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1.
Mar Pollut Bull ; 203: 116432, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38728954

ABSTRACT

Salinity fluctuations significantly impact the reproduction, growth, development, as well as physiological and metabolic activities of fish. To explore the osmoregulation mechanism of aquatic organisms acclimating to salinity stress, the physiological and transcriptomic characteristics of spotted seabass (Lateolabrax maculatus) in response to varying salinity gradients were investigated. In this study, different salinity stress exerted inhibitory effects on lipase activity, while the impact on amylase activity was not statistically significant. Notably, a moderate increase in salinity (24 psu) demonstrated the potential to enhance the efficient utilization of proteins by spotted seabass. Both Na+/K+-ATPase and malondialdehyde showed a fluctuating trend of increasing and then decreasing, peaking at 72 h. Transcriptomic analysis revealed that most differentially expressed genes were involved in energy metabolism, signal transduction, the immune response, and osmoregulation. These results will provide insights into the molecular mechanisms of salinity adaptation and contribute to sustainable development of the global aquaculture industry.


Subject(s)
Bass , Salinity , Transcriptome , Animals , Bass/physiology , Bass/genetics , Osmoregulation , Salt Stress , Sodium-Potassium-Exchanging ATPase/metabolism , Sodium-Potassium-Exchanging ATPase/genetics
2.
Infect Dis Ther ; 13(6): 1215-1233, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38700654

ABSTRACT

INTRODUCTION: Persistent nasal carriage has been associated with Staphylococcus aureus infection. Previous S. aureus studies in Asia have primarily focused on clinical patients, providing limited information on persistent nasal carriage among the general adult population. METHODS: This study examined 143 healthy adults in a community in Jiangsu, China. Nasal swab samples were collected 10 times. The colonization status was identified using SPA typing. We also determined antimicrobial susceptibility, genotype, and genomic characteristics of S. aureus. RESULTS: The prevalence of S. aureus nasal carriage among the community individuals was on average 16.78%. The carriage rates of methicillin-resistant S. aureus and multidrug-resistant S. aureus were 6.29% and 7.69%, respectively. We identified 8.39% persistent carriers, 39.16% intermittent carriers, and 52.45% noncarriers. Furthermore, family members displayed concordance in terms of genotype and genomic characteristics. CONCLUSION: Persistent nasal sampling captured intermittent carriers that were missed during short-term sampling, thus highlighting the necessity for regular community testing. SPA typing can serve as a rapid method for determining S. aureus colonization. The potential for intrafamilial transmission of S. aureus is evident, with persistent carriers being the most probable source of infection.

3.
Int J Biol Macromol ; 271(Pt 2): 132581, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38797301

ABSTRACT

Bamboo shoot is a kind of widely distributed natural green vegetable, which has a long history of consumption and cultivation, and has edible, nutritional and economic value. Bamboo shoot is nutrient-rich food with carbohydrates, fats, proteins, polysaccharides, flavonoids, alkaloids and other chemical components, can meet the body's needs. Notably, bamboo shoot polysaccharides are the most attractive saccharides, most of which are water-soluble polysaccharides, and their various biological activities have been paid more attention by researchers. With the deepening of research on bamboo shoot polysaccharides, they have been found to have anti-diabetic, anti-oxidant, anti-inflammatory, anti-complement activities, immunomodulatory, etc. Further research on bamboo shoot polysaccharides, their sources, molecular weights, chemical structures, monosaccharide compositions and structural characteristics are constantly explored. In order to better research and development of bamboo shoot polysaccharides, it is necessary to carry on a comprehensive arrangement. Here, the extraction and purification methods, structural characteristics, health benefits, structure-activity relationships and product applications of bamboo shoot polysaccharides were systematically reviewed. This article will deepen the understanding of bamboo shoot polysaccharides, provide knowledge base for further research on bamboo shoot polysaccharides, and expand the vision for developing related products.

4.
World J Gastrointest Oncol ; 16(4): 1227-1235, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38660665

ABSTRACT

BACKGROUND: Postoperative delirium, particularly prevalent in elderly patients after abdominal cancer surgery, presents significant challenges in clinical management. AIM: To develop a synthetic minority oversampling technique (SMOTE)-based model for predicting postoperative delirium in elderly abdominal cancer patients. METHODS: In this retrospective cohort study, we analyzed data from 611 elderly patients who underwent abdominal malignant tumor surgery at our hospital between September 2020 and October 2022. The incidence of postoperative delirium was recorded for 7 d post-surgery. Patients were divided into delirium and non-delirium groups based on the occurrence of postoperative delirium or not. A multivariate logistic regression model was used to identify risk factors and develop a predictive model for postoperative delirium. The SMOTE technique was applied to enhance the model by oversampling the delirium cases. The model's predictive accuracy was then validated. RESULTS: In our study involving 611 elderly patients with abdominal malignant tumors, multivariate logistic regression analysis identified significant risk factors for postoperative delirium. These included the Charlson comorbidity index, American Society of Anesthesiologists classification, history of cerebrovascular disease, surgical duration, perioperative blood transfusion, and postoperative pain score. The incidence rate of postoperative delirium in our study was 22.91%. The original predictive model (P1) exhibited an area under the receiver operating characteristic curve of 0.862. In comparison, the SMOTE-based logistic early warning model (P2), which utilized the SMOTE oversampling algorithm, showed a slightly lower but comparable area under the curve of 0.856, suggesting no significant difference in performance between the two predictive approaches. CONCLUSION: This study confirms that the SMOTE-enhanced predictive model for postoperative delirium in elderly abdominal tumor patients shows performance equivalent to that of traditional methods, effectively addressing data imbalance.

5.
Biochem Biophys Res Commun ; 711: 149909, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38615573

ABSTRACT

RNA analysis has shown great value in forensic science, such as body fluids and tissue identification, postmortem interval estimation, biological age prediction, etc. Currently, most RNA follow-up experiments involve reverse transcription (RT) procedures. It has been shown that the RT step is variable and has a greater impact on subsequent data analysis, especially for forensic trace samples. However, the pattern of variation between different RNA template inputs and complementary DNA (cDNA) yield is unclear. In this study, a series of 2-fold gradient dilutions of RNA standards (1 µg/µL - 0.24 ng/µL) and forensic samples (including blood samples, saliva samples, bloodstains, and saliva stains) were reverse-transcribed using EasyQuick RT MasterMix. The obtained cDNA was quantified by droplet digital PCR (ddPCR) to assess the RT yield of the ACTB gene. The results showed that the 125 ng RNA template had the highest RT yield in a 10 µL RT reaction system with the selected kit. For all stain samples, the RT yield improved as the amount of RNA template input increased since RNA quantities were below 125 ng. As many commercialized reverse transcription kits using different kinds of enzymes are available for forensic RNA research, we recommend that systematic experiments should be performed in advance to determine the amount of RNA input at the optimum RT yield when using any kit for reverse transcription experiments.


Subject(s)
RNA , Humans , RNA/genetics , RNA/analysis , Reverse Transcription , Saliva/metabolism , Saliva/chemistry , Forensic Genetics/methods , Forensic Genetics/standards , Reverse Transcriptase Polymerase Chain Reaction/standards , Reverse Transcriptase Polymerase Chain Reaction/methods , Reference Standards , DNA, Complementary/genetics , Blood Stains , Polymerase Chain Reaction/methods , Polymerase Chain Reaction/standards
6.
Neurol Res ; 46(7): 669-678, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38602312

ABSTRACT

OBJECTIVE: Serum globulin is associated with inflammatory or immune disorders. However, it has not been established whether it is associated with myasthenia gravis (MG). We investigated the association between globulin with relapse and prognosis in children with MG. METHODS: A cohort of 148 MG cases and 150 healthy children were retrospectively enrolled from January 2015 to December 2021. Multivariate logistic and Cox regression models were used to analyze the treatment outcomes and recurrence of case group, exploring the influence of globulin. RESULTS: Compared with the control group, globulin levels in the MG group were slightly increased (t = 7.244, p < 0.001). After a mean follow-up of 2.25 ± 1.05 years, 35 cases relapsed, with a relapse rate of 23.65%. Logistic regression analysis showed that globulin levels at admission [adjusted odds ratio (OR) = 1.233, 95% confidence interval (CI) 1.028-1.472, p = 0.018] were independent risk factors for relapse. Cox regression analysis confirmed that globulin levels at admission affects relapse-free time [adjusted hazard ratio (HR) = 0.552, 95% CI 0.357-0.852, p = 0.007]. Receiver operating characteristic curve determined 25.10 as the optimal cutoff value for globulin. Cox regression showed that high globulin levels (>25.10) at admission (adjusted HR = 0.607, 95% CI 0.383-0.961, p = 0.033) were independent risk factors for poor therapeutic outcomes at follow-up. Ordinal logistic regression showed that globulin affects the treatment plan (OR = 1.445, 95% CI 1.223-1.847, p = 0.014). CONCLUSIONS: Elevated globulin levels in children with MG on admission predicts a high relapse rate and poor long-term therapeutic efficacies.


Serum globulin in children with myasthenia gravis: predicting relapse and prognosisFirst, the globulin in the MG children was higher than in the healthy controls, and there was some correlation between the globulin and the level of systemic inflammation.Second, globulin has been associated with relapse of MG in children. The higher the globulin, the higher the relapse rate and the shorter the time to prevent a relapse.Third, both initial and final globulin were related to the effect of MG in children, and the higher the long-term effect, the worse the long-term effect. It also influenced the change in treatment plan.


Subject(s)
Myasthenia Gravis , Recurrence , Serum Globulins , Humans , Myasthenia Gravis/blood , Myasthenia Gravis/diagnosis , Myasthenia Gravis/drug therapy , Male , Female , Child , Serum Globulins/analysis , Serum Globulins/metabolism , Retrospective Studies , Prognosis , Child, Preschool , Adolescent , Follow-Up Studies
7.
Talanta ; 275: 126149, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38678926

ABSTRACT

Species and sex confirmation of the biological specimen play a crucial role in crime investigation. However, the specimen found in the scene is always trace quantity, which is hard to be analyzed by current methods. Moreover, the time-consuming DNA extraction, sophisticated apparatus, and complex data processing make it difficult to satisfy the demand of speediness and convenience for point-of-care tests. In this study, we first exhibit a phosphate-based visual system for field-based species and sex identification derived from trace bloodstain. By introducing phosphate ion-based colorimetry into loop-mediated isothermal amplification (LAMP) for result interpretation, not only the bloodstain can be directly submitted to mitochondrial variant amplification owing to the enhanced amplification efficiency by pyrophosphate ion hydrolyzation, but also the colorimetric signal can be recognized by the naked eye for result output within 30 min through molybdophosphate generation. Aerosol contamination, the major conflict of LAMP, has been solved once and for all by integrating uracil-DNA glycosylase into this system that still holds on a constant temperature. As a demonstration, cytochrome b and Y-chromosomal amelogenin are employed to identify species and sex respectively, which has achieved a highly sensitive and specific distinguishability under a strong interferential background. Accurate results can be obtained from both the simulative degraded and dated specimen, which indicates that this novel system may serve as a promising tool in forensic practice.


Subject(s)
Blood Stains , Colorimetry , Nucleic Acid Amplification Techniques , Phosphates , Colorimetry/methods , Nucleic Acid Amplification Techniques/methods , Phosphates/chemistry , Humans , Female , Animals , Male , Sex Determination Analysis/methods , Molecular Diagnostic Techniques
8.
Endocr Connect ; 13(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38492309

ABSTRACT

Objective: Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, the potential mechanism of how GHD influences liver function remains obscure. In the present study, we aim to perform hepatic metabolomics in Lewis dwarf rats, which were the standard congenital isolated GH-deficient rat, to evaluate the characterizations of hepatic metabolic profiles and explore their relations with liver functions. Methods: Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. Body lengths and weights, liver weights, serum alanine transaminase (ALT), and serum aspartate transaminase (AST) were measured. ELISA and RT-qPCR were used to assess IGF-1 levels in serum and liver, respectively. The non-targeted metabolomics was performed in the livers of dw/+ and dw/dw rats. Differential metabolites were selected according to the coefficient of variation (CV), variable importance in the projection (VIP) > 1, and P < 0.05. Hierarchical clustering of differential metabolites was conducted, and the KEGG database was used for metabolic pathway analysis. Results: The body weights, body lengths, liver weights, and IGF-1 levels in the serum and liver of dw/dw rats were significantly decreased compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 differential metabolites in positive ion mode, and 51 metabolites in negative ion mode were identified. Among them, lysophosphatidylcholine (LPC) 16:2, LPC 18:3, LPC 22:6, fatty acid esters of hydroxy fatty acids (FAHFA)18:1 were significantly decreased, while palmitoyl acid, dehydrocholic acid, and 7-ketolithocholic acid were significantly increased in dw/dw rats compared with dw/+ rats. These seven differential metabolites were significantly associated with phenotypes of rats. Finally, KEGG pathway analysis showed that the arginine and proline metabolism pathway and bile secretion pathway were mainly clustered. Conclusion: Lewis dw/dw rats with congenital isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with the distinctive hepatic metabolic profiles.

9.
Sci Total Environ ; 922: 171337, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38428596

ABSTRACT

Throughout history, there were many fine mural paintings concealed within ancient buildings, hidden beneath layers of plaster, wall or other structure. In recent decades, research and practical efforts had primarily focused on nondestructive diagnosis of these hidden murals and the removal of their surface coverings. However, limited attention had been given to the consequences of overlay removal on mural preservation. This study aims to address this gap by examining the revealed mural paintings in the Prince Shi's Palace as a case study, employing an analysis of mural ontology, investigation into the preservation environment, and simulation experiments to comprehensively analyze the factors contributing to the rapid deterioration of these revealed murals. The findings indicated that certain carbonated lime particles adhered to the mural surface, and in a humid environment, these particles absorbed sulfur dioxide from the atmosphere and converted into calcium sulfate. The strong hygroscopic property of calcium sulfate enhanced the humidity on the surface of murals, thereby increasing their susceptibility to sulfur dioxide absorption. Over time, the murals suffered more sulphate and moisture damage. Additionally, historically inaccurate interventions such as non-breathable shading curtains installation and organic coatings reinforcement exacerbated this deterioration process. Therefore, safeguarding the integrity of these exposed concealed murals necessitated prioritizing the preservation of environmental humidity and acid gas levels.

10.
Int J Biol Macromol ; 265(Pt 2): 131097, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38537845

ABSTRACT

Hovenia dulcis Thunb. (H. dulcis) is a widely distributed plant with a long history of cultivation and consumption. As a common plant, it has economic, edible and medicinal value. H. dulcis polysaccharides are one of their main bioactive ingredients and have many health benefits, such as anti-diabetes, antioxidation, anti-glycosylation, anti-fatigue, immune regulation activities and alcoholic liver disease protection activity. In this paper, the research progress of H. dulcis polysaccharides in extraction, purification, structural characteristics, biological activities, existing and potential applications were reviewed, which could provide new valuable insights for future studies.


Subject(s)
Antioxidants , Liver Diseases, Alcoholic , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry
11.
Front Genet ; 15: 1293477, 2024.
Article in English | MEDLINE | ID: mdl-38482383

ABSTRACT

Studying how populations in various environments differ genetically is crucial for gaining insights into the evolution of biodiversity. In order to pinpoint potential indicators of divergence and adaptation to diverse environments, we conducted a comprehensive analysis of 3,491,868 single nucleotide polymorphisms (SNPs) derived from five populations of Brachymystax lenok. We discovered significant geographic divergence among these 5 populations, which lack evidence of gene flow among them. Our results further demonstrated that the current distribution pattern of Brachymystax lenok are driven by geographical isolation and changes in oceans and rivers. We also performed genome-wide scan and identified the genes evolved to adapt the different environments, including stress response. In general, these results provide genomic support for high-level genetic divergence and the genetic basis of adaptation to different environments.

12.
Fa Yi Xue Za Zhi ; 40(1): 70-76, 2024 Feb 25.
Article in English, Chinese | MEDLINE | ID: mdl-38500464

ABSTRACT

In recent years, with the continuous progress of DNA extraction and detection technology, cell-free DNA(cfDNA)has been widely used in the life science field, and its potential application value in forensic identification is becoming more and more obvious. This paper reviews the concept, formation mechanism, and classification of cfDNA, etc., and describes the latest research progress of cfDNA in personal identification of crime scene touch DNA samples and non-invasive prenatal paternity testing (NIPPT). Meanwhile, this paper summarizes the potential application of cfDNA in injury inference, and discusses the advantages and disadvantages of common cfDNA analysis methods and techniques, and its application prospects, to provide a new idea for the wide application of cfDNA in the field of forensic science.


Subject(s)
Cell-Free Nucleic Acids , Pregnancy , Female , Humans , Cell-Free Nucleic Acids/genetics , Paternity , Forensic Sciences , Touch , DNA/genetics
13.
Phys Chem Chem Phys ; 26(12): 9488-9499, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38450544

ABSTRACT

There are numerous defects existing on the surface and grain boundary of perovskite, which adversely affect the performance and stability of perovskite solar cell devices. Systematic first-principles calculations show that the I vacancy (VI), Pb vacancy (VPb), Pb-I antisite (PbI), and I-Pb antisite (IPb) defects can significantly affect the electronic properties of the surface of formamidinium lead triiodide (FAPbI3); in particular the VPb, PbI and IPb surface defects can introduce defect energy levels in the band gap. Tetrahexylammonium iodide (THAI) that is strongly adsorbed on the (1 0 0) surface of FAPbI3 by forming Pb-I coordination bonds and I⋯H hydrogen bonds could eliminate or reduce the defect states near the band edge or in the band gap by transferring electrons between THAI and the surface of FAPbI3. In particular, the defect states introduced by VPb could be completely eliminated after the adsorption of THAI. This study shows an in-depth understanding of the influence of defects on the electronic properties of the surface of FAPbI3, as well as the passivation mechanism of organic salts on the surface defects of perovskite.

14.
Clin Chim Acta ; 557: 117884, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38522821

ABSTRACT

BACKGROUND: Copy number variation sequencing (CNV-seq) is crucial in prenatal diagnosis, but its limitations in detecting polyploidy, maternal cell contamination (MCC), and uniparental disomy (UPD) restrict its application in the analysis of products of conception (POCs). This study aimed to investigate an optimal genetic testing strategy for POCs in the era of CNV-seq. METHODS: CNV-seq and quantitative fluorescent polymerase chain reaction (QF-PCR) were performed in all 4,211 spontaneous miscarriage cases. Different testing strategies were compared and the optimal testing strategies were proposed. RESULTS: Of the 4,211 cases, 2561 (60.82%) exhibited clinically significant chromosomal abnormalities. CNV-seq alone, without QF-PCR, might misdiagnose 311 (7.39%) cases, including 278 polyploidy, 13 UPD, and 20 MCC. In 20 MCC cases identified by QF-PCR, CNV-seq successfully pinpointed the cause of miscarriage in 13 cases. Furthermore, in cases where QF-PCR suggested polyploidy, CNV-seq improved the diagnostic accuracy in 54 (1.28%) hypo/hypertriploidy cases. After comparing four different strategies, the sequential approach (initiating with CNV-seq followed by QF-PCR if necessary) emerged as advantageous, reducing approximately 70% of the cost associated with QF-PCR while maintaining result accuracy. CONCLUSIONS: We propose an initial CNV-seq followed by QF-PCR if needed-an efficient and cost-effective strategy for the genetic analysis of POCs.


Subject(s)
Abortion, Spontaneous , Chromosome Disorders , Pregnancy , Female , Humans , Chromosome Disorders/genetics , DNA Copy Number Variations/genetics , Abortion, Spontaneous/diagnosis , Abortion, Spontaneous/genetics , Karyotyping , Chromosome Aberrations , Prenatal Diagnosis , Polyploidy
15.
Neuroreport ; 35(5): 299-305, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38305147

ABSTRACT

Hazard perception refers to a driver's ability to identify potential hazards on the road. Although studies have shown that overconfidence affects drivers' ability to perceive hazards, the neural processing of hazard perception in overconfident drivers under different hazard types has rarely been investigated. A mixed experimental design of 2 (hazard type: hazards, no hazards) × 2 (driver group: overconfident driver, control group) was used. A total of 120 images (60 with hazards and 60 without hazards) were presented to 25 overconfident drivers and 25 drivers in the control group. Reaction time, response accuracy, P200 (200-250 ms), and N2 (280-330 ms) components were measured via event-related potential (ERP) technology. Response times of overconfident drivers are slower than those of the control group regardless of hazard types. The P200 latency of overconfident drivers was longer than that of their peers in hazard situations, while the P200 latency was similar between the two groups in no-hazard situations. Although a significant interaction was found on the N2 amplitude, no significant differences were found between the two groups in both hazard and no-hazard situations. Overconfident drivers have worse hazard perception performance in hazard situations with slower reaction times and greater P200 latencies than their peers. More importantly, P200 amplitude and N2 amplitude are sensitive to hazard types, while P200 amplitude and N2 latency can discriminate between driver groups. The findings help understand the negative impact of overconfidence on young drivers and contribute to the development and training of hazard perception tests.


Subject(s)
Automobile Driving , Male , Humans , Accidents, Traffic , Reaction Time , Perception/physiology
16.
Heliyon ; 10(2): e24854, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38312556

ABSTRACT

Background: To exploit hepatocellular carcinoma (HCC) diagnostic substances, we identify potential predictive markers based on machine learning and to explore the significance of immune cell infiltration in this pathology. Method: Three HCC gene expression datasets were used for weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest were applied to identify candidate biomarkers. The diagnostic value of HCC diagnostic gene biomarkers was further assessed by the area under the ROC curve observed in the validation dataset. CIBERSORT was used to analyze 22 immune cell fractions from HCC patients and to analyze their correlation with diagnostic markers. In addition, the prognostic value of the markers and the sensitivity of the drugs were analyzed. Result: WGCNA and differential expression analysis were used to screen 396 distinct gene signatures in HCC tissues. They were mostly engaged in cytoplasmic fusion and the cell division cycle, according to gene enrichment analyses. Five genes were shown to have a high diagnostic value for use as diagnostic biomarkers for HCC, including EFHD1 (AUC = 0.77), KIF4A (AUC = 0.97), UBE2C (AUC = 0.96), SMYD3 (AUC = 0.91), and MCM7 (AUC = 0.93). T cells, NK cells, macrophages, and dendritic cells were found to be related to diagnostic markers in HCC tissues by immune cell infiltration analysis, indicating that these cells are intimately linked to the onset and spread of HCC. Concurrently, these five genes and their constructed models have considerable prognostic value. Conclusion: These five genes (EFHD1, KIF4A, UBE2C, SMYD3, and MCM7) may serve as new candidate molecular markers for HCC, providing new insights for future diagnosis, prognosis, and molecular therapy of HCC.

17.
Front Immunol ; 15: 1341985, 2024.
Article in English | MEDLINE | ID: mdl-38352870

ABSTRACT

Introduction: The host immune response determines the differential outcome of acute or chronic viral infections. The comprehensive comparison of lymphoid tissue immune cells at the single-cell level between acute and chronic viral infections is largely insufficient. Methods: To explore the landscape of immune responses to acute and chronic viral infections, single-cell RNA sequencing(scRNA-seq), scTCR-seq and scBCR-seq were utilized to evaluate the longitudinal dynamics and heterogeneity of lymph node CD45+ immune cells in mouse models of acute (LCMV Armstrong) and chronic (LCMV clone 13) viral infections. Results: In contrast with acute viral infection, chronic viral infection distinctly induced more robust NK cells and plasma cells at the early stage (Day 4 post-infection) and acute stage (Day 8 post-infection), respectively. Moreover, chronic viral infection exerted decreased but aberrantly activated plasmacytoid dendritic cells (pDCs) at the acute phase. Simultaneously, there were significantly increased IgA+ plasma cells (MALT B cells) but differential usage of B-cell receptors in chronic infection. In terms of T-cell responses, Gzma-high effector-like CD8+ T cells were significantly induced at the early stage in chronic infection, which showed temporally reversed gene expression throughout viral infection and the differential usage of the most dominant TCR clonotype. Chronic infection also induced more robust CD4+ T cell responses, including follicular helper T cells (Tfh) and regulatory T cells (Treg). In addition, chronic infection compromised the TCR diversity in both CD8+ and CD4+ T cells. Discussion: In conclusion, gene expression and TCR/BCR immune repertoire profiling at the single-cell level in this study provide new insights into the dynamic and differential immune responses to acute and chronic viral infections.


Subject(s)
CD8-Positive T-Lymphocytes , Lymphocytic Choriomeningitis , Mice , Animals , Lymphocytic choriomeningitis virus , Persistent Infection , Receptors, Antigen, T-Cell , Lymph Nodes , Sequence Analysis, RNA
18.
Environ Sci Pollut Res Int ; 31(6): 9091-9105, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38183550

ABSTRACT

Many studies have established a correlation between air pollution and green space with age-related diseases, yet the relationship between air pollution, green space, and frailty among older adults is not fully understood. The primary objective of this investigation is to examine the longitudinal association among air pollution, green space, and frailty in older adults, as well as the potential interaction and mediating effect. Analyzed data were obtained from the multi-wave CLHLS investigation (2008-2018). The participants' environmental exposure was evaluated using six air pollutants (PM1, PM2.5, PM10, PM10-2.5, O3, and NO2), and normalized difference vegetation index (NDVI). Annual ambient air pollutants were estimated using satellite-based spatiotemporal models. Time-varying Cox proportional risk models were employed to investigate the longitudinal relationships between air pollutants, greenness, and the onset of frailty in the elderly population. We conducted a variety of subgroup analyses, sensitivity analyses, and assessed potential interaction and causal mediating effects. A total of 6953 eligible elderly individuals were enrolled in our study. In the fully adjusted model, per IQR uptick in levels of PM1, PM2.5, PM10, PM10-2.5, O3, and NO2 corresponded to a 17% (95% CI 1.10-1.24), 25% (95% CI 1.17-1.34), 29% (95% CI 1.20-1.39), 35% (95% CI 1.24-1.47), 12% (95% CI 1.04-1.20), and 11% (95% CI 1.05-1.18) increase in frailty risk, respectively. For NDVI, increased IQR was significantly negatively associated with the risk of frailty (aHR 0.82, 95% CI 0.77-0.87). Our results revealed a significant interaction effect among O3, NO2, and residential greenness. PM1, PM2.5, PM10, and PM10-2.5 play a mediating role in the estimated relationship between residential greenness and frailty. In summary, our study reveals that PM1, PM2.5, PM10, PM10-2.5, O3, and NO2 correspond to elevated risks of frailty in the elderly. Residential greenness is associated with a lower risk of frailty in the elderly. Residential greenness can exert a positive impact on frailty by reducing particulate matter concentrations.


Subject(s)
Air Pollutants , Air Pollution , Frailty , Humans , Aged , Nitrogen Dioxide/analysis , Frailty/epidemiology , Prospective Studies , Air Pollution/analysis , Air Pollutants/analysis , Particulate Matter/analysis , Environmental Exposure/analysis , China
20.
Stat Methods Med Res ; 33(1): 80-95, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38062757

ABSTRACT

In recent decades, many phase II clinical trials have used survival outcomes as the primary endpoints. If radiotherapy is involved, the competing risk issue often arises because the time to disease progression can be censored by the time to normal tissue complications, and vice versa. Besides, many existing research has examined that patients receiving the same radiotherapy dose may yield distinct responses due to their heterogeneous radiation susceptibility statuses. Therefore, the "one-size-fits-all" strategy often fails, and it is more relevant to evaluate the subgroup-specific treatment effect with the subgroup defined by the radiation susceptibility status. In this paper, we propose a Bayesian adaptive biomarker stratified phase II trial design evaluating the subgroup-specific treatment effects of radiotherapy. We use the cause-specific hazard approach to model the competing risk survival outcomes. We propose restricting the candidate radiation doses based on each patient's radiation susceptibility status. Only the clinically feasible personalized dose will be considered, which enhances the benefit for the patients in the trial. In addition, we propose a stratified Bayesian adaptive randomization scheme such that more patients will be randomized to the dose reporting more favorable survival outcomes. Numerical studies and an illustrative trial example have shown that the proposed design performed well and outperformed the conventional design ignoring the competing risk issue.


Subject(s)
Clinical Trials, Phase II as Topic , Randomized Controlled Trials as Topic , Research Design , Humans , Bayes Theorem , Biomarkers
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