A superstable sandwich-type composite of a single-benzene-based fluorophore and chitosan as a fluorescent authentication barcode.

Management of diseases through medication accounts for the largest portion of treatment, with people worldwide relying on a variety of medicines to treat and prevent minor to severe diseases in modern society. However, the recent increased use of counterfeit medicines rather than certified medication has emerged as a serious social concern. This study introduces a new hybrid material, named SBBF-chitosan (SC), which integrates a single-benzene-based fluorophore (SBBF) and chitosan, serving as a fluorescence-based authentication barcode for certified medication. The synthesis and characterization of SC, along with an analysis of its photophysical properties, were systematically conducted. SC demonstrated bright emission with high stability under various environmental conditions. In vitro analyses and in vivo animal experiment results further indicated the safety of SC for oral intake, even when directly incorporated into medicines. We are confident that this newly developed formulation SC provides a fundamental solution to address the challenges posed by counterfeit medicines, thereby safeguarding medication authenticity.

Cysteine as an Innovative Biomarker for Kidney Injury.

BACKGROUND: Kidney transplantation is a widely used treatment for end-stage kidney disease. Nevertheless, the incidence of acute kidney injury (AKI) in deceased donors poses a potential hazard because it significantly increases the risk of delayed graft function and potentially exerts an influence on the kidney allograft outcome. It is crucial to develop a diagnostic model capable of assessing the existence and severity of AKI in renal grafts. However, no suitable kidney injury markers have been developed thus far. METHODS: We evaluated the efficacy of the molecular probe NPO-B, which selectively responds to cysteine, as a new diagnostic tool for kidney injury. We used an in vitro model using ischemia/reperfusion injury human kidney-2 cells and an in vivo ischemia/reperfusion injury mouse model. Additionally, cysteine was investigated using urine samples from deceased donors and living donors to assess the applicability of detection techniques to humans. RESULTS: This study confirmed that the NPO-B probe effectively identified and visualized the severity of kidney injury by detecting cysteine in both in vitro and in vivo models. We observed that the fluorescence intensity of urine samples measured using NPO-B from the deceased donors who are at a high risk of renal injury was significantly stronger than that of the living donors. CONCLUSIONS: If implemented in clinical practice, this new diagnostic tool using NPO-B can potentially enhance the success rate of kidney transplantation by accurately determining the extent of AKI in renal grafts.

Multiple-Junction-Based Traffic-Aware Routing Protocol Using ACO Algorithm in Urban Vehicular Networks.

The burgeoning interest in intelligent transportation systems (ITS) and the widespread adoption of in-vehicle amenities like infotainment have spurred a heightened fascination with vehicular ad-hoc networks (VANETs). Multi-hop routing protocols are pivotal in actualizing these in-vehicle services, such as infotainment, wirelessly. This study presents a novel protocol called multiple junction-based traffic-aware routing (MJTAR) for VANET vehicles operating in urban environments. MJTAR represents an advancement over the improved greedy traffic-aware routing (GyTAR) protocol. MJTAR introduces a distributed mechanism capable of recognizing vehicle traffic and computing curve metric distances based on two-hop junctions. Additionally, it employs a technique to dynamically select the most optimal multiple junctions between source and destination using the ant colony optimization (ACO) algorithm. We implemented the proposed protocol using the network simulator 3 (NS-3) and simulation of urban mobility (SUMO) simulators and conducted performance evaluations by comparing it with GSR and GyTAR. Our evaluation demonstrates that the proposed protocol surpasses GSR and GyTAR by over 20% in terms of packet delivery ratio, with the end-to-end delay reduced to less than 1.3 s on average.

Effects of sub-inhibitory concentrations of nafcillin, vancomycin, ciprofloxacin, and rifampin on biofilm formation of clinical methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are often difficult to treat because of their biofilm-forming ability and antimicrobial resistance. We investigated the effects of sub-minimal inhibitory concentrations (MICs) of antibiotics on MRSA biofilm formation. Clinical MRSA isolates were grown with sub-MICs (1/256-1/2 × MICs) of nafcillin, vancomycin, ciprofloxacin, and rifampin. The biofilm biomass was measured using crystal violet staining. Of the 107 MRSA isolates tested, 63 (58.9%) belonged to sequence type 5 (ST5), and 44 (41.1%) belonged to ST72. The MIC50/MIC90 values of nafcillin, vancomycin, ciprofloxacin, and rifampin were 256/512, 1/2, 64/512, and 0.008/0.03 mg/L, respectively. The sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin promoted biofilm formation in 75 (70.1%), 49 (45.8%), 89 (83.2%), and 89 (83.2%) isolates, respectively. At sub-MICs of nafcillin, the factors associated with strong biofilm induction were the ST5 strain (P = 0.001) and agr dysfunction (P = 0.005). For the sub-MICs of ciprofloxacin, the associated factors were the ST5 strain (P = 0.002), staphylococcal protein A type t002 strain (P < 0.001), and ciprofloxacin resistance (P < 0.001). Among the sub-MICs of rifampin, only ST5 was associated with strong biofilm induction (P = 0.006). Because the sub-MICs of rifampin were much lower than clinically relevant concentrations, we further tested the capability of biofilm induction in 0.03[Formula: see text]32 mg/L of rifampin. At these concentrations, rifampin-induced biofilm formation was rare in rifampin-susceptible MRSA [1.0% (1 of 100)] but common in rifampin-resistant MRSA [71.4% (5 of 7), P < 0.001]. Induction of biofilm biomass at sub-MICs of antibiotics is common in clinical MRSA isolates and is differentially affected by the MRSA strain and antibiotic class. IMPORTANCE: Bacteria can be exposed to sub-MICs of antibiotics at the beginning and end of a dosing regimen, between doses, or during low-dose therapies. Growing evidence suggests that sub-MICs of antimicrobials can stimulate MRSA biofilm formation and alter the composition of the biofilm matrix. Pevious studies have found that sub-MICs of oxacillin, methicillin, and amoxicillin promote biofilm formation in some community-acquired MRSA (CA-MRSA). We evaluated biofilm induction by sub-MICs of four different classes of antibiotics in 44 CA-MRSA and 63 healthcare-associated MRSA (HA-MRSA) strains. Our study indicated that sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin frequently promote biofilm induction in clinical MRSA isolates. Strong biofilm induction in sub-MICs of nafcillin, ciprofloxacin, and rifampin was more frequent in HA-MRSA than in CA-MRSA. Antibiotic-induced biofilm formation depends on the antibiotic class, MRSA strain, and antibiotic resistance. Our results emphasize the importance of maintaining effective bactericidal concentrations of antibiotics to treat biofilm-related infections.

Systemic Treatment with Fas-Blocking Peptide Attenuates Apoptosis in Brain Ischemia.

Apoptosis plays a crucial role in neuronal injury, with substantial evidence implicating Fas-mediated cell death as a key factor in ischemic strokes. To address this, inhibition of Fas-signaling has emerged as a promising strategy in preventing neuronal cell death and alleviating brain ischemia. However, the challenge of overcoming the blood-brain barrier (BBB) hampers the effective delivery of therapeutic drugs to the central nervous system (CNS). In this study, we employed a 30 amino acid-long leptin peptide to facilitate BBB penetration. By conjugating the leptin peptide with a Fas-blocking peptide (FBP) using polyethylene glycol (PEG), we achieved specific accumulation in the Fas-expressing infarction region of the brain following systemic administration. Notably, administration in leptin receptor-deficient db/db mice demonstrated that leptin facilitated the delivery of FBP peptide. We found that the systemic administration of leptin-PEG-FBP effectively inhibited Fas-mediated apoptosis in the ischemic region, resulting in a significant reduction of neuronal cell death, decreased infarct volumes, and accelerated recovery. Importantly, neither leptin nor PEG-FBP influenced apoptotic signaling in brain ischemia. Here, we demonstrate that the systemic delivery of leptin-PEG-FBP presents a promising and viable strategy for treating cerebral ischemic stroke. Our approach not only highlights the therapeutic potential but also emphasizes the importance of overcoming BBB challenges to advance treatments for neurological disorders.

Next-Generation Femtech: Urine-Based Cervical Cancer Diagnosis Using a Fluorescent Biothiol Probe with Controlled Smiles Rearrangement.

Cervical cancer screening is a crucial field of femtech (female technology). In this work, we disclosed a new femtech solution─a simple, straightforward, and on-site applicable urine-based cervical cancer diagnostic method using a fluorescent biothiol probe. Our newly developed nitrobenzene-based fluorescent probe, named NPS-B, effectively differentiates between cysteine and homocysteine within urine samples via controlled Smiles rearrangement. The analysis of emission-based signals offers the potential utility of this method in cervical cancer. NPS-B was designed by considering the substitution effect and structural polarity of the nitrobenzene-based fluorophore. This controlled modification of nitrobenzene-induced substantial intramolecular charge transfer changes in the fluorophore when exposed to biothiols, resulting in significant changes in photophysical properties. NPS-B displayed different emissions of cysteine and homocysteine in clinical human urine (without prior urine treatment). Overall, our findings provide insights not only into fundamental chemical science but also into the broader domain of applied sciences.