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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 326: 125215, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39342721

ABSTRACT

Traditional Chinese medicine (TCM) prescription, with its intricate formulations and nuanced compositions, is a cornerstone of holistic health practices. However, the expansion of the TCM market has led to a surge in herb adulteration, which significantly undermines the quality and safety of these medicinal products. A case in point is Lonicerae Japonicae Flos (LJF), a widely utilized herb for treating colds, which has been adulterated by the cheaper Lonicerae Flos (LF), thereby affecting its therapeutic effectiveness. Therefore, a method utilizing handheld NIR spectroscopy combined with chemometrics has been developed to provide a portable, real-time solution for the rapid and accurate detection and quantification of adulterants in TCM. By collecting NIR spectra from LJF, LF and adulterated samples (AS), we've established a spectral database enabling deep insights into the correlation between spectral features and sample compositions. Resultantly, a classification model with a 99.58 % cross-validation accuracy, reaching 100 % for test set, effectively identified adulterants. And further spectral similarity analysis and classification identification of samples with different adulteration ratios were carried out. The cross-validation accuracy under the optimal model reached 98.38 %, and the test set accuracy was 99.20 %. In addition, the study extends to quantifying different levels of adulteration, employing 20 standard adulterated samples across a 0-100 % adulteration gradient. Via data preprocessing, feature extraction, and regression techniques, the full concentration prediction models were developed, later refined by segmenting samples based on high and low adulteration ratios. Under the SGFD_CARS_PLS (Savitzky-Golay smoothing with the first derivative_competitive adaptive reweighted sampling_partial least squares) model, exceptional performance was achieved, with a R2p of 0.983, RMSEp of 3.402, and RPDp of 7.757 for the homemade adulterated prediction set. In conclusion, the application of this technology not only improves the efficiency and accuracy of screening, but also has the advantages of low cost, easy operation and rapid results compared with traditional chemical analysis methods. It effectively protects the safety of drugs for consumers, maintains the integrity of the TCM market, and provides a strong technical support for the on-site rapid detection of TCM.

2.
Environ Int ; 191: 108987, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39217723

ABSTRACT

Triclocarban (TCC) is an antimicrobial ingredient that commonly incorporated in many household and personal care products, raising public concerns about its potential health risks. Previous research has showed that TCC could cross the blood-brain barrier, but to date our understanding of its potential neurotoxicity at human-relevant concentrations remains lacking. In this study, we observed anxiety-like behaviors in mice with continuous percutaneous exposure to TCC. Subsequently, we combined lipidomic, proteomic, and metabolic landscapes to investigate the underlying mechanisms of TCC-related neurotoxicity. The results showed that TCC exposure dysregulated the proteins involved in endocytosis and neurodegenerative disorders in mouse cerebrum. Brain energy homeostasis was also altered, as evidenced by the perturbation of pyruvate metabolism, TCA cycle, and oxidative phosphorylation, which in turn caused mitochondrial dysfunction. Meanwhile, the changing trends of sphingolipid signaling pathway and overproduction of mitochondrial reactive oxygen species (mROS) could enhance the neural apoptosis. The in vitro approach further demonstrated that TCC exposure promoted apoptosis, accompanied by the overproduction of mROS and alteration in the mitochondrial membrane potential in N2A cells. Together, dysregulated endocytosis, mROS-related mitochondrial dysfunction and neural cell apoptosis are considered to be crucial factors for TCC-induced neurotoxicity, which may contribute to the occurrence and development of neurodegenerative disorders. Our findings provide novel perspectives for the mechanisms of TCC-triggered neurotoxicity.


Subject(s)
Brain , Carbanilides , Animals , Mice , Carbanilides/toxicity , Brain/drug effects , Brain/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Reactive Oxygen Species/metabolism , Proteomics , Apoptosis/drug effects , Neurotoxicity Syndromes/etiology , Male , Multiomics
3.
Sci Total Environ ; 953: 176186, 2024 Nov 25.
Article in English | MEDLINE | ID: mdl-39265685

ABSTRACT

Shale gas has been extensively extracted in the Sichuan Basin in China in recent years. To gain insight into the potential impact of shale gas wastewater (SGW) discharge, sediment in a small river receiving treated SGW, as well as cultivated soil and paddy soil irrigated by the river water were collected. The occurrence and distribution of polycyclic aromatic compounds (PACs), including polycyclic aromatic hydrocarbons (PAHs) and their alkylated/oxygenated derivatives (APAHs/OPAHs), and thiophenes were investigated, the resultant potential ecological risks were assessed subsequently. The total concentration of PACs varied in the range of 1299.9-9286.4, 2069.4-11,512.3, and 475.7-2927.9 ng/g in sediment, cultivated soil and paddy soil, respectively, with thiophenes followed by APAHs being the abundant components in all the studied samples, demonstrating the potential impact of SGW discharge on sediment and surrounding soil environment. Based on the measured concentrations, potential ecological risks posed by PAHs and APAHs were calculated, and moderate to high ecological risks were observed in partial sampling sites, which mainly caused by 3-4 rings PAHs and APAHs.

4.
ACS Appl Mater Interfaces ; 16(38): 50630-50639, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39264306

ABSTRACT

Triboelectric nanogenerators (TENGs) have attracted widespread attention as a promising candidate for energy harvesting due to their flexibility and high power density. To meet diverse application scenarios, a highly stretchable (349%), conductive (1.87 S m-1), and antibacterial electrode composed of carbon quantum dots/LiCl/agar-polyacrylamide (CQDs/LiCl/agar-PAAm) dual-network (DN) hydrogel is developed for wearable TENGs. Notably, the concentration of agar alters the pore spacing and pore size of the DN hydrogel, thereby impacting the network cross-linking density and the migration of conductive ions (Li+ and Cl-). This variation further affects the mechanical strength and conductivity of the hydrogel electrode, thus modulating the mechanical stability and electrical output performance of the TENGs. With the optimal agar content, the tensile strength and conductivity of the hydrogel electrode increase by 211 and 719%, respectively. This enhancement ensures the stable output of TENGs during continuous operation (6000 cycles), with open-circuit voltage, short-circuit current, and transferred charge increasing by 200, 530, and 155%, respectively. Additionally, doping with CQDs enables the hydrogel electrode to effectively inhibit the Gram-negative bacterium Escherichia coli. Finally, the TENGs are utilized as a self-power smart ring for efficient and concise information transmission via Morse code. Consequently, this study introduces a creative approach for designing and implementing multifunctional, flexible wearable devices.


Subject(s)
Anti-Bacterial Agents , Electrodes , Escherichia coli , Hydrogels , Wearable Electronic Devices , Escherichia coli/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Quantum Dots/chemistry , Acrylic Resins/chemistry , Electric Conductivity , Electric Power Supplies , Agar/chemistry , Carbon/chemistry , Humans
5.
Plant Dis ; 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39207341

ABSTRACT

Canna indica L., a well-known wetland plant (Lei et al. 2023), was found with leaf spots in a planting area (∼667 m2) in Tiandong, Guangxi, China, in June 2022. 5500 plants were affected by this disease. Symptoms began as yellow lesions, and then developed brown sub-ellipsoid spots with yellow borders, then gradually expanded and encompassed the entire leaves until leaves wilted. 18 diseased leaves were collected and cut into small pieces (3 ×3 mm) from the brown margins. The pieces were moistened with 75% ethanol for 10 seconds, disinfected with 2% NaClO for two minutes and rinsed with sterile water three times. Pieces were placed on potato dextrose agar (PDA) and incubated at 28°C for four days. 15 isolates with similar morphological characterizations were isolated and purified (about 68% isolation frequency) from 18 diseased leaves. Three isolates (CI1-1, CI1-2 and CI1-3) were selected for further morphological and molecular identification. Fungi mycelia on PDA were grayish white initially, and became dark gray after seven days. Conidia were hyaline, guttulate, unicellular, cylindrical, and averaged 15.09 × 5.72 µm. To confirm the identification, genomic DNA was extracted from mycelium of the three isolates, and the partial internal transcribed spacer (ITS) regions, intergenic region of apn2 and MAT1-2-1 (ApMAT), fragments of actin (ACT), glyceraldehydes-3-phosphate dehydrogenase (GAPDH), chitin synthase (CHS-1), and ß-tubulin (TUB2) genes were amplified, sequenced and submitted to GenBank (ITS: OR501461 to OR501463; ApMat: OR684455-OR684457; ACT: OR765956-OR765958; GAPDH: OR779527-OR779529; CHS-1: OR797622-OR797624; TUB2: OR820537-OR820539). The sequences of the three isolates were 99%-100% identical (ApMat, 882/882 bp; ACT, 228/230 bp; GAPDH, 278/280 bp; CHS-1, 298/299 bp and TUB2, 298/299 bp) with those of Colletotrichum fructicola isolate ICMP18581 (JQ807838, FJ907426, JX010033, JX009866 and JX010405) (Liu et al. 2015). Compared with C. fructicola isolate ICMP18581 (JX010165), the ITS sequence identities were 94% (556/594 bp). A Maximum Likelihood phylogenetic tree was constructed by using MEGA v. 10.1.5 based on the concatenation of multiple sequences. Based on these results, the three isolates were identified as C. fructicola. Pathogenicity tests of three isolates were conducted on nine one-year-old seedlings. Three leaves per plant (six sites per leaf) were inoculated with the adjusted conidial suspension of each isolate. Ten µl suspension (106 conidia/ml) was dripped on each inoculation site without wounding. Three additional plants were inoculated with sterile water as negative controls. All plants were covered with plastic bags sprayed with sterile water, and cultured in a light incubator at 28°C, with 14:10 h light/dark cycle. After five days, dark-brown spots (0.1-1.4cm×0.2-1.6cm) appeared on the leaves of experimental groups, while no lesions were found in the controls. The pathogen was reisolated from the symptomatic leaves and confirmed as C. fructicola based on molecular and morphological methods, fulfilling Koch's hypothesis. C. fructicola has been reported in various ornamental plants (Silva-Cabral et al. 2019, Guarnaccia et al. 2021, Sun et al. 2020). This is the first report of C. fructicola causing anthracnose on C. indica in China, according to literature analysis. The findings will help growers to prevent and control this pathogen, and improve the landscape effect.

6.
Microorganisms ; 12(8)2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39203378

ABSTRACT

Probiotics provide health benefits and are used as feed supplements as an alternative prophylactic strategy to antibiotics. However, the effects of Bacillus-based probiotics containing more than two strains when supplemented to pigs are rarely elucidated. SOLVENS (SLV) is a triple-strain Bacillus-based probiotic. In this study, we investigate the effects of SLV on performance, immunity, intestinal morphology, and microbial community in piglets. A total of 480 weaned pigs [initial body weight (BW) of 8.13 ± 0.08 kg and 28 days of age] were assigned to three treatments in a randomized complete block design: P0: basal diet (CON); P200: CON + 200 mg SLV per kg feed (6.5 × 108 CFU/kg feed); and P400: CON + 400 mg SLV per kg feed (1.3 × 109 CFU/kg feed). Each treatment had 20 replicated pens with eight pigs (four male/four female) per pen. During the 31 d feeding period (Phase 1 = wean to d 14, Phase 2 = d 15 to 31 after weaning), all pigs were housed in a temperature-controlled nursery room (23 to 25 °C). Feed and water were available ad libitum. The results showed that the pigs in the P400 group increased (p < 0.05) average daily gain (ADG) in phase 2 and tended (p = 0.10) to increase ADG overall. The pigs in the P200 and P400 groups tended (p = 0.10) to show improved feed conversion ratios overall in comparison with control pigs. The pigs in the P200 and P400 groups increased (p < 0.05) serum immunoglobulin A, immunoglobulin G, and haptoglobin on d 14, and serum C-reactive protein on d 31. The pigs in the P200 group showed an increased (p < 0.01) villus height at the jejunum, decreased (p < 0.05) crypt depth at the ileum compared with other treatments, and tended (p = 0.09) to have an increased villus-crypt ratio at the jejunum compared with control pigs. The pigs in the P200 and P400 groups showed increased (p < 0.05) goblet cells in the small intestine. Moreover, the pigs in the P400 group showed down-regulated (p < 0.05) interleukin-4 and tumor necrosis factor-α gene expressions, whereas the pigs in the P400 group showed up-regulated occludin gene expression in the ileum. These findings suggest that SLV alleviates immunological reactions, improves intestinal microbiota balance, and reduces weaning stress in piglets. Therefore, SOLVENS has the potential to improve health and performance for piglets.

7.
iScience ; 27(8): 110421, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39108719

ABSTRACT

The Streptomyces antibiotic regulatory proteins (SARPs) are ubiquitously distributed transcription activators in Streptomyces and control antibiotics biosynthesis and morphological differentiation. However, the molecular mechanism behind SARP-dependent transcription initiation remains elusive. We here solve the cryo-EM structure of an AfsR-loading RNA polymerase (RNAP)-promoter intermediate complex (AfsR-RPi) including the Streptomyces coelicolor RNAP, a large SARP member AfsR, and its target promoter DNA that retains the upstream portion straight. The structure reveals that one dimeric N-terminal AfsR-SARP domain (AfsR-SARP) specifically engages with the same face of the AfsR-binding sites by the conserved DNA-binding domains (DBDs), replacing σHrdBR4 to bind the suboptimal -35 element, and shortens the spacer between the -10 and -35 elements. Notably, the AfsR-SARPs also recruit RNAP through extensively interacting with its conserved domains (ß flap, σHrdBR4, and αCTD). Thus, these macromolecular snapshots support a general model and provide valuable clues for SARP-dependent transcription activation in Streptomyces.

8.
Arch Toxicol ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39120795

ABSTRACT

Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0 mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in Sprague‒Dawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial-mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions.

9.
Environ Sci Technol ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39133145

ABSTRACT

In the pursuit of carbon neutrality, China's 2060 targets have been largely anchored in reducing greenhouse gas emissions, with less emphasis on the consequential benefits for air quality and public health. This study pivots to this critical nexus, exploring how China's carbon neutrality aligns with the World Health Organization's air quality guidelines (WHO AQG) regarding fine particulate matter (PM2.5) exposure. Coupling a technology-rich integrated assessment model, an emission-concentration response surface model, and exposure and health assessment, we find that decarbonization reduces sulfur dioxide (SO2), nitrogen oxides (NOx), and PM2.5 emissions by more than 90%; reduces nonmethane volatile organic compounds (NMVOCs) by more than 50%; and simultaneously reduces the disparities across regions. Critically, our analysis reveals that further targeted reductions in air pollutants, notably NH3 and non-energy-related NMVOCs, could bring most Chinese cities into attainment of WHO AQG for PM2.5 5 to 10 years earlier than the pathway focused solely on carbon neutrality. Thus, the integration of air pollution control measures into carbon neutrality strategies will present a significant opportunity for China to attain health and environmental equality.

10.
Nano Lett ; 24(32): 9882-9888, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39093596

ABSTRACT

Optical spectroscopy techniques are central for the characterization of two-dimensional (2D) quantum materials. However, the reduced volume of atomically thin samples often results in a cross section that is far too low for conventional optical methods to produce measurable signals. In this work, we developed a scheme based on the stencil lithography technique to fabricate transferable optical enhancement nanostructures for Raman and photoluminescence spectroscopy. Equipped with this new nanofabrication technique, we designed and fabricated plasmonic nanostructures to tailor the interaction of few-layer materials with light. We demonstrate orders-of-magnitude increase in the Raman intensity of ultrathin flakes of 2D semiconductors and magnets as well as selective Purcell enhancement of quenched excitons in WSe2/MoS2 heterostructures. We provide evidence that the method is particularly effective for air-sensitive materials, as the transfer can be performed in situ. The fabrication technique can be generalized to enable a high degree of flexibility for functional photonic devices.

11.
Int Immunopharmacol ; 140: 112823, 2024 Oct 25.
Article in English | MEDLINE | ID: mdl-39083929

ABSTRACT

Arsenic, a poisonous metalloid element, is linked to liver diseases, but the exactmechanisms for this process are not yet to be completely elucidated. Toll like receptor 4 (TLR4), acting as a pathogenic pattern recognition receptor, plays a pivotal role in various inflammatory diseases via the myeloid differentiation factor 88 (MyD88) pathway. This study aims to investigate the involvement of the TLR4-MyD88 signaling pathway in liver injury induced by prolonged exposure to sodium arsenite (NaAsO2) in Sprague-Dawley rats. Our research findings demonstratethe activation of TLR4-MyD88 signaling pathway in long-term NaAsO2-exposed rat liver tissues, leading to a significant release of inflammatory factors, which suggests its potential involvement in the pathogenesis of NaAsO2-induced liver injury. We further administered lipopolysaccharide (LPS), a natural ligand of TLR4, and TAK-242, a specific inhibitor of TLR4, to rats in order to validate the specific involvement of the TLR4-MyD88 signaling pathway in NaAsO2-induced liver injury. The results showed that, 1 mg/kg.bw LPS treatment significantly activated TLR4-MyD88 signalling pathway and its mediated pro-inflammatory factors, leading to up-regulation of activation indicators in hepatic stellate cells (HSCs) as well as increased secretion levels of extracellular matrix (ECM) in the liver, and ultimately induced liver fibrosis and dysfunction in rats. Relevantly, subsequent administration of 0.5 mg/kg.bw TAK-242 significantly attenuated the expression levels of TLR4 and its associated proteins, mitigated collagen deposition, and partially improved liver fibrosis and dysfunction caused by NaAsO2 in rats. Our study fully confirms the pivotal role of the TLR4-MyD88 signaling in promoting liver injury induced by NaAsO2, thereby providing a novel molecular target for preventing and treating patients with arsenic poisoning-related liver injury.


Subject(s)
Arsenites , Chemical and Drug Induced Liver Injury , Liver , Myeloid Differentiation Factor 88 , Signal Transduction , Sodium Compounds , Toll-Like Receptor 4 , Animals , Male , Rats , Arsenites/toxicity , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/metabolism , Lipopolysaccharides , Liver/drug effects , Liver/pathology , Liver/metabolism , Liver Cirrhosis/chemically induced , Liver Cirrhosis/pathology , Liver Cirrhosis/metabolism , Liver Cirrhosis/drug therapy , Myeloid Differentiation Factor 88/metabolism , Rats, Sprague-Dawley , Signal Transduction/drug effects , Sodium Compounds/toxicity , Sulfonamides/pharmacology , Toll-Like Receptor 4/metabolism
12.
Neurosci Bull ; 40(9): 1379-1395, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38976218

ABSTRACT

Endocytosis is a fundamental biological process that couples exocytosis to maintain the homeostasis of the plasma membrane and sustained neurotransmission. Super-resolution microscopy enables optical imaging of exocytosis and endocytosis in live cells and makes an essential contribution to understanding molecular mechanisms of endocytosis in neuronal somata and other types of cells. However, visualization of exo-endocytic events at the single vesicular level in a synapse with optical imaging remains a great challenge to reveal mechanisms governing the synaptic exo-endocytotic coupling. In this protocol, we describe the technical details of stimulated emission depletion (STED) imaging of synaptic endocytosis at the single-vesicle level, from sample preparation and microscopy calibration to data acquisition and analysis.


Subject(s)
Endocytosis , Synapses , Synaptic Vesicles , Endocytosis/physiology , Animals , Synapses/metabolism , Synaptic Vesicles/metabolism , Exocytosis/physiology , Neurons/metabolism , Microscopy, Fluorescence/methods
13.
Sci Rep ; 14(1): 16846, 2024 07 22.
Article in English | MEDLINE | ID: mdl-39039163

ABSTRACT

This study investigates the processing methods of artistic images within the context of Smart city (SC) initiatives, focusing on the visual healing effects of artistic image processing to enhance urban residents' mental health and quality of life. Firstly, it examines the role of artistic image processing techniques in visual healing. Secondly, deep learning technology is introduced and improved, proposing the overlapping segmentation vision transformer (OSViT) for image blocks, and further integrating the bidirectional long short-term memory (BiLSTM) algorithm. An innovative artistic image processing and classification recognition model based on OSViT-BiLSTM is then constructed. Finally, the visual healing effect of the processed art images in different scenes is analyzed. The results demonstrate that the proposed model achieves a classification recognition accuracy of 92.9% for art images, which is at least 6.9% higher than that of other existing model algorithms. Additionally, over 90% of users report satisfaction with the visual healing effects of the artistic images. Therefore, it is found that the proposed model can accurately identify artistic images, enhance their beauty and artistry, and improve the visual healing effect. This study provides an experimental reference for incorporating visual healing into SC initiatives.


Subject(s)
Image Processing, Computer-Assisted , Humans , Image Processing, Computer-Assisted/methods , Algorithms , Quality of Life , Cities , Art , Deep Learning , Mental Health
14.
Cancer Lett ; 598: 217096, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-38969161

ABSTRACT

Metabolic derivatives of numerous microorganisms inhabiting the human gut can participate in regulating physiological activities and immune status of the lungs through the gut-lung axis. The current well-established microbial metabolites include short-chain fatty acids (SCFAs), tryptophan and its derivatives, polyamines (PAs), secondary bile acids (SBAs), etc. As the study continues to deepen, the critical function of microbial metabolites in the occurrence and treatment of lung cancer has gradually been revealed. Microbial derivates can enter the circulation system to modulate the immune microenvironment of lung cancer. Mechanistically, oncometabolites damage host DNA and promote the occurrence of lung cancer, while tumor-suppresive metabolites directly affect the immune system to combat the malignant properties of cancer cells and even show considerable application potential in improving the efficacy of lung cancer immunotherapy. Considering the crosstalk along the gut-lung axis, in-depth exploration of microbial metabolites in patients' feces or serum will provide novel guidance for lung cancer diagnosis and treatment selection strategies. In addition, targeted therapeutics on microbial metabolites are expected to overcome the bottleneck of lung cancer immunotherapy and alleviate adverse reactions, including fecal microbiota transplantation, microecological preparations, metabolite synthesis and drugs targeting metabolic pathways. In summary, this review provides novel insights and explanations on the intricate interplay between gut microbial metabolites and lung cancer development, and immunotherapy through the lens of the gut-lung axis, which further confirms the possible translational potential of the microbiome metabolome in lung cancer treatment.


Subject(s)
Gastrointestinal Microbiome , Immunotherapy , Lung Neoplasms , Humans , Lung Neoplasms/immunology , Lung Neoplasms/microbiology , Lung Neoplasms/metabolism , Lung Neoplasms/therapy , Immunotherapy/methods , Tumor Microenvironment/immunology , Fatty Acids, Volatile/metabolism , Animals , Tryptophan/metabolism , Lung/microbiology , Lung/immunology , Lung/metabolism
15.
Life Sci ; 351: 122794, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38866218

ABSTRACT

BACKGROUND: Ulcerative colitis (UC) is a chronic, recurrent, non-specific inflammatory disease, and the pathogenesis of the disease remains unclear. Ferroptosis is a form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which are simultaneously closely related to reactive oxygen species (ROS). Although seliciclib is highly effective against immune inflammation, its mechanism on colitis is unclear. This study demonstrated that seliciclib administration partially inhibited ferroptosis, alleviating symptoms and inflammation in experimental colitis. METHODS: The mouse UC model was induced by 3.0 % dextran sodium sulfate (DSS) for 7 days and treated with seliciclib (10 mg/kg) for 5 days. In the in vitro model, LPS (100 µg/mL) was used for induction and seliciclib (10 µM) was applied for 2 h. Meanwhile, appropriate histopathology, inflammatory response, oxidative stress, and ferroptosis regulators were measured. RESULTS: This study primarily investigated the role of seliciclib in regulating ferroptosis in UC. Bioinformatics analysis indicated that Dual oxidase 2 (DUOX2) may serve a role involved in the ferroptosis of UC. The experimental findings demonstrated that seliciclib alleviates symptoms and inflammation in DSS-induced UC mice and partially mitigates the occurrence of ferroptosis both in vivo and in vitro, possibly through the modulation of DUOX2. CONCLUSIONS: Ferroptosis is strongly associated with the development of colitis, and seliciclib plays an essential role in ferroptosis and inflammation in UC. The suppression of ferroptosis in the intestinal epithelium could be a therapeutic approach for UC.


Subject(s)
Colitis, Ulcerative , Dextran Sulfate , Ferroptosis , Mice, Inbred C57BL , Animals , Ferroptosis/drug effects , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Colitis, Ulcerative/metabolism , Mice , Male , Dextran Sulfate/toxicity , Inflammation/drug therapy , Inflammation/pathology , Inflammation/metabolism , Reactive Oxygen Species/metabolism , Disease Models, Animal , Oxidative Stress/drug effects
16.
Philos Trans R Soc Lond B Biol Sci ; 379(1906): 20230240, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-38853555

ABSTRACT

Synaptic plasticity is a key cellular model for learning, memory and chronic pain. Most previous studies were carried out in rats and mice, and less is known about synaptic plasticity in non-human primates. In the present study, we used integrative experimental approaches to study long-term potentiation (LTP) in the anterior cingulate cortex (ACC) of adult tree shrews. We found that glutamate is the major excitatory transmitter and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid (AMPA) receptors mediate postsynaptic responses. LTP in tree shrews was greater than that in adult mice and lasted for at least 5 h. N-methyl-d-aspartic acid (NMDA) receptors, Ca2+ influx and adenylyl cyclase 1 (AC1) contributed to tree shrew LTP. Our results suggest that LTP is a major form of synaptic plasticity in the ACC of primate-like animals. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.


Subject(s)
Gyrus Cinguli , Long-Term Potentiation , Receptors, AMPA , Receptors, N-Methyl-D-Aspartate , Tupaiidae , Animals , Long-Term Potentiation/physiology , Gyrus Cinguli/physiology , Tupaiidae/physiology , Mice , Receptors, N-Methyl-D-Aspartate/metabolism , Receptors, AMPA/metabolism , Adenylyl Cyclases/metabolism , Glutamic Acid/metabolism , Male
17.
Environ Sci Technol ; 58(22): 9570-9581, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38781138

ABSTRACT

The increasing level of O3 pollution in China significantly exacerbates the long-term O3 health damage, and an optimized health-oriented strategy for NOx and VOCs emission abatement is needed. Here, we developed an integrated evaluation and optimization system for the O3 control strategy by merging a response surface model for the O3-related mortality and an optimization module. Applying this system to the Yangtze River Delta (YRD), we evaluated driving factors for mortality changes from 2013 to 2017, quantified spatial and temporal O3-related mortality responses to precursor emission abatement, and optimized a health-oriented control strategy. Results indicate that insufficient NOx emission abatement combined with deficient VOCs control from 2013 to 2017 aggravated O3-related mortality, particularly during spring and autumn. Northern YRD should promote VOCs control due to higher VOC-limited characteristics, whereas fastening NOx emission abatement is more favorable in southern YRD. Moreover, promotion of NOx mitigation in late spring and summer and facilitating VOCs control in spring and autumn could further reduce O3-related mortality by nearly 10% compared to the control strategy without seasonal differences. These findings highlight that a spatially and temporally differentiated NOx and VOCs emission control strategy could gain more O3-related health benefits, offering valuable insights to regions with severe ozone pollution all over the world.


Subject(s)
Ozone , Volatile Organic Compounds , China , Air Pollutants , Humans , Nitrogen Oxides
18.
Protein Sci ; 33(6): e5012, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723180

ABSTRACT

The enormous LysR-type transcriptional regulators (LTTRs), which are diversely distributed amongst prokaryotes, play crucial roles in transcription regulation of genes involved in basic metabolic pathways, virulence and stress resistance. However, the precise transcription activation mechanism of these genes by LTTRs remains to be explored. Here, we determine the cryo-EM structure of a LTTR-dependent transcription activation complex comprising of Escherichia coli RNA polymerase (RNAP), an essential LTTR protein GcvA and its cognate promoter DNA. Structural analysis shows two N-terminal DNA binding domains of GcvA (GcvA_DBD) dimerize and engage the GcvA activation binding sites, presenting the -35 element for specific recognition with the conserved σ70R4. In particular, the versatile C-terminal domain of α subunit of RNAP directly interconnects with GcvA_DBD, σ70R4 and promoter DNA, providing more interfaces for stabilizing the complex. Moreover, molecular docking supports glycine as one potential inducer of GcvA, and single molecule photobleaching experiments kinetically visualize the occurrence of tetrameric GcvA-engaged transcription activation complex as suggested for the other LTTR homologs. Thus, a general model for tetrameric LTTR-dependent transcription activation is proposed. These findings will provide new structural and functional insights into transcription activation of the essential LTTRs.


Subject(s)
DNA-Directed RNA Polymerases , Escherichia coli , Transcriptional Activation , Escherichia coli/genetics , Escherichia coli/metabolism , DNA-Directed RNA Polymerases/metabolism , DNA-Directed RNA Polymerases/chemistry , DNA-Directed RNA Polymerases/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Promoter Regions, Genetic , Cryoelectron Microscopy , Escherichia coli Proteins/chemistry , Escherichia coli Proteins/metabolism , Escherichia coli Proteins/genetics , Transcription Factors/chemistry , Transcription Factors/metabolism , Transcription Factors/genetics , Models, Molecular , Molecular Docking Simulation , Gene Expression Regulation, Bacterial , Protein Multimerization , Binding Sites
19.
Mikrochim Acta ; 191(6): 304, 2024 05 06.
Article in English | MEDLINE | ID: mdl-38710810

ABSTRACT

Dual-emissive fluorescence probes were designed by integrating porphyrin into the frameworks of UiO-66 for ratiometric fluorescence sensing of amoxicillin (AMX). Porphyrin integrated UiO-66 showed dual emission in the blue and red region. AMX resulted in the quenching of blue fluorescence component, attributable to the charge neutralization and hydrogen bonds induced energy transfer. AMX was detected using (F438/F654) as output signals. Two linear relationships were observed (from 10 to 1000 nM and 1 to 100 µM), with a limit of detection of 27 nM. The porphyrin integrated UiO-66 probe was used to detect AMX in practical samples. This work widens the road for the development of dual/multiple emissive fluorescence sensors for analytical applications, providing materials and theoretical supporting for food, environmental, and human safety.


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Fluorescent Dyes , Milk , Porphyrins , Spectrometry, Fluorescence , Milk/chemistry , Porphyrins/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Amoxicillin/analysis , Amoxicillin/chemistry , Fluorescent Dyes/chemistry , Animals , Spectrometry, Fluorescence/methods , Limit of Detection , Metal-Organic Frameworks/chemistry , Drug Residues/analysis , Food Contamination/analysis
20.
mBio ; 15(6): e0064024, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38727246

ABSTRACT

Interleukin-18 binding protein (IL-18BP), a natural regulator molecule of the pro-inflammatory cytokine interleukin-18 (IL-18), plays an important role in regulating the expression of the cellular immunity factor interferon-γ (IFN-γ). In a previous RNA-seq analysis of porcine alveolar macrophages (PAM) infected with the TIM and TJ strains of porcine reproductive and respiratory syndrome virus (PRRSV), we unexpectedly found that the mRNA expression of porcine interleukin 18-binding protein (pIL-18BP) in PAM cells infected with the TJM strain was significantly higher than that infected with the TJ strain. Studies have shown that human interleukin-18 binding protein (hIL-18bp) plays an important role in regulating cellular immunity in the course of the disease. However, there is a research gap on pIL-18BP. At the same time, PRRSV infection in pigs triggers weak cellular immune response problems. To explore the expression and the role of pIL-18BP in the cellular immune response induced by PRRSV, we strived to acquire the pIL-18BP gene from PAM or peripheral blood mononuclear cell (PBMC) with RT-PCR and sequencing. Furthermore, pIL-18BP and pIL-18 were both expressed prokaryotically and eukaryotically. The colocalization and interaction based on recombinant pIL-18BP and pIL-18 on cells were confirmed in vitro. Finally, the expression of pIL-18BP, pIL-18, and pIFN-γ was explored in pigs with different PRRSV infection states to interpret the biological function of pIL-18BP in vivo. The results showed there were five shear mutants of pIL-18BP. The mutant with the longest coding region was selected for subsequent functional validation. First, it was demonstrated that TJM-induced pIL-18BP mRNA expression was higher than that of TJ. A direct interaction between pIL-18BP and pIL-18 was confirmed through fluorescence colocalization, bimolecular fluorescent complimentary (BIFC), and co-immunoprecipitation (CO-IP). pIL-18BP also can regulate pIFN-γ mRNA expression. Finally, the expression of pIL-18BP, pIL-18, and pIFN-γ was explored in different PRRSV infection states. Surprisingly, both mRNA and protein expression of pIL-18 were suppressed. These findings fill the gap in understanding the roles played by pIL-18BP in PRRSV infection and provide a foundation for further research.IMPORTANCEPRRSV-infected pigs elicit a weak cellular immune response and the mechanisms of cellular immune regulation induced by PRRSV have not yet been fully elucidated. In this study, we investigated the role of pIL-18BP in PRRSV-induced immune response referring to the regulation of human IL-18BP to human interferon-gamma (hIFN-γ). This is expected to be used as a method to enhance the cellular immune response induced by the PRRSV vaccine. Here, we mined five transcripts of the pIL-18BP gene and demonstrated that it interacts with pIL-18 and regulates pIFN-γ mRNA expression. Surprisingly, we also found that both mRNA and protein expression of pIL-18 were suppressed under different PRRSV strains of infection status. These results have led to a renewed understanding of the roles of pIL-18BP and pIL-18 in cellular immunity induced by PRRSV infection, which has important implications for the prevention and control of PRRS.


Subject(s)
Porcine respiratory and reproductive syndrome virus , RNA, Messenger , Animals , Swine , Porcine respiratory and reproductive syndrome virus/genetics , Porcine respiratory and reproductive syndrome virus/immunology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Porcine Reproductive and Respiratory Syndrome/virology , Porcine Reproductive and Respiratory Syndrome/immunology , Porcine Reproductive and Respiratory Syndrome/genetics , Porcine Reproductive and Respiratory Syndrome/metabolism , Macrophages, Alveolar/virology , Macrophages, Alveolar/immunology , Macrophages, Alveolar/metabolism , Host-Pathogen Interactions/genetics , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interferon-gamma/immunology , Transcription, Genetic
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