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1.
Curr Biol ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38944035

RESUMO

By modulating stomatal opening and closure, plants control gas exchange, water loss, and photosynthesis in response to various environmental signals. During light-induced stomatal opening, the transport of ions and solutes across the plasma membrane (PM) of the surrounding guard cells results in an increase in turgor pressure, leading to cell swelling. Simultaneously, vesicles for exocytosis are delivered via membrane trafficking to compensate for the enlarged cell surface area and maintain an appropriate ion-channel density in the PM. In eukaryotic cells, soluble N-ethylmaleimide-sensitive factor adaptor protein receptors (SNAREs) mediate membrane fusion between vesicles and target compartments by pairing the cognate glutamine (Q)- and arginine (R)-SNAREs to form a core SNARE complex. Syntaxin of plants 121 (SYP121) is a known Q-SNARE involved in stomatal movement, which not only facilitates the recycling of K+ channels to the PM but also binds to the channels to regulate their activity. In this study, we found that the expression of a receptor-like cytoplasmic kinase, low-K+ sensitive 4/schengen 1 (LKS4/SGN1), was induced by light; it directly interacted with SYP121 and phosphorylated T270 within the SNARE motif. Further investigation revealed that LKS4-dependent phosphorylation of SYP121 facilitated the interaction between SYP121 and R-SNARE vesicle-associated membrane protein 722 (VAMP722), promoting the assembly of the SNARE complex. Our findings demonstrate that the phosphorylation of SNARE proteins is an important strategy adopted by plants to regulate the SNARE complex assembly as well as membrane fusion. Additionally, we discovered the function of LKS4/SGN1 in light-induced stomatal opening via the phosphorylation of SYP121.

2.
J Leukoc Biol ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833591

RESUMO

Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.

3.
RSC Adv ; 14(28): 19912-19921, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38903665

RESUMO

Chromite ore processing residue (COPR) is a typical hazardous waste, which contains Cr(vi) and poses a great threat to the ecological environment and human health. In this study, solidification/stabilization (S/S) of COPR was carried out by using blast furnace slag (BFS) and fly ash (FA) to prepare alkali-activated cementitious materials (AACM). The influence of different factors (water glass modulus, liquid-solid ratio, alkali-solid content and curing temperature) on compressive strength was investigated by single-factor experiment. Additionally, solidification effect of AACM was determined according to the compressive strength and the leaching concentration of chromium (Cr(vi) and total Cr). According to the optimal conditions of the single-factor experiment, the highest compressive strength of 147.6 MPa was obtained after using the water glass modulus 1.0, liquid-solid ratio 0.28, alkali-solid content 8%, curing temperature 45 °C. The COPR was solidified in the AACM sample having highest compressive strength. The solidified body still has a good mechanical property (38.2 MPa) with 60% addition COPR. According to leaching tests, the leaching of Cr(vi) and total Cr of solidified body with 50% COPR was far lower than the limit value, which met the purpose of construction and landfill disposal. X-ray diffraction (XRD) analysis, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analysis proved that heavy metal chromium was solidified in AACM by physical and chemical means.

4.
J Agric Food Chem ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899439

RESUMO

Potato common scab (PCS) is a widespread plant disease that lacks effective control measures. Using a small molecule elicitor, we activate the production of a novel class of polyketide antibiotics, streptolateritic acids A-D, in Streptomyces sp. FXJ1.172. These compounds show a promising control efficacy against PCS and an unusual acyclic pentacarboxylic acid structure. A gene cluster encoding a type I modular polyketide synthase is identified to be responsible for the biosynthesis of these metabolites. A cytochrome P450 (CYP) and an aldehyde dehydrogenase (ADH) encoded by two genes in the cluster are proposed to catalyze iterative oxidation of the starter-unit-derived methyl group and three of six branching methyl groups to carboxylic acids during chain assembly. Our findings highlight how activation of silent biosynthetic gene clusters can be employed to discover completely new natural product classes able to combat PCS and new types of modular polyketide synthase-based biosynthetic machinery.

5.
Arab J Gastroenterol ; 25(2): 125-128, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38705812

RESUMO

BACKGROUND AND STUDY AIMS: There are limited data regarding indeterminate acute liver failure (ALF). The study aims to perform a post hoc analysis using genetic methods for the ALF cases with indeterminate etiology. PATIENTS AND METHODS: Stored blood samples from these patients with indeterminate ALF were collected. Whole-exome sequencing (WES) was used to evaluate the pathogenesis of indeterminate ALF. RESULTS: A total of 16 samples from 11 adult patients and 5 pediatric patients with indeterminate ALF were available. Among the adult patients, one female patient was identified with two heterozygous variants (c.2333G > T (p.Arg778Leu) and c.2310C > G (p.Leu770 = )) in the adenosine triphosphatase copper-transporting beta (ATP7B) gene, and two male patients were found to harbor heterozygous and homozygous variants (c.686C > A (p.Pro229Gln) plus homozygousvariantA(TA)6TAAinsTA (-), andc.1456 T > G (p.Tyr486Asp) plus c.211G > A (p.Gly71Arg)) in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. For the pediatric patients, single heterozygous variant (c.2890C > T (p.Arg964Cys)) in the polymerase gamma (POLG) gene was found in 1 male child, and two heterozygous variants (c.1909A > G (p.Lys637Glu) and c.3646G > A (p.Val1216Ile)) in the tetratricopeptide repeat domain 37 (TTC37) gene were found in 1 female child. No variants clinically associated with known liver diseases were revealed in the remaining patients. CONCLUSION: These results expand the knowledge of ALF with indeterminate etiology. WES is helpful to reveal possible candidate genes for indeterminate ALF, but incomplete consistency between the genotype and phenotype in some cases still challenge the accurate diagnosis.


Assuntos
ATPases Transportadoras de Cobre , Sequenciamento do Exoma , Glucuronosiltransferase , Falência Hepática Aguda , Humanos , Falência Hepática Aguda/genética , Falência Hepática Aguda/diagnóstico , Masculino , Feminino , Adulto , Glucuronosiltransferase/genética , Criança , ATPases Transportadoras de Cobre/genética , Heterozigoto , Adolescente , Pessoa de Meia-Idade , Pré-Escolar , Adulto Jovem , Mutação , Homozigoto
6.
Luminescence ; 39(5): e4765, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38769927

RESUMO

Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC50 values of 0.26 ± 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the α-helix content and increasing the ß-fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor.


Assuntos
Apigenina , Dicroísmo Circular , Inibidores Enzimáticos , Lipase , Pâncreas , Espectrometria de Fluorescência , Lipase/antagonistas & inibidores , Lipase/metabolismo , Lipase/química , Pâncreas/enzimologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Apigenina/química , Apigenina/farmacologia , Animais
7.
Mater Horiz ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38745534

RESUMO

Conventional antisolvents such as chlorobenzene and benzotrifluoride are highly toxic and volatile, and therefore not preferred for large-scale fabrication. As such, green antisolvents are favored for the eco-friendly fabrication of perovskite films. This review primarily discusses the impact of various green antisolvents on the fabrication of thin perovskite films and analyzes the main chemical characteristics of these green antisolvents. It also interprets the impact of green antisolvent treatment on crystal growth and nucleation crystallization mechanisms. It introduces the effective fabrication of large-area devices using green antisolvents and analyzes the mechanisms by which green antisolvents enhance device stability. Subsequently, several green antisolvents capable of preparing highly stable and efficient devices are listed. Finally, we outline the key challenges and future prospects of antisolvent treatment. This review paves the way for green fabrication of industrial perovskite solar cells.

8.
Cancer Lett ; 596: 216846, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38582397

RESUMO

Cancer cells employ the unfolded protein response (UPR) or induce autophagy, especially selective removal of certain ER domains via reticulophagy (termed ER-phagy), to mitigate endoplasmic reticulum (ER) stress for ER homeostasis when encountering microenvironmental stress. N6-methyladenosine (m6A) is one of the most abundant epitranscriptional modifications and plays important roles in various biological processes. However, the molecular mechanism of m6A modification in the ER stress response is poorly understood. In this study, we first found that ER stress could dramatically elevate m6A methylation levels through XBP1s-dependent transcriptional upregulation of METTL3/METTL14 in breast cancer (BC) cells. Further MeRIP sequencing and relevant validation results confirmed that ER stress caused m6A methylation enrichment on target genes for ER-phagy. Mechanistically, METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and p62, thus enhancing their mRNA stability. Of note, we further confirmed that the chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase m6A methylation for ER-phagy. Furthermore, the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice. Thus, our data built a novel bridge on the crosstalk between ER stress, m6A methylation and ER-phagy. Most importantly, our work provides novel evidence of METTL3 and METTL14 as potential therapeutic targets for PTX sensitization in breast cancer.


Assuntos
Neoplasias da Mama , Estresse do Retículo Endoplasmático , Metiltransferases , Paclitaxel , Proteína 1 de Ligação a X-Box , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Paclitaxel/farmacologia , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Metiltransferases/genética , Metiltransferases/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/farmacologia , Autofagia/efeitos dos fármacos , Metilação , Camundongos Nus , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Células MCF-7 , Antineoplásicos Fitogênicos/farmacologia
9.
J Pharm Biomed Anal ; 245: 116157, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636192

RESUMO

Penthorum chinense Pursh (PCP), as a traditional medicine of Miao nationality in China, is often used for the treatment of various liver diseases. At present, information regarding the in vivo process of PCP is lacking. Herein, a sensitive and robust ultra-performance liquid chromatography tandem with mass spectrometry (UPLC-MS/MS) was developed and validated for the quantification of several components to study their pharmacokinetics, tissues distribution and excretion in normal and acute alcoholic liver injury (ALI) rats. Prepared samples were separated on a Thermo C18 column (4.6 mm × 50 mm, 2.4 µm) using water containing 0.1 % formic acid (A) and acetonitrile (B) as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) mode for each component. The validated UPLC-MS/MS assay gave good linearity, accuracy, precision, recovery rate, matrix effect and stability. This method was successfully applied to the pharmacokinetics, tissue distribution and excretion in normal and acute ALI rats. There were differences in pharmacokinetic process, tissue distribution and excretion characteristics, indicating that ALI had a significant influence on the in vivo process of PCP in rats. The research provided an experimental basis for the study of PCP quality control and further application in the clinic.


Assuntos
Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Animais , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Ratos , Masculino , Medicamentos de Ervas Chinesas/farmacocinética , Distribuição Tecidual , Reprodutibilidade dos Testes , Hepatopatias Alcoólicas/metabolismo , Espectrometria de Massa com Cromatografia Líquida
10.
J Med Virol ; 96(3): e29530, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38529528

RESUMO

Integration of hepatitis B virus (HBV) DNA into the human genome is recognized as an oncogenic factor and a barrier to hepatitis B cure. In the study, biopsy liver tissues were collected from adolescents and young adults with acute HBV infection younger than or equal to 35 years of age and from HBV-infected infant patients younger than or equal to 6 months of age. A high-throughput sequencing method was used to detect HBV DNA integration. Totally, 12 adolescents, young adults, and 6 infants were included. Among the 12 patients with acute HBV infection, immunohistochemical staining of intrahepatic hepatitis B surface antigen for all displayed negative results, and no HBV DNA integrants in the hepatocyte DNA were confirmed. All infant patients had elevated levels of alanine aminotransferase and high levels of serum HBV DNA. Numerous gene sites of hepatocyte DNA were integrated by HBV DNA for each infant patient, ranging from 120 to 430 integration sites. The fragile histidine triad gene was the high-frequency integrated site in the intragenic region for infant patients. In conclusion, hepatocyte DNA is integrated by HBV DNA in babies with active hepatitis B but seems seldom affected among adolescents and young adults with acute HBV infection. Infantile hepatitis B should be taken seriously considering abundant HBV DNA integration events.


Assuntos
Hepatite B Crônica , Hepatite B , Lactente , Adolescente , Humanos , Adulto Jovem , Vírus da Hepatite B/genética , DNA Viral/genética , Fígado/patologia , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B , Genômica
11.
Nat Commun ; 15(1): 2183, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472217

RESUMO

The reorientation of Earth through rotation of its solid shell relative to its spin axis is known as True polar wander (TPW). It is well-documented at present, but the occurrence of TPW in the geologic past remains controversial. This is especially so for Late Jurassic TPW, where the veracity and dynamics of a particularly large shift remain debated. Here, we report three palaeomagnetic poles at 153, 147, and 141 million years (Myr) ago from the North China craton that document an ~ 12° southward shift in palaeolatitude from 155-147 Myr ago (~1.5° Myr-1), immediately followed by an ~ 10° northward displacement between 147-141 Myr ago (~1.6° Myr-1). Our data support a large round-trip TPW oscillation in the past 200 Myr and we suggest that the shifting back-and-forth of the continents may contribute to the biota evolution in East Asia and the global Jurassic-Cretaceous extinction and endemism.

12.
Epilepsy Res ; 201: 107315, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364765

RESUMO

PURPOSE: Epilepsy is a debilitating disease that can lead to series of social and psychological issues, impairing the quality of life of people with epilepsy (PWE). This survey aimed to investigate the awareness, attitudes, and first-aid knowledge of epilepsy in university students METHOD: This cross-sectional study was conducted in Henan Province, China between January 1 and April 30, 2022. Students majored in education, medicine, science and engineering from 8 universities attended the study. The survey questionnaire comprised 28 questions covering 4 sections: demographic characteristics, awareness of epilepsy, attitudes toward PWE and knowledge of first aid for seizures. RESULTS: A total of 2376 university students completed the questionnaire. 94.7% heard of epilepsy. In the first aid knowledge section, individual question was correctly answered by at least 50% students, 9.3% students correctly answered all questions. Attitude toward PWE was independently (R2 =0.108, F=73.227, p < 0.001) associated with both awareness of epilepsy (B=0.411, p < 0.001) and first aid knowledge of epilepsy (B=0.047, p = 0.001). Among the three majors, medical students had more positive attitudes toward PWE than students majored in education, science and engineering (p < 0.05). However, medical students performed worse among the groups when answering the first aid knowledge questions. CONCLUSION: This survey showed that university students in Central China had a good awareness of epilepsy. For medical students, improvements are necessary for the awareness of the first aid knowledge for seizure.


Assuntos
Epilepsia , Primeiros Socorros , Humanos , Estudos Transversais , Universidades , Qualidade de Vida , Conhecimentos, Atitudes e Prática em Saúde , Epilepsia/terapia , Epilepsia/psicologia , Convulsões , Estudantes/psicologia , Inquéritos e Questionários , China
13.
Epilepsy Res ; 201: 107333, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422800

RESUMO

BACKGROUND: This study aimed to construct prediction models for the recognizing of anxiety disorders (AD) in patients with epilepsy (PWEs) by combining clinical features with quantitative electroencephalogram (qEEG) features and using machine learning (ML). METHODS: Nineteen clinical features and 20-min resting-state EEG were collected from 71 PWEs comorbid with AD and another 60 PWEs without AD who met the inclusion-exclusion criteria of this study. The EEG were preprocessed and 684 Phase Locking Value (PLV) and 76 Lempel-Ziv Complexity (LZC) features on four bands were extracted. The Fisher score method was used to rank all the derived features. We constructed four models for recognizing AD in PWEs, whether PWEs based on different combinations of features using eXtreme gradient boosting (XGboost) and evaluated these models using the five-fold cross-validation method. RESULTS: The prediction model constructed by combining the clinical, PLV, and LZC features showed the best performance, with an accuracy of 96.18%, precision of 94.29%, sensitivity of 98.33%, F1-score of 96.06%, and Area Under the Curve (AUC) of 0.96. The Fisher score ranking results displayed that the top ten features were depression, educational attainment, α_P3LZC, α_T6-PzPLV, α_F7LZC, ß_Fp2-O1PLV, θ_T4-CzPLV, θ_F7-PzPLV, α_Fp2LZC, and θ_T4-PzPLV. CONCLUSIONS: The model, constructed by combining the clinical and qEEG features PLV and LZC, efficiently identified the presence of AD comorbidity in PWEs and might have the potential to complement the clinical diagnosis. Our findings suggest that LZC features in the α band and PLV features in Fp2-O1 may be potential biomarkers for diagnosing AD in PWEs.


Assuntos
Ansiedade , Epilepsia , Humanos , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Comorbidade , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Eletroencefalografia , Aprendizado de Máquina
14.
Biophys Chem ; 307: 107198, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38359582

RESUMO

Wedelolactone (WEL) is a small molecule compound isolated from Eclipta prostrate L., which has been reported to possess various biological activities such as anti-hepatotoxicity, anti-hypertension, anti-tumour, anti-phospholipase A2 and detoxification activity against snake venom. In the present study, we investigated the interaction of WEL with human serum albumin (HSA) using simultaneous fluorescence, UV-visible spectroscopy, 3D fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), molecular docking technique and molecular dynamics simulation. We found that the interaction between HSA and WEL can exhibit a static fluorescence burst mechanism, and the binding process is essentially spontaneous, with the main forces manifested as hydrogen bonding, van der Waals force and electrostatic interactions. Competitive binding and molecular docking studies showed that WEL preferentially bound to HSA in substructural region IIA (site I); molecular dynamics simulations showed that HSA interacted with WEL to form a stable complex, which also induced conformational changes in HSA. The study of the interaction between WEL and HSA can provide a reference for a more in-depth study of the pharmacodynamic mechanism of WEL and its further development and utilisation.


Assuntos
Cumarínicos , Simulação de Dinâmica Molecular , Albumina Sérica Humana , Humanos , Albumina Sérica Humana/química , Simulação de Acoplamento Molecular , Sítios de Ligação , Ligação Proteica , Dicroísmo Circular , Espectrometria de Fluorescência , Termodinâmica
15.
J Nanobiotechnology ; 22(1): 3, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38166978

RESUMO

Chemodynamic therapy (CDT) is seriously limited by the inadequacy of exogenous catalytic ions and endogenous H2O2 in tumors. Herein, a multifunction nano-bomb integrated with calcium peroxide (CaO2) and ß-lapachone as donors of H2O2 and GSH-sensitive Fe-based coordination polymer as provider of catalytic ions was constructed for dual cascade-amplified tumor CDT. This hyaluronic acid (HA)-modified nano-bomb could be specially endocytosed by breast cancer cells through a targeting pathway, degraded and released cargoes in response to the GSH-rich cytoplasm. Furthermore, the released CaO2 and ß-lapachone could significantly self-generated sufficient H2O2, which could dual-cascade amplify CDT and induce severe oxidative to tumors via cooperating with the delivered iron ions from nano-bombs. Moreover, the unloaded iron and calcium ions could further accelerate tumor damage by overloading Ca2+ and ferroptosis, as accompanied by good magnetic resonance imaging (MRI). In vitro and in vivo studies collectively reveal that this nano-bomb not only self-initiates double cascade-amplified CDT via self-generation of H2O2, but also efficiently activates ferroptosis and initiates Ca2+ overloading, consequently significantly tumor growth suppression. This study offers a novel tumor-initiated nano-bomb for dual cascade-amplified CDT and bioimaging with activated ferroptosis and self-supplying H2O2.


Assuntos
Ferroptose , Neoplasias , Humanos , Peróxido de Hidrogênio , Ferro , Linhagem Celular Tumoral
16.
Exp Hematol Oncol ; 13(1): 8, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38268051

RESUMO

BACKGROUND: RNA modifications have been proven to play fundamental roles in regulating cellular biology process. Recently, maladjusted N7-methylguanosine (m7G) modification and its modifiers METTL1/WDR4 have been confirmed an oncogene role in multiple cancers. However, the functions and molecular mechanisms of METTL1/WDR4 in acute myeloid leukemia (AML) remain to be determined. METHODS: METTL1/WDR4 expression levels were quantified using qRT-PCR, western blot analysis on AML clinical samples, and bioinformatics analysis on publicly available AML datasets. CCK-8 assays and cell count assays were performed to determine cell proliferation. Flow cytometry assays were conducted to assess cell cycle and apoptosis rates. Multiple techniques were used for mechanism studies in vitro assays, such as northern blotting, liquid chromatography-coupled mass spectrometry (LC-MS/MS), tRNA stability analysis, transcriptome sequencing, small non-coding RNA sequencing, quantitative proteomics, and protein synthesis measurements. RESULTS: METTL1/WDR4 are significantly elevated in AML patients and associated with poor prognosis. METTL1 knockdown resulted in reduced cell proliferation and increased apoptosis in AML cells. Mechanically, METTL1 knockdown leads to significant decrease of m7G modification abundance on tRNA, which further destabilizes tRNAs and facilitates the biogenesis of tsRNAs in AML cells. In addition, profiling of nascent proteins revealed that METTL1 knockdown and transfection of total tRNAs that were isolated from METTL1 knockdown AML cells decreased global translation efficiency in AML cells. CONCLUSIONS: Taken together, our study demonstrates the important role of METTL1/WDR4 in AML leukaemogenesis, which provides a promising target candidate for AML therapy.

17.
ACS Nano ; 18(4): 3134-3150, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38236616

RESUMO

Immunotherapy is restricted by a complex tumor immunosuppressive microenvironment (TIM) and low drug delivery efficiency. Herein, a multifunctional adjuvant micelle nanosystem (PPD/MPC) integrated with broken barriers and re-education of three classes of immune-tolerant cells is constructed for cancer immunotherapy. The nanosystem significantly conquers the penetration barrier via the weakly acidic tumor microenvironment-responsive size reduction and charge reversal strategy. The detached core micelle MPC could effectively be internalized by tumor-associated macrophages (TAMs), tumor-infiltrating dendritic cells (TIDCs), and myeloid-derived suppressor cells (MDSCs) via mannose-mediated targeting endocytosis and electrostatic adsorption pathways, promoting the re-education of immunosuppressive cells for allowing them to reverse from pro-tumor to antitumor phenotypes by activating TLR4/9 pathways. This process in turn leads to the remodeling of TIM. In vitro and in vivo studies collectively indicate that the adjuvant micelle-based nanosystem not only relieves the intricate immune tolerance and remodels TIM via reprogramming the three types of immunosuppressive cells and regulating the secretion of relevant cytokines/immunity factors but also strengthens immune response and evokes immune memory, consequently suppressing the tumor growth and metastasis.


Assuntos
Micelas , Neoplasias , Humanos , Imunoterapia , Imunossupressores/farmacologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Neoplasias/terapia , Microambiente Tumoral , Linhagem Celular Tumoral
18.
Brain Res ; 1824: 148662, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37924926

RESUMO

OBJECTIVE: Anxiety disorders (AD) are critical factors that significantly (about one-fifth) impact the quality of life (QoL) in patients with epilepsy (PWE). Objective diagnostic methods have contributed to the identification of PWE susceptible to AD. This study aimed to identify AD in PWE by constructing a diagnostic model based on the phase locking value (PLV) and Lempel-Ziv Complexity (LZC) features of the electroencephalogram (EEG). METHODS: EEG data from 131 patients with epilepsy (PWE) were enrolled in this study. Patients were divided into two groups, anxiety disorder (AD, n = 61) and non-anxiety disorder (NAD, n = 70), according to the Hamilton Rating Scale for Anxiety (HAM-A). Support vector machine (SVM) and K-Nearest-Neighbor(KNN) algorithms were used to construct three models - the PLVEEG, LZCEEG, and PLVEEG + LZCEEG feature models. Finally, the area under the receiver operating characteristic curve (AUC) and statistical analyses were performed to evaluate the model performance. RESULTS: The efficiency of the KNN-based PLCEEG + LZCEEG feature model was the best, and the accuracy, precision, recall, F1-score, and AUC of the model after five-fold cross-validations scores were 87.89 %, 82.27 %, 98.33 %, 88.95 %, and 0.89, respectively. When the model efficiency was optimal, 29 EEG features were suggested. Further analysis of these features indicated 22 EEG features that were significantly different between the two groups, including 50 % features of the alpha (α)-band. CONCLUSIONS: The PLVEEG + LZCEEG model features can identify AD in PWE. The PLVEEG and LZCEEG characteristics of the α-band may further be explored as potential biomarkers for AD in PWE.


Assuntos
Epilepsia , Qualidade de Vida , Humanos , Epilepsia/diagnóstico , Ansiedade/diagnóstico , Transtornos de Ansiedade , Eletroencefalografia/métodos
19.
PeerJ ; 11: e16614, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107582

RESUMO

Purpose: To examine the accuracy of transperineal magnetic resonance imaging (MRI)-ultrasound (US) fusion biopsy (FB) in identifying men with prostate cancer (PCa) that has reached a clinically relevant stage. Methods: This investigation enrolled 459 males. In 210 of these patients (FB group), transperineal MRI/US fusion-guided biopsies were performed on the suspicious region, and in 249 others, a systematic biopsy (SB) was performed (SB group). We compared these groups using Gleason scores and rates of cancer detection. Results: PCa cases counted 198/459 (43.1%), including 94/249 (37.8%) in the SB group and 104/210 (49.5%) in the FB group. FB was associated with higher overall diagnostic accuracy relative to SB (88.5% and 72.3%, P = 0.024). FB exhibited greater sensitivity than SB (88.9% and 71.2%, P = 0.025). The area under the curve for FB and SB approaches was 0.837 and 0.737, respectively, such that FB was associated with an 11.9% increase in accuracy as determined based upon these AUC values. Relative to SB, FB was better able to detect high-grade tumors (GS ≥ 7) (78.85% vs. 60.64%, P = 0.025). Conclusion: Transperineal MRI-US fusion targeted biopsy is superior to the systematic one as an approach to diagnosing clinically significant PCa, as it is a viable technical approach to prostate biopsy.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Ultrassonografia de Intervenção/métodos , Neoplasias da Próstata/diagnóstico , Biópsia Guiada por Imagem/métodos , Próstata/diagnóstico por imagem
20.
Int J Mol Sci ; 24(22)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38003631

RESUMO

Secondary xylem produced by stem secondary growth is the main source of tree biomass and possesses great economic and ecological value in papermaking, construction, biofuels, and the global carbon cycle. The secondary xylem formation is a complex developmental process, and the underlying regulatory networks and potential mechanisms are still under exploration. In this study, using hybrid poplar (Populus alba × Populus glandulosa clone 84K) as a model system, we first ascertained three representative stages of stem secondary growth and then investigated the regulatory network of secondary xylem formation by joint analysis of transcriptome and miRNAs. Notably, 7507 differentially expressed genes (DEGs) and 55 differentially expressed miRNAs (DEMs) were identified from stage 1 without initiating secondary growth to stage 2 with just initiating secondary growth, which was much more than those identified from stage 2 to stage 3 with obvious secondary growth. DEGs encoding transcription factors and lignin biosynthetic enzymes and those associated with plant hormones were found to participate in the secondary xylem formation. MiRNA-target analysis revealed that a total of 85 DEMs were predicted to have 2948 putative targets. Among them, PagmiR396d-PagGRFs, PagmiR395c-PagGA2ox1/PagLHW/PagSULTR2/PagPolyubiquitin 1, PagmiR482d-PagLAC4, PagmiR167e-PagbHLH62, and PagmiR167f/g/h-PagbHLH110 modules were involved in the regulating cambial activity and its differentiation into secondary xylem, cell expansion, secondary cell wall deposition, and programmed cell death. Our results give new insights into the regulatory network and mechanism of secondary xylem formation.


Assuntos
MicroRNAs , Populus , Transcriptoma , Populus/metabolismo , Xilema/metabolismo , Fatores de Transcrição/metabolismo , Lignina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação da Expressão Gênica de Plantas , Madeira/genética
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