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JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

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Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

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Purpose: To investigate and analyse the status quo of the self-management of patients living with HIV/AIDS (PLWHA) and its influencing factors and to provide the basis for formulating intervention strategies. Methods: In this cross-sectional study, 300 PLWHA who visited the Infection Center of Beijing Youan Hospital, Capital Medical University between September 2021 and December 2021 were enrolled using the convenience sampling method. Demographic characteristics and disease-related data were collected for each participant. The HIV/AIDS Self-Management Scale was used to evaluate the self-management ability of PLWHA. Results: A total of 251 male and 49 female PLWHA were included in this study, with an average age of 39.08 ± 12.09 years and an average disease duration of 9.61 ± 37.04 months. Univariate analysis showed that the PLWHA's place of residence, educational level, physical condition, family relations, duration of HIV disease, receipt or not of antiviral therapy and knowledge of disease had an influence on the scores of the HIV Self-Management Scale (all p < 0.05). The results of the self-management scores indicated that the total score for self-management was 41.5 ± 6.4 points, with a scoring rate of 69.6%, which was at a medium level. Long-term self-management had the highest scoring rate (12.2 ± 2.5 points), followed by daily health management (22.3 ± 4.3 points), and social support for self-management had the lowest scoring (5.1 ± 0.9 points). Multivariable analysis showed that the self-management ability of PLWHA was related to educational level, duration of disease and family relations (R2 = 0.67, F = 121.7, p < 0.05). Conclusion: The self-management level of patients with AIDS, especially the social support of daily health management and self-management, needs to be further improved. Educational level, duration of disease and family relations are important factors influencing the self-management of PLWHA.

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Agritainment is one of the essential aspects of rural tourism and plays an important role in the economic transformation and revitalization of rural areas. Taking 9200 agritainment resorts in China as a research object, this paper systematically uses geospatial analysis methods to analyze their spatial distribution patterns and influencing mechanisms. The results indicate: (1) All types of agritainment have a condensed distribution in space and are oriented in the northeast-southwest direction, with a central axis generally located in the Beijing-Zhengzhou-Wuhan line. (2) The distribution of agritainment is uneven across different spatial scales, and there are high-density clusters in the Beijing-Tianjin-Hebei region, the Yangtze River Delta, and the Sichuan-Chongqing region as the core, and sub-high-density distribution areas in the Shaanxi-Gansu-Ningxia border, the southern coastal region, and the Xiangan-Jiang-Hubei border, manifesting prominent spatial distribution characteristics of large agglomeration and low dispersion. (3) Agritainment has a significant positive spatial autocorrelation. The Matthew effect is highly significant in space. The distribution of cold hot spots in the agritainment space shows a distribution pattern of "hot in the south and cold in the north." (4) The spatial distribution of agritainment is influenced by human factors such as society, economy, and the tourism industry as well as natural factors such as terrain, water systems, and climate. The intensity of influence of first-level human factors on the spatial distribution of agritainment ranks as follows: tourism industry factors (0.69) > social factors (0.37) > economic factors (0.30). The natural distribution of agritainment tends to be in humid plain and hilly areas with an altitude below 1000 m and annual precipitation above 800 mm. Agritainment is mainly distributed in the subtropical monsoon climate area adjacent to rivers. The research findings offer valuable insights for optimizing the spatial distribution pattern of agritainment in China, promoting the high-quality development of agritainment, and the sustainable development of rural tourism.

Assuntos

População Rural , Turismo , China , Humanos , Análise Espacial , Agricultura

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BACKGROUND This study aimed to evaluate the effectiveness of implementing evidence-based preoperative nursing interventions in reducing postoperative infections and intensive care unit (ICU) length of stay among liver transplant recipients. MATERIAL AND METHODS A controlled study was conducted, comparing postoperative outcomes between an intervention group receiving standardized, evidence-based preoperative care and a control group receiving routine preoperative care. Patients undergoing elective liver transplantation from September 2020 to March 2021 were included and assigned to either the intervention or control group. The intervention group received preoperative interventions based on best available evidence, while the control group received standard preoperative care. The primary outcomes measured were postoperative infection rates and length of ICU stay. RESULTS In the control group the overall Intensive Care Unit (ICU) length of stay was 3 days and the infection rate was 33.30%, while in the intervention group it was 3 days and 13.80% (P<0.05). There was no significant difference in the length of ICU stay between the control and the intervention groups (P>0.05). There was a significant improvement in the awareness, acceptance, and compliance of doctors and nurses. CONCLUSIONS Using the best evidence-based intervention for preoperative nursing of liver transplantation patients can standardize preoperative nursing behavior. Although we did not find significant differences in outcomes before and after the intervention, it is necessary to prevent postoperative infection and improve nursing compliance.

Assuntos

Tempo de Internação , Transplante de Fígado , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Humanos , Transplante de Fígado/efeitos adversos , Feminino , Masculino , Cuidados Pré-Operatórios/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Adulto , Prática Clínica Baseada em Evidências , Unidades de Terapia Intensiva

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In urine drug testing, a cut-off value is often imposed to determine whether the sample is negative or positive. A matrix containing a reference substance helps counteract the adverse effects of the urine matrix across different laboratories to improve the consistency of final results. However, as a biological matrix, urine is prone to corruption and other problems that make it difficult to use as a reference sample. In this study, morphine, nitrazepam, lorazepam, buprenorphine, zolpidem, midazolam, diazepam, and clozapine commonly used in clinical practice were selected as target analytes, and the preparation process was further optimized to repeated lyophilization, in order to obtain more effective, stable, and accurate urine matrix reference materials (mRMs). The appropriate urine density (1.010-1.017 kg/m3) for preparing lyophilized samples was investigated through density determination. Conducting repeated lyophilizations resulted in a denser powder with reduced susceptibility to collapse and improved the quality of lyophilized urine samples. Lyophilized urine mRMs could be stored at room temperature for one month or under refrigeration conditions (4 ℃) for six months.

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Stroke has emerged as the primary cause of disability and death globally in recent years. Intracerebral hemorrhage (ICH), a particularly severe kind of stroke, is occurring in an increasing number of people. The two main clinical treatments for ICH now in use are conservative pharmaceutical therapy and surgical intervention, both of which have risks and drawbacks. Consequently, it is crucial to look into the pathophysiology of ICH and consider cutting-edge therapeutic approaches. Recent research has revealed that pyroptosis is a newly identified type of cell death distinguished by the break of the cell membrane and the discharge of pro-inflammatory substances through different routes. Following ICH, glial cells experience pyroptosis, which worsens neuroinflammation. Hence, the onset and progression of ICH are strongly linked to pyroptosis, which is facilitated by different inflammasomes. It is essential to conduct a comprehensive investigation of ICH damage processes and uncover new targets for treatment. The impact and function of pyroptosis in ICH, as well as the activation and regulation of inflammasomes and their mediated pyroptosis pathways will be fully discussed in this review.

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Hemorragia Cerebral , Imunidade Inata , Inflamassomos , Piroptose , Piroptose/efeitos dos fármacos , Humanos , Inflamassomos/metabolismo , Inflamassomos/imunologia , Hemorragia Cerebral/imunologia , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/tratamento farmacológico , Animais , Imunidade Inata/efeitos dos fármacos , Transdução de Sinais

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Cute, kindchenschema stimuli can evoke a suite of cognitive, physiological, and behavioral tendencies thought to promote caregiving. This research investigated facial expression elements associated with this response to cuteness and assessed the recognizability of an expression combining these elements. In Studies 1 and 2, participants at a community outreach event (Study 1, n = 19) and undergraduate students (Study 2, n = 103) showed spontaneous facial displays while watching videos/photos of baby humans and animals. These were Facial Action Coding System (FACS)-coded, revealing characteristic and statistically distinctive action unit elements of facial expression responses to cuteness. In six follow-up online studies (combined N = 962), including replications with Syrian refugees (n = 103) and Chinese samples (n = 222), a "cuteness prototype" expression combining all elements identified across Studies 1 and 2 (i.e., oblique brows, chin raise, lip tightening, and Duchenne smile) was commonly interpreted as a response to cuteness. These findings add to a growing literature about caregiving-focused motivational states and associated emotion/affect.

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Fruit ripening in tomato is a highly coordinated developmental process accompanied with fruit softening, which is closely associated with cell wall degradation and remodeling. Xyloglucan endotransglucosylase/hydrolases (XTHs) are known to play an essential role in cell wall xyloglucan metabolism. Tomato XTH5 exhibits xyloglucan endotransglucosylase (XET) activity in vitro, but the understanding of its biological role in fruit ripening remains unclear. In this study, we revealed that SlXTH5 is highly expressed in mature fruits. Knockout mutant plants of SlXTH5 were generated by CRISPR/Cas9 gene editing strategy in tomato cultivar Micro-Tom. The mutant fruits showed accelerated transition from unripe to ripe process and earlier ethylene accumulation compared to wild type fruits. Although the mutation of SlXTH5 did not affect the size, weight and number of fruits, it indeed increased fruit firmness and extended shelf life, which is probably attributed to the increased cell layer and cell wall thickness of pericarp tissue. Pathogen infection experiment showed the enhanced resistance of mutant fruits to Botrytis cinerea. These results revealed the role of SlXTH5 in fruit ripening process, and provide new insight into how cell wall metabolism and remodeling regulate fruit softening and shelf life.

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Psoriatic arthritis (PsA) is an immune-mediated, chronic inflammatory joint disease that commonly occurs as a complication of psoriasis. EGF-like repeats and discoidal I-like domain 3 (EDIL3) is a secreted protein with multiple structural domains and associated with various physiological functions. In this study, we employed a mannan-induced psoriatic arthritis model to investigate the impact of EDIL3 on PsA pathogenesis. Notably, a downregulation of EDIL3 expression was observed in the PsA model, which correlated with increased disease severity. EDIL3 knockout mice exhibited a more severe phenotype of PsA, which was ameliorated upon re-infusion of recombinant EDIL3 protein. The mitigation effect of EDIL3 on PsA depends on its regulation of the activation of monocyte-derived DCs (MoDCs) and T-help 17 cells (Th17). After inhibiting the function of MoDCs and Th17 cells with neutralizing antibodies, the beneficial effects of EDIL3 on PsA were lost. By inducing adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and suppressing protein kinase B (AKT) phosphorylation, EDIL3 attenuates intracellular glycolysis in MoDCs stimulated by glucose, thereby impeding their maturation and differentiation. Moreover, it diminishes the differentiation of Th17 cells and decelerates the progression of PsA. In conclusion, our findings elucidate the role and mechanism of EDIL3 in the development of PsA, providing a new target for clinical diagnosis and treatment.

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Class IIa histone deacetylases (HDACs) have been linked to tumorigenesis in various cancers. Previously, we designed phenylhydroxamic acid LH4f as a potent class IIa HDAC inhibitor. However, it also unselectively inhibited class I and class IIb HDACs. To enhance the compound's selectivity towards class IIa HDACs, the ortho-phenyl group from the selective HDAC7 inhibitor 1 is incorporated into ortho position of the phenylhydroxamic acid in LH4f. Compared to LH4f, most resulting compounds displayed substantially improved selectivity towards the class IIa HDACs. Notably, compound 7 g exhibited the strongest HDAC9 inhibition with an IC50 value of 40 nM. Molecular modelling further identified the key interactions of compound 7 g bound to HDAC9. Compound 7 g significantly inhibited several human cancer cells, induced apoptosis, modulated caspase-related proteins as well as p38, and caused DNA damage. These findings suggest the potential of class IIa HDAC inhibitors as lead compounds for the development of cancer therapeutics.

Assuntos

Antineoplásicos , Apoptose , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Histona Desacetilases , Histona Desacetilases , Ácidos Hidroxâmicos , Fenotiazinas , Humanos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Relação Estrutura-Atividade , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/síntese química , Histona Desacetilases/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Fenotiazinas/farmacologia , Fenotiazinas/química , Fenotiazinas/síntese química , Apoptose/efeitos dos fármacos , Modelos Moleculares , Linhagem Celular Tumoral

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Background: Acinetobacter baumannii (A. baumannii) is an widespread pathogen and carbapenem-resistant strains are great threat to hospitalized patients. This study is aimed to investigate the clinical characteristics, antimicrobial resistance patterns, and risk factors associated with carbapenem resistance in nosocomial, healthcare-associated (HCA), and community-acquired (CA) A. baumannii infections. Methods: This study retrospectively reviewed cases in a tertiary hospital in southern China between January 1, 2019, and December 31, 2021. Univariate and multivariate logistic regression analyses were performed to identified the risk factors of carbapenem resistance in nosocomial, HCA and CA A. baumannii infections. Results: A total of 391 patients with A. baumannii infection were included. Of these patients, 96 (24.6%) had nosocomial infections, 215 (55.0%) had HCA infections, and 80 (20.5%) had CA infections. The overall 30-day mortality rates of nosocomial and HCA infection patients was significantly higher than that of CA infection (P<0.05). The incidence of antimicrobial resistance was also higher in nosocomial and HCA bacteremia than that in CA bacteremia (P<0.05). Logistic regression analysis identified age ≥60 years, urethral catheterization, and exposure to two or more antibiotics as the independent risk factors for carbapenem-resistant A. baumannii (CRAB) infection in the nosocomial infection group and exposure to two or more antibiotics and endotracheal intubation in the HCA infection group. However, malignant tumors and hematological diseases were identified as protective factors against CRAB infection in the HCA group. Conclusion: These data suggest that HCA A. baumannii infection is quite different from CA infection, with antimicrobial resistance and 30-day mortality rates similar to those of nosocomial infections. Additionally, the risk factors for CRAB development in the CA, HCA, and nosocomial groups were not the same, which may provides the help for controlling practices and instruction empirical clinical medication.

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The CRISPR (Clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein9) system has emerged as a powerful genetic tool, gaining global recognition as a versatile and efficient gene-editing technique. Its transformation into a high-throughput research platform, CRISPR Screening, has demonstrated wide applicability across various fields such as cancer biology, virology, and drug target discovery, resulting in significant advances. However, its potential in studying retinal degenerative diseases remains largely unexplored, despite the urgent need for effective treatments arising from an incomplete understanding of disease mechanisms. This review aims to present a comprehensive overview of the evolution and current state of CRISPR tools and CRISPR screening methodologies. Noteworthy pioneering studies utilizing these technologies are discussed, alongside experimental design guidelines, including positive and negative selection strategies and delivery methods for sgRNAs (single guide RNAs) and Cas proteins. Furthermore, we explore existing in vitro models appropriate for CRISPR screening in retinal research and identify relevant research questions that could be addressed through this approach. It is anticipated that this review will stimulate innovation in retinal research, facilitating a deeper comprehension of retinal pathophysiology and paving the way for groundbreaking therapeutic interventions and enhanced patient outcomes in the management of retinal degenerative disorders.

Assuntos

Sistemas CRISPR-Cas , Edição de Genes , Degeneração Retiniana , Humanos , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Degeneração Retiniana/genética , Degeneração Retiniana/terapia , Animais , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , RNA Guia de Sistemas CRISPR-Cas/genética

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Dysregulation of the gut microbiome has associated with the occurrence and progression of non-alcoholic fatty liver disease (NAFLD). To determine the diagnostic capacity of this association, we compared fecal microbiomes across 104 participants including non-NAFLD controls and NAFLD subtypes patients that were distinguished by magnetic resonance imaging. We measured their blood biochemical parameters, 16 S rRNA-based gut microbiota and fecal short-chain fatty acids (SCFAs). Multi-omic analyses revealed that NAFLD patients exhibited specific changes in gut microbiota and fecal SCFAs as compared to non-NAFLD subjects. Four bacterial genera (Faecalibacterium, Subdoligranulum, Haemophilus, and Roseburia) and two fecal SCFAs profiles (acetic acid, and butyric acid) were closely related to NAFLD phenotypes and could accurately distinguish NAFLD patients from healthy non-NAFLD subjects. Twelve genera belonging to Faecalibacterium, Subdoligranulum, Haemophilus, Intestinibacter, Agathobacter, Lachnospiraceae_UCG-004, Roseburia, Butyricicoccus, Actinomycetales_unclassified, [Eubacterium]_ventriosum_group, Rothia, and Rhodococcus were effective to distinguish NAFLD subtypes. Of them, combination of five genera can distinguish effectively mild NAFLD from non-NAFLD with an area under curve (AUC) of 0.84. Seven genera distinguish moderate NAFLD with an AUC of 0.83. Eight genera distinguish severe NAFLD with an AUC of 0.90. In our study, butyric acid distinguished mild-NAFLD from non-NAFLD with AUC value of 0.83. And acetic acid distinguished moderate-NAFLD and severe-NAFLD from non-NAFLD with AUC value of 0.84 and 0.70. In summary, our study and further analysis showed that gut microbiota and fecal SCFAs maybe a method with convenient detection advantages and invasive manner that are not only a good prediction model for early warning of NAFLD occurrence, but also have a strong ability to distinguish NAFLD subtypes.

Assuntos

Ácidos Graxos Voláteis , Fezes , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Humanos , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/análise , Masculino , Feminino , Pessoa de Meia-Idade , Fezes/microbiologia , Adulto , Progressão da Doença , RNA Ribossômico 16S/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bactérias/genética

RESUMO

Herein, we report a target-triggered CRISPR/Cas12a assay by coupling lanthanide tagging and inductively coupled plasma mass spectrometry (ICP-MS) for highly sensitive elemental detection. Hepatitis B virus (HBV) DNA was chosen as a model analyte, and recombinase polymerase amplification (RPA) was used for target amplification. The double-stranded RPA amplicons containing a 5' TTTG PAM sequence can be recognized by Cas12a through a specific CRISPR RNA, activating the trans-cleavage activity of CRISPR/Cas12a and nonspecific cleavage of terbium (Tb)-ssDNA modified on magnetic beads (MBs). Following magnetic separation and acid digestion, the released Tb3+ ions were quantitated by ICP-MS and correlated to the concentration of HBV DNA. Taking advantage of the accelerated cleavage of Tb-ssDNA attached to the MB particles, RPA for target amplification, and ICP-MS for highly selective signal readout, this method permits the detection of 1 copy/µL of HBV DNA in serum with high specificity and holds great promise in the early diagnosis of viral infections or tumor development.

Assuntos

Sistemas CRISPR-Cas , DNA Viral , Vírus da Hepatite B , Elementos da Série dos Lantanídeos , Espectrometria de Massas , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , DNA Viral/genética , DNA Viral/análise , Elementos da Série dos Lantanídeos/química , Espectrometria de Massas/métodos , Sistemas CRISPR-Cas/genética , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Recombinases/metabolismo

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Although targeting the androgen signaling pathway by androgen receptor (AR) inhibitors, including enzalutamide, has shown therapeutic effectiveness, inevitable emergence of acquired resistance remains a critical challenge in the treatment of advanced prostate cancer (PCa). Recognizing targetable genomic aberrations that trigger endocrine treatment failure holds great promise for advancing therapeutic interventions. Here, we characterized PLXNA1, amplified in a subset of PCa patients, as a contributor to enzalutamide resistance (ENZR). Elevated PLXNA1 expression facilitated PCa proliferation under enzalutamide treatment due to AKT signaling activation. Mechanistically, PLXNA1 recruited NRP1 forming a PLXNA1-NRP1 complex, which in turn potentiated the phosphorylation of the AKT. Either inhibiting PLXNA1-NRP1 complex with an NRP1 inhibitor, EG01377, or targeting PLXNA1-mediated ENZR with AKT inhibitors, abolished the pro-resistance phenotype of PLXNA1. Taken together, combination of AKT inhibitor and AR inhibitors presents a promising therapeutic strategy for PCa, especially in advanced PCa patients exhibiting PLXNA1 overexpression.

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T cell senescence alters the homeostasis of distinct T cell populations and results in decayed adaptive immune protection in older individuals, but a link between aging and dynamic T cell clone changes has not been made. Here, using a newly developed computational framework, Repertoire Functional Units (RFU), we investigate over 6500 publicly available TCR repertoire sequencing samples from multiple human cohorts and identify age-associated RFUs consistently across different cohorts. Quantification of RFU reduction with aging reveals accelerated loss under immunosuppressive conditions. Systematic analysis of age-associated RFUs in clinical samples manifests a potential link between these RFUs and improved clinical outcomes, such as lower ICU admission and reduced risk of complications, during acute viral infections. Finally, patients receiving bone marrow transplantation show a secondary expansion of the age-associated clones upon stem cell transfer from younger donors. Together, our results suggest the existence of a 'TCR clock' that could reflect the immune functions in aging populations.

Assuntos

Envelhecimento , Receptores de Antígenos de Linfócitos T , Linfócitos T , Humanos , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Envelhecimento/imunologia , Idoso , Linfócitos T/imunologia , Pessoa de Meia-Idade , Adulto , Transplante de Medula Óssea , Masculino , Feminino , Senescência Celular/imunologia , Adulto Jovem , Idoso de 80 Anos ou mais

RESUMO

Melanin is an amino acid derivative produced by melanocyte through a series of enzymatic reactions using tyrosinase as substrate. Human skin and hair color is also closely related to melanin, so understanding the mechanisms and proteins that produce melanin is very important. There are many proteins involved in the process of melanin expression, For example, proteins involved in melanin formation such as p53, HNF-1α (Hepatocyte nuclear factor 1α), SOX10 (Sry-related HMg-Box gene 10) and pax3 (paired box gene 3), MC1R(Melanocortin 1 Receptor), MITF (Microphthalmia-associated transcription factor), TYR (tyrosinase), TYRP1 (tyrosinase-related protein-1), TYRP2 (tyrosinase-related protein-2), and can be regulated by changing their content to control the production rate of melanin. Others, such as OA1 (ocular albinism type 1), Par-2 (protease-activated receptor 2) and Mlph (Melanophilin), have been found to control the transfer rate of melanosomes from melanocytes to keratinocytes, and regulate the amount of human epidermal melanin to control the depth of human skin color. In addition to the above proteins, there are other protein families also involved in the process of melanin expression, such as BLOC, Rab and Rho. This article reviews the origin of melanocytes, the related proteins affecting melanin and the basic causes of related gene mutations. In addition, we also summarized the active ingredients of 5 popular whitening cosmetics and their mechanisms of action.

RESUMO

A nanocrystalline alloy, with an iron-based composition (Fe58.5Si16.7B6.5Nb5.1Cu13.2) and a Curie temperature of 570 °C, was investigated for its effectiveness as magnetic shielding films in an induction heating system. The primary focus of the research was to evaluate the shielding performance of the 3-turned (9-layered) shielding films with dimensions of 135 mm × 17 mm × 0.15 mm. Upon winding, these films formed a cylindrical structure that enveloped the coil, with a diameter of 13.9 mm and a height of 17 mm. The results showed that increasing the degree of fragmentation within the nanocrystalline shielding films significantly reduced the magnetic permeability by decreasing the real component from 11,500 to 400 and the imaginary part from 2800 to 20. However, a lower degree of fragmentation led to a 10 % increase in the resistance (Rs) of the heating module, although this effect was less pronounced as the relative permeability continued to increase. Furthermore, observations on preheating time to a set temperature of 400 °C and total energy consumption over a duration of 250s revealed an initial downward trend, followed by a rapid increase that even exceeded the initial values as the magnetic permeability of the nanocrystalline shielding films augmented. Notably, the study emphasized that nanocrystalline shielding films with a relative permeability value of 1000 demonstrated exceptional magnetic shielding performance, resulting in a 12.5 % reduction in preheat time and 7 % less energy consumption during preheating. In addition to empirical findings, the study developed a theoretical model elucidating the shielding mechanism inherent in induction heating systems. This model serves as a robust framework for the application of nanocrystalline shielding materials in such systems, laying the groundwork for enhanced magnetic shielding capabilities in future applications.