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1.
Nature ; 612(7940): 519-527, 2022 12.
Article in English | MEDLINE | ID: mdl-36477534

ABSTRACT

In mice and humans, sleep quantity is governed by genetic factors and exhibits age-dependent variation1-3. However, the core molecular pathways and effector mechanisms that regulate sleep duration in mammals remain unclear. Here, we characterize a major signalling pathway for the transcriptional regulation of sleep in mice using adeno-associated virus-mediated somatic genetics analysis4. Chimeric knockout of LKB1 kinase-an activator of AMPK-related protein kinase SIK35-7-in adult mouse brain markedly reduces the amount and delta power-a measure of sleep depth-of non-rapid eye movement sleep (NREMS). Downstream of the LKB1-SIK3 pathway, gain or loss-of-function of the histone deacetylases HDAC4 and HDAC5 in adult brain neurons causes bidirectional changes of NREMS amount and delta power. Moreover, phosphorylation of HDAC4 and HDAC5 is associated with increased sleep need, and HDAC4 specifically regulates NREMS amount in posterior hypothalamus. Genetic and transcriptomic studies reveal that HDAC4 cooperates with CREB in both transcriptional and sleep regulation. These findings introduce the concept of signalling pathways targeting transcription modulators to regulate daily sleep amount and demonstrate the power of somatic genetics in mouse sleep research.


Subject(s)
Signal Transduction , Sleep Duration , Transcription, Genetic , Animals , Mice , Gene Expression Regulation , Phosphorylation , Signal Transduction/physiology , Sleep, Slow-Wave/genetics , Gene Expression Profiling
2.
Plant J ; 119(1): 332-347, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38700955

ABSTRACT

The target of rapamycin (TOR) kinase serves as a central regulator that integrates nutrient and energy signals to orchestrate cellular and organismal physiology in both animals and plants. Despite significant advancements having been made in understanding the molecular and cellular functions of plant TOR kinases, the upstream regulators that modulate TOR activity are not yet fully elucidated. In animals, the translationally controlled tumor protein (TCTP) is recognized as a key player in TOR signaling. This study reveals that two TCTP isoforms from Cucumis sativus, when introduced into Arabidopsis, are instrumental in balancing growth and defense mechanisms against the fungal pathogen Golovinomyces cichoracearum. We hypothesize that plant TCTPs act as upstream regulators of TOR in response to powdery mildew caused by Podosphaera xanthii in Cucumis. Our research further uncovers a stable interaction between CsTCTP and a small GTPase, CsRab11A. Transient transformation assays indicate that CsRab11A is involved in the defense against P. xanthii and promotes the activation of TOR signaling through CsTCTP. Moreover, our findings demonstrate that the critical role of TOR in plant disease resistance is contingent upon its regulated activity; pretreatment with a TOR inhibitor (AZD-8055) enhances cucumber plant resistance to P. xanthii, while pretreatment with a TOR activator (MHY-1485) increases susceptibility. These results suggest a sophisticated adaptive response mechanism in which upstream regulators, CsTCTP and CsRab11A, coordinate to modulate TOR function in response to P. xanthii, highlighting a novel aspect of plant-pathogen interactions.


Subject(s)
Ascomycota , Cucumis sativus , Plant Diseases , Plant Proteins , Cucumis sativus/microbiology , Cucumis sativus/genetics , Cucumis sativus/metabolism , Ascomycota/pathogenicity , Ascomycota/physiology , Plant Diseases/microbiology , Plant Diseases/immunology , Plant Proteins/metabolism , Plant Proteins/genetics , Arabidopsis/microbiology , Arabidopsis/genetics , Arabidopsis/metabolism , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Tumor Protein, Translationally-Controlled 1 , Signal Transduction , Plants, Genetically Modified , Gene Expression Regulation, Plant , Disease Resistance/genetics
3.
Cancer Metastasis Rev ; 43(3): 941-957, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38436892

ABSTRACT

Metastasis remains the principal trigger for relapse and mortality across diverse cancer types. Circulating tumor cells (CTCs), which originate from the primary tumor or its metastatic sites, traverse the vascular system, serving as precursors in cancer recurrence and metastasis. Nevertheless, before CTCs can establish themselves in the distant parenchyma, they must overcome significant challenges present within the circulatory system, including hydrodynamic shear stress (HSS), oxidative damage, anoikis, and immune surveillance. Recently, there has been a growing body of compelling evidence suggesting that a specific subset of CTCs can persist within the bloodstream, but the precise mechanisms of their survival remain largely elusive. This review aims to present an outline of the survival challenges encountered by CTCs and to summarize the recent advancements in understanding the underlying survival mechanisms, suggesting their implications for cancer treatment.


Subject(s)
Neoplasms , Neoplastic Cells, Circulating , Neoplastic Cells, Circulating/pathology , Humans , Neoplasms/pathology , Neoplasms/therapy , Animals , Cell Survival
4.
J Clin Immunol ; 44(8): 179, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39150626

ABSTRACT

OBJECTIVES: To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. METHODS: This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. RESULTS: A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48 mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. CONCLUSION: HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5 mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.


Subject(s)
Agammaglobulinemia , Autoimmune Diseases , Infections , Rituximab , Humans , Rituximab/therapeutic use , Rituximab/adverse effects , Female , Male , Agammaglobulinemia/epidemiology , Middle Aged , Autoimmune Diseases/drug therapy , Autoimmune Diseases/complications , Retrospective Studies , Adult , Infections/etiology , Infections/epidemiology , Aged , Glucocorticoids/therapeutic use , Risk Factors , China/epidemiology , Immunoglobulin G/blood
5.
Small ; : e2405921, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39279613

ABSTRACT

Hard carbon (HC) stands out as the most prospective anode for sodium-ion batteries (SIBs) with significant potential for commercial applications. However, some long-standing and intractable obstacles, like low first coulombic efficiency (ICE), poor rate capability, storage capacity, and cycling stability, have severely hindered the conversion process from laboratory to commercialization. The above-mentioned issues are closely related to Na+ transfer kinetics, surface chemistry, and internal pseudo-graphitic carbon content. Herein, constructing molybdenum-modified hard carbon solid spheres (Mo2C/HC-5.0), both the ion transfer kinetics, surface chemistry, and internal pseudo-graphitic carbon content are comprehensively improved. Specifically, Mo2C/HC-5.0 with higher pseudo-graphitic carbon content provides a large number of active sites and a more stable layer structure, resulting in improved sodium storage capacity, rate performance, and cycling stability. Moreover, the lower defect density and specific surface area of Mo2C/HC-5.0 further enhance ICE and sodium storage capacity. Consequently, the Mo2C/HC-5.0 anode achieves a high capacity of 410.7 mA h g-1 and an ICE of 83.9% at 50 mA g-1. Furthermore, the material exhibits exceptional rate capability and cycling stability, maintaining a capacity of 202.8 mA h g-1 at 2 A g-1 and 214.9 mA h g-1 after 800 cycles at 1 A g-1.

6.
Int J Obes (Lond) ; 48(5): 646-653, 2024 May.
Article in English | MEDLINE | ID: mdl-38297032

ABSTRACT

BACKGROUND: We aim to assess the associations between the change in neighborhood socioeconomic score (SES) between birth and 6 years and childhood weight status and body composition from 6 to 13 years. METHODS: Data for 3909 children from the Generation R Study, a prospective population-based cohort in the Netherlands were analyzed. The change in neighborhood SES between birth and 6 years was defined as static-high, static-middle, static-low, upward, and downward mobility. Child body mass index (BMI), overweight and obesity (OWOB), fat mass index (FMI) and lean mass index (LMI) were measured at age 6, 10, and 13 years. The associations were explored using generalized estimating equations. The effect modification by child sex was examined. RESULTS: In total, 19.5% and 18.1% of children were allocated to the upward mobility and downward mobility neighborhood SES group. The associations between the change in neighborhood SES and child weight status and body composition were moderated by child sex (p < 0.05). Compared to girls in the static-high group, girls in the static-low group had relatively higher BMI-SDS (ß, 95% confidence interval (CI): 0.24, 0.09-0.40) and higher risk of OWOB (RR, 95% CI: 1.98, 1.35-2.91), together with higher FMI-SDS (ß, 95% CI: 0.27, 0.14-0.41) and LMI-SDS (ß, 95% CI: 0.18, 0.03-0.33). The associations in boys were not significant. CONCLUSIONS: An increased BMI and fat mass, and higher risk of OWOB from 6 to 13 years were evident in girls living in a low-SES neighborhood or moving downward from a high- to a low-SES neighborhood. Support for children and families from low-SES neighborhoods is warranted.


Subject(s)
Body Composition , Pediatric Obesity , Social Class , Humans , Female , Male , Child , Body Composition/physiology , Adolescent , Netherlands/epidemiology , Pediatric Obesity/epidemiology , Prospective Studies , Child, Preschool , Body Mass Index , Residence Characteristics/statistics & numerical data , Infant , Infant, Newborn , Neighborhood Characteristics/statistics & numerical data , Body Weight/physiology
7.
J Viral Hepat ; 31(2): 78-87, 2024 02.
Article in English | MEDLINE | ID: mdl-38111976

ABSTRACT

This study aims to identify clinically meaningful sex differences in efficacy and selected safety adverse events for the treatment of chronic hepatitis C virus infection (HCV) or HIV/HCV co-infection in those receiving combination direct-acting antiviral (DAA) regimens. Our assessment was based on adult trial participants treated at the approved DAA dosage and treatment duration from 40 phase 3 clinical trials submitted to the FDA. Female enrollment ranged from 11% to 54% (overall mean 38%). Females with HCV genotype (GT) 1 or 3 infection had statistically significant higher unadjusted or covariant-adjusted odds of achieving sustained virologic response at post-treatment Week 12 (SVR12) compared with males. Odds ratios favouring females were observed among Whites and those ≥40 years of age with HCV GT1 or 3 infections, and among those ≥50 years of age, non-cirrhotic and those with HCV GT3 infection who were treatment-experienced. These differences were not clinically relevant due to the high SVR12 rate achieved by females and males, overall or in subgroups. No differences were observed in SVR12 rates between HCV GT1 mono-infected and HCV GT1/ HIV-1 co-infected participants. Numerically, more females reported headache, fatigue and nausea compared to males, but the differences were small and predominately Grade 1 or 2 severity. Discontinuation rates for any reason or due to an adverse event were low and similar between the sexes. Our study demonstrated females successfully complete DAA regimens and achieve high SVR12 rates despite numerically higher adverse events for certain commonly reported events.


Subject(s)
HIV Infections , Hepatitis C, Chronic , Hepatitis C , Adult , Female , Humans , Male , Middle Aged , Antiviral Agents/adverse effects , Drug Therapy, Combination , Genotype , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , HIV Infections/complications , HIV Infections/drug therapy , Sex Characteristics , Sustained Virologic Response , Treatment Outcome , Clinical Trials, Phase III as Topic
8.
Rheumatology (Oxford) ; 63(4): 1113-1122, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-37522862

ABSTRACT

OBJECTIVE: To investigate the health-related quality of life (HR-QoL), work productivity and activity impairment and associated factors among patients with idiopathic inflammatory myopathy (IIM). METHODS: This was an observational, cross-sectional study. The 189 ambulatory patients with IIM were recruited from May 2019 to May 2022. HR-QoL was measured by the European Quality of Life 5-Dimension (EQ-5D) questionnaire. The Work Productivity and Activity Impairment (WPAI) questionnaire was used to evaluate work productivity and activity impairment. The IIM-related parameters were assessed by the 8-item Manual Muscle Test (MMT-8), Myositis Disease Activity Assessment visual analogue scale (MYOACT), Myositis Damage Index (MDI), Disease Activity Score (DAS) and Physician/Patient Global Assessment (PhGA/PtGA). Quantile regression and ordinal logistic regression were performed to identify the factors, considering EQ-5D or WPAI scores as dependent variables, respectively. RESULTS: Of the 189 IIM patients enrolled, 60% had DM, 13% had PM and 27% had clinical amyopathic DM. The median EQ-5D score was 1.00 (95% CI 0.73, 1.00), 28% were employed and 45% of overall work was impaired due to health problems. EQ-5D values were positively associated with MMT-8 and negatively with MYOACT, DAS, MDI-global and PhGA/PtGA. For the WPAI, activity impairment was associated with a lower MMT-8 score, older onset age and higher PhGA only in 25th-75th percentile. Increased PtGA was associated with increased activity and overall working productivity impairment in most quantiles (P<0.05). CONCLUSION: Multiple disease characteristics were associated with reduced HR-QoL or working productivity impairment in patients with IIM, especially for PtGA.


Subject(s)
Myositis , Quality of Life , Humans , Myositis/complications , Efficiency , Patient Reported Outcome Measures , Cross-Sectional Studies
9.
Respir Res ; 25(1): 382, 2024 Oct 19.
Article in English | MEDLINE | ID: mdl-39427175

ABSTRACT

This study explores the role and potential mechanisms of microRNA-125b-5p (miR-125b-5p) in pulmonary fibrosis (PF). PF is a typical outcome of many chronic lung diseases, with poor prognosis and the lack of appropriate medical treatment because PF's molecular mechanisms remain poorly understood. In this study, using in vitro and in vivo analyses, we find that miR-125b-5p is likely a potent regulator of lung fibrosis. The findings reveal that, on the one hand, miR-125b-5p not only specifically decreases in the epithelial-mesenchymal transition (EMT) of lung epithelial cells, but also shows a downregulation trend in the lung tissues of mice with PF. On the other hand, overexpression of miR-125b-5p on the cellular and animal levels downregulates EMT and fibrotic phenotypes, respectively. To clarify the molecular mechanism of the "therapeutic" effect of miR-125b-5p, we use the target prediction tool combined with a dual luciferase assay and complete a rescue experiment by constructing the overexpression vector of the target gene Bcl-2 homologous antagonist/ killer (BAK1), thus confirming that miR-125b-5p can effectively inhibit EMT and fibrosis process by targeting BAK1 gene. MiR-125b-5p inhibits the EMT in lung epithelial cells by negatively regulating BAK1, while overexpression of miR-125b-5p can alleviate lung fibrosis. The findings suggest that MiR-125b-5p/BAK1 can serve as a potential treatment target for PF.


Subject(s)
Epithelial-Mesenchymal Transition , MicroRNAs , Pulmonary Fibrosis , Transforming Growth Factor beta1 , bcl-2 Homologous Antagonist-Killer Protein , Animals , Humans , Male , Mice , bcl-2 Homologous Antagonist-Killer Protein/metabolism , bcl-2 Homologous Antagonist-Killer Protein/genetics , Epithelial-Mesenchymal Transition/physiology , Epithelial-Mesenchymal Transition/genetics , Mice, Inbred C57BL , MicroRNAs/metabolism , MicroRNAs/genetics , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/pathology , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics
10.
BMC Cancer ; 24(1): 230, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38373930

ABSTRACT

BACKGROUND: This study aimed to identify metabolic subtypes in ESCA, explore their relationship with immune landscapes, and establish a metabolic index for accurate prognosis assessment. METHODS: Clinical, SNP, and RNA-seq data were collected from 80 ESCA patients from the TCGA database and RNA-seq data from the GSE19417 dataset. Metabolic genes associated with overall survival (OS) and progression-free survival (PFS) were selected, and k-means clustering was performed. Immune-related pathways, immune infiltration, and response to immunotherapy were predicted using bioinformatic algorithms. Weighted gene co-expression network analysis (WGCNA) was conducted to identify metabolic genes associated with co-expression modules. Lastly, cell culture and functional analysis were performed using patient tissue samples and ESCA cell lines to verify the identified genes and their roles. RESULTS: Molecular subtypes were identified based on the expression profiles of metabolic genes, and univariate survival analysis revealed 163 metabolic genes associated with ESCA prognosis. Consensus clustering analysis classified ESCA samples into three distinct subtypes, with MC1 showing the poorest prognosis and MC3 having the best prognosis. The subtypes also exhibited significant differences in immune cell infiltration, with MC3 showing the highest scores. Additionally, the MC3 subtype demonstrated the poorest response to immunotherapy, while the MC1 subtype was the most sensitive. WGCNA analysis identified gene modules associated with the metabolic index, with SLC5A1, NT5DC4, and MTHFD2 emerging as prognostic markers. Gene and protein expression analysis validated the upregulation of MTHFD2 in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA. CONCLUSION: The established metabolic index and identified metabolic genes offer potential for prognostic assessment and personalized therapeutic interventions for ESCA, underscoring the importance of targeting metabolism-immune interactions in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Prognosis , Esophageal Neoplasms/genetics , Esophageal Neoplasms/therapy , Immunotherapy , Up-Regulation
11.
Chem Res Toxicol ; 37(4): 528-539, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38507288

ABSTRACT

Quinoxaline 1,4-di-N-Oxides (QdNOs) have been used as synthetic antimicrobial agents in animal husbandry and aquaculture. The metabolism and potential toxicity have been also concerns in recently years. The metabolism investigations showed that there were 8 metabolites of Carbadox (CBX), 34 metabolites of Cyadox (CYA), 33 metabolites of Mequindox (MEQ), 35 metabolites of Olaquindox (OLA), and 56 metabolites of Quinocetone (QCT) in different animals. Among them, Cb3 and Cb8, M6, and O9 are metabolic residual markers of CBX, MEQ and OLA, which are associated with N → O reduction. Toxicity studies revealed that QdNOs exhibited severe tumorigenicity, cytotoxicity, and adrenal toxicity. Metabolic toxicology showed that toxicity of QdNOs metabolites might be related to the N → O group reduction, and some metabolites exhibited higher toxic effects than the precursor, which could provide guidance for further research on the metabolic toxicology of QdNOs and provide a wealth of information for food safety evaluation.


Subject(s)
Oxides , Quinoxalines , Animals , Quinoxalines/toxicity , Quinoxalines/metabolism , Carbadox , Oxidative Stress
12.
J Urban Health ; 101(4): 730-739, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38913271

ABSTRACT

Frailty is a dynamic condition encompassing physical, psychological, and social domains. While certain factors are associated with overall or specific frailty domains, research on the correlations between physical, psychological, and social frailty is lacking. This study aims to investigate the associations between physical, psychological, and social frailty in European older adults. The study involved 1781 older adults from the Urban Health Centres Europe project. Baseline and 1-year follow-up data were collected on physical, psychological, and social frailty, along with covariates. Linear regression analyzed unidirectional associations, while cross-lagged panel modeling assessed bi-directional associations. Participants' mean age was 79.57 years (SD = 5.54) and over half were female (61.0%). Physical and psychological frailty showed bi-directional association (effect of physical frailty at baseline on psychological frailty at follow-up: ß = 0.14, 95%CI 0.09, 0.19; reversed direction: ß = 0.05, 95%CI 0.01, 0.09). Higher physical frailty correlated with increased social frailty (ß = 0.05, 95%CI 0.01, 0.68), but no association was found between social and psychological frailty. This longitudinal study found a reciprocal relationship between physical and psychological frailty in older adults. A relatively higher level of physical frailty was associated with a higher level of social frailty. There was no association between social and psychological frailty. These findings underscore the multifaceted interplay between various domains of frailty. Public health professionals should recognize the implications of these interconnections while crafting personalized prevention and care strategies. Further research is needed to confirm these findings and investigate underlying mechanisms.


Subject(s)
Frail Elderly , Frailty , Independent Living , Humans , Aged , Female , Male , Longitudinal Studies , Europe/epidemiology , Aged, 80 and over , Frail Elderly/psychology , Frail Elderly/statistics & numerical data , Frailty/epidemiology , Frailty/psychology , Geriatric Assessment
13.
Nature ; 558(7710): 435-439, 2018 06.
Article in English | MEDLINE | ID: mdl-29899451

ABSTRACT

Sleep and wake have global effects on brain physiology, from molecular changes1-4 and neuronal activities to synaptic plasticity3-7. Sleep-wake homeostasis is maintained by the generation of a sleep need that accumulates during waking and dissipates during sleep8-11. Here we investigate the molecular basis of sleep need using quantitative phosphoproteomic analysis of the sleep-deprived and Sleepy mouse models of increased sleep need. Sleep deprivation induces cumulative phosphorylation of the brain proteome, which dissipates during sleep. Sleepy mice, owing to a gain-of-function mutation in the Sik3 gene 12 , have a constitutively high sleep need despite increased sleep amount. The brain proteome of these mice exhibits hyperphosphorylation, similar to that seen in the brain of sleep-deprived mice. Comparison of the two models identifies 80 mostly synaptic sleep-need-index phosphoproteins (SNIPPs), in which phosphorylation states closely parallel changes of sleep need. SLEEPY, the mutant SIK3 protein, preferentially associates with and phosphorylates SNIPPs. Inhibition of SIK3 activity reduces phosphorylation of SNIPPs and slow wave activity during non-rapid-eye-movement sleep, the best known measurable index of sleep need, in both Sleepy mice and sleep-deprived wild-type mice. Our results suggest that phosphorylation of SNIPPs accumulates and dissipates in relation to sleep need, and therefore SNIPP phosphorylation is a molecular signature of sleep need. Whereas waking encodes memories by potentiating synapses, sleep consolidates memories and restores synaptic homeostasis by globally downscaling excitatory synapses4-6. Thus, the phosphorylation-dephosphorylation cycle of SNIPPs may represent a major regulatory mechanism that underlies both synaptic homeostasis and sleep-wake homeostasis.


Subject(s)
Brain/metabolism , Homeostasis , Phosphoproteins/analysis , Phosphoproteins/metabolism , Proteome/analysis , Proteomics , Sleep/physiology , Animals , Brain/physiology , Gain of Function Mutation , Male , Memory Consolidation/physiology , Mice , Mice, Inbred C57BL , Phosphorylation , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Proteome/metabolism , Sleep Deprivation/metabolism , Sleep Deprivation/physiopathology , Synapses/physiology , Wakefulness/physiology
14.
J Thromb Thrombolysis ; 57(1): 143-154, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37548902

ABSTRACT

The aim of this study was to identify the optimal anti-platelet therapy in older acute coronary syndrome (ACS) patients with a mean age ≥ 60 years by comparing the efficacy and safety of different anti-platelet therapies. The selection of antiplatelet therapy in older patients with ACS is a clinical challenge. Numerous evidences indicate that the de-escalation of dual anti-platelet therapy (DAPT) or P2Y12 inhibitor monotherapy may reduce bleeding risk without increasing thrombotic events. However, there is a lack of systematic reviews and optimal strategy analysis regarding older ACS patients. Randomized controlled trials (RCTs) of anti-platelet therapy in older ACS patients were identified. Major adverse cardiovascular events (MACE) were the primary outcome. Secondary outcomes included all death, cardiovascular death, myocardial infarction, stroke, stent thrombosis, and trial-defined major bleeding. Frequentist and Bayesian network meta-analyses were conducted. Treatments were ranked on posterior probability. Summary odds ratios (ORs) were estimated using Bayesian network meta-analysis. A total of 12 RCTs including 59,284 older ACS patients treated with five anti-platelet strategies were included. Ticagrelor monotherapy after 3 months DAPT was comparable to the other strategies (OR 0.73; 95% CI 0.32-1.6) in terms of MACE risk. Additionally, P score analysis and SUCRA Bayesian analysis showed that it was the most beneficial treatment for all deaths, cardiovascular death and revascularization. For safety, although there was no significant difference in direct comparisons, both SUCRA Bayesian (0.806) and P score (0.519) analysis suggested that ticagrelor monotherapy was the safest strategy. The current evidence demonstrated that ticagrelor monotherapy after 3 months DAPT may be a promising approach for achieving a more favorable balance between risk and benefit for older ACS patients, with a relatively low bleeding risk and without an increased risk of MACE events. Moreover, it remains the preferred option for clinical outcomes such as all death, CV death and revascularization. Further high-quality and long-term studies are required to validate anti-platelet therapies among older ACS patients.


Subject(s)
Acute Coronary Syndrome , Percutaneous Coronary Intervention , Thrombosis , Humans , Aged , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Ticagrelor/therapeutic use , Acute Coronary Syndrome/drug therapy , Network Meta-Analysis , Randomized Controlled Trials as Topic , Systematic Reviews as Topic , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Thrombosis/drug therapy , Treatment Outcome
15.
Plant Cell Rep ; 43(8): 196, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39009888

ABSTRACT

KEY MESSAGE: CsDGAT1A and CsDGAT2D play a positive regulatory role in cucumber's response to low-temperature stress and positively regulate the synthesis of triacylglycerol (TAG). Triacylglycerol (TAG), a highly abundant and significant organic compound in plants, plays crucial roles in plant growth, development, and stress responses. The final acetylation step of TAG synthesis is catalyzed by diacylglycerol acyltransferases (DGATs). However, the involvement of DGATs in cucumber's low-temperature stress response remains unexplored. This study focused on two DGAT genes, CsDGAT1A and CsDGAT2D, investigating their function in enhancing cucumber's low-temperature stress tolerance. Our results revealed that both proteins were the members of the diacylglycerol acyltransferase family and were predominantly localized in the endoplasmic reticulum. Functional analysis demonstrated that transient silencing of CsDGAT1A and CsDGAT2D significantly compromised cucumber's low-temperature stress tolerance, whereas transient overexpression enhanced it. Furthermore, the TAG content quantification indicated that CsDGAT1A and CsDGAT2D promoted TAG accumulation. In conclusion, this study elucidates the lipid metabolism mechanism in cucumber's low-temperature stress response and offers valuable insights for the cultivation of cold-tolerant cucumber plants.


Subject(s)
Cold Temperature , Cucumis sativus , Diacylglycerol O-Acyltransferase , Gene Expression Regulation, Plant , Plant Proteins , Triglycerides , Cucumis sativus/genetics , Cucumis sativus/enzymology , Triglycerides/metabolism , Triglycerides/biosynthesis , Diacylglycerol O-Acyltransferase/genetics , Diacylglycerol O-Acyltransferase/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified , Stress, Physiological/genetics , Cold-Shock Response/genetics
16.
Sleep Breath ; 28(4): 1679-1690, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38739211

ABSTRACT

OBJECTIVE: This investigation seeks to examine the association between serum vitamin D concentrations and the prevalence of sleep disorders, additionally elucidating the causal relationship via Mendelian Randomization (MR) analysis. MATERIALS AND METHODS: This research employed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016, focusing on adults aged 20-50 years reporting sleep disorders. The research encompassed 4913 American adults. Weighted multivariable logistic regression models and cubic spline analyses were utilized to evaluate the association between serum vitamin D concentrations and the incidence of sleep disorders. Additionally, a two-sample Mendelian Randomization analysis was performed to evaluate the potential causal link between serum vitamin D concentrations and the risk of sleep disorders. RESULTS: Within the 2011-2016 NHANES cohort of the U.S. population, a notable inverse association was detected between serum vitamin D concentrations and sleep disorders (ß = - 3.81, 95% CI: - 6.10 to - 1.52, p = 0.003). After multivariate adjustments, a higher incidence of sleep disorders was associated with lower vitamin D Concentrations (OR 1.52, 95% CI 1.10-2.10, trend p = 0.014). Restricted cubic spline regression analysis indicated a linear association between serum vitamin D concentrations and sleep disorders(non-linearity p > 0.05). Lastly, the two-sample MR analysis yielded evidence supporting a potential causal connection between serum vitamin D concentrations and sleep disorders, with each unit increase in genetically predicted serum vitamin D reducing the odds ratio to 0.78 (95% CI 0.61-0.99, p = 0.044). CONCLUSIONS: These results imply that lower vitamin D concentrations in the population might correlate with a heightened risk of sleep disorders, suggesting the importance of considering vitamin D supplementation when treating sleep disorders.


Subject(s)
Mendelian Randomization Analysis , Nutrition Surveys , Sleep Wake Disorders , Vitamin D , Humans , Adult , Middle Aged , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/blood , Sleep Wake Disorders/genetics , Vitamin D/blood , Male , Female , United States/epidemiology , Young Adult , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/blood , Vitamin D Deficiency/genetics
17.
Mikrochim Acta ; 191(5): 262, 2024 04 13.
Article in English | MEDLINE | ID: mdl-38613581

ABSTRACT

Rapid and sensitive detection of carcinoembryonic antigen (CEA) is of great significance for cancer patients. Here, molybdenum (Mo) was doped into bismuth oxide (Bi2O3) by one-pot hydrothermal method forming porous tremella Bi2MoO6 nanocomposites with a larger specific surface area than the spherical structure. Then, a new kind of hydrangea-like TiO2/Bi2MoO6 porous nanoflowers (NFs) was prepared by doping titanium into Bi2MoO6, where titanium dioxide (TiO2) grew in situ on the surface of Bi2MoO6 nanoparticles (NPs). The hydrangea-like structure provides larger specific surface area, higher electron transfer ability and biocompatibility as well as more active sites conducive to the attachment of anti-carcinoembryonic antigen (anti-CEA) to TiO2/Bi2MoO6 NFs. A novel label-free electrochemical immunosensor was then constructed for the quantitative detection of CEA using TiO2/Bi2MoO6 NFs as sensing platform, showing a good linear relationship with CEA in the concentration range 1.0 pg/mL ~ 1.0 mg/mL and a detection limit of 0.125 pg/mL (S/N = 3). The results achieved with the designed immunosensor are comparable with many existing immunosensors used for the detection of CEA in real samples.


Subject(s)
Biosensing Techniques , Bismuth , Hydrangea , Molybdenum , Humans , Biomarkers, Tumor , Carcinoembryonic Antigen , Porosity , Immunoassay
18.
Ren Fail ; 46(2): 2373279, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38967136

ABSTRACT

BACKGROUND AND OBJECTIVE: Chronic kidney disease (CKD) is a global health concern that is frequently associated with hypertension. Inflammation is an important factor in the development of both illnesses. The Dietary Inflammation Index (DII) has evolved as a way to measure how much a diet can cause inflammation, which may impact CKD, especially in hypertensive persons. The study's goal is to investigate the link between DII and the occurrence of CKD in hypertensive individuals. METHODS: This study examined data from 22940 hypertensive patients from 1999 to 2018 of the National Health and Nutrition Examination Survey (NHANES). The DII was computed using 28 dietary components. CKD was diagnosed based on the estimated glomerular filtration rate and urine albumin-to-creatinine ratio. The link between DII and CKD was explored using sampling-weighted logistic regression and restricted cubic splines. RESULTS: Higher DII scores were shown to be strongly related with an increased risk of CKD. In the fully adjusted model, this connection remained consistent across demographic and clinical categories. CONCLUSIONS: The study found a strong association between a pro-inflammatory diet and an elevated risk of CKD in hypertensive individuals, emphasizing the potential of dietary changes in CKD management.


Subject(s)
Diet , Hypertension , Inflammation , Nutrition Surveys , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/complications , Male , Female , Hypertension/epidemiology , Hypertension/complications , Middle Aged , Inflammation/epidemiology , Prevalence , Diet/adverse effects , Glomerular Filtration Rate , Adult , Risk Factors , Aged , Cross-Sectional Studies , United States/epidemiology , Logistic Models
19.
Int J Mol Sci ; 25(6)2024 Mar 17.
Article in English | MEDLINE | ID: mdl-38542376

ABSTRACT

MYB (myoblast) protein comes in large quantities and a wide variety of types and plays a role in most eukaryotes in the form of transcription factors (TFs). One of its important functions is to regulate plant responses to various stresses. However, the role of MYB TFs in regulating stress tolerance in strawberries is not yet well understood. Therefore, in order to investigate the response of MYB family members to abiotic stress in strawberries, a new MYB TF gene was cloned from Fragaria vesca (a diploid strawberry) and named FvMYB108 based on its structural characteristics and evolutionary relationships. After a bioinformatics analysis, it was determined that the gene belongs to the R2R3-MYB subfamily, and its conserved domain, phylogenetic relationships, predicted protein structure and physicochemical properties, subcellular localization, etc. were analyzed. After qPCR analysis of the expression level of FvMYB108 in organs, such as the roots, stems, and leaves of strawberries, it was found that this gene is more easily expressed in young leaves and roots. After multiple stress treatments, it was found that the target gene in young leaves and roots is more sensitive to low temperatures and salt stimulation. After these two stress treatments, various physiological and biochemical indicators related to stress in transgenic Arabidopsis showed corresponding changes, indicating that FvMYB108 may be involved in regulating the plant's ability to cope with cold and high-salt stress. Further research has found that the overexpression of this gene can upregulate the expression of AtCBF1, AtCOR47, AtERD10, and AtDREB1A related to low-temperature stress, as well as AtCCA1, AtRD29a, AtP5CS1, and AtSnRK2.4 related to salt stress, enhancing the ability of overexpressed plants to cope with stress.


Subject(s)
Arabidopsis , Fragaria , Arabidopsis/metabolism , Salt Tolerance/genetics , Fragaria/genetics , Fragaria/metabolism , Phylogeny , Genes, myb , Plant Proteins/metabolism , Plants, Genetically Modified/metabolism , Stress, Physiological/genetics , Gene Expression Regulation, Plant
20.
J Environ Manage ; 352: 120087, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38215592

ABSTRACT

Saline water has proven to be one of the alternative sources of freshwater for agricultural irrigation in water-scarce areas. However, the changes in farmland ecology caused by saline water irrigation remain unclear. In this study, six irrigation water salinities (CK: 1.3 dS m-1, S1: 3.4 dS m-1, S2: 7.1 dS m-1, S3: 10.6 dS m-1, S4: 14.1 dS m-1, S5: 17.7 dS m-1) were set in a three-year (2019, 2021-2022) experiment to investigate their effects on soil environment and greenhouse gas emissions in cotton fields under long-term saline water irrigation. Results show that soil salinity in the same layer increased as increasing water salinity. Soil moisture of S3-S5 increased significantly by 4.99-12.94%. There was no significant difference in soil organic matter content between CK and S1. Saline water irrigation increased soil ammonium nitrogen content by 0.57-49.26%, while decreasing nitrate nitrogen content by 1.43-32.03%. Soil CO2 and N2O emissions and CH4 uptake were lower in S1-S5 than in CK at different cotton growth stages. In addition, saline water irrigation reduced the global warming potential by 6.93-53.86%. A structural equation model was developed to show that soil salinity, moisture, and ammonium nitrogen content were negatively correlated with global warming potential, while organic matter and nitrate nitrogen had positive effects on global warming potential. Considering the comprehensive perspectives of gas emissions and cotton yield, irrigation water with salinity less than 10.6 dS m-1 could effectively reduce greenhouse gas emissions from cotton fields while maintaining stable cotton yields in the experimental area and similar region.


Subject(s)
Ammonium Compounds , Greenhouse Gases , Greenhouse Gases/analysis , Nitrates , Nitrous Oxide/analysis , Soil/chemistry , Agricultural Irrigation/methods , China , Saline Waters , Nitrogen , Agriculture , Fertilizers/analysis , Methane/analysis
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