Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 395
Filtrar
1.
Plant J ; 118(1): 24-41, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38102874

RESUMO

Abscisic acid (ABA) is involved in salt and drought stress responses, but the underlying molecular mechanism remains unclear. Here, we demonstrated that the overexpression of MdMYB44-like, an R2R3-MYB transcription factor, significantly increases the salt and drought tolerance of transgenic apples and Arabidopsis. MdMYB44-like inhibits the transcription of MdPP2CA, which encodes a type 2C protein phosphatase that acts as a negative regulator in the ABA response, thereby enhancing ABA signaling-mediated salt and drought tolerance. Furthermore, we found that MdMYB44-like and MdPYL8, an ABA receptor, form a protein complex that further enhances the transcriptional inhibition of the MdPP2CA promoter by MdMYB44-like. Significantly, we discovered that MdPP2CA can interfere with the physical association between MdMYB44-like and MdPYL8 in the presence of ABA, partially blocking the inhibitory effect of the MdMYB44-like-MdPYL8 complex on the MdPP2CA promoter. Thus, MdMYB44-like, MdPYL8, and MdPP2CA form a regulatory loop that tightly modulates ABA signaling homeostasis under salt and drought stress. Our data reveal that MdMYB44-like precisely modulates ABA-mediated salt and drought tolerance in apples through the MdPYL8-MdPP2CA module.


Assuntos
Arabidopsis , Malus , Malus/genética , Malus/metabolismo , Resistência à Seca , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Cloreto de Sódio/farmacologia , Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Secas , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico
2.
BMC Biol ; 22(1): 87, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38637780

RESUMO

BACKGROUND: Cyprinidae, the largest fish family, encompasses approximately 367 genera and 3006 species. While they exhibit remarkable adaptability to diverse aquatic environments, it is exceptionally rare to find them in seawater, with the Far Eastern daces being of few exceptions. Therefore, the Far Eastern daces serve as a valuable model for studying the genetic mechanisms underlying seawater adaptation in Cyprinidae. RESULTS: Here, we sequenced the chromosome-level genomes of two Far Eastern daces (Pseudaspius brandtii and P. hakonensis), the two known cyprinid fishes found in seawater, and performed comparative genomic analyses to investigate their genetic mechanism of seawater adaptation. Demographic history reconstruction of the two species reveals that their population dynamics are correlated with the glacial-interglacial cycles and sea level changes. Genomic analyses identified Pseudaspius-specific genetic innovations related to seawater adaptation, including positively selected genes, rapidly evolving genes, and conserved non-coding elements (CNEs). Functional assays of Pseudaspius-specific variants of the prolactin (prl) gene showed enhanced cell adaptation to greater osmolarity. Functional assays of Pseudaspius specific CNEs near atg7 and usp45 genes suggest that they exhibit higher promoter activity and significantly induced at high osmolarity. CONCLUSIONS: Our results reveal the genome-wide evidence for the evolutionary adaptation of cyprinid fishes to seawater, offering valuable insights into the molecular mechanisms supporting the survival of migratory fish in marine environments. These findings are significant as they contribute to our understanding of how cyprinid fishes navigate and thrive in diverse aquatic habitats, providing useful implications for the conservation and management of marine ecosystems.


Assuntos
Cyprinidae , Ecossistema , Animais , Filogenia , Cyprinidae/genética , Genômica , Água do Mar , Adaptação Fisiológica/genética
3.
Mol Biol Evol ; 40(6)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37247387

RESUMO

Recent genomic analyses of evolutionary radiations suggest that ancient introgression may facilitate rapid diversification and adaptive radiation. The loach genus Triplophysa, a genus with most species endemic to Tibetan Plateau, shows ecological diversity and rapid evolution and represents a potential example of adaptive radiation linked to the uplift of the Tibetan Plateau. Here, we interrogate the complex evolutionary history of Triplophysa fishes through the analysis of whole-genome sequences. By reconstructing the phylogeny of Triplophysa, quantifying introgression across this clade, and simulating speciation and migration processes, we confirm that extensive gene flow events occurred across disparate Triplophysa species. Our results suggest that introgression plays a more substantial role than incomplete lineage sorting in underpinning phylogenetic discordance in Triplophysa. The results also indicate that genomic regions affected by ancient gene flow exhibit characteristics of lower recombination rates and nucleotide diversity and may associate with selection. Simulation analysis of Triplophysa tibetana suggests that the species may have been affected by the Gonghe Movement in the third uplift of the Tibetan Plateau, resulting in founder effects and a subsequent reduction in Ne.


Assuntos
Altitude , Cipriniformes , Animais , Filogenia , Tibet , Cipriniformes/genética , Adaptação Fisiológica/genética
4.
Cancer ; 130(S8): 1415-1423, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38079306

RESUMO

BACKGROUND: Immune-checkpoint blockade (ICB) therapy shows promise for treating aggressive triple-negative breast cancer (TNBC). However, only some patients benefit from ICB, revealing an urgent need for identifying novel strategies for sensitizing patients to ICB. Previously, the authors demonstrated that type-I protein arginine methyltransferases (PRMTs) regulated antiviral innate-immune responses in TNBC by altering RNA splicing. This study aimed to explore the effects of targeting type-I PRMTs on the tumor microenvironment (TME) and the efficacy of ICB therapy against TNBC. METHODS: Single-cell transcriptomic analysis was performed to investigate the effects of type-I PRMT inhibition on the TME, especially T-cell subsets. Single-cell T-cell receptor sequencing was performed to analyze the diversity and dynamics of the T-cell repertoire. A syngeneic murine model of TNBC was used to evaluate the therapeutic efficacy and immune memory effect of combining a type-I PRMT inhibitor (MS023) with an anti-programmed cell death protein 1 (PD-1) antibody. RESULTS: Type-I PRMT inhibition combined with anti-PD-1 therapy reduced tumor growth. Mechanistically, type-I PRMT inhibition reshaped the TME. Increased CD8 T-cell infiltration was verified using flow cytometry. Increased clonotypes and clonal diversity were also observed after MS023 treatment, which contributed to immune memory following combination treatment. CONCLUSIONS: Targeting type-I PRMT can potentially improve immunotherapeutic efficacies in patients with TNBC. By enhancing the tumor immunogenicity and promoting a more favorable immune microenvironment, this combined approach may enable more patients with TNBC to benefit from immunotherapies.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Receptor de Morte Celular Programada 1 , Proteína-Arginina N-Metiltransferases/genética , Imunoterapia , Morte Celular , Microambiente Tumoral
5.
Genome Res ; 31(6): 947-957, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33858843

RESUMO

Transfer RNAs (tRNAs) are essential for translation, and tRNA expression and modifications are regulated by many factors. However, the interplay between the microbiome and host tRNA profiles through host-microbiome interactions has not been explored. In this study, we investigated host-microbiome interactions via the tRNA profiling of four tissue types from germ-free and specific pathogen-free mice. Our analyses reveal that cytosolic and mitochondrial tRNA expression and tRNA modifications in the host are reprogrammed in a tissue-specific and microbiome-dependent manner. In terms of tRNA expression, the intestines and brains are more sensitive to the influence of the microbiome than the livers and kidneys. In terms of tRNA modifications, cytosolic tRNAs show more obvious changes in the livers and kidneys in the presence of the microbiome. Our findings reveal a previously unexplored relationship among the microbiome, tRNA abundance, and epitranscriptome in a mammalian host.


Assuntos
Microbiota , Transcriptoma , Animais , Camundongos , Microbiota/genética , Mitocôndrias/genética , Processamento Pós-Transcricional do RNA , RNA de Transferência/genética , RNA de Transferência/metabolismo
6.
Small ; 20(14): e2305800, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37991255

RESUMO

Enzyme-driven micro/nanomotors (MNMs) have demonstrated potentials in the biomedical field because of their excellent biocompatibility, versatility, and fuel bioavailability. However, the fragility of enzymes limits their practical application, because of their susceptibility to denaturation and degradation in realistic scenarios. Herein, a simple yet versatile and effective approach is reported to preserve the enzymatic activity and propulsion capability of enzymatic MNMs under various harsh conditions using metal organic frameworks (MOFs) as a protective shell. Urease can be encapsulated within the exoskeleton of zeolitic imidazolate framework-8 (ZIF-8) via biomimetic mineralization to form ZIF-8@urease (ZU-I) nanomotors that exhibit self-propulsion in the presence of urea. When exposed to harsh conditions, including high temperature, presence of proteases, and organic solvents, the ZU-I nanomotors still maintained their activity and mobility, whereas ZIF-8 with externally modified urease (ZU-O) nanomotors with externally modified urease as a control rapidly lost their motion capabilities owing to the inactivation of urease. Furthermore, ZU-I nanomotors exhibit effectively enhanced diffusion within the small intestine fluid, achieving a fourfold higher mucus penetration than the ZU-O nanomotors. The results highlight the effectiveness of using MOFs as protective shells for enzyme nano-engines, which can greatly advance the practical applications of enzymatic MNMs under realistic conditions, especially for biomedical purpose.


Assuntos
Estruturas Metalorgânicas , Urease
7.
Small ; : e2403056, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726792

RESUMO

Energy conversion and transfer of enzyme-catalyzed reactions at molecular level are an interesting and challenging scientific topic that helps understanding biological processes in nature. In this study, it is demonstrated that enzyme-catalyzed reactions can enhance diffusion of surrounding molecules and thus accelerate cargo transport within 1D micro/nanochannels. Specifically, urease is immobilized on the inner walls of silica micro/nano-tubes to construct bio-catalytically active micro/nanochannels. The catalytic reaction inside the channels drives a variety of cargoes, including small dye molecules, polymers, and rigid nanoparticles (e.g., quantum dots, QDs), to pass through these micro/nanochannels much faster than they will by free diffusion. The enhanced diffusion of molecular species inside the channels is validated by direct observation of the Brownian motion of tracer particles, and further confirmed by significantly enhanced Raman intensity of reporter molecules. Finite element and Brownian dynamics simulations provide a theoretical understanding of these experimental observations. Furthermore, the effect of the channels' size on the diffusion enhancement is examined. The acceleration effect of the cargo transport through these enzymatically active micro/nanochannels can be turned on or off via chemical activators or inhibitors. This study provides valuable insights on the design of biomimetic channels capable of controlled and efficient transmembrane transport.

8.
Chemistry ; : e202400276, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38757422

RESUMO

A hydrophobic Ni-PTFE modified electrode has been prepared by constant current and cathodic electroplating with a nickel sheet as substrate in a PTFE suspension. Then the Ni-PTFE modified electrode was used for electroreduction from aromatic amide to diarylimide. The electrochemical characterizations such as cyclic voltammogram, EIS, polarization curves, and electrode stability have been carried out by electrochemical workstation. The structure of the electroreduction product diarylimide was characterized by 1HNMR, FT-IR, MS(Mass Spectrum), and EA(Elemental Analyzer). Based on the hydrophobicity of the electrode, an approach suggested that the phenyl ketone radical may be formed by electroreductive deamination at the cathode. With the construction of C-N bond by the radical coupling, the electrocatalytic reduction may be comprised of a one-electron process including an ECC (Electrochemical-Chemical-Chemical) process. The electroreduction of aromatic amide to diarylimide may be controlled by both charge migration and concentration polarization. Electrocatalytic reduction of aromatic amides on Ni-PTFE-modified electrodes is all well conversion ratio.

9.
Hum Genomics ; 17(1): 59, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420302

RESUMO

BACKGROUND: The influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects of CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients. PATIENTS AND METHODS: This study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications. RESULTS: A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type at ABCB1 rs4148738 locus (TT vs. CC, P = 0.033), and the mutant type was significantly lower than the wild type at ABCB1 rs4728709 locus (AA + GA vs. GG, P = 0.008). ABCB1 (rs1045642, rs1128503), CYP3A4 (rs2242480, rs4646437), CYP3A5 (rs776746), and ABCG2 (rs2231137, rs2231142) gene polymorphisms had no significant effect on the Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci. CONCLUSION: This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Fibrilação Atrial , Citocromo P-450 CYP3A , Rivaroxabana , Humanos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , Citocromo P-450 CYP3A/genética , Proteínas de Neoplasias/genética , Polimorfismo Genético , Estudos Prospectivos , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacocinética
10.
Nat Chem Biol ; 18(8): 821-830, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35578032

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here we identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), which has antitumor growth activity in TNBC. Pathway analysis of TNBC cell lines indicates that the activation of interferon responses before and after MS023 treatment is a functional biomarker and determinant of response, and these observations extend to a panel of human-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway with the induction of double-stranded RNA, which is derived, at least in part, from inverted repeat Alu elements. Together, our results represent a shift in understanding the antitumor mechanism of type I PRMT inhibitors and provide a rationale and biomarker approach for the clinical development of type I PRMT inhibitors.


Assuntos
Proteína-Arginina N-Metiltransferases , Neoplasias de Mama Triplo Negativas , Biomarcadores , Linhagem Celular Tumoral , Humanos , Interferons/uso terapêutico , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo
11.
Soft Matter ; 20(21): 4175-4183, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38506651

RESUMO

Emulsion droplets on the colloidal length scale are a model system of frictionless compliant spheres. Direct imaging studies of the microscopic structure and dynamics of emulsions offer valuable insights into fundamental processes, such as gelation, jamming, and self-assembly. A microscope, however, can only resolve the individual droplets in a densely packed emulsion if the droplets are closely index-matched to their fluid medium. Mitigating perturbations due to gravity additionally requires the droplets to be density-matched to the medium. Creating droplets that are simultaneously index-matched and density-matched has been a long-standing challenge for the soft-matter community. The present study introduces a method for synthesizing monodisperse micrometer-sized siloxane droplets whose density and refractive index can be precisely and independently tuned by adjusting the volume fraction of three silane precursors. A systematic optimization protocol yields fluorescently labeled ternary droplets whose densities and refractive indexes match, to the fourth decimal place, those of aqueous solutions of glycerol or dimethylsiloxane. Because all of the materials in this system are biocompatible, we functionalize the droplets with DNA strands to endow them with programmed inter-droplet interactions. Confocal microscopy then reveals both the three-dimensional structure and the network of droplet-droplet contacts in a class of self-assembled droplet gels, free from gravitational effects. This experimental toolbox creates opportunities for studying the microscopic mechanisms that govern viscoelastic properties and self-assembly in soft materials.


Assuntos
DNA , Emulsões , Emulsões/química , DNA/química , Refratometria , Siloxanas/química
12.
J Bone Miner Metab ; 42(1): 99-114, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38057603

RESUMO

INTRODUCTION: Current research evaluating the association between tea consumption and bone health still has inconsistent findings. MATERIALS AND METHODS: The electronic databases of Embase, PubMed, Scopus, and Web of Science were systematically searched from inception until December 2022 to identify eligible studies. The calculation of summary relative risks (RRs) and 95% confidence intervals (CIs) was carried out using random-effects models. I2 statistics and Forest plots were used to assess the heterogeneity of RR values across studies. RESULTS: The pooled relative risks for bone health-related outcomes of interest among tea drinkers, compared to non-drinkers, were 0.910 (95% confidence interval 0.845 to 0.980) for fractures, based on 20 studies, 0.332 (0.207-0.457) for BMD (13 studies), 0.800 (0.674-0.950) for osteoporosis (10 studies), and 1.006 (0.876-1.156) for osteopenia (5 studies). Subgroup analysis of locations showed that the pooled relative risks were 0.903 (0.844-0.966) for the hip, 0.735 (0.586-0.922) for the femur, 0.776 (0.610-0.988) for the lumbar, 0.980 (0.942-1.021) for the forearm and wrist, 0.804 (0.567-1.139) for the phalanges, and 0.612 (0.468-0.800) for Ward's triangle. One-stage dose-response analysis revealed that individuals who consumed less than 4.5 cups of tea per day had a lower risk of bone health-related outcomes than those who did not consume tea, with statistically significant results. CONCLUSION: There is an association between tea consumption and a reduced risk of fractures, osteoporosis, hip, femur, and lumbar, as well as increased BMD.


Assuntos
Fraturas Ósseas , Osteoporose , Humanos , Densidade Óssea , Osteoporose/epidemiologia , Fraturas Ósseas/epidemiologia , Antebraço , Chá
13.
BMC Neurol ; 24(1): 38, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38262944

RESUMO

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare complication during or after angiography, usually transient and reversible. CIE diagnosis is challenging due to the absence of no formal diagnostic criteria. CIE can mimic stroke symptoms, including visual disturbances, seizures, confusion, coma, and focal neurological deficits. This case reports neurological deficit reversal in a CIE patient due to the embolization of an intracranial aneurysm, the second angiographic procedure in six days. CASE PRESENTATION: A 77-year-old woman was admitted to the hospital for headaches. The cerebral computed tomography (CT) scan indicated a subarachnoid hemorrhage. The first digital subtraction angiography (DSA) identified an aneurysm of 4 mm ∗ 3 mm in size in the M1 segment of the right middle cerebral artery (MCA). Then, embolization surgery was performed for the cerebral aneurysm, which was successful. However, the patient had post-operative headaches, slurred speech, epilepsy, limb weakness, and delirium post-procedure. The non-contrast cerebral CT indicated widespread edema in the right cerebral hemisphere. The patient was diagnosed with CIE and treated with symptomatic supportive therapy. Eventually, the patient's neurological deficits and cerebral edema improved significantly. CONCLUSIONS: The current case emphasized the importance of early diagnosis and symptomatic treatment of CIE. Thus, CIE should be the first consideration during the differential diagnosis of a patient having acute neurological impairment after repeated DSA.


Assuntos
Aneurisma Intracraniano , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Feminino , Humanos , Idoso , Angiografia Digital , Cefaleia
14.
BMC Neurol ; 24(1): 234, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969994

RESUMO

BACKGROUND AND OBJECTIVE: Transcranial magnetic stimulation (TMS) is considered as a promising treatment option for post-stroke cognitive impairment (PSCI).Some meta-analyses have indicated that TMS can be effective in treating cognitive decline in stroke patients, but the quality of the studies included and the methodologies employed were less than satisfactory. Thus, this meta-analysis aimed to evaluate the efficacy and safety of TMS for treating post-stroke cognitive impairment. METHODS: We searched online databases like PubMed, Embase, Cochrane Library, and Web of Science to retrieve randomized controlled trials (RCTs) of TMS for the treatment of patients with PSCI. Two independent reviewers identified relevant literature, extracted purpose-specific data, and the Cochrane Risk of Bias Assessment Scale was utilized to assess the potential for bias in the literature included in this study. Stata 17.0 software was used for data analysis. RESULTS: A total of 10 studies involving 414 patients were included. The results of the meta-analysis showed that TMS was significantly superior to the control group for improving the overall cognitive function of stroke patients (SMD = 1.17, 95% CI [0.59, 1.75], I2 = 86.1%, P < 0.001). Subgroup analyses revealed that high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS), and intermittent theta burst stimulation (iTBS) all have a beneficial effect on the overall cognitive function of stroke patients. However, another subgroup analysis failed to demonstrate any significant advantage of TMS over the control group in terms of enhancing scores on the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and Rivermead Behavioral Memory Test (RBMT) scales. Nonetheless, TMS demonstrated the potential to enhance the recovery of activities of daily living in stroke patients, as indicated by the Modified Barthel Index (MBI) (SMD = 0.76; 95% CI [0.22, 1.30], I2 = 52.6%, P = 0.121). CONCLUSION: This meta-analysis presents evidence supporting the safety and efficacy of TMS as a non-invasive neural modulation tool for improving global cognitive abilities and activities of daily living in stroke patients. However, given the limited number of included studies, further validation of these findings is warranted through large-scale, multi-center, double-blind, high-quality randomized controlled trials. PROSPERO REGISTRATION NUMBER: CRD42022381034.


Assuntos
Disfunção Cognitiva , Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Disfunção Cognitiva/psicologia , Cognição/fisiologia , Resultado do Tratamento
15.
Int J Med Sci ; 21(7): 1204-1212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818479

RESUMO

The mitochondrial unfolded protein response (UPRmt) is a pivotal cellular mechanism that ensures mitochondrial homeostasis and cellular survival under stress conditions. This study investigates the role of UPRmt in modulating the response of nasopharyngeal carcinoma cells to cisplatin-induced stress. We report that the inhibition of UPRmt via AEB5F exacerbates cisplatin cytotoxicity, as evidenced by increased lactate dehydrogenase (LDH) release and apoptosis, characterized by a surge in TUNEL-positive cells. Conversely, the activation of UPRmt with oligomycin attenuates these effects, preserving cell viability and reducing apoptotic markers. Immunofluorescence assays reveal that UPRmt activation maintains mitochondrial membrane potential and ATP production in the presence of cisplatin, countering the rise in reactive oxygen species (ROS) and inhibiting caspase-9 activation. These findings suggest that UPRmt serves as a cytoprotective mechanism in cancer cells, mitigating cisplatin-induced mitochondrial dysfunction and apoptosis. The data underscore the therapeutic potential of modulating UPRmt to improve the efficacy and reduce the side effects of cisplatin chemotherapy. This study provides a foundation for future research on the exploitation of UPRmt in cancer treatment, with the aim of enhancing patient outcomes by leveraging the cellular stress response pathways.


Assuntos
Apoptose , Cisplatino , Mitocôndrias , Espécies Reativas de Oxigênio , Resposta a Proteínas não Dobradas , Humanos , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/genética , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos
16.
Plant Cell Rep ; 43(7): 187, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958739

RESUMO

KEY MESSAGE: MdERF023 is a transcription factor that can reduce salt tolerance by inhibiting ABA signaling and Na+/H+ homeostasis. Salt stress is one of the principal environmental stresses limiting the growth and productivity of apple (Malus × domestica). The APETALA2/ethylene response factor (AP2/ERF) family plays key roles in plant growth and various stress responses; however, the regulatory mechanism involved has not been fully elucidated. In the present study, we identified an AP2/ERF transcription factor (TF), MdERF023, which plays a negative role in apple salt tolerance. Stable overexpression of MdERF023 in apple plants and calli significantly decreased salt tolerance. Biochemical and molecular analyses revealed that MdERF023 directly binds to the promoter of MdMYB44-like, a positive modulator of ABA signaling-mediated salt tolerance, and suppresses its transcription. In addition, MdERF023 downregulated the transcription of MdSOS2 and MdAKT1, thereby reducing the Na+ expulsion, K+ absorption, and salt tolerance of apple plants. Taken together, these results suggest that MdERF023 reduces apple salt tolerance by inhibiting ABA signaling and ion transport, and that it could be used as a potential target for breeding new varieties of salt-tolerant apple plants via genetic engineering.


Assuntos
Ácido Abscísico , Regulação da Expressão Gênica de Plantas , Malus , Proteínas de Plantas , Plantas Geneticamente Modificadas , Tolerância ao Sal , Transdução de Sinais , Sódio , Fatores de Transcrição , Malus/genética , Malus/metabolismo , Malus/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Tolerância ao Sal/genética , Sódio/metabolismo , Regiões Promotoras Genéticas/genética
17.
Chem Biodivers ; 21(6): e202400150, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38548660

RESUMO

Experiments were conducted in this study on the co-hydropyrolysis of three components of biomass (cellulose, hemicellulose, and lignin) and HDPE by using SR-Pd/Trap-HZ-5 as catalyst. To control the variable, we use the same experiment conditions in co-hydropyrolysis: Si/Al ratio of 50, Pd load 1 %, catalyst to reactant ratio of 1 : 10, 1 MPa, 400 °C, reaction time 1 h. Use XRD, TEM, BET, and NH3-TPD to confirm catalyst successful synthesis; use pine sawdust (PW) co-hydropyrolysis with HDPE to analyse catalytic activity; and use GC/MS to characterize the chemical composition of the bio-oil from the co-hydropyrolysis of biomass components and HDPE. The results show that cellulose has a significant synergistic effect with aromatic hydrocarbon production, whose selectivity was 93.3 %; hemicellulose has a synergistic effect; aromatic selectivity can reach 75.1 %; and a negative synergistic effect between lignin and HDPE was shown as the selectivity of aromatic hydrocarbons decreased from 62.1 % to 15.6 %.


Assuntos
Biomassa , Celulose , Hidrocarbonetos Aromáticos , Polissacarídeos , Pirólise , Zeolitas , Catálise , Hidrocarbonetos Aromáticos/química , Polissacarídeos/química , Celulose/química , Zeolitas/química , Lignina/química
18.
J Adv Nurs ; 2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38186229

RESUMO

AIM: To explore the prospective acceptability of an implementation leadership training programme prototype for nurse managers in China to implement evidence-based practices, from the perspectives of potential programme participants and deliverers. DESIGN: A qualitative descriptive study was conducted in Spring 2022 at three tertiary hospitals in Hunan, China. METHODS: We conducted individual semi-structured interviews with unit-level nurse managers (n = 14), including 12 potential participants, and two potential deliverers that have been involved in developing the programme prototype. Interview questions and thematic analysis were guided by the Theoretical Framework of Acceptability. RESULTS: After reviewing the programme content, potential participants and deliverers reported that unit nurse managers would benefit from engaging in the programme, acknowledging that the programme fit with professional nursing values for implementing research evidence. They expressed positive views about being involved in producing academic papers through the training process, and interactive multi-modal training activities such as group work, experience-sharing and coaching. Seven participants were not very confident about being fully engaged in the training, as they could not navigate the English research literature. Both participants and deliverers highlighted factors that would influence their participation, including time constraints, the impact of the COVID-19 pandemic, and support from senior organizational leadership. CONCLUSIONS: The training programme prototype was perceived to be useful and acceptable. The multimodal training activities were considered a strength and managers expressed an interest in writing academic papers about their implementation processes. Support from senior hospital leaders and programme deliverers was identified as critical to the training programme's success. IMPACT: The study helps understand nurse managers' perceptions and concerns of participating in an implementation leadership training programme and could inform the development and refinement of similar programmes in various nursing contexts globally.

19.
BMC Nurs ; 23(1): 359, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816867

RESUMO

BACKGROUND: Unit nurse managers hold essential positions that can facilitate implementation of evidence-based practice. Studies showed that nurse managers in China lacked competencies and behaviours necessary to lead evidence-based practice implementation. The aim of the current study was to develop a context-fit training program prototype to enhance leadership competencies and behaviours regarding evidence-based practice implementation of Chinese unit nurse managers. METHOD: We used a descriptive qualitative study design and followed the integrated knowledge translation approach to co-develop the prototype in a tertiary hospital in Changsha, China. Seven nurse managers from the participated hospital and a researcher co-developed the prototype based on the Ottawa Model of Implementation Leadership (O-MILe). The development process encompassed four phases from November 2021 to March 2022 that involved group discussions (n = 4) and individual interviews (n = 21). All data were analysed by two independent researchers using the thematic analysis method. RESULTS: Managers agreed that all O-MILe behaviours were important to evidence-based practice implementation, and only minor modifications were needed for clarification and adaptation. The actions managers identified that could operationalize the leadership behaviours were related to current clinical practices, evidence-based practice, nurses, patients, interprofessional staff members, incentives and resources, organization and external entities. Three types of general competencies related to evidence-based practice, professional nursing, and implementation leadership were identified. Multimodal activities such as lectures, experience sharing, group discussions, plan development and coaching were suggested to deliver the training program. CONCLUSIONS: All O-MILe leadership behaviours were perceived as essential for unit nurse managers to lead EBP implementation in the hospital context in China. We identified the leadership actions and the competencies required for nursing managers to implement EBP in China. Further studies are required to evaluate the acceptability and impact of this prototype. Further studies with large sample sizes across various clinical settings are needed to facilitate the generalization of the findings and gain an in-depth understanding of the program.

20.
BMC Nurs ; 23(1): 452, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961494

RESUMO

BACKGROUND: The central component in impactful healthcare decisions is evidence. Understanding how nurse leaders use evidence in their own managerial decision making is still limited. This mixed methods systematic review aimed to examine how evidence is used to solve leadership problems and to describe the measured and perceived effects of evidence-based leadership on nurse leaders and their performance, organizational, and clinical outcomes. METHODS: We included articles using any type of research design. We referred nurses, nurse managers or other nursing staff working in a healthcare context when they attempt to influence the behavior of individuals or a group in an organization using an evidence-based approach. Seven databases were searched until 11 November 2021. JBI Critical Appraisal Checklist for Quasi-experimental studies, JBI Critical Appraisal Checklist for Case Series, Mixed Methods Appraisal Tool were used to evaluate the Risk of bias in quasi-experimental studies, case series, mixed methods studies, respectively. The JBI approach to mixed methods systematic reviews was followed, and a parallel-results convergent approach to synthesis and integration was adopted. RESULTS: Thirty-one publications were eligible for the analysis: case series (n = 27), mixed methods studies (n = 3) and quasi-experimental studies (n = 1). All studies were included regardless of methodological quality. Leadership problems were related to the implementation of knowledge into practice, the quality of nursing care and the resource availability. Organizational data was used in 27 studies to understand leadership problems, scientific evidence from literature was sought in 26 studies, and stakeholders' views were explored in 24 studies. Perceived and measured effects of evidence-based leadership focused on nurses' performance, organizational outcomes, and clinical outcomes. Economic data were not available. CONCLUSIONS: This is the first systematic review to examine how evidence is used to solve leadership problems and to describe its measured and perceived effects from different sites. Although a variety of perceptions and effects were identified on nurses' performance as well as on organizational and clinical outcomes, available knowledge concerning evidence-based leadership is currently insufficient. Therefore, more high-quality research and clinical trial designs are still needed. TRAIL REGISTRATION: The study was registered (PROSPERO CRD42021259624).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA