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1.
Food Chem ; 460(Pt 2): 140578, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39106811

ABSTRACT

This investigation employed molten globule state ß-lactoglobulin nanoparticles (MG-BLGNPs) for encapsulating linalool (LN) combined with carboxymethyl chitosan (CMC) coating to enhance the shelf-life of fresh-cut apples. The effect of different MG structures on the encapsulation efficiency of BLGNPs and the properties of coating was studied. Structural characterization and molecular simulation showed structural differences between heat-induced MG state (70-BLGNPs, heated at 70 °C for 1 h) and sodium dodecyl sulfate-co-heat-induced MG state (SDS/70-BLGNPs, treated with 0.192 mg/mL SDS for 10 min, then heated at 70 °C for 1 h), with the latter being more unfolded. LN self-assembles into MG-BLGNPs, among the generated particles, SDS/70-BLG@LN exhibits stronger binding effect and higher LN loading capacity. Integration of MG-BLG@LN into CMC enhanced coating's mechanical properties and adhesion to fresh-cut apples. The SDS/70-BLG@LN/CMC coating showed superior preservation on fresh-cut apples during storage, reducing enzymatic browning, membrane lipid oxidation, and microbial growth while maintaining hardness and overall quality.

2.
Sci Rep ; 14(1): 18232, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39107338

ABSTRACT

To explore the clinical characteristics of patients infected with SARS-CoV-2 nationwide, especially the effect factors of asymptomatic infection and disappearance of clinical symptoms. A total of 66,448 COVID-19 patients in China who have been diagnosed by nucleic acid test or rapid antigen test were surveyed online (December 24, 2022 to January 16, 2023). Our cross-sectional study used descriptive analyses and binary Logistics regression model to assess the correlation between the clinical characteristics and relative factors, including age, gender, pre-existing conditions, reinfection, vaccination and treatment. A total of 64,515 valid questionnaires were collected. Among included participants, 5969 of which were asymptomatic. The symptoms were mainly upper respiratory symptoms, including dry and itchy throat (64.16%), sore throat (59.95%), hoarseness (57.90%), nasal congestion (53.39%). In binary Logistics regression model, we found that male, no pre-existing conditions, reinfection and vaccination have positive correlations with the appearance of asymptomatic COVID-19 patients. In Cox proportional-hazards regression model, considering all clinical symptoms disappeared in 14 days as outcome, we found that ≤ 60 years old, male, no pre-existing conditions, vaccination and adopted treatment have positive correlations with rapid amelioration of clinical symptoms in COVID-19 patients. The clinical symptoms of the participants were mainly upper respiratory symptoms which were according with the infection of Omicron variant. Factors including age, gender, pre-existing conditions and reinfection could influence the clinical characteristics and prognosis of COVID-19 patients. Importantly, vaccination has positive significance for the prevention and treatment of COVID-19. Lastly, the use of Chinese medicine maybe beneficial to COVID-19 patients, however, reasonable guidance is necessary.


Subject(s)
Asymptomatic Infections , COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/diagnosis , COVID-19/virology , Male , Female , China/epidemiology , Cross-Sectional Studies , Middle Aged , Adult , Asymptomatic Infections/epidemiology , SARS-CoV-2/isolation & purification , Aged , Young Adult , Adolescent
3.
Medicine (Baltimore) ; 103(27): e38854, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968458

ABSTRACT

INTRODUCTION: Epidermolysis Bullosa Pruriginosa (EBP) is a persistent, recurring disease that seriously affects quality of life. Fewer than 100 cases of EBP have been reported to date. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling, and inhibition of this pathway using Janus kinase (JAK) inhibitors might be a useful therapeutic strategy for these diseases. PATIENT CONCERNS: A male patient, 28 years of age, was admitted to our hospital because of recurrent papules, nodules, and intense itching on the trunk and extremities for 12 years. Repeated large and intense itching has seriously affected the patient normal life. DIAGNOSIS: The patient was diagnosed with EBP based on examination results. INTERVENTIONS: Oral baricitinib tablets (2 mg, once a day) + Oral desloratadine citrate disodium tablets (8.8 mg, once a day) combined with topical compound flumethasone ointment and Fucidin cream. OUTCOMES: The patient skin rashes had subsided and flattened remarkable, and his itching was markedly relieved. The visual analogue scale (VAS) itching score of the patient gradually declined from 8 to 9 points to 2 to 3 points. CONCLUSION: This study confirms that baricitinib is effective and feasible in treating EBP, especially in remarkable relieving itching, which rendered new ideas for therapeutic approaches for EBP in the future.


Subject(s)
Azetidines , Purines , Pyrazoles , Sulfonamides , Humans , Purines/therapeutic use , Male , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Adult , Azetidines/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Epidermolysis Bullosa Dystrophica/drug therapy , Administration, Oral
5.
Molecules ; 29(13)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38999110

ABSTRACT

Electrochemical biosensors have emerged as powerful tools for the ultrasensitive detection of lung cancer biomarkers like carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and alpha fetoprotein (AFP). This review comprehensively discusses the progress and potential of nanocomposite-based electrochemical biosensors for early lung cancer diagnosis and prognosis. By integrating nanomaterials like graphene, metal nanoparticles, and conducting polymers, these sensors have achieved clinically relevant detection limits in the fg/mL to pg/mL range. We highlight the key role of nanomaterial functionalization in enhancing sensitivity, specificity, and antifouling properties. This review also examines challenges related to reproducibility and clinical translation, emphasizing the need for standardization of fabrication protocols and robust validation studies. With the rapid growth in understanding lung cancer biomarkers and innovations in sensor design, nanocomposite electrochemical biosensors hold immense potential for point-of-care lung cancer screening and personalized therapy guidance. Realizing this goal will require strategic collaboration among material scientists, engineers, and clinicians to address technical and practical hurdles. Overall, this work provides valuable insight for developing next-generation smart diagnostic devices to combat the high mortality of lung cancer.


Subject(s)
Biomarkers, Tumor , Biosensing Techniques , Electrochemical Techniques , Lung Neoplasms , Humans , Biomarkers, Tumor/analysis , Lung Neoplasms/diagnosis , Biosensing Techniques/methods , Electrochemical Techniques/methods , Carcinoembryonic Antigen/analysis , Carcinoembryonic Antigen/blood , Nanocomposites/chemistry , Graphite/chemistry
6.
Article in English | MEDLINE | ID: mdl-39034743

ABSTRACT

STUDY DESIGN: Preclinical experimental study. OBJECTIVE: To develop an intraoperative ultrasound-assisted imaging device, which could be placed at the surgical site through an endoscopic working channel and which could help surgeon recognition of different tissue types during endoscopic spinal surgery (ESS). SUMMARY OF BACKGROUND DATA: ESS remains a challenging task for spinal surgeons. Great proficiency and experience are needed to perform procedures such as intervertebral discectomy and neural decompression within a narrow channel. The limited surgical view poses a risk of damaging important structures, such as nerve roots. METHODS: We constructed a spinal endoscopic ultrasound system, using a 4-mm custom ultrasound probe, which can be easily inserted through the ESS working channel, allowing up to 10 mm depth detection. This system was applied to ovine lumbar spine samples to obtain ultrasound images. Subsequently, we proposed a two-stage classification algorithm, based on a pretrained DenseNet architecture for automated tissue recognition. The recognition algorithm was evaluated using accuracy and consistency. RESULTS: The probe can be easily used in the ESS working channel and produce clear and characteristic ultrasound images. We collected 367 images for training and testing of the recognition algorithm, including images of the spinal cord, nucleus pulposus, adipose tissue, bone, annulus fibrosus and nerve roots. The algorithm achieved over 90% accuracy in recognizing all types of tissues with a Kappa value of 0.875. The recognition times were under 0.1 s using the current configuration. CONCLUSION: Our system was able to be used in existing ESS working channels and clearly identified at-risk spinal structures in vitro. The pretrained algorithms could identify six intraspinal tissue types accurately and quickly. The concept and innovative application of intraoperative ultrasound in ESS may shorten the learning curve of ESS and improve surgical efficiency and safety.

7.
Reproduction ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39042720

ABSTRACT

Oocyte activation failure, one of the main factors of total fertilization failure (TFF) after ICSI, could be induced by abnormal calcium oscillations. Phospholipase C zeta (PLCζ), a sperm factor, was associated with Ca2+ oscillations in oocytes of mammals. To date, only a limited number of mutations in PLCZ1 (the gene encodes PLCζ) have been linked to TFF demonstrated by the observed reduction in protein levels or activity. In this study, males with normozoospermic sperm suffering TFF after ICSI and their families were recruited. Firstly, mutations in the PLCZ1 sequence were identified by Whole exome sequencing and validated by Sanger sequencing. Then the transcript and protein levels and locations of PLCZ1/PLCζ in sperms of patients were studied followed by in vitro function analysis and in silico analysis to investigate the function-structure correlation of mutations identified in PLCZ1 through Western blotting, Immunofluorescence, RT-qPCR and Molecular Simulation. Ca2+ oscillations were detected after cRNA microinjection with MⅡ mouse oocyte to investigate the calcium oscillations of abnormal PLCζ. Five variants in compound heterozygosity were identified including five new mutations and three-reported mutations which were located across the main domains of PLCζ, except the EF hands domain. The transcript and protein levels were decreased among all the mutations identified in PLCZ1 at different degrees when transfected with HEK293T cells. Among these mutations, M138V and R391* of PLCζ could not trigger normal Ca2+ oscillations. In case 5, an abnormal location in the head of sperm and a higher expression of PLCζ in the sperm were found.

8.
Fitoterapia ; 177: 106134, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39047844

ABSTRACT

Herein, six previously undescribed steroids (1-6), were isolated from leaves and twigs of Aphanamixis polystachya (Wall.) R. N. Parker (Meliaceae). Their structures were elucidated by comprehensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR, UV, and IR. Antiviral activity of these compounds were evaluated. Compounds 1-6 showed varying degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 200 µM.

9.
Sci Rep ; 14(1): 16917, 2024 07 23.
Article in English | MEDLINE | ID: mdl-39043753

ABSTRACT

In this study, we investigated the status and influencing factors of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic obstructive pulmonary disease (COPD). A questionnaire on COVID-19 vaccination in patients with COPD was developed. The clinical characteristics, COVID-19 vaccination status, other relevant vaccinations, and vaccination status of the patients with COPD were collected anonymously. Logistic regression analysis was used to analyze the factors influencing COVID-19 vaccination in patients with COPD. There were 1898 returned questionnaires, of which 1874 were valid. The proportion of patients who completed the COVID-19 vaccination program was 78.60%. Factors influencing the COVID-19 vaccination rate were: the age of individuals who were 75-85 years old and > 85 years old, acute exacerbation 3-4 times in the previous year, comorbid cardiovascular and endocrine system diseases, failure to take regular medication for COPD, application of non-invasive ventilation machines, believing that their current health condition has deteriorated, believing that the current COVID-19 vaccine is not safe, medical staff not specifying whether they would recommend vaccination against COVID-19, medical staff not recommending the COVID-19 vaccine, and fear of adverse reactions and aggravation of COPD. Patients with COPD had a high COVID-19 vaccination rate in China, whereas patients with pneumonia, influenza, and herpes zoster had a low vaccination rate. Improving the patients' understanding of the safety and effectiveness of the vaccine and promoting effective communication between medical staff and patients would help increase the vaccination rate of patients with COPD.


Subject(s)
COVID-19 Vaccines , COVID-19 , Pulmonary Disease, Chronic Obstructive , Vaccination , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Surveys and Questionnaires
10.
J Transl Int Med ; 12(3): 299-307, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39081273

ABSTRACT

Background and Objectives: Fever of unknown origin (FUO) has long been a cause for concern among clinicians, and its spectrum has evolved with progress in medicine. This study aimed to investigate the distribution of causes of FUO in China between 2013 and 2022 to facilitate the clinical understanding of the etiology of FUO. Materials and Methods: Case series of FUO in China published between 2013 and 2022 were retrieved from PubMed, Wanfang Data, and CNKI databases and retrospectively analyzed. The rates of different causes of FUO were calculated, and these data were compared with previously published distributions of causes of FUO in China. Results: The causes of FUO with the highest rates from the 51 identified case series (n = 19,874) were infectious, autoimmune, and neoplastic diseases (59.6%, 14.3%, and 7.9%, respectively). A comparison of a subset (43 case series subdivided by disease category, n = 16,278) with previously reported data revealed an increased rate of FUO attributed to infectious diseases in the past decade, with a significantly higher rate attributed to bloodstream infections (10.0% vs. 4.8%) and a significantly lower rate attributed to tuberculosis (9.3% vs. 28.4%), compared with the rates from the previous period. In contrast, the rates of FUO attributed to both autoimmune and neoplastic diseases decreased, with significantly decreased rates attributed to adult-onset Still's disease among autoimmune diseases (4.6% vs. 8.5%) and lung cancer among neoplastic diseases (0.6% vs. 1.6%). Conclusion: Despite an overall increase in the rate attributed to infectious diseases, that attributed to tuberculosis has decreased. The rates attributed to both autoimmune and neoplastic diseases have also decreased.

11.
Article in English | MEDLINE | ID: mdl-39033934

ABSTRACT

BACKGROUND: Cilia loss and impaired motile ciliary functions are one of the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin-17A (IL-17A) and interleukin-22 (IL-22) are the canonical cytokines of type 3 inflammation, exhibiting similar functional effects on epithelial cells. In this study, we sought to examine the effects of IL-17A and IL-22 on ciliated cells and investigate the potential involvement of Hippo-Yes-associated protein (YAP) signaling in their influence on ciliogenesis. METHODS: We assessed both the mRNA and protein expression levels of IL-17A and IL-22 in nasal tissues obtained from patients with CRSwNP and compared them to those from healthy controls. To further explore the impact of IL-17A and IL-22, we established a primary human nasal epithelial cell (hNEC) model using different concentrations (2 ng/mL, 10 ng/mL, 50 ng/mL) for a duration of 28 days in an air-liquid interface (ALI) culture. Additionally, we employed the inhibitor verteporfin (VP) to investigate whether IL-17A andIL-22 exert their effects on ciliated cells via Hippo-YAP pathway. RESULTS: The mRNA and protein levels of IL-17A and IL-22 in CRSwNP were significantly higher than those in healthy controls, revealing a robust correlation between IL-17A and IL-22. YAP was highly expressed in the nucleus of ciliated cells in CRSwNP and displayed a positive correlation with clinical symptoms. Both IL-17A and IL-22 were found to reduce the number of ciliated cells. IL-17A, but not IL-22, suppressed ciliogenesis by disrupting the proper development and docking of the basal body of ciliated cells, resulting in motile ciliary dysfunctions. Furthermore, the expression of YAP within the nucleus of ciliated cells gradually declined as these cells reached the final stage of differentiation. However, this process was obstructed by IL-17A only. YAP inhibitors, such as Verteporfin, markedly reversed the effects of IL-17A by increasing the proportion of ciliated cells, suppressing nuclear YAP expression in these cells, and enhancing ciliary beating frequency. CONCLUSIONS: Both IL-17A and IL-22 are overexpressed in nasal epithelium of CRSwNP, which is associated with the impairment of epithelial cell differentiation. Furthermore, IL-17A has been shown to exert a disruptive effect on morphogenesis of motile cilia via activation of YAP.

12.
Nat Hum Behav ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886532

ABSTRACT

Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (ß [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (ß [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health.

14.
J Virol ; 98(7): e0068624, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38888343

ABSTRACT

Nervous necrosis virus (NNV), an aquatic RNA virus belonging to Betanodavirus, infects a variety of marine and freshwater fishes, leading to massive mortality of cultured larvae and juveniles and substantial economic losses. The enzyme cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is widely recognized as a central component in the innate immune response to cytosolic DNA derived from different pathogens. However, little is known about the response of cGAS to aquatic RNA viruses. This study found that Epinephelus coioides cGAS (EccGAS) overexpression inhibited NNV replication, whereas EccGAS silencing promoted NNV replication. The anti-NNV activity of EccGAS was involved in interferon (IFN) signaling activation including tumor necrosis factor receptor-associated factor family member-associated NF-kappa-B activator-binding kinase 1 (TBK1) phosphorylation, interferon regulatory factor 3 (IRF3) nuclear translocation, and the subsequent induction of IFNc and ISGs. Interestingly, NNV employed its capsid protein (CP) or Protein A (ProA) to negatively or positively modulate EccGAS-mediated IFN signaling by simultaneously targeting EccGAS. CP interacted with EccGAS via the arm-P, S-P, and SD structural domains and promoted its polyubiquitination with K48 and K63 linkages in an EcUBE3C (the ubiquitin ligase)-dependent manner, ultimately leading to EccGAS degradation. Conversely, ProA bound to EccGAS and inhibited its ubiquitination and degradation. In regulating EccGAS protein content, CP's inhibitory action was more pronounced than ProA's protective effect, allowing successful NNV replication. These novel findings suggest that NNV CP and ProA dynamically modulate the EccGAS-mediated IFN signaling pathway to facilitate the immune escape of NNV. Our findings shed light on a novel mechanism of virus-host interaction and provide a theoretical basis for the prevention and control of NNV.IMPORTANCEAs a well-known DNA sensor, cGAS is a pivotal component in innate anti-viral immunity to anti-DNA viruses. Although there is growing evidence regarding the function of cGAS in the resistance to RNA viruses, the mechanisms by which cGAS participates in RNA virus-induced immune responses in fish and how aquatic viruses evade cGAS-mediated immune surveillance remain elusive. Here, we investigated the detailed mechanism by which EccGAS positively regulates the anti-NNV response. Furthermore, NNV CP and ProA interacted with EccGAS, regulating its protein levels through ubiquitin-proteasome pathways, to dynamically modulate the EccGAS-mediated IFN signaling pathway and facilitate viral evasion. Notably, NNV CP was identified to promote the ubiquitination of EccGAS via ubiquitin ligase EcUBE3C. These findings unveil a novel strategy for aquatic RNA viruses to evade cGAS-mediated innate immunity, enhancing our understanding of virus-host interactions.


Subject(s)
Capsid Proteins , Fish Diseases , Immune Evasion , Immunity, Innate , Nodaviridae , Nucleotidyltransferases , RNA Virus Infections , Signal Transduction , Virus Replication , Animals , Fish Diseases/virology , Fish Diseases/immunology , Nucleotidyltransferases/metabolism , Nucleotidyltransferases/genetics , Capsid Proteins/metabolism , Capsid Proteins/immunology , RNA Virus Infections/immunology , RNA Virus Infections/metabolism , Interferons/metabolism , Interferons/immunology , Bass/immunology , Bass/virology , Bass/metabolism , Fish Proteins/metabolism , Fish Proteins/genetics , Fish Proteins/immunology
15.
Fish Shellfish Immunol ; 151: 109718, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38909635

ABSTRACT

Receptors of type I interferon (IFNR) play a vital role in the antiviral immune response. However, little is known about the negative regulatory role of the IFNR. Nervous necrosis virus (NNV) is one of the most significant viruses in cultured fish, resulting in great economic losses for the aquaculture industry. In this study, two orange-spotted grouper (Epinephelus coioides) cytokine receptor family B (CRFB) members, EcCRFB3 and EcCRFB4 were cloned and characterized from NNV infected grouper brain (GB) cells. The open reading frame (ORF) of EcCRFB3 consists of 852 bp encoding 283 amino acids, while EcCRFB4 has an ORF of 990 bp encoding 329 amino acids. The mRNA levels of EcCRFB3 or EcCRFB4 were significantly upregulated after NNV infection and the stimulation of poly (I:C) or NNV-encoded Protein A. In addition, EcCRFB3 or EcCRFB4 overexpression facilitated NNV replication, whereas EcCRFB3 or EcCRFB4 silencing resisted NNV replication. Overexpressed EcCRFB3 or EcCRFB4 inhibited the expression of IFN-I-induced ISGs. Taken together, our research provides the first evidence in fish demonstrating the role of IFNRs to regulate the IFN signaling pathway negatively. Our findings enrich the understanding of the functions of IFNRs and reveal a novel escape mechanism of NNV.


Subject(s)
Amino Acid Sequence , Bass , Fish Diseases , Fish Proteins , Gene Expression Regulation , Immunity, Innate , Nodaviridae , RNA Virus Infections , Virus Replication , Animals , Nodaviridae/physiology , Fish Diseases/immunology , Fish Diseases/virology , RNA Virus Infections/immunology , RNA Virus Infections/veterinary , Fish Proteins/genetics , Fish Proteins/immunology , Bass/immunology , Bass/genetics , Immunity, Innate/genetics , Gene Expression Regulation/immunology , Phylogeny , Sequence Alignment/veterinary , Receptors, Cytokine/genetics , Receptors, Cytokine/immunology , Gene Expression Profiling/veterinary , Interferons/immunology , Interferons/genetics
16.
Sci Rep ; 14(1): 10645, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724583

ABSTRACT

Dyslipidaemias is the leading risk factor of several major cardiovascular diseases (CVDs), but there is still a lack of sufficient evidence supporting a causal role of lipoprotein subspecies in CVDs. In this study, we comprehensively investigated several lipoproteins and their subspecies, as well as other metabolites, in relation to coronary heart disease (CHD), heart failure (HF) and ischemic stroke (IS) longitudinally and by Mendelian randomization (MR) leveraging NMR-measured metabolomic data from 118,012 UK Biobank participants. We found that 123, 110 and 36 analytes were longitudinally associated with myocardial infarction, HF and IS (FDR < 0.05), respectively, and 25 of those were associated with all three outcomes. MR analysis suggested that genetically predicted levels of 70, 58 and 7 analytes were associated with CHD, HF and IS (FDR < 0.05), respectively. Two analytes, ApoB/ApoA1 and M-HDL-C were associated with all three CVD outcomes in the MR analyses, and the results for M-HDL-C were concordant in both observational and MR analyses. Our results implied that the apoB/apoA1 ratio and cholesterol in medium size HDL were particularly of importance to understand the shared pathophysiology of CHD, HF and IS and thus should be further investigated for the prevention of all three CVDs.


Subject(s)
Cardiovascular Diseases , Mendelian Randomization Analysis , Humans , Cardiovascular Diseases/genetics , Male , Female , Risk Factors , Middle Aged , Magnetic Resonance Spectroscopy/methods , Apolipoprotein A-I/blood , Apolipoprotein A-I/genetics , Aged , Cholesterol, HDL/blood , Coronary Disease/genetics , Metabolomics/methods , Apolipoprotein B-100/genetics , Ischemic Stroke/genetics , Ischemic Stroke/blood , Ischemic Stroke/epidemiology , Heart Failure/genetics
18.
Nat Commun ; 15(1): 4659, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38821939

ABSTRACT

In the absence of externally applied mechanical loading, it would seem counterintuitive that a solid particle sitting on the surface of another solid could not only sink into the latter, but also continue its rigid-body motion towards the interior, reaching a depth as distant as thousands of times the particle diameter. Here, we demonstrate such a case using in situ microscopic as well as bulk experiments, in which diamond nanoparticles ~100 nm in size move into iron up to millimeter depth, at a temperature about half of the melting point of iron. Each diamond nanoparticle is nudged as a whole, in a displacive motion towards the iron interior, due to a local stress induced by the accumulation of iron atoms diffusing around the particle via a short and easy interfacial channel. Our discovery underscores an unusual mass transport mode in solids, in addition to the familiar diffusion of individual atoms.

19.
Cell Biol Toxicol ; 40(1): 40, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38797732

ABSTRACT

MYBL1 is a strong transcriptional activator involved in the cell signaling. However, there is no systematic study on the role of MYBL1 in atherosclerosis. The aim of this study is to elucidate the role and mechanism of MYBL1 in atherosclerosis. GSE28829, GSE43292 and GSE41571 were downloaded from NCBI for differentially expressed analysis. The expression levels of MYBL1 in atherosclerotic plaque tissue and normal vessels were detected by qRT-PCR, Western blot and Immunohistochemistry. Transwell and CCK-8 were used to detect the migration and proliferation of HUVECs after silencing MYBL1. RNA-seq, Western blot, qRT-PCR, Luciferase reporter system, Immunofluorescence, Flow cytometry, ChIP and CO-IP were used to study the role and mechanism of MYBL1 in atherosclerosis. The microarray data of GSE28829, GSE43292, and GSE41571 were analyzed and intersected, and then MYBL1 were verified. MYBL1 was down-regulated in atherosclerotic plaque tissue. After silencing of MYBL1, HUVECs were damaged, and their migration and proliferation abilities were weakened. Overexpression of MYBL1 significantly enhanced the migration and proliferation of HUVECs. MYBL1 knockdown induced abnormal autophagy in HUVEC cells, suggesting that MYBL1 was involved in the regulation of HUVECs through autophagy. Mechanistic studies showed that MYBL1 knockdown inhibited autophagosome and lysosomal fusion in HUVECs by inhibiting PLEKHM1, thereby exacerbating atherosclerosis. Furthermore, MYBL1 was found to repress lipid accumulation in HUVECs after oxLDL treatment. MYBL1 knockdown in HUVECs was involved in atherosclerosis by inhibiting PLEKHM1-induced autophagy, which provided a novel target of therapy for atherosclerosis.


Subject(s)
Atherosclerosis , Autophagy , Cell Movement , Cell Proliferation , Down-Regulation , Human Umbilical Vein Endothelial Cells , Animals , Humans , Atherosclerosis/metabolism , Atherosclerosis/genetics , Atherosclerosis/pathology , Autophagy/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Down-Regulation/genetics , Human Umbilical Vein Endothelial Cells/metabolism , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/genetics , Plaque, Atherosclerotic/metabolism , Plaque, Atherosclerotic/genetics , Plaque, Atherosclerotic/pathology , Trans-Activators/metabolism , Trans-Activators/genetics
20.
Biomed Pharmacother ; 175: 116601, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38749177

ABSTRACT

Alzheimer's disease (AD) comprises a group of neurodegenerative disorders with some changes in the brain, which could lead to the deposition of certain proteins and result in the degeneration and death of brain cells. Patients with AD manifest primarily as cognitive decline, psychiatric symptoms, and behavioural disorders. Short-chain fatty acids (SCFAs) are a class of saturated fatty acids (SFAs) produced by gut microorganisms through the fermentation of dietary fibre ingested. SCFAs, as a significant mediator of signalling, can have diverse physiological and pathological roles in the brain through the gut-brain axis, and play a positive effect on AD via multiple pathways. Firstly, differences in SCFAs and microbial changes have been stated in AD cases of humans and mice in this paper. And then, mechanisms of three main SCFAs in treating with AD have been summarized, as well as differences of gut bacteria. Finally, functions of SCFAs played in regulating intestinal flora homeostasis, modulating the immune system, and the metabolic system, which were considered to be beneficial for the treatment of AD, have been elucidated, and the key roles of gut bacteria and SCFAs were pointed out. All in all, this paper provides an overview of SCFAs and gut bacteria in AD, and can help people to understand the importance of gut-brain axis in AD.


Subject(s)
Alzheimer Disease , Brain-Gut Axis , Brain , Fatty Acids, Volatile , Gastrointestinal Microbiome , Humans , Fatty Acids, Volatile/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/microbiology , Animals , Gastrointestinal Microbiome/physiology , Brain-Gut Axis/physiology , Brain/metabolism
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