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1.
J Infect Dis ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39361598

ABSTRACT

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in children. Assessing disease severity and etiology remains challenging in the clinical setting. The objective of this study was to identify mucosal biomarkers that could potentially assist with patient classification. METHODS: We analyzed mucosal concentrations of cytokines in nasopharyngeal samples obtained from a convenience sample of 182 children with CAP and 26 matched healthy controls. Pathogens were identified by cultures and molecular assays. Severe disease was defined by hospital stay ≥ 3 days, and/or PICU admission. Data were analyzed according to identified pathogens and disease severity. RESULTS: Children with CAP and detected atypical bacteria had significantly higher concentrations of MCP-2, IFN-γ and CXCL10 among others compared with those with typical bacteria. Children with influenza virus had significantly higher concentrations of MCP-2, CXCL10, CXCL11, CX3CL1, and IFN-γ than those with typical bacteria. Additionally, children with severe CAP had significantly higher concentrations of CCL23 than children with mild/moderate disease, irrespective of the pathogen(s) identified. CONCLUSIONS: We identified differences in mucosal concentrations of inflammatory and antiviral cytokines in children with CAP according to disease severity and detected pathogens. Mucosal biomarkers represent a promising approach to help assessing disease severity and etiology.

2.
Neural Netw ; 181: 106754, 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39362185

ABSTRACT

Accurate segmentation of thyroid nodules is essential for early screening and diagnosis, but it can be challenging due to the nodules' varying sizes and positions. To address this issue, we propose a multi-attention guided UNet (MAUNet) for thyroid nodule segmentation. We use a multi-scale cross attention (MSCA) module for initial image feature extraction. By integrating interactions between features at different scales, the impact of thyroid nodule shape and size on the segmentation results has been reduced. Additionally, we incorporate a dual attention (DA) module into the skip-connection step of the UNet network, which promotes information exchange and fusion between the encoder and decoder. To test the model's robustness and effectiveness, we conduct the extensive experiments on multi-center ultrasound images provided by 17 local hospitals. The model is trained using the federal learning mechanism to ensure privacy protection. The experimental results show that the Dice scores of the model on the data sets from the three centers are 0.908, 0.912 and 0.887, respectively. Compared to existing methods, our method demonstrates higher generalization ability on multi-center datasets and achieves better segmentation results.

3.
J Proteome Res ; 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39385457

ABSTRACT

Macrophages make up a heterogeneous population of immune cells that exhibit diverse phenotypes and functions in health and disease. Although macrophage epigenomic and transcriptomic profiles have been reported, the proteomes of distinct macrophage populations under various pathological conditions remain largely elusive. Here, we employed a label-free proteomic approach to characterize the diversity of the hepatic macrophage pool in an experimental model of CCl4-induced liver fibrosis. We found a decrease in the proportion of liver resident embryo-derived KCs (EmKCs), and a drastic increase in the proportion of monocyte-derived KCs (MoKCs) and CLEC2-Macs. Proteomic profiling revealed that MoKCs largely resembled EmKCs, whereas CLEC2-Macs exhibited greater proteomic alternations compared with EmKCs, suggesting two distinct destinations for monocyte differentiation during liver fibrosis. Furthermore, CLEC2-Macs were characterized by increased expression of proteins associated with inflammatory response, antigen processing and presentation processes, which may be involved in the pathogenesis of liver fibrosis. Collectively, our study provides insights into the considerable heterogeneity within the hepatic macrophage pool during liver fibrosis.

4.
Vaccines (Basel) ; 12(9)2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39340016

ABSTRACT

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

5.
Sensors (Basel) ; 24(18)2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39338688

ABSTRACT

Objective: This study designed experiments to explore the effects of ischemic preconditioning (IPC) intervention with different cycling periods on the upper limb strength performance of college male bodybuilding athletes. Methods: Ten bodybuilding athletes were recruited for a randomized, double-blind, crossover experimental study. All subjects first underwent pre-tests with two sets of exhaustive bench presses at 60% of their one-repetition maximum (1RM) to assess upper limb strength performance. They then experienced three different IPC intervention modes (T1: 1 × 5 min, T2: 2 × 5 min, T3: 3 × 5 min), as well as a non-IPC intervention mode (CON), followed by a retest of the bench press. An Enode pro device was used to record the barbell's velocity during the bench press movement (peak velocity (PV), mean velocity (MV)); power (peak power (PP), mean power (MP)); and time under tension (TUT) to evaluate upper limb strength performance. Results: PV values: T1 showed significant increases compared to pre-tests in the first (p = 0.02) and second (p = 0.024) tests, and were significantly greater than the CON (p = 0.032); T2 showed a significant increase in PV in the first test (p = 0.035), with no significant differences in other groups. MV values: T1 showed a significant increase in MV in the first test compared to the pre-test (p = 0.045), with no significant differences in other groups. PP values: T1 showed a highly significant increase in PP in the first test compared to the pre-test (p = 0.001), and was significantly higher than the CON (p = 0.025). MP values: T1 showed highly significant increases in MP in both the first (p = 0.004) and second (p = 0.003) tests compared to the pre-test; T2 showed a highly significant increase in MP in the first test (p = 0.039) and a significant increase in the second test (p = 0.039). T1's MP values were significantly higher than the CON in both tests; T2's MP values were significantly higher than the CON in the first (p = 0.005) and second (p = 0.024) tests. TUT values: T1 showed highly significant increases in TUT in the first (p < 0.001) and second (p = 0.002) tests compared to the pre-test, and were significantly higher than the CON. Conclusions: (1) Single-cycle and double-cycle IPC interventions both significantly enhance upper limb strength performance, significantly improving the speed and power in exhaustive bench press tests, with the single-cycle IPC intervention being more effective than the double-cycle IPC intervention. (2) The triple-cycle IPC intervention does not improve the upper limb strength performance of bodybuilding athletes in exhaustive bench presses.


Subject(s)
Athletes , Ischemic Preconditioning , Muscle Strength , Upper Extremity , Humans , Male , Upper Extremity/physiology , Muscle Strength/physiology , Ischemic Preconditioning/methods , Young Adult , Cross-Over Studies , Double-Blind Method , Adult , Weight Lifting/physiology
6.
Transl Pediatr ; 13(8): 1302-1311, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39263300

ABSTRACT

Background: Rebound hyperbilirubinemia (HBB) is still present in as high as 10% of newborn babies. However, the applicability of established prediction models for rebound HBB to Chinese newborns is unclear. This study aimed to establish a model to predict HBB rebound after phototherapy among Chinese neonates. Methods: A retrospective cohort study was conducted on 1,035 HBB infants receiving phototherapy. Rebound HBB was defined as total serum bilirubin (TSB) returning to or above the American Academy of Pediatrics (AAP) phototherapy threshold within 72 hours after the end of phototherapy. The predictive effects of previously published two- and three-variable scores were verified. Neonates were randomly assigned in a 6:4 ratio to the training (n=621) group and the testing (n=414) group. All variables in the training set were used to select predictors by least absolute shrinkage and selection operator (LASSO) regression analysis. The internal validation of the prediction model was performed using the testing set. The model's predictive performance was evaluated by area under the curve (AUC), accuracy, sensitivity, and specificity, each with 95% confidence intervals (CIs). Receiver operating characteristic (ROC) and calibration curves were constructed to evaluate the discrimination ability and fitting effect of the prediction model, respectively. Results: Rebound HBB was observed in 210 patients (20.3%). The AUC for the two- and three-variable scores were 0.498 (95% CI: 0.455-0.540) and 0.498 (95% CI: 0.457-0.540), respectively. Predictive factors for the risk of rebound HBB included formula feeding (>3 times/day), standard phototherapy irradiation time, TSB levels and age at termination of phototherapy, neonatal weight, and differences between TSB levels at the phototherapy termination and phototherapy threshold. The prediction model's AUC was 0.935 (95% CI: 0.911-0.958), the sensitivity was 0.880 (95% CI: 0.809-0.950), the specificity was 0.831 (95% CI: 0.790-0.871), and the accuracy was 0.841 (95% CI: 0.805-0.876). Conclusions: The established model performed well in predicting rebound risk among Chinese infants with HBB, which may be beneficial in treating and managing HBB in infants.

7.
Issues Ment Health Nurs ; : 1-12, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39303164

ABSTRACT

Panic attacks (PAs) are intense episodes of anxiety with severe physical symptoms that can impair an individual's social and occupational functions. Psychoeducation, a structured educational intervention, aims to improve various health aspects, including mental disorders. Delivering psychoeducation via the Internet can overcome barriers to accessing mental health treatment. This study examined the effectiveness of online psychoeducation on panic symptoms, anxiety, and quality of life (QOL) among people experiencing PAs. In this quasi-experimental design, 157 participants with PAs were recruited, and 136 eligible participants were allocated to treatment and control groups. The treatment group received an eight-session online psychoeducational program over 8 weeks, while the control group received reading materials. Outcome variables, including panic symptoms, anxiety, and QOL, were measured at baseline, 1-week post-intervention, and at 8-week follow-up using the Panic Disorder Dimensional (PD-D) scale, the Generalized Anxiety Disorder (GAD-7) scale, and the World Health Organization Quality of Life-BREF (WHOQOL-BREF), respectively. In the treatment group, the split-plot ANOVA showed a significant reduction in panic symptoms [F(1, 98) = 18.86, p < 0.01] and anxiety [F(1, 98) = 18.241, p < 0.01] compared to the control group. However, the intervention did not significantly affect QOL [F(1, 98) = 0.278, MSE = 153.007, p > 0.05]. The online psychoeducational program effectively reduced panic symptoms and anxiety levels but did not significantly impact QOL. Internet-based interventions, including psychoeducation, can improve access to mental health treatment, potentially reducing the treatment gap and enhancing overall mental health outcomes.

8.
J Environ Manage ; 370: 122530, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39293112

ABSTRACT

Vegetation restoration measures have been increasingly employed to alleviate rocky desertification in karst ecosystems. However, the comprehensive effects of these interventions on soil properties and soil organic carbon (SOC) remain poorly understood. Herein, we gathered 644 paired observations from 68 studies and conducted a meta-analysis to quantify the performance of different vegetation restoration measures including moss (MS), grassland (GL), cash crop (CP), shrub (SH), and secondary forest (SF) through soil properties and SOC. Our results demonstrated significant effects of MS, GL, CP, SH, and SF on soil biotic and abiotic factors, each with distinct response characteristics. Particularly, MS significantly enhanced all soil properties (excluding a slight decrease in soil pH by 10.8%). Moreover, MS, GL, CP, SH, and SF could elevate SOC by 32.1%, 17.6%, 24.9%, 59.2%, and 48.7% respectively. Utilizing random forest and linear regression models, we identified primary drivers for SOC in MS, GL, CP, SH, and SF as soil moisture content, arbuscular mycorrhizal fungi, soil microbial phosphorus, total nitrogen, and ß-1,4-glucosidase, respectively. This meta-analysis underlined the varied effects of vegetation restoration measures on soil properties and advocates for restoration measures that prioritize plant productivity and reduce soil temperature during the karst rocky desertification restoration process. Additionally, this study underscores the pivotal role of vegetation rehabilitation in environmental conservation and carbon sequestration of ecologically vulnerable regions.

9.
Food Chem X ; 23: 101759, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-39280221

ABSTRACT

Dried tangerine peel ("Chenpi"), has numerous clinical and nutritional benefits, with its quality being significantly influenced by its storage age, referred to as "Chen Jiu Zhe Liang" in Chinese. Concequently, the rapid and accurate identification of Chenpi's age is important for consumers. In this study, Fourier transform infrared spectroscopy (FTIR) was employed to capture spectral images of Chenpi. These FTIR images were then analyzed using a two-dimensional convolutional neural networks (2D-CNN) model, achieving a discrimination accuracy of 97.92%. To address the "black box" nature of the 2D-CNN, Gradient-weighted Class Activation Mapping Plus Plus (Grad-CAM++) was utilized to highlight the important regions contributing to the model's performance. Additionally, six other machine learning models were developped using features identified by the 2D-CNN to validate their effectiveness. The results demonstrated that the combination of FTIR spectral images and 2D-CNN provides a highly effective method for accurately determining the age of Chenpi.

10.
Bioact Mater ; 42: 573-586, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39308551

ABSTRACT

Mucosal vaccines offer potential benefits over parenteral vaccines for they can trigger both systemic immune protection and immune responses at the predominant sites of pathogen infection. However, the defense function of mucosal barrier remains a challenge for vaccines to overcome. Here, we show that surface modification of exosomes with the fragment crystallizable (Fc) part from IgG can deliver the receptor-binding domain (RBD) of SARS-CoV-2 to cross mucosal epithelial layer and permeate into peripheral lung through neonatal Fc receptor (FcRn) mediated transcytosis. The exosomes F-L-R-Exo are generated by genetically engineered dendritic cells, in which a fusion protein Fc-Lamp2b-RBD is expressed and anchored on the membrane. After intratracheally administration, F-L-R-Exo is able to induce a high level of RBD-specific IgG and IgA antibodies in the animals' lungs. Furthermore, potent Th1 immune-biased T cell responses were also observed in both systemic and mucosal immune responses. F-L-R-Exo can protect the mice from SARS-CoV-2 pseudovirus infection after a challenge. These findings hold great promise for the development of a novel respiratory mucosal vaccine approach.

11.
IET Syst Biol ; 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39308027

ABSTRACT

Long non-coding RNAs (lncRNAs) have emerged as significant contributors to the regulation of various biological processes, and their dysregulation has been linked to a variety of human disorders. Accurate prediction of potential correlations between lncRNAs and diseases is crucial for advancing disease diagnostics and treatment procedures. The authors introduced a novel computational method, iGATTLDA, for the prediction of lncRNA-disease associations. The model utilised lncRNA and disease similarity matrices, with known associations represented in an adjacency matrix. A heterogeneous network was constructed, dissecting lncRNAs and diseases as nodes and their associations as edges. The Graph Attention Network (GAT) is employed to process initial features and corresponding adjacency information. GAT identified significant neighbouring nodes in the network, capturing intricate relationships between lncRNAs and diseases, and generating new feature representations. Subsequently, the transformer captures global dependencies and interactions across the entire sequence of features produced by the GAT. Consequently, iGATTLDA successfully captures complex relationships and interactions that conventional approaches may overlook. In evaluating iGATTLDA, it attained an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95 and an area under the precision recall curve (AUPRC) of 0.96 with a two-layer multilayer perceptron (MLP) classifier. These results were notably higher compared to the majority of previously proposed models, further substantiating the model's efficiency in predicting potential lncRNA-disease associations by incorporating both local and global interactions. The implementation details can be obtained from https://github.com/momanyibiffon/iGATTLDA.

12.
Genet Med ; : 101276, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39306722

ABSTRACT

PURPOSE: To assess the differences in variant classifications using the ACMG/AMP 2015 guidelines and the Bayesian point-based classification system (here referred to as the point system) in 115 hereditary cancer predisposition genes and explore variant sub-tiering by the point system. METHODS: Germline variant classifications for 721 pediatric patients from an in-house panel were retrospectively evaluated using the two scoring systems. RESULTS: 2376 unique variants were identified, with ∼23.5% exhibiting discordant classifications. Unique variants classified by the point system demonstrated a lower rate of variants of uncertain significance (VUS; ∼15%) compared to ACMG/AMP 2015 (∼36%). This change is attributed to unique variants with one benign supporting evidence (∼12%) or one benign strong evidence (∼4%) being classified as likely benign by the point system. Additionally, variants with conflicting/modified evidence (∼5% of 2376) are also resolved by the point system. Sub-tiering unique variants classified by the point system as VUS (n=354) indicates ∼77.4% were VUS-Low (0-1 points), while the remaining ∼22.6% were VUS-Mid (2-3 points) and VUS-High (4-5 points). CONCLUSION: The point system reduces the VUS rate and facilitates their sub-tiering. Future large-scale studies are warranted to explore the impact of the point system on improving VUS reporting and/or VUS clinical management.

13.
Cancer Biol Ther ; 25(1): 2398297, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-39223776

ABSTRACT

Breast cancer ranks the first in the incidence of female cancer and is the most common cancer threatening the life and health of women worldwide.Tumor protein p53-regulated apoptosis-inducing protein 1 (TP53AIP1) is a pro-apoptotic gene downstream of p53. However, the role of TP53AIP1 in BC needs to be investigated. In vitro and in vivo experiments were conducted to assess the biological functions and associated mechanisms. Several bioinformatics analyses were made, CCK8 assay, wound healing, transwell assays, colony formation assay, EDU, flow cytometry, Immunofluorescence, qRT-PCR and Western-blotting were performed. In our study, we discovered that BC samples had low levels of TP53AIP1 expression, which correlated with a lower survival rate in BC patients. When TP53AIP1 was up-regulated, it caused a decrease in cell proliferation, migration, and invasion. It also induced epithelial-to-mesenchymal transition (EMT) and protective autophagy. Furthermore, the over-expression of TP53AIP1 suppressed tumor growth when tested in vivo. We also noticed that TP53AIP1 up-regulation resulted in decreased levels of phosphorylation in AKT and mTOR, suggesting a mechanistic role. In addition, we performed functional rescue experiments where the activation of AKT was able to counteract the impact of TP53AIP1 on the survival and autophagy in breast cancer cell lines. This suggests that TP53AIP1 acts as an oncogene by controlling the AKT/mTOR pathway. These findings reveal TP53AIP1 as a gene that suppresses tumor growth and triggers autophagy through the AKT/mTOR pathway in breast cancer cells. As a result, TP53AIP1 presents itself as a potential target for novel therapeutic approaches in treating breast cancer.


Subject(s)
Apoptosis Regulatory Proteins , Autophagy , Breast Neoplasms , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Animals , Female , Humans , Mice , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/genetics , Autophagy/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Epithelial-Mesenchymal Transition/genetics , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism
14.
Ital J Pediatr ; 50(1): 176, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39278913

ABSTRACT

BACKGROUND: Reports on coronavirus disease 2019 (COVID-19) in neonates are limited, especially in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) Omicron variant. This study aims to analyze the clinical characteristics and identify risk factors associated with severe COVID-19 in neonates infected with Omicron variant. METHODS: The study population was represented by neonates with COVID-19, who were admitted to The Affiliated Children's Hospital of Xi'an Jiaotong University in northwest China, from December 10, 2022 to January 20, 2023. Chinese Center for Disease Control and Prevention (CDC) announced that all local COVID-19 cases were infected with Omicron variant during the study period. Clinical and laboratory data were collected retrospectively. We used logistic regression analysis to investigate the risk factors for severe COVID-19, and derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). RESULTS: A total of 108 neonates, with median age of 18.1 days (interquartile range 9.4-23.0), were affected by COVID-19, of whom 84 had a mild disease, while 24 a severe one (22.2%). Of them, 6.5% were premature. No deaths were observed in the study population. The most common clinical manifestations were fever (88.9%) and cough (55.6%), with 5 cases (4.6%) complicated by pneumonia. 4 cases (3.7%) received respiratory support, including 2 cases of high-flow oxygen and 2 cases of continuous positive airway pressure. Gestational age at birth (OR: 0.615; 95% CI: 0.393-0.961), neutrophil count (NEU) (OR:0.576; 95% CI : 0.344-0.962) and lymphocyte count (LYM) (OR: 0.159; 95% CI: 0.063-0.401) were independent risk factors for severe COVID-19. The combination of NEU and LYM had the largest receiver operating characteristic area under the curve [0.912 (95% CI:0.830-0.993)] for identifying severe COVID-19, with a sensitivity of 0.833 and a specificity of 0.917. CONCLUSIONS: The general presentations and outcomes of neonatal COVID-19 caused by Omicron variant were not severe, and very few patients required respiratory support. The simultaneous decrease in NEU and LYM can be used to identify severe infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Severity of Illness Index , Humans , COVID-19/epidemiology , COVID-19/diagnosis , Infant, Newborn , Retrospective Studies , Male , Risk Factors , Female , China/epidemiology , Hospitalization
15.
Drugs R D ; 24(3): 391-394, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39294511

ABSTRACT

BACKGROUND AND OBJECTIVE: Adult-onset Still's disease (AOSD) is a recognized autoinflammatory disorder of unknown etiology. The standard initial management for AOSD includes conventional corticosteroids and disease-modifying antirheumatic drugs. In cases that are resistant to these treatments, additional therapeutic options such as immunosuppressants, biologics, and other alternative treatments may be considered. Yet, a significant proportion of patients remain unresponsive to these therapeutic interventions. Herein, a case is reported involving a patient with AOSD who had persistent pruritic lesions that did not respond to conventional therapy, but were alleviated with Janus kinase inhibitors (JAKi), namely baricitinib and upadacitinib. The objective is to expand the number of refractory AOSD cases treated with JAKi in clinical practice. Another aim is to offer potentially effective therapeutic options for AOSD patients who experience persistent pruritus. METHODS: A case was reported involving AOSD characterized by persistent pruritic lesions that failed to respond to conventional treatment, but showed favorable outcomes with JAKi therapy. An analysis of the PubMed literature was performed to assess the medication's efficacy and explore possible mechanisms. RESULTS: The present case study is one of the few documented instances exploring the use of JAKi for treating AOSD, aligning with previously published research. After initiating JAKi therapy, the patient exhibited significant improvement in symptoms, most notably a reduction in persistent pruritus. Additionally, there was a substantial decrease in the patient's glucocorticoid dosage. Aside from minor renal function anomalies, no adverse reactions were observed. CONCLUSIONS: The present case illustrates that JAKi can provide rapid and sustained clinical improvement in patients with AOSD, especially those who have not responded to conventional treatment, and they have the ability to alleviate persistent itching. Further investigation is needed to ascertain the precise mechanism.


Subject(s)
Azetidines , Janus Kinase Inhibitors , Pruritus , Purines , Pyrazoles , Still's Disease, Adult-Onset , Sulfonamides , Humans , Still's Disease, Adult-Onset/drug therapy , Pruritus/drug therapy , Janus Kinase Inhibitors/therapeutic use , Purines/therapeutic use , Azetidines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Adult , Heterocyclic Compounds, 3-Ring/therapeutic use , Female , Male , Treatment Outcome
16.
Int Immunopharmacol ; 142(Pt B): 113129, 2024 Dec 05.
Article in English | MEDLINE | ID: mdl-39293317

ABSTRACT

The involvement of the inflammatory response has been linked to the development of liver illnesses. As medications with the potential to prevent and cure liver illness, probiotics have garnered an increasing amount of interest in recent years. The present study used a piglet model with acute liver injury (ALI) induced by lipopolysaccharides (LPS) to investigate the regulatory mechanisms of Bacillus amyloliquefaciens SC06. Our findings indicated that SC06 mitigated the liver structural damage caused by LPS, as shown by the decreased infiltration of inflammatory cells and the enhanced structural integrity. In addition, After the administration of SC06, there was a reduction in the increased levels of the liver damage markers. In the LPS group, there was an increase in the mRNA expression of inflammatory cytokines, apoptosis cell rate, and genes associated with apoptosis, while these alterations were mitigated by SC06 administration. Furthermore, SC06 prevented pigs from suffering liver damage by preventing the activation of the NLRP3 inflammasome, which was normally triggered by LPS. The examination of serum metabolic pathways found that ALI was related to several metabolic processes, including primary bile acid biosynthesis, pentose and glucuronate interconversions and the metabolism of phenylalanine. Significantly, our research revealed that the administration of SC06 effectively controlled the concentrations of bile acids in the serum. The correlation results also revealed clear relationships between bile acids and liver characteristics and NLRP3 inflammasome-related genes. However, in vitro experiments revealed that SC06 could not directly inhibit NLRP3 activation under ATP, monosodium urate, and nigericin stimulation, while taurochenodeoxycholic acid (TCDCA) activated NLRP3 inflammasome related genes. In conclusion, our study proved that the hepaprotective effect of SC06 on liver injury, which was closely associated with the restoration of bile acids homeostasis and NLRP3 inflammasome inhibition.


Subject(s)
Bacillus amyloliquefaciens , Bile Acids and Salts , Chemical and Drug Induced Liver Injury , Inflammasomes , Lipopolysaccharides , Liver , NLR Family, Pyrin Domain-Containing 3 Protein , Probiotics , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Inflammasomes/metabolism , Swine , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/immunology , Bile Acids and Salts/metabolism , Liver/pathology , Liver/metabolism , Liver/drug effects , Liver/immunology , Probiotics/therapeutic use , Cytokines/metabolism , Disease Models, Animal , Apoptosis/drug effects , Male
17.
ACS Appl Mater Interfaces ; 16(40): 53775-53784, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39315993

ABSTRACT

The electrochemical carbon dioxide reduction reaction (CO2RR) to generate feedstocks for chemical products (e.g., carbon monoxide, CO) offers a highly attractive method for achieving the closure of the carbon cycle. Ionic liquids (ILs)-functionalized Cu-based catalyst Cu2O-HKUST-1/IL1/PTFE was developed, configuring metal-organic frameworks(MOFs) based materials with high adsorption and multiple active sites. The modified electrocatalysts exhibited high specific surface area, strong CO2 adsorption capacity, abundant active sites, and fast charge transfer rate. The nucleophilic active site of deprotonation at the C2 site in imidazole ILs further improved the selectivity of proton migration and CO product generation, which was verified through DFT calculations for the low Gibbs free energy of the generated intermediate interactions. In addition, the hydrophobic interface constructed by PTFE facilitated the inhibition of the hydrogen evolution reaction (HER) and significantly improved the efficiency of CO2 electroreduction. The Cu2O-HKUST-1/IL1/PTFE catalyst manifested a high C1 Faraday efficiency (FE) up to 96.5% and in particular 92.7% for FECO at -1.7 V vs RHE. The present work provides an efficient strategy for configuring ILs-functionalized MOFs-based materials with good hydrophobic interfaces to enhance the efficiency of CO2 electroreduction to C1 products.

18.
J Mol Model ; 30(10): 326, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39240367

ABSTRACT

CONTEXT: Revealing the mechanism of intermolecular interactions in dinitroamine ammonium (ADN)-based liquid propellants and exploring the reasons for their performance changes, multi-perspective interaction analyses of ADN and ADN-water (H2O)-methanol (CH3OH) solutions have been conducted via theoretical methods. The band structure, density of states (DOS), surface electrostatic potential (ESP), Hirshfeld surface, reduced density gradient (RDG), AIM topological analysis, and detonation performance were studied and the results showed that both the ADN and ADN-H2O-CH3OH solutions had hydrogen bonds and van der Waals interactions. By introducing the small molecules H2O and CH3OH, the detonation performance of the ADN-H2O-CH3OH solution slightly decreased, but its sensitivity also decreased. Overall, the comprehensive performance of the ADN-H2O-CH3OH solution has improved, and the application range has expanded. These results are helpful for obtaining a deeper understanding of ADN-based liquid propellants at the atomic level and contribute to the development of new liquid propellants. METHODS: The ADN and ADN-H2O-CH3OH solutions were constructed by Amorphous cell module and optimized via GGA with PBE methods in the Dmol3 module of the Materials Studio, and their electronic properties were calculated. Hirshfeld surfaces were generated with CrystalExplorer 3.0. A topological analysis of a variety of molecular clusters was performed via QTAIM. The QTAIM and RDG analyses in this work were generated by Multiwfn 3.0.

19.
Ecol Evol ; 14(9): e70277, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39301297

ABSTRACT

Pine wilt disease (PWD) is a devastating plant disease caused by the pinewood nematode (PWN, Bursaphelenchus xylophilus) that is transmitted by several beetle species in the genus, Monochamus. Once present, the disease is difficult to control. Prevention rather than control is regarded as an effective strategy for PWD management. Central to this prevention strategy is the ability to predict the potential distribution of the disease. Here, we employed an integrated MaxEnt and CLIMEX approach to model the potential distribution of PWD under various climate-change scenarios. Our results indicate that rising temperatures and lower humidity under climate change will render some of the northern regions of China more suitable for the nematode and these beetles, causing the gradual northward movement of PWD. Furthermore, suitable habitats for three pine species, Pinus massoniana, P. taiwanensis and P. shurbergia, overlap with PWN and Monochamus, suggesting that these three species are potentially at high risk of PWD. Thus, PWD management should target the northern regions of China and the three pine species that are most susceptible to PWD.

20.
Immun Inflamm Dis ; 12(9): e70024, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39315855

ABSTRACT

BACKGROUND: Diarrhea is a leading cause of death in young children worldwide. Vitamin D deficiency impairs the body's ability to clear pathogens, reduces tight junction protein expression in intestinal epithelial cells, and enhances Th1-mediated intestinal inflammation. This study aimed to investigate the effects of serum vitamin D levels on acute invasive enteritis in children. METHODS: This prospective cohort study included 82 children aged 1-3 years with clinically diagnosed acute invasive enteritis at Sichuan Maternal and Child Health Hospital from February 2021 to February 2022, alongside a control group of 80 healthy children. Fecal specimens were collected for routine tests and occult blood analysis, while blood samples were taken for routine tests, C-reactive protein, and 25-OHD levels. Comparative analyses were performed between groups, and multifactorial logistic regression was used to identify factors influencing invasive enteritis. RESULTS: The study group showed significantly lower serum 25-OHD levels (27.95 ± 9.91 ng/mL) compared to controls (32.76 ± 10.23 ng/mL, p < .01). Among the study group, 19.5% (16/82) had levels <20 ng/mL, versus 12.5% (10/80) in controls. Regular vitamin D supplementation was lower in the study group (58.5% vs. 77.5%, p < .05). Outdoor activity duration was also reduced (2.57 ± 0.98 h vs. 3.04 ± 0.88 h, p < .01). Multivariate analysis identified that exclusive breastfeeding, greater outdoor activity time and regular vitamin D supplementation were all associated with reduced risk of invasive enteritis (p < .05). CONCLUSION: The findings indicate an association between low serum 25-OHD levels and acute invasive enteritis in children aged 1-3 years, suggesting that consistent vitamin D supplementation and sufficient outdoor activity may protect against this condition.


Subject(s)
Enteritis , Vitamin D Deficiency , Vitamin D , Humans , Vitamin D/blood , Female , Male , Child, Preschool , Enteritis/blood , Infant , Prospective Studies , Vitamin D Deficiency/blood , Vitamin D Deficiency/epidemiology , Acute Disease , Risk Factors , Dietary Supplements
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