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Nitrites (NO2-/HONO), as the primary source of hydroxyl radicals (â¢OH) in the atmosphere, play a key role in atmospheric chemistry. However, the current understanding of the source of NO2-/HONO is insufficient and therefore hinders the accurate quantification of atmospheric oxidation capacity. Herein, we highlighted an overlooked HONO source by the reaction between nitrophenols (NPs) and â¢OH in the aqueous phase and provided kinetic data to better evaluate the contribution of this process to atmospheric HONO. Three typical NPs, including 4-nitrophenol (4NP), 2-nitrophenol (2NP), and 4-nitrocatechol (4NC), underwent a denitration process to form aqueous NO2- and gaseous HONO through the â¢OH oxidation, with the yield of NO2-/HONO varied from 15.0 to 33.5%. According to chemical composition and structure analysis, the reaction pathway, where the ipso addition of â¢OH to the NO2 group on 4NP generated hydroquinone, can contribute to more than 61.9% of the NO2-/HONO formation. The aqueous photooxidation of NPs may account for HONO in the atmosphere, depending on the specific conditions. The results clearly suggest that the photooxidation of NPs should be considered in the field observation and calculation to better evaluate the HONO budget in the atmosphere.
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Background: The global incidence of neurological diseases has been on the rise, creating an urgent need for a validated marker. Neurofilament Light Chain (NfL) holds promise as such a marker and has garnered significant attention in the field of neurological diseases over the past decades. Methods: Corresponding articles from 2013 to 2023 were collected from the Web of Science database, and data were analyzed by CiteSpace and VOSviewer software. Results: A total of 1350 articles were collected from 296 countries/regions, involving 7246 research organizations. Since 2013, among the top ten institutions and authors with the highest number of published papers, the most are from the US and the UK. The United States leads in the number of published papers, but England holds a more momentous position, because it has higher IF. Henrik Zetterberg is the most influential scholar in the field. Conclusions: The output of papers mainly relies on researchers from developed countries, and scholars from the United States and England have contributed the largest number of papers. Until now, the importance of NfL in neurological diseases has attracted global attention. In addition, NfL contributes to the potential diagnosis of various neurological disorders and can be used to improve the accuracy of differential diagnosis and prognostic assessment as well as predict the response to treatments. More and more in-depth studies are highly needed in the future.
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The present study focused on the efficacy and role of triptolide (TPL) in relieving symptoms of acute gouty arthritis (AGA) in vivo and in vitro. The effects of TPL in AGA were investigated in monosodium urate (MSU)-treated rat ankles, RAW264.7 macrophages, and neutrophils isolated from mouse peritoneal cavity. Observation of pathological changes in the ankle joint of rats. Enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of inflammatory factors and chemokines. The levels of the indicators of macrophage M1/M2 polarization, and the mechanistic targets of Akt and rapamycin complex 2, were determined via western blotting and RT-qPCR. The expression levels of CD86 and CD206 were detected using immunohistochemistry. Neutrophil migration was observed via air pouch experiments in vivo and Transwell cell migration assay in vitro. Myeloperoxidase (MPO) and Neutrophil elastase (NE) release was analyzed by via immunohistochemistry and immunofluorescence. The expression levels of beclin-1, LC3B, Bax, Bcl-2, and cleaved caspase-3 in neutrophils were determined via western blotting and immunofluorescence. Neutrophil apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Our results suggest that TPL inhibited inflammatory cell infiltration in rat ankle joints and inflammatory factor and chemokine secretion in rat serum, regulated macrophage polarization through the PI3K/AKT signaling pathway, suppressed inflammatory factor and chemokine expression in neutrophils, and inhibited neutrophil migration, neutrophil extracellular trap formation, transitional autophagy, and apoptosis. This suggests that TPL can prevent and treat MSU-induced AGA by regulating macrophage polarization through the PI3K/Akt pathway and modulating neutrophil activity.
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Steroid hormones exhibit potent endocrine disrupting activity and have been shown to disrupt the equilibrium of aquatic ecosystems and pose a threat to public health through their persistent and carcinogenic effects. Pontibacillus chungwhensis HN14, a moderately halophilic bacterium with the capacity to effectively degrade various polycyclic aromatic hydrocarbons and other organic pollutants, was previously isolated. Additionally, the strain HN14 showed strong environmental adaptability under various environmental stress conditions. In this study, the steroid degradation by strain HN14 was studied for the first time. We demonstrated that strain HN14 could degrade estradiol (E2) to maintain the growth of the strain and could convert E2 to estrone. Additionally, the efficient substrate degradation efficiency of P. chungwhensis HN14 under high salinity and high substrate concentration conditions was demonstrated. Furthermore, a 17ß-hydroxysteroid dehydrogenase, 17ß-HSD(HN14), was identified in strain HN14. Comparative analysis reveals that 17ß-HSD(HN14) shares approximately 38% sequence identity with 17ß-HSDx from Rhodococcus sp. P14. In addition, 100 µg of purified 17ß-HSD(HN14) could effectively convert about 40% of 0.25 mM of E2 within 1 h period, with an enzyme activity of 17.5 U/mg, and catalyze the dehydrogenation of E2 and testosterone at the C-17 position. The characterization of purified enzyme properties reveals that 17ß-HSD(HN14) exhibits exceptional structural robustness and enzymatic efficacy even under high salinity conditions of up to 20%. Overall, this study enhances our comprehension of steroid biodegradation in strain HN14 and contributes novel ideas and theoretical underpinnings for advancing bioremediation technologies targeting steroid pollution in high-saline environments.
Subject(s)
17-Hydroxysteroid Dehydrogenases , Biodegradation, Environmental , Salinity , 17-Hydroxysteroid Dehydrogenases/metabolism , 17-Hydroxysteroid Dehydrogenases/genetics , Bacillaceae/enzymology , Bacillaceae/genetics , Bacillaceae/metabolism , Estradiol/metabolism , Estrone/metabolism , Phylogeny , Endocrine Disruptors/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Steroids/metabolismABSTRACT
Background: The increasing prevalence of depressive symptoms has emerged as a critical public health issue globally, highlighting the need for analyses of the factors contributing to depressive symptoms within the Chinese population and the development of targeted recommendations for improving mental well-being. We aimed to explore the correlation between internet use and depressive symptoms and the role of socioeconomic inequalities in this association. Methods: We included data on 8019 residents aged 18 years and above, which we retrieved from the 2018 and 2020 waves of the China Family Panel Studies. We used latent profile analysis to categorise individuals' internet usage patterns and multiple linear regression to determine their association with depressive symptoms. Results: Higher socioeconomic status (SES) was associated with fewer depressive symptoms (τ = -0.08; 95% confidence interval (CI) = -0.36, -0.18). Individuals in the high-dependence group presented a greater likelihood of developing depressive symptoms (τ = 0.04; 95% CI = 0.007, 0.66). We observed no significant difference in the interaction effect between individual-level SES and the four patterns of internet usage. However, compared with urban-dwelling respondents, those in rural areas had a stronger association between internet usage patterns and depressive symptoms, especially those in the high-dependence group (τ = -0.07; 95% CI = -1.47, -0.20). Conclusions: Our findings indicate a significant association between depressive symptoms and internet usage patterns, indicating a need for interventions related to internet use, especially those targeted at reducing the risk of depressive symptoms in individuals of lower SES.
Subject(s)
Depression , Internet Use , Socioeconomic Factors , Humans , Male , Female , China/epidemiology , Depression/epidemiology , Adult , Middle Aged , Longitudinal Studies , Young Adult , Internet Use/statistics & numerical data , Adolescent , Social Class , Internet/statistics & numerical data , Aged , East Asian PeopleABSTRACT
In conventional knowledge, ferroelectric solid solutions were formed between members belonging to the same crystal structure family. Since both tungsten bronze and perovskite structures are constructed by connecting the corner-sharing oxygen octahedra, it offers a possibility for formatting an unusual solid solution between these two families. Herein, (1 - x)Sr0.6Ba0.4Nb2O6-xBaTiO3, (1 - x)SBN-xBT, solid solutions were synthesized and the solution mechanism was resolved from a structure viewpoint. With increasing BT content, the solid solution persists of tetragonal tungsten bronze structure, but the lattice parameter a (= b) decreases whereas c increases, resulting in the significant reduction of grains anisotropy. The ferroelectric-relaxor phase transition temperature shows a monotonic increase as x increases. However, the ferroelectricity evolution is not monotonous as a function of BT content because of the competitive effects of Ba and Ti on the property. As a result, the x = 0.10 ceramic shows the strongest ferroelectricity and a remarkable electrocaloric effect of 1.4 K near room temperature. This work challenges the traditional view of solid solution formation and provides an alternative way to modulate the structure and properties of ferroelectrics.
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Diaryl-substituted vinyl boronates as potent building modules are challenging to synthesize. Herein, we present a convenient strategy based on a gold-catalyzed Hiyama arylation of (Z)-ß-(borylvinyl)silanes which are easily accessible by hydroboration of silylalkynes. By exploiting the highly electronegative nature of the Au(III) intermediate (which is accessed by the light-assisted oxidation with aryl diazonium salts), a selective activation of the silyl group in the presence of the boron moiety is achieved. This opens a route to selectively synthesize diaryl-substituted vinyl boronates. The reaction shows a broad substrate range, excellent functional group tolerance and perfect chemo-selectivity. Experimental studies and DFT calculations allowed us to elucidate the mechanism of the reaction, the synthetic potential was demonstrated by downstream transformations providing a facile route to bifunctional phenanthrenes and triaryl-substituted olefins.
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Rationale: Cardiomyocytes (CMs) undergo dramatic structural and functional changes in postnatal maturation; however, the regulatory mechanisms remain greatly unclear. Cypher/Z-band alternatively spliced PDZ-motif protein (ZASP) is an essential sarcomere component maintaining Z-disc stability. Deletion of mouse Cypher and mutation in human ZASP result in dilated cardiomyopathy (DCM). Whether Cypher/ZASP participates in CM maturation and thereby affects cardiac function has not been answered. Methods: Immunofluorescence, transmission electron microscopy, real-time quantitative PCR, and Western blot were utilized to identify the role of Cypher in CM maturation. Subsequently, RNA sequencing and bioinformatics analysis predicted serum response factor (SRF) as the key regulator. Rescue experiments were conducted using adenovirus or adeno-associated viruses encoding SRF, both in vitro and in vivo. The molecular mechanisms were elucidated through G-actin/F-actin fractionation, nuclear-cytoplasmic extraction, actin disassembly assays, and co-sedimentation assays. Results: Cypher deletion led to impaired sarcomere isoform switch and morphological abnormalities in mitochondria, transverse-tubules, and intercalated discs. RNA-sequencing analysis revealed significant dysregulation of crucial genes related to sarcomere assembly, mitochondrial metabolism, and electrophysiology in the absence of Cypher. Furthermore, SRF was predicted as key transcription factor mediating the transcriptional differences. Subsequent rescue experiments showed that SRF re-expression during the critical postnatal period effectively rectified CM maturation defects and notably improved cardiac function in Cypher-depleted mice. Mechanistically, Cypher deficiency resulted in the destabilization of F-actin and a notable increase in G-actin levels, thereby impeding the nuclear localisation of myocardin-related transcription factor A (MRTFA) and subsequently initiating SRF transcription. Conclusion: Cypher/ZASP plays a crucial role in CM maturation through actin-mediated MRTFA-SRF signalling. The linkage between CM maturation abnormalities and the late-onset of DCM is suggested, providing further insights into the pathogenesis of DCM and potential treatment strategies.
Subject(s)
Actins , Cardiomyopathy, Dilated , Myocytes, Cardiac , Serum Response Factor , Signal Transduction , Trans-Activators , Animals , Myocytes, Cardiac/metabolism , Serum Response Factor/metabolism , Serum Response Factor/genetics , Mice , Actins/metabolism , Trans-Activators/metabolism , Trans-Activators/genetics , Cardiomyopathy, Dilated/metabolism , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/pathology , Sarcomeres/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Humans , Mice, KnockoutABSTRACT
Purpose: Kidney transplantation (KT) has the potential to reverse the cardiac changes caused by end-stage renal disease, and it may be inaccurate to analysis the left ventricular function by conventional echocardiography due to afterload. This study aimed to investigate the utility of pressure strain loops (PSLs) in evaluating left ventricular performance in patients underwent KT. Methods: We enrolled 60 patients with end-stage renal disease who underwent KT between January 2022 and July 2023, and 60 healthy controls with a similar distribution of gender and age to the patients. All participants underwent conventional echocardiography and three-dimensional speckle tracking echocardiography (3D-STE). Long axis, short axis, and four cavity images were collected and cardiac parameters were measured. The echocardiographic changes of cardiac structure and function of all patients before KT and about 12 months after KT were recorded. Left ventricular myocardial work parameters were acquired by PSLs, including the global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE) and global longitudinal strain (GLS). In addition, the correlation between PSLs and clinical data were explored. Results: Compared with controls, the conventional echocardiographic parameters, myocardial function indicators GWI and GCW appeared no difference in post-KT group, while the GWE and GLS decreased (p < 0.05), and the GWW increased (p < 0.05). Compared with pre-KT, the GLS, GWI, GCW and GWE increased in post-KT group, while the GWW decreased (all p < 0.05). The above indicators were correlated with left ventricular GLS and left ventricular ejection fraction. Conclusion: PSLs were more sensitive than traditional echocardiographic indicators in detecting changes in myocardial work and predicting left ventricular myocardial damage. This indicator could quantitatively evaluate myocardial work and provide a new and reliable non-invasive reference for clinical diagnosis and treatment of patients underwent KT.
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Background: The escalation of global population aging has accentuated the prominence of senile diabetes mellitus (SDM) as a consequential public health concern. Oxidative stress and chronic inflammatory cascades prevalent in individuals with senile diabetes significantly amplify disease progression and complication rates. Traditional Chinese Medicine (TCM) emerges as a pivotal player in enhancing blood sugar homeostasis and retarding complication onset in the clinical management of senile diabetes. Nonetheless, an evident research gap persists regarding the integration of TCM's renal tonification pharmacological mechanisms with experimental validation within the realm of senile diabetes therapeutics. Aims: The objective of this study was to investigate the mechanisms of action of New Shenqi Pills (SQP) in the treatment of SDM and make an experimental assessment. Methods: Network analysis is used to evaluate target pathways related to SQP and SDM. Mitochondrial-related genes were obtained from the MitoCarta3.0 database and intersected with the common target genes of the disease and drugs, then constructing a protein-protein interaction (PPI) network making use of the GeneMANIA database. Representative compounds in the SQP were quantitatively measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to ensure quality control and quantitative analysis of the compounds. A type 2 diabetes mice (C57BL/6) model was used to investigate the pharmacodynamics of SQP. The glucose lowering efficacy of SQP was assessed through various metrics including body weight and fasting blood glucose (FBG). To elucidate the modulatory effects of SQP on pancreatic beta cell function, we measured oral glucose tolerance test (OGTT), insulin histochemical staining and tunel apoptosis detection, then assessed the insulin-mediated phosphoinositide 3-kinase (PI3K)/protein kinase A (Akt)/glycogen synthase kinase-3ß (GSK-3ß) pathway in diabetic mice via Western blotting. Additionally, we observe the structural changes of the nucleus, cytoplasmic granules and mitochondria of pancreatic islet ß cells. Results: In this investigation, we identified a total of 1876 genes associated with senile diabetes, 278 targets of SQP, and 166 overlapping target genes, primarily enriched in pathways pertinent to oxidative stress response, peptide response, and oxygen level modulation. Moreover, an intersection analysis involving 1,136 human mitochondrial genes and comorbidity targets yielded 15 mitochondria-related therapeutic targets. Quality control assessments and quantitative analyses of SQP revealed the predominant presence of five compounds with elevated concentrations: Catalpol, Cinnamon Aldehyde, Rehmanthin D, Trigonelline, and Paeonol Phenol. Vivo experiments demonstrated notable findings. Relative to the control group, mice in the model group exhibited significant increases in body weight and fasting blood glucose levels, alongside decreased insulin secretion and heightened islet cell apoptosis. Moreover, ß-cells nuclear condensation and mitochondrial cristae disappearance were observed, accompanied by reduced expression levels of p-GSK-3ß protein in islet cells (p < 0.05 or p < 0.01). Conversely, treatment groups administered SQP and Rg displayed augmented expressions of the aforementioned protein markers (p < 0.05 or p < 0.01), alongside preserved mitochondrial cristae structure in islet ß cells. Conclusion: Our findings suggest that SQP can ameliorate diabetes by reducing islet cell apoptosis and resist oxidative stress. These insulin-mediated PI3K/AKT/GSK-3ß pathway plays an important regulatory role in this process.
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AIMS: Circular RNAs (circRNAs) are considered important regulators of biological processes, but their impact on atherosclerosis development, a key factor in coronary artery disease (CAD), has not been fully elucidated. We aimed to investigate their potential use in patients with CAD and the pathogenesis of atherosclerosis. METHODS AND RESULTS: Patients with stable angina (SA) or acute coronary syndrome (ACS) and controls were selected for transcriptomic screening and quantification of circRNAs in blood cells. We stained carotid plaque samples for circRNAs and performed gain- and loss-of-function studies in vitro. Western blots, protein interaction analysis, and molecular approaches were used to perform the mechanistic study. ApoE-/- mouse models were employed in functional studies with adeno-associated virus-mediated genetic intervention. We demonstrated elevated circARCN1 expression in peripheral blood mononuclear cells from patients with SA or ACS, especially in those with ACS. Furthermore, higher circARCN1 levels were associated with a higher risk of developing SA and ACS. We also observed elevated expression of circARCN1 in carotid artery plaques. Further analysis indicated that circARCN1 was mainly expressed in monocytes and macrophages, which was also confirmed in atherosclerotic plaques. Our in vitro studies provided evidence that circARCN1 affected the interaction between HuR and ubiquitin-specific peptidase 31 (USP31) mRNA, resulting in attenuated USP31-mediated NF-κB activation. Interestingly, macrophage accumulation and inflammation in atherosclerotic plaques were markedly decreased when circARCN1 was knocked down with adeno-associated virus in macrophages of ApoE-/- mice, while circARCN1 overexpression in the model exacerbated atherosclerotic lesions. CONCLUSIONS: Our findings provide solid evidence macrophagic-expressed circARCN1 plays a role in atherosclerosis development by regulating HuR-mediated USP31 mRNA stability and NF-κB activation, suggesting that circARCN1 may serve as a factor for atherosclerotic lesion formation.
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Fuzheng Huayu recipe (FZHYR) is a Chinese patent medicine for the treatment of fibrosis. The effects of FZHYR on pulmonary fibrosis and macrophage polarization were investigated in vitro. FZHYR inhibited pulmonary inflammation and fibrosis and M2 polarization of macrophages in bleomycin-induced pulmonary fibrosis (BPF) of rat model. Differentially expressed genes were screened by high-throughput mRNA sequencing and GSEA showed that oxidative phosphorylation (OXPHOS) was correlated with BPF. FZHYR inhibited expressions of Ndufa2 and Ndufa6 in lung tissues of BPF rats. These findings suggest that OXPHOS pathway serves as a possible target for pulmonary fibrosis therapy by FZHYR.
Subject(s)
Burns , Cicatrix , Humans , Cicatrix/pathology , Cicatrix/etiology , Cicatrix/complications , Burns/complications , Burns/pathology , Male , Keratosis/pathology , Keratosis/etiology , Female , Chronic DiseaseABSTRACT
Transferrin (TRF), recognized as a glycoprotein clinical biomarker and therapeutic target, has its concentration applicable for disease diagnosis and treatment monitoring. Consequently, this study developed boronic acid affinity magnetic surface molecularly imprinted polymers (B-MMIPs) with pH-responsitivity as the "capture probe" for TRF, which have high affinity similar to antibodies, with a dissociation constant of (3.82 ± 0.24) × 10-8 M, showing 7 times of reusability. The self-copolymerized imprinted layer synthesized with dopamine (DA) and 3-Aminophenylboronic acid (APBA) as double monomers avoided nonspecific binding sites and produced excellent adsorption properties. Taking the gold nanostar (AuNS) with a branch tip "hot spot" structure as the core, the silver-coated AuNS functionalized with the biorecognition element 4-mercaptophenylboronic acid (MPBA) was employed as a surface-enhanced Raman scattering (SERS) nanotag (AuNS@Ag-MPBA) to label TRF, thereby constructing a double boronic acid affinity "sandwich" SERS biosensor (B-MMIPs-TRF-SERS nanotag) for the highly sensitive detection of TRF. The SERS biosensor exhibited a detection limit for TRF of 0.004 ng/mL, and its application to spiked serum samples confirmed its reliability and feasibility, demonstrating significant potential for clinical TRF detection. Moreover, the SERS biosensor designed in this study offers advantages in stability, detection speed (40 min), and cost efficiency. The portable Raman instrument for SERS detection fulfills the requirements for point-of-care testing.
Subject(s)
Biosensing Techniques , Boronic Acids , Gold , Spectrum Analysis, Raman , Boronic Acids/chemistry , Biosensing Techniques/methods , Gold/chemistry , Humans , Spectrum Analysis, Raman/methods , Silver/chemistry , Metal Nanoparticles/chemistry , Limit of Detection , Transferrin/analysis , Transferrin/chemistry , Molecular Imprinting , Molecularly Imprinted Polymers/chemistry , Glycoproteins/blood , Glycoproteins/chemistry , Biomimetic Materials/chemistry , Dopamine/blood , Dopamine/analysis , Sulfhydryl CompoundsABSTRACT
In order to solve the food safety problem better, it is very important to develop a rapid and sensitive technology for detecting food contamination residues. Organic photoelectrochemical transistor (OPECT) biosensor rely on the photovoltage generated by a semiconductor upon excitation by light to regulate the conductivity of the polymer channels and realize biosensor analysis under zero gate bias. This technology integrates the excellent characteristics of photoelectrochemical (PEC) bioanalysis and the high sensitivity and inherent amplification ability of organic electrochemical transistor (OECT). Based on this, OPECT biosensor detection has been proven to be superior to traditional biosensor detection methods. In this review, we summarize the research status of OPECT biosensor in disease markers and food residue analysis, the basic principle, classification, and biosensing mechanism of OPECT biosensor analysis are briefly introduced, and the recent applications of biosensor analysis are discussed according to the signal strategy. We mainly introduced the OPECT biosensor analysis methods applied in different fields, including the detection of disease markers and food hazard residues such as prostate-specific antigen, heart-type fatty acid binding protein, T-2 toxin detection in milk samples, fat mass and objectivity related protein, ciprofloxacin in milk. The OPECT biosensor provides considerable development potential for the construction of safety analysis and detection platforms in many fields, such as agriculture and food, and hopes to provide some reference for the future development of biosensing analysis methods with higher selectivity, faster analysis speed and higher sensitivity.
Subject(s)
Biosensing Techniques , Electrochemical Techniques , Food Contamination , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Food Contamination/analysis , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Animals , Transistors, Electronic , Humans , Photochemical ProcessesABSTRACT
The limitations of two-dimensional (2D) graphene in broadband photodetector are overcome by integrating nitrogen (N) doping into three-dimensional (3D) structures within silicon (Si) via plasma-assisted chemical vapor deposition (PACVD) technology. This contributes to the construction of vertical Schottky heterojunction broad-spectrum photodetectors and applications in logic devices and image sensors. The natural nanoscale resonant cavity structure of 3D-graphene enhances photon capture efficiency, thereby increasing photocarrier generation. N-doping can fine-tune the electronic structure, advancing the Schottky barrier height and reducing dark current. The as-fabricated photodetector exhibits exceptional self-driven photoresponse, especially at 1550 nm, with an excellent photoresponsivity (79.6 A/W), specific detectivity (1013 Jones), and rapid response of 130 µs. Moreover, it enables logic circuits, high-resolution pattern image recognition, and broadband spectra recording across the visible to near-infrared range (400-1550 nm). This research will provide new views and technical support for the development and widespread application of high-performance semiconductor-based graphene broadband detectors.
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BACKGROUD: Li-Fraumeni syndrome is a hereditary tumor syndrome characterized by an elevated risk of malignancy, particularly acute lymphoblastic leukemia (ALL), which can be caused by the heterozygous germline mutation. TP53 gene germline mutation is considered a potential risk factor and crucial prognostic parameter for acute leukemia development and diagnosis, but rarely occurs in adults, and its specific pathogenic significance in acute leukemia is unclear. CASE PRESENTATION: We describes a case of a 45-year-old woman diagnosed with ALL. Whole-exome sequencing approach identified one of the TP53 germline mutations from her bone marrow sample with possible pathogenic significance, c.848G>A (p.Arg283His) heterozygous missense mutation located on exon 8, which was further verified in her hair, oral mucous and nail samples. Family pedigree screening revealed that the same TP53 genetic variant was present in the patient's father and non-donor son, whereas not in the donor. Digital PCR observed that this point mutation frequency dropped post-transplantation but remained low during maintenance therapy when the patient was leukemia-free. CONCLUSION: This suspected Li-Fraumeni syndrome case report with a likely pathogenic heterozygous TP53 variant expands the cancer genetic spectrum. Screening her family members for mutations facilitates identifying the optimal relative donor and avoids unnecessary treatment by monitoring TP53 germline mutations for minimal residual disease following hematopoietic stem cell transplantation. Its potential roles in hematological malignant tumor development and clinical pathogenic implications necessitate further probing.
Subject(s)
Germ-Line Mutation , Li-Fraumeni Syndrome , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Tumor Suppressor Protein p53 , Humans , Female , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Middle Aged , Tumor Suppressor Protein p53/genetics , Li-Fraumeni Syndrome/genetics , Li-Fraumeni Syndrome/diagnosis , PedigreeABSTRACT
Background: Delirium is a preventable and reversible complication for intensive care unit (ICU) patients, which can be linked to negative outcomes. Early intervention to cope with the risk factors of delirium is necessary. Yet no specific description of the Artificial Intelligence Assisted Prevention and Management for Delirium (AI-AntiDelirium) following the Template for Intervention Description and Replication (TIDieR) checklist was reported. This is the first study to describe a detailed process for the development of an evidence-based delirium intervention. Aims: To describe an individualised delirium intervention which is delivered by an artificial intelligence-assisted system in the ICU for critically ill patients. Methods and results: The TIDieR checklist improved the description of ICU delirium interventions, including several key features for improved implementation of the intervention. This descriptive research describes the AI-assisted ICU delirium interventions for improving cognitive load and adherence of nurses and reducing ICU delirium incidence. Following the TIDieR checklist, we standardised the flow chart of ICU delirium assessment tools; formed an evaluation sheet of ICU delirium risk factors; and translated the evidence-based ABCDEF bundle intervention into practice. Therefore, nurses and researchers would benefit from replicating the interventions for clinical use or experimental research. Conclusions: The TIDieR checklist provided a systematic approach for reporting the complex ICU delirium interventions delivered in a clinical interventional trial, which contributes to the nursing practice policy for the standardisation of interventions.
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OBJECTIVE: To study the clinical effect of conjoint fascial sheath (CFS) suspension and levator palpebrae superioris muscle shortening in the treatment of severe blepharoptosis. METHODS: Forty-five patients with severe blepharoptosis (75 eyes) from May 2020 to February 2022 in the authors' hospital were divided into 2 groups: group A (n = 33, 43 eyes) and group B (n = 24, 32 eyes). Group A was operated on by CFS + levator muscle shortening, and group B was operated on by frontal muscle flap suspension + levator muscle shortening. Both groups were followed up for 12 months (until February 2023). The clinical effect was counted in 6 months after operation, the early complications were counted in 1 month after operation, and the late complications were counted in 1 month to 12 months after operation. Margin to corneal reflex distance 1 (MRD1) and palpebral fissure height (PFH) were recorded before, 1 week, 3 months, and 12 months postoperatively, and the amount of eyelid retrogression was counted again. RESULTS: The good correction rate was 90.70% in group A, higher than in group B (71.88%), and the difference was statistically significant (P< 0.05); the early postoperative complication rate was 9.30%, lower than in group B (24.38%), and the difference was statistically significant (P< 0.05); the late postoperative complication rate was 2.33%, lower than group B (18.75%), and the difference was statistically significant (P< 0.05). The MRD1 and PFH of group A were higher than those of group B (P< 0.05) at 3 months postoperatively and 12 months postoperatively; the MRD1 and PFH of group A were lower than those of group B (P< 0.05) at 3 months postoperatively and 12 months postoperatively. Repeated measurement analysis of variance showed that there were significant differences in the main effects of MRD1, PFH, eyelid retrogression, and time in group A and group B (P< 0.05), and there was interaction between intervention and time (P< 0.05). CONCLUSION: Conjoint fascial sheath suspension combined with levator palpebrae superioris muscle shortening can effectively improve MRD1 and PFH, and the amount of upper eyelid retraction is controllable 1 year after operation.