Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 137
Filter
1.
Explor Target Antitumor Ther ; 5(3): 568-580, 2024.
Article in English | MEDLINE | ID: mdl-38966165

ABSTRACT

Background: This article is based on our previous research, which was presented at the 2023 ASCO Annual Meeting I and published in Journal of Clinical Oncology as Conference Abstract (JCO. 2023;41:e16148. doi: 10.1200/JCO.2023.41.16_suppl.e16148). Both anti-programmed death 1/ligand-1 (PD-1/L1) antibody + anti-vascular endothelial growth factor (VEGF) antibody (A + A) and anti-PD-1/L1 antibody + VEGF receptor (VEGFR)-targeted tyrosine kinase inhibitor (A + T) are effective first-line therapies for unresectable hepatocellular carcinoma. However, there lacks evidence from head-to-head comparisons between these two treatments. We conducted a network meta-analysis on the efficacy and safety of them. Methods: After a rigorous literature research, 6 phase III trials were identified for the final analysis, including IMbrave150, ORIENT-32, COSMIC-312, CARES-310, LEAP-002, and REFLECT. The experiments were classified into three groups: A + A, A + T, and intermediate reference group. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and incidence of treatment-related adverse events (TRAEs). Hazard ratio (HR) with 95% confidence intervals (CI) for OS and PFS, odds ratio (OR) for ORR, and relative risk (RR) for all grade and grade ≥3 TRAEs were calculated. Under Bayesian framework, the meta-analysis was conducted using sorafenib as intermediate reference. Results: With the rank probability of 96%, A + A showed the greatest reduction in the risk of death, without significant difference from A + T (HR: 0.82, 95% CI: 0.65-1.04). A + T showed the greatest effect in prolonging PFS and improving ORR with the rank probability of 77%, but there were no statistical differences with A + A. A + A was safer than A + T in terms of all grade of TRAEs (RR: 0.91, 95% CI: 0.82-1.00) and particularly in those grade ≥3 (RR: 0.65, 95% CI: 0.54-0.77). Conclusions: A + A had the greatest probability of delivering the longest OS, while A + T was correlated with larger PFS benefits at the cost of a lower safety rate.

2.
Nat Commun ; 15(1): 5737, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982157

ABSTRACT

Exploring the promiscuity of native enzymes presents a promising strategy for expanding their synthetic applications, particularly for catalyzing challenging reactions in non-native contexts. In this study, we explore the promiscuous potential of old yellow enzymes (OYEs) to facilitate the Morita-Baylis-Hillman reaction (MBH reaction), leveraging substrate similarities between MBH reaction and reduction reaction. Using mass spectrometry and spectroscopic techniques, we confirm promiscuity of GkOYE in both MBH and reduction reactions. By blocking H- and H+ transfer pathways, we engineer GkOYE.8, which loses its reduction ability but enhances its MBH activity. The structural basis of MBH reaction catalyzed by GkOYE.8 is obtained through mutation studies and kinetic simulations. Furthermore, enantiocomplementary mutants GkOYE.11 and GkOYE.13 are obtained by directed evolution, exhibiting the ability to accept various aromatic aldehydes and alkenes as substrates. This study demonstrates the potential of leveraging substrate similarities to unlock enzyme functionalities, enabling the catalysis of new-to-nature reactions.


Subject(s)
Biocatalysis , Substrate Specificity , Kinetics , Aldehydes/metabolism , Aldehydes/chemistry , Catalysis , Mutation , Alkenes/metabolism , Alkenes/chemistry , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Protein Engineering
3.
Endocrine ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824220

ABSTRACT

Male cases diagnosed COVID-19 with more complications and higher mortality compared with females, and the overall consequences of male sex hormones and semen parameters deterioration were observed in COVID-19 patients, whereas the involvement and mechanism for spermatogenic cell remains unclear. The study was aimed to investigate the infection mode of S protein (D614G) pseudovirus (pseu-S-D614G) to spermatogenic cells, as well as the influence on cell growth. Both mouse spermatogonia (GC-1 cell, immortalized spermatogonia) and spermatocyte (GC-2 cell, immortalized spermatocytes) were used to detect the infection of pseu-S-D614G of SARS-CoV-2, and further explored the effect of SARS-CoV-2-spike protein (S-protein) and SARS-CoV-2-spike protein (omicron) (O-protein) on GC-1 cell apoptosis and proliferation. The data showed that the pseu-S-D614G invaded into GC-1 cells through either human ACE2 (hACE2) or human CD147 (hCD147), whereas GC-2 cells were insensitive to viral infection. In addition, the apoptosis and proliferation suppression inflicted by S-protein and O-protein on GC-1 cells was through Bax-Caspase3 signaling rather than arresting cell cycle progression. These findings suggest that CD147, apart from ACE2, may be a potential receptor for SARS-CoV-2 infection in testicular tissues, and that the apoptotic effect was induced in spermatogonia cells by S-protein or O-protein, eventually resulted in the damage to male fertility.

4.
ACS Sens ; 9(6): 3346-3356, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38898684

ABSTRACT

Creating high-performance gas sensors for heptanal detection at room temperature demands the development of sensing materials that incorporate distinct spatial configurations, functional components, and active surfaces. In this study, we employed a straightforward method combining hydrothermal strategy with ultrasonic processing to produce mesoporous graphene quantum dots/bismuth antimonate (GQDs/BiSbO4) with nanorod cluster forms. The BiSbO4 was incorporated with appropriate contents of GQDs resulting in significantly improved attributes such as heightened sensitivity (59.6@30 ppm), a lower threshold for detection (356 ppb), and quicker period for response (40 s). A synergistic mechanism that leverages the inherent advantages of BiSbO4 was proposed, while its distinctive mesoporous hollow cubic structure, the presence of oxygen vacancies, and the catalytic enhancement provided by GQDs lead to a marked improvement in heptanal detection. This work introduces a straightforward and effective method for crafting sophisticated micro-nanostructures that optimize spatial design, functionality, and active mesoporous surfaces, showing great promise for heptanal sensing applications.


Subject(s)
Graphite , Nanotubes , Quantum Dots , Temperature , Nanotubes/chemistry , Quantum Dots/chemistry , Graphite/chemistry , Density Functional Theory , Antimony/chemistry
5.
Sci Total Environ ; 931: 172908, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38697552

ABSTRACT

Shallow lakes, recognized as hotspots for nitrogen cycling, contribute to the emission of the potent greenhouse gas nitrous oxide (N2O), but the current emission estimates for this gas have a high degree of uncertainty. However, the role of N2O-reducing bacteria (N2ORB) as N2O sinks and their contribution to N2O reduction in aquatic ecosystems in response to N2O dynamics have not been determined. Here, we investigated the N2O dynamics and microbial processes in the nitrogen cycle, which included both N2O production and consumption, in five shallow lakes spanning approximately 500 km. The investigated sites exhibited N2O oversaturation, with excess dissolved N2O concentrations (ΔN2O) ranging from 0.55 ± 0.61 to 53.17 ± 15.75 nM. Sediment-bound N2O (sN2O) was significantly positively correlated with the nitrate concentration in the overlying water (p < 0.05), suggesting that nitrate accumulation contributes to benthic N2O generation. High N2O consumption activity (RN2O) corresponded to low ΔN2O. In addition, a significant negative correlation was found between RN2O and nir/nosZ, showing that bacteria encoding nosZ contributed to N2O consumption in the benthic sediments. Redundancy analysis indicated that benthic functional genes effectively reflected the variations in RN2O and ∆N2O. qPCR analysis revealed that the clade II nosZ gene was more sensitive to ΔN2O than the clade I nosZ gene. Furthermore, four novel genera of potential nondenitrifying N2ORB were identified based on metagenome-assembled genome analysis. These genera, which are affiliated with clade II, lack genes responsible for N2O production. Collectively, benthic N2ORB, especially for clade II-type N2ORB, harnesses N2O consumption activity leading to low N2O emissions from shallow lakes. This study advances our knowledge of the role of benthic clade II-type N2ORB in regulating N2O emissions in shallow lakes.


Subject(s)
Bacteria , Lakes , Nitrous Oxide , Nitrous Oxide/analysis , Lakes/chemistry , Bacteria/classification , Environmental Monitoring , Nitrogen Cycle , Air Pollutants/analysis , Geologic Sediments/chemistry
6.
Environ Res ; 258: 119275, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38821463

ABSTRACT

Soil enzyme carbon (C): nitrogen (N): phosphorous (P) stoichiometry and their vector model has been widely used to elucidate the balance between microbial nutrient requirements and soil nutrient availability. However, limited knowledge is available on the dynamics of soil enzyme stoichiometry and microbial nutrient limitation following afforestation, especially in the economic forest. In this study, the effects of citrus plantation on C: N: P stoichiometry were assessed through a comparative study between cropland and citrus plantations with varying durations of afforestation (i.e., 3, 15, 25, and 35 years). It was found that the C, N, and P contents in the soil (SOC, STN, and STP), microbial biomass (MBC, MBN, and MBP), as well as the activities of C-, N-, and P-acquiring enzymes (BG, NAG, and AP), were 1.02-2.51 times higher than those in cropland. Additionally, C, N, and P contents in soil and microbial biomass increased consistently with increasing afforestation time. While the activities of C-, N-, and P-acquiring enzymes increased from 3 years to 25 years and then significantly decreased. In addition to NAG: AP, the stoichiometry of C, N, and P in soil (SOC: STN, SOC: STP, and STN: STP) and microbial biomass (MBC: MBN, MBC: MBP, and MBN: MBP), along with BG: NAG, exhibited a decline of 7.69-27.38% compared to cropland. Moreover, the majority of the C: N: P stoichiometry in soil, microbial biomass, and enzymes consistently decreased with increasing afforestation time, except for SOC: STN and NAG: AP, which exhibited an opposite trend. Furthermore, a significant decrease in microbial carbon limitation and an increase in microbial nitrogen limitation were observed with increasing afforestation time. Collectively, the dynamic of microbial nutrient limitation was primarily influenced by the interaction between soil nutrients and edaphic factors. The findings suggest that with the increasing duration of citrus plantation, it is crucial to focus on nitrogen (N) fertilization while maintaining a delicate balance between fertilization strategies and soil acidity levels.

7.
Heliyon ; 10(5): e27004, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38463813

ABSTRACT

The POFUT1 gene, known to be up-regulated in various tumor tissues and associated with tumor biology, has yet to be explored for its potential role in immune response regulation and tumor immune microenvironment. The normalized pan-cancer dataset (TCGA Pan-Cancer) was downloaded from the UCSC database, followed by analysis of POFUT1 expression in various tumors and functional enrichment analysis. The correlation between POFUT1 expression levels and patient prognosis was assessed. GSEA of POFUT1 based on low-grade glioma (LGG) samples and immune infiltration analyses of LGG and glioblastoma (GBM) were conducted. The correlation between POFUT1 expression levels and infiltration levels of 22 immune cells in LGG and GBM was examined, as well as the correlation between immune cell infiltration levels and LGG patient prognosis. Additionally, the relationship between POFUT1 expression levels and characteristic gene expression of identified immune cells was evaluated. Lastly, external dataset validation was performed using the integrated CGGA dataset. Significant differences were observed in POFUT1 expression levels across 20 tumor types. High POFUT1 expression correlated with poor prognosis in GBMLGG, and LGG patients. Enrichment analysis and GSEA of POFUT1 in LGG demonstrated involvement in tumor-related and immune-related pathways. A positive correlation was identified between POFUT1 expression levels and infiltration levels of resting memory CD4+ T cells, as well as M2 macrophages or M2-like TAMs in the LGG immune microenvironment, potentially contributing to poor prognosis. External dataset validation revealed a positive correlation between M2 macrophages or M2-like TAMs and POFUT1 expression levels in LGG, and a negative correlation with LGG patient prognosis. POFUT1's negative impact on LGG prognosis may result from its influence on M2 macrophage and M2-like TAM infiltration levels within the immune microenvironment. This suggests its potential as a prognostic predictor and therapeutic target for LGG.

8.
Arthritis Res Ther ; 26(1): 62, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38454506

ABSTRACT

BACKGROUND: Primary Sjogren's syndrome (pSS) is a complex autoimmune disease featuring damage to salivary and lacrimal glands, with the possibility of manifestations across multiple organs. Antibody-producing B cells have long been appreciated to play a significant role in pSS pathogenesis, with a number of autoreactive antibody species having been identified to be elevated in pSS patients. While several studies have attempted to characterize the BCR repertoires of peripheral blood B cells in pSS patients, much remains unknown about the repertoire characteristics of gland-infiltrating B cells. METHODS: Through paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq. RESULTS: Via integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity. CONCLUSIONS: Through BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.


Subject(s)
Sjogren's Syndrome , Humans , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/genetics , Salivary Glands/pathology , Salivary Glands, Minor/pathology , B-Lymphocytes , Receptors, Antigen, B-Cell/genetics
9.
Acta Pharmacol Sin ; 45(6): 1189-1200, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38438579

ABSTRACT

Maintenance of intestinal barrier function contributes to gastrointestinal homeostasis and therefore cardiovascular diseases. A number of studies show that intestinal permeability is affected by excessive inflammatory responses. Krüppel-like factor (KLF) 4 is one of the critical transcriptional factors, which controls multiple immune responses. In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found that overexpression of epithelial Klf4 in atherosclerotic mice significantly increased intestinal tight junction expression and ameliorated endotoxemia, whereas replenishment of LPS abolished these benefits. Overexpression of Klf4 reversed LPS-induced permeability and downregulation of ZO-1 and Occludin in Caco-2 cells in vitro. HFHC diet stimulated the expression of epithelial microRNA-34a, whereas silence of epithelial Klf4 abolished the benefits of microRNA-34a sponge, a specific miR-34a inhibitor, on intestinal permeability and atherosclerotic development. A clinical cohort of 24 atherosclerotic patients supported colon KLF4/NF-κB/tight junction protein axis mediated intestine/cardiovascular interaction in patients with atherosclerosis. Taken together, intestinal epithelial KLF4 protects against intestinal inflammation and barrier dysfunction, ameliorating atherosclerotic plaque formation.


Subject(s)
Atherosclerosis , Endotoxemia , Intestinal Mucosa , Kruppel-Like Factor 4 , Kruppel-Like Transcription Factors , Mice, Inbred C57BL , MicroRNAs , NF-kappa B , Kruppel-Like Factor 4/metabolism , Animals , Atherosclerosis/metabolism , Kruppel-Like Transcription Factors/metabolism , NF-kappa B/metabolism , MicroRNAs/metabolism , MicroRNAs/genetics , Humans , Endotoxemia/metabolism , Mice , Intestinal Mucosa/metabolism , Male , Caco-2 Cells , Permeability , Lipopolysaccharides , Intestinal Barrier Function
10.
J Environ Manage ; 356: 120457, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38503231

ABSTRACT

Ferrous sulfate (FeSO4) combined with acid pretreatment is usually employed to remediate contaminated soils containing Cr(VI). However, the long-term efficiency of this stabilization method is important for its sustainability. In this study, a gradient temperature-elevating exposure test was employed to investigate the stability of Cr in FeSO4-remediated soil when exposed to elevated temperatures (40 °C, 120 °C, and 500 °C), possibly caused by hot weather and/or wildfires. The results of chemical extraction and X-ray absorption near edge structure spectroscopy (XANES) showed that the Cr(VI) in contaminated soil was successfully transformed to Cr(III) after stabilization, resulting in the dramatic decrease of water-leachable Cr(VI). The stabilization efficiency was further improved under 40 °C treatment after 30 days. Subsequently, the 120 °C treatment (7 days) had relatively little effect on the Cr speciation and mobility in soils. However, even one day of 500 °C calcination resulted in the deterioration of stabilization efficiency, and the water-leachable Cr(VI) re-increased and became higher than the Chinese environmental standards (total Cr 15 mg/L, Cr(VI) 5 mg/L) for the classification of hazardous solid wastes. XANES results reflected that heating at 500 °C facilitate the formation of Cr2O3, which was mainly caused by thermal decomposition and dehydration of Cr(OH)3 in the soil. Besides, the transformation of Cr species resulted in the enhanced association of Cr with the most stable residual fraction (88.3%-91.6%) in soil. Based on chemical extraction results, it was suggested that the oxidation of Cr(III) to Cr(VI) contributed to the re-increased mobility of Cr(VI) in soil. However, the XANES results showed that almost no significant re-oxidization of Cr(III) to Cr(VI) happened after heating at 500 °C, which was probably caused by XANES linear combination fits (LCF) uncertainties. Moreover, the changes in soil properties, including a rise in pH to a slightly alkaline range and/or the decomposition of organic matter, possibly contributed to the enhanced mobility of Cr(VI) in soil. This study contributes to clarifying the mobility and transformation of Cr in contaminated soils and provides a support for the sustainable management of remediated soils.


Subject(s)
Chromium , Ferrous Compounds , Soil Pollutants , Temperature , Chromium/chemistry , Soil/chemistry , Water , Soil Pollutants/chemistry
11.
Front Endocrinol (Lausanne) ; 15: 1222281, 2024.
Article in English | MEDLINE | ID: mdl-38505747

ABSTRACT

Objectives: Adrenal tumors are common, but adrenocortical carcinomas (ACCs) are a rare and challenging form of cancer to diagnose and manage.This study aimed to explore the critical role of mitochondrial quality in maintaining cellular function and the implications of the abnormal expression of mitochondrial metabolism-related proteins observed in ACC patients. We focused on identifying the connection between mitochondrial quality and the development of ACC at molecular and genomic levels. Methods: We compared mitochondrial quality-related genes (MQRGs) across ACC subtypes using overall survival (OS) and disease-free survival (DFS) as evaluation indicators. Furthermore, a novel MQRG score was developed to predict clinical prognosis and guide immunotherapy responses accurately. Results: The majority of MQRGs were upregulated in the ACC samples, correlating to poor prognosis. The MQRG score was confirmed as an independent prognostic factor for ACC, with the high-risk MQRG score group showing a significantly shorter overall survival period. Conclusions: Multilayer alterations in MQRGs are associated with patient prognosis and immune cell infiltration characteristics. This comprehensive analysis of MQRGs can contribute to a deeper understanding of potential differences in ACC patients' tumor microenvironment. This can influence clinical decision-making and advanced prognosis prediction, thereby offering new insights into personalized treatments in ACC.


Subject(s)
Adrenal Cortex Neoplasms , Adrenocortical Carcinoma , Humans , Adrenocortical Carcinoma/diagnosis , Adrenocortical Carcinoma/genetics , Adrenocortical Carcinoma/metabolism , Prognosis , Adrenal Cortex Neoplasms/diagnosis , Adrenal Cortex Neoplasms/genetics , Adrenal Cortex Neoplasms/metabolism , Disease-Free Survival , Tumor Microenvironment/genetics
12.
Opt Lett ; 49(6): 1544-1547, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38489446

ABSTRACT

Terahertz (THz) metasurfaces have opened up a new avenue for the THz wavefront modulation. However, high-efficient and low-cost fabrication of THz metasurfaces remains a great challenge today. Here, quasi-capsule-shaped polarization-multiplexed holographic THz metasurfaces were printed by a beam-shaped femtosecond laser. The laser beam was spatially modulated by holograms of optimized cylindrical lens loaded on a spatial light modulator (SLM). The size of quasi-capsule apertures can be exquisitely and flexibly controlled by adjusting the focal length in holograms, pulse energy, and pulse number. Based on near-field diffraction and Burch encoding, an array of 100 × 100 basic unit apertures were initially designed, and a polarization-multiplexed THz metasurface was finally printed with a dimension of 8 mm × 8 mm. The function of polarization multiplexing was demonstrated, by which two kinds of images were reconstructed in response to X and Y-polarization THz waves, respectively. The present work highlights a great leap in fabrication method for THz metasurfaces and hopefully stimulates the development of miniaturized and integrated THz systems.

13.
Sci Rep ; 14(1): 2519, 2024 01 30.
Article in English | MEDLINE | ID: mdl-38291067

ABSTRACT

This study aimed to study 3-dimensional (3D) changes of hard and soft tissues of skeletal class II patients after 2-jaw surgery and genioplasty. 32 adult patients diagnosed with mandibular hypoplasia who underwent 2-jaw surgery of maxillary impaction, mandibular advancement and genioplasty were enrolled. Cone-beam computed tomography and 3D stereophotogrammetry was conducted 1 week before and 6 months after surgery. Dolphin imaging software was used to establish a 3D digitizing model and 3D measurement system. Paired t-test was performed to compare the values before and after surgery. Pearson's correlation test assessed the degree of correlations between hard and soft tissue change. The mean impaction of the maxilla was 2.600 ± 3.088 mm at A. The mean advancement of the mandible was 7.806 ± 2.647 mm at B. There was a significant upward and forward movement for most landmarks of the nose and lip, while a significant decrease in nasal tip height (lateral view), upper lip height, and upper and lower vermilion height. The nose's width was significantly increased. For maxillary, Sn, Ac-r, Ac-l, and Ls demonstrated a significant correlation with A and U1 in the anteroposterior axis. However, there were no significant correlations among them in the vertical axis. For mandibular, Li demonstrated a significant correlation with L1 in the anteroposterior axis specifically for the mandible. Notably, correlations between the landmarks of the chin's hard and soft tissues were observed across all axes. The utilization of 3-D analysis facilitated a quantitative comprehension of both hard and soft tissues, thereby furnishing valuable insights for the strategic formulation of orthognathic treatment plans targeting patients with skeletal class II conditions.


Subject(s)
Face , Malocclusion, Angle Class III , Adult , Humans , Face/diagnostic imaging , Face/anatomy & histology , Malocclusion, Angle Class III/surgery , Mandible/diagnostic imaging , Mandible/surgery , Nose , Maxilla/diagnostic imaging , Maxilla/surgery , Lip , Cephalometry/methods , Imaging, Three-Dimensional/methods
14.
iScience ; 27(1): 108723, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38283328

ABSTRACT

The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome has been involved in the pathogenesis of various chronic liver diseases. However, its role in hepatitis B virus (HBV)-associated hepatitis remains unknown. Here we demonstrate the synergistic effect of HBV with potential intrahepatic danger signals on NLRP3 inflammasome activation. HBV exposure at the appropriate temporal points enhances potassium efflux-dependent NLRP3 inflammasome activation in macrophages and also increases NLRP3 inflammasome-mediated inflammation in HBV-transgenic mouse model. HBV-mediated synergism with intrahepatic signals represented by ATP molecules on NLRP3 activation was observed via relevance analysis, confocal microscopy, and co-immunoprecipitation, and its effector cytokines exhibit positive associations with hepatic inflammation in patients with severe hepatitis B. Furthermore, the synergism of HBV on NLRP3 inflammasome activation owes to increased sodium influx into macrophages. Our data demonstrate that HBV contributes to hepatic inflammation via sodium influx-dependent synergistic activation of NLRP3 inflammasome, which provides a deeper understanding of immune pathogenesis in HBV-associated hepatitis.

15.
IEEE Trans Med Imaging ; 43(6): 2125-2136, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38236665

ABSTRACT

Metal artifacts caused by the presence of metallic implants tremendously degrade the quality of reconstructed computed tomography (CT) images and therefore affect the clinical diagnosis or reduce the accuracy of organ delineation and dose calculation in radiotherapy. Although various deep learning methods have been proposed for metal artifact reduction (MAR), most of them aim to restore the corrupted sinogram within the metal trace, which removes beam hardening artifacts but ignores other components of metal artifacts. In this paper, based on the physical property of metal artifacts which is verified via Monte Carlo (MC) simulation, we propose a novel physics-inspired non-local dual-domain network (PND-Net) for MAR in CT imaging. Specifically, we design a novel non-local sinogram decomposition network (NSD-Net) to acquire the weighted artifact component and develop an image restoration network (IR-Net) to reduce the residual and secondary artifacts in the image domain. To facilitate the generalization and robustness of our method on clinical CT images, we employ a trainable fusion network (F-Net) in the artifact synthesis path to achieve unpaired learning. Furthermore, we design an internal consistency loss to ensure the data fidelity of anatomical structures in the image domain and introduce the linear interpolation sinogram as prior knowledge to guide sinogram decomposition. NSD-Net, IR-Net, and F-Net are jointly trained so that they can benefit from one another. Extensive experiments on simulation and clinical data demonstrate that our method outperforms state-of-the-art MAR methods.


Subject(s)
Artifacts , Metals , Phantoms, Imaging , Tomography, X-Ray Computed , Metals/chemistry , Humans , Tomography, X-Ray Computed/methods , Image Processing, Computer-Assisted/methods , Algorithms , Prostheses and Implants , Monte Carlo Method , Deep Learning
16.
Anal Chim Acta ; 1279: 341774, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37827672

ABSTRACT

Latent fingerprint (LFP) powders are crucial in the detection of LFPs in forensic science. However, it is often plagued by poor image resolution and low contrast. Herein, enhanced LFP fluorescence (FL) visualizations are achieved by doping Eu(III) coordination compound Eu(TTA)3phen directly into SiO2 microspheres instead of Eu(III) ions. Using the synthesized Eu(TTA)3phen-SiO2 microspheres, the fine characteristic structure of LFP can be seen and recognized under 365 nm irradiation, up to Level 3. However, the Eu3+-SiO2 microspheres were difficult to recognize the Level 2,3 fingerprint structure. The difference between the ridge and furrow gray values of Eu(TTA)3phen-SiO2 microspheres is 2.1 times that of Eu3+-SiO2 microspheres. The coordination effect increased the asymmetry around Eu(III) ions, resulting in the ultrasensitive 5D0→7F2 transition, thus increasing the FL intensity, and the uniform doping of the Eu(III) coordination compound into SiO2 also reduced the surface FL quenching due to shielding from oxygen. Under this dual effect, the LFP performance of Eu(TTA)3phen-SiO2 microspheres has been significantly improved. We believe that this novel and easy LFP visualization method is a promising routine in specific target detection including criminal investigation, customhouse check-in, and drug control.

17.
Open Life Sci ; 18(1): 20220661, 2023.
Article in English | MEDLINE | ID: mdl-37589002

ABSTRACT

Inflammatory cytokine storms (CS) in COVID-19 patients are associated with elevated levels of 13 specific cytokines, potentially impacting male fertility by causing testicular cell damage and disrupting the immune microenvironment. Some patients present with scrotal discomfort and orchitis. However, few studies have explored cytokine expression in testicular cells and their role in cell-to-cell communication. In this study, we integrated single-cell sequencing data sets of testicular cells, annotating 20 cell clusters using marker genes and the Human Cell Landscape database. We constructed cell pseudo-chronological trajectories, hub genes, and analyzed the cytokine interaction network between sperm cells using CellChat. Our findings identified 12 types of testicular cells, with four cytokines (IL8, CCL2, CCL3, and TNF) potentially involved in immune processes. Pseudo-chronological trajectory analysis indicated IL8 and CCL3's essential roles in testicular macrophages and endothelial cell development, affecting the immune microenvironment. We determined eight key cytokines (IL1, IL2, IL4, IL6, CCL, CSF3, TNF, and IFN-II) functions in cell interaction networks. Network analysis of exogenous cytokines directly acting on testicular cells showed IL2 potentially affecting all testicular cells, suggesting a vital role in cell communication. This research offers valuable insights into CSs effects on testicular cells and their potential impact on male fertility during COVID-19 infection.

18.
J Leukoc Biol ; 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37395700

ABSTRACT

Primary Sjogren's syndrome (pSS) is a complex chronic autoimmune disease in which local tissue damage in exocrine glands are combined with broader systemic involvement across the body in tissues including the skin. These combined manifestations negatively impact patient health and quality of life. While studies have previously reported differences in immune cell composition in the peripheral blood of pSS patients relative to healthy controls, a detailed immune cell landscape of the damaged exocrine glands of these patients remains lacking. Through single-cell transcriptomics and repertoire sequencing of immune cells in paired peripheral blood samples and salivary gland biopsies, we present here a preliminary picture of adaptive immune response in pSS. We characterize a number of points of divergence between circulating and glandular immune responses that have been hitherto underappreciated, and identify a novel population of CD8+CD9+ cells with tissue-residential properties that are highly enriched in the salivary glands of pSS patients. Through comparative analyses with other sequencing data, we also observe a potential connection between these cells and the tissue-resident memory cells found in cutaneous vasculitis lesions. Together, these results indicate a potential role for CD8+CD9+ cells in mediating glandular and systemic effects associated with pSS and other autoimmune disorders.

19.
J Wound Ostomy Continence Nurs ; 50(4): 331-336, 2023.
Article in English | MEDLINE | ID: mdl-37467414

ABSTRACT

BACKGROUND: Abdominal wound dehiscence (AWD) is a costly postoperative complication; its management is particularly challenging for WOC nurses when it occurs secondary to an ostomy closure. CASE: We present a case of AWD secondary to ileostomy closure in Baby Q, a 9-month 19-day-old female infant. A silver wound contact dressing was used on her dehisced wound followed by negative pressure wound therapy and adhesive tape to pull the wound edge together and promote granulation. We used a combination of enteral nutrition, parenteral nutrition, total parenteral nutrition, and total enteral nutrition adjusting the feeding plan stepwise according to her nutritional status. CONCLUSIONS: Malnutrition and severe peristomal skin complications may contribute to the risk of AWD in infants undergoing reversal of a temporary ostomy. Assessing and treating nutritional status and peristomal skin is imperative before performing ostomy closure.


Subject(s)
Dermatitis , Malnutrition , Ostomy , Infant , Humans , Female , Ileostomy/adverse effects , Postoperative Complications , Malnutrition/complications
20.
Pathol Res Pract ; 248: 154589, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37285733

ABSTRACT

For the complex and multifaceted challenge of cancer eradication, a comprehensive approach is required. Molecular strategies are critical in the fight against cancer as they allow us to understand the underlying fundamental mechanisms and develop specialized treatments. The role of long non-coding RNAs (lncRNAs), a class of ncRNA molecules longer than 200 nucleotides, in cancer biology has attracted growing attention in recent years. These roles include but are not limited to regulating gene expression, protein localization, and chromatin remodeling. LncRNAs can influence a range of cellular functions and pathways, including those involved in cancer development. The first study on RHPN1 antisense RNA 1 (RHPN1-AS1), a 2030-bp transcript originating from human chromosome 8q24, in uveal melanoma (UM) demonstrated that this lncRNA was significantly upregulated in several UM cell lines. Further studies in various cancer cell lines showed that this lncRNA is significantly overexpressed and exerts oncogenic functions. This review will provide an overview of current knowledge regarding the roles played by RHPN1-AS1 in the emergence of various cancers, focusing on its biological and clinical functions.


Subject(s)
Melanoma , MicroRNAs , RNA, Long Noncoding , Humans , Cell Line, Tumor , Cell Proliferation/genetics , Clinical Relevance , Gene Expression Regulation, Neoplastic/genetics , Melanoma/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...