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Epitranscriptomic RNA modifications can regulate the stability of mRNA and affect cellular and viral RNA functions. The N4-acetylcytidine (ac4C) modification in the RNA viral genome was recently found to promote viral replication; however, the mechanism by which RNA acetylation in the host mRNA regulates viral replication remains unclear. To help elucidate this mechanism, the roles of N-acetyltransferase 10 (NAT10) and ac4C during the infection and replication processes of the alphavirus, Sindbis virus (SINV), were investigated. Cellular NAT10 was upregulated, and ac4C modifications were promoted after alphavirus infection, while the loss of NAT10 or inhibition of its N-acetyltransferase activity reduced alphavirus replication. The NAT10 enhanced alphavirus replication as it helped to maintain the stability of lymphocyte antigen six family member E mRNA, which is a multifunctional interferon-stimulated gene that promotes alphavirus replication. The ac4C modification was thus found to have a non-conventional role in the virus life cycle through regulating host mRNA stability instead of viral mRNA, and its inhibition could be a potential target in the development of new alphavirus antivirals.IMPORTANCEThe role of N4-acetylcytidine (ac4C) modification in host mRNA and virus replication is not yet fully understood. In this study, the role of ac4C in the regulation of Sindbis virus (SINV), a prototype alphavirus infection, was investigated. SINV infection results in increased levels of N-acetyltransferase 10 (NAT10) and increases the ac4C modification level of cellular RNA. The NAT10 was found to positively regulate SINV infection in an N-acetyltransferase activity-dependent manner. Mechanistically, the NAT10 modifies lymphocyte antigen six family member E (LY6E) mRNA-the ac4C modification site within the 3'-untranslated region (UTR) of LY6E mRNA, which is essential for its translation and stability. The findings of this study demonstrate that NAT10 regulated mRNA stability and translation efficiency not only through the 5'-UTR or coding sequence but also via the 3'-UTR region. The ac4C modification of host mRNA stability instead of viral mRNA impacting the viral life cycle was thus identified, indicating that the inhibition of ac4C could be a potential target when developing alphavirus antivirals.
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Infecções por Alphavirus , Antígenos de Superfície , Proteínas Ligadas por GPI , Acetiltransferases N-Terminal , Sindbis virus , Replicação Viral , Humanos , Infecções por Alphavirus/genética , Antígenos de Superfície/genética , Citidina/análogos & derivados , Proteínas Ligadas por GPI/genética , RNA Mensageiro/genética , Sindbis virus/fisiologia , Linhagem Celular , Acetiltransferases N-Terminal/genética , Estabilidade de RNARESUMO
OBJECTIVE: Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome. DESIGN: We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified. RESULTS: Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion. CONCLUSION: Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.
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Electrocatalytic conversion of nitrates and carbon dioxide to urea under ambient conditions shows promise as a potential substitute for traditional urea synthesis processes characterized by high consumption and pollution. In this study, a straightforward one-pot method is employed to prepare a highly efficient FeNC-Fe1N4 electrocatalyst, consisting of atomically dispersed Fe1N4 sites and metallic Fe clusters (FeNC) with particle size of 4-7 nm. The FeNC-Fe1N4 catalyst exhibits remarkable electrocatalytic activity for urea synthesis from nitrate anion (NO3 -) and carbon dioxide (CO2), achieving a urea production rate of 38.2 mmol gcat -1 h-1 at -0.9 V (vs RHE) and a Faradaic efficiency of 66.5% at -0.6 V (vs RHE). Both experimental and theoretical results conclusively demonstrate that metallic Fe clusters and Fe1N4 species provide active sites for the adsorption and activation of NO3 - and CO2, respectively, and the synergistic effect between Fe1N4 and metallic Fe clusters significantly enhances the electrochemical efficiency of urea synthesis. In all, this work contributes to the rational design and comprehensive synthesis of a dual-active site iron-based electrocatalyst, facilitating efficient and sustainable urea synthesis.
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Peptides and proteins undergo crucial modifications to alter their physicochemical properties to expand their applications in diverse fields. Various techniques, such as unnatural amino acid incorporation, enzyme catalysis, and chemoselective methods, have been employed for site-selective peptide and protein modification. While traditional methods remain valuable, advancement in host-guest chemistry introduces innovative and promising approaches for the selective modification of peptides and proteins. Macrocycles exhibit robust binding affinities, particularly with natural amino acids, which facilitates their use in selectively binding to specific sequences. This distinctive property endows macrocycles with the potential for modification of target peptides and proteins. This review provides a comprehensive overview of strategies utilizing macrocycles for the selective modification of peptides and proteins. These strategies unlock new possibilities for constructing antibody-drug conjugates and stabilizing volatile medications.
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Peptídeos , Proteínas , Peptídeos/química , Proteínas/química , Aminoácidos/química , Processamento de Proteína Pós-TraducionalRESUMO
We propose a method for simulating a 1D non-Hermitian Su-Schrieffer-Heeger model with modulated nonreciprocal hopping using a cyclic three-mode optical system. The current system exhibits different localization of topologically nontrivial phases, which can be characterized by the winding number. We find that the eigenenergies of such a system undergo a real-complex transition as the nonreciprocal hopping changes, accompanied by a non-Bloch parity-time symmetry breaking. We explain this phase transition by considering the evolution of saddle points on the complex energy plan and the ratio of complex eigenenergies. Additionally, we demonstrate that the skin states resulting from the non-Hermitian skin effect possess higher-order exceptional points under the critical point of the non-Bloch parity-time phase transition. Furthermore, we investigate the non-Hermitian skin phase transition by the directional mean inverse participation ratio and the generalized Brillouin zone. This work provides an alternative way to investigate the novel topological and non-Hermitian effects in nonreciprocal optical systems.
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N6-methyladenosine (m6A) is present in diverse viral RNA and plays important regulatory roles in virus replication and host antiviral innate immunity. However, the role of m6A in regulating JEV replication has not been investigated. Here, we show that the JEV genome contains m6A modification upon infection of mouse neuroblast cells (neuro2a). JEV infection results in a decrease in the expression of m6A writer METTL3 in mouse brain tissue. METTL3 knockdown by siRNA leads to a substantial decrease in JEV replication and the production of progeny viruses at 48 hpi. Mechanically, JEV triggered a considerable increase in the innate immune response of METTL3 knockdown neuro2a cells compared to the control cells. Our study has revealed the distinctive m6A signatures of both the virus and host in neuro2a cells infected with JEV, illustrating the positive role of m6A modification in JEV infection. Our study further enhances understanding of the role of m6A modification in Flaviviridae viruses.
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Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Animais , Camundongos , Vírus da Encefalite Japonesa (Espécie)/genética , Metiltransferases/genética , Metiltransferases/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Imunidade Inata , Replicação Viral/genéticaRESUMO
BACKGROUND: Twenty-four-hour urinary total protein excretion is an essential parameter used for evaluation of renal function and early detection of gestational complications. However, data on reference ranges of 24-hour urinary total protein excretion in normal pregnancy are scarce. OBJECTIVE: This study aimed to determine reference ranges for 24-hour urinary total protein excretion in a population with uncomplicated singleton pregnancies using a standard method for urinary total protein. In addition, the values of 24-hour urinary total protein were stratified by maternal age and prepregnancy body mass index. STUDY DESIGN: This study was based on a prospective cohort study in Shenzhen, China. The pregnant women were enrolled at their first prenatal clinical visit. All the participants were instructed to collect 24-hour urine samples during the following successive gestational periods: 6+0 to 13+6, 14+0 to 27+6, and 28+0 to 41+6 weeks. Total urinary protein excretion was analyzed by a colorimetric method. Ultimately, the study encompassed a total of 4844 pregnant women with uncomplicated pregnancies. The nonparametric percentile method was used to determine reference ranges for 24-hour urinary total protein excretion during different trimesters in women with uncomplicated pregnancies (excluding those with previous kidney disorders, gestational or chronic hypertension, preeclampsia, and pregestational diabetes mellitus, among others). RESULTS: The 24-hour urinary total protein levels expressed as medians and percentiles (5th, 95th) for each trimester were as follows: 72.0 (28.4, 165.0), 88.0 (34.0, 185.0), and 108.0 (37.5, 258.0) mg in the first, second, and third trimesters, respectively. A significant increase in 24-hour urinary total protein excretion was observed throughout pregnancy (all P values <.001). Moreover, 24-hour urinary total protein levels were higher in the older (≥35 years) than in the younger (<35 years) group from mid-gestation. Specifically, the median (interquartile range) 24-hour urinary total protein levels by age were 72.2 (50.6-100.0) vs 70.5 (50.5-100.0) mg, 85.8 (62.0-117.0) vs 96.0 (68.0-127.8) mg, and 106.6 (76.0-146.2) vs 114.7 (81.5-153.6) mg in the first, second, and third trimesters, respectively. In addition, 24-hour proteinuria was significantly increased in higher-weight (overweight or obese) subgroups compared with lower-weight (underweight or normal-weight) subgroups (all P values <.05). CONCLUSION: Our study provides reference values for 24-hour urinary total protein excretion with apparently uncomplicated pregnancies. Understanding these changes in low-risk pregnancies is essential for optimizing maternal management.
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Trimestres da Gravidez , Proteinúria , Humanos , Feminino , Gravidez , Adulto , Proteinúria/urina , Valores de Referência , Estudos Prospectivos , Trimestres da Gravidez/urina , Índice de Massa Corporal , China , Adulto Jovem , Idade Materna , Estudos de CoortesRESUMO
PURPOSE: Renal artery aneurysm (RAA) is a rare disease. This study proposed and evaluated a new classification for RAA to assist in surgical decision-making. MATERIALS AND METHODS: Single-center data of 105 patients with RAAs from the vascular department of vascular surgery were collected retrospectively. A new classification scheme was proposed. Type I aneurysms arise from the main trunk, accessory branch, or first-order branches away from any bifurcation. Type II aneurysms arise from the first bifurcation with narrow necks (defined as dome-to-neck ratio >2) or from intralobular branches. Type III aneurysms with a wide neck arise from the first bifurcation and affect 2 or more branches that cannot be sacrificed without significant infarction of the kidney. RESULTS: There was 50 (47.62%) type I, 33 (31.43%) type II, and 22 (20.95%) type III aneurysms. The classification assigned endovascular repair as first-line treatment (for type I or II), while open techniques were conducted if anatomically suitable (for type III). A kappa level of 0.752 was achieved by the classification compared with a level of 0.579 from the classic Rundback classification. Technical primary success was achieved in 100% and 96.05%, and symptoms were completely resolved in 100% and 84.85%, while hypertension was relieved in 84.21% and 72.92% of patients receiving open surgery or endovascular repair, respectively. No significant difference was observed for perioperative or long-term complications among the 3 classification types. CONCLUSION: The new classification proved to be a convenient and effective method for facilitating choice of intervention for RAAs. CLINICAL IMPACT: This study proposed and evaluated a new classification scheme for renal artery aneurysms, which proved to be a convenient and effective method for facilitating surgical decision-making. Coil embolization was the first-line treatment if suitable, while aneurysm resection and reconstruction with vein graft were conducted for some complex lesions. The safety and efficacy of both open and endovascular methods were validated.
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ABSTRACT: Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein cholesterol is the primary goal in preventing and treating AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in regulating low-density lipoprotein cholesterol metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20( S )-protopanaxatriol (20( S )-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20( S )-PPT were investigated in vivo and in vitro by Western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and other assays. The in vitro experiments revealed that 20( S )-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low-density lipoprotein receptor protein levels, promoted low-density lipoprotein uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of forkhead box O3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20( S )-PPT upregulated aortic α-smooth muscle actin expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol diet in ApoE -/- mice (high-cholesterol diet-fed group). Additionally, 20( S )-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the high-cholesterol diet-fed group. The study revealed that 20( S )-PPT inhibited low-density lipoprotein receptor degradation via PCSK9 to alleviate AS.
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Aorta , Doenças da Aorta , Aterosclerose , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Placa Aterosclerótica , Pró-Proteína Convertase 9 , Receptores de LDL , Sapogeninas , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Aterosclerose/genética , Sapogeninas/farmacologia , Pró-Proteína Convertase 9/metabolismo , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Receptores de LDL/metabolismo , Humanos , Masculino , Doenças da Aorta/patologia , Doenças da Aorta/prevenção & controle , Doenças da Aorta/metabolismo , Doenças da Aorta/genética , Doenças da Aorta/tratamento farmacológico , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Proteólise/efeitos dos fármacos , Células Hep G2 , Inibidores de PCSK9 , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Camundongos , Dieta Hiperlipídica , Apolipoproteínas ERESUMO
BACKGROUND: Previous research has demonstrated that neuroinflammation is a key element in the progress of epilepsy. Nevertheless, it is currently unidentified which inflammatory factors and proteins increase or decrease the risk of epilepsy. METHODS: We adopted Mendelian randomization techniques to explore the causal relationship between circulating inflammatory factors and proteins and various epilepsy. Our principal approach was inverse variance weighting, supplemented by several sensitivity analyses to guarantee the robustness of our findings. RESULTS: Studies have identified associations between epilepsy and specific inflammatory factors and proteins: three inflammatory factors and six proteins are linked to epilepsy in general; one inflammatory factor and four proteins are associated with focal epilepsy with no documented lesions; two inflammatory factors and three proteins are related to focal epilepsy, excluding cases with hippocampal sclerosis; two inflammatory factors and two proteins are connected to juvenile myoclonic epilepsy; two inflammatory factors and five proteins are linked to juvenile absence epilepsy; four inflammatory proteins are associated with childhood absence epilepsy; two inflammatory factors are related to focal epilepsy overall; two inflammatory factors and two proteins are connected to generalized epilepsy; and two inflammatory proteins are linked to generalized epilepsy with tonic-clonic seizures. Additionally, six inflammatory factors may play a downstream role in focal epilepsy. CONCLUSION: Our study uncovers various inflammatory factors and proteins that influence the risk of epilepsy, offering instructive insights to the diagnosis and therapy of the condition.
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Citocinas , Epilepsia , Análise da Randomização Mendeliana , Humanos , Epilepsia/sangue , Epilepsia/genética , Citocinas/sangue , Inflamação/sangueRESUMO
Endothelial senescence, aging-related inflammation, and mitochondrial dysfunction are prominent features of vascular aging and contribute to the development of aging-associated vascular disease. Accumulating evidence indicates that DNA damage occurs in aging vascular cells, especially in endothelial cells (ECs). However, the mechanism of EC senescence has not been completely elucidated, and so far, there is no specific drug in the clinic to treat EC senescence and vascular aging. Here we show that various aging stimuli induce nuclear DNA and mitochondrial damage in ECs, thus facilitating the release of cytoplasmic free DNA (cfDNA), which activates the DNA-sensing adapter protein STING. STING activation led to a senescence-associated secretory phenotype (SASP), thereby releasing pro-aging cytokines and cfDNA to further exacerbate mitochondrial damage and EC senescence, thus forming a vicious circle, all of which can be suppressed by STING knockdown or inhibition. Using next-generation RNA sequencing, we demonstrate that STING activation stimulates, whereas STING inhibition disrupts pathways associated with cell senescence and SASP. In vivo studies unravel that endothelial-specific Sting deficiency alleviates aging-related endothelial inflammation and mitochondrial dysfunction and prevents the development of atherosclerosis in mice. By screening FDA-approved vasoprotective drugs, we identified Cilostazol as a new STING inhibitor that attenuates aging-related endothelial inflammation both in vitro and in vivo. We demonstrated that Cilostazol significantly inhibited STING translocation from the ER to the Golgi apparatus during STING activation by targeting S162 and S243 residues of STING. These results disclose the deleterious effects of a cfDNA-STING-SASP-cfDNA vicious circle on EC senescence and atherogenesis and suggest that the STING pathway is a promising therapeutic target for vascular aging-related diseases. A proposed model illustrates the central role of STING in mediating a vicious circle of cfDNA-STING-SASP-cfDNA to aggravate age-related endothelial inflammation and mitochondrial damage.
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Senescência Celular , Cilostazol , Inflamação , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Mitocôndrias , Animais , Proteínas de Membrana/metabolismo , Cilostazol/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Senescência Celular/efeitos dos fármacos , Camundongos , Envelhecimento/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Citosol/metabolismo , DNA/metabolismo , Masculino , Células Endoteliais da Veia Umbilical Humana , Fenótipo Secretor Associado à Senescência , Células CultivadasRESUMO
SIGNIFICANCE: Characterisation of tobacco product emissions is an important step in assessing their impact on public health. Accurate and repeatable emissions data require that a leak-tight seal be made between the smoking or vaping machine and the mouth-end of the tobacco product being tested. This requirement is challenging because of the variety of tobacco product mouth-end geometries being puffed on by consumers today. We developed and tested a prototype universal smoking machine adaptor (USMA) that interfaces with existing machines and reliably seals with a variety of tobacco product masses and geometries. METHODS: Emissions were machine-generated using the USMA and other available adaptors for a variety of electronic cigarettes (n=7 brands), cigars (n=4), cigarillos (n=2), a heated tobacco product, and a reference cigarette (1R6F), and mainstream total particulate matter (TPM) and nicotine were quantified. Data variability (precision, n≥10 replicates/brand) for all products and error (accuracy) from certified values (1R6F) were compared across adaptors. RESULTS: TPM and nicotine emissions generated using the USMA were accurate, precise and agreed with certified values for the 1R6F reference cigarette. Replicate data indicate that USMA repeatability across all tobacco products tested generally meets or exceeds that from the comparison adaptors and extant data. CONCLUSION: The USMA seals well with a variety of combustible tobacco products, e-cigarettes with differing geometries and plastic-tipped cigarillos. Variability for all measures was similar or smaller for the USMA compared with other adaptors.
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SIGNIFICANCE: Historically, tobacco product emissions testing using smoking machines has largely focused on combustible products, such as cigarettes and cigars. However, the popularity of newer products, such as electronic cigarettes (e-cigarettes), has complicated emissions testing because the products' mouth-end geometries do not readily seal with existing smoking and vaping machines. The demand for emissions data on popularly used products has led to inefficient and non-standardised solutions, such as laboratories making their geometry-specific custom adaptors and/or employing flexible tubing, for each unique mouth-end geometry tested. A user-friendly, validated, universal smoking machine adaptor (USMA) is needed for testing the variety of tobacco products reflecting consumer use, including e-cigarettes, heated tobacco products, cigarettes, plastic-tipped cigarillos and cigars. METHODS: A prototype USMA that is compatible with existing smoking/vaping machines was designed and fabricated. The quality of the seal between the USMA and different tobacco products, including e-cigarettes, cigars and cigarillos, was evaluated by examining the leak rate. RESULTS: Unlike commercial, product-specific adaptors, the USMA seals well with a wide range of tobacco product mouth-end geometries and masses. This includes e-cigarettes with non-cylindrical mouth ends and cigarillos with cuboid-like plastic tips. USMA leak rates were lower than or equivalent to commercial, product-specific adaptors. CONCLUSION: This report provides initial evidence that the USMA seals reliably with a variety of tobacco product mouth-end geometries and can be used with existing linear smoking/vaping machines to potentially improve the precision, repeatability and reproducibility of machine smoke yield data. Accurate and reproducible emissions testing is critical for regulating tobacco products.
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Early detection of rice blast disease is pivotal to ensure rice yield. We collected in situ images of rice blast and constructed a rice blast dataset based on variations in lesion shape, size, and color. Given that rice blast lesions are small and typically exhibit round, oval, and fusiform shapes, we proposed a small object detection model named GCPDFFNet (global context-based parallel differentiation feature fusion network) for rice blast recognition. The GCPDFFNet model has three global context feature extraction modules and two parallel differentiation feature fusion modules. The global context modules are employed to focus on the lesion areas; the parallel differentiation feature fusion modules are used to enhance the recognition effect of small-sized lesions. In addition, we proposed the SCYLLA normalized Wasserstein distance loss function, specifically designed to accelerate model convergence and improve the detection accuracy of rice blast disease. Comparative experiments were conducted on the rice blast dataset to evaluate the performance of the model. The proposed GCPDFFNet model outperformed the baseline network CenterNet, with a significant increase in mean average precision from 83.6 to 95.4% on the rice blast test set while maintaining a satisfactory frames per second drop from 147.9 to 122.1. Our results suggest that the GCPDFFNet model can accurately detect in situ rice blast disease while ensuring the inference speed meets the real-time requirements.
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Oryza , Doenças das Plantas , Processamento de Imagem Assistida por Computador/métodos , AlgoritmosRESUMO
Introduction: Hepatocellular carcinoma (HCC) is the fourth most prevalent cancer in China. Transcatheter arterial chemoembolization (TACE) is a common interventional therapy for HCC. In this study, we aimed to explore specific metabolites that can accurately predict prognosis after TACE in patients with HCC. Methods: Patients with HCC and healthy volunteers (n = 20 each) were recruited to our study; plasma samples were collected from patients before and after TACE and from healthy volunteers. Plasma samples were subjected to untargeted ultra-high performance liquid chromatography-high resolution mass spectrometry metabolomics analysis, to identify metabolites significantly associated with the prognosis of patients with HCC after TACE. Results: Orthogonal filtered partial least squares discriminant analysis confirmed significant separation of the pre-TACE, post-TACE, and healthy groups, and 34 differential metabolites were identified between the pre-TACE and post-TACE groups. KEGG analysis revealed that phenylalanine, tyrosine, and tryptophan biosynthesis pathways and the phenylalanine metabolism pathway were potentially altered in HCC genesis and during TACE. Phenylalanine and tyrosine are involved in both pathways and were increased in the pre-TACE group relative to controls, with phenylalanine further increased in the post-TACE group. Receiver operating characteristic (ROC) curve analysis indicated that PC 36:4|PC 18:2_18:2 (area under the ROC curve (AUC) = 0.798) is a potential marker for assessment of prognosis in patients with HCC after TACE. Moreover, ROC curve analysis indicated that palmitoylcarnitine (AUC = 1) is a marker with potential value for HCC diagnosis. Conclusions: Limited studies had been conducted on the detection of metabolites in the plasma of HCC patients before and after TACE. PC 36:4|PC 18:2_18:2 is a potential marker for evaluation of the therapeutic effects of TACE. This finding may be beneficial for the treatment of patients with HCC after TACE.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Quimioembolização Terapêutica/métodos , Fenilalanina , TirosinaRESUMO
OBJECTIVE: This study focused on the metabolic characteristics of tongue coating in patients with intra-oral halitosis (IOH) to investigate potential diagnostic biomarkers for IOH. METHODS: Oral healthy participants were enrolled in this study. Halitosis was evaluated with an organoleptic assessment, a Halimeter®, and an OralChroma™. Tongue coating samples were collected from 18 halitosis patients and 18 healthy controls. Liquid chromatography-mass spectrometry was conducted to reveal the IOH-related metabolic variations in tongue coating. RESULTS: A total of 2214 metabolites were obtained. Most metabolites were shared between the two groups. A total of 274 upregulated metabolites, such as paramethasone acetate and indole-3-acetic acid, and 43 downregulated metabolites, including deoxyadenosine and valyl-arginine, were detected in the halitosis group. Functional analysis indicated that several metabolic pathways, including arginine biosynthesis, arginine and proline metabolism, histidine metabolism, and lysine degradation were significantly enriched in the IOH group. The least absolute shrinkage and selection operator logistic regression analysis revealed that paramethasone acetate, {1-[2-(4-carbamimidoyl-benzoylamino)-propionyl]-piperidin-4-yloxy}-acetic acid, indole-3-acetic acid, and valyl-arginine were remarkably associated with IOH. CONCLUSIONS: This study revealed the metabolites present in tongue coating and identified effective biomarkers, providing essential insights into the prediction, pathogenesis, and diagnosis of IOH.
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BACKGROUND: An idiopathic macular hole (IMH) is a full-thickness anatomic defect extending from the internal limiting membrane to the photoreceptor layer of the macula without any known cause. Recently, clinical laboratory markers of systemic inflammatory status derived from complete blood counts have been evaluated in ocular diseases. This study aimed to explore whether they could predict the development and progression of IMHs. METHODS: A retrospective review of 36 patients with IMH and 36 sex-and-age-matched patients with cataracts was conducted. We collected complete blood counts of all participating individuals and calculated systemic immunoinflammatory indicators. The maximum base diameter of the IMH (BD), minimum diameter of the IMH (MIN), height of the IMH (H), area of the intraretinal cyst (IRC), and curve lengths of the detached photoreceptor arms were measured on optical coherence tomography (OCT) images. We used these values to calculate the macular hole index (MHI), tractional hole index (THI), diameter hole index (DHI), hole form factor (HFF), and macular hole closure index (MHCI). We performed a receiver operating characteristic (ROC) curve analysis of 30 patients with IMH who were followed up 1 month after surgery. RESULTS: Lymphocyte counts were significantly higher in the IMH group. No other significant differences were observed between the IMH and control groups. Lymphocyte counts in the IMH group were significantly negatively correlated with MIN and BD and were significantly positively correlated with MHI, THI, and MHCI. However, lymphocyte counts were not significantly correlated with H, IRC, DHI, and HFF. In the ROC analysis, BD, MIN, MHI, THI, and MHCI were significant predictors of anatomical outcomes. According to the cut-off points of the ROC analysis, lymphocyte counts were compared between the above-cut-off and below-cut-off groups. Lymphocyte counts were significantly higher in the MIN ≤ 499.61 µm, MHI ≥ 0.47, THI ≥ 1.2, and MHCI ≥ 0.81 groups. There were no significant differences between the above-cut-off and below-cut-off BD groups. CONCLUSIONS: Although inflammation may not be an initiating factor, it may be involved in IMH formation. Lymphocytes may play a relatively important role in tissue repair during the developmental and postoperative recovery phases of IMH.
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Linfócitos , Perfurações Retinianas , Tomografia de Coerência Óptica , Humanos , Perfurações Retinianas/cirurgia , Perfurações Retinianas/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Idoso , Linfócitos/patologia , Pessoa de Meia-Idade , Curva ROC , Acuidade Visual/fisiologia , Contagem de Linfócitos , VitrectomiaRESUMO
Limited evidence is available regarding the impact of ambient inhalable particulate matter (PM) on mental disorder (MD) or dementia-related deaths, particularly PM1, PM1-2.5, and coarse particles (PM2.5-10). Moreover, individual confounders have rarely been considered. In addition, evidence from low-pollution areas is needed but is inadequate. Using death records from the Death Registration System during 2015-2021 in Ningde, a coastal city in southeast China, we combined a conditional quasi-Poisson model with a distributed lag nonlinear model to estimate the nonlinear and lagged associations of PM exposure with MD or dementia-related deaths in Ningde, China, comprehensively controlling for individual time-invariant confounders using a time-stratified case-crossover design. The attributable fraction and number were calculated to quantify the burden of MD or dementia-related deaths that were related to PMs. We found J-shaped relationships between MD or dementia-related deaths and PMs, with different thresholds of 13, 9, 19, 33 and 12 µg/m3 for PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10. An inter-quartile range increase for PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10 above the thresholds led to an increase of 31.8% (95% confidence interval, 14.3-51.9%), 53.7% (22.4-93.1%), 32.6% (15.0-53.0%), 35.1% (17.7-55.0%) and 25.9% (13.0-40.3%) in MD-related deaths at lag 0-3 days, respectively. The associations were significant in the cool season rather than in the warm season and were significantly greater among people aged 75-84 years than in others. The fractions of MD-related deaths attributable to PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10 were 5.55%, 6.49%, 7.68%, 10.66%, and 15.11%, respectively; however, only some of them could be protected by the concentrations recommended by the World Health Organisation or China grade I standard. Smaller associations and similar patterns were observed between PMs and dementia-related death. These findings suggest stricter standards, and provide evidence for the development of relevant policies and measures.
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Poluentes Atmosféricos , Poluição do Ar , Demência , Humanos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China , Estudos Cross-Over , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Idoso , Idoso de 80 Anos ou maisRESUMO
Kiwifruit is widely cultivated for its high vitamin C content and nutritional value. In January 2022, root rot symptoms were found in about 30% of Actinidia chinensis cv. Jinyan plants grafted on A. deliciosa rootstocks in an orchard located in Sanming (26.32°N, 117.23°E), Fujian Province of China. The affected plants appeared stunted, with brown and decaying roots, some of which were covered with white hyphae. To isolate the pathogen, the surfaces of typical symptomatic roots were sterilized for 30 s using 75% ethanol, followed by four rinses in sterile water, placing on potato dextrose agar (PDA), and incubating away from light at 25°C for 7 days. 16 Globisporangium-like isolates were obtained through hyphal tip isolation, displaying a milky-white appearance with irregular protuberances on the surface, and yellow-white backs with radial fold lines. The isolates were then cultured on corn meal agar for 5 days at 25°C in dark for morphological characteristics. Under microscope, the hyphae appeared as long strips without septa and 4.1 to 8.2 µm wide (average 6.7 µm), containing irregularly sized spherical droplets. Both terminal and intercalary hyphae swellings were observed; these appeared either spherical or subspherical, with some having projections. Their dimensions were 12.3 to 27.6 µm (average 17.3 µm). The oospores were mostly spherical, either plerotic or aplerotic, 11.8 to 22.3 µm wide (average 18.9 µm), with occasional projections. The antheridia were rod-shaped and curved, with one end attached to the oogonia. Amplification of the sequences of internal transcribed spacer (ITS) regions and cytochrome c oxidase subunit I (COI) were conducted using the primers ITS1/ITS4 (White et al. 1990) and OomCoxI-Levlo/OomCoxI-Levup (Robideau et al. 2011), respectively. The sequencing results revealed identical ITS and COI sequences in all 16 isolates. BLASTn analysis of the 969-bp ITS sequence ON202808 showed 99.38-99.59% similarity (965/971bp, 967/971bp) with the KJ162353 and AY598701 sequences from Globisporangium spinosum isolates, while the 700-bp COI sequence ON075783 showed 100% and 99.41% identity (680/680bp, 676/680bp) with the GenBank sequences HQ708835 and HQ708832, respectively, from G. spinosum. Phylogenetic analysis also showed that the obtained isolate (termed MA16) clustered with isolates from G. spinosum on the same evolutionary branch. For pathogenicity testing, four-month-old healthy Jinyan (A. chinensis) plants grown in sterilized media were transferred to sterile petri dishes covered with wet filter paper, and their roots were inoculated with a 5-mm-wide disk of MA16 when cultivated on PDA medium for 5 days. Miliang-1 (A. deliciosa) and Hongyang (A. chinensis) plants were treated similarly. The control groups each included three plants that were inoculated with non-colonized PDA. The plants were kept at 25 °C with a 12-/12-h light/dark cycle for 10 days when the inoculated plants exhibited root rot symptoms similar to those seen in the field, together with rotting and browning of the leaves. The control plants appeared healthy with no symptoms. After re-isolated from infected tissues, the pathogen was verified to be G. spinosum according to its ITS sequence, thus fulfilling the Koch's postulates. Recently, Pythium spinosum has been classified as G. spinosum according to whole-genome sequencing and phylogenomic analysis (Nguyen et al. 2022). Based on the morphological features and pathogenicity results, MA16 was identified as G. spinosum (van der Plaats-Niterink 1981; Huo et al. 2023). This report appears to be the first description of kiwifruit root rots caused by G. spinosum in China, and its identification will assist the development of strategies to counteract the disease.
RESUMO
Previously, we documented the synthesis and assessed the biological effects of chalcones containing selenium against HT-29 human colorectal adenocarcinoma cells, demonstrating their significant potential. As research on selenium-containing flavonoids remains limited, this article outlines our design and synthesis of three selenium-based flavonols and three 2-styrylchromones. We conducted evaluations of these compounds to determine their impact on human lung cancer cells (A549, H1975, CL1-0, and CL1-5) and their influence on normal lung fibroblast MRC5 cells. Additionally, we included selenium-based chalcones in our testing for comparative purposes. Our findings highlight that the simplest compound, designated as compound 1, exhibited the most promising performance among the tested molecules.