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A label-free optical sandwich immunoassay sensor, utilizing weak value amplification and total internal reflection, was devised for real-time, high-sensitivity analysis and detection of low-concentration targets. 3D printed channels and sodium chloride solution were employed to ensure reproducibility, reliability, and stability of the measurements for calibration. The sandwich structure demonstrated enhanced responsiveness in the proposed optical biosensor through a comparative analysis of the direct assay and sandwich assay for detecting alpha-fetoprotein (AFP) at the same concentration. By optimizing the binding sequences of the coating antibody, target, and detection antibody in the sandwich method, a more suitable sandwich sensing approach based on weak value amplification was achieved. With this approach, the limit of detection (LOD) of 6.29 ng/mL (pM level) for AFP in PBS solution was achieved. AFP testing and regeneration experiments in human serum have proved the feasibility of our methods in detecting complex samples and the reusability of sensing chips. Additionally, the method demonstrated excellent selectivity for unpaired antigens. The efficacy of this methodology was evaluated by simultaneously detecting AFP, carcinoembryonic antigen (CEA), and CA15-3 on a singular sensor chip. In conclusion, the label-free sandwich immunoassay sensing scheme holds promise for advancing the proposed optical sensors based on weak value amplification in early diagnosis and prevention applications. Compared to other biomarker detection methods, it will be easier to promote in practical applications.
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Técnicas Biosensibles , Antígeno Carcinoembrionario , Límite de Detección , alfa-Fetoproteínas , Técnicas Biosensibles/métodos , alfa-Fetoproteínas/análisis , Humanos , Antígeno Carcinoembrionario/sangre , Antígeno Carcinoembrionario/análisis , Inmunoensayo/métodos , Mucina-1/sangre , Mucina-1/análisis , Anticuerpos Inmovilizados/inmunología , Anticuerpos Inmovilizados/químicaRESUMEN
OBJECTIVE: Placenta-derived inflammation plays a vital role in the pathophysiology of gestational diabetes mellitus (GDM). IL-32 is a novel pro-inflammatory cytokine and metabolic regulator involved in the development of metabolic disease. We investigated the effect of IL-32 in GDM. MATERIALS AND METHODS: First-trimester C-reactive protein (CRP) level was monitored in a case-control study of 186 women with GDM and 186 women without. Placental tissue was lysed and analyzed by high-resolution liquid chromatography-tandem mass spectrometry. Circulating level of inflammatory cytokines IL-32, IL-6, and TNF-α were measured by ELISA kits. The expression of placenta-derived macrophages, inflammatory cytokines, and related pathway proteins were assessed by reverse transcriptase-quantitative PCR, western blot, immunohistochemistry, or immunofluorescence. RESULTS: First-trimester CRP level in peripheral blood was closely associated with glucose and insulin resistance index and was an independent correlation with the development of GDM. High-resolution liquid chromatography-tandem mass spectrometry revealed that placenta-derived CRP expression was dramatically elevated in women with GDM. Interestingly, the expression of placenta-derived IL-32 was also increased and located in the macrophages of placental tissue. Meanwhile, the expression of IL-6, TNF-α, and p-p38 were up-regulated in the placental tissues with GDM. Either IL-6 or TNF-α was colocated with IL-32 in the placental tissue. Importantly, circulating IL-32 throughout pregnancy was increased in GDM and was related to placental-derived IL-32 expression, circulating IL-6, and TNF-α, glucose and insulin resistance index. CONCLUSION: Increased circulating IL-32 throughout pregnancy was closely associated with placenta macrophage-derived IL-32 expression and GDM. First trimester IL-32 level in peripheral blood may serve to predict the development of GDM.
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Diabetes Gestacional , Resistencia a la Insulina , Embarazo , Femenino , Humanos , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Estudios de Casos y Controles , Placenta/metabolismo , Citocinas , Insulina , GlucosaRESUMEN
In this study, an interfacial biosensing scheme with ultra-precision is proposed. The scheme uses weak measurement techniques to ensure ultra-high sensitivity of the sensing system while improving the stability of the system through self-referencing and pixel point averaging, thus achieving ultra-high detection accuracy of biological samples. In specific experiments, we have used the biosensor in this study to perform specific binding reaction experiments for protein A and Mouse IgG with a detection line of 2.71 ng/mL for IgG. In addition, the sensor is non-coated, simple in structure, easy to operate, and low in cost of use.
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Técnicas Biosensibles , Animales , Ratones , Técnicas Biosensibles/métodos , Inmunoglobulina GRESUMEN
The surface area is key to electrochemical systems, including those in electrocatalysis and energy storage. Studies have shown that the surface area of the electrocatalyst directly affects the electrochemical activity, adsorption performance, and stability of the electrocatalyst. This paper used an optical weak measurement (WM) method, which has little impact on the analyte, to measure the reaction surface area (RSA) that actually participated in the electrochemical reaction. Then compared the RSA obtained by the WM with the total surface area (TSA) obtained by the standard Brunauer-Emmett-Teller (BET) measurement and the active surface area (ASA) obtained by the electrochemical double-layer capacitance (EDLC) method. Their growth trend was consistent, indicating the reliability of the WM method. Compared with the above two methods, the WM method is an in situ detection and easy to operate experimentally, which can help researchers to consider the effect of surface area on electrocatalyst performance more rationally.
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In this work, the difference between the weak measurement method and the weak value amplification process and the classical measurement process is thoroughly discussed, and the transition conditions of the weak value enhancement are obtained. A transition mode of the weak measurement and the classical measurement is proposed for the first time, and a better fitting model of the measurement results is found by performing a systematic analysis. On top of that, the importance of the new fitting method for the application of the weak measurement system is verified during the industrial production of organic molecular -nucleic acid, protein, polysaccharide-hydrolysis or synthesis. At the same time, a variety of spectral characterization methods are proposed and the advantages and disadvantages of the different characterization methods are analyzed through carrying out experiments. Consequently, the wide implementation of weak measurement-based detection technology is attained.
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Diabetes is an important public health problem and finding quick testing methods with high accuracy, reliability, and convenience are important to control the blood glucose of diabetic patients. In this study, a sensor based on a weak measurement scheme was developed for the specific detection of glucose for the first time. The detection of glucose using the proposed method was completed by the high sensitivity and resolution of the weak measurement based on optical rotation detection, as well as the change in the optical rotation before and after the specific oxidation of glucose. The resolution of the as-obtained glucose sensor was around 2.71×10-3 g/L (1.50×10-2 mmol/L), and the detection range was 0-11 g/L (0-61 mmol/L).
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Flow battery electrodes are vital for performing redox reactions, and an in-depth understanding of reaction kinetics and spatial distribution differences in electrodes is very important for improving the efficiency of electrochemical reactions. In this study, a reflection-type phase-sensitive weak measurement imaging system was developed for the detection of flow batteries. The phase difference between two polarization components in total internal reflection caused by electrode redox processes was measured by weak value amplification. The resulting refractive index resolution of the imaging system was estimated to be 2.8-4.2 × 10-6 RIU. The real-time monitoring ability of the system was demonstrated by linear sweep voltammetry tests of vanadium redox batteries. Compared to traditional optical methods, the proposed weak measurement imaging sensor did not require coating, as it can be used in acid electrolytes of vanadium flow batteries. Meanwhile, the weak value amplification effect led to a higher resolution than the total internal reflection system shown in our previous work, thereby resulting in more accurate detection of electrochemical reactions. In sum, the proposed sensor looks very promising for the detection of electrochemical reactions in flow batteries, water splitting, electrochemical corrosion, and electrocatalysis.
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Suministros de Energía Eléctrica , Electrólitos , Electrodos , Oxidación-Reducción , VanadioRESUMEN
In the field of electrochemical energy storage systems, the use of in situ detection technology helps to study the mechanism of electrochemical reaction. Our group has previously in situ detected the electrochemical reaction in vanadium flow batteries by total internal reflection (TIR) imaging. In order to further improve the detection resolution, in this study, the weak measurement (WM) method was introduced to in situ detect the electrochemical reaction during the linear sweep voltammetry or the cyclic voltammetry tests with quantitative measurement of the absolute current density, which lays a foundation for replacing the TIR for two-dimensional imaging of electrochemical reactions in vanadium flow batteries, oxygen/hydrogen evolution reaction, surface treatments, electrochemical corrosion and so on.
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Lung cancer is the most common and lethal malignant disease for which the development of efficacious chemotherapeutic agents remains an urgent need. Pristimerin (PRIS), a natural bioactive component isolated from various plant species in the Celastraceae and Hippocrateaceae families, has been reported to exhibit outstanding antitumor effects in several types of cells. However, the underlying mechanisms involved remain poorly understood. Here, we reported the novel finding that PRIS significantly suppressed lung cancer growth in conditionally reprogrammed patient-derived lung adenocarcinoma cells (CRLCs). We demonstrated that PRIS inhibited the cell viabilities, migrative and invaded abilities, and capillary structure formation of CRLCs. Furthermore, our results clarified that PRIS induced mitochondrial dysfunction through reactive oxygen species (ROS) generation, activation of caspase-9, caspase-3, and caspase-4, and expression of endoplasmic reticulum (ER) stress-associated proteins. Inhibition of ER stress by 4-PBA (4-phenylbutyric acid, a specific ER stress inhibitor) or CHOP siRNA transfection ameliorated PRIS-induced loss of mitochondrial membrane potential and intrinsic apoptosis. The present study also provides mechanistic evidence that PRIS suppressed the EphB4/CDC42/N-WASP signaling pathway, which is required for mitochondrial-mediated intrinsic apoptosis, activation of ER stress, and stimulation of caspase-4 induced by PRIS, and consequently resulting in suppressed cell viability, migration, and angiogenesis in CRLCs. Taken together, by providing a mechanistic insight into the modulation of ER stress-induced cell death in CRLCs by PRIS, we suggest that PRIS has a strong potential of being a new antitumor therapeutic agent with applications in the fields of human lung adenocarcinoma.
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Adenocarcinoma del Pulmón/fisiopatología , Mitocondrias/efectos de los fármacos , Triterpenos Pentacíclicos/efectos adversos , Tripterygium/efectos adversos , Movimiento Celular , Proliferación Celular , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Transducción de Señal , TransfecciónRESUMEN
The ability to identify L(+)-ascorbic acid from D(-)-isoascorbic acid in medicinal products is of practical interest. Based on the method of frequency domain weak measurement, a set of common optical path sensors for identification of L(+)-ascorbic acid and D(-)-isoascorbic acid is established. By quantificationally analyzing the magnitude and offset direction of the spectral central wavelength, a good identification of the concentration and the optically active forms of ascorbic acid has been achieved. The sensitivity and resolution of the sensor for optical rotation can reach 34.35 nm/° and ${5.53} \times {{10}^{ - 5}}^\circ $5.53×10-5 ∘, respectively. The detection resolution for L(+)-ascorbic acid is ${2.00} \times {{10}^{ - 4}}\;{\rm mol}/{\rm mL}$2.00×10-4mol/mL, and that for D(-)-isoascorbic acid is ${2.73} \times {{10}^{ - 4}}\;{\rm mol}/{\rm mL}$2.73×10-4mol/mL. The potential of the sensor in the detection of transparent but optically inactive impurities has been verified by comparative experiments of sodium chloride solution. The sensor also has been applied to identify medicinal vitamin C tablets, which verified the feasibility of the method in optically active pharmaceutical solutions with water-insoluble, optically inactive impurities. Since the sensor has the advantages of high precision, real-time, high robustness, and being non-destructive, it has a great prospect in the field of drug detection containing chiral molecules.
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In this paper, we propose a linear differential detection system based on a frequency domain weak measurement. The system can be used for detecting optical substances. Moreover, we completed an experiment to detect himan serum albumin (HSA) content in a mixture of human serum albumin and l-proline via dialysis. This work also proves the differential function of the system. This experiment can be further extended to detecting protein content in a mixed solution that contains protein macromolecules and various small molecules. It is very important for detecting molecules without photomarking in solutions of complex biological samples. In this paper, the system has an optical resolution of 1.39 × 10-5, and resolution of 4.06 × 10-8 mol/L for himan serum protein solution.
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Óptica y Fotónica/métodos , Albúmina Sérica Humana/análisis , Glucosa/química , Humanos , Rotación Óptica , Prolina/química , Teoría CuánticaRESUMEN
In this paper, we propose a post-Gaussian filtering theory for weak measurement in the frequency domain, and propose a highly deformed digital filtering technique that can be used to optimize sensors based on weak-frequency measurement techniques. We completed the experimental verification based on the weak measurement total internal reflection sensor. The experimental results show that digital filtering technology can optimize the system in the working range, sensitivity, and resolution of the frequency domain weak measurement system, so that it can reach 0.210 rad, 3210.9 nm/RIU, and 7.12×10-7 RIU, respectively.
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We propose a self-referential fast detection scheme for a frequency domain weak measurement system for the detection of enantiomeric impurities in chiral molecules. In a transmissive weak measurement system, the optical rotation (OR) is used to modify the pre-selected polarization state and the post-selection polarization state. We obtained the sum and difference of the optical rotations produced by the sample and the standard by rotating the quarter wave plate in the system. Then, we estimate the ratio of chiral molecules to enantiomeric impurities using the ratio of the central wavelength shifts caused by the addition and subtraction states described above. In this paper, our system has an optical resolution of 1.88 × 10-5°. At the same time, we completed the detection of the ratio of the two substances in the mixture of L-proline and D-proline in different proportions, which proved that our system can quickly detect the content of enantiomeric impurities in chiral molecules.
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Resins derived from natural rosin have been described recently as environmentally-friendly adsorbents with potential uses in the clean-up of wastewaters and the treatment of drinking waters. However, in order to improve the design of these products it is important to understand the chemical mechanisms through which they act. We now describe the combined use of EPR spectroscopy and Cu(II) to probe directly the metal coordination environment after uptake by various rosin-derived products. Clear distinctions are demonstrated between the copper bonding in different adsorbent preparations. Furthermore, in the case of nitrogen cross-linked products, the spectral parameters also provide information on the number of nitrogen atoms in the immediate atomic environment of the copper atom when covalent bonding is involved. This methodology works well for adsorption from solutions containing multiple components, because only those that are paramagnetic are detected, and different types of paramagnetic metal ion produce distinctly different EPR spectra.
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Cobre/química , Espectroscopía de Resonancia por Spin del Electrón/métodos , Resinas de Plantas/química , AdsorciónRESUMEN
The study aimed to investigate the effects of small ubiquitin-related modifier (SUMO) specific protease 1 (SENP1) on human PXR-mediated MDR1 transcriptional activity and mRNA expression. Empty vector and expression plasmids, including PXR, SENP1 and SENP1 mutant (SENP1m) were transiently transfected into HepG2 and LS174T cells using Lipo2000. Transcriptional activity was detected by dual luciferase reporter gene assay, and mRNA level was measured using real-time polymerase chain reaction. The results showed that SENP1 could remarkably reduce the rifampicin (RIF)-induced MDR1 reporter activity and mRNA level in hPXR over expressed HepG2 and LS174T cells (P < 0.05), whereas adding SENP1m restored the RIF-induced increases (P < 0.05). These results indicated that SENP1 could repress the RIF-induced hPXR-mediated MDR1 transcriptional activity and mRNA expression.
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Endopeptidasas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Activación Transcripcional , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Cisteína Endopeptidasas , Expresión Génica , Células Hep G2 , Humanos , Receptor de la Señal 1 de Direccionamiento al Peroxisoma , ARN MensajeroRESUMEN
This study was purposed to investigate the conditions for improving human-mouse xenograft and the erythroid differentiation of human hematopoietic stem cells (HSC) in the xenotransplant model. The engraftments of different mouse strains (NOD/SCID or NOD/SCID/IL2rγ(null)), schemes of irradiation (single-time or 2-times radiation; Co(60)γ-ray or X-ray) and strategies of CB CD34(+) cells ex vivo culture time and lentivirus infection were compared. The results showed that at 4 weeks after transplantation, the ratio of hCD45 positive cells in bone marrow of NOD/SCID/IL2rγ(null) mice increased to (51.4 ± 13.9)%, and erythroid precursor could be detected. All of the mice receiving X-ray irradiation for 2 times (a dose of 1 Gy, then the second of 1.5 Gy, with an interval of 15 min) survived. Fresh isolated CB CD34(+) cells were cultured and infected with lentivirus for 72 h and then transplanted into receptor mouse. After 4 weeks, higher engraftment [hCD45 (51.4 ± 13.9)%] and better erythroid development [hCD71(+) GPA(+) (5.98 ± 3.46)%] were observed. It is concluded that NOD/SCID/IL2rγ(null) mice receiving X-ray irradiation for 2 times and were injected with fresh isolated CB CD34(+) cells cultured and infected with lentivirus ex vivo within 72 h show a better xenograft and erythroid development.
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Eritrocitos/citología , Eritropoyesis , Trasplante de Células Madre Hematopoyéticas/métodos , Animales , Antígenos CD34 , Células de la Médula Ósea/citología , Células Cultivadas , Femenino , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Trasplante HeterólogoRESUMEN
OBJECTIVE: To observe the effect of Yangyin Humo Decoction (YHD) on oral mucomembranous reaction in patients with head-neck tumor undergoing radiotherapy. METHODS: Forty-Forty-two patients with head-neck tumor undergoing radiotherapy were randomized equally into two groups. The two conventional Western medical treatment was administered to all, including intravenous dripping of 2% lidocaine 20 mL, dexamethasone 5 mg, gentamycin 80,000 units, vitamin B(12) 5 mg, dissolved in saline 250 mL, and 5% sodium bicarbonate solution for gargling, but to the patients in the tested group, YHD was given additionally. The medication was started simultaneously all through the whole course of the radiotherapy. Patients were examined every day to observe and compare the degree, initiating time, and repairing time of their oral lesions; the dosage of radiation they received was recorded as well. RESULTS: The degree of mucomembranous reaction that appeared in most patients in the test group was of grade 1-2, while in the control group, it was grade 2-3. The average time for oral lesion of 1, 2, 3 grades to be initiated in the test group was 12.0+/-1.1, 11.0+/-1.3 and 10.0+/-0.8 days, respectively, after radiation started, which was later than that in the control group (P<0.01). Moreover, the average repairing time for the lesions of grades 1, 2, and 3 in the test group was 3.0+/-0.7, 10.0+/-1.3 and 19.0+/-0.8 days, which were shorter than those in the control group respectively (P<0.01). The radiation applied on the primary tumor of patients with oral lesion of grade 1-3 in the test group was 24.2+/-2.2, 42.0+/-2.6 and 58.0+/-1.6 Gy on the average, respectively, which were higher than that applied on patients in the control group (P<0.05 or P<0.01). CONCLUSION: The Chinese herbal preparation YHD could alleviate oral mucomembranous reaction to radiation applied in patients with head-neck tumor.