ABSTRACT
tRNA is a central component of protein synthesis and the cell signaling network. One salient feature of tRNA is its heavily modified status, which can critically impact its function. Here, we show that mammalian ALKBH1 is a tRNA demethylase. It mediates the demethylation of N1-methyladenosine (m1A) in tRNAs. The ALKBH1-catalyzed demethylation of the target tRNAs results in attenuated translation initiation and decreased usage of tRNAs in protein synthesis. This process is dynamic and responds to glucose availability to affect translation. Our results uncover reversible methylation of tRNA as a new mechanism of post-transcriptional gene expression regulation.
Subject(s)
AlkB Homolog 1, Histone H2a Dioxygenase/metabolism , Gene Expression Regulation , Protein Biosynthesis/genetics , RNA, Transfer/metabolism , Adenosine/analogs & derivatives , Adenosine/metabolism , AlkB Homolog 1, Histone H2a Dioxygenase/genetics , Glucose/deficiency , HeLa Cells , Humans , Methylation , Polyribosomes/metabolismABSTRACT
Testicular fusion of Spodoptera litura occures during metamorphosis, which benefits sperms development. Previous research identified involvement of ECM-integrin interaction pathways, MMPs in testicular fusion, but the regulatory mechanism remains unclear. RNA-seq was performed to analyze long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in testes, aiming to uncover potential regulatory mechanisms of testicular fusion. 2150 lncRNAs, 2742 targeted mRNAs, and 347 miRNAs were identified in testes at three different developmental stages. Up-regulated DElncRNAs and DEmRNAs, as well as down-regulated DEmiRNAs, were observed during testicular fusion, while the opposite expression pattern was observed after fusion. Enrichment analysis of DEmRNAs revealed that cAMP signal pathway, ECM remodeling enzymes, ECM-integrin interaction pathways, and cell adhesion molecules were potentially associated with testicular fusion. The identified DElncRNA-DEmiRNA-DEmRNA regulatory network related to cAMP signal pathway, ECM remodeling enzymes suggests their roles during testicular fusion. Our research will provide new targets for studying the mechanism of testicular fusion.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Male , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Testis/metabolism , Spodoptera/genetics , Spodoptera/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Integrins/genetics , Gene Regulatory NetworksABSTRACT
The jasmonic acid (JA) signaling pathway is involved in the plant response to drought stress. JA and other hormones synergistically regulate the drought response in plants. However, the molecular mechanism underlying this synergism remains poorly defined. In the present study, transcriptome analyses of guard cells and quantitative PCR experiments revealed that MYC2 negatively regulated the negative regulator of ABA signaling, SlPP2C1, and the type-B response regulator in the cytokinin pathway, SlRR26, and this negative regulation was direct. SlRR26 overexpression reduced drought tolerance in transgenic tomatoes, whereas slrr26cr lines were more tolerant to drought. SlRR26 negatively modulated reactive oxygen species levels in stomata and stomatal closure through RobhB. Moreover, SlRR26 overexpression counteracted JA-mediated stomatal closure, suggesting that SlRR26 played a negative role in the JA-mediated drought response. These findings suggest that MYC2 plays a key role in JA-regulated stomatal closure under drought stress by inhibiting SlPP2C1 and SlRR26.
Subject(s)
Solanum lycopersicum , Transcription Factors , Transcription Factors/metabolism , Abscisic Acid/metabolism , Solanum lycopersicum/genetics , Osmoregulation , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological , Plant Stomata/physiology , Gene Expression Regulation, Plant , Plants/metabolism , Phosphoprotein Phosphatases/metabolism , DroughtsABSTRACT
Transfer RNAs (tRNAs) are essential for translation, and tRNA expression and modifications are regulated by many factors. However, the interplay between the microbiome and host tRNA profiles through host-microbiome interactions has not been explored. In this study, we investigated host-microbiome interactions via the tRNA profiling of four tissue types from germ-free and specific pathogen-free mice. Our analyses reveal that cytosolic and mitochondrial tRNA expression and tRNA modifications in the host are reprogrammed in a tissue-specific and microbiome-dependent manner. In terms of tRNA expression, the intestines and brains are more sensitive to the influence of the microbiome than the livers and kidneys. In terms of tRNA modifications, cytosolic tRNAs show more obvious changes in the livers and kidneys in the presence of the microbiome. Our findings reveal a previously unexplored relationship among the microbiome, tRNA abundance, and epitranscriptome in a mammalian host.
Subject(s)
Microbiota , Transcriptome , Animals , Mice , Microbiota/genetics , Mitochondria/genetics , RNA Processing, Post-Transcriptional , RNA, Transfer/genetics , RNA, Transfer/metabolismABSTRACT
BACKGROUND: Anisodus tanguticus (Maxim.) Pascher (A. tanguticus) is a valuable botanical for extracting tropane alkaloids, which are widely used in the pharmaceutical industry. Implementing appropriate cultivation methods can improve both the quality and yield of A. tanguticus. A two-year field experiment was conducted from 2021 to 2023 using a single-factor randomized complete block design replicated three times. The study examined the effects of different nutrient levels (nitrogen: 0, 75, 150, 225, 300, 375 kg/ha; phosphorus: 0, 600, 750, 900, 1050, 1200 kg/ha; potassium: 0, 75, 112.5, 150, 187.5, 225 kg/ha) on the growth, primary alkaloid contents, and alkaloid yield of A. tanguticus at different growth stages (S-Greening, S-Growing, S-Wilting; T-Greening, T-Growing, and T-Wilting) in both the roots and aboveground portions. RESULTS: Our results demonstrate that nutrient levels significantly affect the growth and alkaloid accumulation in A. tanguticus. High nitrogen levels (375 kg/ha) notably increased both root and aboveground biomass, while phosphorus had a minimal effect, especially on aboveground biomass. For alkaloid content (scopolamine, anisodamine, anisodine, atropine), a moderate nitrogen level (225 kg/ha) was most effective, followed by low potassium (75 kg/ha), with phosphorus showing a limited impact. Increased phosphorus levels led to a decrease in scopolamine content. During the T-Growing period, moderate nitrogen addition (225 kg/ha) yielded the highest alkaloid levels per unit area (205.79 kg/ha). In the T-Wilting period, low potassium (75 kg/ha) and low phosphorus (750 kg/ha) resulted in alkaloid levels of 146.91 kg/ha and 142.18 kg/ha, respectively. This indicates nitrogen has the most substantial effect on alkaloid accumulation, followed by potassium and phosphorus. The Douglas production function analysis suggests focusing on root biomass and the accumulation of scopolamine and atropine in roots to maximize alkaloid yield in A. tanguticus cultivation. CONCLUSIONS: Our findings show that the optimum harvesting period for A. tanguticus is the T-Wilting period, and that the optimal nitrogen addition is 225 kg/ha, the optimal potassium addition is 75 kg/ha, and the optimal phosphorus addition is 600 kg/ha or less.
Subject(s)
Alkaloids , Nitrogen , Nutrients , Phosphorus , Phosphorus/metabolism , Nitrogen/metabolism , Alkaloids/metabolism , Nutrients/metabolism , Potassium/metabolism , Plant Roots/metabolism , Plant Roots/growth & development , Ranunculaceae/metabolismABSTRACT
Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.
ABSTRACT
BACKGROUND: The increasing problems of drug and radiotherapy resistance in cervical cancer underscores the need for novel methods for its management. Reports indicate that the expression of MPC1 may be associated with the tumor microenvironment and the occurrence of ferroptosis in cervical cancer. The objective of this study was to visually illustrate the prognostic significance and immunological characterization of MPC1 in cervical cancer. METHODS: The expression profile and prognostic significance of MPC1 were analyzed using various databases, including UALCAN, TIMER2, GEPIA2, and Kaplan-Meier Plotter. TISIDB, TIMER2, and immunohistochemical analysis were used to investigate the correlation between MPC1 expression and immune infiltration. GO enrichment analysis, KEGG analysis, Reactome analysis, ConsensusPathDB, and GeneMANIA were used to visualize the functional enrichment of MPC1 and signaling pathways related to MPC1. The correlation analysis was carried out to examine the relationship between MPC1 and Ferroptosis gene in TIMER 2.0, ncFO, GEPIA Database and Kaplan-Meier Plotter. RESULTS: We demonstrated that the expression levels of MPC1 in cervical cancer tissues were lower than those in normal cervical tissues. Kaplan-Meier survival curves showed shorter overall survival in cervical cancer patients with low levels of MPC1 expression. The expression of MPC1 was related to the infiltrating levels of tumor-infiltrating immune cells in cervical cancer. Moreover, MPC1 expression was associated with the iron-mediated cell death pathway, and several important ferroptosis genes were upregulated in cervical cancer cells. Furthermore, after knocking down MPC1 in HeLa cells, the expression of these genes decreased. CONCLUSION: These findings indicate that MPC1 functions as a prognostic indicator and plays a role in the regulation of the ferroptosis pathway in cervical cancer.
Subject(s)
Biomarkers, Tumor , Ferroptosis , Tumor Microenvironment , Uterine Cervical Neoplasms , Female , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Ferroptosis/genetics , Gene Expression Regulation, Neoplastic , Kaplan-Meier Estimate , Mitochondrial Membrane Transport Proteins/genetics , Mitochondrial Membrane Transport Proteins/metabolism , Prognosis , Signal Transduction , Tumor Microenvironment/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/mortality , Monocarboxylic Acid TransportersABSTRACT
The objective of this study was to examine the lipid spectrum of aqueous humor (AH) in patients with neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy and to investigate the lipid alteration response to anti-vascular endothelial growth factor (anti-VEGF) treatment. Lipidomic analysis using ultra-high performance liquid chromatography-tandem mass spectrometry was conducted to compare the lipid profiles of the AH in NVG patients with those of a control group. Lipid changes in the AH of NVG patients before and after intravitreal conbercept injections were also evaluated. The identification of lipids showing differential expression was accomplished through both multivariate and univariate analyses. This study included 13 NVG patients and 20 control subjects. Based on LipidSearch software, 639 lipid species across 33 lipid classes were detected in the participants' AH. The combination of univariate and multivariate statistical analyses yielded 53 differentially expressed lipids (VIP >1 and P < 0.05). In addition, 9 lipids were found to be differentially expressed before and after the intravitreal conbercept injections in the NVG patients. Significant alterations in the metabolic pathways of glycerophospholipid and glycerolipid exhibited notable changes. Our results highlighted the lipid changes in patients' AH in relation to the progression of NVG, and indicated that the modified lipids could potentially be utilized as therapeutic targets for NVG.
Subject(s)
Angiogenesis Inhibitors , Aqueous Humor , Diabetic Retinopathy , Glaucoma, Neovascular , Intravitreal Injections , Lipidomics , Lipids , Vascular Endothelial Growth Factor A , Humans , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/metabolism , Aqueous Humor/metabolism , Male , Glaucoma, Neovascular/metabolism , Glaucoma, Neovascular/drug therapy , Glaucoma, Neovascular/etiology , Female , Angiogenesis Inhibitors/therapeutic use , Lipidomics/methods , Middle Aged , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolism , Lipids/analysis , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , Recombinant Fusion Proteins/therapeutic use , Aged , Intraocular Pressure , Lipid MetabolismABSTRACT
BACKGROUND: Rapid identification and classification of bats are critical for practical applications. However, species identification of bats is a typically detrimental and time-consuming manual task that depends on taxonomists and well-trained experts. Deep Convolutional Neural Networks (DCNNs) provide a practical approach for the extraction of the visual features and classification of objects, with potential application for bat classification. RESULTS: In this study, we investigated the capability of deep learning models to classify 7 horseshoe bat taxa (CHIROPTERA: Rhinolophus) from Southern China. We constructed an image dataset of 879 front, oblique, and lateral targeted facial images of live individuals collected during surveys between 2012 and 2021. All images were taken using a standard photograph protocol and setting aimed at enhancing the effectiveness of the DCNNs classification. The results demonstrated that our customized VGG16-CBAM model achieved up to 92.15% classification accuracy with better performance than other mainstream models. Furthermore, the Grad-CAM visualization reveals that the model pays more attention to the taxonomic key regions in the decision-making process, and these regions are often preferred by bat taxonomists for the classification of horseshoe bats, corroborating the validity of our methods. CONCLUSION: Our finding will inspire further research on image-based automatic classification of chiropteran species for early detection and potential application in taxonomy.
ABSTRACT
Mammalian cells utilize Akt-dependent signaling to deploy intracellular Glut4 toward cell surface to facilitate glucose uptake. Low-density lipoprotein receptor (LDLR) is the cargo receptor mediating endocytosis of apolipoprotein B-containing lipoproteins. However, signaling-controlled regulation of intracellular LDLR trafficking remains elusive. Here, we describe a unique amino acid stress response, which directs the deployment of intracellular LDLRs, causing enhanced LDL endocytosis, likely via Ca2+ and calcium/calmodulin-dependent protein kinase II-mediated signalings. This response is independent of induction of autophagy. Amino acid stress-induced increase in LDL uptake in vitro is comparable to that by pravastatin. In vivo, acute AAS challenge for up to 72 h enhanced the rate of hepatic LDL uptake without changing the total expression level of LDLR. Reducing dietary amino acids by 50% for 2 to 4 weeks ameliorated high fat diet-induced hypercholesterolemia in heterozygous LDLR-deficient mice, with reductions in both LDL and VLDL fractions. We suggest that identification of signaling-controlled regulation of intracellular LDLR trafficking has advanced our understanding of the LDLR biology, and may benefit future development of additional therapeutic strategies for treating hypercholesterolemia.
Subject(s)
Amino Acids , Receptors, LDL , Amino Acids/metabolism , Animals , Carrier Proteins/metabolism , Endocytosis , Lipoproteins/metabolism , Liver/metabolism , Mice , Receptors, LDL/genetics , Receptors, LDL/metabolismABSTRACT
Incidences of thyroid disease, which has long been hypothesized to be partially caused by exposure to thyroid hormone disrupting chemicals (TDCs), have rapidly increased in recent years. However, known TDCs can only explain a small portion (â¼1%) of in vitro human transthyretin (hTTR) binding activities in environmental samples, indicating the existence of unknown hTTR ligands. In this study, we aimed to identify the major environmental hTTR ligands by employing protein Affinity Purification with Nontargeted Analysis (APNA). hTTR binding activities were detected in all 11 indoor dust and 9 out of 10 sewage sludge samples by the FITC-T4 displacement assay. By using APNA, 31 putative hTTR ligands were detected including perfluorooctanesulfonate (PFOS). Two of the most abundant ligands were identified as hydrocarbon surfactants (e.g., dodecyl benzenesulfonate). Moreover, another abundant ligand was surprisingly identified as a disulfonate fluorescent brightener, 4,4'-bis(2-sulfostyryl)biphenyl sodium (CBS). CBS was validated as a nM-affinity hTTR ligand with an IC50 of 345 nM. In total, hydrocarbon surfactants and fluorescent brighteners explain 1.92-17.0 and 5.74-54.3% of hTTR binding activities in dust and sludge samples, respectively, whereas PFOS only contributed <0.0001%. Our study revealed for the first time that hydrocarbon sulfonates are previously overlooked hTTR ligands in the environment.
Subject(s)
Prealbumin , Prealbumin/metabolism , Ligands , Humans , Hydrocarbons , Fluorocarbons , Alkanesulfonic Acids , Dust , Sulfonic AcidsABSTRACT
The spikes of gramineous plants are composed of specialized units called spikelets. Two bracts at the spikelet bases are known as glumes. The spikelet glumes in barley are degenerated into threadlike structures. Here, we report a long glume mutant, lgm1, similar in appearance to a lemma with a long awn at the apex. Map-based cloning showed that the mutant lgm1 allele has an approximate 1.27 Mb deletion of in chromosome 2H. The deleted segment contains five putative high-confidence genes, among which HORVU.MOREX.r3.2HG0170820 encodes a C2H2 zinc finger protein, an ortholog of rice NSG1/LRG1 and an important candidate for the Lgm1 allele. Line GA01 with a long glume and short awn was obtained in progenies of crosses involving the lgm1 mutant. Interestingly, lsg1, a mutant with long glumes on lateral spikelets, was obtained in the progenies of the lgm1 mutant. The long glume variant increased the weight of kernels in the lateral spikelets and increased kernel uniformity across the entire spike, greatly improving the potential of six-rowed barley for malting. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01448-x.
ABSTRACT
BACKGROUND: The Asteraceae family, the largest and one of the most diverse families of angiosperms, presents significant challenges in taxonomic classification and systematic research due to its vast species diversity and morphological complexity. A comprehensive understanding of the chloroplast genomes within this family is essential for refining taxonomic classifications and advancing phylogenetic studies. METHODS AND RESULTS: In this study, we sequenced the complete chloroplast genomes of 14 Asteraceae species and conducted a thorough bioinformatic analysis of their characteristics. The chloroplast genomes, ranging from 150,907 bp to 152,858 bp, exhibit a typical quadripartite structure: a large single-copy (LSC) region (83,044 bp to 84,625 bp), a small single-copy (SSC) region (18,223 bp to 18,673 bp), and a pair of inverted repeats (IRs) (24,806 bp to 25,201 bp). These genomes encode 87 to 89 protein-coding genes (PCGs), 36 to 37 tRNA genes, and 8 rRNA genes, with high conservation in size, structure, gene content, and order. Comparative analysis with other Asteraceae species' chloroplast genomes revealed notable similarities and structural variations, particularly in the IR regions. Nucleotide polymorphism analysis identified four genes-trnY-GUA, trnE-UUC, ycf1, and rrn23-with higher Pi values, suggesting potential hotspots for evolutionary studies. Phylogenetic analysis using maximum likelihood (ML) and Bayesian inference (BI) approaches provided new insights, proposing the reclassification of Himalaiella auriculata and Jacobaea raphanifolia as independent genera, distinct from Saussurea and Senecio. CONCLUSIONS: This study presents a comprehensive analysis of the chloroplast genome structures and phylogenetic relationships of 14 Asteraceae species, offering critical data for future molecular identification, evolutionary biology, and population genetics research. The findings hold significant implications for the ongoing refinement of Asteraceae taxonomic classifications and enhance our understanding of the evolutionary dynamics within this complex family.
Subject(s)
Asteraceae , Genome, Chloroplast , Phylogeny , Genome, Chloroplast/genetics , Asteraceae/genetics , Asteraceae/classification , Chloroplasts/genetics , Evolution, Molecular , Sequence Analysis, DNA/methods , RNA, Transfer/geneticsABSTRACT
Anoikis emerges when a cell finds itself extricated from the appropriate extracellular matrix, leading to an interruption in integrin ligation and thus triggering programmed cellular demise. The cardinal role of Anoikis in the realms of tumor invasion and metastasis is undeniable, although our grasp on its precise influence within the convoluted landscape of cancer biology remains somewhat circumscribed. Notably, both the immune milieu of the tumor and its inherent aggression are correlated with the fluctuating variables of Anoikis. We conducted a thorough evaluation of the genes associated with anoikis and studied the regulatory patterns of these genes as well as the prognostic impact of anoikis in 33 different types of tumors. We provided functional annotations for the regulatory patterns linked to Anoikis. Additionally, we described the associations between immunological factors and genes associated with Anoikis. By applying gene set variation analysis (GSVA), we utilized the inherent abilities of 34 basic genes to calculate the Anoikis index. The Anoikis index is closely related to prognosis, immune microenvironment, immunotherapy, and other aspects. Our functional research revealed a correlation between immune cell infiltration, EMT, and a regulatory gene that is synonymous with adverse survival outcomes. In addition, our observations revealed a direct relationship between the expression of CEACAM5 and CEACAM6,the amplification of epithelial mesenchymal transition (EMT) phenomenon, and a decrease in survival outcomes.The potential therapeutic utility of anoikis-related genes was highlighted by the possible links between TME, clinical samples, genetic mutations, drug resistance, and immunotherapy.
Subject(s)
Anoikis , Neoplasms , Humans , Anoikis/genetics , Cell Line, Tumor , Neoplasms/geneticsABSTRACT
Acute lung injury (ALI) is still associated with high mortality. Growing evidence suggests that Club Cell Protein 16 (CC16) plays a protective role against ALI. However, the doses of recombinant CC16 (rCC16) used in preclinical studies are supraphysiological for clinical applications. Extracellular vesicles (EVs) are nanovesicles endogenously generated by mammalian cells. Our study demonstrated that CC16 is released via small EVs and EV-encapsulated CC16 (sEV-CC16) and has anti-inflammatory activities, which protect mice from lipopolysaccharide (LPS) or bacteria-induced ALI. Additionally, sEV-CC16 can activate the DNA damage repair signaling pathways. Consistent with this activity, we observed more severe DNA damage in lungs from Cc16 knockout (KO) than wild-type (WT) mice. Mechanistically, we elucidated that CC16 suppresses nuclear factor κB (NF-κB) signaling activation by binding to heat shock protein 60 (HSP60). We concluded that sEV-CC16 could be a potential therapeutic agent for ALI by inhibiting the inflammatory and DNA damage responses by reducing NF-κB signaling.
Subject(s)
Acute Lung Injury , NF-kappa B , Mice , Animals , NF-kappa B/metabolism , Lung/metabolism , Acute Lung Injury/drug therapy , Signal Transduction , Anti-Inflammatory Agents/pharmacology , Lipopolysaccharides/pharmacology , MammalsABSTRACT
BACKGROUND: Cervical spondylotic myelopathy (CSM) is the most common chronic spinal cord injury with poor surgical and neurologic recovery in the advanced stages of the disease. DTI parameters can serve as important biomarkers for CSM prognosis. The study aimed to investigate the predictive value of dynamic diffusion tensor imaging (DTI) for the postoperative outcomes of CSM. METHODS: One hundred and five patients with CSM who underwent surgery were included in this study. Patients were assessed using the Modified Japanese Orthopedic Association Score (mJOA) before and one year after surgery and then divided into groups with good (≥ 50%) and poor (< 50%) prognoses according to the rate of recovery. All patients underwent preoperative dynamic magnetic resonance imaging of the cervical spine, including T2WI and DTI in natural(N), extension (E), and flexion (F) positions. ROM, Cross-sectional area, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were measured at the narrowest level in three neck positions. Univariate and multivariate logistic regression were used to identify risk factors for poor postoperative recovery based on clinical characteristics, dynamic T2WI, and DTI parameters. Predictive models were developed for three different neck positions. RESULTS: Forty-four (41.9%) patients had a good postoperative prognosis, and 61 (58.1%) had a poor prognosis. Univariate analysis showed statistically significant differences in diabetes, number of compression segments, preoperative mJOA score, cross-sectional area ((Area-N), (Area-E), (Area-F)), ADC((ADC-N), (ADC-E), (ADC-F)) and FA (((FA-N), (FA-E), (FA-F)) (p < 0.05). Multivariable logistic regression showed that natural neck position: Area-N ([OR] 0.226; [CI] 0.069-0.732, p = 0.013),FA-N([OR]3.028;[CI]1.12-8.19,p = 0.029); extension ne-ck position: Area-E([OR]0.248;[CI]0.076-0.814,p = 0.021), FA-E([OR]4.793;[CI]1.737-13.228,p = 0.002);And flextion neck postion: Area-F([OR] 0.288; [CI] 0.095-0.87, p = 0.027),FA-F ([OR] 2.964; [CI] 1.126-7.801, p = 0.028) were independent risk factors for poor prognosis.The area under the curve (AUC) of the prediction models in the natural neck position, extension neck position, and flexion neck positions models were 0.708[(95% CI:0.608â¼0.808), P < 0.001]; 0.738 [(95% CI:0.641â¼0.835), P < 0.001]; 0.703 [(95% CI:0.602â¼0.803), P < 0.001], respectively. CONCLUSION: Dynamic DTI can predict postoperative outcomes in CSM. Reduced FA in the extension position is a valid predictor of poor postoperative neurological recovery in patients with CSM.
Subject(s)
Cervical Vertebrae , Diffusion Tensor Imaging , Spondylosis , Humans , Diffusion Tensor Imaging/methods , Female , Male , Middle Aged , Spondylosis/diagnostic imaging , Spondylosis/surgery , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Aged , Prognosis , Predictive Value of Tests , Treatment Outcome , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/surgery , AdultABSTRACT
OBJECTIVE: The objective of this study is to elucidate the causal association between asthma and alopecia areata (AA) through the application of Mendelian randomization (MR) analysis, leveraging summary data from genome-wide association studies (GWAS). Additionally, it explores potential mediating factors. MATERIALS AND METHODS: Mendelian randomization (MR) analysis was employed to investigate the causal relationship between asthma and AA using genetic instrumental variables (IVs) for asthma, 91 circulating inflammatory proteins, and AA extracted from large-scale GWAS. The primary analytical approach utilized the inverse-variance weighted (IVW) method, supplemented by weighted median and MR-Egger methods to assess robustness. Tests for heterogeneity and pleiotropy were conducted to ensure result reliability. Furthermore, the study examined the mediating role of circulating inflammatory proteins in the asthma-AA relationship. RESULTS: The findings revealed an increased risk of AA among asthma patients (odds ratio (OR) = 14.070; 95% confidence interval (CI) = 1.410-140.435; P = 0.024). Interleukin-33 (IL-33) emerged as a significant mediator in the asthma-AA relationship, explaining 13.1% of the mediation effect. Bidirectional Mendelian randomization analyses did not establish a causal effect of AA on asthma occurrence. CONCLUSION: This study, utilizing Mendelian Randomization, elucidates the causal link between asthma and AA, highlighting the mediating role of IL-33. These findings underscore the importance of considering AA risk in asthma management and offer insights for potential therapeutic strategies targeting IL-33. Future research should explore additional biomarkers and mediating mechanisms between asthma and AA to enhance treatment approaches and patient quality of life.
Subject(s)
Alopecia Areata , Asthma , Genome-Wide Association Study , Interleukin-33 , Mendelian Randomization Analysis , Humans , Alopecia Areata/genetics , Asthma/genetics , Asthma/epidemiology , Asthma/blood , Interleukin-33/genetics , Interleukin-33/blood , Mediation Analysis , Polymorphism, Single Nucleotide , Genetic Predisposition to Disease/geneticsABSTRACT
OBJECTIVE: To investigate the relationship of dyslipidemia and menopausal symptoms in Chinese menopausal women. MATERIAL AND METHODS: A total of 989 eligible participants with menopausal syndrome were recruited from outpatient clinics in several cities in China. Menopausal symptoms were assessed using the Chinese Menopause Rating Scale (CMRS), the Self-rating Depression Scale (SDS), and the Self-rating Anxiety Scale (SAS). Serum lipid profile was measured using enzyme colorimetry. The relationship between lipid profile and menopausal symptoms was assessed using Student's t test/nonparametric Mann-Whitney U test, Spearman's correlation test, and binary logistic regression analysis. RESULTS: Among the 989 patients, 527 had dyslipidemia while 462 did not. Patients with dyslipidemia had significantly higher Self-rating Anxiety Scale (SAS) scores than those without (p < 0.001), while there was no significant difference in Self-rating Depression Scale (SDS) scores. Patients without dyslipidemia had higher scores on the Chinese Menopause Rating Scale (CMRS) vascular dimension compared to those with dyslipidemia (p = 0.003). The correlation test revealed that variables associated with dyslipidemia included age (p = 0.031), CMRS hot flashes dimension score (P = 0.003), and SAS score (p < 0.001). Regression analysis demonstrated that BMI (OR: 1.08, 95% CI: 1.01-1.16, p = 0.027), SAS scores (OR = 1.10, 95% CI = 1.07-1.13), vasomotor dimension (OR = 0.89, 95% CI = 0.83-0.95), physical dimension (OR = 0.96, 95% CI = 0.93-1.00), and social dimension (OR = 0.84, 95% CI = 0.74-0.95) were independently associated with an increased risk of dyslipidemia. CONCLUSIONS: This study showed that anxiety was associated with an unfavorable lipid profile, and menopausal depression seemed to have no relationship with lipid profile, while vasomotor symptoms appeared to be a favorable factor for dyslipidemia in Chinese menopausal women.
ABSTRACT
Tetrabromobisphenol A (TBBPA), a widely-used brominated flame retardant, has been revealed to exert endocrine disrupting effects and induce adipogenesis. Given the high structural similarities of TBBPA analogues and their increasing exposure risks, their effects on lipid metabolism are necessary to be explored. Herein, 9 representative TBBPA analogues were screened for their interference on 3T3-L1 preadipocyte adipogenesis, differentiation of C3H10T1/2 mesenchymal stem cells (MSCs) to brown adipocytes, and lipid accumulation of HepG2 cells. TBBPA bis(2-hydroxyethyl ether) (TBBPA-BHEE), TBBPA mono(2-hydroxyethyl ether) (TBBPA-MHEE), TBBPA bis(glycidyl ether) (TBBPA-BGE), and TBBPA mono(glycidyl ether) (TBBPA-MGE) were found to induce adipogenesis in 3T3-L1 preadipocytes to different extends, as evidenced by the upregulated intracellular lipid generation and expressions of adipogenesis-related biomarkers. TBBPA-BHEE exhibited a stronger obesogenic effect than did TBBPA. In contrast, the test chemicals had a weak impact on the differentiation process of C3H10T1/2 MSCs to brown adipocytes. As for hepatic lipid formation test, only TBBPA mono(allyl ether) (TBBPA-MAE) was found to significantly promote triglyceride (TG) accumulation in HepG2 cells, and the effective exposure concentration of the chemical under oleic acid (OA) co-exposure was lower than that without OA co-exposure. Collectively, TBBPA analogues may perturb lipid metabolism in multiple tissues, which varies with the test tissues. The findings highlight the potential health risks of this kind of emerging chemicals in inducing obesity, non-alcoholic fatty liver disease (NAFLD) and other lipid metabolism disorders, especially under the conditions in conjunction with high-fat diets.