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1.
Nature ; 602(7897): 431-436, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35173341

RESUMO

Marked evolution of properties with minute changes in the doping level is a hallmark of the complex chemistry that governs copper oxide superconductivity as manifested in the celebrated superconducting domes and quantum criticality taking place at precise compositions1-4. The strange-metal state, in which the resistivity varies linearly with temperature, has emerged as a central feature in the normal state of copper oxide superconductors5-9. The ubiquity of this behaviour signals an intimate link between the scattering mechanism and superconductivity10-12. However, a clear quantitative picture of the correlation has been lacking. Here we report the observation of precise quantitative scaling laws among the superconducting transition temperature (Tc), the linear-in-T scattering coefficient (A1) and the doping level (x) in electron-doped copper oxide La2-xCexCuO4 (LCCO). High-resolution characterization of epitaxial composition-spread films, which encompass the entire overdoped range of LCCO, has enabled us to systematically map its structural and transport properties with unprecedented accuracy and with increments of Δx = 0.0015. We have uncovered the relations Tc ~ (xc - x)0.5 ~ (A1□)0.5, where xc is the critical doping in which superconductivity disappears and A1□ is the coefficient of the linear resistivity per CuO2 plane. The striking similarity of the Tc versus A1□ relation among copper oxides, iron-based and organic superconductors may be an indication of a common mechanism of the strange-metal behaviour and unconventional superconductivity in these systems.

2.
Chem Rev ; 124(5): 2081-2137, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38393351

RESUMO

Gallium-based liquid metal (LM) exhibits exceptional properties such as high conductivity and biocompatibility, rendering it highly valuable for the development of conformal bioelectronics. When combined with polymers, liquid metal-polymer conductors (MPC) offer a versatile platform for fabricating conformal cyborg devices, enabling functions such as sensing, restoration, and augmentation within the human body. This review focuses on the synthesis, fabrication, and application of MPC-based cyborg devices. The synthesis of functional materials based on LM and the fabrication techniques for MPC-based devices are elucidated. The review provides a comprehensive overview of MPC-based cyborg devices, encompassing their applications in sensing diverse signals, therapeutic interventions, and augmentation. The objective of this review is to serve as a valuable resource that bridges the gap between the fabrication of MPC-based conformal devices and their potential biomedical applications.


Assuntos
Polímeros , Dispositivos Eletrônicos Vestíveis , Humanos
3.
BMC Plant Biol ; 24(1): 372, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714917

RESUMO

BACKGROUND: High-affinity potassium transporters (HKTs) are crucial in facilitating potassium uptake by plants. Many types of HKTs confer salt tolerance to plants through regulating K+ and Na+ homeostasis under salinity stress. However, their specific functions in cassava (Manihot esculenta) remain unclear. RESULTS: Herein, an HKT gene (MeHKT1) was cloned from cassava, and its expression is triggered by exposure to salt stress. The expression of a plasma membrane-bound protein functions as transporter to rescue a low potassium (K+) sensitivity of yeast mutant strain, but the complementation of MeHKT1 is inhibited by NaCl treatment. Under low K+ stress, transgenic Arabidopsis with MeHKT1 exhibits improved growth due to increasing shoot K+ content. In contrast, transgenic Arabidopsis accumulates more Na+ under salt stress than wild-type (WT) plants. Nevertheless, the differences in K+ content between transgenic and WT plants are not significant. Additionally, Arabidopsis expressing MeHKT1 displayed a stronger salt-sensitive phenotype. CONCLUSION: These results suggest that under low K+ condition, MeHKT1 functions as a potassium transporter. In contrast, MeHKT1 mainly transports Na+ into cells under salt stress condition and negatively regulates the response of transgenic Arabidopsis to salt stress. Our results provide a reference for further research on the function of MeHKT1, and provide a basis for further application of MeHKT1 in cassava by molecular biological means.


Assuntos
Arabidopsis , Manihot , Proteínas de Plantas , Plantas Geneticamente Modificadas , Potássio , Estresse Salino , Arabidopsis/genética , Arabidopsis/fisiologia , Arabidopsis/metabolismo , Manihot/genética , Manihot/metabolismo , Manihot/fisiologia , Plantas Geneticamente Modificadas/genética , Potássio/metabolismo , Estresse Salino/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Regulação da Expressão Gênica de Plantas , Tolerância ao Sal/genética , Sódio/metabolismo
4.
BMC Plant Biol ; 24(1): 4, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38163897

RESUMO

BACKGROUND: Understanding how plants and pathogens regulate each other's gene expression during their interactions is key to revealing the mechanisms of disease resistance and controlling the development of pathogens. Despite extensive studies on the molecular and genetic basis of plant immunity against pathogens, the influence of pitaya immunity on N. dimidiatum metabolism to restrict pathogen growth is poorly understood, and how N. dimidiatum breaks through pitaya defenses. In this study, we used the RNA-seq method to assess the expression profiles of pitaya and N. dimidiatum at 4 time periods after interactions to capture the early effects of N. dimidiatum on pitaya processes. RESULTS: The study defined the establishment of an effective method for analyzing transcriptome interactions between pitaya and N. dimidiatum and to obtain global expression profiles. We identified gene expression clusters in both the host pitaya and the pathogen N. dimidiatum. The analysis showed that numerous differentially expressed genes (DEGs) involved in the recognition and defense of pitaya against N. dimidiatum, as well as N. dimidiatum's evasion of recognition and inhibition of pitaya. The major functional groups identified by GO and KEGG enrichment were responsible for plant and pathogen recognition, phytohormone signaling (such as salicylic acid, abscisic acid). Furthermore, the gene expression of 13 candidate genes involved in phytopathogen recognition, phytohormone receptors, and the plant resistance gene (PG), as well as 7 effector genes of N. dimidiatum, including glycoside hydrolases, pectinase, and putative genes, were validated by qPCR. By focusing on gene expression changes during interactions between pitaya and N. dimidiatum, we were able to observe the infection of N. dimidiatum and its effects on the expression of various defense components and host immune receptors. CONCLUSION: Our data show that various regulators of the immune response are modified during interactions between pitaya and N. dimidiatum. Furthermore, the activation and repression of these genes are temporally coordinated. These findings provide a framework for better understanding the pathogenicity of N. dimidiatum and its role as an opportunistic pathogen. This offers the potential for a more effective defense against N. dimidiatum.


Assuntos
Cactaceae , Reguladores de Crescimento de Plantas , Transcriptoma , Cactaceae/genética , Interações Hospedeiro-Patógeno/genética , Resistência à Doença/genética , Redes e Vias Metabólicas , Perfilação da Expressão Gênica , Doenças das Plantas/genética , Regulação da Expressão Gênica de Plantas
5.
Plant Cell Environ ; 47(5): 1486-1502, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38238896

RESUMO

For plant growth under salt stress, sensing and transducing salt signals are central to cellular Na+ homoeostasis. The calcineurin B-like protein (CBL)-CBL-interacting protein kinase (CIPK) complexes play critical roles in transducing salt signals in plants. Here, we show that CBL5, an ortholog of CBL4 and CBL10 in Arabidopsis, interacts with and recruits CIPK8/CIPK24 to the plasma membrane. Yeast cells coexpressing CBL5, CIPK8/CIPK24 and SOS1 demonstrated lesser Na+ accumulation and a better growth phenotype than the untransformed or SOS1 transgenic yeast cells under salinity. Overexpression of CBL5 improved the growth of the cipk8 or cipk24 single mutant but not the cipk8 cipk24 double mutant under salt stress, suggesting that CIPK8 and CIPK24 were the downstream targets of CBL5. Interestingly, seed germination in cbl5 was severely inhibited by NaCl, which was recovered by the overexpression of CBL5. Furthermore, CBL5 was mainly expressed in the cotyledons and hypocotyls, which are essential to seed germination. Na+ efflux activity in the hypocotyls of cbl5 was reduced relative to the wild-type under salt stress, enhancing Na+ accumulation. These findings indicate that CBL5 functions in seed germination and protects seeds and germinating seedlings from salt stress through the CBL5-CIPK8/CIPK24-SOS1 pathways.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Germinação , Calcineurina/genética , Calcineurina/metabolismo , Saccharomyces cerevisiae/metabolismo , Sementes , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas Quinases/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/metabolismo , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo
6.
Microb Ecol ; 87(1): 68, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722447

RESUMO

It is necessary to predict the critical transition of lake ecosystems due to their abrupt, non-linear effects on social-economic systems. Given the promising application of paleolimnological archives to tracking the historical changes of lake ecosystems, it is speculated that they can also record the lake's critical transition. We studied Lake Dali-Nor in the arid region of Inner Mongolia because of the profound shrinking the lake experienced between the 1300 s and the 1600 s. We reconstructed the succession of bacterial communities from a 140-cm-long sediment core at 4-cm intervals and detected the critical transition. Our results showed that the historical trajectory of bacterial communities from the 1200 s to the 2010s was divided into two alternative states: state1 from 1200 to 1300 s and state2 from 1400 to 2010s. Furthermore, in the late 1300 s, the appearance of a tipping point and critical slowing down implied the existence of a critical transition. By using a multi-decadal time series from the sedimentary core, with general Lotka-Volterra model simulations, local stability analysis found that bacterial communities were the most unstable as they approached the critical transition, suggesting that the collapse of stability triggers the community shift from an equilibrium state to another state. Furthermore, the most unstable community harbored the strongest antagonistic and mutualistic interactions, which may imply the detrimental role of interaction strength on community stability. Collectively, our study showed that sediment DNA can be used to detect the critical transition of lake ecosystems.


Assuntos
Bactérias , DNA Bacteriano , Sedimentos Geológicos , Lagos , Lagos/microbiologia , Lagos/química , Sedimentos Geológicos/microbiologia , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , China , DNA Bacteriano/genética , Ecossistema , RNA Ribossômico 16S/genética , Microbiota
7.
Nano Lett ; 23(19): 9056-9064, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37738391

RESUMO

Sepsis is an acute systemic infectious syndrome with high fatality. Fast and accurate diagnosis, monitoring, and medication of sepsis are essential. We exploited the fluorescent metal-AIEgen frameworks (MAFs) and demonstrated the dual functions of protein detection and bacteria identification: (i) ultrasensitive point-of-care (POC) detection of sepsis biomarkers (100 times enhanced sensitivity); (ii) rapid POC identification of Gram-negative/positive bacteria (selective aggregation within 20 min). Fluorescent lateral flow immunoassays (LFAs) are convenient and inexpensive for POC tests. MAFs possess a large surface area, excellent photostability, high quantum yield (∼80%), and multiple active sites serving as protein binding domains for ultrasensitive detection of sepsis biomarkers (IL-6/PCT) on LFAs. The limit of detection (LOD) for IL-6/PCT is 0.252/0.333 pg/mL. Rapid appraisal of infectious bacteria is vital to guide the use of medicines. The dual-functional fluorescent MAFs have great potential in POC tests for the clinical diagnosis of bacterial infections.

8.
Nano Lett ; 23(24): 11874-11883, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38097378

RESUMO

Antibiotic resistance is a global threat. Antimicrobial peptides (AMPs) are highly desirable to treat multidrug-resistant pathogen infection. However, few AMPs are clinically available, due to high cost, instability, and poor selectivity. Here, ultrashort AMPs (2-3 residues with an N-terminal cysteine) are designed and assembled as gold nanoparticles. Au-S conjugation and ultrashort size restrict nonspecific reactions and peptide orientation, thus concentrating positively charged residues on the surface. The nanostructured assemblies enormously enhance antimicrobial abilities by 1000-6000-fold and stability. One representative (Au-Cys-Arg-NH2, Au_CR) shows selective antibacterial activity against Staphylococcus aureus with 10 nM minimal inhibitory concentration. Au_CR has comparable or better in vivo antimicrobial potency than vancomycin and methicillin, with low propensity to induce resistance, little side effects, and high stability (17.5 h plasma half-life). Au_CR acts by inducing collapse of membrane potential and rupture of the bacterial membrane. The report provides insights for developing AMP-metal nanohybrids, particularly tethering nonspecific reactions and AMP orientation on the metal surface.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Ouro/química , Dipeptídeos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Nanopartículas Metálicas/química , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana
9.
Plant J ; 112(2): 322-338, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35979653

RESUMO

Soil salinity is a significant threat to global agriculture. Understanding salt exclusion mechanisms in halophyte species may be instrumental in improving salt tolerance in crops. Puccinellia tenuiflora is a typical salt-excluding halophytic grass often found in potassium-deprived saline soils. Our previous work showed that P. tenuiflora possesses stronger selectivity for K+ than for Na+ ; however, the mechanistic basis of this phenomenon remained elusive. Here, P. tenuiflora PutHKT1;5 was cloned and the functions of PutHKT1;5 and PutSOS1 were characterized using heterologous expression systems. Yeast assays showed that PutHKT1;5 possessed Na+ transporting capacity and was highly selective for Na+ over K+ . PutSOS1 was located at the plasma membrane and operated as a Na+ /K+ exchanger, with much stronger Na+ extrusion capacity than its homolog from Arabidopsis. PutHKT2;1 mediated high-affinity K+ and Na+ uptake and its expression levels were upregulated by mild salinity and K+ deprivation. Salinity-induced changes of root PutHKT1;5 and PutHKT1;4 transcript levels matched the expression pattern of root PutSOS1, which was consistent with root Na+ efflux. The transcript levels of root PutHKT2;1 and PutAKT1 were downregulated by salinity. Taken together, these findings demonstrate that the functional activity of PutHKT1;5 and PutSOS1 in P. tenuiflora roots is fine-tuned under saline conditions as well as by operation of other ion transporters/channel (PutHKT1;4, PutHKT2;1, and PutAKT1). This leads to the coordination of radial Na+ and K+ transport processes, their loading to the xylem, or Na+ retrieval and extrusion under conditions of mild salinity and/or K+ deprivation.


Assuntos
Arabidopsis , Potássio , Potássio/metabolismo , Sódio/metabolismo , Salinidade , Poaceae/genética , Poaceae/metabolismo , Plantas Tolerantes a Sal/genética , Plantas Tolerantes a Sal/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Solo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
10.
Anal Chem ; 95(17): 6940-6947, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37083348

RESUMO

There is a growing urgent need for point-of-care testing (POCT) devices that integrate sample pretreatment and nucleic acid detection in a rapid, economical, and non-labor-intensive way. Here, we have developed an automated, portable nucleic acid detection system employing microfluidic chips integrating rotary valve-assisted sample pretreatment and recombinase polymerase amplification (RPA)-T7-Cas13a into one-step nucleic acid detection. The RPA and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a were integrated into a single-chamber reaction. As a validation model, we used this method to detect Group B streptococci (GBS) DNA and achieved a detection sensitivity of 8 copies/reaction, which is 6 times more sensitive than gold-standard polymerase chain reactions (PCRs). Dual specific recognition of RPA with CRISPR/Cas13a makes our method ultraspecific, with correct detection of Group B streptococci from 8 kinds of pathogenic bacteria. For the 16 positive and 24 negative clinical GBS samples, our assay achieved 100% accuracy compared to the PCR technique. The whole procedure can be automatically completed within 30 min, providing a more robust, sensitive, and accurate molecular diagnostic tool for POCT.


Assuntos
Ácidos Nucleicos , Recombinases , Microfluídica , Nucleotidiltransferases , Reação em Cadeia da Polimerase , Técnicas de Amplificação de Ácido Nucleico
11.
Small ; 19(26): e2207917, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36942987

RESUMO

The high throughput deposition of microscale objects with precise spatial arrangement represents a key step in microfabrication technology. This can be done by creating physical boundaries to guide the deposition process or using printing technologies; in both approaches, these microscale objects cannot be further modified after they are formed. The utilization of dynamic acoustic fields offers a novel approach to facilitate real-time reconfigurable miniaturized systems in a contactless manner, which can potentially be used in physics, chemistry, biology, as well as materials science. Here, the physical interactions of microscale objects in an acoustic pressure field are discussed and how to fabricate different acoustic trapping devices and how to tune the spatial arrangement of the microscale objects are explained. Moreover, different approaches that can dynamically modulate microscale objects in acoustic fields are presented, and the potential applications of the microarrays in biomedical engineering, chemical/biochemical sensing, and materials science are highlighted alongside a discussion of future research challenges.

12.
Exp Dermatol ; 32(10): 1598-1612, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37382420

RESUMO

Psoriasis is a chronic immune-mediated inflammatory skin disease that involves a complex interplay between infiltrated immune cells and keratinocytes. Great progress has been made in the research on the molecular mechanism of coding and non-coding genes, which has helped in clinical treatment. However, our understanding of this complex disease is far from clear. MicroRNAs (miRNAs) are small non-coding RNA molecules that are involved in post-transcriptional regulation, characterised by their role in mediating gene silencing. Recent studies on miRNAs have revealed their important role in the pathogenesis of psoriasis. We reviewed the current advances in the study of miRNAs in psoriasis; the existing research has found that dysregulated miRNAs in psoriasis notably affect keratinocyte proliferation and/or differentiation processes, as well as inflammation progress. In addition, miRNAs also influence the function of immune cells in psoriasis, including CD4+ T cells, dendritic cells, Langerhans cells and so on. In addition, we discuss possible miRNA-based therapy for psoriasis, such as the topical delivery of exogenous miRNAs, miRNA antagonists and miRNA mimics. Our review highlights the potential role of miRNAs in the pathogenesis of psoriasis, and we expect more research progress with miRNAs in the future, which will help us understand this complex skin disease more accurately.


Assuntos
Dermatite , MicroRNAs , Psoríase , Humanos , MicroRNAs/genética , Pele/patologia , Queratinócitos/fisiologia , Dermatite/patologia
13.
BMC Cancer ; 23(1): 514, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280528

RESUMO

BACKGROUND: The association involving mismatch repair (MMR) genes, molecular subtype and specific immune cell group in tumor microenvironment has been focused by more recent studies. Its prognosis value in lung adenocarcinoma (LUAD) neoadjuvant chemotherapy remains elusive. METHODS: The correlation between the MMR gene patterns and the immune landscape were comprehensively evaluated. The MMRScore was calculated using principal component analysis (PCA) after grouping using R/mclust package. The prognostic significance of the MMRScore was evaluated by Kaplan-merrier analysis. Then a cohort of 103 Chinese LUAD patients was collected for neoadjuvant chemotherapy prognosis evaluation and validation using MMRScore. RESULTS: Four MMRclusters (mc1, 2, 3, 4)-characterized by differences in extent of aneuploidy, expression of immunomodulatory (IM) genes, mRNA expression, lncRNA expression and prognosis were identified. We established MMRscore to quantify the MMR pattern of individual LUAD patients. As is shown in further analyses, the MMRscore was a potential independent prognostic factor of LUAD. Finally, the prognostic value of the MMRscore and its association with tumor immune microenvironment (TIME) of LUAD were verified in Chinese LUAD cohort. CONCLUSIONS: We demonstrated the correlation between MMR gene pattern, the CNV and tumor immune landscape in LUAD. A MMRcluster mc2 with high MMRscore, high TMB and high CNV subtype was identified with poor prognosis and infiltrating immunocyte. The comprehensive evaluation of MMR patterns in individual LUAD patients enhances the understanding of TIME and gives a new insight toward improved immune treatment strategies for LUAD patients compared to neoadjuvant chemotherapy.


Assuntos
Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Reparo de Erro de Pareamento de DNA/genética , Imunoterapia , Imunomodulação , Pulmão , Prognóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Microambiente Tumoral/genética
14.
Trends Analyt Chem ; 158: 116871, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36506265

RESUMO

The coronavirus disease 2019 (COVID-19) has extensively promoted the application of nucleic acid testing technology in the field of clinical testing. The most widely used polymerase chain reaction (PCR)-based nucleic acid testing technology has problems such as complex operation, high requirements of personnel and laboratories, and contamination. The highly miniaturized microfluidic chip provides an essential tool for integrating the complex nucleic acid detection process. Various microfluidic chips have been developed for the rapid detection of nucleic acid, such as amplification-free microfluidics in combination with clustered regularly interspaced short palindromic repeats (CRISPR). In this review, we first summarized the routine process of nucleic acid testing, including sample processing and nucleic acid detection. Then the typical microfluidic chip technologies and new research advances are summarized. We also discuss the main problems of nucleic acid detection and the future developing trend of the microfluidic chip.

15.
RNA Biol ; 20(1): 334-347, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-37310201

RESUMO

Psoriasis is a chronic inflammatory skin disease characterized by skin infiltration of immune cells and abnormal epidermal thickening. The initial pathogenesis has not been fully elucidated. Non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs) and circular RNAs (circRNAs), comprise the majority of genome transcripts and are important influencers of gene transcription and post-transcription modulations. Emerging roles of ncRNAs in psoriasis were identified recently. This review summarizes the existing studies of psoriasis-related lncRNAs and circRNAs. A considerable proportion of the studied lncRNAs and circRNAs regulate keratinocyte mobility, such as keratinocyte proliferation and differentiation. Some lncRNAs and circRNAs are tightly related to keratinocyte inflammation reactions. Other reports demonstrated that they are also implicated in modulating immune cell differentiation, proliferation, and activation. This review might illuminate future psoriasis research and highlight that lncRNAs and circRNAs might act as therapeutic targets.


Assuntos
Psoríase , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Circular/genética , Psoríase/genética , Pele , Queratinócitos
16.
BMC Endocr Disord ; 23(1): 271, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057752

RESUMO

BACKGROUND: The association involving N6-methyladenosine (m6A) modification, molecular subtype and specific immune cell group in tumor microenvironment has been the focus of recent studies. The underlying function of m6A modification in thyroid cancer (TC) remains elusive. METHODS: The m6A modification regulations, molecular character and tumor immune profile of 461 TC patients were explored and then the correlation between them were comprehensively evaluated. The m6Ascore was established using principal component analysis (PCA) to quantify the m6A pattern of individual TC patients. The prognostic significance of the m6Ascore was evaluated by multivariate Cox regression analysis. RESULTS: Four m6Aclusters (mc1, 2, 3, 4)-characterized by differences in extent of aneuploidy, expression of immunomodulatory genes, mRNA or lncRNA expression pattern and prognosis were identified. T Preliminary validation of m6Ascore was a potential independent prognostic factor of TC involving in mc3. Finally, the prognostic value of the m6Ascore and its association with copy number variation (CNV) and tumor immune microenvironment (TIME) of TC in mc3 were verified. CONCLUSIONS: The correlation between m6A modification, the copy number burden and tumor immune landscape in TC was demonstrated. A m6Acluster-mc3 with low m6Ascore and high CNV molecular subtype was identified with poor clinical prognosis, low infiltrating immunocyte and weak effector T cell. A three-gene clinical prognosis model for TC based on 4 m6a cluster expression was established. Understanding of TIME is enhanced by comprehensive assessment of m6A patterns in individual TC patients and gives a new insight toward improved immunotherapy strategies for TC cancer patients.


Assuntos
Variações do Número de Cópias de DNA , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Adenina , Imunomodulação , Microambiente Tumoral/genética
17.
J Nanobiotechnology ; 21(1): 128, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37046252

RESUMO

Chronic non-healing wounds, a prevalent complication of diabetes, are associated with increased mortality in diabetic patients. Excessive accumulation of M1 macrophages in diabetic wounds promotes inflammation and results in dysregulated tissue repair. Adipose tissue macrophages (ATMs) derived from healthy lean donors have the ability to improve glucose tolerance and insulin sensitivity, as well as modulate inflammation. MicroRNAs (miRs), which can be packaged into exosomes (Exos) and secreted from cells, serve as essential regulators of macrophage polarization. Here, we revealed that ATMs isolated from lean mice secrete miRs-containing Exos, which modulate macrophage polarization and promote rapid diabetic wound healing when administered to diabetes-prone db/db mice. The miRs sequence of tissue samples from wounds treated with Exos secreted by lean ATMs (ExosLean) revealed that miR-222-3p was up-regulated. Further analyses showed that inhibiting miR-222-3p using a miR inhibitor impaired the macrophage-reprogramming effect of ExosLean. In the excisional skin wound mouse model, locally inhibiting miR-222-3p disrupted healing dynamics and failed to modulate macrophage polarization. Mechanistic studies revealed a connection between miR-222-3p, Bcl2l11/Bim, an inflammatory response effector, macrophage polarization, and diabetic wound healing. In summary, ExosLean act as positive regulators of macrophage polarization by regulating miR levels in wounds and accelerating wound healing, and thus have important implications for wound management in diabetes.


Assuntos
Diabetes Mellitus , Exossomos , MicroRNAs , Camundongos , Animais , Tecido Adiposo , MicroRNAs/genética , MicroRNAs/farmacologia , Inflamação , Macrófagos , Cicatrização
18.
Nano Lett ; 22(18): 7554-7562, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36122317

RESUMO

Safe and effective local drug delivery is challenging due to complex physiological barriers that limit the entry of drugs. Here, we report the metal-polymer conductors (MPCs) for local drug delivery via iontophoresis or electroporation. The MPCs are stretchable, conductive, and biocompatible. The flexible MPCs of different geometries are used both on a dry, flat surface (skin) and a moist, curved surface (cornea) with conformability. Conformal integration with the tissues enables good mechanical/electrical properties and realizes application of electrical voltage to the target areas for local drug delivery. By iontophoresis and electroporation, the MPCs achieve efficient delivery of doxorubicin and siRNA, leading to tumor regression and inhibition of corneal neovascularization, respectively. Our work presents an efficient strategy to harness the power of the MPCs to broaden the scope of local drug delivery to dry and wet organs with different surface topography.


Assuntos
Iontoforese , Polímeros , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Eletroporação , Metais , RNA Interferente Pequeno
19.
Nano Lett ; 22(9): 3576-3582, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35486905

RESUMO

Nanomaterials usually kill bacteria via multiple mechanisms which are not explicit to the same degree as those of conventional antibiotics. This situation may hinder the development of novel nanoscale antibiotics. Here, we present aminophenol (AP) to modify gold nanoparticles (AP_Au NPs) which show a broad antibacterial spectrum and potent antibacterial effects against multidrug-resistant (MDR) bacteria with clear antibacterial mechanisms. AP_Au NPs can not only damage bacterial cell walls but also bind to the 16S rRNA to block bacterial protein synthesis. Moreover, AP_Au NPs show excellent performance in curing abdominal bacterial infections in an in vivo model. AP_Au NPs thus have the potential to become a novel antibacterial agent for clinical applications.


Assuntos
Infecções Bacterianas , Nanopartículas Metálicas , Aminofenóis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Infecções Bacterianas/tratamento farmacológico , Ouro/farmacologia , Humanos , Nanopartículas Metálicas/uso terapêutico , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S
20.
Nano Lett ; 22(3): 1091-1099, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35089039

RESUMO

The potential toxicity of nanoplastics on plants has previously been illustrated, but whether nanoplastics could cause neurotoxicity, especially to higher animals, remains unclear. We now demonstrate that nanoplastics can be deposited in the brain via nasal inhalation, triggering neuron toxicity and altering the animal behavior. Polystyrene nanoparticles (PS-NPs) of PS-COOH and PS-NH2 are used as models for nanoplastics. We designed a microfluidic chip to evaluate the PS-NPs with different concentrations, surface ligands, and sizes to interact with neurons. Smaller PS-NPs can induce more cellular uptake than larger PS-NPs. PS-NPs with a size of 80 nm can reach and deposit in the brain of mice via aerosol inhalation. Mice inhaling PS-NPs exhibit fewer activities in comparison to those inhaling water droplets. An obvious neurotoxicity of the nanoplastics could be observed from the results of the inhibition of AChE activities. Our results show the potential significance of the physiochemical properties of organic nanoplastics on depositing in mammalian brains by nasal inhalation.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Animais , Comportamento Animal , Encéfalo/metabolismo , Camundongos , Microplásticos , Nanopartículas/química , Neurônios/metabolismo , Poliestirenos/química , Poliestirenos/toxicidade , Poluentes Químicos da Água/química
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