performance. In conclusion, it explores future trends in HER catalysts by integrating theoretical, experimental and industrial perspectives, while acknowledging the challenges that remain.

6.
Article En | MEDLINE | ID: mdl-38729522

BACKGROUND AND AIMS: Dysfunction of the intestinal epithelial barrier comprising the junctional complex of tight junctions and adherent junctions leads to increased intestinal permeability, which is a major cause of uncontrolled inflammation related to Inflammatory Bowel Disease (IBD). The NAD+-dependent deacetylase SIRT1 is implicated in inflammation and the pathological process of IBD. We aimed to elucidate the protective role and underlying mechanism of SIRT1 in cell-cell junction and intestinal epithelial integrity. METHODS: The correlation of SIRT1 expression and human IBD was analyzed by GEO or immunohistochemical analyses. BK5.mSIRT1 transgenic mice and WT mice were given dextran sodium sulfate (DSS) and the manifestation of colitis-related phenotypes were analyzed. Intestinal permeability was measured by FITC-Dextran and cytokines expression was analyzed by QPCR. The expression of the cell junction-related proteins in DSS-treated or SIRT1-knockdown Caco2 or HCT116 cells was analyzed by Western blotting. The effects of Nicotinamide mononucleotide (NMN) in DSS-induced mice colitis were investigated. Correlations of the SIRT1-ß-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway with human IBD samples were analyzed. RESULTS: Reduced SIRT1 expression is associated with human IBD specimens. SIRT1 transgenic mice exhibit much-reduced manifestations of DSS-induced colitis. the activation of SIRT1 by NMN bolsters intestinal epithelial barrier function and ameliorates DSS-induced colitis in mice. Mechanistically, DSS down-regulates SiRT1 expression, leading to destabilization of ß-TrCP1 and upregulation of Snail1, accompanied by reduced expression of E-cadherin, Occludin, and Claudin-1, consequently resulting in increased epithelial permeability and inflammation. The deregulated SIRT1-ß-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway correlates with human IBD. CONCLUSION: SIRT1 is pivotal in maintaining the intestinal epithelial barrier integrity via modulation of the ß-TrCP1-Snail1-E-cadhein/Occludin/Claudin-1 pathway.

8.
Sci Adv ; 10(20): eadl1947, 2024 May 17.
Article En | MEDLINE | ID: mdl-38748796

Forest canopy structural complexity (CSC) plays a crucial role in shaping forest ecosystem productivity and stability, but the precise nature of their relationships remains controversial. Here, we mapped the global distribution of forest CSC and revealed the factors influencing its distribution using worldwide light detection and ranging data. We find that forest CSC predominantly demonstrates significant positive relationships with forest ecosystem productivity and stability globally, although substantial variations exist among forest ecoregions. The effects of forest CSC on productivity and stability are the balanced results of biodiversity and resource availability, providing valuable insights for comprehending forest ecosystem functions. Managed forests are found to have lower CSC but more potent enhancing effects of forest CSC on ecosystem productivity and stability than intact forests, highlighting the urgent need to integrate forest CSC into the development of forest management plans for effective climate change mitigation.


Biodiversity , Climate Change , Ecosystem , Forests , Conservation of Natural Resources , Trees/growth & development
9.
Clin Exp Med ; 24(1): 100, 2024 May 17.
Article En | MEDLINE | ID: mdl-38758217

BACKGROUND: The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology. OBJECTIVE: To explore the epidemiology of various types of non-paraneoplastic pemphigus associated with malignant tumors. METHODS: Five databases from establishment through October 20, 2023, were searched. STATA SE 17 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies. RESULTS: A total of 6679 participants were included in our meta-analysis from 16 studies. The aggregated prevalence of tumors in patients diagnosed with pemphigus was 8%. The prevalence was 7% in patients with pemphigus vulgaris, 10% in those with pemphigus foliaceus, and 12% in individuals diagnosed with other types of pemphigus. The prevalence was 8% in Asia, 11% in Europe, and 8% in North America. From a country-specific perspective, patients with pemphigus from Israel, Greece, and Germany exhibited a higher prevalence of tumors at 11%. Furthermore, when categorized by the duration of the study period, the highest prevalence was observed in studies spanning 10 to 20 years, at 11%. CONCLUSION: These findings demonstrate the incidence and prevalence of malignant tumors in patients with non-paraneoplastic pemphigus, which may achieve early detection and intervention, and then reduce mortality rates.


Neoplasms , Pemphigus , Pemphigus/epidemiology , Humans , Prevalence , Incidence , Neoplasms/epidemiology , Neoplasms/complications , Europe/epidemiology , North America/epidemiology , Asia/epidemiology
10.
J Agric Food Chem ; 72(18): 10570-10578, 2024 May 08.
Article En | MEDLINE | ID: mdl-38652024

Amadori rearrangement products (ARPs) are gaining more attention for their potential usage in the food flavor industry. Peptide-ARPs have been studied, but pyrazinones that were theoretically found in the Maillard reaction (MR) have not been reported to be formed from small peptide-ARPs. This study found four pyrazinones: 1-methyl-, 1,5-dimethyl-, 1,6-dimethyl-, and 1,5,6-trimethyl-2(1H)-pyrazinones in both MR and ARP systems. It was the first time 1-methyl-2(1H)-pyrazinone was reported, along with 1,5-dimethyl- and 1,5,6-trimethyl-2(1H)-pyrazinones being purified and analyzed by nuclear magnetic resonance for the first time. The primary formation routes of the pyrazinones were also proven as the reaction between diglycine and α-dicarbonyls, including glyoxal, methylglyoxal, and diacetyl. The pyrazinones, especially 1,5-dimethyl-2(1H)-pyrazinone, have strong fluorescence intensity, which may be the reason for the increase of fluorescence intensity in MR besides α-dicarbonyls. Cytotoxicity analysis showed that both Gly-/Digly-/Trigly-ARP and the three pyrazinones [1-methyl-, 1,5-dimethyl-, and 1,5,6-trimethyl-2(1H)-pyrazinones] showed no prominent cytotoxicity in the HepG2 cell line below 100 µg/mL, further suggesting that ARPs or pyrazinones could be used as flavor additives in the future. Further research should be conducted to investigate pyrazinones in various systems, especially the peptide-ARPs, which are ubiquitous in real food systems.


Maillard Reaction , Pyrazines , Pyrazines/chemistry , Humans , Flavoring Agents/chemistry , Volatile Organic Compounds/chemistry , Peptides/chemistry , Glyoxal/chemistry
11.
J Hazard Mater ; 471: 134385, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38678711

Nitric oxide (NO) is a signaling molecule with diverse roles in various organisms. However, its role in the opportunistic pathogen Aspergillus flavus remains unclear. This study investigates the potential of NO, mediated by metabolites from A. oryzae (AO), as an antifungal strategy against A. flavus. We demonstrated that AO metabolites effectively suppressed A. flavus asexual development, a critical stage in its lifecycle. Transcriptomic analysis revealed that AO metabolites induced NO synthesis genes, leading to increased intracellular NO levels. Reducing intracellular NO content rescued A. flavus spores from germination inhibition caused by AO metabolites. Furthermore, exogenous NO treatment and dysfunction of flavohemoglobin Fhb1, a key NO detoxification enzyme, significantly impaired A. flavus asexual development. RNA-sequencing and metabolomic analyses revealed significant metabolic disruptions within tricarboxylic acid (TCA) cycle upon AO treatment. NO treatment significantly reduced mitochondrial membrane potential (Δψm) and ATP generation. Additionally, aberrant metabolic flux within the TCA cycle was observed upon NO treatment. Further analysis revealed that NO induced S-nitrosylation of five key TCA cycle enzymes. Genetic analysis demonstrated that the S-nitrosylated Aconitase Acon and one subunit of succinate dehydrogenase Sdh2 played crucial roles in A. flavus development by regulating ATP production. This study highlights the potential of NO as a novel antifungal strategy to control A. flavus by compromising its mitochondrial function and energy metabolism.


Aspergillus flavus , Citric Acid Cycle , Mitochondria , Nitric Oxide , Citric Acid Cycle/drug effects , Aspergillus flavus/metabolism , Aspergillus flavus/growth & development , Aspergillus flavus/drug effects , Nitric Oxide/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Antifungal Agents/pharmacology , Membrane Potential, Mitochondrial/drug effects , Spores, Fungal/drug effects , Spores, Fungal/growth & development , Fungal Proteins/metabolism , Fungal Proteins/genetics
12.
Phytomedicine ; 128: 155412, 2024 Jun.
Article En | MEDLINE | ID: mdl-38579666

BACKGROUND: Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes. Currently, corticosteroids are the preferred option. However, prolonged use of traditional topical medication can lead to adverse reactions and relapse, presenting a significant therapeutic obstacle. Improved alternative treatment options are urgently required. Formononetin (FMN) is a representative component of isoflavones in Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.]. It possesses properties that reduce inflammation, combat oxidation, inhibit tumor growth, and mimic estrogen. Although FMN has been shown to ameliorate skin barrier devastation via regulating keratinocyte apoptosis and proliferation, there are no reports of its effectiveness in treating psoriasis. OBJECTIVE: Through transcriptomics clues and experimental investigation, we aimed to elucidate the fundamental mechanisms underlying FMN's action on psoriasis. MATERIALS AND METHODS: Cell viability was examined using CCK8 assay in this study. The results of analysis of differentially expressed genes (DEGs) between FMN-treated HaCaT cells and normal HaCaT cells using RNA-sequencing (RNA-seq) were presented on volcano plots and heatmap. Enrichment analysis was conducted on DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and results were validated through RT-qPCR verification. After 12 days of FMN treatment in psoriasis mouse model, we gauged the PASI score and epidermis thickness. A variety of techniques were used to assess FMN's effectiveness on inhibiting inflammation and proliferation related to psoriasis, including RT-qPCR, HE staining, western blot, and immunohistochemistry (IHC). RESULTS: The findings indicated that FMN could suppress the growth of HaCaT cells using CCK8 assay (with IC50 = 40.64 uM) and 20 uM FMN could reduce the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to the greatest extent. FMN-treated HaCaT cells exhibited 985 up-regulated and 855 down-regulated DEGs compared to normal HaCaT cells. GO analysis revealed that DEGs were linked to interferon (IFN) signaling pathway. Furthermore, FMN improved pathological features, which encompassed decreased erythema, scale, and thickness scores of skin lesions in psoriasis mouse model. In vivo experiments confirmed that FMN down-regulated expression of IFN-α, IFN-ß, IFN-γ, decreased secretion of TNF-α and IL-17 inflammatory factors, inhibited expression of IFN-related chemokines included Cxcl9, Cxcl10, Cxcl11 and Cxcr3 and reduced expression of transcription factors p-STAT1, p-STAT3 and IFN regulatory factor 1 (IRF1) in the imiquimod (IMQ) group. CONCLUSIONS: In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent.


HaCaT Cells , Isoflavones , Psoriasis , Signal Transduction , Isoflavones/pharmacology , Psoriasis/drug therapy , Animals , Signal Transduction/drug effects , Humans , Mice , Interferons , Cell Survival/drug effects , Keratinocytes/drug effects , Inflammation/drug therapy , Astragalus propinquus/chemistry , Mice, Inbred BALB C , Male , Disease Models, Animal
13.
Phys Rev Lett ; 132(13): 133603, 2024 Mar 29.
Article En | MEDLINE | ID: mdl-38613308

An integrated quantum light source is increasingly desirable in large-scale quantum information processing. Despite recent remarkable advances, a new material platform is constantly being explored for the fully on-chip integration of quantum light generation, active and passive manipulation, and detection. Here, for the first time, we demonstrate a gallium nitride (GaN) microring based quantum light generation in the telecom C-band, which has potential toward the monolithic integration of quantum light source. In our demonstration, the GaN microring has a free spectral range of 330 GHz and a near-zero anomalous dispersion region of over 100 nm. The generation of energy-time entangled photon pair is demonstrated with a typical raw two-photon interference visibility of 95.5±6.5%, which is further configured to generate a heralded single photon with a typical heralded second-order autocorrelation g_{H}^{(2)}(0) of 0.045±0.001. Our results pave the way for developing a chip-scale quantum photonic circuit.

14.
Brain Res ; 1836: 148933, 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38604554

OBJECTIVE: To investigate the potential changes of glucose metabolism and glucose transporter protein (GLUT) in the visual cortex of formally deprived amblyopic rats, as well as the effects of enriched environments on the levels of nerve conduction and glucose metabolism in the visual cortex of amblyopic rats. METHODS: 36 rats were randomly divided into three groups: CON + SE (n = 12), MD + SE (n = 12) and MD + EE (n = 12). The right eyelids of both MD + SE and MD + EE groups were sutured. After successful modelling, the MD + EE group was maintained in an enriched environment, and the other two groups were kept in the same environment. Pattern visual evoked potentials (PVEP) was used to confirm models' effect, glucose metabolism was analyzed by Micro-PET/CT (18F-FDG), and the protein as well as mRNA expression levels of GLUT were detected by Western Blot and quantitative RT-PCR (quantitative Reverse Transcription-Polymerase Chain Reaction) analyses, site of GLUT expression by immunofluorescence (IF). RESULTS: After suture modelling, both the MD + EE and MD + SE groups objective visual nerve conduction function decreased, the glucose metabolism in the visual cortex was markedly lower. After the enriched environment intervention, it recovered in the MD + EE group. The expression levels of GLUT1 and GLUT3 were increased in the MD + EE group in comparison with the MD + SE group. GLUT1 was primarily expressed on astrocytes and endothelial cells, but GLUT3 was mainly expressed on neurons. CONCLUSION: Enrichment of the environment exhibited a therapeutic effect on amblyopia, which could be related to the enhancement of glucose metabolism and GLUT expression in the visual cortex.

15.
Transfusion ; 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38661221

BACKGROUND: Limited studies have explored the association between clinical symptoms and titers of SARS-CoV-2 antibodies. STUDY DESIGN AND METHODS: In this cross-sectional study, whole-blood donors who had experienced a confirmed or suspected COVID-19 infection completed questionnaires at the time of blood donation. Plasma SARS-CoV-2 immunoglobulin G (IgG) titers were measured using an enzyme-linked immunosorbent assay. Logistic regression models were used to calculate odds ratios (ORs) for high-titer COVID-19 convalescent plasma (CCP) for each variable. RESULTS: Among the total 386 donors, 120 (31%) donors with IgG titers ≥1:160 were classified as high-titer donors. The multivariable ORs (95% confidence intervals [CIs]) for high titers were 2.33 (1.45-3.75), 2.11 (1.29-3.43), 1.10 (1.01-1.21), 1.19 (1.00-1.43), and 1.97 (1.05-3.71) for sore throat, cough, symptom count, fever duration, and low fever (compared with non-fever), respectively. No significant association was observed between other symptoms and medical visits and the odds of high-titer CCP. The association between high-titer CCP and fever duration was restricted to confirmed COVID-19-infected donors, while associations with sore throat and cough remained significant in suspected infected donors. In addition, medical visit was positively associated with high-titer CCP in suspected donors, but not in confirmed donors. In bootstrapped logistic regression models, the associations remained significant and reproducible for medical visit in suspected donors and for sore throat and cough in both suspected donors and total donors. DISCUSSION: Experiencing a sore throat and cough were associated with high-titer CCP in overall donors. We also identified sore throat, cough, and medical visits as potential predictors of high-titer CCP for suspected donors during the pandemic.

16.
Am J Physiol Endocrinol Metab ; 326(5): E723-E734, 2024 May 01.
Article En | MEDLINE | ID: mdl-38506753

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of beta cells by immune cells. The interactions among cells within the islets may be closely linked to the pathogenesis of T1D. In this study, we used single-cell RNA sequencing (scRNA-Seq) to analyze the cellular heterogeneity within the islets of a T1D mouse model. We established a T1D mouse model induced by streptozotocin and identified cell subpopulations using scRNA-Seq technology. Our results revealed 11 major cell types in the pancreatic islets of T1D mice, with heterogeneity observed in the alpha and beta cell subgroups, which may play a crucial role in the progression of T1D. Flow cytometry further confirmed a mature alpha and beta cell reduction in T1D mice. Overall, our scRNA-Seq analysis provided insights into the cellular heterogeneity of T1D islet tissue and highlighted the potential importance of alpha and beta cells in developing T1D.NEW & NOTEWORTHY In this study, we created a comprehensive single-cell atlas of pancreatic islets in a T1D mouse model using scRNA-Seq and identified 11 major cell types in the islets, highlighting the role of alpha and beta cells in T1D. This study revealed a significant reduction in the maturity alpha and beta cells in T1D mice through flow cytometry. It also demonstrated the heterogeneity of alpha and beta cells, potentially crucial for T1D progression. Overall, our scRNA-Seq analysis provided new insights for understanding and treating T1D by studying cell subtype changes and functions.


Diabetes Mellitus, Type 1 , Insulin-Secreting Cells , Islets of Langerhans , Sequence Analysis, RNA , Single-Cell Analysis , Animals , Mice , Diabetes Mellitus, Type 1/genetics , Single-Cell Analysis/methods , Islets of Langerhans/metabolism , Islets of Langerhans/cytology , Insulin-Secreting Cells/metabolism , Sequence Analysis, RNA/methods , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Glucagon-Secreting Cells/metabolism , Female , RNA-Seq/methods , Mice, Inbred C57BL
17.
Article En | MEDLINE | ID: mdl-38547523

ABSTRACT: Sepsis-induced myocardial dysfunction (SIMD) commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. The current study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing (RNA-seq) demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. Additionally, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NLRP3 upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for SIMD therapy.

18.
Sci Rep ; 14(1): 6072, 2024 03 13.
Article En | MEDLINE | ID: mdl-38480826

Blood transfusions from convalescent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients could be used to treat patients with severe infections or immunocompromised patients. However, it is necessary to select the optimal donors to maximize the utilization of resources. In this study, we investigated the associations among body mass index (BMI), tobacco smoking, exercise frequency and duration, and alcohol consumption with the SARS-CoV-2 immunoglobulin-G (IgG) antibody titer levels with in the Chinese convalescent blood donor population. Here we show that BMI, smoking habits, and exercise frequency appear to be predictive factors for IgG levels in convalescent male blood donors. However, these variables were not observed as predictive of IgG levels in female convalescent blood donors. The findings could be used to optimize the screening for potential blood donors to treat immunocompromised or severely ill COVID-19 patients.


COVID-19 , Humans , Male , Female , SARS-CoV-2 , Blood Donors , Cross-Sectional Studies , Immunization, Passive , COVID-19 Serotherapy , Antibodies, Viral , Immunoglobulin G , China
19.
Diabetes Ther ; 15(3): 585-609, 2024 Mar.
Article En | MEDLINE | ID: mdl-38302838

Diabetic macroangiopathy, a prevalent and severe complication of diabetes mellitus, significantly contributes to the increased morbidity and mortality rates among affected individuals. This complex disorder involves multifaceted molecular mechanisms that lead to the dysfunction and damage of large blood vessels, including atherosclerosis (AS) and peripheral arterial disease. Understanding the intricate pathways underlying the development and progression of diabetic macroangiopathy is crucial for the development of effective therapeutic interventions. This review aims to shed light on the molecular mechanism implicated in the pathogenesis of diabetic macroangiopathy. We delve into the intricate interplay of chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulated angiogenesis, all of which contribute to the vascular complications observed in this disorder. By exploring the molecular mechanism involved in the disease we provide insight into potential therapeutic targets and strategies. Moreover, we discuss the current therapeutic approaches used for treating diabetic macroangiopathy, including glycemic control, lipid-lowering agents, and vascular interventions.

20.
Eur J Clin Microbiol Infect Dis ; 43(4): 713-721, 2024 Apr.
Article En | MEDLINE | ID: mdl-38347245

BACKGROUND AND AIM: Patients with end-stage liver disease (ESLD) are susceptible to invasive pulmonary aspergillosis (IPA). This study aimed to investigate the risk factors affecting the occurrence and short-term prognosis of ESLD complicated by IPA. METHODS: This retrospective case-control study included 110 patients with ESLD. Of them, 27 ESLD-IPA received antifungal therapy with amphotericin B (AmB); 27 AmB-free-treated ESLD-IPA patients were enrolled through 1:1 propensity score matching. Fifty-six ESLD patients with other comorbid pulmonary infections were enrolled as controls. The basic features of groups were compared, while the possible risk factors affecting the occurrence and short-term outcomes of IPA were analyzed. RESULTS: Data analysis revealed invasive procedures, glucocorticoid exposure, and broad-spectrum antibiotic use were independent risk factors for IPA. The 54 patients with ESLD-IPA exhibited an overall treatment effectiveness and 28-d mortality rate of 50.00% and 20.37%, respectively, in whom patients treated with AmB-containing showed higher treatment efficacy than patients treated with AmB-free antifungal regimens (66.7% vs. 33.3%, respectively, χ2 = 6.000, P = 0.014). Multivariate logistic regression analysis revealed that the treatment regimen was the only predictor affecting patient outcomes, with AmB-containing regimens were 4.893 times more effective than AmB-free regimens (95% CI, 1.367-17.515; P = 0.015). The only independent predictors affecting the 28-d mortality rate were neutrophil-to-lymphocyte ratio and IPA diagnosis (OR = 1.140 and 10.037, P = 0.046 and 0.025, respectively). CONCLUSIONS: Glucocorticoid exposure, invasive procedures, and broad-spectrum antibiotic exposure increased the risk of IPA in ESLD patients. AmB alone or combined with other antifungals may serve as an economical, safe, and effective treatment option for ESLD-IPA.


End Stage Liver Disease , Invasive Pulmonary Aspergillosis , Humans , Antifungal Agents , Retrospective Studies , Case-Control Studies , Glucocorticoids , Amphotericin B/therapeutic use , Prognosis , Risk Factors , Anti-Bacterial Agents/therapeutic use
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