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1.
EMBO J ; 43(10): 1990-2014, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38605226

RESUMO

Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development.


Assuntos
Células-Tronco Hematopoéticas , Metiltransferases , Metilação de RNA , Proteínas de Ligação a RNA , Fatores de Transcrição , Peixe-Zebra , Animais , Humanos , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proliferação de Células , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Metiltransferases/metabolismo , Metiltransferases/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Metilação de RNA/genética
2.
Toxicol Appl Pharmacol ; 484: 116884, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38442791

RESUMO

BACKGROUND: The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. OBJECTIVE: This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia. METHODS: A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors. RESULTS: PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5. CONCLUSION: PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.


Assuntos
Lignanas , Osteoporose , Peixe-Zebra , Humanos , Animais , Idoso , Simulação de Acoplamento Molecular , Osteogênese , Dexametasona/farmacologia , Osteoporose/induzido quimicamente , Osteoporose/prevenção & controle , Receptores Wnt , Diferenciação Celular
3.
Phys Rev Lett ; 132(23): 230601, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38905646

RESUMO

Fast and high-fidelity qubit initialization is crucial for low-frequency qubits such as fluxonium, and in applications of many quantum algorithms and quantum error correction codes. In a circuit quantum electrodynamics system, the initialization is typically achieved by transferring the state between the qubit and a short-lived cavity through microwave driving, also known as the sideband cooling process in atomic system. Constrained by the selection rules from the parity symmetry of the wave functions, the sideband transitions are only enabled by multiphoton processes which require multitone or strong driving. Leveraging the flux tunability of fluxonium, we circumvent this limitation by breaking flux symmetry to enable an interaction between a noncomputational qubit transition and the cavity excitation. With single-tone sideband driving, we realize qubit initialization with a fidelity exceeding 99% within a duration of 300 ns, robust against the variation of control parameters. Furthermore, we show that our initialization scheme has a built-in benefit in simultaneously removing the second-excited state population of the qubit, and can be easily incorporated into a large-scale fluxonium processor.

4.
Phys Rev Lett ; 132(6): 060602, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38394561

RESUMO

The fluxonium qubits have emerged as a promising platform for gate-based quantum information processing. However, their extraordinary protection against charge fluctuations comes at a cost: when coupled capacitively, the qubit-qubit interactions are restricted to XX interactions. Consequently, effective ZZ or XZ interactions are only constructed either by temporarily populating higher-energy states, or by exploiting perturbative effects under microwave driving. Instead, we propose and demonstrate an inductive coupling scheme, which offers a wide selection of native qubit-qubit interactions for fluxonium. In particular, we leverage a built-in, flux-controlled ZZ interaction to perform qubit entanglement. To combat the increased flux-noise-induced dephasing away from the flux-insensitive position, we use a continuous version of the dynamical decoupling scheme to perform noise filtering. Combining these, we demonstrate a 20 ns controlled-z gate with a mean fidelity of 99.53%. More than confirming the efficacy of our gate scheme, this high-fidelity result also reveals a promising but rarely explored parameter space uniquely suitable for gate operations between fluxonium qubits.

5.
Cephalalgia ; 44(3): 3331024241235193, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38501875

RESUMO

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.


Assuntos
Cefaleia Histamínica , Feminino , Humanos , Masculino , China/epidemiologia , Cefaleia Histamínica/diagnóstico , Cefaleia Histamínica/epidemiologia , Cefaleia Histamínica/terapia , Estudos Longitudinais , Estudos Prospectivos , Adulto
6.
Connect Tissue Res ; 65(3): 253-264, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38753365

RESUMO

OBJECTIVE: Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. METHODS: We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. RESULTS: Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine's promotive effect. CONCLUSION: Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway.


Assuntos
Benzilisoquinolinas , Diferenciação Celular , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais , Osteogênese , Osteoporose , Ovariectomia , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Benzilisoquinolinas/farmacologia , Osteogênese/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Feminino , Diferenciação Celular/efeitos dos fármacos , Osteoporose/patologia , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ratos
7.
Gastric Cancer ; 27(2): 308-323, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38270815

RESUMO

BACKGROUND: Chromosome gains or localized amplifications are frequently observed in human gastric cancer (GC) and are major causes of aberrant oncogene activation. However, the significance of long non-coding RNAs (LncRNAs) in the above process is largely unknown. METHODS: The copy number aberrations (CNAs) data of GC samples were downloaded and analyzed from the TCGA database. qRT-PCR and fluorescence in situ hybridization were used to evaluate the expression of Linc01711 in GC. The effects of Linc01711 on GC progression were investigated through in vitro and in vivo assays. The mechanism of Linc01711 action was explored through transcriptome sequencing, chromatin immunoprecipitation sequencing, RNA immunoprecipitation, RNA pull-down and chromatin isolation by RNA purification (ChIRP) assays. RESULTS: We report for the first time a novel DNA copy number amplification-driven LncRNA on chromosome 20q13, designated Linc01711 in human GC, which is highly associated with malignant features. Functionally, Linc01711 significantly accelerates the proliferation and metastasis of GC. Mechanistically, Linc01711 acts as a modular scaffold to promote the binding of histone acetyltransferase HBO1 and histone demethylase KDM9. By coordinating the localization of the HBO1/KDM9 complex, Linc01711 specifies the histone modification pattern on the target genes, such as LPCAT1, and consequently facilitates the cholesterol synthesis, thereby contributing to tumor progression. CONCLUSIONS: Our findings suggest that copy number amplification-driven Linc01711 may serve as a promising prognostic predictor for GC patients and targeting Linc01711-related cholesterol metabolism pathway may be meaningful in anticancer strategies.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Variações do Número de Cópias de DNA , Código das Histonas , Hibridização in Situ Fluorescente , Linhagem Celular Tumoral , RNA , Colesterol , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética
8.
Environ Sci Technol ; 58(1): 371-380, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38146194

RESUMO

Cyclic desulfurization-regeneration-denitrification based on metal-free carbon materials is one of the most promising ways to remove NOx and SO2 simultaneously. However, the impact of S-doping induced by the cyclic desulfurization and regeneration (C-S-R) process on the selective catalytic reduction (SCR) is not well understood. Herein, it is demonstrated that the C-S-R process at 500 °C induces in situ S-doping with a significant accumulation of C-S-C structures. NOx conversion was dramatically enhanced from 18.95% of the original sample to 84.55% of the S-doped sample. Density functional theory calculations revealed that the C-S-C structure significantly regulates the electronic structure of the C atom adjacent to the ketonic carbonyl group, thereby significantly altering the NH3 adsorption configuration with superior adsorption capacity. Moreover, S-doping induces an extra electron transfer between the N atom of the NH3 molecule and the C atom of the carbon plane, thereby promoting the activation of NH3 over the ketonic carbonyl group with a reduced energy barrier. This study elucidates a synergetic promotional mechanism between the ketonic carbonyl group and the C-S-C structure for SCR, offering a novel design strategy for high-performance heteroatom-doped carbon catalysts in industrial applications.


Assuntos
Amônia , Carbono , Oxirredução , Amônia/química , Metais , Titânio , Catálise
9.
Environ Sci Technol ; 58(28): 12685-12696, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38959026

RESUMO

Fabrication of robust isolated atom catalysts has been a research hotspot in the environment catalysis field for the removal of various contaminants, but there are still challenges in improving the reactivity and stability. Herein, through facile doping alkali metals in Pt catalyst on zirconia (Pt-Na/ZrO2), the atomically dispersed Ptδ+-O(OH)x- associated with alkali metal via oxygen bridge was successfully fabricated. This novel catalyst presented remarkably higher CO and hydrocarbon (HCs: C3H8, C7H8, C3H6, and CH4) oxidation activity than its counterpart (Pt/ZrO2). Systematically direct and solid evidence from experiments and density functional theory calculations demonstrated that the fabricated electron-rich Ptδ+-O(OH)x- related to Na species rather than the original Ptδ+-O(OH)x-, serving as the catalytically active species, can readily react with CO adsorbed on Ptδ+ to produce CO2 with significantly decreasing energy barrier in the rate-determining step from 1.97 to 0.93 eV. Additionally, owing to the strongly adsorbed and activated water by Na species, those fabricated single-site Ptδ+-O(OH)x- linked by Na species could be easily regenerated during the oxidation reaction, thus considerably boosting its oxidation reactivity and durability. Such facile construction of the alkali ion-linked active hydroxyl group was also realized by Li and K modification which could guide to the design of efficient catalysts for the removal of CO and HCs from industrial exhaust.


Assuntos
Oxirredução , Zircônio , Catálise , Zircônio/química , Álcalis/química , Platina/química
10.
Environ Sci Technol ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134451

RESUMO

Tandem catalysis is widely adopted for multipollutant control in mobile sources but has rarely been reported in stationary source emission elimination. This work proposed a tandem arrangement way with up-streamed V2O5/TiO2 + down-streamed Cr2O3/TiO2 catalysts, which could achieve the efficient synergistic control of NOx and C3H8 in industrial flue gas. Moreover, this arrangement successfully alleviated the unwanted N2O formation during the NH3 -SCR process. Compared to the conventional impregnation method of the Cr2O3-V2O5/TiO2 catalyst, the tandem catalysts of V2O5/TiO2 + Cr2O3/TiO2 could enhance the NOx and C3H8 conversion by 4.2% and 39.5%, respectively, at 350 °C. It might be attributed to the fact that Cr species was the active site for C3H8 oxidation, and the tandem arrangement of catalysts was beneficial to even dispersion of active components on supports. Furthermore, due to the preferential NOx removal over the up-streamed V2O5/TiO2 catalyst, the tandem catalysts obviously alleviated the N2O formation caused by Cr species during the NH3-SCR process. Herein, it significantly decreased N2O formation by 240.5% at 350 °C compared to the Cr2O3-V2O5/TiO2 catalyst, achieving multipollutant emission control from industrial flue gas with the performance of "one stone three birds".

11.
Avian Pathol ; : 1-10, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38922304

RESUMO

RESEARCH HIGHLIGHTS: First confirmation of AOAV-16 in domestic and wild birds in China.AOAV-16 are low virulent viruses for chickens.Co-circulation/co-infection of AOAV-16 and H9N2 subtype AIV enhanced pathogenicity.Different intergenic sequences and recombination events exist within AOAV-16.

12.
Bioorg Chem ; 147: 107376, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38640722

RESUMO

The inhibition of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway with small molecules is a promising approach for cancer immunotherapy. Herein, novel small molecules compounds bearing various scaffolds including thiophene, thiazole, tetrahydroquinoline, benzimidazole and indazole were designed, synthesized and evaluated for their inhibitory activity against the PD-1/PD-L1 interaction. Among them, compound Z13 exhibited the most potent activity with IC50 of 189.6 nM in the homogeneous time-resolved fluorescence (HTRF) binding assay. Surface plasmon resonance (SPR) assay demonstrated that Z13 bound to PD-L1 with high affinity (KD values of 231 nM and 311 nM for hPD-L1 and mPD-L1, respectively). In the HepG2/Jurkat T co-culture cell model, Z13 decreased the viability rate of HepG2 cells in a concentration-dependent manner. In addition, Z13 showed significant in vivo antitumor efficacy (TGI = 52.6 % at 40 mg/kg) without obvious toxicity in the B16-F10 melanoma model. Furthermore, flow cytometry analysis demonstrated that Z13 inhibited tumor growth in vivo by activating the tumor immune microenvironment. These findings indicate that Z13 is a promising PD-1/PD-L1 inhibitor deserving further investigation.


Assuntos
Antineoplásicos , Antígeno B7-H1 , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Indazóis , Receptor de Morte Celular Programada 1 , Humanos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Relação Estrutura-Atividade , Indazóis/química , Indazóis/farmacologia , Indazóis/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Animais , Estrutura Molecular , Camundongos , Proliferação de Células/efeitos dos fármacos , Descoberta de Drogas , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Camundongos Endogâmicos C57BL , Células Hep G2 , Sobrevivência Celular/efeitos dos fármacos
13.
Environ Res ; 252(Pt 1): 118811, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38555090

RESUMO

Tributyltin (TBT) can be used as an antifouling agent with anticorrosive, antiseptic and antifungal properties and is widely used in wood preservation and ship painting. However, it has recently been found that TBT can be harmful to aquatic organisms. In this study, to gain insight into the effects of TBT with respect to the development of the cardiovascular system in zebrafish embryos, zebrafish embryos were exposed to different concentrations of TBT solutions (0.2 µg/L, 1 µg/L, and 2 µg/L) at 2 h post-fertilization (hpf) TBT exposure resulted in decreased hatchability and heart rate, deformed features such as pericardial edema, yolk sac edema, and spinal curvature in zebrafish embryos, and impaired heart development. Expression of cardiac development-related genes (vmhc, myh6, nkx2.5, tbx5a, gata4, tbx2b, nppa) is dysregulated. Transgenic zebrafish Tg (fli1: EGFP) were used to explore the effects of TBT exposure on vascular development. It was found that TBT exposure could lead to impaired development of intersegmental vessels (ISVs), common cardinal vein (CCV), subintestinal vessels (SIVs) and cerebrovascular. The expression of vascular endothelial growth factor (VEGF) signaling pathway-related genes (flt1, flt4, kdr, vegfa) was downregulated. Biochemical indices showed that ROS and MDA levels were significantly elevated and that SOD and CAT activities were significantly reduced. The expression of key genes for prostacyclin synthesis (pla2, ptgs2a, ptgs2b, ptgis, ptgs1) is abnormal. Therefore, it is possible that oxidative stress induced by TBT exposure leads to the blockage of arachidonic acid (AA) production in zebrafish embryos, which affects prostacyclin synthesis and consequently the normal development of the heart and blood vessels in zebrafish embryos.


Assuntos
Sistema Cardiovascular , Estresse Oxidativo , Compostos de Trialquitina , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Compostos de Trialquitina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Embrião não Mamífero/efeitos dos fármacos
14.
J Opt Soc Am A Opt Image Sci Vis ; 41(3): 392-395, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437426

RESUMO

An all-fiber temperature sensor employing intentional refractive index modulation is experimentally demonstrated. The sensor consists of four sections of polarization maintaining fiber (FPMF) sandwiched between multi-mode fiber (MMF). The stress region of two sections of polarization maintaining fibers (PMFs) is aligned and then anti-clockwise rotates one PMF in 10 deg angles while the other keeps still. Finally, the discharge proceeds. The remaining two PMFs are fusion spliced with the same method. Then the prepared FPMF-MMF structure is connected to the 3 dB coupler to construct a Sagnac loop. The temperature sensitivity reaches 1.49 nm/°C for a temperature range from 16°C to 55°C. The proposed temperature sensor with easy fabrication and good linearity in measuring temperature can be a promising candidate for various applications in environmental monitoring and industrial production.

15.
Appl Opt ; 63(10): 2621-2629, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568545

RESUMO

When a binocular vision sensor (BVS) is installed in a narrow space, traditional calibration methods are limited as all targets should be placed in more than three different positions. To solve this problem, an on-site calibration method based on the phase-shift algorithm is proposed in our paper. Intrinsic parameters of these two cameras should be first calibrated offline. Series of phase-shift patterns are projected onto any one target with known three-dimensional information to determine the relationship between two cameras. The target utilized in our proposed method can be selected arbitrarily, which is suitable to achieve the on-site calibration of BVS, especially in industrial vibration environments. Experiments are conducted to validate the effectiveness and robustness of our proposed method.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38330588

RESUMO

Objective: To improve the understanding of aggressive NK-cell leukemia (ANKL) and summarize the progress of its diagnosis and treatment. Methods: We retrospectively analyzed a case of a patient who was initially diagnosed with T-cell lymphoma (non-specific type) and later transformed into ANKL through examinations such as bone marrow smear, flow cytometry, Q-mNGS, and pathology. We described the patient's diagnostic and treatment journey and conducted a literature review. Results: The patient presented with concomitant hemophagocytic syndrome upon admission. After treatment with the HLH-94 regimen, the patient developed tumor lysis syndrome, leading to a sudden onset of ventricular tachycardia and respiratory and cardiac arrest on the third day of admission. Despite aggressive resuscitation efforts, the patient did not survive. Conclusions: ANKL is rare in the world, and the disease is aggressive, so it is necessary to diagnose early and intervene timely. Bone marrow smear, flow cytometer and Q-mNGS are helpful to identify tumors quickly and determine the direction of diagnosis and treatment. This disease is often accompanied by hemophagocytic syndrome. When the pathogenesis is not clear, it is recommended to treat it with hormone and gamma globulin first, and after clarification, chemotherapy containing L-asparaginase may be added; pay attention to supportive treatment and vigilance against oncolysis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be performed as soon as possible, and the application of targeted drugs may further improve the curative effect. In a word, ANKL needs more data statistics and analysis to guide clinical diagnosis and treatment.

17.
Sensors (Basel) ; 24(14)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39066031

RESUMO

OBJECTIVE: Motivated by Health Care 4.0, this study aims to reducing the dimensionality of traditional EEG features based on manual extracted features, including statistical features in the time and frequency domains. METHODS: A total of 22 multi-scale features were extracted from the UNM and Iowa datasets using a 4th order Butterworth filter and wavelet packet transform. Based on single-channel validation, 29 channels with the highest R2 scores were selected from a pool of 59 common channels. The proposed channel selection scheme was validated on the UNM dataset and tested on the Iowa dataset to compare its generalizability against models trained without channel selection. RESULTS: The experimental results demonstrate that the proposed model achieves an optimal classification accuracy of 100%. Additionally, the generalization capability of the channel selection method is validated through out-of-sample testing based on the Iowa dataset Conclusions: Using single-channel validation, we proposed a channel selection scheme based on traditional statistical features, resulting in a selection of 29 channels. This scheme significantly reduced the dimensionality of EEG feature vectors related to Parkinson's disease by 50%. Remarkably, this approach demonstrated considerable classification performance on both the UNM and Iowa datasets. For the closed-eye state, the highest classification accuracy achieved was 100%, while for the open-eye state, the highest accuracy reached 93.75%.


Assuntos
Eletroencefalografia , Doença de Parkinson , Humanos , Eletroencefalografia/métodos , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Algoritmos , Processamento de Sinais Assistido por Computador , Masculino , Feminino , Pessoa de Meia-Idade , Análise de Ondaletas
18.
J Environ Sci (China) ; 139: 460-472, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38105069

RESUMO

As an increasingly used alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been widely detected in global water environments. However, little is known regarding its toxic effects on cardiovascular development. Here, zebrafish embryos were treated with egg water containing 0, 60, 120, or 240 mg/L HFPO-TA. Results showed that HFPO-TA treatment led to a significant reduction in both larval survival percentage and heart rate. Furthermore, HFPO-TA exposure caused severe pericardial edema and elongation of the sinus venous to bulbus arteriosus distance (SV-BA) in Tg (myl7: GFP) transgenic larvae, disrupting the expression of genes involved in heart development and thus causing abnormal heart looping. Obvious sprouting angiogenesis was observed in the 120 and 240 mg/L exposed Tg (fli: GFP) transgenic larvae. HFPO-TA treatment also impacted the mRNA levels of genes involved in the vascular endothelial growth factor (VEGF) pathway and embryonic vascular development. HFPO-TA exposure significantly decreased erythrocyte number in Tg (gata1: DsRed) transgenic embryos and influenced gene expression associated with the heme metabolism pathway. HFPO-TA also induced oxidative stress and altered the transcriptional levels of genes related to cell cycle and apoptosis, inhibiting cell proliferation while promoting apoptosis. Therefore, HFPO-TA exposure may induce abnormal development of the cardiovascular and hematopoietic systems in zebrafish embryos, suggesting it may not be a suitable or safe alternative for PFOA.


Assuntos
Fluorocarbonos , Peixe-Zebra , Animais , Fator A de Crescimento do Endotélio Vascular/genética , Fluorocarbonos/toxicidade , Água
19.
Cancer Treat Res ; 190: 3-24, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38112997

RESUMO

RNA modifications have recently been recognized as essential posttranscriptional regulators of gene expression in eukaryotes. Investigations over the past decade have revealed that RNA chemical modifications have profound effects on tumor initiation, progression, refractory, and recurrence. Tumor cells are notorious for their robust plasticity in response to the stressful microenvironment and undergo metabolic adaptations to sustain rapid cell proliferation, which is termed as metabolic reprogramming. Meanwhile, cancer-associated metabolic reprogramming leads to substantial alterations of intracellular and extracellular metabolites, which further reshapes the tumor microenvironment (TME). Moreover, cancer cells compete with tumor-infiltrating immune cells for the limited nutrients to maintain their proliferation and function in the TME. In this chapter, we review recent interesting findings on the engagement of epitranscriptomic pathways, especially the ones associated with N6-methyladenosine (m6A), in the regulation of cancer metabolism and the surrounding microenvironment. We also discuss the promising therapeutic approaches targeting RNA modifications for anti-tumor therapy.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Reprogramação Metabólica , Neoplasias/genética , RNA
20.
Adv Exp Med Biol ; 1442: 105-123, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38228961

RESUMO

Over 170 nucleotide variants have been discovered in messenger RNAs (mRNAs) and non-coding RNAs so far. However, only a few of them, including N6-methyladenosine (m6A), 5-methylcytidine (m5C), and N1-methyladenosine (m1A), could be mapped in the transcriptome. These RNA modifications appear to be dynamically regulated, with writer, eraser, and reader proteins being identified for each modification. As a result, there is a growing interest in studying their biological impacts on normal bioprocesses and tumorigenesis over the past few years. As the most abundant internal modification in eukaryotic mRNAs, m6A plays a vital role in the post-transcriptional regulation of mRNA fate via regulating almost all aspects of mRNA metabolism, including RNA splicing, nuclear export, RNA stability, and translation. Studies on mRNA m6A modification serve as a great example for exploring other modifications on mRNA. In this chapter, we will review recent advances in the study of biological functions and regulation of mRNA modifications, specifically m6A, in both normal hematopoiesis and malignant hematopoiesis. We will also discuss the potential of targeting mRNA modifications as a treatment for hematopoietic disorders.


Assuntos
Adenosina/análogos & derivados , Regulação da Expressão Gênica , Hematopoese , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Metilação , Hematopoese/genética , RNA/genética , RNA/metabolismo
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