ABSTRACT
Developing ultrasensitive lateral flow immunoassays (LFIAs) has garnered significant attention in the field of point-of-care testing. In this study, a trimetallic dendritic nanozyme (Pd@Pt-Ru) was synthesized through Ru deposition on a Pd@Pt core and utilized to enhancing the sensitivity of LFIAs. Pd@Pt-Ru exhibited a Km value of 5.23 mM for detecting H2O2, which indicates an H2O2 affinity comparable with that of horseradish peroxidase. The Ru surface layer reduces the activation energy barrier, which increases the maximum reaction rate. As a proof of concept, the proposed Pd@Pt-Ru nanozyme was incorporated into LFIAs (A-Pd@Pt-Ru-LFIAs) for detecting human chorionic gonadotropin (hCG). Compared with conventional gold nanoparticle (AuNP)-LFIAs, A-Pd@Pt-Ru-LFIAs demonstrated 250-fold increased sensitivity, thereby enabling a visible detection limit as low as 0.1 IU/L. True positive and negative rates both reached 100%, which renders the proposed Pd@Pt-Ru nanozyme suitable for detecting hCG in clinical samples.
Subject(s)
Chorionic Gonadotropin , Hydrogen Peroxide , Limit of Detection , Metal Nanoparticles , Palladium , Platinum , Ruthenium , Palladium/chemistry , Platinum/chemistry , Immunoassay/methods , Humans , Ruthenium/chemistry , Chorionic Gonadotropin/analysis , Metal Nanoparticles/chemistry , Hydrogen Peroxide/analysis , Hydrogen Peroxide/chemistry , Gold/chemistry , Dendrimers/chemistry , Biosensing Techniques/methods , Peroxidase/chemistry , CatalysisABSTRACT
New strategies for the simultaneous and portable detection of multiple enzyme activities are highly desirable for clinical diagnosis and home care. However, the methods developed thus far generally suffer from high costs, cumbersome procedures, and heavy reliance on large-scale instruments. To satisfy the actual requirements of rapid, accurate, and on-site detection of multiple enzyme activities, we report herein a smartphone-assisted programmable microfluidic paper-based analytical device (µPAD) that utilizes colorimetric and photothermal signals for simultaneous, accurate, and visual quantitative detection of alkaline phosphatase (ALP) and butyrylcholinesterase (BChE). Specifically, the operation of this µPAD sensing platform is based on two sequential steps. Cobalt-doped mesoporous cerium oxide (Co-m-CeO2) with remarkable peroxidase-like activities under neutral conditions first catalytically decomposes H2O2 for effectively converting colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxidized TMB (oxTMB). The subsequent addition of ALP or BChE to their respective substrates produces a reducing substance that can somewhat inhibit the oxTMB transformation for compromised colorimetric and photothermal signals of oxTMB. Notably, these two-step bioenzyme-nanozyme cascade reactions strongly support the straightforward and excellent processability of this platform, which exhibit lower detection limits for ALP and BChE with a detection limit for BChE an order of magnitude lower than those of the other reported paper-based detection methods. The practicability and efficiency of this platform are further demonstrated through the analysis of clinical serum samples. This innovative platform exhibits great potential as a facile yet robust approach for simultaneous, accurate, and on-site visual detection of multiple enzyme activities in authentic samples.
Subject(s)
Alkaline Phosphatase , Butyrylcholinesterase , Colorimetry , Paper , Alkaline Phosphatase/metabolism , Alkaline Phosphatase/analysis , Alkaline Phosphatase/chemistry , Humans , Butyrylcholinesterase/metabolism , Butyrylcholinesterase/blood , Lab-On-A-Chip Devices , Benzidines/chemistry , Smartphone , Cerium/chemistry , Cobalt/chemistry , Microfluidic Analytical Techniques/instrumentation , Limit of Detection , Enzyme Assays/methods , Enzyme Assays/instrumentation , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysisABSTRACT
A standardized phase retrieval algorithm is presented and applied to an industry-grade high-energy ultrashort pulsed laser to uncover its spatial phase distribution. We describe in detail how to modify the well-known algorithm in order to characterize particularly strong light sources from intensity measurements only. With complete information about the optical field of the unknown light source at hand, virtual back propagation can reveal weak points in the light path such as apertures or damaged components.
ABSTRACT
Although lipophilic shellfish toxins (LSTs) pose a significant threat to the health of seafood consumers, their systematic investigation and risk assessment remain scarce. The goals of this study were as follows: (1) analyze LST levels in commercially available shellfish in Zhejiang province, China, and determine factors influencing LST distribution; (2) assess the acute dietary risk of exposure to LSTs for local consumers during the red tide period; (3) explore potential health risks of LSTs in humans; and (4) study the acute risks of simultaneous dietary exposure to LSTs and paralytic shellfish toxins (PSTs). A total of 546 shellfish samples were collected. LSTs were detected in 89 samples (16.3%) at concentrations below the regulatory limits. Mussels were the main shellfish species contaminated with LSTs. Spatial variations were observed in the yessotoxin group. Acute exposure to LSTs based on multiple scenarios was low. The minimum tolerable exposure durations for LSTs calculated using the mean and the 95th percentile of consumption data were 19.7 and 4.9 years, respectively. Our findings showed that Zhejiang province residents are at a low risk of combined exposure to LSTs and PSTs; however, the risk may be higher for children under 6 years of age in the extreme scenario.
Subject(s)
Dietary Exposure , Marine Toxins , Shellfish , China , Humans , Shellfish/analysis , Marine Toxins/analysis , Marine Toxins/toxicity , Animals , Risk Assessment , Dietary Exposure/analysis , Shellfish Poisoning/prevention & control , Shellfish Poisoning/etiology , Food Contamination/analysis , Adult , Child , Middle Aged , Seafood/analysis , Child, Preschool , Bivalvia/chemistry , Female , Young AdultABSTRACT
Outer membrane vesicles (OMVs) are attractive for biomedical applications based on their intrinsic properties in relation to bacteria and vesicles. However, their widespread use is hampered by low yields and purities. In this study, EVscore47 multifunctional chromatography microspheres were synthesized and used to efficiently isolate functional OMVs from Escherichia coli. Through this technology, OMV loss can be kept to a minimum, and OMVs can be harvested using EVscore47 at 11-fold higher yields and ~13-fold higher purity than those achieved by means of ultracentrifugation. Based on the results presented here, we propose a novel EVscore47-based isolation of OMVs that is fast and scalable.
Subject(s)
Escherichia coli , Extracellular Vesicles , Microspheres , Extracellular Vesicles/chemistry , Extracellular Vesicles/metabolism , Bacterial Outer Membrane/metabolism , Bacterial Outer Membrane Proteins/chemistry , Ultracentrifugation , Chromatography/methodsABSTRACT
Surface-enhanced infrared absorption (SEIRA) spectroscopy is an emerging research field that has received much attention from the research community. Unlike conventional infrared absorption spectroscopy, SEIRA spectroscopy is a surface sensitive technique that exploits the electromagnetic properties of nanostructured substrates to amplify the vibrational signals of adsorbed molecules. Unique advantages like high sensitivity, wide adaptability, and convenient operation allow SEIRA spectroscopy to be applied in qualitative and quantitative analyses for traces of gases, biomolecules, polymers, and so on. In this review, we summarize recent advances in nanostructured substrates for SEIRA spectroscopy, including the developing history and widely accepted SEIRA mechanisms of SEIRA spectroscopy. Most importantly, characteristics and preparation methods of representative SEIRA-active substrates are introduced. In addition, current deficiencies and prospects in the field of SEIRA spectroscopy are discussed.
Subject(s)
Nanostructures , Spectrophotometry, Infrared/methodsABSTRACT
This study presents the first-ever synthesis of samarium-doped indium vanadate nanosheets (IVONSs:Sm) via microemulsion-mediated solvothermal method. The nanosheets were subsequently utilized as a nano-matrix in laser desorption/ionization mass spectrometry (LDI-MS). It was discovered that the as-synthesized IVONSs:Sm possessed the following advantages: improved mass spectrometry signal, minimal matrix-related background, and exceptional stability in negative-ion mode. These qualities overcame the limitations of conventional matrices and enabled the sensitive detection of small biomolecules such as fatty acids. The negative-ion LDI mechanism of IVONSs:Sm was examined through the implementation of density functional theory simulation. Using IVONSs:Sm-assisted LDI-MS, fingerprint recognitions based on morphology and chemical profiles of endogenous/exogenous compounds were also achieved. Notably, crucial characteristics such as the age of an individual's fingerprints and their physical state could be assessed through the longitudinal monitoring of particular biomolecules (e.g., ascorbic acid, fatty acid) or the specific biomarker bilirubin glucuronide. Critical information pertinent to the identification of an individual would thus be facilitated by the analysis of the compounds underlying the fingerprint patterns.
Subject(s)
Indium , Vanadates , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Fatty Acids , LasersABSTRACT
As acute gastrointestinal (AGI) disease patients only sometimes seek medical care or submit stool samples for testing, and laboratories cannot detect or identify the pathogen, most cases of foodborne gastroenteritis still need to be identified through public health monitoring. We conducted a population survey and sentinel hospital surveillance to determine the burden of foodborne gastroenteritis caused by non-typhoidal Salmonella enterica (NTS) and Vibrio parahaemolyticus infection, from July 2018 to June 2019 in Zhejiang province, China, and a model for calculating disease burden established. Using the burden of illness pyramid model, we estimated that there were 140.3 cases of NTS infection and 136.2 cases of V. parahaemolyticus infection. We estimated annual incidence per 100,000 population in Zhejiang province as 236 (95% confidence interval [CI] 208-267) and 206 (95% CI 155-232) cases for foodborne NTS and V. parahaemolyticus gastroenteritis, respectively. The results show that AGI caused by these two pathogens constitutes a substantial burden in the Zhejiang population. The health burden of AGI estimations caused by NTS and V. parahaemolyticus in this study can serve as a strategic framework to direct policy and intervention.
ABSTRACT
OBJECTIVE: To investigate the occurrence data for 2-chloropropanol(2-MCPD) ester in edible vegetable oils purchased in Zhejiang Province during 2016-2020, and to estimate dietary exposures of 2-MCPD ester via vegetable oil. METHODS: A total of 404 samples of edible oils were collected from markets, stores, online shopping in Zhejiang Province, the occurrence of 2-MCPD ester was detected by gas chromatography mass spectrometry from 2016-2020. Data of vegetable oils consumption was obtained from the survey result of urban and rural residents in Zhejiang Province in 2008. The exposure levels of 2-chloropropanol ester was calculated for people aged 4-6, 7-10, 11-17, 18-59 and 60 years old and older from the consumption of vegetable oils. RESULTS: The detection rate of 2-MCPD esters in 404 samples was 82.7%(334/404) with the mean level of 0.32 mg/kg. Among them, the mean content of camellia oil was the highest with 1.23 mg/kg, followed by rice oil(0.69 mg/kg); sunflower oil, olive oil and soybean oil have relatively low average values, respectively with 0.11, 0.12 and 0.13 mg/kg. There are significant differences in 2-MCPD ester content in different types of edible oils of the same brand(P<0.05), the content of 2-MCPD ester in different brands of peanut oil was significant(P<0.05), but in different brands of corn oil was not statistically significant. Among the edible vegetable oil consumers, the average exposure of 2-MCPD esters in different age groups ranged from 0.21 to 0.69 µg/(kg·BW·d). CONCLUSION: 2-MCPD esters pollution is widespread in vegetable oils, the severity of pollution was affected by the type and brand of the edible vegetable oil, and the intake of 2-MCPD esters was relatively high among people with high vegetable oil consumption and the general population of 4-10 years old.
Subject(s)
Dietary Exposure , Plant Oils , Humans , Child, Preschool , Child , Vegetables , Esters , GlycerolABSTRACT
OBJECTIVE: To monitor fumonisins(FBs) in grains and grain products in Zhejiang and assess the exposure risks of FBs to local residents. METHODS: Liquid chromatography coupled with tandem mass spectrometry method was used to determine the occurrence of FBs in rice, millet, dried noodles, instant noodles, and maize grains, and food frequency questionnaires were used to collect the food consumption data of Zhejiang population. Then, the simple probability distribution model was used to assess the exposure risk. RESULTS: The levels of FBs in rice, millet, dried noodles and instant noodles were relatively low. The occurrence of FB_1, FB_2 and FB_3 in these foods was 0-23.7%, 0-16.7% and 0-5.4%, respectively, and the mean levels were not detected(ND)-22.36, ND-20.63 and ND-7.19 µg/kg correspondingly. However, the levels of FBs in maize grains were relatively high. The occurrence of FB_1, FB_2, and FB_3 in maize grains was 100%, 93.6% and 90.3%, respectively, and the mean levels were 638.99, 103.54 and 59.69 µg/kg correspondingly. In 12.9% of the maize grain samples, the levels of FBs were higher than the standard reference. The residents were at low exposure risk overall. The mean estimated daily intake(EDI) of FBs was far lower than the provisional maximum tolerable daily intake of 2 µg/(kg·BW·d). However, 0.30% of the residents were at high risk. Among people of different ages, the mean EDI of children, adults, and elderly were 0.43, 0.28 and 0.29 µg/(kg·BW·d) respectively, and children were in the highest exposure levels of FBs. Among the tested five foodstuffs, rice and maize grains were the main sources of FBs exposure. CONCLUSION: Except for maize grains, the levels of FBs in grains and grain products were relatively low, and Zhejiang residents were at low FBs exposure risk generally.
Subject(s)
Edible Grain , Fumonisins , Adult , Aged , Child , Humans , Chromatography, Liquid , Edible Grain/chemistry , Food Contamination/analysis , Fumonisins/analysis , Fumonisins/chemistry , Tandem Mass Spectrometry , Zea mays/chemistry , Risk AssessmentABSTRACT
The simultaneous analysis of diversified biomarkers with high sensitivity and in a point-of-care (POC) manner is of great significance for facile and early cancer diagnosis. Herein, we develop a target amplification-assisted ratiometric fluorescence assay (TARFA) platform integrating the dual-amplification strategy and colorimetric readout technology for sensitive and specific detection of two malignancy-associated biomarkers. Meanwhile, the NIR-excited alkaline-earth sulfide nanodots (ASNDs) with an ultrasmall (<10 nm) diameter and tunable emission wavelength are employed to replace commonly UV/visible light-excited fluorescent labels to minimize background interference from the sample matrix. Unique advantages of the ASNDs, together with superiority of consecutive signal amplification of enzymatic target recycling (ETR) and hybridization chain reaction (HCR), realize the pg/mL-range detection limit in specifically recognizing the vascular endothelial growth factor (VEGF) and soluble interleukin-6 receptors (sIL-6R). The combination detection of the dual analyte exhibits an improved sensitivity for cancer diagnosis. The addition of the target biomarkers leads to an increasingly ratiometric RGB signal, and quantification based on the ratio-dependent signal is more reliable rather than measuring the absolute RGB signals. Moreover, perceptible color transformation makes the TARFA platform competent for visual analysis of the target analytes as convenient as reading the pH indicator strip, and hue-based image analysis also improves the method with fine precision by quantitatively identifying the visual color. This work provides a new kind of NIR-excited aptasensing platform with a low detection limit, high throughput, and great portability, which also highlights the potential of the ASNDs in biomolecular fluorescent labeling.
Subject(s)
Biosensing Techniques , Neoplasms , Biomarkers, Tumor , Coloring Agents , Humans , Limit of Detection , Neoplasms/diagnosis , Nucleic Acid Hybridization , Vascular Endothelial Growth Factor AABSTRACT
BACKGROUND: This study aimed to identify the epidemiology, seasonality, aetiology and clinical characteristics of sporadic foodborne diseases in Zhejiang province during 2016-2020. METHODS: Descriptive statistical methods were used to analyze the data from surveillance network established by the Zhejiang Provincial Center for Disease Control and Prevention. There were 31 designated hospitals in all 11 cities which were selected using probability proportionate to size sampling method. RESULTS: During the study period, the surveillance system received 75,124 cases with 4826 (6.42%) hospitalizations from 31 hospitals. The most common cause was Norovirus, 6120 cases (42.56%), followed by Salmonella, 3351 cases (23.30%). A significant seasonal trend was observed for the V. parahaemolyticus, with the highest rates over the summer period, peaking in August, 1171 cases (38.75%), a similar trend was also observed with Salmonella and Diarrheagenic E. coli. Norovirus infections showed the highest rate in November (904, 14.77%) and March (660,10.78%), the lowest in August, 215 cases (3.51%). Patients between 19 ~ 40 years were more likely to infected by Norovirus, V. parahaemolyticus and Diarrheagenic E. coli, patients below 1 year were the highest among patients with Salmonella infection, 881 cases (26.3%). The Norovirus, V. parahaemolyticus and Diarrheagenic E. coli infection with the highest positive detection rates among the workers were observed. The largest number cases of food categories were from aquatic product infection. The private home was the most common exposure setting. CONCLUSION: Our study highlighted the necessity for conducting an active, comprehensive surveillance for pathogens in all age groups, to monitor the changing dynamics in the epidemiology and aetiology of foodborne diseases to guide policies that would reduce related illnesses.
Subject(s)
Caliciviridae Infections , Escherichia coli Infections , Foodborne Diseases , Norovirus , Caliciviridae Infections/epidemiology , China/epidemiology , Escherichia coli , Foodborne Diseases/epidemiology , Foodborne Diseases/etiology , Humans , SalmonellaABSTRACT
A versatile triple cascade amplification strategy was developed for ultrasensitive simultaneous detection of multiple cancer biomarkers using single particle inductively coupled plasma mass spectrometry (spICP-MS). The triple cascade amplification strategy consisted of an enhanced RecJf exonuclease-assisted target recycling amplification module, a hybridization chain reaction amplification module, and a signal amplification module based on DNA-templated multiple metal nanoclusters. In the enhanced RecJf exonuclease-assisted target recycling amplification module, the DNA bases at the 5' ends of aptamers for specific recognition of biomarkers were deliberately replaced by the corresponding RNA bases to enhance amplification efficiency. The signal amplification module based on DNA-templated multiple metal nanoclusters was innovatively used to amplify the signals measured by spICP-MS and at the same time effectively suppress possible background interferences. The proposed spICP-MS platform achieved satisfactory quantitative results for both carcinoembryonic antigen (CEA) and a-fetoprotein (AFP) in human serum samples with accuracy comparable to that of the commercial ELISA kits. Moreover, it has wide dynamic ranges for both CEA (0.01-100 ng/mL) and AFP (0.01-200 ng/mL). The limit of detection for CEA and AFP was 0.6 and 0.5 pg/mL, respectively. Compared with conventional biomarkers detection methods, the proposed spICP-MS platform has the advantages of operational simplicity, ultra-high sensitivity, wide dynamic range, and low background. Therefore, it is reasonable to expect that the proposed spICP-MS platform can be further developed to be a promising alternative tool for biomarker detection in fields of clinical diagnosis and biomedical research.
Subject(s)
Biosensing Techniques , Neoplasms , Humans , Carcinoembryonic Antigen/analysis , Biosensing Techniques/methods , Biomarkers, Tumor , alpha-Fetoproteins , DNA/chemistry , Exonucleases , Mass Spectrometry , Neoplasms/diagnosisABSTRACT
The multiple-metal-nanoparticle tagging strategy has generally been applied to the multiplexed detection of multiple analytes of interest such as microRNAs (miRNAs). Herein, it was used for the first time to improve both the specificity and sensitivity of a novel mass spectroscopic platform for miRNA detection. The mass spectroscopic platform was developed through the integration of the ligation reaction, hybridization chain reaction amplification, multiple-metal-nanoparticle tagging, and inductively coupled plasma mass spectrometry. The high specificity resulted from the adoption of the ligation reaction is further enhanced by the multiple-metal-nanoparticle tagging strategy. The combination of hybridization chain reaction amplification and metal nanoparticle tagging endows the proposed platform with the feature of high sensitivity. The proposed mass spectrometric platform achieved quite satisfactory quantitative results for Let-7a in real-world cell line samples with accuracy comparable to that of the real-time quantitative reverse-transcriptase polymerase chain reaction method. Its limit of detection and limit of quantification for Let-7a were experimentally determined to be about 0.5 and 10 fM, respectively. Furthermore, due to the unique way of utilizing the multiple-metal-nanoparticle tagging strategy, the proposed platform can unambiguously discriminate between the target miRNA and nontarget ones with single-nucleotide polymorphisms based on their response patterns defined by the relative mass spectral intensities among the multiple tagged metal elements and can also provide location information of the mismatched bases. Its unique advantages over conventional miRNA detection methods make the proposed platform a promising and alternative tool in the fields of clinical diagnosis and biomedical research.
Subject(s)
Metal Nanoparticles , MicroRNAs , Limit of Detection , Mass Spectrometry , MicroRNAs/genetics , Nucleic Acid HybridizationABSTRACT
Leaked blood components, injured endothelial cells, local inflammatory response and vasospasm may converge to promote microthrombosis following subarachnoid hemorrhage (SAH). Previously, we showed that the milk fat globule-epidermal growth factor 8 (MFGE8) can mitigate SAH-induced microthrombosis. This present study was aimed to explore the molecular pathway participated in MFGE8-dependent protection on vascular endothelium. Immunofluorescence, immunoblot and behavioral tests were used to determine the molecular partner and signaling pathway mediating the effect of MFGE8 in vascular endothelium in rats with experimental SAH and controls, together with the applications of RNA silencing and pharmacological intervention methods. Relative to control, recombinant human MFGE8 (rhMFGE8) treatment increased 5-bromo-2'-deoxyuridine (BrdU) labeled new endothelial cells, reduced TUNUL-positive endothelial cells and elevated the expression of phosphatidylinositol 3-kinase (PI3K) and chemokine (C-X-C motif) ligand 12 (CXCL12), in the brains of SAH rats. These effects were reversed by MFGE8 RNA silencing, as well as following cilengitide and wortmannin intervention. These results suggest that MFGE8 promotes endothelial regeneration and mitigates endothelial DNA damage through the activation of the TIGß5/PI3K/CXCL12 signaling pathway.
Subject(s)
Antigens, Surface , Brain Injuries , Milk Proteins , Subarachnoid Hemorrhage , Animals , Chemokine CXCL12 , Disease Models, Animal , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Glycolipids , Glycoproteins , Lipid Droplets , Phosphatidylinositol 3-Kinases/metabolism , Rats , Rats, Sprague-Dawley , Signal TransductionABSTRACT
Anti-Stokes fluorescence induced by near-IR (NIR) radiation is particularly advantageous for the bioassay of complex samples, but most of the commonly used NIR-induced fluorescence nanomaterials such as up-conversion nanoparticles (UCNPs) do not exhibit satisfactory fluorescence intensity and work against achieving a highly sensitive bioassay. In this study, we a construct sensitive and specific bacteria biosensor based on the NIR-stimulated CaS: Eu, Sm, Mn and SrS: Ce, Sm, Mn nanoparticles. The fluorescent nanoparticles are conjugated with bacteria recognition fragments. In addition, the independent emission bands of these two types of fluorescent nanoparticles make it possible to detect and quantify Gram-positive strain and Gram-negative strain, simultaneously. Intense fluorescence and magnetic enrichment of magneto-fluorescence systems enable bacteria discrimination with the naked eye and improve sensitivity in trace bacteria detection (<20 CFU mL-1). The linear relationship between the fluorescence intensity and bacterial concentration is established with a detection range of 25-106 CFU mL-1. Furthermore, this NIR-excited assay strategy demonstrates better anti-interference capability than UV/visible-excited assay methods, showing high potential and practical value for medical diagnostics and bacteria monitoring.
Subject(s)
Bacteriological Techniques/methods , Escherichia coli/isolation & purification , Fluorescent Dyes/chemistry , Metal Nanoparticles/chemistry , Staphylococcus aureus/isolation & purification , Animals , Calcium Compounds/chemistry , Calcium Compounds/radiation effects , Escherichia coli/chemistry , Fluorescence , Food Contamination/analysis , Infrared Rays , Limit of Detection , Magnetic Phenomena , Metal Nanoparticles/radiation effects , Metals, Heavy/chemistry , Metals, Heavy/radiation effects , Microscopy, Fluorescence , Milk/microbiology , Polymyxin B/chemistry , Spectrometry, Fluorescence , Staphylococcus aureus/chemistry , Sulfides/chemistry , Sulfides/radiation effects , Teicoplanin/chemistryABSTRACT
BACKGROUND: Microthrombosis after subarachnoid hemorrhage has an adverse effect on prognosis. Milk fat globule-epidermal growth factor 8 promotes phagocytosis of phagocytic cells and may reduce microthrombosis. This study investigated the effects of recombinant human milk fat globule-epidermal growth factor 8 on microthrombosis and neurological function after subarachnoid hemorrhage. METHODS: Rats subarachnoid hemorrhage model was induced by intravascular puncture method. Western blot was performed to measure the expression of endogenous milk fat globule-epidermal growth factor 8 after subarachnoid hemorrhage. Microthrombosis was quantified by microthrombi count using immunohistochemistry and immunofluorescence. The neuroprotective effect of recombinant human milk fat globule-epidermal growth factor 8 administration was evaluated by modified Garcia score, beam balance, Rotarod test, and Morris water maze. RESULTS: Endogenous milk fat globule-epidermal growth factor 8 protein level increased after subarachnoid hemorrhage. Microthrombosis was significantly increased in subarachnoid hemorrhage rats brain, while recombinant human milk fat globule-epidermal growth factor 8 dramatically reduced microthrombosis as well as improve short- and long- term neurobehavior after subarachnoid hemorrhage. CONCLUSIONS: Recombinant human milk fat globule-epidermal growth factor 8 reduces microthrombosis and improves neurological function after subarachnoid hemorrhage, which may be an effective strategy for treating subarachnoid hemorrhage.
Subject(s)
Antigens, Surface/administration & dosage , Blood Coagulation/drug effects , Fibrinolytic Agents/administration & dosage , Intracranial Thrombosis/prevention & control , Milk Proteins/administration & dosage , Neuroprotective Agents/administration & dosage , Subarachnoid Hemorrhage/drug therapy , Animals , Antigens, Surface/metabolism , Behavior, Animal/drug effects , Disease Models, Animal , Intracranial Thrombosis/blood , Intracranial Thrombosis/physiopathology , Male , Maze Learning/drug effects , Milk Proteins/metabolism , Motor Activity/drug effects , Postural Balance/drug effects , Rats, Sprague-Dawley , Recombinant Proteins/administration & dosage , Subarachnoid Hemorrhage/blood , Subarachnoid Hemorrhage/physiopathology , Time FactorsABSTRACT
Eu,Sm,Mn-doped CaS (ESM-CaS) nanoparticles demonstrate a remarkable upconversion luminescence (UCL) efficiency with a quantum yield of nearly 60%, enabling many new applications and devices. We describe an ESM-CaS nanoparticle-based paper test strip for one-shot quantitative measurement of sulfite concentration using a smartphone-based reader. The integrated UCL-based sulfite detection system features high sensitivity and facile operation without the need for separation and pretreatment. Moreover, the design principles are general in nature and so can be tailored for the detection and quantification of a variety of other analytes.
ABSTRACT
BACKGROUND: Mood swings is linked to a higher risk of cardiovascular diseases (CVDs). However, the causal relationships between them remain unknown. METHODS: We conducted this Mendelian randomization (MR) analysis to evaluate the causal associations between mood swings (n = 373,733) and 5 CVDs, including CAD, MI, HF, AF, and stroke using summary data of large-scale genome-wide association studies (GWAS). FinnGen datasets validated the results. Various MR approaches, sensitivity analyses, multivariable MR (MVMR), and two-step MR mediation analyses were applied. RESULTS: The MR analysis revealed significant causal effects of mood swings on CAD (OR = 1.45, 95 % CI 1.24-1.71; P = 5.52e-6), MI (OR = 1.60, 95 % CI 1.32-1.95; P = 1.77e-6), HF (OR = 1.42, 95 % CI 1.18-1.71; P = 2.32e-4), and stroke (OR = 1.48, 95 % CI 1.19-1.83; P = 3.46e-4), excluding AF (P = 0.16). In the reverse MR analysis, no causal relationships were observed. The results were reproducible using FinnGen data. In the MVMR analysis, the causal effects of mood swings on CAD, MI, HF and stroke still remain significant after adjusting potential confounding factors including BMI, smoking and T2DM, but not for LDL and hypertension. Further mediation analysis indicated hypertension may mediate the causal pathways from mood swings to CAD (18.11 %, 95 % CI: 8.83 %-27.39 %), MI (16.40 %, 95 % CI: 7.93 %-24.87 %), HF (13.06 %, 95 % CI: 6.25 %-19.86 %), and stroke (18.04 %, 95 % CI: 8.73 %-27.34 %). CONCLUSION: Mood swings has a significant causal impact on the development of CAD, MI, HF, and stroke, partly mediated by hypertension.