Insights into preeclampsia: a bioinformatics approach to deciphering genetic and immune contributions.

Background: Preeclampsia (PE) is a global pregnancy concern, characterized by hypertension with an unclear etiology. This study employs Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to clarify its genetic and molecular roots, offering insights into diagnosis and treatment avenues. Methods: We integrated PE-specific genome-wide association study (GWAS) data, expression and protein quantitative trait loci (eQTL and pQTL) data, and single-cell data from peripheral blood mononuclear cells (PBMCs). We identified highly variable genes using single-cell information and employed MR to determine potential causality. We also combined pQTL and GWAS data, discerned genes positively associated with PE through scRNA-seq, and leveraged the Enrichr platform to unearth drug-gene interactions. Results: Our scRNA-seq pinpointed notable cell type distribution variances, especially in T helper cells (Th cells), between PE and control groups. We unveiled 591 highly variable genes and 6 directly PE-associated genes. Although MR revealed correlations with PE risk, pQTL analysis was inconclusive due to data constraints. Using DSigDB, 93 potential therapeutic agents, like Retinoic acid targeting core genes (IFITM3, NINJ1, COTL1, CD69, and YWHAZ), emerged as prospective multi-target treatments. Conclusion: Utilizing MR and scRNA-seq, this study underscores significant cellular disparities, particularly in Th cells, and identifies crucial genes related to PE. Despite some limitations, these genes have been revealed in PE's underlying mechanism. Potential therapeutic agents, such as Retinoic acid, suggest promising treatment pathways.

CRISPR/Cas13a analysis based on NASBA amplification for norovirus detection.

Human norovirus (HuNoV) is a leading cause of foodborne diseases worldwide, making rapid and accurate detection crucial for prevention and control. In recent years, the CRISPR/Cas13a system, known for its single-base resolution in RNA recognition and unique collateral cleavage activity, is particularly suitable for sensitive and rapid RNA detection. However, isothermal amplification-based CRISPR/Cas13 assays often require an external transcription step, complicating the detection process. In our study, an efficient diagnostic technique based on the NASBA/Cas13a system was established to identify conserved regions at the ORF1-ORF2 junction of norovirus. The RNA amplification techniques [Nucleic Acid Sequence-Based Amplification (NASBA)] integrates reverse transcription and transcription steps, enabling sensitive, accurate, and rapid enrichment of low-abundance RNA. Furthermore, the CRISPR/Cas13a system provides secondary precise recognition of the amplified products, generating a fluorescence signal through its activated accessory collateral cleavage activity. We optimized the reaction kinetics parameters of Cas13a and achieved a detection limit as low as 51pM. The conditions for the cascade reaction involving CRISPR analysis and RNA amplification were optimized. Finally, we validated the reliability and accuracy of the NASBA/Cas13a method by detecting norovirus in shellfish, achieving results comparable to qRT-PCR in a shorter time and detecting viral loads as low as 10 copies/µL.

A colorimetric/electrochemical microfluidic biosensor using target-triggered DNA hydrogels for organophosphorus detection.

Organophosphorus compounds are widely distributed and highly toxic to the environment and living organisms. The current detection of organophosphorus compounds is based on a single-mode method, which makes it challenging to achieve good portability, accuracy, and sensitivity simultaneously. This study designed a multifunctional microfluidic chip to develop a dual-mode biosensor employing a DNA hydrogel as a carrier and aptamers as recognition probes for the colorimetric/electrochemical detection of malathion, an organophosphorus compound. The biosensor balanced portability and stability by combining a microfluidic chip and target-triggered DNA hydrogel-sensing technologies. Moreover, the biosensor based on target-triggered DNA hydrogel modified microfluidic developed in this study exhibited a dual-mode response to malathion, providing both colorimetric and electrochemical signals. The colorimetric mode enables rapid visualization and qualitative detection and, when combined with a smartphone, allows on-site quantitative analysis with a detection limit of 56 nM. The electrochemical mode offers a broad linear range (0.01-3000 µM) and high sensitivity (a limit of detection of 5 nM). The two modes could validate each other and improve the accuracy of detection. The colorimetric/electrochemical dual-mode biosensor based on target-triggered DNA hydrogel modified microfluidic chip offers a portable, simple, accurate, and sensitive strategy for detecting harmful environmental and food substances.

CLICK-FLISA Based on Metal-Organic Frameworks for Simultaneous Detection of Fumonisin B1 (FB1) and Zearalenone (ZEN) in Maize.

Mycotoxins are secondary products produced primarily by fungi and are pathogens of animals and cereals, not only affecting agriculture and the food industry but also causing great economic losses. The development of rapid and sensitive methods for the detection of mycotoxins in food is of great significance for livelihood issues. This study employed an amino-functionalized zirconium luminescent metal-organic framework (LOF) (i.e., UiO-66-NH2). Click chemistry was utilized to assemble UiO-66-NH2 in a controlled manner, generating LOF assemblies to serve as probes for fluorescence-linked immunoassays. The proposed fluoroimmunoassay method for Zearalenone (ZEN) and Fumonisin B1 (FB1) detection based on the UiO-66-NH2 assembled probe (CLICK-FLISA) afforded a linear response range of 1-20 µmol/L for ZEN, 20 µmol/L for FB1, and a very low detection limit (0.048-0.065 µmol/L for ZEN; 0.048-0.065 µmol/L for FB1). These satisfying results demonstrate promising applications for on-site quick testing in practical sample analysis. Moreover, the amino functionalization may also serve as a modification strategy to design luminescent sensors for other food contaminants.

Micro-/nanostructures for surface-enhanced Raman spectroscopy: Recent advances and perspectives.

Surface-enhanced Raman spectroscopy (SERS) has great potential for the analysis of molecules adsorbed on metals with rough surfaces or substrates with micro-/nanostructures. Plasmonic coupling between metal nanoparticles and the morphology of the rough metal surface can produce "hot spots" that enhance Raman scattering by adsorbed molecules, typically at micro- to nanomolar concentrations, although high enhancement factors can also facilitate single-molecule detection. This phenomenon is widely applicable for chemical analysis and sensing in various fields. In this review, the latest research progress on SERS micro-/nanosensors is evaluated, and the sensors are classified according to their individual functions. Furthermore, the design principles and working mechanisms of reported SERS-active micro-/nanostructured substrates are analyzed, and the design features adopted to overcome the difficulties associated with precision detection are explored. Finally, challenges and directions for future development in this field are discussed. This review serves as a design guide for novel SERS-active substrates.

Synthetic biology for the food industry: advances and challenges.

As global environmental pollution increases, climate change worsens, and population growth continues, the challenges of securing a safe, nutritious, and sustainable food supply have become enormous. This has led to new requirements for future food supply methods and functions. The use of synthetic biology technology to create cell factories suitable for food industry production and renewable raw material conversion into: important food components, functional food additives, and nutritional chemicals, represents an important method of solving the problems faced by the food industry. Here, we review the recent progress and applications of synthetic biology in the food industry, including alternatives to: traditional (artificial pigments, meat, starch, and milk), functional (sweeteners, sugar substitutes, nutrients, flavoring agents), and green (green fiber, degradable packing materials, green packaging materials and food traceability) foods. Furthermore, we discuss the future prospects of synthetic biology-based applications in the food industry. Thus, this review may serve as a reference for research on synthetic biology in the: food safety, food nutrition, public health, and health-related fields.

Rapid detection of melamine by DNA Walker mediated SERS sensing technique based on signal amplification function.

A new method is proposed for detecting typical melamine dopants in food using surface-enhanced Raman scattering (SERS) biosensing technology. Melamine specific aptamer was used as the identification probe, and gold magnets (AuNPs@MNPs) and small gold nanoparticles (AuNPs@MBA) were used as the basis for Raman detection. The Raman signal of the detection system can directly detect melamine quantitatively. Under optimized conditions, the detection of melamine was carried out in the low concentration range of 0.001-500 mg/kg, the enhancement factor (EF) was 2.3 × 107, and the detection limit was 0.001 mg/kg. The method is sensitive and rapid, and can be used for the rapid detection of melamine in the field environment.

Carboxyl-functionalized two-dimensional MXene-Au nanocomposites were prepared as SERS substrates for the detection of melamine in dairy products.

In the present study, we address the limitations of conventional surface-enhanced Raman scattering (SERS) techniques for sensitive and stable detection of melamine in food products, especially dairy. To overcome these challenges, we developed a novel SERS-active substrate by incorporating gold nanoparticles (AuNPs) onto carboxyl-functionalized two-dimensional (2D) MXene material doped with nitrides, specifically Au-Ti2N-COOH. Our strategy leverages the unique physicochemical properties of MXene, a class of atomically thin, 2D transition metal carbides/nitrides, with tunable surface functionalities. By modifying the MXene surface with AuNPs and introducing carboxyl groups (-COOH), we successfully enhanced the interaction between the substrate and melamine molecules. The carboxyl groups form hydrogen bonds with the amino groups on the melamine's triazine ring, facilitating the adsorption of melamine molecules within the 'hotspot' regions responsible for SERS signal amplification. A series of characterization methods were used to confirm the successful synthesis of Au-Ti2N-COOH composites.Using Au-Ti2N-COOH as the SERS substrate, we detected melamine in spiked dairy product samples with significantly enhanced sensitivity and stability compared to nitride-doped MXene alone. The detection limit in liquid milk stands at 3.7008 µg kg-1, with spike recovery rates ranging from 99.84% to 107.55% and an approximate RSD of 5%. This work demonstrates the effectiveness of our approach in designing a label-free, rapid, and robust SERS platform for the accurate quantitation of melamine contamination in food, thereby mitigating health risks associated with melamine adulteration.

A comparative study of INSM1 (clone MRQ70) immunoreactivity on CytoLyt® pretreated cytology and resection specimens of pancreatic neuroendocrine tumors.

INTRODUCTION: Insulinoma-associated protein 1 (INSM1) is a newly characterized sensitive and specific immunohistochemical marker for neuroendocrine (NE) tumors. Whereas more traditional NE markers, such as chromogranin A and synaptophysin, are cytoplasmic, INSM1 is uniquely nuclear and thus could serve as a useful addition to NE tumor workup. While application of immunohistochemical studies to cytology specimens is becoming increasingly relevant, knowledge of the effects of the certain fixatives as well as the pattern and intensity of immunoexpression are important considerations. METHODS: Sixteen cases of pancreatic neuroendocrine tumor (PanNET) diagnosed between 2015 and 2021 underwent both fine-needle aspiration, which was subsequently prepared in CytoLyt®-fixed cytology cell block (CCB), and surgical resection, in which specimens were prepared into formalin-fixed paraffin embedded blocks (FFPE). For all samples, INSM1 immunoreactivity was classified according to staining intensity and extent, then compared between CCBs and matched FFPEs. RESULTS: All 16 FFPE specimens demonstrated strong and diffuse INSM1 immunoreactivity, while only 10/16 (62.5%) CCBs were positive. Of those 10, only 2/10 (20%) demonstrated strong and diffuse reactivity. CONCLUSION: The choice of fixative has a demonstrable effect on the immunoreactivity of INSM1 in PanNET. Even though the sensitivity is lower in CytoLyt®-fixed cell block specimens, the addition of INSM1 is useful, especially in challenging cases that may be negative for one or more of the traditional NE markers.

Machine learning assisted biosensing technology: An emerging powerful tool for improving the intelligence of food safety detection.

Recently, the application of biosensors in food safety assessment has gained considerable research attention. Nevertheless, the evaluation of biosensors' sensitivity, accuracy, and efficiency is still ongoing. The advent of machine learning has enhanced the application of biosensors in food security assessment, yielding improved results. Machine learning has been preliminarily applied in combination with different biosensors in food safety assessment, with positive results. This review offers a comprehensive summary of the diverse machine learning methods employed in biosensors for food safety. Initially, the primary machine learning methods were outlined, and the integrated application of biosensors and machine learning in food safety was thoroughly examined. Lastly, the challenges and limitations of machine learning and biosensors in the realm of food safety were underscored, and potential solutions were explored. The review's findings demonstrated that algorithms grounded in machine learning can aid in the early detection of food safety issues. Furthermore, preliminary research suggests that biosensors could be optimized through machine learning for real-time, multifaceted analyses of food safety variables and their interactions. The potential of machine learning and biosensors in real-time monitoring of food quality has been discussed.

Programmable DNA tweezers-SDA for ultra-sensitive signal amplification fluorescence sensing strategy.

BACKGROUND: DNA tweezers, classified as DNA nanomachines, have gained prominence as multifunctional biosensors due to their advantages, including a straightforward structure, response mechanism, and high programmability. While the DNA tweezers demonstrate simultaneous, rapid, and stable responses to different targets, their detection sensitivity requires enhancement. Some small molecules, such as mycotoxins, often require more sensitive detection due to their extremely high toxicity. Therefore, more effective signal amplification strategies are needed to further enhance the sensitivity of DNA tweezers in biosensing. RESULTS: We designed programmable DNA tweezers that detect small-molecule mycotoxins and miRNAs through simple sequence substitution. While the DNA tweezers demonstrate simultaneous, rapid, and stable responses to different targets, their detection sensitivity requires enhancement. We introduced the Strand Displacement Amplification (SDA) technique to address this limitation, proposing a strategy of novel programmable DNA tweezers-SDA ultrasensitive signal amplification fluorescence sensing. We specifically investigate the effectiveness of this approach concerning signal amplification for two critical mycotoxins: aflatoxin B1 (AFB1) and zearalenone (ZEN). Results indicate that the detection ranges of AFB1 and ZEN via this strategy were 1-10,000 pg mL -1 and 10-100,000 pg mL -1, respectively, with corresponding detection limits of 0.933 pg mL -1 and 1.07 pg mL -1. Compared with the DNA tweezers direct detection method for mycotoxins, the newly constructed programmable DNA tweezers-SDA fluorescence sensing strategy achieved a remarkable 104-fold increase in the detection sensitivity for AFB1 and ZEN. SIGNIFICANCE: The constructed programmable DNA tweezers-SDA ultrasensitive signal-amplified fluorescence sensing strategy exhibits excellent detection performance for mycotoxins. The superb versatility of this strategy allows the developed method to be easily used for detecting other analytes by simply replacing the aptamer and cDNA, which has incredible potential in various fields such as food safety screening, clinical diagnostics, and environmental analysis.

Multisignal Biosensors Based on Mn Paramagnetic Relaxation and Nanocatalysis for Norovirus Detection.

A multisignal method for the sensitive detection of norovirus based on Mn paramagnetic relaxation and nanocatalysis was developed. This dual-modality sensing platform was based on the strong relaxation generated by cracked Au@MnO2 nanoparticles (NPs) and their intrinsic enzyme-like activity. Ascorbic acid rapidly cracked the MnO2 layer of Au@MnO2 NPs to release Mn(II), resulting in the relaxation modality being in a "switch-on" state. Under the optimal conditions, the relaxation modality exhibited a wide working range (6.02 × 103-3.01 × 107 copies/µL) and a limit of detection (LOD) of 2.29 × 103 copies/µL. Using 4,4',4″,4″'-(porphine-5,10,15,20-tetrayl) tetrakis (benzenesulfonic acid) (tpps)-ß-cyclodextrin (tpps-ß-CD) as a T1 relaxation signal amplification reagent, a lower LOD was obtained. The colorimetric modality exploited the "peroxidase/oxidase-like" activity of Au@MnO2 NPs, which catalyzed the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB, which exhibited a working range (6.02 × 104-6.02 × 106 copies/µL) and an LOD of 2.6 × 104 copies/µL. In addition, the rapid amplification reaction of recombinase polymerase enabled the detection of low norovirus levels in food samples and obtained a working range of 101-106 copies/mL and LOD of 101 copies/mL (relaxation modality). The accuracy of the sensor in the analysis of spiked samples was consistent with that of the real-time quantitative reverse transcription polymerase chain reaction, demonstrating the high accuracy and practical utility of the sensor.

MOF-on-MOF heterostructure boosting AIE sensing and triggered structural collapse for histamine detection.

We explored a novel preparation method for MOF-on-MOF heterostructured material (Zn-BTEC@ZIF-8). This prepared heterostructured material acts as a container, capable of adsorbing tetracycline hydrochloride molecules into its backbone through hydrogen bonding and π-π interactions. This phenomenon triggers an aggregation induced emission (AIE) effect, leading to the formation of luminescent bodies. The coordination between histamine and MOF was found to collapse the originally stabilized MOF-on-MOF structure. This collapse causes the splitting of the initially stabilized MOF-on-MOF structure from the aggregated state into fragments, resulting in the quenching of fluorescence in the fluorophore. Remarkably, the fluorescence quenching efficiency of this composite surpasses that of single-layer metal-organic framework (MOF) zeolitic imidazolate framework-8 (ZIF-8) or zinc-based MOF of pyromellitic acid (Zn-BTEC), enabling more sensitive detection of histamine. In this investigation, we constructed a label-free fluorescent sensor specifically designed for the detection of histamine, capitalizing on the AIE effect inherent in MOF-on-MOF architecture and the presence of tetracycline hydrochloride (Tet). The sensor demonstrates a rapid, straightforward, and stable response, allowing for histamine detection within 20 min. Notably, the sensor covers a detection range of 2-400 mg L-1, achieving a low detection limit of 1.458 mg L-1 The practical application of this sensor for quantitative detection of histamine in river water and various fish species exhibited robust performance, ensuring reliability and accuracy in real samples. Its potential application in food safety and environmental monitoring is evident, making it a valuable tool for addressing histamine-related challenges in these domains.

Application of DNA-fueled molecular machines in food safety testing.

Food is consumed by humans, which is indispensable to human life. Therefore, considerable attention of the whole society has been paid to food safety. Over the last few years, dramatic social development has brought new challenges to food safety, making developing new and quick methods for on-site food safety testing an important necessity. As a result, DNA-fueled molecular machines, characterized by high efficiency, accuracy, and sensitivity in testing, have come into the spotlight, based on which sensors can be constructed to detect toxic and harmful substances in food products. This study reviewed recent research on several DNA-fueled molecular machines, including DNA tweezers, DNA walkers, and DNA origami, for rapidly detecting toxic and harmful substances. Based on the above studies, the sensitivity and timeliness of several DNA molecular machines were summarized and compared, and the development prospect of DNA fuel molecular machines in the field of food safety detection was prospected.

Ni-Pt nanozyme-mediated relaxation and colorimetric sensor for dual-modality detection of norovirus.

An NiPt nanozyme-mediated relaxation and colorimetric sensor is developed for dual-modality detection of norovirus (NoV). The relaxation modality is based on the "catalase-like" activity of the NiPt nanozyme, which adjusts the hydrogen peroxide (H2O2) mediated Fe (II)/Fe(III) conversion, thereby changing the relaxation signal. Poly-γ-glutamic acid (MW ≈ 1w) can enhance the relaxivity of Fe(III) (r1 = 7.11 mM-1 s-1; r2 = 8.94 mM-1 s-1). The colorimetric modality exploits the "peroxidase-like" activity of the NiPt nanozyme, which can catalyze the oxidation of colorless 3, 3', 5, 5'-tetramethylbenzidine (TMB) to blue oxTMB in H2O2. Under optimal conditions, the relaxation modality exhibits a wide working range (1.0 × 101-1.0 × 104 fM) and a limit of detection (LOD) of 4.7 fM (equivalent to 2820 copies/µL). The spiked recoveries range from 99.593 to 106.442 %, and the relative standard deviation (RSD) is less than 5.124 %. The colorimetric modality exhibited the same working range with a lower LOD of 2.9 fM (equivalent to 1740 copies/µL) and an RSD of less than 2.611 %. Additionally, the recombinase polymerase amplification reaction enabled the detection of low NoV levels in food samples with a working range of 102-106 copies/mL and LOD of 102 copies/mL. The accuracy of the sensor in the analysis of spiked samples is consistent with the gold standard method (real-time quantitative reverse transcription-polymerase chain reaction), demonstrating the high accuracy and practical utility of the sensor.

A facile dual-mode immunosensor based on speckle Ag-doped nanohybrids for ultrasensitive detection of Ochratoxin A.

Ochratoxin A (OTA) is a potent carcinogen, and is among the most dangerous mycotoxins in agricultural products. In this study, an ultrasensitive dual-mode immunosensor was developed for naked-eye and fluorescence detection of OTA based on Ag-doped core-shell nanohybrids (Ag@CSNH). Complete antigen-labeled Ag@CSNH (CA-Ag@CSNH) were used as a competitive bind and dual-mode probe. The diffused doping structure of CA-Ag@CSNH provided improved stability, color and fluorescence quencher performance. Antibodies modified magnetic beads were used as a capture probe. The competitive binding between OTA and CA-Ag@CSNH produced both color change and fluorescence quenching. Ultraviolet and fluorescence intensitie correlated linearly with OTA concentration ranges of 0.03-3 ng/mL and 10-10000 pg/mL, and limits of detection of 0.0235 ng/mL and 0.9921 pg/mL, respectively. The practical applicability of proposed strategy was demonstrated by analysis of OTA in spiked corn, soybean and flour samples. This study offers a new insight on multi-mode platforms for various applications.

Classification and Quantitative Characterization of Archean Metamorphic Buried Hill Reservoirs in the Bohai Sea.

Based on productivity test data and physical property test results from multiple wells, a classification scheme of Archean metamorphic buried hill reservoirs in the Bohai Sea is established by means of mathematical function fitting. By combining data from cores, casting thin sections, scanning electron microscopy, imaging logging, and high-pressure mercury injection and nitrogen adsorption tests, we clarified the reservoir composition and pore structure characteristics of different types of reservoirs are clarified. Furthermore, taking the BZ19-6 and 13-2 wells in the Archean metamorphic buried hills as an example, the development sites of different types of reservoirs are analyzed and the reservoir development model is established. The results show that the Archean metamorphic buried hill reservoirs in the Bohai Sea can be divided into three categories and six subcategories, including type I reservoirs with porosities greater than 8% or permeabilities greater than 1 × 10-3 µm2 and type II reservoirs with porosities of 5-8% or permeabilities in the range of 0.1-1 × 10-3 µm2. Reservoirs with porosities of 2-5% and permeabilities of 0.01-0.1 × 10-3 µm2 are type III reservoirs. Each type of reservoir can be further divided into a fracture-pore type and a fracture type according to the relative contribution of the porosity and permeability to the reservoir. From type I to type III, the dissolution degree and fracture development gradually weaken, the pore size gradually decreases, and the pore volume gradually decreases. The distribution of favorable reservoirs is comprehensively controlled by weathering and tectonic transformation. The presence of a weathered glutenite zone, weathered leaching zone, or weathered disintegration zone is favorable for the development of type I reservoirs in the weathering crust. In the inner part of the buried hill, the presence of a fracture zone with a thickness of more than 10 m or a dense fracture zone with a thickness of more than 40 m is favorable for the formation of type I reservoirs.

A multifunctional polyacrylamide/chitosan hydrogel for dyes adsorption and metal ions detection in water.

Removing noxious dyes and detecting excessive metal ions in water are both effective means to prevent damage from contaminants and ensure water safety. The emphasis problems were addressed by preparation a polyacrylamide chitosan (PAAM/CS) hydrogel. Polyacrylamide (PAAM) provides overall mechanical strength to carry loads and facilitate circulation, chitosan (CS) provides adsorption positions with high adsorption capacity. Which made that PAMM/CS hydrogel efficiently performed sorption of xylenol orange (XO). As the functional dye, XO binds to PAAM/CS and confers colorimetric properties on PAAM/CS hydrogels. XO sorbed hydrogel realized fluorescence dual-signal detection of Fe3+ and Al3+ in water. The significant swelling and adsorption potency of the hydrogel, combined with the dual-signal detection capability of XO sorbed hydrogel, make this hydrogel a versatile material for environmental applications.

Application of DNA Nanotweezers in biosensing: Nanoarchitectonics and advanced challenges.

Deoxyribonucleic acid (DNA) is a carrier of genetic information. DNA hybridization is characterized by predictability, diversity, and specificity owing to the strict complementary base-pairing assembly mode, which stimulates the use of DNA to build a variety of nanomachines, including DNA tweezers, motors, walkers, and robots. DNA nanomachines have become prevalent for signal amplification and transformation in the field of biosensing, providing a new method for constructing highly sensitive sensing analysis strategies. DNA tweezers have exhibited unique advantages in biosensing applications owing to their simple structures and fast responses. The two-state conformation of DNA tweezers, the open and closed states, enable them to open and close autonomously after stimulation, thus facilitating the quick detection of corresponding signal changes of different targets. This review discusses the recent progress in the application of DNA nanotweezers in the field of biosensing, and the trends in their development for application in the field of biosensing are summarized.