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1.
Front Endocrinol (Lausanne) ; 15: 1327903, 2024.
Article in English | MEDLINE | ID: mdl-38846495

ABSTRACT

Objectives: To research the connection between the indexes of the indexes of triglyceride-glucose (TyG) combined with obesity indices and the initial neurological severity and short-term outcome of new-onset acute ischemic stroke. Methods: Data of patients with acute ischemic stroke admitted to the Stroke Ward of the Affiliated Hospital of Beihua University from November 2021 to October 2023, were collected. The two indexes were calculated by combining TyG and obesity indices: TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC). The National Institute of Health Stroke Scale (NIHSS) was used to assess and group patients with neurological deficits within 24 hours of admission: mild stroke (NIHSS ≤5) and moderate-severe stroke (NIHSS >5). Short-term prognosis was evaluated using the modified Rankin Scale (mRS) at discharge or 14 days after onset of the disease and grouped: good outcome (mRS ≤2) and poor outcome (mRS >2). According to the quartiles of TyG-BMI and TyG-WC, the patients were placed into four groups: Q1, Q2, Q3 and Q4. Multi-factor logistic regression analysis was utilized to evaluate the correlation of TyG-BMI and TyG-WC with the severity and short-term outcome. Results: The study included 456 patients. After adjusting for multiple variables, the results showed that compared with the quartile 1, patients in quartile 4 of TyG-BMI had a reduced risk of moderate-severe stroke [Q4: OR: 0.407, 95%CI (0.185-0.894), P = 0.025]; Patients in quartiles 2, 3 and 4 of TyG-BMI had sequentially lower risk of short-term adverse outcomes [Q2: OR: 0.394, 95%CI (0.215-0.722), P = 0.003; Q3: OR: 0.324, 95%CI (0.163-0.642), P = 0.001; Q4: OR: 0.158, 95%CI (0.027-0.349), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of moderate-severe stroke [Q3: OR: 0.355, 95%CI (0.173-0.728), P = 0.005; Q4: OR: 0.140, 95%CI (0.056-0.351), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of short-term adverse outcomes [Q3: OR: 0.350, 95%CI (0.175-0.700), P = 0.003; Q4: OR: 0.178, 95%CI (0.071-0.451), P <0.001]. Conclusions: TyG-WC and TyG-BMI were correlated with the severity and short-term outcome of new-onset acute ischemic stroke. As TyG-WC and TyG-BMI increased, stroke severity decreased and short-term outcome was better.


Subject(s)
Blood Glucose , Body Mass Index , Ischemic Stroke , Severity of Illness Index , Triglycerides , Humans , Male , Female , Ischemic Stroke/blood , Middle Aged , Aged , Triglycerides/blood , Prognosis , Blood Glucose/analysis , Blood Glucose/metabolism , Waist Circumference , Obesity/blood , Obesity/complications
2.
Inorg Chem ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848541

ABSTRACT

A pair of water-stable and highly porous homochiral fluorescent silver-organic framework enantiomers, namely, R-Ag-BPA-TPyPE (R-1) and S-Ag-BPA-TPyPE (S-1), had been prepared as enantioselective fluorescence sensors. Combining homochiral 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BPA) with an AIE-based ligand tetrakis[4-(pyridin-4-yl)phenyl]ethene (TPyPE) in complexes R-1 and S-1 made them possess favorable circularly polarized luminescence (CPL) properties, and their CPL spectra were almost mirror images of each other. The luminescence dissymmetry factors (glum) are ±2.2 × 10-3 for R-1 and S-1, and the absolute fluorescence quantum yields (ΦFs) are 32.0% for R-1 and S-1, respectively. Complex R-1 could enantioselectively recognize two enantiomers of amino acids in water or DMF with high Stern-Volmer constants of 236-573 M-1 and enantioselectivity ratios of 1.40-1.78.

3.
Clin Transl Med ; 14(6): e1702, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38861300

ABSTRACT

BACKGROUND: Patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD) have an increased risk of disease exacerbation and decreased survival. We aimed to develop and validate a non-invasive nomogram for predicting COPD associated with severe PH and a prognostic nomogram for patients with COPD and concurrent PH (COPD-PH). METHODS: This study included 535 patients with COPD-PH from six hospitals. A multivariate logistic regression analysis was used to analyse the risk factors for severe PH in patients with COPD and a multivariate Cox regression was used for the prognostic factors of COPD-PH. Performance was assessed using calibration, the area under the receiver operating characteristic curve and decision analysis curves. Kaplan-Meier curves were used for a survival analysis. The nomograms were developed as online network software. RESULTS: Tricuspid regurgitation velocity, right ventricular diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), the red blood cell count, New York Heart Association functional class and sex were non-invasive independent variables of severe PH in patients with COPD. These variables were used to construct a risk assessment nomogram with good discrimination. NT-proBNP, mean pulmonary arterial pressure, partial pressure of arterial oxygen, the platelet count and albumin were independent prognostic factors for COPD-PH and were used to create a predictive nomogram of overall survival rates. CONCLUSIONS: The proposed nomograms based on a large sample size of patients with COPD-PH could be used as non-invasive clinical tools to enhance the risk assessment of severe PH in patients with COPD and for the prognosis of COPD-PH. Additionally, the online network has the potential to provide artificial intelligence-assisted diagnosis and treatment. HIGHLIGHTS: A multicentre study with a large sample of chronic obstructive pulmonary disease (COPD) patients diagnosed with PH through right heart catheterisation. A non-invasive online clinical tool for assessing severe pulmonary hypertension (PH) in COPD. The first risk assessment tool was established for Chinese patients with COPD-PH.


Subject(s)
Hypertension, Pulmonary , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/physiopathology , Male , Female , Hypertension, Pulmonary/mortality , Hypertension, Pulmonary/complications , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Aged , Middle Aged , Nomograms , Prognosis , Risk Factors
4.
Article in English | MEDLINE | ID: mdl-38769261

ABSTRACT

In response to China's policies on pollution control and carbon emission (CE) reductions, more stringent regulations have been implemented to evaluate CE in wastewater treatment facilities. In this study, we have analyzed CE from China's wastewater treatment plants (WWTPs) and influencing factor. Emission factor (EF) and operational data integrated methods (ODIM) were utilized to measure emissions, using data collected from 247 WWTPs over a 1-year period across seven regions in China. The average CE intensity was 0.45 kgCO2-eq/m3, affected by region, season, influent water quality, treatment processes, effluent discharge standards, and facilities. The scale effect was obvious only in the range of 2 × 105 m3/day. Underground WWTPs exhibited significantly higher CE compared to aboveground WWTPs. In summary, the assessment of CE in 247 actual WWTPs not only identifies emission reduction potential but also provides a scientific basis for formulating targeted emission reduction measures.

5.
Front Plant Sci ; 15: 1326387, 2024.
Article in English | MEDLINE | ID: mdl-38807783

ABSTRACT

Rehmannia glutinosa is an economically significant medicinal plant. Yet, the structure and sequence of its mitochondrial genome has not been published, which plays a crucial role in evolutionary analysis and regulating respiratory-related macromolecule synthesis. In this study, the R. glutinosa mitogenome was sequenced employing a combination of Illumina short reads and Nanopore long reads, with subsequent assembly using a hybrid strategy. We found that the predominant configuration of the R. glutinosa mitogenome comprises two circular chromosomes. The primary structure of the mitogenome encompasses two mitochondrial chromosomes corresponding to the two major configurations, Mac1-1 and Mac1-2. The R. glutinosa mitogenome encoded an angiosperm-typical set of 24 core genes, nine variable genes, three rRNA genes, and 15 tRNA genes. A phylogenetic analysis using the 16 shared protein-coding genes (PCG) yielded a tree consistent with the phylogeny of Lamiales species and two outgroup taxa. Mapping RNA-seq data to the coding sequences (CDS) of the PCGs revealed 507 C-to-U RNA editing sites across 31 PCGs of the R. glutinosa mitogenome. Furthermore, one start codon (nad4L) and two stop codons (rpl10 and atp6) were identified as products of RNA editing events in the R. glutinosa mitogenome.

6.
N Engl J Med ; 390(20): 1862-1872, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38752650

ABSTRACT

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).


Subject(s)
Ambulances , Blood Pressure , Hypertension , Stroke , Humans , Male , Female , Aged , Middle Aged , Stroke/therapy , Hypertension/complications , Antihypertensive Agents/therapeutic use , Emergency Medical Services , Time-to-Treatment , Aged, 80 and over , Ischemic Stroke/therapy
7.
J Cancer ; 15(11): 3427-3440, 2024.
Article in English | MEDLINE | ID: mdl-38817863

ABSTRACT

Purpose: Platinum-based chemotherapy is effective but limited by resistance in high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing (scRNA-seq) can reveal tumour cell heterogeneity and subclonal differentiation. We aimed to analyze resistance mechanisms and potential targets in HGSOC using scRNA-seq. Methods: We performed 10× genomics scRNA-seq sequencing on tumour tissues from 3 platinum-sensitive and 3 platinum-resistant HGSOC patients. We analyzed cell subcluster communication networks and spatial distribution using cellchat. We performed RNA-seq analysis on TACSTD2, a representative resistance gene in the E0 subcluster, to explore its molecular mechanism. Results: Epithelial cells, characterized by distinct chemotherapy resistance traits and highest gene copy number variations, revealed a specific cisplatin-resistant cluster (E0) associated with poor prognosis. E0 exhibited malignant features related to resistance, fostering growth through communication with fibroblasts and endothelial cells. Spatially, E0 promoted fibroblasts to protect tumour cells and impede immune cells infiltration. Furthermore, TACSTD2 was identified as a representative gene of the E0 subcluster, elucidating its role in platinum resistance through the Rap1/PI3K/AKT pathway. Conclusions: Our study reveals a platinum-resistant epithelial cell subcluster E0 and its association with TACSTD2 in HGSOC, uncovers new insights and evidence for the platinum resistance mechanism, and provides new ideas and targets for the development of therapeutic strategies against TACSTD2+ epithelial cancer cells.

8.
Clin Transl Sci ; 17(6): e13850, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38807464

ABSTRACT

Cold-inducible RNA-binding protein (CIRP) is a damage-associated molecular pattern that plays a critical role in triggering inflammatory responses. It remains unknown whether CIRP is strongly associated with bacterial load, inflammatory response, and mortality in sepsis model. Pneumonia was induced in specific pathogen-free 8-9-week old male rats by injecting bacteria via puncture of the tracheal cartilage. The expressions of CIRP and proinflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß] in lung tissues, alveolar macrophages (AMs), plasma, and bronchoalveolar lavage fluid (BALF) were determined by reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The numbers of bacteria recovered from the lungs were correlated with the bacterial loads injected and mortality. The expressions of CIRP increased sharply as the bacterial loads increased in the lung tissues and AMs. The amounts of TNF-α, IL-6 and IL-1ß proteins synthesized were dependent on the bacterial load in the lung tissues. Releases of CIRP, TNF-α, IL-6, and IL-1ß increased with the bacterial load in the blood plasma. The proteins confirmed similar patterns in the BALF. CIRP was strongly associated with the releases of TNF-α, IL-6, and IL-1ß in the lung tissues, blood plasma, and BALF, and showed a close correlation with mortality. CIRP demonstrated a strong association with bacterial load, which is new evidence, and close correlations with proinflammatory cytokines and mortality of pneumonia in rats, suggesting that it might be an interesting pneumonic biomarker for monitoring host response and predicting mortality, and a promising target for immunotherapy.


Subject(s)
Bacterial Load , Cytokines , RNA-Binding Proteins , Animals , Male , RNA-Binding Proteins/metabolism , Cytokines/metabolism , Cytokines/blood , Rats , Lung/microbiology , Lung/immunology , Lung/pathology , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/microbiology , Macrophages, Alveolar/immunology , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/microbiology , Pneumonia/microbiology , Pneumonia/immunology , Pneumonia/metabolism , Pneumonia/mortality , Rats, Sprague-Dawley , Interleukin-1beta/metabolism , Interleukin-1beta/blood , Disease Models, Animal , Inflammation Mediators/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/blood , Pneumonia, Bacterial/immunology , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/mortality
9.
Plant Mol Biol ; 114(3): 47, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632206

ABSTRACT

Natural Antisense Transcripts (NATs) are a kind of complex regulatory RNAs that play crucial roles in gene expression and regulation. However, the NATs in Cannabis Sativa L., a widely economic and medicinal plant rich in cannabinoids remain unknown. In this study, we comprehensively predicted C. sativa NATs genome-wide using strand-specific RNA sequencing (ssRNA-Seq) data, and validated the expression profiles by strand-specific quantitative reverse transcription PCR (ssRT-qPCR). Consequently, a total of 307 NATs were predicted in C. sativa, including 104 cis- and 203 trans- NATs. Functional enrichment analysis demonstrated the potential involvement of the C. sativa NATs in DNA polymerase activity, RNA-DNA hybrid ribonuclease activity, and nucleic acid binding. Finally, 18 cis- and 376 trans- NAT-ST pairs were predicted to produce 621 cis- and 5,679 trans- small interfering RNA (nat-siRNAs), respectively. These nat-siRNAs were potentially involved in the biosynthesis of cannabinoids and cellulose. All these results will shed light on the regulation of NATs and nat-siRNAs in C. sativa.


Subject(s)
Cannabinoids , Cannabis , RNA, Antisense/analysis , RNA, Antisense/genetics , RNA, Antisense/metabolism , Cannabis/genetics , RNA, Small Interfering/analysis , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Genome, Plant
10.
Plant Physiol Biochem ; 210: 108570, 2024 May.
Article in English | MEDLINE | ID: mdl-38560957

ABSTRACT

The WUSCHEL-related homeobox (WOX) gene family is vital for plant development and stress response. In this study, we conducted a comprehensive analysis of WOX genes in Cunninghamia lanceolata (C. lanceolata) and subsequently explored the potential roles of two ClWOX genes within the WUS clade. In total, six ClWOX genes were identified through a full-length transcriptome analysis. These genes, exhibiting conserved structural and functional motifs, were assigned to the ancient clade and Modern/WUS clade, respectively, through a phylogenetic analysis. Our expression analysis indicated that these ClWOX genes were highly expressed in the middle and late developmental stages of zygotic embryos in C. lanceolata. Moreover, only ClWOX5 and ClWOX6 within the Modern/WUS clade exhibited transcriptional activity, and their expressions were also induced in response to auxin and wounding. Overexpression of ClWOX5 and ClWOX6 in Arabidopsis caused a partially sterile phenotype, resulting in a very low seed setting rate. Transcriptomic analysis revealed that expressions of many embryo-defective (EMB) genes, phytohormone-related genes, and transcription factors (TFs) were dramatically altered in ClWOX5 and ClWOX6 transgenic plants, which suggested that ClWOX5 and ClWOX6 may play specific important roles in embryo development via complex gene networks. In addition, overexpression of ClWOX5 and ClWOX6 in leaf segments promoted shoot regeneration in tobacco, indicating that ClWOX5 and ClWOX6 can promote plant regeneration and could be used to improve genetic transformation. In conclusion, these results help to elucidate the function of the WOX gene and provide a valuable basis for future studies of the developmental regulation and applications of WOX genes in C. lanceolata.


Subject(s)
Cunninghamia , Gene Expression Regulation, Plant , Plant Proteins , Plant Proteins/genetics , Plant Proteins/metabolism , Cunninghamia/genetics , Multigene Family , Arabidopsis/genetics , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Seeds/genetics , Seeds/growth & development , Phylogeny , Plants, Genetically Modified/genetics , Genes, Plant
11.
Environ Geochem Health ; 46(5): 149, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38578493

ABSTRACT

There is limited evidence linking exposure to heavy metals, especially mixed metals, to stress urinary incontinence (SUI). This study aimed to explore the relationship between multiple metals exposure and SUI in women. The data were derived from the National Health and Nutrition Examination Survey (NHANES), 2007-2020. In the study, a total of 13 metals were analyzed in blood and urine. In addition, 5155 adult women were included, of whom 2123 (41.2%) suffered from SUI. The logistic regression model and restricted cubic spline (RCS) were conducted to assess the association of single metal exposure with SUI risk. The Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) were used to estimate the combined effect of multiple metals exposure on SUI. First, we observed that blood Pb, Hg and urinary Pb, Cd were positively related to SUI risk, whereas urinary W was inversely related by multivariate logistic regression (all p-FDR < 0.05). Additionally, a significant non-linear relationship between blood Hg and SUI risk was observed by RCS analysis. In the co-exposure models, WQS model showed that exposure to metal mixtures in blood [OR (95%CI) = 1.18 (1.06, 1.31)] and urine [OR (95%CI) = 1.18 (1.03, 1.34)] was positively associated with SUI risk, which was consistent with the results of BKMR model. A potential interaction was identified between Hg and Cd in urine. Hg and Cd were the main contributors to the combined effects. In summary, our study indicates that exposure to heavy metal mixtures may increase SUI risk in women.


Subject(s)
Mercury , Metals, Heavy , Urinary Incontinence, Stress , Adult , Female , Humans , Nutrition Surveys , Bayes Theorem , Cadmium/toxicity , Lead , Urinary Incontinence, Stress/chemically induced , Urinary Incontinence, Stress/epidemiology , Metals, Heavy/toxicity
12.
J Med Chem ; 67(10): 8309-8322, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38669059

ABSTRACT

Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), a subfamily of the PDE super enzyme, might work as a potent target for liver fibrosis by regulating the concentration of cAMP and cGMP. However, there are few PDE1 selective inhibitors, and none has been investigated for liver fibrosis treatment yet. Herein, compound AG-205/1186117 with the dihydropyrimidine scaffold was selected as the hit by virtual screening. A hit-to-lead structural modification led to a series of dihydropyrimidine derivatives. Lead 13h exhibited the IC50 of 10 nM against PDE1, high selectivity over other PDEs, as well as good safety properties. Administration of 13h exerted significant anti-liver fibrotic effects in bile duct ligation-induced fibrosis rats, which also prevented TGF-ß-induced myofibroblast differentiation in vitro, confirming that PDE1 could work as a potential target for liver fibrosis.


Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 1 , Drug Design , Liver Cirrhosis , Phosphodiesterase Inhibitors , Pyrimidines , Animals , Cyclic Nucleotide Phosphodiesterases, Type 1/antagonists & inhibitors , Cyclic Nucleotide Phosphodiesterases, Type 1/metabolism , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Pyrimidines/chemistry , Pyrimidines/therapeutic use , Humans , Rats , Phosphodiesterase Inhibitors/pharmacology , Phosphodiesterase Inhibitors/chemical synthesis , Phosphodiesterase Inhibitors/therapeutic use , Phosphodiesterase Inhibitors/chemistry , Male , Structure-Activity Relationship , Rats, Sprague-Dawley , Molecular Docking Simulation , Molecular Structure
13.
Int J Mol Sci ; 25(8)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38673941

ABSTRACT

Abdominal aortic aneurysm (AAA) is a serious vascular disease which is associated with vascular remodeling. CD38 is a main NAD+-consuming enzyme in mammals, and our previous results showed that CD38 plays the important roles in many cardiovascular diseases. However, the role of CD38 in AAA has not been explored. Here, we report that smooth-muscle-cell-specific deletion of CD38 (CD38SKO) significantly reduced the morbidity of AngII-induced AAA in CD38SKOApoe-/- mice, which was accompanied with a increases in the aortic diameter, medial thickness, collagen deposition, and elastin degradation of aortas. In addition, CD38SKO significantly suppressed the AngII-induced decreases in α-SMA, SM22α, and MYH11 expression; the increase in Vimentin expression in VSMCs; and the increase in VCAM-1 expression in smooth muscle cells and macrophage infiltration. Furthermore, we demonstrated that the role of CD38SKO in attenuating AAA was associated with the activation of sirtuin signaling pathways. Therefore, we concluded that CD38 plays a pivotal role in AngII-induced AAA through promoting vascular remodeling, suggesting that CD38 may serve as a potential therapeutic target for the prevention of AAA.


Subject(s)
ADP-ribosyl Cyclase 1 , Angiotensin II , Aortic Aneurysm, Abdominal , Mice, Knockout , Myocytes, Smooth Muscle , Vascular Remodeling , Animals , Male , Mice , ADP-ribosyl Cyclase 1/metabolism , ADP-ribosyl Cyclase 1/genetics , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/pathology , Disease Models, Animal , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/genetics , Mice, Inbred C57BL , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Myosin Heavy Chains/metabolism , Myosin Heavy Chains/genetics , Signal Transduction , Vascular Remodeling/genetics
14.
Aging (Albany NY) ; 16(9): 7704-7732, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38683136

ABSTRACT

BACKGROUND: Liver metastasis (LM) stands as a primary cause of mortality in metastatic colorectal cancer (mCRC), posing a significant impediment to long-term survival benefits from targeted therapy and immunotherapy. However, there is currently a lack of comprehensive investigation into how senescent and exhausted immune cells contribute to LM. METHODS: We gathered single-cell sequencing data from primary colorectal cancer (pCRC) and their corresponding matched LM tissues from 16 mCRC patients. In this study, we identified senescent and exhausted immune cells, performed enrichment analysis, cell communication, cell trajectory, and cell-based in vitro experiments to validate the results of single-cell multi-omics. This process allowed us to construct a regulatory network explaining the occurrence of LM. Finally, we utilized weighted gene co-expression network analysis (WGCNA) and 12 machine learning algorithms to create prognostic risk model. RESULTS: We identified senescent-like myeloid cells (SMCs) and exhausted T cells (TEXs) as the primary senescent and exhausted immune cells. Our findings indicate that SMCs and TEXs can potentially activate transcription factors downstream via ANGPTL4-SDC1/SDC4, this activation plays a role in regulating the epithelial-mesenchymal transition (EMT) program and facilitates the development of LM, the results of cell-based in vitro experiments have provided confirmation of this conclusion. We also developed and validated a prognostic risk model composed of 12 machine learning algorithms. CONCLUSION: This study elucidates the potential molecular mechanisms underlying the occurrence of LM from various angles through single-cell multi-omics analysis in CRC. It also constructs a network illustrating the role of senescent or exhausted immune cells in regulating EMT.


Subject(s)
Cellular Senescence , Colorectal Neoplasms , Epithelial-Mesenchymal Transition , Liver Neoplasms , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/genetics , Epithelial-Mesenchymal Transition/genetics , Liver Neoplasms/secondary , Liver Neoplasms/immunology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Single-Cell Analysis , Myeloid Cells/immunology , Myeloid Cells/metabolism , Myeloid Cells/pathology , Male , Female , Prognosis , Gene Expression Regulation, Neoplastic , T-Lymphocytes/immunology
15.
Methods Mol Biol ; 2782: 39-63, 2024.
Article in English | MEDLINE | ID: mdl-38622391

ABSTRACT

T cells are a heterogeneous group of cells that can be classified into different subtypes according to different classification methods. The body's immune system has a highly complex and effective regulatory network that allows for the relative stability of immune system function. Maintaining proper T cell homeostasis is essential for promoting protective immunity and limiting autoimmunity and tumor formation. Among the T cell family members, more and more T cell subsets have gradually been characterized. In this chapter, we summarize the functions of some key T cell subsets and their impact on immune homeostasis.


Subject(s)
Neoplasms , T-Lymphocytes, Regulatory , Humans , T-Lymphocyte Subsets , Autoimmunity , Homeostasis
16.
Stem Cell Res ; 77: 103423, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38640637

ABSTRACT

Sorsby fundus dystrophy (SFD) is a rare autosomal dominant disorder with macular dystrophy and severe visual loss. Mutations in TIMP3 gene has been related to SFD with mechanisms unclear. We have successfully reprogrammed the peripheral blood mononuclear cells (PBMCs) from an SFD patient carrying c.484G>A mutation in TIMP3 gene to induced pluripotent stem cells (iPSCs) and characterized their pluripotency and genetic stability. This line may serve as a useful tool to explore the role of TIMP3 in SFD pathogenesis.


Subject(s)
Induced Pluripotent Stem Cells , Mutation , Tissue Inhibitor of Metalloproteinase-3 , Female , Humans , Male , Cell Line , Induced Pluripotent Stem Cells/metabolism , Macular Degeneration/genetics , Macular Degeneration/pathology , Tissue Inhibitor of Metalloproteinase-3/genetics
17.
Article in English | MEDLINE | ID: mdl-38687857

ABSTRACT

Objective: The objective of this study was to investigate and analyze the effects of esketamine combined with comprehensive nursing intervention on postoperative pain, postpartum depression, and quality of life in women undergoing cesarean section. Methods: This study included 140 parturients who underwent cesarean section in The Second Hospital of Dalian Medical University (from May 2021 to May 2022). The participants were divided into two groups: the control group and the study group, based on random allocation. The control group received traditional treatment and routine nursing care, while the study group received esketamine combined with comprehensive nursing intervention. Postoperative pain, postpartum depression, and quality of life were assessed using the Visual Analog Scale (VAS), Edinburgh Postnatal Depression Scale (EPDS), and SF-36 questionnaire, respectively. Results: The two groups had no significant differences in baseline data (P > .05). The postoperative VAS scores of the study group (1.86 ± 0.65) were lower than those of the control group (3.04 ± 0.79) (P < .05). The postoperative EPDS scores of the study group (5.23 ± 1.07) were lower than those of the control group (8.11 ± 1.84) (P < .05). The postoperative physiological recovery of the study group was superior to that of the control group (P < .05). The postoperative SF-36 scores of the study group were higher than those of the control group (P < .05). Practical Implications: The combined use of esketamine and comprehensive nursing in cesarean sections offers practical benefits for patient care. Notably, it leads to reduced postoperative pain, as indicated by lower VAS scores, promising improved satisfaction for parturients. The intervention also demonstrates a positive impact on postpartum mental health, with lower EPDS scores suggesting potential benefits in alleviating depression. Moreover, the observed accelerated physiological recovery in the study group, along with shorter hospital stays, signifies efficiency gains in healthcare delivery. This not only optimizes resource utilization but also contributes to an enhanced overall recovery experience for women undergoing cesarean sections. Conclusion: The application of esketamine combined with comprehensive nursing intervention after cesarean section has a positive impact on the pain relief, postpartum depression, and quality of life of parturients. This study provides new insights and guidance for clinical practice, potentially enhancing the postoperative experience of women undergoing cesarean section. These findings furnish healthcare professionals with valuable insights and guidance, fostering a nuanced and improved standard of care in obstetric practices.

18.
PeerJ ; 12: e17176, 2024.
Article in English | MEDLINE | ID: mdl-38560479

ABSTRACT

The effects of nitrogen application or earthworms on soil respiration in the Huang-Huai-Hai Plain of China have received increasing attention. However, the response of soil carbon dioxide (CO2) emission to nitrogen application and earthworm addition is still unclear. A field experiment with nitrogen application frequency and earthworm addition was conducted in the Huang-Huai-Hai Plain. Results showed nitrogen application frequency had a significant effect on soil respiration, but neither earthworms nor their interaction with nitrogen application frequency were significant. Low-frequency nitrogen application (NL) significantly increased soil respiration by 25%, while high-frequency nitrogen application (NH), earthworm addition (E), earthworm and high-frequency nitrogen application (E*NH), and earthworm and low-frequency nitrogen application (E*NL) also increased soil respiration by 21%, 21%, 12%, and 11%, respectively. The main reason for the rise in soil respiration was alterations in the bacterial richness and keystone taxa (Myxococcales). The NH resulted in higher soil nitrogen levels compared to NL, but NL had the highest bacterial richness. The abundance of Corynebacteriales and Gammaproteobacteria were positively connected with the CO2 emissions, while Myxococcales, Thermoleophilia, and Verrucomicrobia were negatively correlated. Our findings indicate the ecological importance of bacterial communities in regulating the carbon cycle in the Huang-Huai-Hai Plain.


Subject(s)
Myxococcales , Oligochaeta , Animals , Carbon Dioxide , Glycine max , Nitrogen/pharmacology , Soil , Crops, Agricultural
19.
Crit Rev Oncol Hematol ; 196: 104323, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38462148

ABSTRACT

BACKGROUND: Smoking history is a heterogeneous situation for different populations, and numerous studies suggest that smoking cessation is conducive to reduce the mortality of lung cancer. However, no quantitative meta-analysis regarding smoking cessation duration based on different populations has demonstrated it clearly. METHODS: We systematically searched four electronic databases (PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Scoups) till February 2023. Eligible studies reported the association between lung cancer survival and duration of smoking cessation. Additionally, we stratified the study population according to whether they had lung cancer at the time they quit smoking. Studies were pooled with the random-effects model. RESULTS: Out of the 11,361 potential studies initially identified, we included 24 studies involving 969,560 individuals in our analysis. Lung cancer mortality varied across two groups: general quitters and peri-diagnosis quitters. For general quitters, those who had quit smoking for less than 10 years exhibited an RR of 0.64 (95% CI [0.55-0.76]), while those who quit for 10-20 years had an RR of 0.33 (0.25-0.43), over 20 years had an RR of 0.16 (0.11-0.24), and never-smokers had an RR at 0.11 (0.07-0.15). Among peri-diagnosis quitters, the 1-year Overall Survival (OS) showed an RR of 0.80 (0.67-0.96), the 2-year OS had an RR of 0.89 (0.80-0.98), the 3-year OS had an RR of 0.93 (0.84-1.03), and the 5-year OS had an RR of 0.85 (0.76-0.96). CONCLUSIONS: Earlier and longer smoking cessation is associated with reduced lung cancer mortality, no matter in which cessation stage for two different populations.


Subject(s)
Lung Neoplasms , Smoking Cessation , Humans , Lung Neoplasms/etiology , Smoking/adverse effects , Smoking/epidemiology , Tobacco Smoking
20.
Stem Cell Res ; 77: 103390, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38507880

ABSTRACT

Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinopathy resulting in irreversible loss of vision. Mutations in RAX2 gene has been related to RP with mechanisms unclear. Here, we generated a human induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a RP patient carrying c.77C > T mutation in RAX2 gene. This cell line was induced by integration-free episomal vectors and validated for pluripotency and differentiation capacity, which may serve as a model to study the role of RAX2 in RP pathogenesis.


Subject(s)
Homeodomain Proteins , Induced Pluripotent Stem Cells , Mutation , Retinitis Pigmentosa , Humans , Retinitis Pigmentosa/genetics , Retinitis Pigmentosa/pathology , Induced Pluripotent Stem Cells/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Cell Line , Cell Differentiation , Eye Proteins/genetics , Eye Proteins/metabolism , Male , Transcription Factors
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