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1.
Sci Total Environ ; : 176808, 2024 Oct 11.
Article in English | MEDLINE | ID: mdl-39396785

ABSTRACT

The rhizosphere, where plant roots interact intensely with the soil, is a crucial but understudied area in terms of the impact of virus infection. In this study, we investigated the effects of lily symptomless virus (LSV) and cucumber mosaic virus (CMV) on the Lanzhou lily (Lilium davidii var. unicolor) rhizosphere using metagenomics and bioinformatics analysis. We found that virus infection significantly altered soil pH, inorganic carbon, nitrate nitrogen, and total sulfur. Co-infection with LSV and CMV had a greater influence than single infections on the α- and ß-diversity of the rhizosphere viral community in which the absolute abundance of certain virus families (Siphoviridae, Podoviridae, and Myoviridae) increased significantly, whereas bacteria, fungi, and archaea remained relatively unaffected. These altered virus populations influenced the rhizosphere microbial carbon and nitrogen cycles by exerting top-down control on bacteria. Co-infection potentially weakened rhizosphere carbon fixation and promoted processes such as methane oxidation, nitrification, and denitrification. In addition, the co-occurrence network of bacteria and viruses in the rhizosphere revealed substantial changes in microbial community composition under co-infection. Our partial-least-squares path model confirmed that the diversity of the rhizosphere viral community indirectly regulated the carbon and nitrogen cycling functions of the microbial community, thus affecting the accumulation of carbon and nitrogen nutrients in the soil. Our results are the first report of the effects of virus infection on the lily rhizosphere, particularly for co-infection; they therefore complement research on the plant virus pathogenic mechanisms, and increase our understanding of the ecological role of rhizosphere soil viruses.

2.
Sci Rep ; 14(1): 22629, 2024 09 30.
Article in English | MEDLINE | ID: mdl-39349514

ABSTRACT

The emerging class of multi-functional proteins known as moonlighters challenges the "one protein, one function" mentality by demonstrating crosstalk between biological pathways that were previously thought to be functionally discrete. Here, we present new links between amino acid metabolism and chromatin regulation, two biological pathways that are critical for cellular and organismal homeostasis. We discovered that the threonine biosynthetic pathway is required for the transcriptional silencing of ribosomal DNA (rDNA) in Saccharomyces cerevisiae. The enzymes in the pathway promote rDNA silencing through distinct mechanisms as a subset of silencing phenotypes was rescued with exogenous threonine. In addition, we found that a key pathway enzyme, homoserine dehydrogenase, promotes DNA repair through a mechanism involving the MRX complex, a major player in DNA double strand break repair. These data further the understanding of enzymes with non-canonical roles, here demonstrated within the threonine biosynthetic pathway, and provide insight into their roles as potential anti-fungal pharmaceutical targets.


Subject(s)
Chromatin , DNA Repair , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae , Threonine , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics , Threonine/metabolism , Chromatin/metabolism , Chromatin/genetics , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae Proteins/genetics , Metabolic Networks and Pathways , DNA, Ribosomal/genetics , DNA, Ribosomal/metabolism , Gene Silencing , Gene Expression Regulation, Fungal
3.
bioRxiv ; 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39345537

ABSTRACT

HDACs (histone deacetylase) play a crucial role in regulating gene expression, and the inhibition of these enzymes is gaining attention as a promising therapeutic approach for cancer treatment. Despite their significant physiological and clinical importance, the mechanisms of HDAC activation remain poorly understood. This study reveals that inositol polyphosphate multikinase (IPMK) is essential for activating HDAC1 and HDAC3 in cell lines and mice. IPMK deletion or inactivation of its kinase activity selectively impairs HDAC1/3's deacetylase activity, significantly influencing gene expression. Disruption of the IPMK-HDAC1/3 epigenetic axis results in transcriptional upregulation of matrix metalloproteinase (MMP) genes, exacerbating cell and intestinal permeability. Remarkably, treatment of IPMK KO cells with cell-permeable inositol hexaphosphate (InsP6) rescues these defects. This study elucidates the role of IPMK's kinase activity in HDAC1/3 activation and its implications for intestinal barrier function.

4.
Curr Opin Biotechnol ; 90: 103196, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39276615

ABSTRACT

Cellular synthesis of phytic acid sequesters phosphates in the sugar inositol. Phytic acid in soil represents the most abundant form of organic phosphates. The supplementation of phytase or phytase-producing organisms has been considered as a strategy to improve usable soil phosphates. However, the impacts on the environmental flow of inositol, which is generated along with phosphate by phytase, have not been examined. In this review, we discuss the origin and nature of inositol produced in soil and the several possible destinations of inositol released by phytase activities. We emphasise how an improved understanding of soil inositol flow could help to provide new solutions to the phosphate shortage problem in agriculture.

5.
Cancer Biol Ther ; 25(1): 2382531, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-39206791

ABSTRACT

Mouse orthotopic xenograft tumor models are commonly employed in studies investigating the mechanisms underlying the development and progression of tumors and their preclinical treatment. However, the unavailability of mature and visualized orthotopic xenograft models of nasopharyngeal carcinoma limits the development of treatment strategies for this cancer. The aim of this study was to provide a simple and reliable method for building an orthotopic xenograft model of nasopharyngeal carcinoma. Human nasopharyngeal carcinoma (C666-1-luc) cells, stably expressing the firefly luciferase gene, were injected subcutaneously into the right axilla of BALB/C nude mice. Four weeks later, the resulting subcutaneous tumors were cut into small blocks and grafted into the nasopharynx of immunodeficient BALB/C nude mice to induce tumor formation. Tumor growth was monitored by bioluminescence imaging and small animal magnetic resonance imaging (MRI). The expression of histological and immunological antigens associated with orthotopic xenograft nasopharyngeal carcinoma was analyzed by tissue section analysis and immunohistochemistry (IHC). A visualized orthotopic xenograft nasopharyngeal carcinoma model was successfully developed in this study. Luminescence signal detection, micro-MRI, and hematoxylin and eosin staining revealed the successful growth of tumors in the nasopharynx of the nude mice. Moreover, IHC analysis detected cytokeratin (CK), CK5/6, P40, and P63 expression in the orthotopic tumors, consistent with the reported expression of these antigens in human nasopharyngeal tumors. This study established a reproducible, visual, and less lethal orthotopic xenograft model of nasopharyngeal carcinoma, providing a platform for preclinical research.


Subject(s)
Disease Models, Animal , Mice, Nude , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Animals , Humans , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/diagnostic imaging , Mice , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/genetics , Cell Line, Tumor , Mice, Inbred BALB C , Carcinoma/pathology , Carcinoma/genetics , Carcinoma/metabolism , Magnetic Resonance Imaging/methods , Xenograft Model Antitumor Assays , Heterografts , Luminescent Measurements/methods
6.
BMC Pediatr ; 24(1): 455, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014321

ABSTRACT

The impact of the Coronavirus Disease 2019 (COVID-19) on society is continuous, resulting in negative psychological consequences. Given the vulnerability and sensitivity to the environment among preschool children, their emotional and behavioral problems deserve more attention. The current study aimed to explore the impact of the epidemic on preschool children's mental health by determining the pooled prevalence of emotional and behavioral problems amidst the Coronavirus Disease 2019 pandemic and to reveal potential reasons for variations between studies. Published studies were searched in Embase, PubMed, ProQuest, PsycINFO, Web of Science, CNKI, and Wanfang. Based on the inclusion criteria outlined in this study, a total of 10 studies encompassing 38,059 participants were incorporated. Employing a random-effect model for estimating the prevalence of emotional and behavioral problems, the results revealed a pooled prevalence rate of 24.3% (95% CI, 0.15-0.38; I²=99.9%) among preschool children. This rate surpasses the pre-outbreak prevalence observed in different countries, signifying a detrimental influence of the epidemic on the mental well-being of preschoolers. Therefore, mental health care and recovery are essential for the vulnerable group during and after the public health crisis. Specific emotional and behavioral problems among preschool children are expected to be researched in the future to provide more targeted guidance for intervention.


Subject(s)
COVID-19 , Humans , COVID-19/psychology , COVID-19/epidemiology , Child, Preschool , Child Behavior Disorders/epidemiology , Child Behavior Disorders/psychology , Prevalence , Problem Behavior/psychology , Affective Symptoms/epidemiology , Affective Symptoms/psychology , SARS-CoV-2
7.
Biomed Environ Sci ; 37(5): 511-520, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38843924

ABSTRACT

Objective: This study employs the Geographically and Temporally Weighted Regression (GTWR) model to assess the impact of meteorological elements and imported cases on dengue fever outbreaks, emphasizing the spatial-temporal variability of these factors in border regions. Methods: We conducted a descriptive analysis of dengue fever's temporal-spatial distribution in Yunnan border areas. Utilizing annual data from 2013 to 2019, with each county in the Yunnan border serving as a spatial unit, we constructed a GTWR model to investigate the determinants of dengue fever and their spatio-temporal heterogeneity in this region. Results: The GTWR model, proving more effective than Ordinary Least Squares (OLS) analysis, identified significant spatial and temporal heterogeneity in factors influencing dengue fever's spread along the Yunnan border. Notably, the GTWR model revealed a substantial variation in the relationship between indigenous dengue fever incidence, meteorological variables, and imported cases across different counties. Conclusion: In the Yunnan border areas, local dengue incidence is affected by temperature, humidity, precipitation, wind speed, and imported cases, with these factors' influence exhibiting notable spatial and temporal variation.


Subject(s)
Dengue , Dengue/epidemiology , China/epidemiology , Humans , Spatio-Temporal Analysis , Incidence , Disease Outbreaks , Spatial Regression
8.
Plant Sci ; 346: 112149, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38851591

ABSTRACT

TOPLESS/TOPLESS-RELATED (TPL/TPR) proteins belong to the Groucho (Gro)/Tup1 family co-repressors and act as broad co-repressors that modulate multiple phytohormone signalling pathways and various developmental processes in plant. However, TPL/TPR co-repressors so far are poorly understood in the rapeseed, one of the world-wide important oilseed crops. In this study, we comprehensively characterized eighteen TPL/TPR genes into five groups in the rapeseed genome. Members of TPL/TPR1/TPR4 and TPR2/TPR3 had close evolutionary relationship, respectively. All TPL/TPRs had similar expression patterns and encode conserved protein domain. In addition, we demonstrated that BnaA9.TPL interacted with all known plant repression domain (RD) sequences, which were distributed in non-redundant 24,238 (22.6 %) genes and significantly enriched in transcription factors in the rapeseed genome. These transcription factors were largely co-expressed with the TPL/TPR genes and involved in diverse pathway, including phytohormone signal transduction, protein kinases and circadian rhythm. Furthermore, BnaA9.TPL was revealed to regulate apical embryonic fate by interaction with Bna.IAA12 and suppression of PLETHORA1/2. BnaA9.TPL was also identified to regulate leaf morphology by interaction with Bna.AS1 (Asymmetric leaves 1) and suppression of KNOTTED-like homeobox genes and YABBY5. These data not only suggest the rapeseed TPL/TPRs play broad roles in different processes, but also provide useful information to uncover more TPL/TPR-mediated control of plant development in rapeseed.


Subject(s)
Gene Expression Regulation, Plant , Plant Leaves , Plant Proteins , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Leaves/genetics , Plant Leaves/growth & development , Brassica napus/genetics , Brassica napus/growth & development , Brassica napus/metabolism , Genome-Wide Association Study , Co-Repressor Proteins/genetics , Co-Repressor Proteins/metabolism , Phylogeny , Genome, Plant
9.
Sci Data ; 11(1): 463, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714688

ABSTRACT

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.


Subject(s)
Brain , Child Development , Child , Child, Preschool , Humans , Brain/growth & development , Brain/diagnostic imaging , China , Cognition , Databases, Factual , Neuroimaging
10.
Mol Cell ; 84(9): 1811-1815.e3, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38701742

ABSTRACT

Post-translational modifications of proteins (PTMs) introduce an extra layer of complexity to cellular regulation. Although phosphorylation of serine, threonine, and tyrosine residues is well-known as PTMs, lysine is, in fact, the most heavily modified amino acid, with over 30 types of PTMs on lysine having been characterized. One of the most recently discovered PTMs on lysine residues is polyphosphorylation, which sees linear chains of inorganic polyphosphates (polyP) attached to lysine residues. The labile nature of phosphoramidate bonds raises the question of whether this modification is covalent in nature. Here, we used buffers with very high ionic strength, which would disrupt any non-covalent interactions, and confirmed that lysine polyphosphorylation occurs covalently on proteins containing PASK domains (polyacidic, serine-, and lysine-rich), such as the budding yeast protein nuclear signal recognition 1 (Nsr1) and the mammalian protein nucleolin. This Matters Arising Response paper addresses the Neville et al. (2024) Matters Arising paper, published concurrently in Molecular Cell.


Subject(s)
Lysine , Phosphoproteins , Protein Processing, Post-Translational , RNA-Binding Proteins , Phosphorylation , Lysine/metabolism , Phosphoproteins/metabolism , Phosphoproteins/chemistry , Phosphoproteins/genetics , Humans , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/chemistry , Nucleolin , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/chemistry , Animals , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics , Polyphosphates/metabolism , Polyphosphates/chemistry , Osmolar Concentration
11.
J Phys Chem Lett ; 15(20): 5436-5444, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38743952

ABSTRACT

The excellent reactivity of frustrated Lewis pairs (FLP) to activate small molecules has gained increasing attention in recent decades. Though the development of surface FLP (SFLP) is prompting the application of FLP in the chemical industry, the design of SFLP with superior activity, high density, and excellent stability for small-molecule activation is still challenging. Herein, we review the progress of designing SFLP by surface engineering, screening natural SFLP, and the dynamic formation of SFLP from theoretical perspectives. We highlight the breakthrough in fine-tuning the activity, density, and stability of the designed SFLP studied by using computational methods. We also discuss future challenges and directions in designing SFLP with outstanding capabilities for small-molecule activation.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 131-138, 2024 Feb 15.
Article in Chinese | MEDLINE | ID: mdl-38436309

ABSTRACT

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.


Subject(s)
Empyema , Hydrocephalus , Meningitis, Pneumococcal , Subdural Effusion , Infant , Female , Male , Humans , Child , Infant, Newborn , Adolescent , Meningitis, Pneumococcal/drug therapy , Meningitis, Pneumococcal/epidemiology , Meropenem , Vancomycin , Levofloxacin , Linezolid , Moxifloxacin , Retrospective Studies , Rifampin , Streptococcus pneumoniae , Chloramphenicol
13.
Mol Divers ; 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38240951

ABSTRACT

Akt1, as an important member of the Akt family, plays a controlled role in cancer cell growth and survival. Inhibition of Akt1 activity can promote cancer cell apoptosis and inhibit tumor growth. Therefore, in this investigation, a multilayer virtual screening approach, including receptor-ligand interaction-based pharmacophore, 3D-QSAR, molecular docking, and deep learning methods, was utilized to construct a virtual screening platform for Akt1 inhibitors. 17 representative compounds with different scaffolds were identified as potential Akt1 inhibitors from three databases. Among these 17 compounds, the Hit9 exhibited the best inhibitory activity against Akt1 with inhibition rate of 33.08% at concentration of 1 µM. The molecular dynamics simulations revealed that Hit9 and Akt1 could form a compact and stable complex. Moreover, Hit9 interacted with some key residues by hydrophobic, electrostatic, and hydrogen bonding interactions and induced substantial conformation changes in the hinge region of the Akt1 active site. The average binding free energies for the Akt1-CQU, Akt1-Ipatasertib, and Akt1-Hit9 systems were - 34.44, - 63.37, and - 39.14 kJ mol-1, respectively. In summary, the results obtained in this investigation suggested that Hit9 with novel scaffold may be a promising lead compound for developing new Akt1 inhibitor for treatment of various cancers with Akt1 overexpressed.

14.
BMC Pulm Med ; 24(1): 59, 2024 Jan 27.
Article in English | MEDLINE | ID: mdl-38281038

ABSTRACT

BACKGROUND: Lung cancer remains a major global health concern due to its high incidence and mortality rates. With advancements in medical treatments, an increasing number of early-stage lung cancer cases are being detected, making surgical treatment the primary option for such cases. However, this presents challenges to the physical and mental recovery of patients. Peplau known as the "mother of psychiatric associations" has formulated a theory of interpersonal relationships in nursing. Through effective communication between nurses and patients over four periods, she has established a good therapeutic nurse-patient relationship. Therefore, this study aimed to explore the effect of perioperative multimodal nursing based on Peplau's interpersonal relationship theory on the rehabilitation of patients with surgical lung cancer. METHODS: We retrospectively analyzed 106 patients with non-small cell lung cancer who underwent thoracoscopic lobectomy at our department between June 2021 and April 2022. Patients were categorized into two groups according to the different nursing intervention techniques. The Peplau's group comprised 53 patients who received targeted nursing interventions, and the control group comprised 53 patients who received conventional nursing care. We observed the patients' illness uncertainty, quality of life, and clinical symptoms in both groups. RESULTS: Patients in the Peplau's group had significantly lower illness uncertainty scores and a significantly higher quality of recovery than those in the control group. However, there were no significant differences in length of post-anesthesia care unit stay, complication rates, and visual analog scores between both groups. CONCLUSION: The multimodal perioperative nursing based on Peplau's interpersonal relationship theory not only reduces the illness uncertainty of patients with lung cancer surgery and improves their QoR but also expands the application of this theory in clinical practice, guiding perioperative nursing of patients with lung cancer. IMPLICATIONS: These findings provide practical information for standardized care in a hectic anesthetic care setting. IMPACT: The assessed anesthesia nursing model helps reduce uncertainty and promote early recovery in patients with cancer at various stages of their disease, which expands the scope of therapeutic practice and existing theories. It also serves as a guide for care in the anesthesia recovery room. REPORTING METHOD: We adhered to the relevant Equator guidelines and the checklist of items in the case-control study report. PATIENT OR PUBLIC CONTRIBUTION: Patients cooperated with medical staff to complete relevant scales.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Female , Humans , Nursing Theory , Retrospective Studies , Case-Control Studies , Lung Neoplasms/surgery , Carcinoma, Non-Small-Cell Lung/surgery , Quality of Life
15.
Genomics ; 115(6): 110726, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37832857

ABSTRACT

Simple sequence repeats (SSRs) have been widely used for parentage testing, marker-assisted selection, and evolutionary studies. The insufficient availability of SSR markers in Bactrian camels partially accounts for the lack of systematic breeding. Therefore, we aimed to establish a comprehensive SSR dataset for the Bactrian camel. Our approach involved genome searching to locate every SSR in the genome, SSR-enriched sequencing to acquire polymorphism information, and literature research to collect published data. The resulting dataset contains 213,711 SSRs and details their characteristics, including genome coordinates, motifs, lengths, annotations, PCR primers, and polymorphism information. The dataset reveals a biased distribution of SSRs in the Bactrian camel genome, reflecting the mutation mechanism and complex evolution of SSRs. In practice, we successfully demonstrated the utility of the dataset through parentage testing using 15 randomly selected SSRs. This comprehensive dataset can facilitate systematic breeding and enable QTL mapping and GWAS of the Bactrian camel.


Subject(s)
Camelus , Genome, Plant , Animals , Camelus/genetics , Genetic Markers , Polymorphism, Genetic , Microsatellite Repeats
16.
Cancer Med ; 12(20): 20437-20449, 2023 10.
Article in English | MEDLINE | ID: mdl-37795758

ABSTRACT

BACKGROUND: Previous studies have shown that ALDH2 and ADH1B genes may be associated with alcohol metabolism and the risk of esophageal squamous cell carcinoma (ESCC), with inconsistent results. This meta-analysis aimed at comprehensively assessing the associations between ALDH2 and ADH1B polymorphisms and the risk of ESCC to synthesize and clarify the evidence. METHODS: We calculated summary estimates of the associations between four genetic variants (rs671 and rs674 in ALDH2, and rs1229984 and rs1042026 in ADH1B) and the ESCC risk across 23 publications in the additive model and allelic model. Venice criteria, Bayesian false discovery probability (BFDP), and false-positive reporting probability (FPRP) were used to assess the strength of epidemiological evidence. Heterogeneity among studies was evaluated by using the Higgin's I2 statistic, and publication bias was assessed by using funnel plots and Begg's test. A Mendelian randomization (MR) analysis was performed to determine the causal association between alcohol intake and esophageal cancer risk. Data from the HaploReg v4.1 and PolyPhen-2 were analyzed for functional annotations. RESULTS: Of the four genetic variants, rs671 of ALDH2 was associated with a significantly reduced risk of ESCC (OR: 0.60, 95% CI: 0.50-0.73), whereas rs1229984 of ADH1B was associated with a significantly increased risk (2.50, 95% CI: 1.70-3.69) in the additive model. In the allelic model, the variant rs1229984 of ADH1B also increased the risk of ESCC (OR: 1.50; 95% CI: 1.21-1.87). The result for the variant rs671 was considered as strong epidemiological evidence. Functional annotations identified that the four variants were related to the enhancer histone marks and motif changes. The other two variants were not associated with the ESCC risk (rs674 of ALDH2 OR: 1.22, 95% CI: 0.71-2.12; rs1042026 of ADH1B OR: 1.28, 95% CI: 0.52-3.14) in the additive model. The MR analysis did not find a causal effect of alcohol on the esophageal cancer risk. CONCLUSIONS: The results showed that ADH1B rs1229984 was significantly associated with an increased the risk of ESCC.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/genetics , Mendelian Randomization Analysis , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/genetics , Bayes Theorem , Risk Factors , Genetic Predisposition to Disease , Aldehyde Dehydrogenase, Mitochondrial/genetics , Alcohol Drinking/adverse effects , Alcohol Drinking/genetics , Ethanol , Genotype , Polymorphism, Single Nucleotide
17.
Zhongguo Zhong Yao Za Zhi ; 48(15): 4187-4200, 2023 Aug.
Article in Chinese | MEDLINE | ID: mdl-37802787

ABSTRACT

This study aimed to explore the mechanism of Qilongtian Capsules in treating acute lung injury(ALI) based on network pharmacology prediction and in vitro experimental validation. Firstly, UPLC-Q-TOF-MS/MS was used to analyze the main chemical components of Qilongtian Capsules, and related databases were used to obtain its action targets and ALI disease targets. STRING database was used to build a protein-protein interaction(PPI) network. Metascape database was used to conduct enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). AutoDock software was used to perform molecular docking verification on the main active components and key targets. Then, the RAW264.7 cells were stimulated with lipopolysaccharide(LPS) for in vitro experiments. Cell viability was measured by MTT and ROS level was measured by DCFH-DA. NO content was measured by Griess assay, and IL-1ß, IL-6, and TNF-α mRNA expression was detected by RT-PCR. The predicted targets were preliminarily verified by investigating the effect of Qilongtian Capsules on downstream cytokines. Eighty-four compounds were identified by UPLC-Q-TOF-MS/MS. Through database retrieval, 44 active components with 589 target genes were screened out. There were 560 ALI disease targets, and 65 intersection targets. PPI network topology analysis revealed 10 core targets related to ALI, including STAT3, JUN, VEGFA, CASP3, and MMP9. KEGG enrichment analysis showed that Qilongtian Capsules mainly exerted an anti-ALI effect by regulating cancer pathway, AGE-RAGE, MAPK, and JAK-STAT signaling pathways. The results of molecular docking showed that the main active components in Qilongtian Capsules, including crenulatin, ginsenoside F_1, ginsenoside Rb_1, ginsenoside Rd, ginsenoside Rg_1, ginsenoside Rg_3, notoginsenoside Fe, notoginsenoside G, notoginsenoside R_1, notoginsenoside R_2, and notoginsenoside R_3, had good binding affinities with the corresponding protein targets STAT3, JUN, VEGFA, CASP3, and MMP9. Cellular experiments showed that Qilongtian Capsules at 0.1, 0.25, and 0.5 mg·mL~(-1) reduced the release of NO, while Qilongtian Capsules at 0.25 and 0.5 mg·mL~(-1) reduced ROS production, down-regulated mRNA expression of IL-1ß, IL-6, TNF-α, and inhibited the inflammatory cascade. In summary, Qilongtian Capsules may exert therapeutic effects on ALI through multiple components and targets.


Subject(s)
Acute Lung Injury , Drugs, Chinese Herbal , Ginsenosides , Humans , Tumor Necrosis Factor-alpha , Caspase 3 , Matrix Metalloproteinase 9 , Interleukin-6 , Molecular Docking Simulation , Network Pharmacology , Reactive Oxygen Species , Tandem Mass Spectrometry , Acute Lung Injury/drug therapy , Acute Lung Injury/genetics , Capsules , RNA, Messenger , Drugs, Chinese Herbal/pharmacology
18.
Prev Med Rep ; 36: 102394, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37766721

ABSTRACT

Background: This study examined the intent to be COVID-19 vaccinated and its correlates among patients with a pacemaker. Methods: This observational study was carried out between July 1, 2021, and May 17, 2022 in Beijing, China. Patients with a pacemaker were consecutively invited by a research physician to participate in the study. Intent to be COVID-19 vaccinated, depression, anxiety, insomnia, pain and smoking were measured with standard scales or questions. Results: Of the 206 participating patients, 72.82% (N = 150; 95% confidence interval [CI]: 66.74%-78.89%) expressed an intention to be COVID-19 vaccinated. Intent to be COVID-19 vaccinated was not significantly associated with severity of depression, anxiety, and insomnia. Multiple logistic regression analysis revealed that patients believing that COVID-19 vaccines provided protection and smokers were more likely to express an intention to receive COVID-19 vaccines. In contrast, older patients and those with higher level of physical pain were less likely to express an intention to be vaccinated against COVID-19. Conclusions: Specific vaccination promotion strategies should be implemented targeting this vulnerable segment of the population.

19.
Sci Data ; 10(1): 545, 2023 08 21.
Article in English | MEDLINE | ID: mdl-37604823

ABSTRACT

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.


Subject(s)
Asian People , Brain , Humans , Brain/diagnostic imaging , China , Data Warehousing , Databases, Factual , Neurosciences
20.
Proc Natl Acad Sci U S A ; 120(34): e2306868120, 2023 08 22.
Article in English | MEDLINE | ID: mdl-37579180

ABSTRACT

Inositol pyrophosphates (PP-InsPs) are energetic signaling molecules with important functions in mammals. As their biosynthesis depends on ATP concentration, PP-InsPs are tightly connected to cellular energy homeostasis. Consequently, an increasing number of studies involve PP-InsPs in metabolic disorders, such as type 2 diabetes, aspects of tumorigenesis, and hyperphosphatemia. Research conducted in yeast suggests that the PP-InsP pathway is activated in response to reactive oxygen species (ROS). However, the precise modulation of PP-InsPs during cellular ROS signaling is unknown. Here, we report how mammalian PP-InsP levels are changing during exposure to exogenous (H2O2) and endogenous ROS. Using capillary electrophoresis electrospray ionization mass spectrometry (CE-ESI-MS), we found that PP-InsP levels decrease upon exposure to oxidative stressors in HCT116 cells. Application of quinone drugs, particularly ß-lapachone (ß-lap), under normoxic and hypoxic conditions enabled us to produce ROS in cellulo and to show that ß-lap treatment caused PP-InsP changes that are oxygen-dependent. Experiments in MDA-MB-231 breast cancer cells deficient of NAD(P)H:quinone oxidoreductase-1 (NQO1) demonstrated that ß-lap requires NQO1 bioactivation to regulate the cellular metabolism of PP-InsPs. Critically, significant reductions in cellular ATP concentrations were not directly mirrored in reduced PP-InsP levels as shown in NQO1-deficient MDA-MB-231 cells treated with ß-lap. The data presented here unveil unique aspects of ß-lap pharmacology and its impact on PP-InsP levels. The identification of different quinone drugs as modulators of PP-InsP synthesis will allow the overall impact on cellular function of such drugs to be better appreciated.


Subject(s)
Diabetes Mellitus, Type 2 , Naphthoquinones , Humans , Adenosine Triphosphate , Cell Line, Tumor , Diphosphates , Hydrogen Peroxide/metabolism , Inositol , NAD(P)H Dehydrogenase (Quinone)/genetics , NAD(P)H Dehydrogenase (Quinone)/metabolism , Naphthoquinones/pharmacology , Oxygen , Reactive Oxygen Species/metabolism
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