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Abstract Although intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) presents with persistent inflammatory stimulation of the blood vessels and an increased risk of coronary artery dilatation. However, the pathogenesis of this disease is unclear, with no established biomarkers to predict its occurrence. This study intends to explore the utility of S100A12/TLR2-related signaling molecules and clinical indicators in the predictive modeling of IVIG-resistant KD. The subjects were classified according to IVIG treatment response: 206 patients in an IVIG-sensitive KD group and 49 in an IVIG-resistant KD group. Real-time PCR was used to measure the expression of S100A12, TLR2, MYD88, and NF-κB in peripheral blood mononuclear cells of patients, while collecting demographic characteristics, clinical manifestations, and laboratory test results of KD children. Multi-factor binary logistic regression analysis identified procalcitonin (PCT) level (≥ 0.845 ng/mL), Na level (≤ 136.55 mmol/L), and the relative expression level of S100A12 (≥ 10.224) as independent risk factors for IVIG-resistant KD and developed a new scoring model with good predictive ability to predict the occurrence of IVIG-resistant KD.

Early life stress alters gut microbiota and increases the risk of neuropsychiatric disorders, including social deficits and anxiety, in the host. However, the role of gut commensal bacteria in early life stress-induced neurobehavioral abnormalities remains unclear. Using the maternally separated (MS) mice, our research has unveiled a novel aspect of this complex relationship. We discovered that the reduced levels of amino acid transporters in the intestine of MS mice led to low glutamine (Gln) levels in the blood and synaptic dysfunction in the medial prefrontal cortex (mPFC). Abnormally low blood Gln levels limit the brain’s availability of Gln, which is required for presynaptic glutamate (Glu) and γ-aminobutyric acid (GABA) replenishment. Furthermore, MS resulted in gut microbiota dysbiosis characterized by a reduction in the relative abundance of Lactobacillus reuteri (L. reuteri). Notably, supplementation with L. reuteri ameliorates neurobehavioral abnormalities in MS mice by increasing intestinal amino acid transport and restoring synaptic transmission in the mPFC. In conclusion, our findings on the role of L. reuteri in regulating intestinal amino acid transport and buffering early life stress-induced behavioral abnormalities provide a novel insight into the microbiota-gut-brain signaling basis for emotional behaviors.

Myocardial ischemia-reperfusion (MI/R) injury is common in patients who undergo revascularization therapy for myocardial infarction, often leading to cardiac dysfunction. Carbon monoxide (CO) has emerged as a therapeutic molecule due to its beneficial properties such as anti-inflammatory, anti-apoptotic, and mitochondrial biogenesis-promoting properties. However, its clinical application is limited due to uncontrolled release, potential toxicity, and poor targeting efficiency. To address these limitations, a peroxynitrite (ONOO−)-triggered CO donor (PCOD585) is utilized to generate a poly (lactic-co-glycolic acid) (PLGA)-based, biomimetic CO nanogenerator (M/PCOD@PLGA) that is coated with the macrophage membrane, which could target to the ischemic area and neutralize proinflammatory cytokines. In the ischemic area, local produced ONOO− triggers the continuous release of CO from M/PCOD@PLGA, which efficiently ameliorates MI/R injury by clearing harmful ONOO−, attenuating the inflammatory response, inhibiting cardiomyocyte apoptosis, and promoting mitochondrial biogenesis. This study provides a novel insight into the safe therapeutic use of CO for MI/R injury by utilizing a novel CO donor combined with biomimetic technology. The M/PCOD@PLGA nanogenerator offers targeted delivery of CO to the ischemic area, minimizing potential toxicity and enhancing therapeutic efficacy.

Abstract A high‐density Raman photometry based on a dual‐recognition strategy is created for accurately quantifying acetylcholinesterase (AchE) activity in 24 brain regions of free‐moving animals with network. A series of 5‐ethynyl‐1,2,3,3‐tetramethyl‐based molecules with different conjugated structures and substitute groups are designed and synthesized for specific recognition of AchE by Raman spectroscopy. After systematically evaluating the recognition ability toward AchE, 2‐(4‐((4‐(dimethylamino)benzoyl)oxy)styryl)‐5‐ethynyl‐1,3,3‐trimethyl‐3H‐indol‐1‐ium (ET‐5) is finally optimized for AchE determination, which shows the highest selectivity, the greatest sensitivity, and the fastest response time among the investigated seven molecules. More interestingly, using the developed probe for AchE with high accuracy and sensitivity, the optimized AchE regulated by nitric oxide (NO) is discovered for promoting the neurogenesis of neural stem cells (NSCs). Benefiting from the high‐density photometry, it is found that the activity and distribution of AchE varied in 24 brain regions, and the levels of AchE activity in 24 brain regions of Alzheimer's mice (AD) are lower than those of normal mice. It is the first time that a functional network of AchE in 24 brain regions is established. It is also found that the loss of AchE functional network in AD mice is restored and reconstructed by the controlled release of AchE regulated by NO.

Plasma flow vorticity is ubiquitous in space and plays a key role in material mixing and energy transfer. The five THEMIS satellites orbiting in different regions of the terrestrial magnetotail provide an unprecedented opportunity to study the temporal–spatial evolution characteristics of a plasma flow vortex on large spatial scales. We present an analysis of the flow vorticity that occurred between 05:50 and 06:30 UT on 2009 March 23 during a quiet time of the terrestrial magnetotail. The uneven distributions of the density and temperature of the vortex observed by the three near-Earth satellites (THA, THD, and THE) indicate that the plasma in the solar wind gradually mixed into the near-Earth magnetotail through a series of nonequilibrium processes. Both the flow vortices and dipolarization observed by the three near-Earth satellites were about 10 minutes earlier than those observed by the two satellites (THB and THC) in the mid-magnetotail. Further analysis of the relationship between vorticity, field-aligned current, and energy transport reveals that the flow vortex interacted with the surrounding plasma during its tailward propagation. The field-aligned current related to the vorticity could only generate a pseudo-breakup of the aurora in the ionosphere. Thus, we speculate that this flow vortex mainly transports mass and energy from the solar wind to the near-magnetotail, propagates tailward to the mid-magnetotail, and heats the encountered plasma by dissipating its bulk flow and dominant thermal energy. These results shed light on the mass mixing, energy transport, and dissipation of the plasma flow vortex during quiet levels of geomagnetic activity on large spatial scales.

Abstract In vivo imaging in the deep near‐infrared (NIR) spectral region, that is, beyond 800 nm, has become popular due to its penetration depth. While imaging of the neutral medium/tissue has been repeatedly showcased, imaging of the high‐acidic medium remains challenging partly because of the high‐lying HOMO orbital and hence a high pKa of the electron‐donating group of the NIR fluorophores. We devised a novel electron‐donating group (D6) with which we further synthesized ECJ. ECJ exhibits an absorption wavelength beyond 900 nm and is fluorescent. Its pKa was found to be lower than zero, rendering it suitable for bioimaging of a highly‐acidic medium. Its potential for practical applications was showcased in proof‐of‐concept in vivo imaging with a mouse model.

Plastic mulch film is often believed to be a significant contributor to microplastic pollution in farmland soil, however, its direct impact in areas with high human activities remains unclear due to the presence of multiple pollution sources. This study aims to address this knowledge gap by investigating the impact of plastic film mulching on microplastic pollution in farmland soils in Guangdong province, China's largest economic province. The macroplastic residues in soils were investigated in 64 agricultural sites, and the microplastics were analyzed in typical plastic film mulched and nearby non-mulched farmland soils. The average concentration of macroplastic residues was 35.7 kg/ha and displayed a positive correlation with mulch film usage intensity. Contrarily, no significant correlation was found between macroplastic residues and microplastics, which exhibited an average abundance of 22,675 particles/kg soil. The pollution load index (PLI) model indicated that the microplastic pollution level was category I and comparatively higher in mulched farmland soils. Interestingly, polyethylene accounted for only 2.7% of the microplastics, while polyurethane was found to be the most abundant microplastic. According to the polymer hazard index (PHI) model, polyethylene posed a lower environmental risk than polyurethane in both mulched and non-mulched soils. These findings suggest that multiple sources other than plastic film mulching primarily contribute to microplastic pollution in farmland soils. This study enhances our understanding of microplastic sources and accumulation in farmland soils, offering crucial information on potential risks to the agroecosystem.

Coronary artery lesions (CALs) are the most common and serious complication of Kawasaki disease (KD), and the pathogenesis is unknown. Exploring KD-specific biomarkers and related risk factors is significant for clinical diagnosis and treatment. This study aimed to explore the feasibility of combining clinical indicators with S100A12/TLR2-associated signaling molecules for the predictive modeling of CALs in KD. A total of 346 patients (224 males and 122 females) with KD who visited the rheumatology department of Wuhan Children's Hospital between April 2022 and March 2025 were enrolled and divided into two groups according to the presence or absence of CALS (292 patients had CALs and 54 patients did not). Forty-one variables were collected from the two groups, including demographic characteristics, clinical manifestations, and laboratory data. Single nucleated cells from each patient were extracted, and the expression of the S100A12/TLR2 signal transduction-related molecules S100A12, TLR2, MYD88, and NF-κB were detected by real-time fluorescent quantitative polymerase chain reaction. Statistically significant variables were subjected to logistic regression analysis to determine the independent risk factors for KD with CALs, and a new risk score model was established to assess the predictive efficacy based on receiver operating characteristic curves. Sixteen variables significantly differed between the no-CALs and CALs groups: gender, fever duration, white blood cells (WBC), hemoglobin (HGB), Ce reactive protein (CRP), procalcitonin, serum ferritin (SF), erythrocyte sedimentation rate (ESR), fibrinogen (FIB), aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT), serum albumin (ALB), sodium (Na), Interleukin (IL-10), tumor necrosis factor (TNF-α), S100 calcium binding protein A12 (S100A12), and Myeloid Differentiation Factor 88 (MYD88) (p < 0.05). After performing a univariate analysis, 12 variables (gender, fever duration, WBC, HGB, CRP, SF, ESR, FIB, AST/ALT, ALB, Na, and S100A12) were included in the multifactorial binary logistic regression, which showed that fever duration ≥ 6.5 days, ESR ≥ 46.5 mm/h, AST/ALT ≤ 1.51, and S100A12 ≥ 10.02 were independent risk factors for KD with CALs and were assigned scores of 3, 2, 1, and 2, respectively, according to the odds ratio (OR). The total score of each patient was counted, and a new prediction model for KD combined with CALs was established, where < 3.5 was considered low risk and ≥ 3.5 was regarded as high risk; the sensitivity, specificity, Jorden index, and area under the curve of this scoring system were 0.667, 0.836, 0.502, and 0.838, respectively. This new scoring model has good efficacy for predicting the occurrence of KD with CALs. The expression of S100A12 was significantly increased in the CALs group and was an independent risk factor for the occurrence of CALs, and has the potential as a biomarker for predicting KD with CALs.

Obesity, a growing health problem in the world, is related to a series of mental disorders, including anxiety and depression. XiaoYao San (XYS), a prescription of traditional Chinese medicine (TCM), has been widely used in the clinical treatment of anxiety and depression in China. However, the efficacy of XYS on obesity-related neuropsychiatric dysfunction and the underlying neural mechanisms remain unclear. Here, using a high-fat diet (HFD)-induced obese model, we found that XYS treatment significantly improves obesity-related anxiety- and depression-like behaviors and alters the gut microbiome, particularly by increasing the relative abundance of Faecalibaculum rodentium (F. rodentium), in mice. Interestingly, selective supplementation with F. rodentium or its metabolic products, short-chain fatty acids (SCFAs), is sufficient to rescue anxiety- and depression-like behaviors in HFD-fed mice. Next, we determined that the transcriptional level of dopamine D2 receptor (DRD2), which activation usually inhibits inflammation in the central nervous system (CNS), is significantly increased in the medial prefrontal cortex (mPFC) of XYS-treated mice when compared with that of vehicle-treated controls. Moreover, enriched pathways analysis with the differential expression genes (DEGs) showed that some of these DEGs are enriched in neuroinflammatory pathways. We further noticed that treatment with XYS contributes to controlling microglial activation and proinflammatory responses in the mPFC and hippocampus of HFD-fed mice. Overall, this study reveals that XYS rescues HFD-induced anxiety and depression via modulating gut microbiota-derived metabolites and that XYS is a potential therapeutic strategy for treating obesity-associated mental disorders.

Maslinic acid (MA) is a pentacyclic triterpene acid, which exists in many plants, including olive, and is highly safe for human beings. In recent years, it has been reported that MA has anti-inflammatory, antioxidant, anti-tumor, hypoglycemic, neuroprotective and other biological activities. More and more experimental data has shown that MA has a good therapeutic effect on multiple organ diseases, indicating that it has great clinical application potential. In this paper, the extraction, purification, identification and analysis, biological activity, pharmacokinetics in vivo and molecular mechanism of MA in treating various organ diseases are reviewed. It is hoped to provide a new idea for MA to treat various organ diseases.

Determination of pH values has a vital influence in many chemical and biological processes. To accurately determine pH values, we fabricated a highly photostable ratiometric fluorescent pH−sensitive nanosensor by staining the core of mesoporous silica nanoparticle with a rhodol dye and chemically labelling its outer shell with a rhodamine derivative dye. The two dyes possess opposite pH−responding directions, which increases the band of the signal change. There is a nine−fold change in fluorescence intensity ratios when the solution pH changes from 3.0 and 9.0. Meanwhile, the nanosensors displayed yellowish emission in low pH value, orange emission in mid pH value, and reddish emission in high pH value, which can be readily inspected by bare eyes. Last but not least, excellent photostability and reversibility features make the nanosensors useful for the continuous measuring of pH with high accuracy.

Preparation of xanthene-containing compounds has been limited due to structural bias existing methods pose. Here, the authors developed a mild, diversity-oriented method for rhodamines synthesis, leading to the finding of compounds with antibacterial potency against a variety of bacterial species.

Viscosity of body fluid is an established biomarker of pathological conditions. Abnormality of cellular viscosity occurs when cells are challenged with external stresses. Small molecule probes to assess the viscosity are sought after for both disease diagnostics and basic studies. Fluorescence based probes are particular attractive due to their potentials for convenient and high spatiotemporal resolution microscopic monitoring of biological samples. The dyes with a floppy push-pull backbone or dyes with a rotatable substituent exhibits a viscosity responsive fluorescence enhancement and therefore viable viscosity probes. The scaffold of the existing viscosity probes contains typically one such floppy site. Therefore, they typically linearly respond to log(viscosity). We argue that minor viscosity fluctuation could potentially be physiological as the biological system is dynamic. We wish to develop a type of conceptually-new, threshold-limited viscosity probes, to complement the existing probes. Such probes do not exhibit a fluorescence enhancement when challenged with minor and presumably physiological enhancement of viscosity. When the viscosity is higher than a certain threshold, their fluorescence turns on. We hypothesize that a dye with two far-apart floppy sites could potentially yield such a threshold-limited signal and designed VPZ2 and VPZ3. Through spectral titration, VPZ3 was found to yield the desired threshold-limited signal. VPZ3 was suitable for in vitro bioimaging of viscosity under one-photon or two-photon excitation. VPZ3 is potentially useful in many downstream applications. Future work includes fine-tune of the threshold to allow tailored limit for fluorescence turn-on to better meet the need of different applications. Besides the implications in the real-world applications, the design concept could also be translated to design of alternative substrates.

The synthesis of new type [a] and [b] benzoxanthene dye frameworks is described. It is shown that a type [a]benzofluorone, seminaphtho[a]fluorone (SNAFR-1), displays unique properties, including white light emission as well as excitation over a 400 nm range and the compound can also be used in cellular imaging studies.

Aspirin is a commonly used anti-inflammatory, analgesic and antithrombotic drug. It has attracted attention due to its potential antifungal therapeutic effect; however, the molecular mechanism is poorly understood. Here, the effects of aspirin on the cell wall of Saccharomyces cerevisiae were explored. We observed by scanning electron microscopy that aspirin could damage the cell wall ultrastructure. Meanwhile, a cellular surface hydrophobicity (CSH) assay showed that aspirin increased the hydrophobicity of the yeast cell surface. A drug sensitivity assay indicated that the overexpression of dolichol phosphate mannose synthase 1 (DPM1) reversed the cell wall damage and decreased the CSH induced by aspirin. Importantly, aspirin decreased the expression and enzyme activity of DPM1 in S. cerevisiae. Molecular docking results demonstrated that aspirin could directly bind to the Ser141 site of DPM1. Similarly, we found that aspirin damaged the cell wall and inhibited the expression of DPM1 in Candida albicans. These findings improve the current understanding of the action mode of aspirin and provide new strategies for antifungal drug design. [ABSTRACT FROM AUTHOR]

A novel sensing mechanism for nitric oxide (NO) detection with a particular easily synthesized embodiment ([NO.sub.550]), which exhibits a rapid and linear response to NO with a red-shifted 1500-fold turn-on signal from a dark background, is presented. The high specificity, dark background, facile synthesis, and low pH dependence make [NO.sub.550] a superior probe for NO detection when used as an imaging agent.

A facile synthetic route utilizing readily available reagents is used in a study to develop a series of regiosomerically pure xanthene dye derivatives. Advantages of the method include relatively mild conditions and good to excellent yields.

A turn-on signal from zero background allows sensitive detection of a weak signal and is highly desired. The "covalent-assembly" probe design principle is powerful in this regard. Herein, we report an embodiment of this principle (NA570) for detection of Sarin related threats, based on a phenylogous Vilsmeier-Haack reaction. NA570 bears a concise molecular construct, exhibits a colorimetric and a fluorimetric signal, and has potential for real applications. [ABSTRACT FROM AUTHOR]

A readily accessible new class of near infrared (NIR) molecular probes has been synthesized and evaluated. Specific fluorophores in this unique xanthene based regiolsomeric seminaphthofluorone dye series exhibit a combination of desirable characteristics including (i) low molecular weight (339 amu), (ii) aqueous solubility, and (iii) dual excitation and emission from their fluorescent neutral and anionic forms. Importantly, systematic changes in the regiochemistry of benzannulation and the ionizable moieties afford (iv) tunable deep-red to NIR emission from anionic species and (v) enhanced Stokes shifts. Anionic SNAFR-6, exhibiting an unusually large Stokes shift of ≈200 nm (5,014 cm-1) in aqueous buffer, embodies an unprecedented fluorophore that emits NIR fluorescence when excited in the blue/green wavelength region. The successful use of SNAFR-6 in cellular imaging studies demonstrates proof-of-concept that this class of dyes possesses photophysical characteristics that allow their use in practical applications. Notably. each of the new fluorophores described is a minimal template structure for evaluation of their basic spectral properties, which may be further functionalized and optimized yielding concomitant improvements in their photophysical properties. [ABSTRACT FROM AUTHOR]