Gibberellic acid targeting ZBTB16 reduces NF-κB dependent inflammatory stress in sepsis-induced neuroinflammation.

OBJECTIVE: Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation. METHODS: C57BL/6J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1ß, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA. RESULTS: GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1ß in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16. CONCLUSIONS: Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation.

Chiral BINOL-phosphate assembled single hexagonal nanotube in aqueous solution for confined rearrangement acceleration.

Creating microenvironments that mimic an enzyme's active site is a critical aspect of supramolecular confined catalysis. In this study, we employ the commonly used chiral 1,1'-bi-2-naphthol (BINOL) phosphates as subcomponents to construct supramolecular hollow nanotube in an aqueous medium through non-covalent intermolecular recognition and arrangement. The hexagonal nanotubular structure is characterized by various techniques, including X-ray, NMR, ESI-MS, AFM, and TEM, and is confirmed to exist in a homogeneous aqueous solution stably. The nanotube's length in solution depends on the concentration of chiral BINOL-phosphate as a monomer. Additionally, the assembled nanotube can accelerate the rate of the 3-aza-Cope rearrangement reaction by up to 85-fold due to the interior confinement effect. Based on the detailed kinetic and thermodynamic analyses, we propose that the chain-like substrates are constrained and pre-organized into a reactive chair-like conformation, which stabilizes the transition state of the reaction in the confined nanospace of the nanotube. Notably, due to the restricted conformer with less degrees of freedom, the entropic barrier is significantly reduced compared to the enthalpic barrier, resulting in a more pronounced acceleration effect.

General anesthesia alters the diversity and composition of the lung microbiota in rat.

BACKGROUND: The lung microbiome plays a crucial role in human health and disease. Extensive studies have demonstrated that the disturbance of the lung microbiome influences immune response, cognition, and behavior. The goal of this study was to investigate the effect of general anesthetics on lung microbiome. METHODS: Eight-week-old male SD rats received a continuous intravenous infusion of propofol or inhalation of isoflurane for 4 h. 16S rRNA gene amplification from BALF samples was used to investigate the changes in the lung microbiome after interventions. We further performed neurobehavioral assessments to find the differential strains' association with behavior disorder after isoflurane anesthesia. RESULTS: The absolute and relative quantitation of 16S rRNA sequencing data showed that isoflurane altered the diversity and abundance of the lung microbiome in rats more than propofol. Elusimicrobia increased significantly in the isoflurane group. Both EPM and OFT results showed that rats exhibited depression-like behaviors after inhalation of isoflurane. In addition, significant differences were found in the COG/KO/MetaCyc/KEGG pathway enrichment analyses among the groups. CONCLUSION: Continuous inhalation of isoflurane changed the diversity and composition of the lung microbiota in rats, resulting in post-anesthesia depression.

Ginsenoside Rg1 in neurological diseases: From bench to bedside.

Ginseng has been used in China as a superior medicinal material for thousands of years that can nourish the five internal organs, calm the mind and benefit wisdom. Due to its anti-inflammatory, antioxidant and neuroprotective activities, one of the active components of ginseng, ginsenoside Rg1, has been extensively investigated in the remedy of brain disorders, especially dementia and depression. In this review, we summarized the research progress on the action mechanisms of Rg1 ameliorating depression-like behaviors, including inhibition of hyperfunction of hypothalamic-pituitary-adrenal (HPA) axis, regulation of synaptic plasticity and gut flora. Rg1 may alleviate Alzheimer's disease in the early phase, as well as in the middle-late phases through repairing dendrite, axon and microglia- and astrocyte-related inflammations. We also proposed that Rg1 could regulate memory state (the imbalance of working and aversive memory) caused by distinct stimuli. These laboratory studies would further the clinical trials on Rg1. From the prospective of drug development, we discussed the limitations of the present investigations and proposed our ideas to increase permeability and bioavailability of Rg1. Taken together, Rg1 has the potential to treat neuropsychiatric disorders, but a future in-depth investigation of the mechanisms is still required. In addition, drug development will benefit from the clinical trials in one specific neuropsychiatric disorder.

[Effects of Microplastic Exposure on Crucian Growth, Liver Damage, and Gut Microbiome Composition].

Microplastics (MPs), which are widely present in the natural environment, may be harmful to the growth and health of aquatic organisms, though studies in this area are lacking. In this study, the crucian carp (Carassius carassius), a type of omnivorous freshwater fish, was chosen as the target, which was fed with fish food containing different concentrations of MPs for a 30-day food exposure experiment to study the effects of MPs on crucian growth, liver damage, and gut microbiome composition. Compared with that in the control group, the body length of the crucians in the environmental groups did not change significantly. The weight of the crucians in the low PE-MPs group increased significantly, but the weight of crucians in the medium and high PE-MPs groups decreased markedly. The liver tissues of the low PE-MPs group of crucians were basically normal, whereas crucians in the medium and high PE-MPs groups had varying degrees of liver damage, and crucians in the high PE-MPs group had the most serious liver damage. At the phylum level, Proteobacteria, Fusobacteria, Firmicutes, and Bacteroides were the dominant species in the gut of the crucians. Pathogens such as Staphylococcus and Ralstonia were present in the crucian gut of environmental groups. Alpha diversity results showed that the gut microbiome of crucians in the high PE-MPs group was the most abundant. PCoA results indicated that the gut microbiome of crucians in the control and environmental groups had obvious clustering characteristics.

[Spatial Variation and Potential Sources of Microplastics in Rivers in Tongzhou District, Beijing].

Microplastics are emerging contaminants, which can also absorb other contaminants, threatening the health of river ecosystems. However, research on the pollution of microplastics in rivers in northern China is still lacking. In this study, based on the sampling and analysis of water samples in 19 sites in six rivers in Tongzhou district, Beijing, the composition, spatial variation, and potential sources of microplastics were explored. The results showed that all sites were contaminated by microplastics, and the abundance of microplastics in the Xiaozhong River was the highest among all sites (3.50×104 n·m-3), which was 4.04 times that in the Yunchaojian River. The proportion of microplastics with particle sizes smaller than 2000 µm was 90.49%, and microplastics with particle sizes larger than 4000 µm were only found in two out of 19 sampling sites. The microplastics were fiber, film, fragment, and granule shaped. The proportion of fiber microplastics was the highest (90.23%) among all shapes. Most (84.29%) of the microplastics were transparent and blue. Rayon was the most common microplastic in each site, and its proportion in each site was over 66.67%. The proportions of other types of microplastics differed largely among different sites. Spatially, the abundance and types of microplastics in the upper reaches were higher than those in the lower reaches. According to spatial variations in shapes, types, colors, and abundance of microplastics, the potential sources of microplastics were identified. The potential sources of fiber microplastics were washing clothing and using fishing gear and dust-proof nets.

Precise heteroatom doping determines aqueous solubility and self-assembly behaviors for polycyclic aromatic skeletons.

Developing effective strategies to improve the hydrophilicity or aqueous solubility of hydrophobic molecular scaffolds is meaningful for both academic research and industrial applications. Herein, we demonstrate that stepwise and precise N/O heteroatoms doping on a polycyclic aromatic skeleton can gradually alter these structures from hydrophobic to hydrophilic, even resulting in excellent aqueous solubility. The Hansen solubility parameters (HSP) method shows that the three partial solubility parameters are closely related to N/O doping species, numbers and positions on the molecular panel. The hydrogen bonding solubility parameter indicates that the hydrogen bonding interactions between N/O doped molecules and water play a key role in enhancing hydrophilicity. Moreover, three optimized water-soluble molecules underwent a self-assembly process to form stable nanoparticles in water, thus facilitating better hydrogen bonding interactions disclosed by HSP calculations, NMR and single crystal X-ray analysis. These ensembles even show quasi-solid properties in water from NMR and luminescence perspectives.

[Composition and Distribution of Microplastics in the Water and Sediments of Urban Rivers in Beijing].

It has been confirmed that microplastics widely exist in the natural environment, causing potential harm to organisms and humans. An investigation into the occurrence of microplastics is helpful to understand the level of pollution of microplastics in urban rivers and sediments. In this study, eight sampling points of water samples and three of sediments samples were placed along the North Canal and Huaihe River in Beijing, to compare the composition and distribution characteristics of the abundance, particle size, color, shape, and species of microplastics. The results showed that the abundance of microplastics in the water and sediments of the North Canal were(1941±201)-(8155±1781) n·m-3(n refers to the number of microplastics) and (120±11)-(268±31) n·kg-1, respectively. The average abundance of microplastics in the water of the North Canal was 4160 n·m-3. Compared with the North Canal, the pollution degree of microplastics in the Huaihe River was lower with an average abundance of 2357 n·m-3. Furthermore, the abundance of microplastics in the water and sediments in the upper reaches of the North Canal was higher than that in the lower reaches. No significant difference of microplastics distribution was observed in the water of the Huaihe River on the whole; however, there was a marked difference in abundance between the two distant locations. The main particle size range of microplastics at all site points was<300 µm, and mostly white/transparent(50.75%-83.91%); the main shape were fragments(50.00%-95.08%) and fibers(3.86%-30.00%). Polyurethane(PU) and ethylene vinyl acetate(EVA) were two main plastic species found at all sites. Microplastics in the water and sediments of the North Canal might have originated from urban construction and development, while the surrounding villages might have only affected the abundance of microplastics in the Huaihe River.

Identification of hub genes correlated with sleep deprivation using co-expression analysis.

BACKGROUND: Sleep deprivation (SD) has become a serious concern worldwide. This study aimed to identify key modules and candidate hub genes correlated with diseases caused by SD, using co-expression analysis. METHODS: The weighted gene co-expression network analysis was performed to construct a co-expression network of hub genes correlated with SD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to search for signaling pathways. The protein-protein interaction network analysis of central genes was performed to recognize the interactions among central genes. Molecular Complex Detection, a plugin in Cytoscape, was used to discover the hub gene clusters involved in SD. RESULTS: A total of 564 genes in the yellow module were identified based on the results of topological overlap measure-based clustering. The yellow module showed a pivotal correlation with SD. Six hub gene clusters prominently associated with SD were identified. Heat shock protein family and circadian clock genes among them may be the hub genes involved in SD. CONCLUSIONS: These genes and pathways might become therapeutic targets with clinical usefulness in the future.

Fire-needle acupuncture for upper limb spastic paralysis after stroke: Study protocol for a randomized controlled trial.

BACKGROUND: Fire-needle acupuncture, an important kind of acupuncture therapy, has been clinically used to treat upper limb spastic paralysis (ULSP) after stroke. Clinical experience has indicated that fire-needle acupuncture treatment takes less time, requires fewer visits, and has more rapid results and fewer side effects compared to chemical medicine alternatives. This study will evaluate the effects of fire-needle acupuncture for ULSP in the context of standardized clinical research and provide high-quality data to inform clinical procedures and future study design. METHODS/DESIGN: A randomized controlled trial will be carried out to evaluate the effects of fire-needle acupuncture therapy in patients with ULSP from stroke. ULSP patients (n = 120) will be recruited at Changhai Hospital in Shanghai, China. Patients will be randomly divided into three groups, including fire-needle acupuncture group (FAG), filiform-needle acupuncture group (FFAG) and rehabilitation treatment group (RTG). During the 3-week treatment, the FAG will be treated every two days, while FFAG and RTG will be treated 5 d in a row and then rest for 2 d. The Simplified Fugl-Meyer Motor Function Scale and Modified Ashworth Scale will be used as the primary outcome measures. Statistical analysis will be conducted by an independent statistician. DISCUSSION: Through this study, the utility of fire-needle acupuncture in treating ULSP after stroke will be tested, and some specific claims of fire-needle acupuncture therapy will be evaluated, such as relieving spasm and muscular tension, improving activities of daily living, rapidity of response and less frequency of treatment compared with other treatments. TRIAL REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR-IOR-17013875; registration date: 28 December 2016).