Phase retrieval algorithm applied to high-energy ultrafast lasers.

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.

Isolation of Extracellular Outer Membrane Vesicles (OMVs) from Escherichia coli Using EVscore47 Beads.

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.

Occurrence and Exposure Assessment of Nickel in Zhejiang Province, China.

Nickel (Ni) is a silver-white metal with high antioxidative properties, often existing in a bivalent form in the environment. Despite being the fifth most abundant metal on Earth, anthropogenic activities, including industrial processes, have elevated Ni levels in environmental media. This study investigated Ni contamination in various food groups in Zhejiang Province, China, mainly focusing on Ni levels in beans, vegetables, aquatic foods, meat products, cereal products, and fruits. A total of 2628 samples were collected and analyzed. Beans exhibited the highest Ni content in all samples. The overall detection rate of Ni was 86.5%, with variation among food categories. For plant-origin foods, legumes had the highest Ni concentration while for animal-origin foods, shellfish showed the highest median Ni concentration. The results indicate generally acceptable Ni exposure levels among Zhejiang residents, except for children aged 0-6. Beans were identified as the primary contributor to high Ni exposure risk. The paper suggests monitoring Ni contamination in food, especially for vulnerable populations, and provides insights into exposure risks in different age groups.

Genetically predicted mood swings increased risk of cardiovascular disease: Evidence from a Mendelian randomization analysis.

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.

Novel Ag-modified vanadate nanosheets for determination of small organic molecules with laser desorption ionization mass spectrometry.

Laser desorption ionization mass spectrometry (LDI-MS) aroused intensive concerns for the merits of label-free and high-throughput analysis. Here, we designed a silver nanoparticles (AgNP)-modified indium vanadate nanosheets with doping samarium (AgNP@InVO4:Sm) nanosheets. The developed AgNP@InVO4:Sm nanosheets (AIVON) were synthesized based on the microemulsion-mediated solvothermal method and ultraviolet-assisted in situ formation of AgNP, then for the first time applied as a matrix in LDI-MS analysis. With the advantages including enhanced MS signal, little matrix-related background, high reproducibility, and good salt tolerance, AIVON exhibited much better prospect than non-modified indium vanadate nanosheets with doping samarium (IVON) and traditional organic matrix, thus allowing sensitive MS detection for a wide range of low-molecular-weight (LMW) molecules. Moreover, by coupling with headspace sampling thin-film microextraction (TFME), a kind of representative pollutant chlorophenols were identified and quantified via AIVON-assisted LDI-MS in environmental and biological samples. Volatile LMW pollutants could be preconcentrated after TFME, hence a sensitive and rapid assay with negligible sample matrix effect was realized by using AIVON-assisted LDI-MS. It is anticipated that this novel nano-matrix AIVON and the proposed TFME coupling detection strategy were of competitive merits for LDI-MS analysis in the fields of environment, biomedicine, and agriculture.

Temporally and spatially resolved molecular profiling in fingerprint analysis using indium vanadate nanosheets-assisted laser desorption ionization mass spectrometry.

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.

An Occurrence and Exposure Assessment of Paralytic Shellfish Toxins from Shellfish in Zhejiang Province, China.

The intake of paralytic shellfish toxins (PSTs) may adversely affect human health. Therefore, this study aimed to show the prevalence of PSTs from commercially available shellfish in Zhejiang Province, China, during the period of frequent red tides, investigate the factors affecting the distribution of PSTs, and assess the risk of PST intake following the consumption of bivalve shellfish among the Zhejiang population. A total of 546 shellfish samples were collected, 7.0% of which had detectable PSTs at concentrations below the regulatory limit. Temporal, spatial, and interspecific variations in the occurrence of PSTs were observed in some cases. The dietary exposure to PSTs among the general population of consumers only was low. However, young children in the extreme scenario (the 95th percentile of daily shellfish consumption combined with the maximum PST concentration), defined as 89-194% of the recommended acute reference doses, were possibly at risk of exposure. Notably, Arcidae and mussels were the major sources of exposure to toxins. From the public health perspective, PSTs from commercially available shellfish do not pose a serious health risk; however, more attention should be paid to acute health risks, especially for young children, during periods of frequent red tides.

[Occurrence and exposure assessment of fumonisins from grains and grain products in Zhejiang Province in 2018-2019].

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.

[Contamination and dietary exposure assessment of 2-chloropropanol esters in vegetable oils available on Zhejiang market during 2016-2020].

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.

Cadmium Exposure in Aquatic Products and Health Risk Classification Assessment in Residents of Zhejiang, China.

Cadmium (Cd) pollution of food safety is a prominent food safety concern worldwide. The concentration of Cd in six aquatic food categories collected from 2018 to 2022 was analyzed using inductively coupled plasma mass spectrometry, and the Cd exposure levels were calculated by combining the Cd concentration and food consumption data of 18913 urban and rural residents in Zhejiang Province in 2015-2016. The mean Cd concentration was 0.699 mg/kg and the mean Cd exposure of aquatic foods was 0.00951 mg/kg BW/month for the general population. Marine crustaceans were the largest Cd contributor, corresponding to 82.7%. The regional distribution results showed that the average Cd exposure levels of 11 cities did not exceed the provisional tolerable monthly intake (PTMI). According to the subgroups, the Cd mean exposure level of 2-3-year-old children was significantly higher than that of the other age groups but did not exceed the PTMI. Health risk classification assessment demonstrated that the final risk score was six, and the health risk level of Cd exposure in aquatic products in the Zhejiang population was medium. These results demonstrated that the risk of Cd exposure in certain food types or age groups should be given more concern.

Estimating the health burden of foodborne gastroenteritis caused by non-typhoidal Salmonella enterica and Vibrio parahaemolyticus in Zhejiang province, China.

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.

Epidemiological characteristics of Vibrio parahaemolyticus outbreaks, Zhejiang, China, 2010-2022.

Background: Vibrio parahaemolyticus is one of the most common foodborne pathogens and poses a significant disease burden. The purpose of the study was to elucidate the epidemiological characteristics of Vibrio parahaemolyticus outbreaks in Zhejiang Province, and provide insights for the targeted prevention and control of foodborne diseases. Methods: Descriptive statistical methods were utilized to analyze the data on Vibrio parahaemolyticus outbreaks reported by all Centers for Disease Control and Prevention (CDCs) through Foodborne Disease Outbreaks Surveillance System (FDOSS) in Zhejiang Province from 2010 to 2022. Results: From 2010 to 2022, a total of 383 outbreaks caused by Vibrio parahaemolyticus were reported by 90 CDCs in 11 prefectures of Zhejiang Province, resulting in 4,382 illnesses, 326 hospitalizations and 1 death. The main symptoms of the outbreak-related cases were diarrhea (95.18%), abdominal pain (89.23%), nausea (55.64%), vomiting (50.57%), fever (24.21%), etc. The outbreaks occurring between July and September accounted for 77.54% of all outbreaks (297 out of 383). Outbreaks associated with restaurants accounted for the majority (57.96%, 222/383) of all outbreaks, followed by those linked to staff canteens (15.40%, 59/383) and rural banquets (11.23%, 43/383). 31.85% of all outbreaks were associated with the consumption of aquatic products, while ready-to-eat foods such as Chinese cold dishes and cooked meat products accounted for 12.53% of all outbreaks. Serotype O3:K6 (81.94%, 118/144) was the predominant serotype responsible for outbreaks from 2010 to 2020, while serotype O10:K4 (57.89%, 33/57) was the predominant serotype from 2021 to 2022. Conclusion: In-depth and comprehensive analysis of long-term surveillance data on Vibrio parahaemolyticus outbreaks is essential to gain insight into the epidemiological characteristics, identify long-term patterns and recent trends, and enable governments to prioritize interventions and develop targeted policies to mitigate such outbreaks.

Pd(II)-based coordination polymer nanosheets for ratiometric colorimetric and photothermal dual-mode assay of serum alkaline phosphatase.

Fabrication of a multi-signal readout assay with high sensitivity and selectivity is highly desirable for clinical and biochemical analysis, but remains a challenge due to laborious procedures, large-scale instruments, and inadequate accuracy. Herein, a straightforward, rapid, and portable detection platform based on palladium(II) methylene blue (MB) coordination polymer nanosheets (PdMBCP NSs) was unveiled for the ratiometric dual-mode detection of alkaline phosphatase (ALP) with temperature and colorimetric signal readout properties. The sensing mechanism is the ALP-catalyzed generation of ascorbic acid for competitive binding and etching PdMBCP NSs to release free MB in a quantitive means for detection. Specifically, ALP addition led to the decrease of temperature signal readout from the decomposed PdMBCP NSs under 808 nm laser excitation, and simultaneous increase of the temperature from the generated MB with a 660 nm laser, together with the corresponding absorbance changes at both wavelengths. Notably, this ratiometric nanosensor exhibited a detection limit of 0.013 U/L (colorimetric) and 0.095 U/L (photothermal) within 10 min, respectively. The reliability and satisfactory sensing performance of the developed method were further confirmed by clinic serum samples. Therefore, this study provides a new insight for the development of dual-signal sensing platforms for convenient, universal, and accurate detection of ALP.

Recent advances in nanostructured substrates for surface-enhanced infrared absorption spectroscopy.

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.

Integrated analysis based on vesicle trafficking-related genes identifying CNIH4 as a novel therapeutic target for glioma.

BACKGROUND: Vesicle trafficking is a highly important process in numerous human diseases, especially in the central nervous system dysfunctions. However, as a key component of vesicle trafficking-related genes (VRGs), Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) has not been systematically elucidated in glioma so far. METHODS: Differentially expressed VRGs were selected using molecular signatures database (MSigDB), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) mRNA expression profiles. Further exploration of CNIH4 was determined using LASSO-Cox regression algorithms. Then Kaplan-Meier (K-M) plotter, receiver operating characteristic (ROC) curves, and multivariate Cox regression analyses were utilized to assess the independent significance of CNIH4 in the CGGA validation cohort. Functional exploration was performed with Gene Set Enrichment Analysis (GSEA) and then verified using a series of functional experiments in glioma cells. Finally, the consensus clustering algorithm was applied to identify clusters in glioma samples. After that, differences in prognosis, the tumor immune microenvironment (TIME), and therapy response were evaluated between clusters. RESULTS: CNIH4 was shown to be overexpressed in malignant glioma variants and was frequently observed in GCSs and TMZ-resistant cell lines. Higher CNIH4 levels were significantly related to poor outcomes and positively correlated with adverse clinicopathological characteristics. Survival analyses revealed CNIH4 as an independent risk factor that outperformed traditional measures. Enrichment analysis indicated that overactive CNIH4 significantly gathered in stem cell processes. Furthermore, functional assays of silencing CNIH4 expression suppressed stem cell-like properties in vitro and inhibited tumorigenicity in vivo. Finally, the CNIH4-enriched subgroup negatively modulated immunotherapeutic response and reflected lower chemotherapy sensitivity for glioma patients. CONCLUSION: Our study identified CNIH4 as a potential VRG that regulates tumor stemness, microenvironment immunity, and chemotherapy sensitivity. It may serve as a novel prognostic factor and a promising target against glioma therapy.

Epidemiology of foodborne diseases caused by Salmonella in Zhejiang Province, China, between 2010 and 2021.

Objective: Salmonella infection is a common cause of bacterial foodborne diseases (FBDs) globally. In this study, we aimed to explore the epidemiological and etiological characteristics of Salmonella infection from 2012-2021 in Zhejiang Province, China. Methods: Descriptive statistical methods were used to analyze the data reported by the Centers for Disease Control and Prevention at all levels in Zhejiang Province through the China National Foodborne Diseases Surveillance Network from 2012-2021. Results: A total of 11,269 Salmonella cases were reported, with an average positive rate of 3.65%, including 1,614 hospitalizations. A significant seasonal trend was observed for Salmonella cases, with the highest rate over the summer period, peaking from May to October, accounting for 77.96%. The results indicated a higher positive rate among respondents aged 0-4 years, especially for the scattered children (P < 0.05). The highest number of Salmonella infections were caused due to contaminated fruit and fruit products. Households (54.69%) had the most common exposure settings. Serotypes analysis revealed that Salmonella typhimurium (36.07%), Salmonella enteritidis (15.17%), and Salmonella london (6.05%) were the dominant strains among the 173 serotypes. Diarrhea, abdominal pain, fever, nausea, and vomiting were the main symptoms of these serotypes. Conclusions: FBDs caused by Salmonella are important issues for public health in Zhejiang Province, and there is a need to focus on the epidemiological and etiological characteristics to control Salmonella infections.

ASK1 inhibitor NQDI­1 decreases oxidative stress and neuroapoptosis via the ASK1/p38 and JNK signaling pathway in early brain injury after subarachnoid hemorrhage in rats.

Oxidative stress and neuroapoptosis are key pathological processes after subarachnoid hemorrhage (SAH). The present study evaluated the anti­oxidation and anti­apoptotic neuroprotective effects of the apoptosis signal­regulating kinase 1 (ASK1) inhibitor ethyl­2,7­dioxo­2,7­dihydro­3H­naphtho(1,2,3­de)quinoline­1­carboxylate (NQDI­1) in early brain injury (EBI) following SAH in a rat model. A total of 191 rats were used and the SAH model was induced using monofilament perforation. Western blotting was subsequently used to detect the endogenous expression levels of proteins. Immunofluorescence was then used to confirm the nerve cellular localization of ASK1. Short­term neurological function was assessed using the modified Garcia scores and the beam balance test 24 h after SAH, whereas long­term neurological function was assessed using the rotarod test and the Morris water maze test. Apoptosis of neurons was assessed by TUNEL staining and oxidative stress was assessed by dihydroethidium staining 24 h after SAH. The protein expression levels of phosphorylated (p­)ASK1 and ASK1 rose following SAH. NQDI­1 was intracerebroventricularly injected 1 h after SAH and demonstrated significant improvements in both short and long­term neurological function and significantly reduced oxidative stress and neuronal apoptosis. Injection of NQDI­1 caused a significant decrease in protein expression levels of p­ASK1, p­p38, p­JNK, 4 hydroxynonenal, and Bax and significantly increased the protein expression levels of heme oxygenase 1 and Bcl­2. The use of the p38 inhibitor BMS­582949 or the JNK inhibitor SP600125 led to significant decreases in the protein expression levels of p­p38 or p­JNK, respectively, and a significant reduction in oxidative stress and neuronal apoptosis; however, these inhibitors did not demonstrate an effect on p­ASK1 or ASK1 protein expression levels. In conclusion, treatment with NQDI­1 improved neurological function and decreased oxidative stress and neuronal apoptosis in EBI following SAH in rats, possibly via inhibition of ASK1 phosphorylation and the ASK1/p38 and JNK signaling pathway. NQDI­1 may be considered a potential agent for the treatment of patients with SAH.

Evaluating the Importance of Monetary Policy Uncertainty: The Long- and Short-Term Effects and Responses.

Monetary policy changes have an irreplaceable impact on economic activity. Considering the close linkage among economic policies, we employ a bi-directional Granger causality test to investigate the potential linkages between monetary policy uncertainty (MPU) and other categorical economic policy uncertainty (CEPU) in the time and frequency domains. We consider all news-based U.S. categorical economic policy uncertainty indices (CEPU). All monthly CEPU indicators, covering January 1986 to January 2022, can be obtained from the website of Economic Policy Uncertainty. On an average, causality running from each CEPU to MPU is not apparent, while MPU can significantly affect six policy-related uncertainties: taxes, government spending, health care, national security, entitlement programs and regulation. A further frequency-domain study showed the dynamic changes in the relationship between them. For instance, we capture mid- and long-run causality running from tax uncertainty to MPU, while MPU has an impact on taxes in the medium run. Our findings provide policymakers with a better understanding of the nexus between MPU and other CEPU for formulating appropriate economic policies. Particularly, if a sectional government considers the long- and short-term effects of different policies when formulating strategies, risk transmission may be curbed to some extent.

Ultrasensitive detection of multiple cancer biomarkers by a triple cascade amplification strategy in combination with single particle inductively coupled plasma mass spectrometry.

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.