RESUMEN
Histamine is a biogenic amine that is critical in various physiological and pathophysiological processes, including but not limited to allergic reactions, wakefulness, gastric acid secretion and neurotransmission. Here, we determine 9 cryo-electron microscopy (cryo-EM) structures of the 4 histamine receptors in complex with four different G protein subtypes, with endogenous or synthetic agonists bound. Inside the ligand pocket, we identify key motifs for the recognition of histamine, the distinct binding orientations of histamine and three subpockets that facilitate the design of specific ligands. In addition, we also identify key residues responsible for the selectivity of immethridine. Moreover, we reveal distinct structural features as determinants of Gq vs. Gs or Gs vs. Gi coupling differences among the histamine receptors. Our study provides a structural framework for understanding the ligand recognition and G protein coupling of all 4 histamine receptors, which may facilitate the rational design of ligands targeting these receptors.
Asunto(s)
Microscopía por Crioelectrón , Histamina , Receptores Histamínicos , Ligandos , Humanos , Histamina/metabolismo , Histamina/química , Receptores Histamínicos/metabolismo , Receptores Histamínicos/química , Células HEK293 , Unión Proteica , Sitios de Unión , Agonistas de los Receptores Histamínicos/química , Agonistas de los Receptores Histamínicos/metabolismo , Agonistas de los Receptores Histamínicos/farmacología , Modelos MolecularesRESUMEN
BACKGROUND: The perioperative use of remifentanil is associated with postoperative hyperalgesia, which can impair recovery and extend hospitalization. Recent studies have revealed that microglia-mediated activation of the NLRP3 inflammasome plays a critical role in opioid-induced hyperalgesia, with NF-κB acting as a pivotal activation point for NLRP3. Despite these findings, the specific molecular mechanisms underlying remifentanil-induced postoperative hyperalgesia remain unclear. This study aims to develop a model of remifentanil-induced hyperalgesia and investigate the molecular mechanisms, focusing on the NF-κB/NLRP3 pathway, using both in vitro and in vivo approaches. METHOD: We established a remifentanil-induced hyperalgesia model and performed proteomic analysis to identify differential protein expression in the spinal cord tissue of rats. NLRP3 or PAK4 antagonists were administered intrathecally in vivo, and mechanical pain thresholds in the hind paws were measured using Von Frey testing. In vitro, we applied NLRP3 or PAK4 inhibitors or used lentivirus infection to silence PAK4, NF-κB, and NLRP3 genes. Protein expression was assessed through immunohistochemistry, immunofluorescence, and Western blotting. Additionally, ELISA was performed to measure IL-1ß and IL-18 levels, and RT-qPCR was conducted to evaluate the transcription of target genes. RESULTS: Proteomic analysis revealed that remifentanil upregulates PAK4 protein in spinal cord tissue two hours after the surgery. In addition, remifentanil induces morphological changes in the spinal cord dorsal horn, characterized by increased expression of PAK4, p-p65, NLRP3 and Iba-1 proteins, which in turn leads to elevated IL-1ß and IL-18 levels and an inflammatory response. Intrathecal injection of NLRP3 or PAK4 inhibitors mitigates remifentanil-induced hyperalgesia and associated changes. In vitro, downregulation of PAK4 inhibits the increase in PAK4, p-p65, NLRP3 and Caspase-1 induced by LPS. Conversely, the downregulation of NLRP3 does not impact the levels of PAK4 and p-p65 proteins, aligning with the in vivo results and suggesting that PAK4 acts as an upstream signaling molecule of NLRP3. CONCLUSION: Remifentanil can increase PAK4 expression in spinal cord dorsal horn cells by activating the NF-κB/NLRP3 pathway and mediating microglial activation, thereby contributing to postoperative hyperalgesia.
RESUMEN
Nitrogen (N) is essential for the physiological processes of plants. However, the specific mechanisms by which different nitrogen forms influence rice blast pathogenesis remain poorly understood. This study used hydroponic assays to explore how ammonium (NH4+) and nitrate (NO3-) affect rice after inoculation with Magnaporthe oryzae (M. oryzae). The results showed that NH4+, compared to NO3-, significantly reduced disease severity, fungal growth, fungal hyphae number, the expansion capacity of infectious hyphae, and disease-related loss of photosynthesis. Additionally, NH4+ enhanced the expression of defense-related genes, including OsPBZ1, OsCHT1, OsPR1a, and OsPR10. NH4+-treated rice also exhibited higher hydrogen peroxide (H2O2) accumulation and increased antioxidant enzyme activities. Moreover, susceptibility to rice blast disease increased when H2O2 was scavenged, while a reduction in susceptibility was observed with the application of exogenous H2O2. These results suggest that ammonium enhances rice resistance to M. oryzae, potentially through H2O2 accumulation. The findings provide valuable insights into how different nitrogen forms affect plant immunity in rice, which is crucial for controlling rice blast and ensuring stable food production.
Asunto(s)
Compuestos de Amonio , Resistencia a la Enfermedad , Peróxido de Hidrógeno , Oryza , Enfermedades de las Plantas , Oryza/microbiología , Oryza/metabolismo , Oryza/genética , Oryza/inmunología , Peróxido de Hidrógeno/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Compuestos de Amonio/metabolismo , Compuestos de Amonio/farmacología , Resistencia a la Enfermedad/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Magnaporthe/fisiología , Ascomicetos/patogenicidad , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genéticaRESUMEN
Magnetite (Fe3O4) has a large theoretical reversible capacity and rich Earth abundance, making it a promising anode material for LIBs. However, it suffers from drastic volume changes during the lithiation process, which lead to poor cycle stability and low-rate performance. Hence, there is an urgent need for a solution to address the issue of volume expansion. Taking inspiration from how glycophyte cells mitigate excessive water uptake/loss through their cell wall to preserve the structural integrity of cells, we designed Fe3O4@PMMA multi-core capsules by microemulsion polymerization as a kind of anode materials, also proposed a new evaluation method for real-time repair effect of the battery capacity. The Fe3O4@PMMA anode shows a high reversible specific capacity (858.0â mAh g-1 at 0.1â C after 300â cycles) and an excellent cycle stability (450.99â mAh g-1 at 0.5â C after 450â cycles). Furthermore, the LiNi0.8Co0.1Mn0.1O2/Fe3O4@PMMA pouch cells exhibit a stable capacity (200.6 mAh) and high-capacity retention rate (95.5 %) after 450â cycles at 0.5â C. Compared to the original battery, the capacity repair rate of this battery is as high as 93.4 %. This kind of bionic capsules provide an innovative solution for improving the electrochemical performance of Fe3O4 anodes to promote their industrial applications.
RESUMEN
Epidermal growth factor receptor (EGFR) plays a pivotal role in the initiation and progression of gliomas. In particular, in glioblastoma, EGFR amplification emerges as a catalyst for invasion, proliferation, and resistance to radiotherapy and chemotherapy. Current approaches are not capable of providing rapid diagnostic results of molecular pathology. In this study, we propose a terahertz spectroscopic approach for predicting the EGFR amplification status of gliomas for the first time. A machine learning model was constructed using the terahertz response of the measured glioma tissues, including the absorption coefficient, refractive index, and dielectric loss tangent. The novelty of our model is the integration of three classical base classifiers, i.e., support vector machine, random forest, and extreme gradient boosting. The ensemble learning method combines the advantages of various base classifiers, this model has more generalization ability. The effectiveness of the proposed method was validated by applying an individual test set. The optimal performance of the integrated algorithm was verified with an area under the curve (AUC) maximum of 85.8 %. This signifies a significant stride toward more effective and rapid diagnostic tools for guiding postoperative therapy in gliomas.
Asunto(s)
Receptores ErbB , Glioma , Espectroscopía de Terahertz , Humanos , Glioma/genética , Glioma/patología , Glioma/diagnóstico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Espectroscopía de Terahertz/métodos , Aprendizaje Automático , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Amplificación de Genes , Algoritmos , Máquina de Vectores de SoporteRESUMEN
The intestinal microbiota community is a fundamental component of the human body and plays a significant regulatory role in maintaining overall health and in the management disease states.The intestinal microbiota-gut-brain axis represents a vital connection in the cognitive regulation of the central nervous system by the intestinal microbiota.The impact of intestinal microbiota on cognitive function is hypothesized to manifest through both the nervous system and circulatory system. Imbalances in intestinal microbiota during the perioperative period could potentially contribute to perioperative neurocognitive dysfunction. This article concentrates on a review of existing literature to explore the potential influence of intestinal microbiota on brain and cognitive functions via the nervous and circulatory systems.Additionally, it summarizes recent findings on the impact of perioperative intestinal dysbacteriosis on perioperative neurocognitive dysfunction and suggests novel approaches for prevention and treatment of this condition.
Asunto(s)
Eje Cerebro-Intestino , Cognición , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiología , Eje Cerebro-Intestino/fisiología , Cognición/fisiología , Animales , Encéfalo , DisbiosisRESUMEN
OBJECTIVE: To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST) in the treatment of patients with acute myeloid leukemia(AML). METHODS: Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed. The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor (GPBSC), followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission (CR). The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated. Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype, including KIR ligand mismatch, 2DS1, haplotype, and HLA-Cw ligands on survival prognosis of patients. RESULTS: Forty-two patients received MST induction therapy, and the CR rate was 57.1% after 1 course and 73.7% after 2 courses. Multivariate analysis showed that, medium and high doses of NK cells was significantly associated with improved disease-free survival (DFS) of patients (HR=0.27, P =0.005; HR=0.21, P =0.001), and high doses of NK cells was significantly associated with improved overall survival (OS) of patients (HR=0.15, P =0.000). Donor 2DS1 positive significantly increases OS of patients (HR=0.25, P =0.011). For high-risk patients under 60 years old, patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group (P =0.036); donor 2DS1 positive significantly prolonged OS of patients (P =0.009). CONCLUSION: NK cell dose, KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST, improve the survival of AML patients.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Células Asesinas Naturales , Leucemia Mieloide Aguda , Trasplante Homólogo , Humanos , Leucemia Mieloide Aguda/terapia , Estudios Retrospectivos , Citarabina , Supervivencia sin Enfermedad , Masculino , Femenino , Pronóstico , Inducción de Remisión , Factor Estimulante de Colonias de Granulocitos , Adulto , Persona de Mediana EdadRESUMEN
Respiratory signals are critical clinical diagnostic criteria for respiratory diseases and health conditions, and respiratory sensors play a crucial role in achieving the desired respiratory monitoring effect. High sensitivity to a single factor can improve the reliability of respiratory monitoring, and maintaining the hygiene of the sensors is also important for daily health monitoring. Herein, we propose a flexible Au-modified anatase titanium dioxide resistive respiratory sensor, which can be mechanically compliantly attached to curved surfaces for respiratory monitoring in different modalities (i.e., respiratory intensity, frequency, and rate). The uniform and preferentially oriented anatase titanium dioxide films gained by the polymer-assisted deposition technique can be fabricated on flexible substrates through a liquid-assisted transferring process. The Au modification can enhance surface plasmon resonance to facilitate the photocatalytic activity of titanium dioxide, and the optimized distribution of Au on the surface of titanium dioxide film made the sensor have an excellent antibacterial effect. The uniquely designed encapsulation can effectively control the contact between the surface of titanium dioxide films and electrodes, allowing the flexible sensor to exhibit fast response time (0.71 s) and recovery time (1.06 s) to respiratory as well as insensitivity or low sensitivity to other factors (i.e., gas composition, humidity, temperature, stress, and strain). This work provided an effective strategy for flexible wearable respiratory sensors and has great potential in daily respiratory monitoring for health management and pandemic control.
Asunto(s)
Antibacterianos , Titanio , Reproducibilidad de los Resultados , Titanio/farmacología , Titanio/química , Antibacterianos/farmacología , Antibacterianos/químicaRESUMEN
The concentration of dopamine (DA) and tyrosine (Tyr) reflects the condition of patients with Parkinson's disease, whereas moderate paracetamol (PA) can help relieve their pain. Therefore, real-time measurements of these bioanalytes have important clinical implications for patients with Parkinson's disease. However, previous sensors suffer from either limited sensitivity or complex fabrication and integration processes. This work introduces a simple and cost-effective method to prepare high-quality, flexible titanium dioxide (TiO2) thin films with highly reactive (001)-facets. The as-fabricated TiO2 film supported by a carbon cloth electrode (i.e., TiO2-CC) allows excellent electrochemical specificity and sensitivity to DA (1.390 µA µM-1 cm-2), Tyr (0.126 µA µM-1 cm-2), and PA (0.0841 µA µM-1 cm-2). More importantly, accurate DA concentration in varied pH conditions can be obtained by decoupling them within a single differential pulse voltammetry measurement without additional sensing units. The TiO2-CC electrochemical sensor can be integrated into a smart diaper to detect the trace amount of DA or an integrated skin-interfaced patch with microfluidic sampling and wireless transmission units for real-time detection of the sweat Try and PA concentration. The wearable sensor based on TiO2-CC prepared by facile manufacturing methods holds great potential in the daily health monitoring and care of patients with neurological disorders.
Asunto(s)
Acetaminofén , Dopamina , Técnicas Electroquímicas , Titanio , Tirosina , Dispositivos Electrónicos Vestibles , Titanio/química , Acetaminofén/análisis , Dopamina/análisis , Tirosina/química , Técnicas Electroquímicas/métodos , Humanos , Electrodos , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentaciónRESUMEN
BACKGROUND: Gastroscopy is one of the most commonly used diagnostic modalities for upper gastrointestinal disorders. Remazolam besylate, a new type of ultrashort-acting benzodiazepine drug, has been less studied in gastroscopy. In this study, we studied the efficacy and safety of remazolam combined with propofol for painless gastroscopy. METHODS: This is a single-center, randomized controlled clinical trial. Hundred patients undergoing painless gastroscopy were included in this study and randomly divided into 2 groups (n = 50 per group): the remazolam 3 mg group (R3 group) and the remazolam 6 mg group (R6 group). Sufentanil, remazolam, and propofol are used to anesthetize the patients, and then, the effects of different dosages of remazolam on these patients are compared and analyzed. The patient's general condition, vital signs at different times, the dosage of propofol (mg) and additional times, complications, duration of gastroscopy (minute), awakening time (minute), residence time in the resuscitation room (minute), and adverse reactions were recorded. RESULTS: R3 group systolic blood pressure and diastolic blood pressure are more stable (P < .05); The number of additional propofol in R6 group was less (P < .05). The incidence of hypotension was lower in R3 group, as well as the time of awakening and staying in the resuscitation room were shorter (P < .05). CONCLUSION: Remazolam 3mg combined with sufentanil and propofol have less effect on hemodynamics in painless gastroscopy, and the patients have shorter awakening time.
Asunto(s)
Propofol , Sufentanilo , Humanos , Sufentanilo/efectos adversos , Gastroscopía , Benzodiazepinas , EtnicidadRESUMEN
BACKGROUND: Dementia is characterized by progressive neurodegeneration and therefore early intervention could have the best chance of preserving brain health. There are significant differences in health awareness, living customs, and daily behaviors among Chinese older adults compared to Europeans and Americans. Because the synergistic benefits of multidomain non-pharmacological interventions are consistent with the multifactorial pathogenicity of MCI, such interventions are more appealing, easier to adhere to, and more relevant to daily life than single-mode interventions. One of the aims of this study is to verify the effect of multidomain intervention strategies for MCI patients based on Chinese population characteristics, and the other is to establish a biobank and image database to investigate the pathogenesis and pathways of cognitive impairment. METHODS: Our study was designed as a national multicenter, community-based randomized controlled trial (RCT). Twelve medical institutions in ten Chinese cities will participate in our study from 2020 to 2024, and 1080 community residents aged 50 and above will be enrolled as participants. Each sub-center will be responsible for 90 participants (30 people per community) across three communities (non-contact control group, health education group, and multidomain intervention group). The community will be the basic unit of the present study, and all participants in each community will receive the same intervention/control measure. Three working groups are set up in each sub-center to manage the three communities independently to minimize interference at the implementation level between the groups. The multidomain intervention group will receive integrated interventions including exercise, nutrition, sleep, health education and mindfulness meditation. All data generated by the research will be analyzed and processed by statistical software (such as SPSS 21.0, Python 3.0, etc.), and part of the research data will be displayed in the form of graphs and tables. DISCUSSION: In order to achieve a high-quality community intervention study, it is crucial to have a well-designed experimental protocol that follows rigorous scientific methodology. In addition, effective management of quality control measures and monitoring compliance throughout the study process are essential components. This study provides a detailed discussion of stakeholder compliance, research quality control, potential harm and mitigation, auditing, and future plans in order to better address research issues. TRIAL REGISTRATION: ChiCTR2000035012 (July 27, 2020).
Asunto(s)
Disfunción Cognitiva , Terapia por Ejercicio , Humanos , Anciano , Terapia por Ejercicio/métodos , Disfunción Cognitiva/terapia , Disfunción Cognitiva/psicología , Ejercicio Físico , Encéfalo , Sueño , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Malocclusion is a prevalent dental health problem plaguing over 56% worldwide. Mechanical orthodontic aligners render directional teeth movement extensively used for malocclusion treatment in the clinic, while mechanical regulation inefficiency prolongs the treatment course and induces adverse complications. As a noninvasive physiotherapy, an appropriate electric field plays a vital role in tissue metabolism engineering. Here, we propose an occlusion-activated electromechanical synergistic dental aligner that converts occlusal energy into a piezo-excited alternating electric field for accelerating orthodontic tooth movement. Within an 18-day intervention, significantly facilitated orthodontic results were obtained from young and aged Sprague-Dawley rats, increasing by 34% and 164% in orthodontic efficiency, respectively. The different efficiencies were attributed to age-distributed periodontal tissue status. Mechanistically, the electromechanical synergistic intervention modulated the microenvironment, enhanced osteoblast and osteoclast activity, promoted alveolar bone metabolism, and ultimately accelerated tooth movement. This work holds excellent potential for personalized and effective treatment for malocclusions, which would vastly reduce the suffering of the long orthodontic course.
Asunto(s)
Maloclusión , Técnicas de Movimiento Dental , Ratas , Animales , Ratas Sprague-Dawley , Electricidad , Ingeniería , Maloclusión/terapiaRESUMEN
The Brewster effect has been previously reported as an essential mechanism for terahertz (THz) wave sensing application. However, generally in a sensing application, a complex rotation apparatus is required for detecting the slight change in Brewster angle. Here, we propose a graphene-based Brewster angle device operating at a specific terahertz frequency capable of sensing the refractive index at a fixed incident angle. In other words, our sensing device could avoid the impact of Brewster angle shift and eliminate the need for high-precision rotating equipment, which is usually required in traditional sensing applications. The conversion from the refractive index to a Volt-level detectable voltage roots from the tunability of graphene's Fermi level in the external electrical field. A linear correlation between the output voltage and the background refractive index is observed and theocratically analyzed. Furthermore, we present the improvement of our device in terms of sensing range and sensitivity by adjusting the permittivity of the dielectric substrate. As a demonstration of our proposed device, a detection range of 1.1-2.4 and a sensitivity of 20.06â V/RIU for refractive index is achieved on a high-resistance silicon substrate operating at 0.3 THz.
RESUMEN
Introduction: Emerging data suggest that perioperative gut dysbiosis is prevalent and may be associated with postoperative neurocognitive disorders (PND). Antibiotics and probiotics are key factors influencing the microbiota. Many antibiotics have anti-microorganisms and direct anti-inflammatory properties, which may have cognitive repercussions. NLRP3 inflammasome activation has been reported to be involved with cognitive deficits. This study aimed to determine the effect and mechanism of probiotics on neurocognitive problems associated with perioperative gut dysbiosis by the NLRP3 pathway. Methods: In a randomized, controlled trial, adult male Kunming mice undergoing surgery were administered cefazolin, FOS + probiotics, CY-09, or a placebo in four distinct experimental cohorts. Fear conditioning (FC) tests evaluate learning and memory. Following FC tests to evaluate inflammatory response (IR) and the permeability of barrier systems, the hippocampus and colon were extracted, and feces were collected for 16 s rRNA. Results: One week after surgery, surgery/anesthesia decreased the frozen behavior. Cefazolin attenuated this declination but aggravated postoperative freezing behavior 3 weeks after surgery. Probiotics ameliorated surgery/anesthesia-induced memory deficits and perioperative cefazolin-induced postoperative memory deficits 3 weeks after surgery. NLRP3, caspase-1, Interleukin-1ß (IL-1ß), and Interleukin-18 (IL-18) levels were increased 1 week after the hippocampus and colon surgery, which were attenuated by CY-09 and probiotics, respectively. Discussion: Probiotics could correct dysbacteria and IR caused by surgery/anesthesia stress and cefazolin alone. These findings imply that probiotics are an efficient and effective way of maintaining the balance of gut microbiota, which may reduce NLRP3-related inflammation and alleviate PND.
RESUMEN
Odorants are detected as smell in the nasal epithelium of mammals by two G-protein-coupled receptor families, the odorant receptors and the trace amine-associated receptors1,2 (TAARs). TAARs emerged following the divergence of jawed and jawless fish, and comprise a large monophyletic family of receptors that recognize volatile amine odorants to elicit both intraspecific and interspecific innate behaviours such as attraction and aversion3-5. Here we report cryo-electron microscopy structures of mouse TAAR9 (mTAAR9) and mTAAR9-Gs or mTAAR9-Golf trimers in complex with ß-phenylethylamine, N,N-dimethylcyclohexylamine or spermidine. The mTAAR9 structures contain a deep and tight ligand-binding pocket decorated with a conserved D3.32W6.48Y7.43 motif, which is essential for amine odorant recognition. In the mTAAR9 structure, a unique disulfide bond connecting the N terminus to ECL2 is required for agonist-induced receptor activation. We identify key structural motifs of TAAR family members for detecting monoamines and polyamines and the shared sequence of different TAAR members that are responsible for recognition of the same odour chemical. We elucidate the molecular basis of mTAAR9 coupling to Gs and Golf by structural characterization and mutational analysis. Collectively, our results provide a structural basis for odorant detection, receptor activation and Golf coupling of an amine olfactory receptor.
Asunto(s)
Aminas Biogénicas , Odorantes , Percepción Olfatoria , Poliaminas , Receptores Odorantes , Animales , Ratones , Aminas Biogénicas/análisis , Aminas Biogénicas/química , Aminas Biogénicas/metabolismo , Microscopía por Crioelectrón , Subunidades alfa de la Proteína de Unión al GTP Gs/química , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gs/ultraestructura , Odorantes/análisis , Percepción Olfatoria/fisiología , Poliaminas/análisis , Poliaminas/química , Poliaminas/metabolismo , Receptores de Amina Biogénica/química , Receptores de Amina Biogénica/genética , Receptores de Amina Biogénica/metabolismo , Receptores de Amina Biogénica/ultraestructura , Receptores Odorantes/química , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores Odorantes/ultraestructura , Olfato/fisiología , Espermidina/análisis , Espermidina/química , Espermidina/metabolismoRESUMEN
Microsphere-assisted super-resolution imaging technology offers label-free, real-time dynamic imaging via white light, which has potential applications in living systems and the nanoscale detection of semiconductor chips. Scanning can aid in overcoming the limitations of the imaging area of a single microsphere superlens. However, the current scanning imaging method based on the microsphere superlens cannot achieve super-resolution optical imaging of complex curved surfaces. Unfortunately, most natural surfaces are composed of complex curved surfaces at the microscale. In this study, we developed a method to overcome this limitation through a microsphere superlens with a feedback capability. By maintaining a constant force between the microspheres and the sample, noninvasive super-resolution optical imaging of complex abiotic and biological surfaces was achieved, and the three-dimensional information on the sample was simultaneously obtained. The proposed method significantly expands the universality of scanning microsphere superlenses for samples and promotes their widespread use.
RESUMEN
OBJECTIVE: Diabetes mellitus-induced oxidative stress (OS) causes liver injury. Intraoperative pumping of dexmedetomidine (DEX) effectively reduced the postoperative OS response in patients with type 2 diabetes mellitus (T2DM) and had a certain protective effect on liver function. However, the mechanisms of the protective effect on the liver remained unclear. In this study, we investigated the antagonistic effects and the possible mechanism of DEX on T2DM-induced liver injury in the mouse model and Palmitic acid (Pal)-induced injury in hepatocellular carcinoma cells (HepG2). METHODS: Seven wt/wt mice served as Control group, and 28 db/db mice were randomly divided into four groups using a random number table method: Model group (n=7), D25 group (n=7), D50 group (n=7) and D75 group (n=7). Different concentrations of DEX were injected intraperitoneally in the D25 group, D50 group and D75 group, while the Control group and the Model group were intraperitoneally injected with the same amount of normal saline for 3 weeks. In the cell intervention experiments, HepG2 cell line was used. The control group (Con group), the palmitic acid group (Pal group) and the DEX treatment group (Pal + Dex group) were set up. The test results were compared among mice groups and cell groups, respectively. RESULTS: DEX alleviated the increase of alanine aminotransferase, triglyceride, total cholesterol and aspartate aminotransferase contents induced by high fat or T2DM. DEX reversed the decrease of nuclear factor E2 related factor 2 (Nrf2) in the nuclear translocation and the lower transcriptional activity of Nrf2 to inhibit the expression of heme oxygenase-1, NADPH quinone oxidoreductase-1 and superoxide dismutase 2 and reduced the activity of superoxide dismutase to increase reactive oxygen species content induced by high fat or T2DM. CONCLUSION: By attenuating the high-fat or T2DM-induced Nrf2 pathway impairment, DEX can reduce OS injury and inhibit the disorder of lipid anabolism and protect liver function. This study provides a theoretical basis for the protection of liver function by DEX in clinical T2DM patients.
RESUMEN
Gliomas are the most common type of primary tumor in the central nervous system in adults. Isocitrate dehydrogenase (IDH) mutation status is an important molecular biomarker for adult diffuse gliomas. In this study, we were aiming to predict IDH mutation status based on terahertz time-domain spectroscopy technology. Ninety-two frozen sections of glioma tissue from nine patients were included, and terahertz spectroscopy data were obtained. Through Least Absolute Shrinkage and Selection Operator (LASSO), Principal component analysis (PCA), and Random forest (RF) algorithms, a predictive model for predicting IDH mutation status in gliomas was established based on the terahertz spectroscopy dataset with an AUC of 0.844. These results indicate that gliomas with different IDH mutation status have different terahertz spectral features, and the use of terahertz spectroscopy can establish a predictive model of IDH mutation status, providing a new way for glioma research.
Asunto(s)
Neoplasias Encefálicas , Glioma , Adulto , Humanos , Isocitrato Deshidrogenasa/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Imagen por Resonancia Magnética/métodos , Glioma/genética , Glioma/patología , MutaciónRESUMEN
A quantitative analysis method for corrosion products based on terahertz spectroscopy is proposed in this paper. Mixture samples consisting of three major corrosion products (magnetite, hematite, and goethite) were prepared in 51 different concentrations. The refractive index spectra measured by terahertz time-domain spectroscopy were projected to the 2D score diagram by performing principal component analysis. The Euclidean distances between the mixtures and pure analyte on the diagram were used to build a concentration prediction model. The results indicate that the established model can precisely predict the concentration of magnetite, which is essential for a stability evaluation of the corrosion system.
RESUMEN
Fast, simple, and label-free detections and distinctions are desirable in cell biology analysis and diagnosis. Here, a biosensor based on terahertz metamaterial has luxuriant gaps, which can excite dipole resonance is designed. Filling the gaps with various analytes can change the biosensor's capacitance resulting in electromagnetic properties changing. The idea is verified by simulations and experiments. The theoretical sensitivity of the biosensor approaches 290 GHz/RIU, and the experimental concentration sensitivity of the biosensor is ≥ 275 kHz mL/cell. Candida Albicans, Escherichia Coli, and Shigella Dysenteriae were selected as analytes, and the measurement frequency shift is 270 GHz, 290 GHz, and 310 GHz, respectively, which indicates that the biosensor can detect and distinguish these bacteria. Successfully detection of low-concentration glioblastoma (200 cells/mL), showing great potential for the early diagnosis of glioblastoma of the biosensor. This biosensor supplies a new horizon for cell detection, which will significantly benefit cell biology investigation.