Essential oil components are the most common agents used to inhibit pathogens. Ethyl cinnamate (ECIN) is a hydrophobic essential oil component with well-known antibacterial properties but is poorly soluble in water, which limits its applications. In this study, inclusion complexes (ICs) were prepared by encapsulating ECIN in (3-cyclodextrin ((3CD), 2-hydroxypropyl-(3CD, or methyl-(3CD using an ultrasonication method to enhance water solubility and thermal and antibacterial properties. UV-Vis absorption and fluorescence spectral results indicated strong non-covalent interactions between ECIN and (3CD derivatives in aqueous solution, and double reciprocal profiles revealed a guest:host stoichiometry of 1:1. Fourier-transform infrared and proton nuclear magnetic resonance spectroscopy investigations revealed that the phenyl ring of ECIN is located deeply in the CD nano- cavities. X-ray diffraction, ultraviolet-visible diffuse reflectance spectroscopy, photoluminescence, and field emission scanning electron microscopy were performed to obtain crystalline, optical, and morphological information on solid ECIN-CDs. Thermogravimetric/differential thermal studies confirmed the improved stability of ECIN in solid CD-ICs by detecting an increase in the degradation temperature of ECIN from 50-140 degrees C to 310-410 degrees C. Further, the geometrical and frontier molecular orbital structures of the ECIN-CDs were theoretically evaluated using parametric method-3. Finally, antibacterial assays conducted against the foodborne pathogens Staphylococcus aureus and Escherichia coli and revealed that encapsulated ECIN had a greater inhibitory effect, which suggested the devised nanocarriers promote the solubilization of essential oil components in aqueous solutions.

Nanomaterial-based field-effect transistor (FET) biosensors hold significant potential for food safety monitoring and early disease detection due to their exceptional sensitivity and rapid response capabilities. However, many academically engineered FET biosensors lag behind in terms of real-word reproducibility, scalability, and insufficient methodological validation. Herein, we report a novel electrohydrodynamically (EHD)-printed organic field-effect transistor (OFET) sensor for the rapid detection of carcinogenic aflatoxin B1 (AFB1) in food samples. A poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) channel, deposited via EHD printing, was functionalized with L-cysteine and conjugated with AFB1 antibodies. Optimization of fabrication parameters-printing speed (100 mm s(-1)), layer count (100 layers), ink concentration (5 mu L mL(-1)), and immobilization time (5 h)-enabled the sensor to achieve a detection limit of 2.01 ppb over a linear range of 0.35-40 ppb in an aqueous medium, demonstrating high sensitivity and selectivity (similar to 99.9 % for AFB1) against prominent interfering mycotoxins (zearalenone (ZEA) similar to 2.26 %, ochratoxin A (OTA) similar to 5.03 %, AFG2 similar to 6.34 %, AFG1 similar to 36.30 %, and AFB2 similar to 35.26 %) with a response time of approximately 5 s. Moreover, the OFET biosensor could detect AFB1 in real food samples (e.g. peanut butter) without requiring complex sample preparation method. The OFET biosensor showed good reusability after washing with 0.1 % acetic acid in methanol and exhibited minimal interference in the presence of other mycotoxins like AFB2, AFG1, AFG2, OTA, and ZEA. This study demonstrates that the printable OFET biosensor is practical for food safety due to its high sensitivity, selectivity, and reusability.

Thioredoxin-interacting protein (TXNIP) has emerged as a key player in cancer and diabetes since it targets thioredoxin (TRX)-mediated redox regulation and glucose transporter (GLUT)-mediated metabolism. TXNIP consists of two arrestin (ARR, N-ARR and C-ARR) domains at its amino-terminus and two PPxY (PY) motifs and a di-leucine (LL) motif for endocytosis at its carboxyl-terminus. Here, we report that TXNIP shuffles between TRX and GLUTs to regulate homeostasis of intracellular oxidative stress and glucose metabolism. While TXNIP functions as a gatekeeper of TRX by default, it robustly interacted with class I GLUTs through its C-ARR domain upon increase of intracellular reactive oxygen species. This interaction prompted the surface expression downregulation and lysosomal degradation of GLUTs by its carboxyl-terminal LL endocytic signaling motif to attenuate glucose uptake. Consequently, TXNIP expression significantly limited glucose uptake, leading to the suppression of glycolysis, hexosamine biosynthesis, and the pentose phosphate pathway. Our findings establish a fundamental link between ROS and glucose metabolism through TXNIP and provide a promising target for the drug development against GLUT-related metabolic disorders.

Heavy metal ions (HMIs) are major water pollutants, and their toxicity for humans is a great concern for scientists and environmentalists. They are harmful to health even at trace levels; therefore, identifying and removing heavy metals from water is critical. Herein, we report highly selective and sensitive multi-analyte detection of HMIs in water using an electrochemical sensor probe based on Ag nanoparticles and single-walled carbon nanotubes incorporating copper benzene tri-carboxylate metal–organic frameworks (Ag/SWNTs@CuBTC-MOFs). The materials were characterized using FTIR, XPS, XRD, and FE-SEM with EDX mapping, TEM, TG-DTA, BET surface area, CV, and EIS. The Ag/SWNTs@CuBTC-MOF electrochemical sensor was tested by differential pulse voltammetry over a pH range of 3–10 for various HMIs. It shows high pH-dependent sensitivity towards Hg2+ (pH-5.0), Ni2+ (pH 7.0), and Fe3+ (pH 10.0) ions and a limit of detection of 1.39nM, 2.6nM, and 3.03nM, respectively. The fabricated sensor probe exhibits high selectivity, good linearity, and a detection limit below the maximum contamination limit, as the US Environmental Protection Agency suggested.

Prunus mume (maesil) is an economically important fruit in Korea. Recently, public interest in maesil sugar syrup is increasing. However, the presence of toxic amygdalin in the fruit syrup is a concern. Thus, the current investigation aimed to observe effects of maesil maturity, ripening methods, processing, and fermentation period on the amygdalin level in maesil sugar syrup. Six different types of maesil sugar syrup were prepared and amygdalin content was monitored at 3-month intervals. Higher levels (>63 mg/L) of amygdalin were found in syrups prepared from unripe fruit compared to those in syrups made from ripe fruit after 3 months of fermentation. A rapid reduction in amygdalin content was observed until 9 months in all syrups, gradually reducing to <5 mg/L at 12 months. More than 9 months of maturation is crucial for reducing the amygdalin content maesil sugar syrup, regardless of fruit maturity, source of fruit, and processing method.

Toxin- and drug-induced tubulointerstitial nephritis (TIN), characterized by interstitial infiltration of immune cells, frequently necessitates dialysis for patients due to irreversible fibrosis. However, agents modulating interstitial immune cells are lacking. Here, we addressed whether the housekeeping enzyme glutamyl-prolyl-transfer RNA synthetase 1 (EPRS1), responsible for attaching glutamic acid and proline to transfer RNA, modulates immune cell activity during TIN and whether its pharmacological inhibition abrogates fibrotic transformation. The immunological feature following TIN induction by means of an adenine-mixed diet was infiltration of EPRS1high T cells, particularly proliferating T and γδ T cells. The proliferation capacity of both CD4+ and CD8+ T cells, along with interleukin-17 production of γδ T cells, was higher in the kidneys of TIN-induced Eprs1+/+ mice than in the kidneys of TIN-induced Eprs1+/- mice. This discrepancy contributed to the fibrotic amelioration observed in kidneys of Eprs1+/- mice. TIN-induced fibrosis was also reduced in Rag1-/- mice adoptively transferred with Eprs1+/- T cells compared to the Rag1-/- mice transferred with Eprs1+/+ T cells. The use of an EPRS1-targeting small molecule inhibitor (bersiporocin) under clinical trials to evaluate its therapeutic potential against idiopathic pulmonary fibrosis alleviated immunofibrotic aggravation in TIN. EPRS1 expression was also observed in human kidney tissues and blood-derived T cells, and high expression was associated with worse patient outcomes. Thus, EPRS1 may emerge as a therapeutic target in toxin- and drug-induced TIN, modulating the proliferation and activity of infiltrated T cells.

During the 2021/2022 winter season, we isolated highly pathogenic avian influenza (HPAI) H5N1 viruses harbouring an amino acid substitution from Asparagine(N) to Aspartic acid (D) at residue 193 of the hemagglutinin (HA) receptor binding domain (RBD) from migratory birds in South Korea. Herein, we investigated the characteristics of the N193D HA-RBD substitution in the A/CommonTeal/Korea/W811/2021[CT/W811] virus by using recombinant viruses engineered via reverse genetics (RG). A receptor affinity assay revealed that the N193D HA-RBD substitution in CT/W811 increases alpha 2,6 sialic acid receptor binding affinity. The rCT/W811-HA193N virus caused rapid lethality with high virus titres in chickens compared with the rCT/W811-HA193D virus, while the rCT/W811-HA193D virus exhibited enhanced virulence in mammalian hosts with multiple tissue tropism. Surprisingly, a ferret-to-ferret transmission assay revealed that rCT/W811-HA193D virus replicates well in the respiratory tract, at a rate about 10 times higher than that of rCT/W811-HA193N, and all rCT/W811-HA193D direct contact ferrets were seroconverted at 10 days post-contact. Further, competition transmission assay of the two viruses revealed that rCT/W811-HA193D has enhanced growth kinetics compared with the rCT/W811-HA193N, eventually becoming the dominant strain in nasal turbinates. Further, rCT/W811-HA193D exhibits high infectivity in primary human bronchial epithelial (HBE) cells, suggesting the potential for human infection. Taken together, the HA-193D containing HPAI H5N1 virus from migratory birds showed enhanced virulence in mammalian hosts, but not in avian hosts, with multi-organ replication and ferret-to-ferret transmission. Thus, this suggests that HA-193D change increases the probability of HPAI H5N1 infection and transmission in humans.

Ochratoxin A (OTA) is a toxic secondary metabolite synthesized by certain fungal strains of Penicillium and Aspergillus and is characterized as a Group 2B carcinogen. OTA infiltrates food and feeds through diverse chains, posing health risks to humans and animals. Herein, seven distinct edible plant materials were screened for their OTA reduction activity. Amidst them, ginger juice in aqueous (2.5%, v/v) showed the highest OTA reduction (95.63%), following first-order reaction kinetics (R2 = 0.92) with 0.72 d-1 rate constant. OTA reduction activity of ginger juice was substantially compromised in the presence of salt (>2.5%) and temperature (>40 °C). The response surface methodology-based approach employing Box-Behnken experimental design revealed an integrated effect of temperature, pH, and salt concentrations on OTA reduction (27.44-100%) by ginger juice. In addition, heat treatment (100 °C) and dialysis (12-14 kDa cutoff) of ginger juice implied the inclusion of heat-stable small molecules in reducing OTA. Ginger-treated OTA ameliorated hepatocellular carcinoma (HepG2) cell viability and diminished reactive oxygen species (ROS) levels compared to native OTA. In zebrafish embryos, OTA-induced teratogenic effects, diminished hatching (22.91%), and elevated ROS levels leading to embryo mortality (75%) were significantly reversed by OTA treated with ginger, underscoring the curtailed toxicity of OTA-converted products by ginger.

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

The rising prevalence of diabetes has led to an increased focus on real-time glucose monitoring. Wearable glucose sensor patches allow noninvasive, real-time monitoring, reducing patient discomfort compared to invasive sensors. However, most existing glucose sensor patches rely on complex and contaminating metal vapor deposition technologies, which pose limitations in practical production. In this study, we propose a novel approach for preparing graphite/multiwall carbon nanotubes (MWCNT)/reduced graphene oxide (rGO) using a high-viscosity ink, which can be easily obtained through simple mechanical stirring. To create intricate patterns and enable printing on curved substrates, we employed a 3D printer equipped with an infrared laser ranging system. The ink served as a working electrode, and we developed a three-electrode system patch with a concentric circle structure. Subsequently, the working electrode underwent enzymatic modification with glucose dehydrogenase with flavin adenine dinucleotide (GDH-FAD) using a polymer embedding method. The resulting wearable glucose sensor exhibited a sensitivity of 2.42 μA mM-1 and a linear detection range of 1-12 mM. In addition, the glucose sensor has excellent anti-interference capability and demonstrates good repeatability in simulated real human wear scenarios, which meets the requirements for accurate human detection. These findings provide valuable insights into the development of human health monitoring technologies.

Multiple bacterial genera take advantage of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin to invade host cells. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly opportunistic pathogen that causes primary septicemia, the precursor of sepsis, is a major driver of infection; however, the molecular mechanism via which the toxin contributes to septicemia remains unclear. Here, we report the crystal and cryo-electron microscopy (EM) structures of a toxin effector duet comprising the domain of unknown function in the first position (DUF1)/Rho inactivation domain (RID) complexed with human targets. These structures reveal how the duet is used by bacteria as a potent weapon. The data show that DUF1 acts as a RID-dependent transforming NADase domain (RDTND) that disrupts NAD+ homeostasis by hijacking calmodulin. The cryo-EM structure of the RDTND-RID duet complexed with calmodulin and Rac1, together with immunological analyses in vitro and in mice, provide mechanistic insight into how V. vulnificus uses the duet to suppress ROS generation by depleting NAD(P)+ and modifying Rac1 in a mutually-reinforcing manner that ultimately paralyzes first line immune responses, promotes dissemination of invaders, and induces sepsis. These data may allow development of tools or strategies to combat MARTX toxin-related human diseases.

Abstract Kidney fibrosis causes irreversible structural damage in chronic kidney disease and is characterized by aberrant extracellular matrix (ECM) accumulation. Although glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is a crucial enzyme involved in proline-rich protein synthesis, its role in kidney fibrosis remains unclear. The present study revealed that EPRS1 expression levels were increased in the fibrotic kidneys of patients and mice, especially in fibroblasts and proximal tubular epithelial cells, on the basis of single-cell analysis and immunostaining of fibrotic kidneys. Moreover, C57BL/6 EPRS1tm1b heterozygous knockout (Eprs1 +/−) and pharmacological EPRS1 inhibition with the first-in-class EPRS1 inhibitor DWN12088 protected against kidney fibrosis and dysfunction by preventing fibroblast activation and proximal tubular injury. Interestingly, in vitro assays demonstrated that EPRS1-mediated nontranslational pathways in addition to translational pathways under transforming growth factor β-treated conditions by phosphorylating SMAD family member 3 in fibroblasts and signal transducers and activators of transcription 3 in injured proximal tubules. EPRS1 knockdown and catalytic inhibition suppressed these pathways, preventing fibroblast activation, proliferation, and subsequent collagen production. Additionally, we revealed that EPRS1 caused mitochondrial damage in proximal tubules but that this damage was attenuated by EPRS1 inhibition. Our findings suggest that the EPRS1-mediated ECM accumulation induces kidney fibrosis via fibroblast activation and mitochondrial dysfunction. Therefore, targeting EPRS1 could be a potential therapeutic target for alleviating fibrotic injury in chronic kidney disease.

Gochujang, a fermented red pepper paste, is often vulnerable to pack burst spoilage, leading to significant economic loss. Zygosaccharomyces rouxii is responsible for the aerogenesis and volume expansion of gochujang. . This study aimed to develop optimal physical methods, including thermal treatments (direct heat and steam heat) and non-thermal treatments (high-pressure processing (HPP) and sonication), to reduce the activity of Z. rouxii and prevent pack burst spoilage of gochujang. . Among the various physical treatments, HPP and direct heat treatment significantly reduced pack burst spoilage compared to sonication and steam heat treatments. Yeast counts were decreased considerably after HPP (1.26-4.49 log CFU/g) and direct heat treatment (0.59-3.0 log CFU/g). However, the reduction in aerobic bacterial count was minimal, ranging from 0.18 to 0.43 log CFU/g with direct heat and 0-0.18 log CFU/g with HPP. This reduction in yeast count effectively controlled aerogenesis and volume expansion in gochujang, , subsequently reducing the incidence of pack burst spoilage by 80%-90%. No significant difference was observed in the overall acceptability of HPP (5.18 +/- 0.24) and direct heat-treated (5.24 +/- 0.24) gochujang products compared to the control (5.02 +/- 0.27), with favorable hedonic scores (on a 7-point scale) achieved in the sensory analysis. These findings indicate that direct heat treatment for 3 min at 75 degrees C or HPP treatment at 550 Mpa for 4 min at 15 degrees C prevents pack burst spoilage in gochujang products.

Cancer vaccines have been developed as a promising way to boost cancer immunity. However, their clinical potency is often limited due to the imprecise delivery of tumor antigens. To overcome this problem, we conjugated an endogenous Toll-like receptor (TLR)2/6 ligand, UNE-C1, to human papilloma virus type 16 (HPV-16)-derived peptide antigen, E7, and found that the UNE-C1-conjugated cancer vaccine (UCV) showed significantly enhanced antitumor activity in vivo compared with the noncovalent combination of UNE-C1 and E7. The combination of UCV with PD-1 blockades further augmented its therapeutic efficacy. Specifically, the conjugation of UNE-C1 to E7 enhanced its retention in inguinal draining lymph nodes, the specific delivery to dendritic cells and E7 antigen-specific T cell responses, and antitumor efficacy in vivo compared with the noncovalent combination of the two peptides. These findings suggest the potential of UNE-C1 derived from human cysteinyl-tRNA synthetase 1 as a unique vehicle for the specific delivery of cancer antigens to antigen-presenting cells via TLR2/6 for the improvement of cancer vaccines.

Microarray patterns fabricated using printing technology have attracted significant research interest for the production of portable, implantable, feasible, wearable, and flexible electronics. Electrohydrodynamic (EHD) printing is an emerging, simple, and rapid electrode-patterning technology for academic and industrial applications. The development of devices composed of MXenes, 2D hexagonal crystals, which demonstrate great potential for electronic and energy storage applications, is one of the main focuses of current research efforts. Herein, we report the EHD-printed Ti3C2Tx MXene-based field-effect transistors (FET) as promising biosensors for aflatoxin B1 (AFB1) detection. The printing cycles and ink concentration were considered as the optimization objectives, and the optimized FET was validated using the output and transfer characteristics of the device. The optimized EHD-printed FET exhibited good adhesion to the substrate, high electrical conductivity, and an ideal range of resistance. The biosensor was created by functionalizing the EHD-printed MXene layers with a specific antibody against AFB1. This FET biosensor could detect the AFB1 at a concentration of 0.01 ppb with a linearity range of 0.7-20 ppb in a water medium (limit of detection = 5.689 ppb). In addition, the FET biosensor successfully detected AFB1 in food samples, such as peanut butter and meju. Thus, we have successfully demonstrated a promising EHD-printed FET biosensor for AFB1. The device is a highly selective and sensitive immunoanalytical method for AFB1 that requires no complex sample preparation steps compared with highperformance liquid chromatography.

We report an ultrasensitive and selective carbon monoxide (CO) chemiresistive sensor based on ironoctaethylporphyrin (FeOEP)-functionalized reduced graphene oxide (rGO) (rGO/FeOEP). The graphene oxide (GO) was synthesized using Hummers ' improved method and was thermally reduced to obtain rGO, which was then drop-cast onto copper electrodes on a glass substrate. The sensors based on rGO/OEP and rGO/FeOEP were prepared by functionalizing rGO with OEP and FeOEP, respectively. GO, rGO, and rGO/FeOEP were characterized using various techniques such as Fourier transform infrared spectroscopy, UV -visible spectroscopy, Raman spectroscopy, X-ray diffraction, current -voltage characteristics, and scanning electron microscopy. The rGO/FeOEP-based sensor exhibited a superior sensing performance in the chemiresistive modality, with response and recovery times of 55 s and 120 s, respectively. The rGO/FeOEP sensor exhibited high sensitivity, selectivity, stability, repeatability, and reproducibility for CO, with a limit of detection of 1 ppm, which is far below the permissible exposure limit suggested by the Occupational Safety and Health Administration, USA.

Heavy metal ions pollutants pose remarkable hazards to humans and the environment. Their toxicity is a concern for both aquatic life and humans. Still, it directly threatens humans when consumed through drinking water or aquatic species such as fish. Therefore, detecting, quantifying, and removing these pollutants from water sources is necessary. In this study, we fabricated a highly selective and sensitive Hg2+ ion electrochemical sensor using a solvothermally synthesized composite of silver nanoparticles (Ag NPs) and zinc benzene dicarboxylate (ZnBDC) (Ag@ZnBDC) metal–organic framework (MOF) at trace levels. The synthesized Ag@ZnBDC MOFs composite was studied using various characterization techniques: structural, spectroscopic, thermal, Brunauer-Emmett-Teller (BET) surface area, morphological, elemental, and electrochemical techniques. The electrochemical sensor was fabricated by drop-casting the Ag@ZnBDC composite onto a glassy carbon electrode (GCE), and its sensing properties were evaluated using cyclic voltammetry and differential pulse voltammetry techniques. Remarkably, the sensor exclusively and highly selectively responded to Hg2+ ions among Cd2+, Cr3+, Cu2+, Fe3+, and Pb2+ ions at a concentration of 1μM. The Ag@ZnBDC/GCE sensor shows a limit of detection (LOD) of 4.16 nM in the linear response within the concentration range of 1-10 nM for Hg2+ ions.

Essential oil components are the most common agents used to inhibit pathogens. Ethyl cinnamate (ECIN) is a hydrophobic essential oil component with well-known antibacterial properties but is poorly soluble in water, which limits its applications. In this study, inclusion complexes (ICs) were prepared by encapsulating ECIN in β-cyclodextrin (βCD), 2-hydroxypropyl-βCD, or methyl-βCD using an ultrasonication method to enhance water solubility and thermal and antibacterial properties. UV-Vis absorption and fluorescence spectral results indicated strong non-covalent interactions between ECIN and βCD derivatives in aqueous solution, and double reciprocal profiles revealed a guest:host stoichiometry of 1:1. Fourier-transform infrared and proton nuclear magnetic resonance spectroscopy investigations revealed that the phenyl ring of ECIN is located deeply in the CD nanocavities. X-ray diffraction, ultraviolet-visible diffuse reflectance spectroscopy, photoluminescence, and field emission scanning electron microscopy were performed to obtain crystalline, optical, and morphological information on solid ECIN-CDs. Thermogravimetric/differential thermal studies confirmed the improved stability of ECIN in solid CD-ICs by detecting an increase in the degradation temperature of ECIN from 50-140 °C to 310-410 °C. Further, the geometrical and frontier molecular orbital structures of the ECIN-CDs were theoretically evaluated using parametric method-3. Finally, antibacterial assays conducted against the foodborne pathogens Staphylococcus aureus and Escherichia coli and revealed that encapsulated ECIN had a greater inhibitory effect, which suggested the devised nanocarriers promote the solubilization of essential oil components in aqueous solutions.

The significance of AIMP2 for Smurf2-dependent downregulation of FBP and the interaction of Smurf2 and FBP.