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1.
Nature ; 610(7930): 205-211, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36171285

RESUMO

Translation is the fundamental process of protein synthesis and is catalysed by the ribosome in all living cells1. Here we use advances in cryo-electron tomography and sub-tomogram analysis2,3 to visualize the structural dynamics of translation inside the bacterium Mycoplasma pneumoniae. To interpret the functional states in detail, we first obtain a high-resolution in-cell average map of all translating ribosomes and build an atomic model for the M. pneumoniae ribosome that reveals distinct extensions of ribosomal proteins. Classification then resolves 13 ribosome states that differ in their conformation and composition. These recapitulate major states that were previously resolved in vitro, and reflect intermediates during active translation. On the basis of these states, we animate translation elongation inside native cells and show how antibiotics reshape the cellular translation landscapes. During translation elongation, ribosomes often assemble in defined three-dimensional arrangements to form polysomes4. By mapping the intracellular organization of translating ribosomes, we show that their association into polysomes involves a local coordination mechanism that is mediated by the ribosomal protein L9. We propose that an extended conformation of L9 within polysomes mitigates collisions to facilitate translation fidelity. Our work thus demonstrates the feasibility of visualizing molecular processes at atomic detail inside cells.


Assuntos
Microscopia Crioeletrônica , Mycoplasma pneumoniae , Biossíntese de Proteínas , Proteínas Ribossômicas , Ribossomos , Antibacterianos/farmacologia , Mycoplasma pneumoniae/citologia , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/metabolismo , Mycoplasma pneumoniae/ultraestrutura , Elongação Traducional da Cadeia Peptídica/efeitos dos fármacos , Polirribossomos/efeitos dos fármacos , Polirribossomos/metabolismo , Polirribossomos/ultraestrutura , Biossíntese de Proteínas/efeitos dos fármacos , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/ultraestrutura , Ribossomos/efeitos dos fármacos , Ribossomos/metabolismo , Ribossomos/ultraestrutura
2.
Genome Res ; 34(6): 822-836, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39009472

RESUMO

N 6-Methyladenosine (m6A) is a prevalent and highly regulated RNA modification essential for RNA metabolism and normal brain function. It is particularly important in the hippocampus, where m6A is implicated in neurogenesis and learning. Although extensively studied, its presence in specific cell types remains poorly understood. We investigated m6A in the hippocampus at a single-cell resolution, revealing a comprehensive landscape of m6A modifications within individual cells. Through our analysis, we uncovered transcripts exhibiting a dense m6A profile, notably linked to neurological disorders such as Alzheimer's disease. Our findings suggest a pivotal role of m6A-containing transcripts, particularly in the context of CAMK2A neurons. Overall, this work provides new insights into the molecular mechanisms underlying hippocampal physiology and lays the foundation for future studies investigating the dynamic nature of m6A RNA methylation in the healthy and diseased brain.


Assuntos
Adenosina , Hipocampo , Análise de Célula Única , Hipocampo/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Análise de Célula Única/métodos , Camundongos , Neurônios/metabolismo , Processamento Pós-Transcricional do RNA , Metilação , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , RNA/metabolismo , RNA/genética , Humanos , Metilação de RNA
3.
Plant Cell ; 36(10): 4293-4308, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39056470

RESUMO

In Arabidopsis (Arabidopsis thaliana), overproduction of salicylic acid (SA) increases disease resistance and abiotic stress tolerance but penalizes growth. This growth-defense trade-off has hindered the adoption of SA-based disease management strategies in agriculture. However, investigation of how SA inhibits plant growth has been challenging because many SA-hyperaccumulating Arabidopsis mutants have developmental defects due to the pleiotropic effects of the underlying genes. Here, we heterologously expressed a bacterial SA synthase gene in Arabidopsis and observed that elevated SA levels decreased plant growth and reduced the expression of cold-regulated (COR) genes in a dose-dependent manner. Growth suppression was exacerbated at below-ambient temperatures. Severing the SA-responsiveness of individual COR genes was sufficient to overcome the growth inhibition caused by elevated SA at ambient and below-ambient temperatures while preserving disease- and abiotic-stress-related benefits. Our results show the potential of decoupling SA-mediated growth and defense trade-offs for improving crop productivity.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Ácido Salicílico , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Plantas Geneticamente Modificadas , Estresse Fisiológico/genética
4.
Proc Natl Acad Sci U S A ; 120(15): e2213149120, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37027429

RESUMO

Cryoelectron tomography directly visualizes heterogeneous macromolecular structures in their native and complex cellular environments. However, existing computer-assisted structure sorting approaches are low throughput or inherently limited due to their dependency on available templates and manual labels. Here, we introduce a high-throughput template-and-label-free deep learning approach, Deep Iterative Subtomogram Clustering Approach (DISCA), that automatically detects subsets of homogeneous structures by learning and modeling 3D structural features and their distributions. Evaluation on five experimental cryo-ET datasets shows that an unsupervised deep learning based method can detect diverse structures with a wide range of molecular sizes. This unsupervised detection paves the way for systematic unbiased recognition of macromolecular complexes in situ.


Assuntos
Tomografia com Microscopia Eletrônica , Processamento de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador/métodos , Análise por Conglomerados , Estrutura Molecular , Tomografia com Microscopia Eletrônica/métodos , Substâncias Macromoleculares/química , Microscopia Crioeletrônica/métodos
5.
J Cell Sci ; 136(23)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38126809

RESUMO

Regulation of glucose transport, which is central for control of whole-body metabolism, is determined by the amount of GLUT4 glucose transporter (also known as SLC2A4) in the plasma membrane (PM) of fat and muscle cells. Physiologic signals [such as activated insulin receptor or AMP-activated protein kinase (AMPK)] increase PM GLUT4. Here, we show that the distribution of GLUT4 between the PM and interior of human muscle cells is dynamically maintained, and that AMPK promotes PM redistribution of GLUT4 by regulating exocytosis and endocytosis. Stimulation of exocytosis by AMPK is mediated by Rab10 and the Rab GTPase-activating protein TBC1D4. APEX2 proximity mapping reveals that GLUT4 traverses both PM-proximal and PM-distal compartments in unstimulated muscle cells, further supporting retention of GLUT4 by a constitutive retrieval mechanism. AMPK-stimulated translocation involves GLUT4 redistribution among the same compartments traversed in unstimulated cells, with a significant recruitment of GLUT4 from the Golgi and trans-Golgi network compartments. Our comprehensive proximal protein mapping provides an integrated, high-density, whole-cell accounting of the localization of GLUT4 at a resolution of ∼20 nm that serves as a structural framework for understanding the molecular mechanisms regulating GLUT4 trafficking downstream of different signaling inputs in a physiologically relevant cell type.


Assuntos
Transportador de Glucose Tipo 4 , Células Musculares , Proteoma , Humanos , Proteínas Quinases Ativadas por AMP , Membrana Celular , Músculos , Transportador de Glucose Tipo 4/metabolismo
6.
J Cell Mol Med ; 28(16): e70022, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39205384

RESUMO

Under the long-term pressure overload stimulation, the heart experiences embryonic gene activation, leading to myocardial hypertrophy and ventricular remodelling, which can ultimately result in the development of heart failure. Identifying effective therapeutic targets is crucial for the prevention and treatment of myocardial hypertrophy. Histone lysine lactylation (HKla) is a novel post-translational modification that connects cellular metabolism with epigenetic regulation. However, the specific role of HKla in pathological cardiac hypertrophy remains unclear. Our study aims to investigate whether HKla modification plays a pathogenic role in the development of cardiac hypertrophy. The results demonstrate significant expression of HKla in cardiomyocytes derived from an animal model of cardiac hypertrophy induced by transverse aortic constriction surgery, and in neonatal mouse cardiomyocytes stimulated by Ang II. Furthermore, research indicates that HKla is influenced by glucose metabolism and lactate generation, exhibiting significant phenotypic variability in response to various environmental stimuli. In vitro experiments reveal that exogenous lactate and glucose can upregulate the expression of HKla and promote cardiac hypertrophy. Conversely, inhibition of lactate production using glycolysis inhibitor (2-DG), LDH inhibitor (oxamate) and LDHA inhibitor (GNE-140) reduces HKla levels and inhibits the development of cardiac hypertrophy. Collectively, these findings establish a pivotal role for H3K18la in pathological cardiac hypertrophy, offering a novel target for the treatment of this condition.


Assuntos
Cardiomegalia , Histonas , Ácido Láctico , Miócitos Cardíacos , Animais , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Histonas/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Miócitos Cardíacos/efeitos dos fármacos , Camundongos , Ácido Láctico/metabolismo , Processamento de Proteína Pós-Traducional , Modelos Animais de Doenças , Glucose/metabolismo , Masculino , Lisina/metabolismo , Camundongos Endogâmicos C57BL , Glicólise
7.
J Gen Virol ; 105(9)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39331030

RESUMO

Human noroviruses are the most common cause of viral gastroenteritis, resulting annually in 219 000 deaths and a societal cost of $60 billion, and no antivirals or vaccines are available. The minor capsid protein may play a significant role in the evolution of norovirus. GII.4 is the predominant genotype of norovirus, and its VP2 undergoes epochal co-evolution with the major capsid protein VP1. Since the sudden emergence of norovirus GII.2[P16] in 2016, it has consistently remained a significant epidemic strain in recent years. In the construction of phylogenetic trees, the phylogenetic trees of VP2 closely parallel those of VP1 due to the shared tree topology of both proteins. To investigate the interaction patterns between the major and minor capsid proteins of norovirus GII.2, we chose five representative strains of GII.2 norovirus and investigated their evolutionary patterns using a yeast two-hybrid experiment. Our study shows VP1-VP2 interaction in GII.2, with critical interaction sites at 167-178 and 184-186 in the highly variable region. In the intra-within GII.2, we observed no temporal co-evolution between VP1 and VP2 of GII.2. Notable distinctions were observed in the interaction intensity of VP2 among inter-genotype (P<0.05), highlighting the divergent evolutionary patterns of VP2 within different norovirus genotypes. In summary, the interactions between VP2 and VP1 of GII.2 norovirus exhibit out-of-sync evolutionary patterns. This study offered valuable insights for further understanding and completing the evolutionary mechanism of norovirus.


Assuntos
Proteínas do Capsídeo , Evolução Molecular , Norovirus , Filogenia , Norovirus/genética , Norovirus/classificação , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Humanos , Infecções por Caliciviridae/virologia , Genótipo , Técnicas do Sistema de Duplo-Híbrido , Ligação Proteica , Gastroenterite/virologia
8.
Nat Methods ; 18(2): 186-193, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33542511

RESUMO

Cryo-electron microscopy (cryo-EM) enables macromolecular structure determination in vitro and inside cells. In addition to aligning individual particles, accurate registration of sample motion and three-dimensional deformation during exposures are crucial for achieving high-resolution reconstructions. Here we describe M, a software tool that establishes a reference-based, multi-particle refinement framework for cryo-EM data and couples a comprehensive spatial deformation model to in silico correction of electron-optical aberrations. M provides a unified optimization framework for both frame-series and tomographic tilt-series data. We show that tilt-series data can provide the same resolution as frame-series data on a purified protein specimen, indicating that the alignment step no longer limits the resolution obtainable from tomographic data. In combination with Warp and RELION, M resolves to residue level a 70S ribosome bound to an antibiotic inside intact bacterial cells. Our work provides a computational tool that facilitates structural biology in cells.


Assuntos
Antibacterianos/metabolismo , Microscopia Crioeletrônica/métodos , Ribossomos/metabolismo , Processamento de Imagem Assistida por Computador/métodos , Interface Usuário-Computador
9.
J Med Virol ; 96(3): e29487, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38482901

RESUMO

Human norovirus (HuNoV) is the most predominant viral agents of acute gastroenteritis. Point-of-care testing (POCT) based on lateral flow immunochromatography (LIFC) has become an important tool for rapid diagnosis of HuNoVs. However, low sensitivity and lack of quantitation are the bottlenecks of traditional LIFC. Thus, we established a rapid and accurate technique that combined immunomagnetic enrichment (IM) with LFIC to identify GII HuNoVs in fecal specimens. Before preparing immunofluorescent nanomagnetic microspheres and achieving the effect of HuNoV enrichment in IM and fluorescent signal in LFIC, amino-functionalized magnetic beads (MBs) and carboxylated quantum dots (QDs) were coupled at a mass ratio of 4:10. Anti-HuNoV monoclonal antibody was then conjugated with QDs-MB. The limit of detection was 1.56 × 104 copies/mL, and the quantitative detection range was 1.56 × 104 copies/mL-1 × 106 copies/mL under optimal circumstances. The common HuNoV genotypes GII.2, GII.3, GII.4, and GII.17 can be detected, there was no cross-reaction with various enteric viruses, including rotavirus, astrovirus, enterovirus, and sapovirus. A comparison between IM-LFIC and RT-qPCR for the detection of 87 fecal specimens showed a high level of agreement (kappa = 0.799). This suggested that the method is rapid and sensitive, making it a promising option for point-of-care testing in the future.


Assuntos
Infecções por Caliciviridae , Gastroenterite , Norovirus , Rotavirus , Sapovirus , Humanos , Norovirus/genética , Microesferas , Rotavirus/genética , Sapovirus/genética , Fezes , Infecções por Caliciviridae/diagnóstico
10.
Microb Pathog ; 194: 106792, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39004153

RESUMO

Foodborne pathogens have become a major concern for public health. Bacillus cereus, a representative foodborne pathogen, is particularly challenging due to its ability to cause food poisoning and its resilient spores that are difficult to completely eradicate. Therefore, it is crucial to develop measures to prevent and control B. cereus. Bacteriophages, which are high specific towards their host strains and cannot infect eukaryotes, have proven to be effective in combating foodborne pathogens and are safe for human use. In this study, we isolated and characterized a novel bacteriophage named vBce-DP7 that specifically targets B. cereus strains belonging to three different sequence types (STs). Phage vBce-DP7 is a lytic one and has a short latent time of only 15 min. Moreover, it exhibites a good temperature tolerance, retaining high activity across a broad range of 4-55 ℃. Additionally, its activity remains unaffected within a wide pH range spanning from 2 to 10. Interestingly, with only 4 % genetic similarity with known bacteriophages, vBce-DP7 shows a possible classification on a family level though it shares many similar functional proteins with Salasmaviridae bacteriophages. Taken together, vBce-DP7 demonstrates its significant potential for further exploration in terms of phage diversity and its application in controlling B. cereus.


Assuntos
Fagos Bacilares , Bacillus cereus , Genoma Viral , Especificidade de Hospedeiro , Filogenia , Temperatura , Bacillus cereus/virologia , Fagos Bacilares/isolamento & purificação , Fagos Bacilares/classificação , Fagos Bacilares/genética , Fagos Bacilares/fisiologia , Concentração de Íons de Hidrogênio , DNA Viral/genética
11.
Cancer Cell Int ; 24(1): 299, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39182054

RESUMO

It is accepted that cancer stem cells (CSCs) are key to the occurrence, progression, drug resistance, and recurrence of bladder cancer (BLCA). Here, we aimed to characterize the landscapes of CSCs and investigate the biological and clinical signatures based on a prognostic model constructed by genes associated with CSCs. The malignant epithelial cells were discovered and sorted into six clusters through single cell analysis. C2 was identified as the CSCs. The signaling involved in the interactions between C2, cancer-associated fibroblasts (CAFs), and immune cells mainly consisted of MK, THBS, ANGPTL, VISFATIN, JAM, and ncWNT pathways. The CSC-like prognostic index (CSCLPI) constructed by the random survival forest was a reliable risk factor for BLCA and had a stable and powerful effect on predicting the overall survival of patients with BLCA. The level of CAFs was higher among patients with higher CSCLPI scores, suggesting that CAFs play a significant role in regulating biological characteristics. The CSCLPI-developed survival prediction nomogram has the potential to be applied clinically to predict the 1-, 2-, 3-, and 5-year overall survival of patients with BLCA. The CSCLPI can be used for prognostic prediction and drug treatment evaluation in the clinic.

12.
Chemistry ; 30(24): e202304287, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38380560

RESUMO

Aqueous zinc ion batteries have been extensively researched due to their distinctive advantages such as low cost and high safety. Vanadium oxides are important cathode materials, however, poor cycle life caused by vanadium dissolution limits their application. Recent studies show that the lattice NH4 + in vanadium oxides can act as a pillar to enhance structural stability and play a crucial role in improving its cycling stability. Nevertheless, there is still a lack of research on the effect of the lattice NH4 + content on structural evolution and electrochemical performance. Herein, we synthesize vanadium oxides with different contents of lattice NH4 + by a one-step hydrothermal reaction. The vanadium oxides with lattice NH4 + exhibit high initial capacity, as well as good cycling stability and rate performance compared to bare vanadium oxide. Combined with electrochemical analyses, ex-situ structural characterizations, and in-situ X-ray diffraction tests, we reveal that the lattice NH4 + content plays a positive role in vanadium oxides' structural stability and cation diffusion kinetics. This work presents a direction for designing high-performance vanadium cathodes for aqueous zinc ion batteries.

13.
Fish Shellfish Immunol ; 151: 109708, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38908810

RESUMO

Leukocyte-derived chemotaxin-2 (LECT2) is a multifunctional immunoregulator that plays several pivotal roles in the host's defense against pathogens. This study aimed to elucidate the specific functions and mechanisms of LECT2 (CaLECT2) in the northern snakehead (Channa argus) during infections with pathogens such as Nocardia seriolae (N. seriolae). We identified CaLECT2 in the northern snakehead, demonstrating its participation in the immune response to N. seriolae infection. CaLECT2 contains an open reading frame (ORF) of 459 bp, encoding a peptide of 152 amino acids featuring a conserved peptidase M23 domain. The CaLECT2 protein shares 62%-84 % identities with proteins from various other fish species. Transcriptional expression analysis revealed that CaLECT2 was constitutively expressed in all examined tissues, with the highest expression observed in the liver. Following intraperitoneal infection with N. seriolae, CaLECT2 transcription increased in the spleen, trunk kidney, and liver. In vivo challenge experiments showed that injecting recombinant CaLECT2 (rCaLECT2) could protect the snakehead against N. seriolae infection by reducing bacterial load, enhancing serum antibacterial activity and antioxidant capacity, and minimizing tissue damage. Moreover, in vitro analysis indicated that rCaLECT2 significantly enhanced the migration, respiratory burst, and microbicidal activity of the head kidney-derived phagocytes. These findings provide new insights into the role of LECT2 in the antibacterial immunity of fish.


Assuntos
Doenças dos Peixes , Proteínas de Peixes , Imunidade Inata , Nocardiose , Nocardia , Animais , Nocardiose/veterinária , Nocardiose/imunologia , Nocardia/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Imunidade Inata/genética , Filogenia , Sequência de Aminoácidos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Regulação da Expressão Gênica/imunologia , Alinhamento de Sequência/veterinária , Perfilação da Expressão Gênica/veterinária , Peixes/imunologia , Peixes/genética , Perciformes/imunologia , Perciformes/genética , Sequência de Bases
14.
Appl Microbiol Biotechnol ; 108(1): 156, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38244075

RESUMO

Cardiometabolic disease (CMD) encompasses a range of diseases such as hypertension, atherosclerosis, heart failure, obesity, and type 2 diabetes. Recent findings about CMD's interaction with gut microbiota have broadened our understanding of how diet and nutrition drive microbes to influence CMD. However, the translation of basic research into the clinic has not been smooth, and dietary nutrition and probiotic supplementation have yet to show significant evidence of the therapeutic benefits of CMD. In addition, the published reviews do not suggest the core microbiota or metabolite classes that influence CMD, and systematically elucidate the causal relationship between host disease phenotypes-microbiome. The aim of this review is to highlight the complex interaction of the gut microbiota and their metabolites with CMD progression and to further centralize and conceptualize the mechanisms of action between microbial and host disease phenotypes. We also discuss the potential of targeting modulations of gut microbes and metabolites as new targets for prevention and treatment of CMD, including the use of emerging technologies such as fecal microbiota transplantation and nanomedicine. KEY POINTS: • To highlight the complex interaction of the gut microbiota and their metabolites with CMD progression and to further centralize and conceptualize the mechanisms of action between microbial and host disease phenotypes. • We also discuss the potential of targeting modulations of gut microbes and metabolites as new targets for prevention and treatment of CMD, including the use of emerging technologies such as FMT and nanomedicine. • Our study provides insight into identification-specific microbiomes and metabolites involved in CMD, and microbial-host changes and physiological factors as disease phenotypes develop, which will help to map the microbiome individually and capture pathogenic mechanisms as a whole.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Insuficiência Cardíaca , Microbiota , Humanos , Microbioma Gastrointestinal/fisiologia , Diabetes Mellitus Tipo 2/terapia , Dieta
15.
Appl Opt ; 63(10): A70-A77, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568513

RESUMO

Tungsten oxide (W O 3) has been widely used in hydrogen sensing due to its stable chemical properties and high oxygen vacancy diffusion coefficient. However, the response of pure W O 3 to hydrogen is slow, and doping is an effective way to improve the hydrogen sensing performance of W O 3 materials. In this paper, W O 3/P t/P E G/S i O 2 porous film was prepared by the sol-gel method using tungsten powder, H 2 O 2 and C 2 H 5 O H as precursors, polyethylene glycol (PEG) as the pore-forming agent, and tetraethyl orthosilicate (TEOS) as the S i O 2 source material. The sensing properties of the W O 3 composite for hydrogen were characterized by a transmission optical fiber hydrogen sensing system made at home. The process parameters such as water bath time, aging time, W:PEG ratio, and W:TEOS ratio were optimized to improve the sensitivity and response time of the sensing film. The experimental results indicate that the sensitivity is 15.68%, the average response time is 45 s, and the repeatability is up to 98.74% in 16 consecutive tests. The linearity index R 2 is 0.9946 within the hydrogen concentration range of 5000 ppm to 50,000 ppm. The film responds only to H 2 when the concentration of interfering gases (C H 4, CO, C O 2) is 2000 ppm. The hydrogen sensing performance of the optimized film is significantly improved compared with that of the undoped film.

16.
Photodermatol Photoimmunol Photomed ; 40(4): e12987, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38968385

RESUMO

BACKGROUND: Skin microbiota is essential for health maintenance. Photoaging is the primary environmental factor that affects skin homeostasis, but whether it influences the skin microbiota remains unclear. OBJECTIVE: The objective of this study is to investigate the relationship between photoaging and skin microbiome. METHODS: A cohort of senior bus drivers was considered as a long-term unilateral ultraviolet (UV) irradiated population. 16S rRNA amplicon sequencing was conducted to assess skin microbial composition variations on different sides of their faces. The microbiome characteristics of the photoaged population were further examined by photoaging guinea pig models, and the correlations between microbial metabolites and aging-related cytokines were analyzed by high-throughput sequencing and reverse transcription polymerase chain reaction. RESULTS: Photoaging decreased the relative abundance of microorganisms including Georgenia and Thermobifida in human skin and downregulated the generation of skin microbe-derived antioxidative metabolites such as ectoin. In animal models, Lactobacillus and Streptobacillus abundance in both the epidermis and dermis dropped after UV irradiation, resulting in low levels of skin antioxidative molecules and leading to elevated expressions of the collagen degradation factors matrix metalloproteinase (MMP)-1 and MMP-2 and inflammatory factors such as interleukin (IL)-1ß and IL-6. CONCLUSIONS: Skin microbial characteristics have an impact in photoaging and the loss of microbe-derived antioxidative metabolites impairs skin cells and accelerates the aging process. Therefore, microbiome-based therapeutics may have potential in delaying skin aging.


Assuntos
Microbiota , Envelhecimento da Pele , Pele , Raios Ultravioleta , Humanos , Animais , Cobaias , Pele/microbiologia , Pele/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , RNA Ribossômico 16S
17.
PLoS Genet ; 17(3): e1009355, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33760820

RESUMO

Neurogenesis in the developing neocortex begins with the generation of the preplate, which consists of early-born neurons including Cajal-Retzius (CR) cells and subplate neurons. Here, utilizing the Ebf2-EGFP transgenic mouse in which EGFP initially labels the preplate neurons then persists in CR cells, we reveal the dynamic transcriptome profiles of early neurogenesis and CR cell differentiation. Genome-wide RNA-seq and ChIP-seq analyses at multiple early neurogenic stages have revealed the temporal gene expression dynamics of early neurogenesis and distinct histone modification patterns in early differentiating neurons. We have identified a new set of coding genes and lncRNAs involved in early neuronal differentiation and validated with functional assays in vitro and in vivo. In addition, at E15.5 when Ebf2-EGFP+ cells are mostly CR neurons, single-cell sequencing analysis of purified Ebf2-EGFP+ cells uncovers molecular heterogeneities in CR neurons, but without apparent clustering of cells with distinct regional origins. Along a pseudotemporal trajectory these cells are classified into three different developing states, revealing genetic cascades from early generic neuronal differentiation to late fate specification during the establishment of CR neuron identity and function. Our findings shed light on the molecular mechanisms governing the early differentiation steps during cortical development, especially CR neuron differentiation.


Assuntos
Diferenciação Celular , Genômica , Neurogênese/genética , Neurônios/metabolismo , Lobo Temporal/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores , Diferenciação Celular/genética , Células Cultivadas , Córtex Cerebral/metabolismo , Expressão Gênica , Regulação da Expressão Gênica , Genes Reporter , Heterogeneidade Genética , Genômica/métodos , Histonas , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Neurônios/citologia , RNA Longo não Codificante/genética , Análise de Célula Única , Fatores de Transcrição , Sítio de Iniciação de Transcrição
18.
BMC Surg ; 24(1): 161, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762478

RESUMO

BACKGROUND: Because the cases are quite scarce, we aimed to review cases of foreign body impaction penetrating the neck through the esophagus to analyze the characteristics of these cases. The open surgery skills of the surgeon, the treatment procedure and the surgeons' experience in the rare diseases were analyzed. METHODS: We collected and analyzed all cases from 2015-2020 in our hospital. Surgical skills and procedures for fasting and anti-infection treatment were reviewed retrospectively. Follow-up was telephone communication. RESULTS: Our series included 15 cases. Tenderness in the pre-cervical site was a physical sign for screening. Thirteen cases underwent a lateral neck open surgery with the incision including the left side of neck and only two cases were incised from the right side of the neck. Pus was found 3 days after the impaction in one case, the shortest time observed in our series. The esophageal laceration was only sutured primarily in 5 cases (33.33%) among all fifteen cases. After sufficient drainage (average more than 9 days), antibiotic treatment and fasting (normally 2-3 weeks), patients gradually began to switch to solid foods from fluids after complete blood counts and confirmations from esophageal radiography result. No severe complications occurred, and all the patients have no swallowing dis-function and recovered well. CONCLUSION: Surgery should be performed as soon as possible after impaction. Lateral neck approach surgery and the therapeutic procedure described in this article are safe and effective treatments.


Assuntos
Esôfago , Corpos Estranhos , Pescoço , Humanos , Corpos Estranhos/cirurgia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Esôfago/cirurgia , Pescoço/cirurgia , Adulto Jovem , Adolescente , Idoso
19.
Nano Lett ; 23(12): 5762-5769, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37310729

RESUMO

Lithium-sulfur batteries (LSBs) are known to be potential next-generation energy storage devices. Recently, our group reported an LSB cathode made using sulfur spheres that has been spherically templated by MXene nanosheets decorated with CoSe2 nanoparticles, forming a "loose-templating" configuration. It was postulated that the minimal restacking of the outer nanoparticle-decorated MXene layer helps to enable facile ionic transport. However, as the nanosheets do not adhere conformally to the internal sphere's surface, such a configuration can be controversial, thus requiring a more systematic understanding. In this work, we report and quantify for the first time the independent and dependent variables involved in this morphology, allowing us to identify that having smaller nanoparticles resulted in better Li+ ion transport and enhanced electrochemical performances. The optimized cathode structure exhibited an initial specific capacity of 1274 mAh/g and a 0.06% decay rate per cycle at 0.5 C over 1000 cycles in LSBs.

20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 161-168, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38686711

RESUMO

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable. Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the Department of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing University of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy+laparoscopic primary resection+hepatectomy)and a microwave ablation group(conversion therapy+laparoscopic primary resection+microwave ablation).The surgical indicators(operation duration,time to first postoperative anal exhaust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens. Results A total of 198 patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first postoperative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as incision infection(P=0.740),anastomotic fistula(P=1.000),and anastomotic stenosis(P=1.000),the overall survival period(P=0.191),and the disease-free survival period(P=0.934)showed no significant differences between the two groups. Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection+surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outperformed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Micro-Ondas , Humanos , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Micro-Ondas/uso terapêutico , Laparoscopia/métodos , Masculino , Feminino , Resultado do Tratamento , Fluoruracila/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Taxa de Sobrevida
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