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1.
Plant Cell ; 35(8): 2952-2971, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37132478

RESUMO

Heat stress (HS) adversely affects plant growth and productivity. The Class A1 HS transcription factors (HSFA1s) act as master regulators in the plant response to HS. However, how HSFA1-mediated transcriptional reprogramming is modulated during HS remains to be elucidated. Here, we report that a module formed by the microRNAs miR165 and miR166 and their target transcript, PHABULOSA (PHB), regulates HSFA1 at the transcriptional and translational levels to control plant HS responses. HS-triggered induction of MIR165/166 in Arabidopsis thaliana led to decreased expression of target genes including PHB. MIR165/166 overexpression lines and mutations in miR165/166 target genes enhanced HS tolerance, whereas miR165/166 knockdown lines and plants expressing a miR165/166-resistant form of PHB were sensitive to HS. PHB directly repressed the transcription of HSFA1s and globally modulated the expression of HS-responsive genes. PHB and HSFA1s share a common target gene, HSFA2, which is essential for activation of plant responses to HS. PHB physically interacted with HSFA1s and exerted an antagonistic effect on HSFA1 transcriptional activity. PHB and HSFA1s co-regulated transcriptome reprogramming upon HS. Together, these findings indicate that heat-triggered regulation of the miR165/166-PHB module controls HSFA1-mediated transcriptional reprogramming and plays a critical role during HS in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , MicroRNAs , Termotolerância , Termotolerância/genética , Proteínas de Arabidopsis/metabolismo , Resposta ao Choque Térmico/genética , Arabidopsis/metabolismo , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Regulação da Expressão Gênica de Plantas/genética , MicroRNAs/genética , MicroRNAs/metabolismo
2.
J Biol Chem ; 300(9): 107669, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39128717

RESUMO

Hexavalent chromium (Cr(VI)) exposure has been linked with gastrointestinal toxicity, whereas the molecular pathways and key targets remain elusive. Computational toxicology analysis predicted the correlation between protein phosphatase 2A (PP2A) and genes regarding Cr(VI)-induced intestinal injury. Here, we generated a mouse model with intestinal epithelium-specific knock out of Ppp2r1a (encoding PP2A Aα subunit) to investigate the mechanisms underlying Cr(VI)-induced small intestinal toxicity. Heterozygous (HE) mice and matched WT littermates were administrated with Cr(VI) at 0, 5, 20, and 80 mg/l for 28 successive days. Cr(VI) treatment led to crypt hyperplasia, epithelial cell apoptosis, and intestinal barrier dysfunction, accompanied by the decline of goblet cell counts and Occludin expression in WT mice. Notably, these effects were aggravated in HE mice, indicating that PP2A Aα deficiency conferred mice with susceptibility to Cr(VI)-induced intestinal injury. The combination of data analysis and biological experiments revealed Cr(VI) exposure could decrease YAP1 phosphorylation at Ser127 but increase protein expression and activity, together with elevated transcriptional coactivator with PDZ-binding motif protein driving epithelial crypt cells proliferation following damage, suggesting the involvement of Hippo/YAP1 signaling pathway in Cr(VI)-induced intestinal toxicity. Nevertheless, the enhanced phosphorylation of YAP1 in HE mice resulted in proliferation/repair defects in intestinal epithelium, thereby exacerbating Cr(VI)-induced gut barrier dysfunction. Notably, by molecular docking and further studies, we identified urolithin A, a microbial metabolite, attenuated Cr(VI)-induced disruption of intestinal barrier function, partly by modulating YAP1 expression and activity. Our findings reveal the novel molecular pathways participated in Cr(VI)-caused small intestinal injury and urolithin A could potentially protect against environmental hazards-induced intestinal diseases.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Cromo , Intestino Delgado , Proteína Fosfatase 2 , Transdução de Sinais , Proteínas de Sinalização YAP , Animais , Proteínas de Sinalização YAP/metabolismo , Cromo/toxicidade , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteína Fosfatase 2/metabolismo , Proteína Fosfatase 2/genética , Intestino Delgado/metabolismo , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Via de Sinalização Hippo , Camundongos Knockout , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia
3.
Mol Ther ; 32(8): 2728-2740, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-38879754

RESUMO

Despite the remarkable success of chimeric antigen receptor (CAR) T therapy in hematological malignancies, its efficacy in solid tumors remains limited. Cytokine-engineered CAR T cells offer a promising avenue, yet their clinical translation is hindered by the risks associated with constitutive cytokine expression. In this proof-of-concept study, we leverage the endogenous interferon (IFN)-γ promoter for transgenic interleukin (IL)-15 expression. We demonstrate that IFN-γ expression is tightly regulated by T cell receptor signaling. By introducing an internal ribosome entry site IL15 into the 3' UTR of the IFN-γ gene via homology directed repair-mediated knock-in, we confirm that IL-15 expression can co-express with IFN-γ in an antigen stimulation-dependent manner. Importantly, the insertion of transgenes does not compromise endogenous IFN-γ expression. In vitro and in vivo data demonstrate that IL-15 driven by the IFN-γ promoter dramatically improves CAR T cells' antitumor activity, suggesting the effectiveness of IL-15 expression. Last, as a part of our efforts toward clinical translation, we have developed an innovative two-gene knock-in approach. This approach enables the simultaneous integration of CAR and IL-15 genes into TRAC and IFN-γ gene loci using a single AAV vector. CAR T cells engineered to express IL-15 using this approach demonstrate enhanced antitumor efficacy. Overall, our study underscores the feasibility of utilizing endogenous promoters for transgenic cytokines expression in CAR T cells.


Assuntos
Imunoterapia Adotiva , Interferon gama , Interleucina-15 , Regiões Promotoras Genéticas , Receptores de Antígenos Quiméricos , Interferon gama/metabolismo , Humanos , Animais , Camundongos , Imunoterapia Adotiva/métodos , Interleucina-15/genética , Interleucina-15/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/metabolismo , Linfócitos T/imunologia , Vetores Genéticos/genética , Linhagem Celular Tumoral , Transgenes , Citocinas/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Expressão Gênica
4.
Nucleic Acids Res ; 51(10): 4760-4773, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-36912084

RESUMO

Besides entrapping sister chromatids, cohesin drives other high-order chromosomal structural dynamics like looping, compartmentalization and condensation. ESCO2 acetylates a subset of cohesin so that cohesion must be established and only be established between nascent sister chromatids. How this process is precisely achieved remains unknown. Here, we report that GSK3 family kinases provide higher hierarchical control through an ESCO2 regulator, CRL4MMS22L. GSK3s phosphorylate Thr105 in MMS22L, resulting in homo-dimerization of CRL4MMS22L and ESCO2 during S phase as evidenced by single-molecule spectroscopy and several biochemical approaches. A single phospho-mimicking mutation on MMS22L (T105D) is sufficient to mediate their dimerization and rescue the cohesion defects caused by GSK3 or MMS22L depletion, whereas non-phosphorylable T105A exerts dominant-negative effects even in wildtype cells. Through cell fractionation and time-course measurements, we show that GSK3s facilitate the timely chromatin association of MMS22L and ESCO2 and subsequently SMC3 acetylation. The necessity of ESCO2 dimerization implicates symmetric control of cohesion establishment in eukaryotes.


Assuntos
Acetiltransferases , Cromátides , Proteínas Cromossômicas não Histona , Acetiltransferases/metabolismo , Proteínas de Ciclo Celular/metabolismo , Cromátides/metabolismo , Segregação de Cromossomos , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas Nucleares/metabolismo , Fase S , Humanos , Linhagem Celular , Leveduras , Proteínas Cromossômicas não Histona/metabolismo , Coesinas
5.
Crit Rev Biochem Mol Biol ; 57(3): 333-350, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35112600

RESUMO

Cohesin, a four-subunit ring comprising SMC1, SMC3, RAD21 and SA1/2, tethers sister chromatids by DNA replication-coupled cohesion (RC-cohesion) to guarantee correct chromosome segregation during cell proliferation. Postreplicative cohesion, also called damage-induced cohesion (DI-cohesion), is an emerging critical player in DNA damage response (DDR). In this review, we sum up recent progress on how cohesin regulates the DNA damage checkpoint activation and repair pathway choice, emphasizing postreplicative cohesin loading and DI-cohesion establishment in yeasts and mammals. DI-cohesion and RC-cohesion show distinct features in many aspects. DI-cohesion near or far from the break sites might undergo different regulations and execute different tasks in DDR and DSB repair. Furthermore, some open questions in this field and the significance of this new scenario to our understanding of genome stability maintenance and cohesinopathies are discussed.


Assuntos
Proteínas Cromossômicas não Histona , Proteínas Nucleares , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Dano ao DNA , Reparo do DNA , Mamíferos/metabolismo , Proteínas Nucleares/genética , Coesinas
6.
Plant J ; 115(4): 937-951, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37154288

RESUMO

Plant height (PH) is an important agronomic trait affecting crop architecture, biomass, resistance to lodging and mechanical harvesting. Elucidating the genetic governance of plant height is crucial because of the global demand for high crop yields. However, during the rapid growth period of plants the PH changes a lot on a daily basis, which makes it difficult to accurately phenotype the trait by hand on a large scale. In this study, an unmanned aerial vehicle (UAV)-based remote-sensing phenotyping platform was applied to obtain time-series PHs of 320 upland cotton accessions in three different field trials. The results showed that the PHs obtained from UAV images were significantly correlated with ground-based manual measurements, for three trials (R2 = 0.96, 0.95 and 0.96). Two genetic loci on chromosomes A01 and A11 associated with PH were identified by genome-wide association studies (GWAS). GhUBP15 and GhCUL1 were identified to influence PH in further analysis. We obtained a time series of PH values for three field conditions based on remote sensing with UAV. The key genes identified in this study are of great value for the breeding of ideal plant architecture in cotton.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Mapeamento Cromossômico , Locos de Características Quantitativas/genética , Dispositivos Aéreos não Tripulados , Fatores de Tempo , Melhoramento Vegetal
7.
Anal Chem ; 96(13): 5188-5194, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38506628

RESUMO

In the field of chiral recognition, chiral cyclic organic compounds, especially heterocyclic organic compounds, have attracted little attention and have been rarely studied as chiral substrates by means of 1H NMR spectroscopy. In this paper, enantiomers of thiohydantoin derivatives, representing typical five-membered N,N-heterocycles, have been synthesized and utilized for assignment of absolute configuration and analysis of enantiomeric excess. All enantiomers have been successfully differentiated with the assistance of novel tetraaza macrocyclic chiral solvating agents (TAMCSAs) by 1H NMR spectroscopy. Surprisingly, unprecedented nonequivalent chemical shift values (up to 2.052 ppm) of the NH proton of substrates have been observed, a new milestone in the evaluation of enantiomers. To better understand the intermolecular interactions between host and guest, Job plots and theoretical calculations of (S)-G1 and (R)-G1 with TAMCSA 1a were investigated and revealed significant geometric differentiation between the diastereomers. In order to evaluate practical applications of the present systems in analyzing optical purity of chiral substrates, enantiomeric excesses of a typical substrate (G1) with different optical compositions in the presence of a representative TAMCSA (1a) can be accurately calculated based on the integration of the NH proton's signal peaks. Importantly, this work provides a significant breakthrough in exploring and developing the chiral recognition of chiral heterocyclic organic compounds by 1H NMR spectroscopy.

8.
J Gene Med ; 26(1): e3657, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282150

RESUMO

BACKGROUND: Natural killer (NK) cells are crucial to cancer development and prognosis. However, the role of NK cell-related genes in immunotherapy and the tumor immune microenvironment (TIME) is not well understood. This study aimed to develop reliable risk signatures associated with NK cell-related genes for predicting thyroid cancer (THCA). METHODS: The single-cell RNA sequencing (scRNA-seq) data from seven THCA samples (GSE184362) and bulk-RNA-seq data of 502 THCA patients (TCGA-THCA) were included. The scRNA-seq data was analyzed using the "Seurat" R package to identify differentially expressed genes in NK cells. The clustering analysis was carried out using the R package "ConsensusClusterPlus". The gene set variation analysis (GSVA) algorithm was applied to assess the variations in biological pathways among subtypes. The ESTIMATE algorithm was utilized to calculate the scores for stromal, immune and estimate variables. In addition, we used the single sample Gene Set Enrichment Analysis and CIBERSORT algorithms to assess the degree to which immune cells and pathways related to immunity were enriched based on the meta-cohort. In the TCGA-THCA cohort, the "glmnet" R package was used for the gene selection, and LASSO Cox analysis was used to construct prognostic features. The "maftools" R package was used to examine the somatic mutation landscape of THCA in both low- and high-risk groups. RESULTS: One-hundred and eighty-five NK cell marker genes were screened, and nine genes were associated with the THCA prognosis. KLF2, OSTF1 and TAPBP were finally identified and constructed a risk signature with significant prognostic value. KLF2 and OSTF1 were protective genes, and TAPBP was a risk gene. Patients at high risk had a considerably lower overall survival compared with those at low risk. Mutations in the TCGA-THCA cohort were predominantly C > T. Increased tumor mutation burden (TMB) levels were linked to overall survival. The low-risk H-TMB+ group had a better prognosis, while the high-risk L-TMB+ group had the worst prognosis. CONCLUSION: Natural killer cell-related genes KLF2, OSTF1 and TAPBP were used to develop a novel prognostic risk signature, offering a new perspective on the prognosis and treatment of THCA.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/terapia , Imunoterapia , Células Matadoras Naturais , Algoritmos , Análise por Conglomerados , Microambiente Tumoral/genética
9.
Phys Rev Lett ; 133(12): 126501, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39373426

RESUMO

The recent discovery of high-temperature superconductivity in La_{3}Ni_{2}O_{7} offers a fresh platform for exploring unconventional pairing mechanisms. Starting with the basic argument that the electrons in d_{z^{2}} orbitals nearly form local moments, we examine the effect of the Hubbard interaction U on the binding strength of Cooper pairs based on a single-orbital bilayer model with intralayer hopping t_{∥} and interlayer superexchange J_{⊥}. By extensive density matrix renormalization group calculations, we observe a remarkable enhancement in binding energy as much as 10-20 times larger with U/t_{∥} increasing from 0 to 12 at J_{⊥}/t_{∥}∼1. We demonstrate that such a substantial enhancement stems from a kinetic-energy-driven mechanism. Specifically, a Z_{2} Berry phase will emerge at large U due to the Hilbert space restriction (Mottness), which strongly suppresses the mobility of single particle propagation as compared to U=0. However, the kinetic energy of the electrons (holes) can be greatly restored by forming an interlayer spin-singlet pairing, which naturally results in a superconducting state even for relatively small J_{⊥}. An effective hard-core bosonic model is further proposed to estimate the superconducting transition temperature at the mean-field level.

10.
Biotechnol Bioeng ; 121(3): 980-990, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38088435

RESUMO

Bacteria capable of direct ammonia oxidation (Dirammox) play important roles in global nitrogen cycling and nutrient removal from wastewater. Dirammox process, NH3 → NH2 OH → N2 , first defined in Alcaligenes ammonioxydans HO-1 and encoded by dnf gene cluster, has been found to widely exist in aquatic environments. However, because of multidrug resistance in Alcaligenes species, the key genes involved in the Dirammox pathway and the interaction between Dirammox process and the physiological state of Alcaligenes species remain unclear. In this work, ammonia removal via the redistribution of nitrogen between Dirammox and microbial growth in A. ammonioxydans HO-1, a model organism of Alcaligenes species, was investigated. The dnfA, dnfB, dnfC, and dnfR genes were found to play important roles in the Dirammox process in A. ammonioxydans HO-1, while dnfH, dnfG, and dnfD were not essential genes. Furthermore, an unexpected redistribution phenomenon for nitrogen between Dirammox and cell growth for ammonia removal in HO-1 was revealed. After the disruption of the Dirammox in HO-1, more consumed NH4 + was recovered as biomass-N via rapid metabolic response and upregulated expression of genes associated with ammonia transport and assimilation, tricarboxylic acid cycle, sulfur metabolism, ribosome synthesis, and other molecular functions. These findings deepen our understanding of the molecular mechanisms for Dirammox process in the genus Alcaligenes and provide useful information about the application of Alcaligenes species for ammonia-rich wastewater treatment.


Assuntos
Compostos de Amônio , Compostos de Amônio/metabolismo , Alcaligenes/genética , Alcaligenes/metabolismo , Amônia/toxicidade , Amônia/metabolismo , Águas Residuárias , Nitrogênio/metabolismo , Desnitrificação , Oxirredução , Reatores Biológicos
11.
Langmuir ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017586

RESUMO

Silicone rubber has broad applications in the field of industrial engineering due to its stable physical and chemical properties. However, the superhydrophobic properties, of silicone rubber, especially large deformation superhydrophobic properties, were not satisfactory for many harsh application environments and complex engineering structures. Here, we report the preparation of superhydrophobic tensile designable silicone rubber composites by a mixed deposition process that included powder deposition and smoke deposition. The infrared test showed that the deposited powder from silicone rubber combustion was mainly composed of SiO2 and short chain siloxane. The mixed deposited surface with a rich micro-nanostructure, which was the key to the formation of superhydrophobic properties. The water contact angle (WCA) and sliding angle (SA) of coating surface could reach 157.6° and 5° ± 1°, respectively, and the tensile designability of superhydrophobic surface is closely related to the prestretched process. In addition, bounce tests, high temperature tests, and solvent resistance tests showed the application potential of modified silicone rubber composites in the field of engineering.

12.
Int Microbiol ; 27(2): 449-457, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37490176

RESUMO

Indole is a typical heterocyclic compound derived from tryptophan widespread in nature. Pseudomonas aeruginosa is one of the most common opportunistic pathogens everywhere in the world. Indole and P. aeruginosa will encounter inevitably; however, the indole transformation process by P. aeruginosa remains unclear. Herein, an indole-degrading strain of P. aeruginosa Jade-X was isolated from activated sludge. Strain Jade-X could degrade 1 mmol/L indole within 48 h with the inoculum size of 1% (v/v). It showed high efficiency in indole degradation under the conditions of 30-42 °C, pH 5.0-9.0, and NaCl concentration less than 2.5%. The complete genome of strain Jade-X was sequenced which was 6508614 bp in length with one chromosome. Bioinformatic analyses showed that strain Jade-X did not contain the indole oxygenase gene. Three cytochrome P450 genes were identified and up-regulated in the indole degradation process by RT-qPCR analysis, while cytochrome P450 inhibitors did not affect the indole degradation process. It suggested that indole oxidation was catalyzed by an unraveled enzyme. An ant gene cluster was identified, among which the anthranilate 1,2-dioxygenase and catechol 1,2-dioxygenase genes were upregulated. An indole-anthranilate-catechol pathway was proposed in indole degradation by strain P. aeruginosa Jade-X. This study enriched our understanding of the indole biodegradation process in P. aeruginosa.


Assuntos
Genômica , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Biodegradação Ambiental , Indóis/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo
13.
Phys Chem Chem Phys ; 26(9): 7343-7350, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38369913

RESUMO

Two-dimensional (2D) materials are an excellent platform for surface-enhanced Raman spectroscopy (SERS). For ReS2, the Raman enhancement effect can be highly improved through the dipole-dipole interactions and synergistic resonance effects in the phase-engineering ReS2 films. However, the performance of the substrate can be improved further through regulating the electronic interaction between the ReS2 and probe molecules. Herein, a dynamic coulomb repulsion strategy is proposed to trigger an electronic state redistribution by asymmetric electrostatic interactions. With the phase-engineering ReS2/graphene heterostructure as a prototype, under laser excitation, the generated hot electrons in graphene and ReS2 can repel each other due to Coulomb interaction, which breaks the symmetrical distribution of hot electrons in ReS2, and increases the electronic concentration at the interface between ReS2 and the probe molecule. With R6G as the probe molecule, the asymmetric electron distribution and synergistic resonance effects on their interface improve the limit of detection to 10-12 M with an EF of 2.15 × 108. Meanwhile, the heterostructure also shows good uniformity, stability as well as unique anisotropy. This strategy can be generalized to other 2D heterostructures to obtain the ultrasensitive SERS substrates.

14.
Acta Pharmacol Sin ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179867

RESUMO

Abdominal aortic aneurysm (AAA) is a degenerative disease that caused mortality in people aged >65. Senescence plays a critical role in AAA pathogenesis. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. Our Previous study found cyclic nucleotide phosphodiesterase 1C (PDE1C) exacerbate AAA through aggravate vascular smooth muscle cells (VSMCs) senescence by downregulating Sirtuin1 (SIRT1) expression and activity. Vinpocetine as a selective inhibitor of PDE1 and a clinical medication for cerebral vasodilation, it is unclear whether vinpocetine can rely on SIRT1 to alleviate AAA. This study showed that pre-treatment with vinpocetine remarkably prevented aneurysmal dilation and reduced aortic rupture in elastase-induced AAA mice. In addition, the elastin degradation, MMP (matrix metalloproteinase) activity, macrophage infiltration, ROS production, collagen fibers remodeling, and VSMCs senescence were decreased in AAA treated with vinpocetine. While these effects were unable to exert in VSMCs-specific SIRT1 knockout AAA mice. Accordingly, we revealed that vinpocetine suppressed migration, proliferation, and senescence in VSMCs. Moreover, vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy. In conclusion, this study indicated that vinpocetine may be as a potential drug for therapy AAA through alleviate VSMCs senescence via the SIRT1-dependent pathway.

15.
Environ Res ; 259: 119511, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38950811

RESUMO

Recently, microplastics (MPs) have attracted extensive attention to their wide distribution and potential toxicity in ecosystems. However, there was a lack of research focused on MPs in seaweed bed ecosystems. This study investigated the distribution and toxicity of MPs in macrobenthos in Sargassum ecosystem. According to the in-situ investigation results, the abundance of MPs in the sediment was 0.9-2.3 items/g, the indoor microcosmic experiment was constructed. After exposure to MPs (0, 2, and 20 items/g) for 30 days, the abundance of MPs in macrobenthos exhibits a concentration-dependent increase. However, there was no significant bioaccumulation of MPs at the trophic level. The indoor toxicity test revealed that MPs induced oxidative stress and altered intestinal microflora composition in macrobenthos, even at actual environmental concentrations (2 items/g). It may result in a perturbation of the organism's homeostatic equilibrium. High-concentration (20 items/g) MPs had a greater impact on alkaline phosphatase (AKP) in Mollusks. The increase in AKP activity could be indicative of an adaptive mechanism in some macrobenthos while the decline in AKP activity might signal a decrease in their survival. These results elucidated the fate of MPs in ecosystem and the ecological risks of MPs to large benthic animals on model environmental conditions.


Assuntos
Ecossistema , Microplásticos , Sargassum , Poluentes Químicos da Água , Sargassum/química , Microplásticos/toxicidade , Animais , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Sedimentos Geológicos/química , Monitoramento Ambiental , Moluscos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
16.
J Nanobiotechnology ; 22(1): 487, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143493

RESUMO

Mitochondria are crucial organelles responsible for energy generation in eukaryotic cells. Oxidative stress, calcium disorders, and mitochondrial DNA abnormalities can all cause mitochondrial dysfunction. It is now well documented that mitochondrial dysfunction significantly contributes to the pathogenesis of numerous illnesses. Hence, it is vital to investigate innovative treatment methods targeting mitochondrial dysfunction. Extracellular vesicles (EVs) are cell-derived nanovesicles that serve as intercellular messengers and are classified into small EVs (sEVs, < 200 nm) and large EVs (lEVs, > 200 nm) based on their sizes. It is worth noting that certain subtypes of EVs are rich in mitochondrial components (even structurally intact mitochondria) and possess the ability to transfer them or other contents including proteins and nucleic acids to recipient cells to modulate their mitochondrial function. Specifically, EVs can modulate target cell mitochondrial homeostasis as well as mitochondria-controlled apoptosis and ROS generation by delivering relevant substances. In addition, the artificial modification of EVs as delivery carriers for therapeutic goods targeting mitochondria is also a current research hotspot. In this article, we will focus on the ability of EVs to modulate the mitochondrial function of target cells, aiming to offer novel perspectives on therapeutic approaches for diverse conditions linked to mitochondrial dysfunction.


Assuntos
Vesículas Extracelulares , Mitocôndrias , Vesículas Extracelulares/metabolismo , Humanos , Mitocôndrias/metabolismo , Animais , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Apoptose , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/terapia , Sistemas de Liberação de Medicamentos/métodos
17.
J Nanobiotechnology ; 22(1): 240, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735931

RESUMO

Zinc oxide nanoparticles (ZnO NPs) stand as among the most significant metal oxide nanoparticles in trigger the formation of reactive oxygen species (ROS) and induce apoptosis. Nevertheless, the utilization of ZnO NPs has been limited by the shallowness of short-wavelength light and the constrained production of ROS. To overcome these limitations, a strategy involves achieving a red shift towards the near-infrared (NIR) light spectrum, promoting the separation and restraining the recombination of electron-hole (e--h+) pairs. Herein, the hybrid plasmonic system Au@ZnO (AZ) with graphene quantum dots (GQDs) doping (AZG) nano heterostructures is rationally designed for optimal NIR-driven cancer treatment. Significantly, a multifold increase in ROS generation can be achieved through the following creative initiatives: (i) plasmonic Au nanorods expands the photocatalytic capabilities of AZG into the NIR domain, offering a foundation for NIR-induced ROS generation for clinical utilization; (ii) elaborate design of mesoporous core-shell AZ structures facilitates the redistribution of electron-hole pairs; (iii) the incorporation GQDs in mesoporous structure could efficiently restrain the recombination of the e--h+ pairs; (iv) Modification of hyaluronic acid (HA) can enhance CD44 receptor mediated targeted triple-negative breast cancer (TNBC). In addition, the introduced Au NRs present as catalysts for enhancing photothermal therapy (PTT), effectively inducing apoptosis in tumor cells. The resulting HA-modified AZG (AZGH) exhibits efficient hot electron injection and e--h+ separation, affording unparalleled convenience for ROS production and enabling NIR-induced PDT for the cancer treanment. As a result, our well-designed mesoporous core-shell AZGH hybrid as photosensitizers can exhibit excellent PDT efficacy.


Assuntos
Ouro , Grafite , Estresse Oxidativo , Pontos Quânticos , Espécies Reativas de Oxigênio , Neoplasias de Mama Triplo Negativas , Óxido de Zinco , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Feminino , Linhagem Celular Tumoral , Ouro/química , Grafite/química , Óxido de Zinco/química , Animais , Pontos Quânticos/química , Camundongos , Nanopartículas Metálicas/química , Apoptose/efeitos dos fármacos , Ácido Hialurônico/química , Elétrons
18.
Gerontology ; 70(9): 991-1012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38857587

RESUMO

INTRODUCTION: Anxiety and depression are prevalent among older adults, and digital interactive interventions have shown promise in promoting their mental well-being. However, limited research has explored the effects of different types of digital interactive interventions across various devices on anxiety and depression in older adults with different health conditions. METHODS: A systematic literature review and meta-analysis were conducted using seven selected databases to identify relevant studies up to July 19, 2023. Two reviewers independently conducted study selection, data extraction, and quality appraisals. The risk of bias in the included studies was assessed using the Cochrane risk-of-bias tool. For the meta-analysis, the effect size was calculated as the standardized mean difference (SMD) using a random-effects model. RESULTS: A total of 20 randomized control trails involving 1,309 older adults fulfilled inclusion criteria. The meta-analysis results demonstrates that the digital interactive intervention technologies had a significance on depression (SMD = -0.656 s, 95% confidence interval [CI] = -0.992 to -0.380, p < 0.001) and anxiety (SMD = -0.381 s, 95% CI = -0.517 to -0.245, p < 0.001). Physical interactive interventions demonstrated a significant effect on depression and anxiety (SMD = -0.711 s, 95% CI = -1.102 to -0.319, p < 0.001) and (SMD = -0.573 s, 95% CI = -0.910 to -0.236, p = 0.001). Similarly, immersive interactive interventions also showed a significant effect on depression and anxiety (SMD = -0.699 s, 95% CI = -1.026 to -0.373, p < 0.001) and (SMD = -0.343 s, 95% CI = -0.493 to -0.194, p < 0.001). Additionally, in the internal medicine group, significant intervention effects were observed for depression (SMD = -0.388, 95% CI = -0.630 to -0.145, p = 0.002) and anxiety (SMD = -0.325, 95% CI = -0.481 to -0.169, p < 0.001). Similarly, in the neurocognitive disorders group, significant intervention effects were found for depression (SMD = -0.702, 95% CI = -0.991 to -0.413, p < 0.001) and anxiety (SMD = -0.790, 95% CI = -1.237 to -0.342, p = 0.001). CONCLUSION: The results indicated that various digital interactive devices, including physical and immersive interactive devices, have a positive impact on depression and anxiety among older adults. However, mobile games were not effective in addressing depression. Digital interactive technologies did not significantly influence anxiety intervention, except for elderly individuals undergoing surgical procedures. Nevertheless, these interventions effectively addressed depression and anxiety in older individuals with neurocognitive disorders, internal medical issues, and those without health issues.


Assuntos
Ansiedade , Depressão , Saúde Digital , Idoso , Humanos , Ansiedade/terapia , Ansiedade/psicologia , Ansiedade/prevenção & controle , Depressão/prevenção & controle , Depressão/psicologia , Depressão/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Gerontology ; 70(9): 978-990, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843781

RESUMO

INTRODUCTION: Smart healthcare technologies (SHCTs) exhibit the great potential to support older Hong Kong adults with their health problems. Although there are various SHCTs in the Hong Kong market, and some adoption predictors have been proposed and investigated, little is known about older users' views on and real-life experiences with these technologies. This exploratory study examined the experiences, functional needs, and barriers of three kinds of SHCT (i.e., smart wearable devices, smart health monitors, and healthcare applications) with older adults in real life. METHODS: A convenience sampling method was applied to recruit twenty-two older adults from the Hong Kong community. The interview was designed in semi-structured and conducted in a face-to-face setting. The content analysis was used to summarize the older adults' functional needs and barriers in real life. RESULTS: We found older adults mainly applied SHCTs to address physical health, but there are few technological solutions for mental health in practice. There are four types of barriers in using SHCT. However, social support in Hong Kong community greatly helps reduce the barriers in technology use. Based on the findings, we discussed the possible solutions based on the social and technology perspective. CONCLUSION: Current technologies still could not fully address older adults' needs for healthy aging, and various barriers still hinder the actual adoption. By deeply understanding and considering the social context, technology innovation can facilitate the adoption of SHCT and promote a healthy aging society.


Assuntos
Tecnologia Biomédica , Humanos , Idoso , Masculino , Feminino , Hong Kong , Idoso de 80 Anos ou mais , Dispositivos Eletrônicos Vestíveis , Entrevistas como Assunto , Apoio Social , Pessoa de Meia-Idade
20.
Graefes Arch Clin Exp Ophthalmol ; 262(8): 2593-2600, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38446197

RESUMO

PURPOSE: To evaluate cytokine levels of aqueous humor in patients with cytomegalovirus (CMV) corneal endotheliitis and their relationships with CMV DNA load. METHODS: 44 aqueous humor samples were obtained from 26 patients with CMV corneal endotheliitis at various stages of treatment. 33 samples obtained from cataract patients during the same period were selected as a control group. Each sample was used to measure the concentration of the CMV DNA load using real-time quantitative polymerase chain reaction, and to examine the levels of IL-6, IL-8, IL-10, MCP-1, VCAM-1, VEGF, IP-10, G-CSF, ICAM-1 and IFN-γ using a cytometric bead array. RESULTS: All 10 cytokines were found to have statistically significant differences between the CMV endotheliitis and cataract groups. The Spearman correlation test showed that the concentration of CMV DNA load was significantly associated with the levels of IL-6 (P = 0.005, r = 0.417), IL-8 (P < 0.001, r = 0.514), IL-10 (P < 0.001, r = 0.700), MCP-1 (P = 0.001, r = 0.487), VEGF (P < 0.001, r = 0.690), IP-10 (P = 0.001, r = 0.469), G-CSF (P < 0.001, r = 0.554) and ICAM-1 (P < 0.001, r = 0.635), but not significantly associated with VCAM-1 (P = 0.056) and IFN-γ (P = 0.219). CONCLUSIONS: There was a combined innate and adaptive immune response in aqueous humor in patients with CMV endotheliitis. Levels of multiple cytokines were significantly correlated with viral particle. Cytokines are potential indicators to help diagnose CMV endotheliitis, evaluate disease activity and assess treatment response.


Assuntos
Humor Aquoso , Citocinas , Infecções por Citomegalovirus , Citomegalovirus , DNA Viral , Endotélio Corneano , Infecções Oculares Virais , Humanos , Humor Aquoso/virologia , Humor Aquoso/metabolismo , Masculino , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/metabolismo , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Citocinas/metabolismo , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Endotélio Corneano/virologia , Endotélio Corneano/metabolismo , Endotélio Corneano/patologia , Infecções Oculares Virais/virologia , Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/metabolismo , Infecções Oculares Virais/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , DNA Viral/análise , Ceratite/virologia , Ceratite/diagnóstico , Ceratite/metabolismo , Adulto , Reação em Cadeia da Polimerase em Tempo Real
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