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1.
Small ; : e2401796, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38966879

ABSTRACT

As a novel type of catalytic material, hollow nanoreactors are expected to bring new development opportunities in the field of persulfate-based advanced oxidation processes due to their peculiar void-confinement, spatial compartmentation, and size-sieving effects. For such materials, however, further clarification on basic concepts and construction strategies, as well as a discussion of the inherent correlation between structure and catalytic activity are still required. In this context, this review aims to provide a state-of-the-art overview of hollow nanoreactors for activating persulfate. Initially, hollow nanoreactors are classified according to the constituent components of the shell structure and their dimensionality. Subsequently, the different construction strategies of hollow nanoreactors are described in detail, while common synthesis methods for these construction strategies are outlined. Furthermore, the most representative advantages of hollow nanoreactors are summarized, and their intrinsic connections to the nanoreactor structure are elucidated. Finally, the challenges and future prospects of hollow nanoreactors are presented.

2.
Sci Rep ; 14(1): 15683, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977794

ABSTRACT

We explored physiological effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on intact experimentally hypertrophic murine hearts following transverse aortic constriction (TAC). Postoperative drug (2-6 weeks) challenge resulted in reduced late Na+ currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na+/Ca2+ exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual voltage- and Ca2+-optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD80), Ca2+ transient peak signals and durations at 80% recovery (CaTD80), times to peak Ca2+ (TTP100) and Ca2+ decay constants (Decay30-90) during regular 10-Hz stimulation, and Ca2+ transient alternans with shortening cycle length. Isoproterenol shortened APD80 in sham-operated and TAC-only hearts, shortening CaTD80 and Decay30-90 but sparing TTP100 and Ca2+ transient alternans in all groups. All groups showed similar APD80, and TAC-only hearts showed greater CaTD80, heterogeneities following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca2+ homeostatic, and pro-arrhythmogenic changes in intact hearts.


Subject(s)
Benzhydryl Compounds , Calcium , Glucosides , Homeostasis , Animals , Benzhydryl Compounds/pharmacology , Glucosides/pharmacology , Mice , Calcium/metabolism , Homeostasis/drug effects , Male , Action Potentials/drug effects , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , NAV1.5 Voltage-Gated Sodium Channel/metabolism , Sodium-Calcium Exchanger/metabolism , Aorta/drug effects , Aorta/metabolism , Aorta/surgery , Mice, Inbred C57BL , Isoproterenol/pharmacology , Disease Models, Animal
3.
Foods ; 13(13)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38998592

ABSTRACT

This paper investigated the effects of steam explosion (SE) pretreatment on the structural characteristics and antioxidant activity of Hypsizygus marmoreus polysaccharides (HPS). Hypsizygus marmoreus samples were pretreated at different SE temperatures (120-200 °C) and polysaccharides were extracted using the water extraction and alcohol precipitation method. The results showed that SE pretreatment improved the extraction rate of HPS. Under the conditions of SE treatment time of 60 s and temperature of 160 °C, the extraction rate of HPS was the highest (8.78 ± 0.24%). After SE pretreatment, the structural changes of HPS tended to enhance the antioxidant activity, which showed that the content of Gal and Man in the monosaccharide composition increased and the molecular weight decreased. When testing antioxidant activity in vitro, the ability of SE-pretreated HPS to scavenge DPPH radicals, hydroxyl radicals, and superoxide anion radicals was better than that of HPS without SE pretreatment. Our findings shed light on SE pretreatment as an efficient method for extracting active polysaccharides, providing a new way to improve their extraction rate and biological activity.

4.
J Surv Stat Methodol ; 12(3): 578-592, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38911251

ABSTRACT

This article presents the results of an adaptive design experiment in the recruitment of households and individuals for a two-stage national probability web or mail mixed-mode survey, the American Family Health Study (AFHS). In the screening stage, we based the adaptive design's subgroup differentiation on Esri Tapestry segmentation. We used tailored invitation materials for a subsample where a high proportion of the population was Hispanic and added a paper questionnaire to the initial mailing for a subsample with rural and older families. In the main-survey stage, the adaptive design targeted the households where a member other than the screening respondent was selected for the survey. The adaptations included emailing and/or texting, an additional prepaid incentive, and seeking screening respondents' help to remind the selected individuals. The main research questions are (i) whether the adaptive design improved survey production outcomes and (ii) whether combining adaptive design and postsurvey weighting adjustments improved survey estimates compared to performing postsurvey adjustments alone. Unfortunately, the adaptive designs did not improve the survey production outcomes. We found that the weighted AFHS estimates closely resemble those of a benchmark national face-to-face survey, the National Survey of Family Growth, although the adaptive design did not additionally change survey estimates beyond the weighting adjustments. Nonetheless, our experiment yields useful insights about the implementation of adaptive design in a self-administered mail-recruit web or mail survey. We were able to identify subgroups with potentially lower response rates and distinctive characteristics, but it was challenging to develop effective protocol adaptations for these subgroups under the constraints of the two primary survey modes and the operational budget of the AFHS. In addition, for self-administered within-household selection, it was difficult to obtain contact information from, reach, and recruit selected household members that did not respond to the screening interview.

5.
Environ Res ; 258: 119495, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38936500

ABSTRACT

OBJECTIVE: Emerging evidence supports that brain dysfunction may be attributable to environmental factors. This study aims to examine associations of ambient temperature and temperature variability (TV) with seizure incidence in children, which has not been explored. MATERIAL AND METHODS: Data on 2718 outpatient visits due to seizure were collected in Shanghai, China, from 2018 to 2023. Exposure to ambient temperature was estimated at children's residential addresses using spatial-temporal models. A time-stratified case-crossover design with a distributed lag non-linear model (DLNM) was conducted to assess the association between seizure incidence and daily average of ambient temperature over a period of 21 days prior to a case date of disease onset. For a given case date, we selected all dates falling on the same day of the week within the same month as control dates. We calculated a composite index of intra-day and inter-day TV, which was the standard deviation of the daily minimum and maximum temperatures, respectively, over 7 days preceding a case date. We then assessed the association between TV and seizure incidence. Stratified analyses were conducted by age (73.51% < 5 years old and 26.49 % ≥ 5 years old), sex (41.83% female), presence of fever (69.72%), and diagnosis of epilepsy (27.63%). RESULTS: We observed inversed J-shaped temperature-response curves. Lower temperatures had a significant and prolonged effect than higher temperatures. Using 20 °C (with the minimum effect) as the reference, the cumulative odds ratios (ORs) for over 0-21 days preceding the onset at the 5th percentile of the temperature (3 °C) and at the 95th percentile (29 °C) were 3.17 (95% CI: 1.77, 5.68) and 1.54 (95% CI: 0.97, 2.44), respectively. In addition, per 1 °C increases in TV0-7 was associated with OR of 1.08 (95% CI: 1.01, 1.15). Older children and those experiencing seizure with fever exhibited a higher risk of seizure onset at both lower and higher ambient temperatures. CONCLUSION: Both low and high temperatures can contribute to the morbidity related to pediatric seizure. Lower temperatures, however, exerted a longer period of effect prior to seizure onset than higher temperatures. An increased risk for incident seizure was significantly associated with temperature variability during preceding 7 days.

6.
J Environ Manage ; 365: 121634, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38943752

ABSTRACT

The impact of NaOH-modified biochar on the release of NH3 and H2S from laying hens' manure was examined for 44 days, using a small-scale simulated aerobic composting system. The findings revealed that the NaOH-modified biochar reduced NH3 and H2S emissions by 40.63% and 77.78%, respectively, compared to the control group. Moreover, the emissions of H2S were significantly lower than those of the unmodified biochar group (p < 0.05). The increased specific surface area and microporous structure of the biochar, as well as the higher content of alkaline and oxygenated functional groups, were found to facilitate the adsorption of NH3 and H2S. This enhanced adsorption capability was the primary reason for the significant reduction in NH3 emissions. Furthermore, during the high-temperature phase of composting, there was a notable alteration in the microbial community. The abundance of Limnochordaceae, Savagea, and IMCC26207 increased significantly which aided in the conversion of H2S to stable sulfate. These microorganisms also influenced the abundance of functional genes involved in sulfur metabolism, thereby inhibiting cysteine synthesis, along with the decomposition and conversion of sulfate to sulfite. This led to a significant decrease in H2S emissions. This study provides valuable data for the selection of deodorizers in the composting process of egg-laying hens. The results have significant implications for the application of NaOH-modified biochar for odor reduction in aerobic composting processes.


Subject(s)
Ammonia , Charcoal , Chickens , Composting , Hydrogen Sulfide , Manure , Hydrogen Sulfide/chemistry , Animals , Charcoal/chemistry , Ammonia/chemistry , Sodium Hydroxide/chemistry , Female
7.
Pest Manag Sci ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38860488

ABSTRACT

BACKGROUND: Negative cofactor 2 NC2ß (Ncb2 or Dr1) is the beta subunit of a conserved heterodimeric regulator of transcription negative cofactor 2 (NC2) complex that has been identified as key regulator of drug resistance in model fungi. However, its role in plant pathogens is still unclear. RESULTS: We identified an NC2ß orthologue, FpNcb2, in Fusarium pseudograminearum, which is not only a significant regulatory function in drug resistance, but also essential for growth, conidiation and penetration. Moreover, FpNcb2 undergoes alternative splicing which creates two mRNA isoforms. As a putative CCAAT binding protein, FpNcb2 concentrates in the nuclei, contributing to the expression of two spliced mRNA of FpNcb2 in hypha, conidiophores and conidia, with exception of FpNcb2ISOA in germlings. Expression of each spliced mRNA of FpNcb2 in Δfpncb2 mutant could full complement the defects on growth, conidiation and fungicides sensitivity to that of wild type. However, FpNcb2ISOA and FpNcb2ISOB have different effects on virulence. FpNcb2 acts as a regulator for the transcription of some genes encoding drug efflux and hydrolases. CONCLUSION: Our analysis showed the existence of alternative mRNA splicing in the NC2ß orthologue, which is associated with protein subcellular localization and fungal virulence. The further elucidation of the target genes of NC2ß will provide insights into the potential regulation mechanisms in the antifungal resistance and pathogenesis of F. pseudograminearum. © 2024 Society of Chemical Industry.

8.
J Stroke Cerebrovasc Dis ; : 107829, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901472

ABSTRACT

BACKGROUND: Cerebral small vessel disease (CSVD) includes vascular disorders characterized by heterogeneous pathomechanisms and different neuropathological clinical manifestations. Cognitive dysfunction in CSVD is associated with reductions in structural covariance networks (SCNs). A majority of research conducted on SCNs focused on group-level analysis. However, it is crucial to investigate the individualized variations in order to gain a better understanding of heterogeneous disorders such as CSVD. Therefore, this study aimed to utilize individualized differential structural covariance network (IDSCN) analysis to detect individualized structural covariance aberration. METHODS: A total of 35 healthy controls and 33 CSVD patients with cognitive impairment participated in this investigation. Using the regional gray matter volume in their T1 images, the IDSCN was constructed for each participant. Finally, the differential structural covariance edges between the two groups were determined by comparing their IDSCN using paired-sample t-tests. On the basis of these differential edges, the two subtypes of cognitively impaired CSVD patients were identified. RESULTS: The findings revealed that the differential structural covariance edges in CSVD patients with cognitive impairment showed a highly heterogeneous idistribution, with the edges primarily cross-distributed between the occipital lobe (specifically inferior occipital gyrus and cuneus), temporal lobe (specifically superior temporal gyrus), and the cerebellum. To varying degrees, the inferior frontal gyrus and the superior parietal gyrus were also distributed. Subsequently, a correlation analysis was performed between the resulting differential edges and the cognitive scale scores. A significant negative association was observed between the cognitive scores and the differential edges distributed in the inferior frontal gyrus and inferior occipital gyrus, the superior temporal gyrus and inferior occipital gyrus, and within the temporal lobe. Particularly in the cognitive domain of attention, the two subtypes separated by differential edges exhibited differences in cognitive scale scores [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)]. The differential edges of the subtype 1, characterized by lower cognitive level, were mainly cross-distributed in the limbic lobe (specifically the cingulate gyrus and hippocampus), the parietal lobe (including the superior parietal gyrus and precuneus), and the cerebellum. In contrast, the differential edges of the subtype 2 with a relatively high level of cognition were distributed between the cuneus and the cerebellum. CONCLUSIONS: The differential structural covariance was investigated between the healthy controls and the CSVD patients with cognitive impairment, showing that differential structural covariance existed between the two groups. The edge distributions in certain parts of the brain, such as cerebellum and occipital and temporal lobes, verified this. Significant associations were seen between cognitive scale scores and some of those differential edges .The two subtypes that differed in both differential edges and cognitive levels were also identified. The differential edges of subtype 1 with relatively lower cognitive levels were more distributed in the cingulate gyrus, hippocampus, superior parietal gyrus, and precuneus. This could potentially offer significant benefits in terms of accurate diagnosis and targeted treatment of heterogeneous disorders such as CSVD.

9.
Oncol Lett ; 28(2): 349, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38872862

ABSTRACT

Metadherin (MTDH), initially discovered in primary astrocytes of the human fetus through rapid subtraction hybridization and labeled as astrocyte elevated gene-1, represents a widely recognized oncogene present in multiple types of cancers. However, the role of MTDH in different types of cancer remains unclear. To address this, a comprehensive analysis of MTDH across various types of cancers was conducted by utilizing multiple databases such as The Cancer Genome Atlas. The present analysis discovered that MTDH exhibits differential expression in different types of cancer and is associated with important factors including tumor mutational burden and microsatellite instability. These findings highlighted the significance of MTDH in the tumor microenvironment and its involvement in the development of immune cells in specific cancers. Furthermore, the results of the present study indicated that the expression of MTDH is strongly correlated with clinical prognosis, mutations and immune cell infiltration. MTDH could serve as a potential indicator of patient prognosis and potentially play a role in modulating the immune system. Given its potential as a novel immunological checkpoint, MTDH may be a viable target for tumor immunotherapy.

10.
J Am Chem Soc ; 146(22): 15176-15185, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38770641

ABSTRACT

Stepwise oxidative addition of copper(I) complexes to form copper(III) species via single electron transfer (SET) events has been widely proposed in copper catalysis. However, direct observation and detailed investigation of these fundamental steps remain elusive owing largely to the typically slow oxidative addition rate of copper(I) complexes and the instability of the copper(III) species. We report herein a novel aryl-radical-enabled stepwise oxidative addition pathway that allows for the formation of well-defined alkyl-CuIII species from CuI complexes. The process is enabled by the SET from a CuI species to an aryl diazonium salt to form a CuII species and an aryl radical. Subsequent iodine abstraction from an alkyl iodide by the aryl radical affords an alkyl radical, which then reacts with the CuII species to form the alkyl-CuIII complex. The structure of resultant [(bpy)CuIII(CF3)2(alkyl)] complexes has been characterized by NMR spectroscopy and X-ray crystallography. Competition experiments have revealed that the rate at which different alkyl iodides undergo oxidative addition is consistent with the rate of iodine abstraction by carbon-centered radicals. The CuII intermediate formed during the SET process has been identified as a four-coordinate complex, [CuII(CH3CN)2(CF3)2], through electronic paramagnetic resonance (EPR) studies. The catalytic relevance of the high-valent organo-CuIII has been demonstrated by the C-C bond-forming reductive elimination reactivity. Finally, localized orbital bonding analysis of these formal CuIII complexes indicates inverted ligand fields in σ(Cu-CH2) bonds. These results demonstrate the stepwise oxidative addition in copper catalysis and provide a general strategy to investigate the elusive formal CuIII complexes.

11.
J Am Chem Soc ; 146(22): 15036-15044, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38770819

ABSTRACT

Multicopper oxidases (MCOs) utilize a tricopper active site to reduce dioxygen to water through 4H+ 4e- proton-coupled electron transfer (PCET). Understanding the thermodynamics of PCET at a tricopper cluster is essential for elucidating how MCOs harness the oxidative power of O2 while mitigating oxidative damage. In this study, we determined the O-H bond dissociation free energies (BDFEs) and pKa values of a series of tricopper hydroxo and tricopper aqua complexes as synthetic models of the tricopper site in MCOs. Tricopper intermediates on the path of alternating electron and proton transfer (ET-PT-ET-PT-ET) have modest BDFE(O-H) values in the range of 53.0-57.1 kcal/mol. In contrast, those not on the path of ET-PT-ET-PT-ET display much higher (78.1 kcal/mol) or lower (44.7 kcal/mol) BDFE(O-H) values. Additionally, the pKa of bridging OH and OH2 motifs increase by 8-16 pKa units per oxidation state. The same oxidation state changes have a lesser impact on the pKa of N-H motif in the secondary coordination sphere, with an increase of ca. 5 pKa units per oxidation state. The steeper pKa increase of the tricopper center promotes proton transfer from the secondary coordination sphere. Overall, our study shed light on the PCET pathway least prone to decomposition, elucidating why tricopper centers are an optimal choice for promoting efficient oxygen reduction reaction.

12.
Biomolecules ; 14(5)2024 May 18.
Article in English | MEDLINE | ID: mdl-38786003

ABSTRACT

Oral squamous cell carcinoma (OSCC) stands as a prevalent subtype of head and neck squamous cell carcinoma, leading to disease recurrence and low survival rates. PPARγ, a ligand-dependent nuclear transcription factor, holds significance in tumor development. However, the role of PPARγ in the development of OSCC has not been fully elucidated. Through transcriptome sequencing analysis, we discovered a notable enrichment of ferroptosis-related molecules upon treatment with PPARγ antagonist. We subsequently confirmed the occurrence of ferroptosis through transmission electron microscopy, iron detection, etc. Notably, ferroptosis inhibitors could not completely rescue the cell death caused by PPARγ inhibitors, and the rescue effect was the greatest when disulfidptosis and ferroptosis inhibitors coexisted. We confirmed that the disulfidptosis phenotype indeed existed. Mechanistically, through qPCR and Western blotting, we observed that the inhibition of PPARγ resulted in the upregulation of heme oxygenase 1 (HMOX1), thereby promoting ferroptosis, while solute carrier family 7 member 11 (SLC7A11) was also upregulated to promote disulfidptosis in OSCC. Finally, a flow cytometry analysis of flight and multiplex immunohistochemical staining was used to characterize the immune status of PPARγ antagonist-treated OSCC tissues in a mouse tongue orthotopic transplantation tumor model, and the results showed that the inhibition of PPARγ led to ferroptosis and disulfidptosis, promoted the aggregation of cDCs and CD8+ T cells, and inhibited the progression of OSCC. Overall, our findings reveal that PPARγ plays a key role in regulating cell death in OSCC and that targeting PPARγ may be a potential therapeutic approach for OSCC.


Subject(s)
Ferroptosis , PPAR gamma , Ferroptosis/drug effects , Animals , PPAR gamma/metabolism , PPAR gamma/antagonists & inhibitors , Humans , Mice , Cell Line, Tumor , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/antagonists & inhibitors , Amino Acid Transport System y+/genetics , Heme Oxygenase-1/metabolism , Antineoplastic Agents/pharmacology , Mouth Neoplasms/drug therapy , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/genetics , Gene Expression Regulation, Neoplastic/drug effects
13.
Oncol Lett ; 27(6): 280, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38699662

ABSTRACT

Breast cancer (BC) is the most common type of cancer found in women. ADP-ribosylation factors (ARFs) are a group of small proteins that bind to GTP and are involved in controlling different cellular functions. The function and evolution of multiple ARFs in BC have remained to be fully elucidated, despite existing studies on this protein family in Homo sapiens and other species. In the present study, a systematic analysis of ARF expression levels in BC tissues compared to normal breast tissues was performed using data from The Cancer Genome Atlas database. The analysis revealed significantly higher expression of ARFs in BC tissues. In addition, the prognostic significance of ARF1 and ARF3-6 expression levels was assessed in patients with BC. Of note, elevated ARF1 expression was associated with reduced rates of distant metastasis-free survival (DMFS), overall survival (OS) and recurrence-free survival (RFS) in affected individuals. Similarly, patients with high expression levels of ARF3 had lower post-progression survival (PPS) rates. In addition, patients with higher ARF4 expression had worse PPS and patients with high ARF5 expression exhibited lower DMFS. Patients with high ARF6 expression had worse DMFS, OS, RFS and predictive power score values. Furthermore, the expression of ARF was found to be strongly linked to the infiltration of various immune cell types, namely dendritic cells, macrophages, neutrophils, CD8+ T cells and B cells. These significant associations offer a solid foundation for the potential utilization of new therapeutic targets and predictive markers for the treatment of BC.

14.
Langmuir ; 40(19): 9873-9891, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38695884

ABSTRACT

Inspired by nature, superhydrophobic surfaces have been widely studied. Usually the wettability of a superhydrophobic surface is quantified by the macroscopic contact angle. However, this method has various limitations, especially for precision micro devices with superhydrophobic surfaces, such as biomimetic artificial compound eyes and biomimetic water strider robots. These precision micro devices with superhydrophobic surfaces proposed a higher demand for the quantification of contact angles, requiring contact angle quantification technology to have micrometer-scale measurement capabilities. In this review, it is proposed to achieve micrometer-scale quantification of superhydrophobic surface contact angles through droplet adhesion characteristics (adhesion force and contact radius). Existing contact angle quantification techniques and droplet characteristics' measurement methods were described in detail. The advancement of micrometer-scale quantification technology for the contact angle of superhydrophobic surfaces will enhance our understanding of superhydrophobic surfaces.

15.
Clin Transl Med ; 14(5): e1652, 2024 May.
Article in English | MEDLINE | ID: mdl-38741204

ABSTRACT

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.


Subject(s)
Carcinoma, Hepatocellular , DNA Methylation , Early Detection of Cancer , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/genetics , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , Female , Male , DNA Methylation/genetics , Middle Aged , Prognosis , Early Detection of Cancer/methods , Circulating Tumor DNA/blood , Circulating Tumor DNA/genetics , Cohort Studies , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Aged , Adult
16.
BMJ Med ; 3(1): e000451, 2024.
Article in English | MEDLINE | ID: mdl-38800667

ABSTRACT

Objective: To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death. Design: Prospective cohort study. Setting: UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years). Participants: 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study. Main outcome measures: Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). Results: Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99). Conclusions: Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

17.
Sci Data ; 11(1): 538, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796526

ABSTRACT

Mixed reality navigation (MRN) technology is emerging as an increasingly significant and interesting topic in neurosurgery. MRN enables neurosurgeons to "see through" the head with an interactive, hybrid visualization environment that merges virtual- and physical-world elements. Offering immersive, intuitive, and reliable guidance for preoperative and intraoperative intervention of intracranial lesions, MRN showcases its potential as an economically efficient and user-friendly alternative to standard neuronavigation systems. However, the clinical research and development of MRN systems present challenges: recruiting a sufficient number of patients within a limited timeframe is difficult, and acquiring low-cost, commercially available, medically significant head phantoms is equally challenging. To accelerate the development of novel MRN systems and surmount these obstacles, the study presents a dataset designed for MRN system development and testing in neurosurgery. It includes CT and MRI data from 19 patients with intracranial lesions and derived 3D models of anatomical structures and validation references. The models are available in Wavefront object (OBJ) and Stereolithography (STL) formats, supporting the creation and assessment of neurosurgical MRN applications.


Subject(s)
Neuronavigation , Humans , Neurosurgical Procedures , Magnetic Resonance Imaging , Head/surgery , Tomography, X-Ray Computed , Imaging, Three-Dimensional
18.
Quant Imaging Med Surg ; 14(5): 3302-3311, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38720836

ABSTRACT

Background: The parietal pleural adhesion/invasion of lung cancer can contribute substantially to poor prognosis and difficulty in surgery. The value of ultrasound in evaluating the parietal pleural adhesion or invasion (pleural adhesion/invasion) of lung cancer remains uncertain. This study investigated the value of B-mode ultrasound and contrast-enhanced ultrasound (CEUS) in diagnosing parietal pleural adhesion/invasion of subpleural lung cancer. Methods: The study animals included 40 male New Zealand white rabbits. A rabbit subpleural lung cancer model was constructed by injecting VX2 tumor tissue under ultrasound guidance. In the 1-3 weeks after subpleural lesion formation, parietal pleural adhesion/invasion of the largest subpleural lesion was evaluated with B-mode ultrasound and CEUS by two sonographers. The parietal pleural adhesion/invasion was also determined using the gold standard method of findings from anatomical and pathological examination. Results: Ultimately, 34 rabbits were subjected to complete ultrasonic evaluation. There were 20 and 14 cases with and without parietal pleural adhesion/invasion, respectively, as confirmed by anatomical and pathological evaluations. The diagnostic sensitivity, specificity, and accuracy of sonographer 1 using B-mode ultrasound were 50.0% [95% confidence interval (CI): 26.0-74.0%], 100%, and 70.6% (95% CI: 54.5-86.7%), respectively; for CEUS, they were 90.0% (95% CI: 75.6-100.0%), 100.0%, and 94.1% (95% CI: 85.8-100.0%), respectively. The diagnostic sensitivity, specificity, and accuracy of sonographer 2 using B-mode ultrasound were 45.0% (95% CI: 21.1-68.9%), 92.9% (95% CI: 77.5-100.0%), and 64.7% (95% CI: 47.8-81.6%), respectively; for CEUS, they were 85.0% (95% CI: 67.9-100.0%), 100.0%, and 91.2% (95% CI: 81.1-100.0%), respectively. The diagnostic accuracy of sonographer 1 was higher with CEUS than with B-mode ultrasound, but not significantly so (94.1% vs. 70.6%; P=0.08). The diagnostic accuracy of sonographer 2 was significantly higher with CEUS than with B-mode ultrasound (91.2% vs. 64.7%; P=0.03). The interrater reliability was higher for CEUS than for B-mode ultrasound (κ=0.941 vs. κ =0.717). Conclusions: Based on an animal model, B-mode ultrasound and CEUS both exhibited good diagnostic efficacy and interrater reliability in evaluating parietal pleural adhesion/invasion of subpleural lung cancer although CEUS outperformed B-mode ultrasound for both measures.

19.
MedComm (2020) ; 5(5): e561, 2024 May.
Article in English | MEDLINE | ID: mdl-38721005

ABSTRACT

Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa, the mechanism of its inflammatory progression has not yet been fully elucidated. PA28γ plays a significant role in a variety of immune-related diseases. However, the exact role of PA28γ in the pathogenesis of OLP remains unclear. Here, we demonstrated that PA28γ is overexpressed in epithelial cells and inflammatory cells of OLP tissues but has no significant relationship with OLP subtypes. Functionally, keratinocytes with high PA28γ expression could induce dendritic cell (DC) maturation and promote the T-cell differentiation into Th1 cells in response to the immune response. In addition, we found that a high level of PA28γ expression is associated with high numbers of infiltrating mature DCs and activated T-cells in OLP tissues. Mechanistically, keratinocytes with high PA28γ expression could promote the secretion of C-C motif chemokine (CCL)5, blocking CCL5 or/and its receptor CD44 could inhibit the induction of T-cell differentiation by keratinocytes with high PA28γ expression. In conclusion, we reveal that keratinocytes with high expression of PA28γ in OLP can induce DC maturation and promote T-cell differentiation through the CCL5-CD44 pathway, providing previously unidentified mechanistic insights into the mechanism of inflammatory progression in OLP.

20.
Neuropsychiatr Dis Treat ; 20: 1025-1040, 2024.
Article in English | MEDLINE | ID: mdl-38764747

ABSTRACT

Purpose: With the further development of attention-deficit/hyperactivity disorder (ADHD) research, more and more assessment tools related to ADHD have been used. However, there is still no measurement instrument to evaluate the compensatory behavior of ADHD in China. This study aimed to examine the reliability and validity of the Compensatory ADHD Behaviors Scale (CABS) adapted in Chinese and explore ecological characteristics in adults with ADHD using the CABS. Patients and Methods: Data were collected from a sample of 306 adults (Mage = 26.43 years, SD = 5.32; 46.08% male). The original version CABS was translated into Chinese using the forward and backward translation procedures. Participants completed the CABS and questionnaires assessing ADHD symptoms and executive function. We utilized content validity, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and criterion validity to test the validity. Internal consistency and test-retest reliability were employed to test the reliability. Analysis of variance (ANOVA) was employed to compare ADHD subgroups based on gender, ADHD subtype, comorbidities, and medication status, while controlling for demographic variables as covariates. Results: CABS exhibited good construct validity (two factors: present-oriented and future-oriented), content validity (content validity index: 0.98), internal consistency reliability (Cronbach's alpha coefficient: 0.85 to 0.87) and test-retest reliability (intraclass correlation coefficient: 0.59 to 0.88). The results of CFA showed acceptable fitness for each subscale. CABS demonstrated significant associations with inattention symptoms and plan/organizational abilities. Medicated ADHD individuals scored higher on future-oriented effectiveness subscale of CABS than non-medicated (F = 6.106, p = 0.014). Conclusion: The results indicate that the Chinese CABS exhibited good validity and reliability. It can be considered a valid tool for assessing compensatory behaviors in Chinese adults with ADHD. Further research is needed to explore the connection between medication and compensatory behavior.

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