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The development of advanced neural modulation techniques is crucial to neuroscience research and neuroengineering applications. Recently, optical-based, nongenetic modulation approaches have been actively investigated to remotely interrogate the nervous system with high precision. Here, we show that a thin-film, silicon (Si)-based diode device is capable to bidirectionally regulate in vitro and in vivo neural activities upon adjusted illumination. When exposed to high-power and short-pulsed light, the Si diode generates photothermal effects, evoking neuron depolarization and enhancing intracellular calcium dynamics. Conversely, low-power and long-pulsed light on the Si diode hyperpolarizes neurons and reduces calcium activities. Furthermore, the Si diode film mounted on the brain of living mice can activate or suppress cortical activities under varied irradiation conditions. The presented material and device strategies reveal an innovated optoelectronic interface for precise neural modulations.
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Neurônios , Optogenética , Silício , Animais , Silício/química , Neurônios/fisiologia , Camundongos , Optogenética/métodos , Cálcio/metabolismo , Luz , Encéfalo/fisiologiaRESUMO
BACKGROUND: Keloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids. METHOD: Bulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids. RESULTS: In the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion. CONCLUSION: In summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment.
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Queloide , RNA-Seq , Queloide/genética , Queloide/diagnóstico , Queloide/patologia , Queloide/imunologia , Queloide/tratamento farmacológico , Humanos , Transcriptoma/genética , Perfilação da Expressão Gênica , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibroblastos/imunologia , Redes Reguladoras de Genes , Tretinoína/farmacologia , Tretinoína/uso terapêutico , Análise de Célula Única/métodos , Diferenciação Celular/genética , Análise de Sequência de RNA/métodos , Aprendizado de Máquina , Análise da Expressão Gênica de Célula ÚnicaRESUMO
Inorganic/organic heterojunctions show promising applications as high-performance sensing platforms for photoelectrochemical (PEC) immunosensors. This work reports constructing a PEC biosensor for CA15-3 based on a self-assembled perylene diimide (PDI) nanowire sensitized In2O3@MgIn2S4 S-scheme heterojunction platform. P-type semiconductor Cu2O nanoparticles were designed as a signal burst source and were used as immunoassay labels. The carboxyl group on self-assembled PDI nanowires eliminates the step of additional surface functionalization for covalent immobilization of the capture elements. The π-π stacking of PDI enhances electron generation efficiency, while the carboxylic acid groups on PDI promote electron transfer. The performance of the constructed sensor was validated using CA15-3 as a model. The experimental results showed that the sensor based on In2O3@MgIn2S4/PDI has excellent selectivity, stability, and reproducibility, and can sensitively detect CA15-3 in the range of 0.001-100 U·mL-1 with the detection limit of 0.00056 U·mL-1. The sensor has a broad application prospect. It is hoped that this research work based on the unique advantages of the organic compound PDI will inspire other researchers to design light-responsive materials and promote the development of the field of photoelectrochemical sensing.
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Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.
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Técnicas Biossensoriais , Antígeno Carcinoembrionário , Técnicas Eletroquímicas , alfa-Fetoproteínas , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/imunologia , Antígeno Carcinoembrionário/análise , Antígeno Carcinoembrionário/imunologia , Técnicas Biossensoriais/métodos , Humanos , Imunoensaio/métodos , Ouro/química , Limite de DetecçãoRESUMO
This study was designed to evaluate the safety and feasibility of laparoscopic radical cystectomy (LRC) for male octogenarian patients with muscle-invasive bladder cancer (MIBC). Briefly, a total of 57 male octogenarian patients (A group) with bladder carcinoma were enrolled and underwent LRC and intracorporeal pelvic lymph node dissection with bilateral cutaneous ureterostomy from May 2016 to December 2022. Besides, 63 male patients (age < 80 years old) with bladder carcinoma undergoing LRC and 17 octogenarian male patients with bladder carcinoma undergoing open radical cystectomy (ORC) were enrolled in B and C groups as control. All perioperative clinical materials and outcomes of long-term follow-up, and complication were collected. The specific results were shown as follows. Compared with C group, the operation time and resected lymph node in A group was increased, and the estimated blood loss, the number of transfusion needed, duration of pelvic drainage and hospital stay after surgery was decreased. The death rate and ileus complication rate were higher in A group (12 cases) than in C group (15 cases). The cases of ureteral stricture in A group (13 cases) was decreased compared with that in C group. Overall, LRC and bilateral cutaneous ureterostomy are safe, feasible and better choices for the treatment of male octogenarian patients with MIBC. The octogenarian receiving cutaneous ureterostomy heals slowly and exists certain incomplete intestinal obstruction after surgery.
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Carcinoma , Laparoscopia , Neoplasias da Bexiga Urinária , Idoso de 80 Anos ou mais , Humanos , Masculino , Cistectomia/efeitos adversos , Cistectomia/métodos , Bexiga Urinária/patologia , Octogenários , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Estudos de Viabilidade , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Carcinoma/cirurgia , Músculos/patologiaRESUMO
OBJECTIVE: To evaluate and explore the efficacy of CO2 fractional laser in treating post-burn hypertrophic scars in children through Meta-analysis. METHODS: English databases (PubMed, Web of Science and The National Library of Medicine), as well as Chinese databases (China National Knowledge Infrastructure and Wanfang Data) were searched. RevMan 5.3 software was used to data analysis. RESULTS: A total of 10 pieces of literature were included, involving 413 children. Meta-analysis showed that: (1) The average Vancouver Scar Scale after surgery was significantly lower than that before surgery [weight mean difference (WMD) = -3.56, 95% confidence interval (CI):-4.53,-2.58, p < 0.001]; (2) After CO2 fractional laser, pigmentation [WMD = -0.74, 95% CI:-1.10,-0.38, p < 0.001], pliability [WMD = -0.92, 95% CI:-1.20,-0.65, p < 0.001], vascularity [WMD = -0.77, 95% CI:-1.09,-0.46, p < 0.001], height [WMD = -0.57, 95% CI:-0.95,-0.19, p < 0.001] were improved compared with those before surgery. (3) The average Visual Analogue Scale (VAS) after surgery was significantly lower than that before surgery [WMD = -3.94, 95% CI:-5.69,-2.22, p < 0.001]. (4) Both Patient and Observer Scar Assessment Scale (POSAS)-Observer [WMD = -3.98, 95% CI:-8.44,0.47, p < 0.001] and POSAS-Patient [WMD = -4.98, 95% CI:-8.09,-1.87, p < 0.001] were significantly lower than those before surgery. (5) Erythema and vesicles were the most common complications after CO2 fractional laser therapy, with an incidence of 4.09%. CONCLUSION: CO2 fractional laser is beneficial to the recovery of hypertrophic scar after burn in children, and can effectively improve the scar symptoms and signs in children, with desirable clinical efficacy.
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Cicatriz Hipertrófica , Lasers de Gás , Criança , Humanos , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/cirurgia , Cicatriz Hipertrófica/patologia , Cicatriz/etiologia , Cicatriz/cirurgia , Dióxido de Carbono , Estudos Prospectivos , Resultado do Tratamento , Lasers de Gás/uso terapêuticoRESUMO
BACKGROUND: Atopic dermatitis (AD), psoriasis (PSO), rosacea, and other related immune skin diseases are affected by multiple complex factors such as genetic and microbial components. This research investigates the causal relationships between specific skin microbiota and these diseases by using Mendelian randomization (MR), and Bayesian weighted Mendelian randomization (BWMR). METHODS: We utilized genome-wide association study (GWAS) data to analyze the associations between various skin bacteria and three dermatological diseases. Single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) in MR methods, including inverse variance weighted (IVW), and MR Egger. BWMR was employed to validate results and address pleiotropy. RESULTS: The IVW analysis identified significant associations between specific skin microbiota and dermatological diseases. ASV006_Dry, ASV076_Dry, and Haemophilus_Dry were significantly positively associated with AD, whereas Kocuria_Dry was negatively associated. In PSO, ASV005_Dry was negatively associated, whereas ASV004_Dry, Rothia_Dry, and Streptococcus_Moist showed positive associations. For rosacea, ASV023_Dry was significantly positively associated, while ASV016_Moist, Finegoldia_Dry, and Rhodobacteraceae_Moist were significantly negatively associated. These results were corroborated by BWMR analysis. CONCLUSION: Bacterial species such as Finegoldia, Rothia, and Streptococcus play crucial roles in the pathogenesis of AD, PSO, and rosacea. Understanding these microbial interactions can aid in developing targeted treatments and preventive strategies, enhancing patient outcomes and quality of life.
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Teorema de Bayes , Dermatite Atópica , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Microbiota , Polimorfismo de Nucleotídeo Único , Humanos , Microbiota/genética , Dermatite Atópica/microbiologia , Dermatite Atópica/genética , Pele/microbiologia , Rosácea/microbiologia , Rosácea/genética , Dermatopatias/microbiologia , Dermatopatias/genética , Psoríase/microbiologia , Psoríase/genéticaRESUMO
BACKGROUND: Recent studies increasingly suggest that microbial infections and the immune responses they elicit play significant roles in the pathogenesis of chronic inflammatory skin diseases. This study uses Mendelian randomization (MR) and Bayesian weighted Mendelian randomization (BWMR) to explore the causal relationships between immune antibody responses and four common skin diseases: psoriasis, atopic dermatitis (AD), rosacea, and vitiligo. METHODS: We utilized summary statistics from genome-wide association studies (GWAS) for antibody responses to 13 infectious pathogens and four skin diseases. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) to assess causal relationships using multiple MR methods, including inverse variance weighted (IVW), MR Egger, and weighted median. BWMR was also employed to confirm findings and address potential pleiotropy. RESULTS: The IVW analysis identified significant associations between specific antibody responses and the skin diseases studied. Key findings include protective associations of anti-Epstein-Barr virus (EBV) IgG seropositivity and Helicobacter pylori UREA antibody levels with psoriasis and AD. anti-chlamydia trachomatis IgG seropositivity, anti-polyomavirus 2 IgG seropositivity, and varicella zoster virus glycoprotein E and I antibody levels were negatively associated with rosacea, while EBV Elevated levels of the early antigen (EA-D) antibody levels and HHV-6 IE1B antibody levels were positively associated with rosacea. H. pylori Catalase antibody levels were protectively associated with vitiligo, whereas anti-herpes simplex virus 2 (HSV-2) IgG seropositivity was positively associated with vitiligo. The BWMR analysis confirmed these associations. CONCLUSION: This study underscores the significant role of H. pylori and other pathogens in these skin diseases, suggesting both protective and exacerbating effects depending on the specific condition. Understanding these pathogen-immune interactions can lead to the development of more effective, personalized treatments and preventative strategies, ultimately improving patient outcomes and quality of life.
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Teorema de Bayes , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Dermatite Atópica/imunologia , Dermatite Atópica/genética , Dermatite Atópica/microbiologia , Dermatite Atópica/sangue , Rosácea/imunologia , Rosácea/genética , Vitiligo/genética , Vitiligo/imunologia , Formação de Anticorpos/genética , Psoríase/imunologia , Psoríase/genética , Dermatopatias/imunologia , Dermatopatias/genéticaRESUMO
A smartphone-based electrochemical aptasensing platform was developed for the point-of-care testing (POCT) of carcinoembryonic antigen (CEA) based on the ferrocene (Fc) and PdPt@PCN-224 dual-signal labeled strategy. The prepared PdPt@PCN-224 nanocomposite showed a strong catalytic property for the reduction of H2O2. Phosphate group-labeled aptamer could capture PdPt@PCN-224 by Zr-O-P bonds to form PdPt@PCN-224-P-Apt. Therefore, a dual signal labeled probe was formed by the hybridization between Fc-DNA and PdPt@PCN-224-P-Apt. The presence of CEA forced PdPt@PCN-224-P-Apt to leave the electrode surface due to the specific affinity, leading to the decrease of the reduction current of H2O2. At the same time, the Fc-DNA strand changed to hairpin structure, which made Fc closer to the electrode and resulted in the increase of the oxidation current of Fc. Thus, CEA can be accurately determined through both signals: the decrease of H2O2 reduction current and the increase of Fc oxidation current, which could avoid the false positive signal. Under the optimal conditions, the prepared aptasensor exhibited a wide linear range from 1 pg·mL-1 to 100 ng·mL-1 and low detection limits of 0.98 pg·mL-1 and 0.27 pg·mL-1 with Fc and PdPt@PCN-224 as signal labels, respectively. The aptasensor developed in this study has successfully demonstrated its capability to detect CEA in real human serum samples. These findings suggest that the proposed sensing platform will hold great potential for clinical tumor diagnosis and monitoring.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Antígeno Carcinoembrionário , Técnicas Eletroquímicas , Compostos Ferrosos , Peróxido de Hidrogênio , Limite de Detecção , Paládio , Testes Imediatos , Smartphone , Antígeno Carcinoembrionário/sangue , Antígeno Carcinoembrionário/análise , Aptâmeros de Nucleotídeos/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Humanos , Técnicas Biossensoriais/métodos , Peróxido de Hidrogênio/química , Paládio/química , Compostos Ferrosos/química , Metalocenos/química , Platina/químicaRESUMO
Three new diterpenoid alkaloids (1, 2, 3) and seventeen known (4-20) compounds were isolated from the whole plant of Delphinium sherriffii Munz (Ranunculaceae). Their structures were elucidated by various spectroscopic analyses, including IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were evaluated for the inhibitory activity of Sf9 cells and compound 5 exhibited the strongest cytotoxicity (IC50 = 8.97 µM) against Sf9 cell line.
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Present study aimed to compare the effects of SSIT intervention with varying rest distributions on hormonal, physiological, and performance adaptations in soccer players. Thirty-six players were randomly divided into three SSIT groups, each performing 4 sets of 6-10 repetitions of 6-second all-out running with rest intervals at ratios of 1:3, 1:6, and 1:9. Prior to and following the 7-week training period, aerobic fitness indices and anaerobic power were evaluated using a graded exercise test with a gas collection system and a lower-body Wingate test, respectively. Also, sport-specific bio-motor abilities were determined by measuring vertical jump, 20-m sprint, and T-test change of direction speed, Yo-Yo IR1 and maximal kicking distance. Hormonal status was also monitored by evaluating testosterone and cortisol levels. Following the 7-week training period, all SSIT interventions resulted in significant enhancements (p < 0.05) in soccer-related performance, physiological parameters, and hormonal adaptations, exhibiting effect sizes that ranged from small to large. Comparative analysis indicated that the 1:9 SSIT results in greater adaptive responses (p < 0.05) in the vertical jump, peak power, testosterone, and cortisol compared to the 1:3 SSIT group. By contrast, the 1:3 SSIT group induced more adaptive responses (p < 0.05) in the mean power output, maximum oxygen consumption (VÌO2max), and Yo-Yo IR1 compared to the 1:9 SSIT group. Hence, for enhancing physical performance, especially vertical jump height, anaerobic peak power, and hormonal adaptations, the 1:9 SSIT ratio is preferable. Conversely, shorter rest intervals (specifically, the 1:3 SSIT ratio) are better suited for eliciting heightened adaptive responses in mean power output, VÌO2max, and Yo-Yo IR1 over the 7-week training period among young male soccer players.
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Adaptação Fisiológica , Desempenho Atlético , Treinamento Intervalado de Alta Intensidade , Hidrocortisona , Consumo de Oxigênio , Descanso , Corrida , Futebol , Testosterona , Humanos , Futebol/fisiologia , Hidrocortisona/sangue , Desempenho Atlético/fisiologia , Testosterona/sangue , Corrida/fisiologia , Masculino , Adolescente , Treinamento Intervalado de Alta Intensidade/métodos , Descanso/fisiologia , Consumo de Oxigênio/fisiologia , Teste de EsforçoRESUMO
OBJECTIVE: To assess the safety and efficacy of antimicrobial peptide PL-5 (Peceleganan) spray in the treatment of wound infections. BACKGROUND: Antimicrobial peptide PL-5 spray is a novel topical antimicrobial agent. METHODS: We conducted a multicenter, open-label, randomized, controlled phase IIb clinical trial to evaluate the efficacy and safety of PL-5 spray, as compared with silver sulfadiazine, in patients with skin wound infections. The primary efficacy outcome was the clinical efficacy rate on the first day after ending the treatment (D8). The secondary efficacy outcome was the clinical efficacy rate on the fifth day posttreatment (D5), the bacteria clearance rate, and the overall efficacy rate at the mentioned 2 time points. The safety outcomes included adverse reactions and pharmacokinetic analysis posttreatment. RESULTS: A total of 220 patients from 27 hospitals in China were randomly assigned to 4 groups. On D8, the efficacy rate was 100.0%, 96.7%, 96.7% for the 1 PL-5, 2 PL-5, 4 PL-5 groups, respectively, as compared with 87.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). On D5, the efficacy rate was 100.0%, 93.4%, 98.3% for the 1 PL-5, 2 PL-5, 4 PL-5 groups, respectively, as compared with 82.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). The blood concentration of PL-5 was not detectable in pharmacokinetic analysis. No severe adverse event related to the application of PL-5 was reported. CONCLUSIONS: Antimicrobial peptide PL-5 spray is safe and effective for the treatment of skin wound infections. TRIAL REGISTRATION: ChiCTR2000033334.
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Anti-Infecciosos Locais , Infecção dos Ferimentos , Humanos , Resultado do Tratamento , Bactérias , China , Método Duplo-CegoRESUMO
Rapid and accurate detection of biomolecules is of vital importance for the diagnosis of disease and for performing timely treatments. The point-of-care analysis of cancer biomarkers in the blood with low cost and easy processing is still challenging. Herein, an advanced and robust strategy, which integrates the buoyant recognition probe with the magnetic reporter probe in one solution, was first proposed for immobilization-free electrochemical immunosensing. The tumor marker of alpha fetoprotein (AFP) can be captured immune-buoyantly, and then a multifunctional magnetic reporter probe in pseudo-homogeneous solution was further captured to fulfill a sandwich-type immunoreaction. The residual magnetic reporter probe can be firmly and efficiently attracted on a magnetic glassy carbon electrode to fulfill the conversion of the target AFP amount into the residual magnetic electrochemical signal indicator. As a result, the electrochemical signal of methylene blue can accurately reflect the original level of target antigen AFP concentration. By integrating buoyancy-driven quasi-homogenous biorecognition with magnetism-mediated amplification and signal output, the proposed immobilization-free electrochemical immunosensing strategy displayed a wide range of linear response (100 fg mL-1 to 10 ng mL-1), low detection limit (14.52 fg mL-1), and good reproducibility, selectivity, and stability. The designed strategy manifests remarkable advantages including assay simplicity, rapidness, and high sensitivity owing to the in-solution instead of on-electrode biorecognition that could accelerate and improve the biorecognition efficiency. To the best of our knowledge, this is the first cooperation of buoyancy-driven biorecognition with magnetism-mediated signal output in bioanalysis, which would be attractive for rapid clinic biomedical application. Thus, this work provides a fresh perspective for convenient and favorable immobilization-free electrochemical biosensing of universal biomolecules.
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Técnicas Biossensoriais , alfa-Fetoproteínas , alfa-Fetoproteínas/análise , Técnicas Eletroquímicas , Reprodutibilidade dos Testes , Biomarcadores Tumorais/análise , Limite de Detecção , Imunoensaio , Ouro/químicaRESUMO
The neuroprotective effects of hydrogen have been demonstrated, but the mechanism is still poorly understood. In a clinical trial of inhaled hydrogen in patients with subarachnoid hemorrhage (SAH), we found that hydrogen reduced the accumulation of lactic acid in the nervous system. There are no studies demonstrating the regulatory effect of hydrogen on lactate and in this study we hope to further clarify the mechanism by which hydrogen regulates lactate metabolism. In cell experiments, PCR and Western Blot showed that HIF-1α was the target related to lactic acid metabolism that changed the most before and after hydrogen intervention. HIF-1α levels were suppressed by hydrogen intervention treatment. Activation of HIF-1α inhibited the lactic acid-lowering effect of hydrogen. We have also demonstrated the lactic acid-lowering effect of hydrogen in animal studies. Our work clarifies that hydrogen can regulate lactate metabolism via the HIF-1αpathway, providing new insights into the neuroprotective mechanisms of hydrogen.
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Ácido Láctico , Hemorragia Subaracnóidea , Animais , Ácido Láctico/metabolismo , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Western Blotting , Terapia Respiratória , Subunidade alfa do Fator 1 Induzível por HipóxiaRESUMO
BACKGROUND: The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. METHODS: We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. RESULTS: In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. CONCLUSION: P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract.
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Microglia , Hemorragia Subaracnóidea , Humanos , Fagocitose , Autofagia , Inflamação , Proteínas Quinases Associadas com Morte CelularRESUMO
As a prognostic biomarker for breast cancer, human epidermal growth factor receptor 2 (HER-2) is of crucial diagnostic value. Here, a label-free electrochemical aptasensor was established for the ultrasensitive detection of HER-2 using a modified electrode of Bi-Sb alloy materials (Bi-Sb AMs). The performance of the aptasensor was enhanced greatly due to the introduction of Bi-Sb alloy materials (Bi-Sb AMs) with high conductivity. Furthermore, by integrating the aptasensor with the Sensit Smart U-disk electrochemical analyzer, the point-of-care testing (POCT) for HER-2 was realized. Under the optimal experimental parameters, the POCT analyzer showed a wide linear response from 0.01 pg mL-1 to 100 ng mL-1, with a low detection limit (LOD) of 5.96 fg mL-1 for the detection of HER-2. The presented POCT analyzer exhibited good specificity, stability, and reproducibility. Benefiting from the simple operation and rapid testing, the developed analyzer will have potential application in the prognostic diagnosis and treatment of breast cancer.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Humanos , Técnicas Eletroquímicas , Ligas , Reprodutibilidade dos Testes , Limite de Detecção , OuroRESUMO
This study aimed to develop a quenching-type electrochemiluminescence (ECL) immunosensor for human epidermal growth factor receptor (Her-2) detection. Firstly, Pd/NiFeOx nanoflowers decorated by in situ formation of gold nanoparticles (Au NPs) and 2D Ti3C2 MXene nanosheets were synthesized (AuPd/NiFeOx/Ti3C2) as carriers to load luminol and primary antibodies. Impressively, AuPd/NiFeOx/Ti3C2 with excellent peroxidase-like activity could accelerate the decomposition of the coreactant H2O2 generating more reactive oxygen species (ROSs) under the working potential from 0 to 0.8 V, resulting in highly efficient ECL emission at 435-nm wavelengths. The introduction of tungsten-based polyoxometalate nanoclusters (W-POM NCs) which exhibit remarkable ROSs-scavenging activity as secondary antibody labels could improve the sensitivity of immunosensors. The ZnO nanoflowers were employed to encapsulate minute-sized W-POM NCs, and polydopamine was self-polymerized on the surface of Zn(W-POM)O to anchor secondary antibodies. The mechanism of the quenching strategy was explored and it was found that W-POM NCs could consume ROSs by the redox reaction of W5+ resulting in W6+. The proposed ECL immunosensor displayed a wide linear response range of 0.1 pg·mL-1 to 50 ng·mL-1, and a low detection limit of 0.036 pg mL-1 (S/N = 3). The recoveries ranged from 93.9 to 99.4%, and the relative standard deviation (RSD) was lower than 10%. This finding is promising for the design of detecting new protein biomarkers.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Luminol , Espécies Reativas de Oxigênio , Técnicas Biossensoriais/métodos , Tungstênio , Ouro , Peróxido de Hidrogênio , Medições Luminescentes/métodos , ImunoensaioRESUMO
In the hexaploid wheat genome, there are three Gα genes, three Gß and twelve Gγ genes, but the function of Gß in wheat has not been explored. In this study, we obtained the overexpression of TaGB1 Arabidopsis plants through inflorescence infection, and the overexpression of wheat lines was obtained by gene bombardment. The results showed that under drought and NaCl treatment, the survival rate of Arabidopsis seedlings' overexpression of TaGB1-B was higher than that of the wild type, while the survival rate of the related mutant agb1-2 was lower than that of the wild type. The survival rate of wheat seedlings with TaGB1-B overexpression was higher than that of the control. In addition, under drought and salt stress, the levels of superoxide dismutase (SOD) and proline (Pro) in the wheat overexpression of TaGB1-B were higher than that of the control, and the concentration of malondialdehyde (MDA) was lower than that of the control. This indicates that TaGB1-B could improve the drought resistance and salt tolerance of Arabidopsis and wheat by scavenging active oxygen. Overall, this work provides a theoretical basis for wheat G-protein ß-subunits in a further study, and new genetic resources for the cultivation of drought-tolerant and salt-tolerant wheat varieties.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Subunidades beta da Proteína de Ligação ao GTP , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas Geneticamente Modificadas/genética , Triticum/genética , Triticum/metabolismo , Secas , Estresse Fisiológico/genética , Plântula/genética , Plântula/metabolismo , Proteínas de Ligação ao GTP/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Arabidopsis/genética , Subunidades beta da Proteína de Ligação ao GTP/genéticaRESUMO
This study explores the antifungal properties of Agaricus blazei Murrill, a valuable medicinal and edible fungus. Six compounds (1-6) were first isolated from A. blazei using various isolation techniques and identified using spectroscopic methods. These compounds include linoleic acid, 1,1'-oxybis(2,4-di-tert-butylbenzene), glycerol monolinoleate, volemolide (17R)-17-methylincisterol, (24s)-ergosta-7-en-3-ol, and dibutyl phthalate. This study also assesses the antifungal activities of these compounds against Trichophyton mentagrophology, Trichophyton rubrum, Candida albicans, and Cryptococcus neoformans. The results demonstrate varied sensitivities against these pathogenic fungi, with compound 2 showing significant inhibition against T. mentagrophology, compound 3 showing significant inhibition against T. rubrum, and compound 6 showing significant inhibition against C. albicans. This study underscores the medicinal potential of A. blazei as an antifungal agent and sheds light on its valuable research implications.
Assuntos
Agaricus , Antifúngicos , Antifúngicos/farmacologia , Agaricus/química , Candida albicans , TrichophytonRESUMO
As COVID-19 increased people's dependency on urban parks for physical and psychological well-being, it also has uncertain impacts on park utilization. Understanding these impacts and how the pandemic has contributed to them is an issue that warrants urgent attention. We used multi-source spatio-temporal data to examine urban park use before and during COVID-19 in Guangzhou, China, and constructed a set of regression models to evaluate the associated factors. We found that COVID-19 has significantly reduced the overall utilization of urban parks while also exacerbating spatial unevenness. This was due to residents' limited movement distance, and the diminished role of urban transportation affecting the efficient citywide use of parks. Meanwhile, residents' increased demand for nearby parks amplified the importance of community parks, which exacerbated the consequences caused by the uneven distribution of park resources. We propose that city administrators improve the efficiency of existing parks and prioritize the adequate placement of community parks at urban fringes to improve access. Furthermore, cities with similar layouts as Guangzhou should plan for urban parks from a multi-perspective and consider the sub-city level differences to address unevenness during the current pandemic and in the future.