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Pyridine carboxylic acid isomers - picolinic acid, nicotinic acid, and isonicotinic acid - have historically resulted in a plethora of drugs against tuberculosis, cancer, diabetes, Alzheimer's, angina, dementia, depression, allergy, respiratory acidosis, psoriasis, acne, hypertension, hyperlipidemia, HIV/AIDS (specifically HIV-1), among others. Despite the large number of therapeutic agents derived from these isomers, the research involving these scaffolds is still exceptionally active. The current surge in enzyme inhibitory activities by the compounds derived from them has further created space for the discovery of new drug candidates. This review focuses on the medicinal relevance of these isomers by analyzing structure-activity relationships (SARs) and highlighting emerging trends from patents filed over the last decade. Notably, pharmaceutical giants like Bayer, Bristol-Myers Squibb, Novartis, Curis, and Aurigene have developed enzyme inhibitors based on these scaffolds with nanomolar potency. The role of these isomers in the development of antiviral agents, including protease inhibitors, is also discussed. Overall, this review brings to the readers, a pragmatic opportunity to comprehend the recent literature, highlighting the scaffolds' importance in the design of new enzyme inhibitors. Furthermore, it discusses the structure-activity relationship of pyridine carboxylic acid-derived compounds and highlights the current patenting trends in medicinal chemistry.

The rapid in situ detection of pesticide residues in real samples based on surface-enhanced Raman spectroscopy (SERS) remains a challenge, necessitating an urgent need for a feasible solution that addresses issues such as sample complexity, reproducibility, and SERS substrate stability. This paper proposes a flexible SERS substrate, which consists of a composite gel made of sodium alginate-chitosan loaded with silver nanocubes (SACTS@AgNCs). The flexible nature of the SERS substrate enables the analysis of irregular surfaces of apples, dispensing with laborious pretreatment and promoting an effective contact with target molecules. By utilizing the SA-CTS@AgNCs substrate in conjunction with a portable Raman instrument, an exceptional sensitivity was achieved with a detection limit of 0.055 mg/L for thiram in apples. In addition, the stability, homogeneity, and batch-to-batch reproducibility of the substrates were evaluated. The experimental results showed that after 45 days of storage, the substrate still maintained more than 84.40 % SERS activity, demonstrating long-term stability. Within a single substrate, the point-to-point relative standard deviation (RSD) was only 4.2 %, while among different batches of substrates, the RSD was as low as 6.8 %, displaying better homogeneity and reproducibility. Hence, this flexible SERS substrate provides a reliable and convenient platform for rapid detection and on-site monitoring of food safety.

Flexible surface-enhanced Raman scattering (SERS) sensors offer a promising solution for the rapid in situ monitoring of food safety. The sensor's capability to furnish quantitative detection and retain recyclability is crucial in practical applications. This study proposes a self-cleaning flexible SERS sensor, augmented with an intelligent algorithm designed for expeditious in situ and non-destructive thiram detection on apples. Flexible carriers were prepared via electrostatic spinning, while cuprous oxide spheres decorated with silver (Cu₂O@Ag) were synthesized through surfactant-mediated in situ reduction of silver spheres. Then, PAN/Cu₂O@Ag/Au@AgNPs flexible sensors with both SERS enhancement and photocatalytic degradation effects were generated by self-assembling core-shell Au@Ag nanoparticles on the flexible carriers. Convolutional neural network (CNN) and competitive adaptive reweighted sampling-partial least squares (CARS-PLS) algorithms were applied for the quantitative prediction of thiram. The results showed that the CNN algorithm has better performance, with correlation coefficient of 0.9963 and detection limit of 0.020 mg/L, respectively. Notably, the flexible SERS sensor could be recycled at least 5 times, with thiram detection recovery ranging from 88.32 % to 111.80 %. This self-cleaning flexible sensor combined with deep learning algorithm has shown significant potential for applications in food safety monitoring.

Patulin (PAT), a major contaminant in apples, poses a considerable food safety risk, necessitating a rapid, sensitive and reliable detection method. This study developed a novel magnetic metal-organic frameworks (MOFs)-based ratiometric surface-enhanced Raman scattering (SERS) aptasensor. The sensor consists of magnetic MOFs loaded with 4-Mercaptobenzoic acid (4-MBA) internal labeled Au^MBA@Ag as the SERS substrate, and gold nanorods (AuNRs) modified with Rhodamine 6G and aptamers as capture probes. This strategy enhances sensitivity through magnetic separation and abundant SERS hotspots provided by the magnetic MOF nanocomposites. The SERS intensity ratio showed a negative correlation with PAT concentrations from 0.01 to 100 ng/mL, with a LOD of 0.0465 ng/mL. Moreover, the aptasensor achieved 95.90 % ∼105.83 % recoveries in apple samples, indicating high accuracy and anti-interference capability. The excellent sensing performance demonstrates great potential of the SERS nanosensor for mycotoxin detection in actual food matrices.

A microfluidic-surface enhanced Raman spectroscopy (SERS) platform for rapid detection of Escherichia coli in food products is proposed. By implementing a Y-junction serpentine microfluidic channel, we achieved in-situ synthesis of silver nanoparticles (AgNPs), for enhancing SERS signal intensity. The synthesis of AgNPs was guided by specific aptamers bound to the bacterial cell, which facilitated formation of nanoparticles. This aptamer guided in-situ synthesis ensured specificity and accuracy in detecting E. coli with a limit of detection of 1.1 CFU/mL and a linear detection range from 10² to 10⁸ CFU/mL, showing superior sensitivity compared to other reported methods. The technique also showed recovery value ranging from 83 to 125 % for lettuce sample. The platform combines the advantages of microfluidics and SERS, enabling rapid, sensitive, and label-free detection of pathogens in food. This method addresses limitations of conventional culture-based techniques and other molecular diagnostics, offering a promising tool for microbial food safety analysis.

Aflatoxin B1 (AFB1) is a prevalent contaminant in maize, posing significant threats to human health. This study designed Au-Ag Janus NPs with intrinsic Raman signals as signal probes and SiO2@AgNPs as capture probes. The two were coupled through complementary base pairing to ensure the ordered, controlled distribution of noble metal nanoparticles. The Au-Ag Janus NPs and the highly stable SiO2 carrier is expected to avoid the adverse effects on stability caused by using signal molecules and the formation of random aggregates when using the noble metal nanoparticle gap effect to concentrate on the electromagnetic field. This study improved the negative impact of AgNPs' high surface energy on their uniformity, while enhancing the pH adaptability of Au-Ag Janus NPs. In the presence of AFB1, the composite disintegrates, and the SERS intensity showed a negative correlation with AFB1 concentration, enabling highly sensitive and stable detection of AFB1.

Indicator migration within intelligent packaging systems can compromise the safety of the food matrix and the accuracy of coloration, particularly in high humidity packaging. Herein, Eu-BDC-NH2-Fluorescein (MOF-Flu) nanofillers were synthesized by the amide coupling, followed by an analysis of their structural, morphological characteristics, and optical response. The MOF-Flu and microcrystalline cellulose (MCC) nanomaterials were embedded into a sodium carboxymethyl cellulose (CMC-Na) substrate to fabricate enhanced packaging films. Several beneficial properties, including superior hydrophobicity and water resistance, improved mechanical properties, and enhanced thermal stability, were observed for CMC-Na/MOF-Flu compared to CMC-Na/MCC. Additionally, the MOF-Flu composite film exhibited improved UV-visible barrier properties, exceptional resistance to pigment migration, and good time-temperature stability. Finally, a significant linear correlation (R2 = 0.9938, LOD: 1.79-2.90 N/cm2, RSD: 2.16%, recovery: 103.93%) was established using a smartphone application to display the relationship between the SRGB-values of MOFs-based films and hardness of fresh-cut Narcissus mangoes at 4 degrees C. The digital sensing platform utilizing smartphones has pioneered a powerful approach for the on-site rapid quantitative assessment of fresh-cut fruit freshness, significantly enhancing the precision and convenience of intelligent packaging. Furthermore, the developed indicator material MOF-Flu can accurately and non-destructively monitor changes of fruit freshness, alleviating concerns regarding dye contamination during migration.

Patulin (PAT) commonly contaminates fruits, posing a significant risk to human health. Therefore, a highly effective and sensitive approach in identifying PAT is warranted. Herein, a SERS aptasensor was constructed based on a two-dimensional film -like structure. GO@Au nanosheets modified with SH-cDNA were employed as capture probes, while core -shell Au@Ag nanoparticles modified with 4 -MBA and SH-Apt were utilized as signal probes. Through the interaction between capture probes and signal probes, adjustable hotspots were formed, yielding a significant Raman signal. During sensing, the GO@Au-cDNA competitively attached to Au@AgNPs@MBA-Apt, resulting in an inverse relationship between PAT levels and SERS intensity. The acquired results exhibited linear responses to PAT within the range of 1-70 ng/mL, with a calculated limit of detection of 0.46 ng/mL. In addition, the SERS aptasensor exhibited satisfactory recoveries in apple samples, which aligned closely with HPLC. With high sensitivity and specificity, this method holds significant potential for PAT detection.

Acetamiprid is an organic and highly toxic compound. Despite being widely used as a pesticide agent on a large scale, acetamiprid poses numerous health risks to living organisms, particularly humans. Herein, a strategy for the detection of acetamiprid in tea employing surface-enhanced Raman scattering (SERS) technology incorporated with a microfluidic chip was developed. Significantly, a seed-mediated growth approach was utilized to engineer Ag-coated tetrapod gold nanostars (core–shell Au@AgNSs) with four sharp tips. The synthesized Au@AgNSs showed an enhancement factor of 7.2 × 10⁶. Solid works was used to figure out the two-channel microfluidic chip featuring four circular split hybrid structures, and COMSOL (Software for Multiphysics Simulation) was utilized to model the fusion effect between the substrate (Au@AgNSs) and the sample (acetamiprid). For the first time, the core–shell Au@AgNSs and acetamiprid were fused in the microfluidic channel to facilitate the detection of acetamiprid using SERS. The outcomes pointed out that the standard curve correlation coefficient between SERS intensity (876 cm⁻¹) and the concentration of acetamiprid in tea specimens was calculated as 0.991, while the limit of detection (LOD) was 0.048 ng mL⁻¹, which is well below the minimum limit set by the European Union (10 ng mL⁻¹). Thus, the developed technique combining SERS and microfluidics demonstrated high potential for the rapid and efficient detection of acetamiprid in tea.

Self-assembly of peptides is a powerful method of preparing nanostructured materials. Peptides frequently utilize charged groups as a convenient switch for controlling assembly state by pH, ionic strength or temperature. In this study, the molecular properties and gel-forming ability of Chlamys farreri protein hydrolysates were studied. According to self-assembled theory, the presence of isoleucine at position 'a' and leucine at 'd' causes a switch between coiled-coil structures. Compared to P-2-CG, the components of & alpha;-helix (23.60 & PLUSMN; 0.56%) were changed into 8-sheet (4.83 & PLUSMN; 2.86%) in the secondary structure of the hydrogel induced by ZnCl2. NMR siginals appeared at high field,which indicated hydrogen bonds were formed between P-2-CG and solvent environments at 20 degrees C. With temperature going up, the hydrogen bonds were broken and nanofibrils were changed into dense aggre-gates. We expected that P-2-CG could provide a new candidate for preparing metal-induced nanofibers or hydrogels with further applications in food industry.