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1.
Rev Cardiovasc Med ; 25(4): 121, 2024 Apr.
Article in English | MEDLINE | ID: mdl-39076555

ABSTRACT

Following long-term hypertension, mechanical stretching and neuroendocrine stimulation, cause multiple heterogeneous cells of the heart to interact, and result in myocardial remodeling with myocardial hypertrophy and fibrosis. The immune system, specifically macrophages, plays a vital role in this process. Macrophages are heterogeneous and plastic. Regulated by factors such as microenvironment and cytokines, polarization can be divided into two main forms: M1/M2, with different polarizations playing different roles in left ventricular structural remodeling associated with hypertension. However, descriptions of macrophage phenotypes in hypertension-induced myocardial hypertrophy models are not completely consistent. This article summarizes the phenotypes of macrophages in several models, aiming to assist researchers in studying macrophage phenotypes in hypertension-induced left ventricular structural remodeling models.

2.
Ecotoxicol Environ Saf ; 282: 116676, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38986336

ABSTRACT

The liver toxicity of alkylphenols (APs) has been demonstrated in animal studies. However, relevant epidemiological evidence is still lacking in humans, especially during pregnancy. We obtained the levels of biochemical indicators of liver function in early (<13 weeks, mean gestation=9.80±1.96 weeks) and late (≥32 weeks, mean gestation = 37.23±2.45 weeks) pregnancies from 219 pregnant women in the Guangxi Zhuang birth cohort from 2015-2017. We also examined the serum levels of APs in these pregnant women in early pregnancy. The present study aimed to investigate the correlations between the exposure of pregnant women to APs and their serum liver function indices. The results of the generalized linear model (GLM) in this study revealed that nonylphenol (NP) was positively correlated with total bilirubin (TBIL) (P=0.04) in early pregnancy, and 4-n-nonylphenol (4-N-NP) was negatively correlated with glutamyl transferase (GGT) (P=0.012). In late pregnancy, NP was positively associated with TBIL (P=0.002), and 4-tert-octylphenol (4-T-OP) was positively correlated with alanine aminotransferase (ALT) (P=0.02). Restricted cubic spline (RCS) results revealed doseresponse relationships between NP and TBIL (Poverall=0.011) and between 4-N-NP and GGT (Poverall=0.007) in early pregnancy. In late pregnancy, there were doseresponse relationships between NP and TBIL (Poverall=0.001) and between 4-T-OP and ALT (Poverall=0.033). There was also a doseresponse relationship between NP volume and GGT with an inverted 'U' shape (Poverall=0.041, Pnonlinear=0.012). Bayesian kernel machine regression modeling (BKMR) revealed that TBIL increased significantly (P<0.05) with increasing levels of coexposure to APs in both early and late pregnancy. Overall, exposure to APs during pregnancy affects maternal liver function to varying degrees. The present study provides new epidemiological evidence that exposure to alkylphenols in pregnant women interferes with liver function.

3.
Yi Chuan ; 46(7): 560-569, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39016089

ABSTRACT

Genomic prediction has emerged as a pivotal technology for the genetic evaluation of livestock, crops, and for predicting human disease risks. However, classical genomic prediction methods face challenges in incorporating biological prior information such as the genetic regulation mechanisms of traits. This study introduces a novel approach that integrates mRNA transcript information to predict complex trait phenotypes. To evaluate the accuracy of the new method, we utilized a Drosophila population that is widely employed in quantitative genetics researches globally. Results indicate that integrating mRNA transcript data can significantly enhance the genomic prediction accuracy for certain traits, though it does not improve phenotype prediction accuracy for all traits. Compared with GBLUP, the prediction accuracy for olfactory response to dCarvone in male Drosophila increased from 0.256 to 0.274. Similarly, the accuracy for cafe in male Drosophila rose from 0.355 to 0.401. The prediction accuracy for survival_paraquat in male Drosophila is improved from 0.101 to 0.138. In female Drosophila, the accuracy of olfactory response to 1hexanol increased from 0.147 to 0.210. In conclusion, integrating mRNA transcripts can substantially improve genomic prediction accuracy of certain traits by up to 43%, with range of 7% to 43%. Furthermore, for some traits, considering interaction effects along with mRNA transcript integration can lead to even higher prediction accuracy.


Subject(s)
Drosophila , Genomics , RNA, Messenger , Animals , RNA, Messenger/genetics , Male , Genomics/methods , Female , Drosophila/genetics , Phenotype
4.
Nat Commun ; 15(1): 5994, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39013863

ABSTRACT

Chromatin remodeler ARID1A regulates gene transcription by modulating nucleosome positioning and chromatin accessibility. While ARID1A-mediated stage and lineage-restricted gene regulation during cell fate canalization remains unresolved. Using osteoclastogenesis as a model, we show that ARID1A transcriptionally safeguards the osteoclast (OC) fate canalization during proliferation-differentiation switching at single-cell resolution. Notably, ARID1A is indispensable for the transcriptional apparatus condensates formation with coactivator BRD4/lineage-specifying transcription factor (TF) PU.1 at Nfatc1 super-enhancer during safeguarding the OC fate canalization. Besides, the antagonist function between ARID1A-cBAF and BRD9-ncBAF complex during osteoclastogenesis has been validated with in vitro assay and compound mutant mouse model. Furthermore, the antagonistic function of ARID1A-"accelerator" and BRD9-"brake" both depend on coactivator BRD4-"clutch" during osteoclastogenesis. Overall, these results uncover sophisticated cooperation between chromatin remodeler ARID1A, coactivator, and lineage-specifying TF at super-enhancer of lineage master TF in a condensate manner, and antagonist between distinct BAF complexes in the proper and balanced cell fate canalization.


Subject(s)
Cell Differentiation , Cell Lineage , DNA-Binding Proteins , Osteoclasts , Osteogenesis , Transcription Factors , Animals , Transcription Factors/metabolism , Transcription Factors/genetics , Osteoclasts/metabolism , Osteoclasts/cytology , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Mice , Osteogenesis/genetics , Osteogenesis/physiology , NFATC Transcription Factors/metabolism , NFATC Transcription Factors/genetics , Chromatin Assembly and Disassembly , Gene Expression Regulation , Mice, Inbred C57BL , Cell Proliferation , Single-Cell Analysis , Bromodomain Containing Proteins , Nuclear Proteins
5.
ISME J ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39018220

ABSTRACT

Phenotypic plasticity, which involves phenotypic transformation in the absence of genetic change, may serve as a strategy for organisms to survive in complex and highly-fluctuating environments. However, its reaction norm, molecular basis, and evolution remain unclear in most organisms, especially microbial eukaryotes. In this study, we explored these questions by investigating the reaction norm, regulation, and evolution of phenotypic plasticity in the cosmopolitan marine free-living ciliates Glauconema spp., which undergo significant phenotypic changes in response to food shortages. This study led to the de novo assembly of macronuclear genomes using long-read sequencing, identified hundreds of differentially expressed genes associated with phenotypic plasticity in different life stages, validated the function of two of these genes, and revealed that the reaction norm of body shape in response to food density follows a power-law distribution. Purifying selection may be the dominant evolutionary force acting on the genes associated with phenotypic plasticity, and the overall data support the hypothesis that phenotypic plasticity is a trait maintained by natural selection. This study provides novel insight into the developmental genetics of phenotypic plasticity in non-model unicellular eukaryotes, and sheds light on the complexity and long evolutionary history of this important survival strategy.

6.
Nat Biomed Eng ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834752

ABSTRACT

The manufacturing of autologous chimaeric antigen receptor (CAR) T cells largely relies either on fed-batch and manual processes that often lack environmental monitoring and control or on bioreactors that cannot be easily scaled out to meet patient demands. Here we show that human primary T cells can be activated, transduced and expanded to high densities in a 2 ml automated closed-system microfluidic bioreactor to produce viable anti-CD19 CAR T cells (specifically, more than 60 million CAR T cells from donor cells derived from patients with lymphoma and more than 200 million CAR T cells from healthy donors). The in vitro secretion of cytokines, the short-term cytotoxic activity and the long-term persistence and proliferation of the cell products, as well as their in vivo anti-leukaemic activity, were comparable to those of T cells produced in a gas-permeable well. The manufacturing-process intensification enabled by the miniaturized perfusable bioreactor may facilitate the analysis of the growth and metabolic states of CAR T cells during ex vivo culture, the high-throughput optimization of cell-manufacturing processes and the scale out of cell-therapy manufacturing.

7.
Tree Physiol ; 44(7)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38905265

ABSTRACT

With climate warming and economic globalization, insect-microbe assemblages are becoming increasingly responsible for various devastating forest diseases worldwide. Japanese larch (Larix kaempferi) is extensively cultivated in China because of its high survival rate, rapid maturation and robust mechanical properties. Endoconidiophora fujiensis, an ophiostomatoid fungus associated with Ips subelongatus, has been identified as a lethal pathogen of L. kaempferi in Japan. However, there is a dearth of research on the pathogenicity of E. fujiensis in larches in China. Therefore, we investigated the pathogenicity of E. fujiensis in introduced L. kaempferi and indigenous larch (Larix olgensis) trees and compared the induced resistance responses to the pathogen in both tree species in terms of physiology and gene expression. Five-year-old saplings and 25-year-old adult trees of L. olgensis and L. kaempferi were inoculated in parallel during the same growing season. Endoconidiophora fujiensis exhibited high pathogenicity in both larch species, but particularly in L. kaempferi compared with L. olgensis adult trees; adult L. olgensis was more resistant to E. fujiensis than adult L. kaempferi, which was reflected in higher accumulation of defensive monoterpenes, such as myrcene, 3-carene and limonene and the earlier induction of defense genes catalase (CAT) and pathogenesis-related protein 1 (PR1). This study contributes to our understanding of the interactions between bark beetle-associated ophiostomatoid fungi and host larches, from phenotypic responses to alterations in secondary metabolites via defense- and metabolism-related gene activation, providing a valuable foundation for the management of larch diseases and pests in the future.


Subject(s)
Ascomycota , Disease Resistance , Larix , Plant Diseases , Larix/microbiology , Plant Diseases/microbiology , Ascomycota/physiology , Ascomycota/pathogenicity , China , Virulence
8.
J Cell Sci ; 137(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38700490

ABSTRACT

Hepatocyte organoids (HOs) generated in vitro are powerful tools for liver regeneration. However, previously reported HOs have mostly been fetal in nature with low expression levels of metabolic genes characteristic of adult liver functions, hampering their application in studies of metabolic regulation and therapeutic testing for liver disorders. Here, we report development of novel culture conditions that combine optimized levels of triiodothyronine (T3) with the removal of growth factors to enable successful generation of mature hepatocyte organoids (MHOs) of both mouse and human origin with metabolic functions characteristic of adult livers. We show that the MHOs can be used to study various metabolic functions including bile and urea production, zonal metabolic gene expression, and metabolic alterations in both alcoholic liver disease and non-alcoholic fatty liver disease, as well as hepatocyte proliferation, injury and cell fate changes. Notably, MHOs derived from human fetal hepatocytes also show improved hepatitis B virus infection. Therefore, these MHOs provide a powerful in vitro model for studies of human liver physiology and diseases. The human MHOs are potentially also a robust research tool for therapeutic development.


Subject(s)
Hepatocytes , Liver , Organoids , Hepatocytes/metabolism , Hepatocytes/cytology , Organoids/metabolism , Organoids/cytology , Humans , Animals , Mice , Liver/metabolism , Liver/cytology , Mice, Inbred C57BL , Cell Differentiation
9.
Proteome Sci ; 22(1): 5, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38693542

ABSTRACT

Hair is an advantageous biological sample due to its recordable, collectable, and storable nature. Hair's primary components are keratin and keratin-associated proteins. Owing to its abundance of cystine, keratin possesses impressive mechanical strength and chemical stability, formed by creating disulfide bonds as crosslinks within the protein peptide chain. Furthermore, keratin is cross-linked with keratin-associated proteins to create a complex network structure that provides the hair with strength and rigidity. Protein extraction serves as the foundation for hair analysis research. Bleaching hair causes damage to the structure between keratin and keratin-associated proteins, resulting in texture issues and hair breakage. This article outlines various physical treatment methods and lysate analysis that enhance the efficiency of hair protein extraction. The PLEE method achieves a three-fold increase in hair protein extraction efficiency when using a lysis solution containing SDS and combining high temperatures with intense shaking, compared to previous methods found in literature. We utilized the PLEE method to extract hair from both normal and damaged groups. Normal samples identified 156-157 proteins, including 51 keratin and keratin-associated proteins. The damaged group consisted of 155-158 identified proteins, of which 48-50 were keratin and keratin-associated proteins. Bleaching did not cause any notable difference in the protein identification of hair. However, it did reduce coverage of keratin and keratin-associated proteins significantly. Our hair protein extraction method provides extensive coverage of the hair proteome. Our findings indicate that bleaching damage results in subpar hair quality due to reduced coverage of protein primary sequences in keratin and keratin-associated proteins.

10.
Antioxidants (Basel) ; 13(5)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38790659

ABSTRACT

Hydrogen peroxide (H2O2) is a prevalent reactive oxygen species (ROS) found in cells and takes a central role in plant development and stress adaptation. The root apical meristem (RAM) has evolved strong plasticity to adapt to complex and changing environmental conditions. Recent advances have made great progress in explaining the mechanism of key factors, such as auxin, WUSCHEL-RELATED HOMEOBOX 5 (WOX5), PLETHORA (PLT), SHORTROOT (SHR), and SCARECROW (SCR), in the regulation of RAM activity maintenance. H2O2 functions as an emerging signaling molecule to control the quiescent center (QC) specification and stem cell niche (SCN) activity. Auxin is a key signal for the regulation of RAM maintenance, which largely depends on the formation of auxin regional gradients. H2O2 regulates the auxin gradients by the modulation of intercellular transport. H2O2 also modulates the expression of WOX5, PLTs, SHR, and SCR to maintain RAM activity. The present review is dedicated to summarizing the key factors in the regulation of RAM activity and discussing the signaling transduction of H2O2 in the maintenance of RAM activity. H2O2 is a significant signal for plant development and environmental adaptation.

11.
J Trace Elem Med Biol ; 84: 127460, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38703538

ABSTRACT

BACKGROUND: Exposure to metals during pregnancy can potentially influence blood pressure (BP) in children, but few studies have examined the mixed effects of prenatal metal exposure on childhood BP. We aimed to assess the individual and combined effects of prenatal metal and metalloid exposure on BP in preschool children. METHODS: A total of 217 mother-child pairs were selected from the Zhuang Birth Cohort in Guangxi, China. The maternal plasma concentrations of 20 metals [e.g. lead (Pb), rubidium (Rb), cesium (Cs), and zinc (Zn)] in early pregnancy were measured by inductively coupled plasmamass spectrometry. Childhood BP was measured in August 2021. The effects of prenatal metal exposure on childhood BP were explored by generalized linear models, restricted cubic spline and Bayesian kernel machine regression (BKMR) models. RESULTS: In total children, each unit increase in the log10-transformed maternal Rb concentration was associated with a 10.82-mmHg decrease (95% CI: -19.40, -2.24) in childhood diastolic BP (DBP), and each unit increase in the log10-transformed maternal Cs and Zn concentrations was associated with a 9.67-mmHg (95% CI: -16.72, -2.61) and 4.37-mmHg (95% CI: -8.68, -0.062) decrease in childhood pulse pressure (PP), respectively. The log10-transformed Rb and Cs concentrations were linearly related to DBP (P nonlinear=0.603) and PP (P nonlinear=0.962), respectively. Furthermore, an inverse association was observed between the log10-transformed Cs concentration and PP (ß =-12.18; 95% CI: -22.82, -1.54) in girls, and between the log10-transformed Rb concentration and DBP (ß =-12.54; 95% CI: -23.87, -1.21) in boys, while there was an increasing association between the log10-transformed Pb concentration and DBP there was an increasing in boys (ß =6.06; 95% CI: 0.36, 11.77). Additionally, a U-shaped relationship was observed between the log10-transformed Pb concentration and SBP (P nonlinear=0.015) and DBP (P nonlinear=0.041) in boys. Although there was no statistically signiffcant difference, there was an inverse trend in the combined effect of maternal metal mixture exposure on childhood BP among both the total children and girls in BKMR. CONCLUSIONS: Prenatal exposure to both individual and mixtures of metals and metalloids influences BP in preschool children, potentially leading to nonlinear and sex-specific effects.


Subject(s)
Blood Pressure , Maternal Exposure , Metalloids , Metals , Humans , Female , Blood Pressure/drug effects , Child, Preschool , Pregnancy , Maternal Exposure/adverse effects , Male , Metalloids/blood , Metals/blood , Adult , Prenatal Exposure Delayed Effects/chemically induced , Lead/blood , China , Zinc/blood , Bayes Theorem
12.
Aging (Albany NY) ; 16(8): 7043-7059, 2024 04 17.
Article in English | MEDLINE | ID: mdl-38637111

ABSTRACT

Osteoarthritis (OA) is a prevalent degenerative condition commonly observed in the elderly, leading to consequential disability. Despite notable advancements made in clinical strategies for OA, its pathogenesis remains uncertain. The intricate association between OA and metabolic processes has yet to receive comprehensive exploration. In our investigation, we leveraged public databases and applied machine learning algorithms, including WGCNA, LASSO, RF, immune infiltration analysis, and pathway enrichment analysis, to scrutinize the role of lipid metabolism-associated genes (LAGs) in the OA. Our findings identified three distinct biomarkers, and evaluated their expression to assess their diagnostic value in the OA patients. The exploration of immune infiltration in these patients revealed an intricate relationship between immune cells and the identified biomarkers. In addition, in vitro experiments, including qRT-PCR, Western blot, chondrocyte lipid droplets detection and mitochondrial fatty acid oxidation measurement, further verified abnormal expressions of selected LAGs in OA cartilage and confirmed the correlation between lipid metabolism and OA.


Subject(s)
Biomarkers , Lipid Metabolism , Machine Learning , Osteoarthritis , Humans , Lipid Metabolism/genetics , Osteoarthritis/genetics , Osteoarthritis/immunology , Osteoarthritis/metabolism , Biomarkers/metabolism , Algorithms , Chondrocytes/metabolism , Chondrocytes/immunology
13.
Sci Data ; 11(1): 344, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38582756

ABSTRACT

The research of plant seeds has always been a focus of agricultural and forestry research, and seed identification is an indispensable part of it. With the continuous application of artificial intelligence technology in the field of agriculture, seed identification through computer vision can effectively promote the development of agricultural and forestry wisdom. Data is the foundation of computer vision, but there is a lack of suitable datasets in the agricultural field. In this paper, a seed dataset named LZUPSD is established. A device based on mobile phones and macro lenses was established to acquire images. The dataset contains 4496 images of 88 different seeds. This dataset can not only be used as data for training deep learning models in the computer field, but also provide important data support for agricultural and forestry research. As an important resource in this field, this dataset plays a positive role in modernizing agriculture and forestry.


Subject(s)
Artificial Intelligence , Seeds , Agriculture , Forestry
14.
Ann Med ; 56(1): 2337740, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38574398

ABSTRACT

BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) is recognized as a crucial regulator in lipid metabolism. Acetyl-CoA carboxylases (ACACAs) play a role in the ß-oxidation of fatty acids. Yet, the functions of ANGPTL4 and ACACA in dyslipidemia of obstructive sleep apnea (OSA) remain unclear. METHODS: This study included 125 male OSA subjects from the Shanghai Sleep Health Study (SSHS) who were matched for age, body mass index (BMI), and lipid profile. Serum ANGPTL4 levels were measured via ELISA. The ANGPTL4 T266M variants of 4455 subjects along with their anthropometric, fasting biochemical, and standard polysomnographic parameters were collected. Linear regression was used to analyze the associations between quantitative traits and ANGPTL4 T266M. Molecular docking and molecular dynamic simulation were employed to compare the effects of the wild-type ANGPTL4 and its T266M mutation on ACACA. RESULTS: Serum ANGPTL4 levels significantly decreased with increasing OSA severity (non-OSA: 59.6 ± 17.4 ng/mL, mild OSA: 50.0 ± 17.5 ng/mL, moderate OSA: 46.3 ± 15.5 ng/mL, severe OSA: 19.9 ± 14.3 ng/mL, respectively, p = 6.02 × 10-16). No associations were found between T266M and clinical characteristics. Molecular docking indicated that mutant ANGTPL4 T266M had stronger binding affinity for the ACACA protein, compared with wild-type ANGPTL4. In terms of protein secondary structure, mutant ANGTPL4 T266M demonstrated greater stability than wild-type ANGPTL4. CONCLUSIONS: Serum ANGTPL4 levels were significantly decreased in OSA patients, particularly among individuals with severe OSA. Although functional ANGTPL4 T266M variants were not associated with lipid levels in OSA, ANGTPL4 T266M could enhance binding affinity for the ACACA protein, potentially regulating lipid metabolism.


Subject(s)
Acetyl-CoA Carboxylase , Sleep Apnea, Obstructive , Humans , Male , Angiopoietin-Like Protein 4/genetics , Lipid Metabolism/genetics , Molecular Docking Simulation , China , Sleep Apnea, Obstructive/genetics , Lipids
15.
J Dairy Sci ; 107(7): 4804-4821, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38428495

ABSTRACT

Johne's disease (JD) is an infectious enteric disease in ruminants, causing substantial economic loss annually worldwide. This work aimed to estimate JD's genetic parameters and the phenotypic and genetic trends by incorporating recent data. It also explores the feasibility of a national genetic evaluation for JD susceptibility in Holstein cattle in the United States. The data were extracted from a JD data repository, maintained at the Council on Dairy Cattle Breeding, and initially supplied by 2 dairy record processing centers. The data comprised 365,980 Holstein cows from 1,048 herds participating in a voluntary control program for JD. Two protocol kits, IDEXX Paratuberculosis Screening Ab Test (IDX) and Parachek 2 (PCK), were used to analyze milk samples with the ELISA technique. Test results from the first 5 parities were considered. An animal was considered infected if it had at least one positive outcome. The overall average of JD incidence was 4.72% in these US Holstein cattle. Genotypes of 78,964 SNP markers were used for 25,000 animals randomly selected from the phenotyped population. Variance components and genetic parameters were estimated based on 3 models, namely, a pedigree-only threshold model (THR), a single-step threshold model (ssTHR), and a single-step linear model (ssLR). The posterior heritability estimates of JD susceptibility were low to moderate: 0.11 to 0.16 based on the 2 threshold models and 0.05 to 0.09 based on the linear model. The average reliability of EBVs of JD susceptibility using single-step analysis for animals with or without phenotypes varied from 0.18 (THR) to 0.22 (ssLR) for IDX and from 0.14 (THR) to 0.18 (ssTHR and ssLR) for PCK. Despite no prior direct genetic selection against JD, the estimated genetic trends of JD susceptibility were negative and highly significant. The correlations of bulls' PTA with economically important traits such as milk yield, milk protein, milk fat, somatic cell score, and mastitis were low, indicating a nonoverlapping genetic selection process with traits in current genetic evaluations. Our results suggest the feasibility of reducing the JD incidence rate by incorporating it into the national genetic evaluation programs.


Subject(s)
Cattle Diseases , Genotype , Paratuberculosis , Phenotype , Animals , Cattle/genetics , Paratuberculosis/genetics , Cattle Diseases/genetics , Female , Milk , Breeding , United States
16.
Commun Biol ; 7(1): 383, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38553628

ABSTRACT

Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here we develop a strategy to determine the tumor clonality of three independent HCC cohorts of 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identify two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divided into classes, which we call shallow branching and deep branching. We find that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations are enriched in HCC with linear evolution, while TP53 mutations are the most frequent genetic alterations in HCC with non-linear models. Furthermore, we observe significant B cell enrichment in linear trees compared to non-linear trees suggesting the need for further research to uncover potential variations in immune cell types within genomically determined phylogeny types. These results hint at the possibility that tumor cells and their microenvironment may collectively influence the tumor evolution process.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Phylogeny , Oncogenes , Mutation , Tumor Microenvironment/genetics
17.
J Orthop Surg Res ; 19(1): 187, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38493285

ABSTRACT

BACKGROUND: Anterior cervical discectomy and fusion surgery (ACDF) is a common technique in treating degenerative cervical spondylosis. This study is to evaluate the changes of cervical muscles after ACDF and analyze the correlation between related muscle changes and clinical efficacy. METHODS: Sixty-five postoperative patients (single-level ACDF) with cervical spondylotic myelopathy from January 2013 to December 2022 were analyzed. The measured parameters include: the axial section of longus colli cross-sectional area (AxCSA), the volume of cervical longus, the ratio of long and short diameter line (RLS), the cervical extensor cross-sectional area (CESA), the vertebral body area (VBA), and the CESA/VBA. The visual analog scale (VAS), modified Japanese Orthopedic Association score (mJOA), and neck disability index (NDI) were evaluated. The changes in muscle morphology were analyzed, and the correlation analysis was conducted between morphological changes and function scores. RESULTS: The postoperative AxCSA of surgical segment (3rd month, 12th month, and the last follow-up) was decreased compared to preoperative (141.62 ± 19.78), and the differences were significant (P < 0.05). The corresponding data reduced to (119.42 ± 20.08) mm2, (117.59 ± 19.69) mm2, and (117.41 ± 19.19) mm2, respectively (P < 0.05). The RLS increased, and the volume of cervical longus decreased significantly after surgery (P < 0.05). Negative correlation was found between postoperative volume of cervical longus and VAS at the 3rd month (r = - 0.412), 12th month (r = - 0.272), and last follow-up (r = - 0.391) (P < 0.05). Negative correlation existed between postoperative volume of cervical longus and NDI at the 3rd month (r = - 0.552), 12th month (r = - 0.293), and last follow-up (r = - 0.459) (P < 0.05). CONCLUSION: The volume of cervical longus decreased and its morphology changed after ACDF surgery. The mainly affected muscle was the cervical longus closing to the surgical segment. Negative correlation was found between the postoperative volume of cervical longus and function scores (VAS and NDI).


Subject(s)
Spinal Fusion , Spondylosis , Humans , Spinal Fusion/methods , Retrospective Studies , Diskectomy/methods , Neck/surgery , Treatment Outcome , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Spondylosis/diagnostic imaging , Spondylosis/surgery , Muscles
18.
Stress Biol ; 4(1): 19, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38498254

ABSTRACT

Drought-induced osmotic stress severely affects the growth and yield of maize. However, the mechanisms underlying the different responses of young and old maize leaves to osmotic stress remain unclear. To gain a systematic understanding of age-related stress responses, we compared osmotic-stress-induced changes in maize leaves of different ages using multi-omics approaches. After short-term osmotic stress, old leaves suffered more severe water deficits than young leaves. The adjustments of transcriptomes, proteomes, and hormones in response to osmotic stress were more dynamic in old leaves. Metabolic activities, stress signaling pathways, and hormones (especially abscisic acid) responded to osmotic stress in an age-dependent manner. We identified multiple functional clusters of genes and proteins with potential roles in stress adaptation. Old leaves significantly accumulated stress proteins such as dehydrin, aquaporin, and chaperones to cope with osmotic stress, accompanied by senescence-like cellular events, whereas young leaves exhibited an effective water conservation strategy mainly by hydrolyzing transitory starch and increasing proline production. The stress responses of individual leaves are primarily determined by their intracellular water status, resulting in differential transcriptomes, proteomes, and hormones. This study extends our understanding of the mechanisms underlying plant responses to osmotic stress.

19.
Ecotoxicol Environ Saf ; 273: 116164, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38447517

ABSTRACT

BACKGROUND: An increasing amount of evidence suggests that telomere length (TL) at birth can predict lifespan and is associated with chronic diseases later in life, but newborn TL may be affected by environmental pollutants. Neonicotinoids (NEOs) are widely used worldwide, and despite an increasing number of studies showing that they may have adverse effects on birth in mammals and even humans, few studies have examined the effect of NEO exposure on newborn TLs. OBJECTIVE: To investigate the effects of prenatal exposure to NEOs and the interactions between NEOs and sampling season on newborn TL. METHODS: We conducted a prospective cohort study of 500 mother-newborn pairs from the Guangxi Zhuang Birth Cohort. Ultraperformance liquid chromatographymass spectrometry was used to detect ten NEOs in maternal serum, and fluorescence quantitative PCR was used to estimate the newborn TL. A generalized linear model (GLM) was used to evaluate the relationships between individual NEO exposures and TLs , and quantile g-computation (Qgcomp) model and Bayesian kernel machine regression (BKMR) model were used to evaluate the combined effect of mixtures of components. RESULTS: The results of the GLM showed that compared with maternal TMX levels < LOD, maternal TMX levels < median were negatively correlated with newborn TL (-6.93%, 95% CI%: -11.92%, -1.66%), and the decrease in newborn TL was more pronounced in girls (-9.60%, 95% CI: -16.84%, -1.72%). Moreover, different kinds of maternal NEO exposure had different effects on newborn TL in different sampling seasons, and the effect was statistically significant in all seasons except in autumn. Mixed exposure analysis revealed a potential positive trend between NEOs and newborn TL, but the association was not statistically significant. CONCLUSION: Prenatal exposure to TMX may shorten newborn TL, and this effect is more pronounced among female newborns. Furthermore, the relationship between NEO exposure and TL may be modified by the sampling season.


Subject(s)
Prenatal Exposure Delayed Effects , Pregnancy , Humans , Infant, Newborn , Female , Prenatal Exposure Delayed Effects/genetics , Seasons , Prospective Studies , Bayes Theorem , Cohort Studies , China , Maternal Exposure/adverse effects , Telomere
20.
Infect Drug Resist ; 17: 1085-1098, 2024.
Article in English | MEDLINE | ID: mdl-38525475

ABSTRACT

Purpose: The knowledge, attitude, and practices (KAP) concerning antibiotics by healthcare students have the potential impact on controlling antibiotic abuse and antimicrobial resistance (AMR) growth. This study aims to evaluate the levels and explore the associated factors with KAP on antibiotic use and AMR in Chinese nursing students. Methods: A cross-sectional survey using a self-administered questionnaire consisting of demographics and selected features and KAP on antibiotic use and AMR was conducted to measure KAP levels among nursing students at various universities in Hubei Province, China. The logistic regression analyses were performed to analyze the potential factors associated with the KAP. Results: The survey eventually included a total of 1959 nursing students. The mean scores for KAP were 57.89 ±26.32, 55.00 ±12.50, and 71.88 ±15.63, respectively. Regarding knowledge, 54.3% of participants were unaware that antibiotic was ineffective against viral infections. Regarding attitude, 36% of participants agreed that current antibiotic abuse existed; 96.2% of participants thought it necessary to set up a special course on antibiotics. Regarding practice, only 48.4% of participants usually purchased antibiotics with a prescription. Multivariable analyses indicated that lack of discussion on AMR in school courses was an independent risk factor against KAP, respectively. The main knowledge sources of antibiotic being outside the classroom was an independent risk factor related to knowledge and practice. The average score >80 points was an independent protective factor related to knowledge and practice. Conclusion: The KAP level on antibiotic use and AMR among Hubei nursing students was general and required further strengthening. Nursing students with risk factors should be prioritized in educational interventions. The findings of our study pointed out some directions for tailored interventions to improve the training on antibiotics.

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