In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*

A microchannel-based electrochemiluminescence(ECL)sensor was developed for detection of tetracycline(TC)utilizing luminol/H2O2 as ECL reporting system.The low excitation potential of luminol/H2O2 effectively mitigated the impact of clamping voltage,thereby enhancing the detection performance of the microchannel-based ECL sensor.The microchannel modified with TC aptamer selectively recognized and captured target TC.The positively charged TC reduced the surface charge density within the microchannel,thereby increasing the ionic current in the microchannel,leading to change of ECL signal of system.The experimental conditions such as electrolyte concentration,TC-aptamer concentration,and reaction time between TC and TC-aptamer were optimized.Under optimal conditions,the difference of ECL signal in the absence and presence of TC(?ECL)exhibited a good linear relationship with TC concentration in the range from 1.00 ng/mL to 200 ng/mL,with a detection limit as low as 0.69 ng/mL.The sensor had good selectivity and was successfully used in detection of TC in milk samples.

Fluorescent probes L1 to L5 containing two recognition sites based on Schiff base were prepared for detection of Al3+.The probes were constituted by introducing two salicylaldehyde derivatives through hydrazide groups on isophthalic hydrazide.Among them,a fast turn-on fluorescence probe L1 for Al3+with high fluorescence quantum yield was found.The recognition performance and mechanism of probe L1 to Al3+were studied by multiple analysis methods.The results showed that probe L1 could rapidly and highly selectively recognize Al3+by fluorescent enhancement at 446 nm and the detection limit was as low as 4.65 nmol/L,and it was found that L1 complexed with Al3+in the molar ratio of 1:1.In addition,the calculation results of density functional theory(DFT)showed that two binding sites in the probe molecule connected two different Al3+,and each Al3+connected two adjacent probe molecules.Using quinine sulfate as a reference,the fluorescence quantum yield of L1-Al3+complex was as high as 30%.Probe L1 could also be applied to the detection of Al3+in real water samples.

Objective Sleep is an important physiological process for maintaining normal cognitive functions,but with the accelerated pace and increased work pressure in modern society,sleep deprivation has become a common phenomenon.It has been shown that sleep deprivation interferes with higher cognitive functions such as working memory,but the specific mechanism of its effect is still not completely clear.The present study aimed to systematically investigate the effects of 36 hours of sleep deprivation on the stages of the working memory processing chain and its neural mechanisms through behavioral and event-related potential(ERP)techniques.Methods Using a randomized controlled experimental design,48 healthy adult subjects were recruited and randomly assigned to sleep deprivation and control groups.All subjects completed a 2-back phonological working memory task,and behavioral data(response time and correctness)and ERP data(P2,N2,and P3 component wave amplitudes)were collected at 0 and 36 hours,respectively.The effects of sleep deprivation on working memory behavioral performance and neurophysiological indices were assessed by ANOVA.Results Behavioral results showed that the sleep deprivation group had a significantly longer response time after 36 hours,but no significant decrease in correctness,indicating a decrease in response efficiency but stable accuracy.ERP results showed that P2 amplitude did not change significantly before and after sleep deprivation,indicating that the early perception and categorization stages were limitedly affected by sleep deprivation;whereas,N2 and P3 amplitudes decreased significantly after sleep deprivation,reflecting that later cognitive processing such as conflict monitoring and resource allocation and other late cognitive processing were significantly disturbed.Conclusion Through ERP technology,this study uncovers the phased impact of 36-hour sleep deprivation on the working memory processing chain.The study found that early perceptual and categorization stages may be less susceptible to the effects of sleep deprivation,likely due to their relatively automatic processing and lower demand for cognitive resources.In contrast,during later stages of cognitive processing,particularly in higher-order functions such as conflict monitoring and resource allocation,sleep deprivation significantly impaired task performance efficiency by disrupting prefrontal cortex function.This finding deepens the understanding of the mechanisms underlying the effects of sleep deprivation and provides a scientific basis for cognitive intervention and management strategies in high-stress occupational groups.Future studies can further explore the long-term effects of sleep deprivation and its neural mechanisms by combining multimodal techniques.

Objective To analyze the expression level of triggering receptor expressed on myeloid cells-1(TREM-1)in serum and ascites of patients with cirrhotic ascites,and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation.Methods A total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled,and according to the presence or absence of intra-abdominal infection,they were divided into infection group with 72 patients and non-infection group with 38 patients.The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients.Clinical data and laboratory markers were collected from all patients.Serum and ascites samples were collected,and ELISA was used to measure the level of TREM-1.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups,and the Kruskal-Wallis H test was used for comparison between multiple groups;the chi-square test was used for comparison of categorical data between two groups.A Spearman correlation analysis was used to investigate the correlation between indicators.A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic and prognostic efficacy of each indicator,and the Delong test was used for comparison of the area under the ROC curve(AUC).Results The level of TREM-1 in ascites was significantly positively correlated with that in serum(r=0.50,P<0.001).Compared with the improvement group,the non-improvement group had a significantly higher level of TREM-1 in ascites(Z=-2.391,P=0.017)and serum(Z=-2.544,P=0.011),and compared with the non-infection group,the infection group had a significantly higher level of TREM-1 in ascites(Z=-3.420,P<0.001),while there was no significant difference in the level of TREM-1 in serum between the two groups(P>0.05).The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein(CRP),procalcitonin(PCT),white blood cell count,and neutrophil-lymphocyte ratio(r=0.288,0.344,0.530,0.510,0.534,0.454,0.330,and 0.404,all P<0.05).The ROC curve analysis showed that when PCT,CRP,and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection,the AUCs were 0.715 and 0.740,respectively.The multivariate Logistic regression analysis showed that CRP(odds ratio[OR]=1.019,95%confidence interval[CI]:1.001-1.038,P=0.043)and serum TREM-1(OR=1.002,95%CI:1.000-1.003,P=0.016)were independent risk factors for the prognosis of patients with cirrhotic ascites and infection,and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis.Conclusion The level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites,and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.

Objective Chronic atrophic gastritis(CAG)is often accompanied by intestinal flora disorder and intestinal symptoms,forming the phenomenon of"stomach disease involving intestine".This study explored the dynamic correlation between intestinal symptoms and qi-stagnation degree in patients with CAG qi-stagnation syndrome and analyzed the characteristics of gut microbiota from the perspective of"spleen-stomach system serving as the pivotal hub of qi movement"in TCM.Methods According to the syndrome element differentiation method,410 patients with CAG were divided into four groups:non-qi-stagnation group,mild qi-stagnation group,moderate qi-stagnation group and severe qi-stagnation group.Correlation analysis and 16S intestinal flora sequencing technology were used to analyze the correlation and differential flora between the degree of CAG qi-stagnation and intestinal symptoms.Results Patients with CAG qi-stagnation syndrome were often accompanied by intestinal symptoms such as frequent flatulence,poor defecation and alternating loose-constipated stools.The frequency of cases was significantly positively correlated with the degree of qi-stagnation"non-mild-moderate-severe"(P<0.05).There was a difference in the abundance of gut microbiota between the four groups of CAG qi-stagnation none,mild,moderate and severe.The relative abundance of Streptococcus,Subdoligranulum,Eubacterium_coprostanoligenes_group and Haemophilus was positively correlated with the degree of qi-stagnation.The relative abundance of Ruminococcus_torques_group and Butyricicoccus showed a negative correlation,and Haemophilus was statistically significant among the four groups(P<0.05).Conclusion This study can provide clinical evidence and micro-mechanism for the connotation of"gastrointestinal co-morbidities"and"different diseases with the same syndrome",which may open up new ideas for clinical diagnosis and treatment.

Aim To investigate the intestinal protection and possible mechanism of magnolol(MG)in newborn rats with necrotizing enterocolitis(NEC).Methods The rats were randomly divided into control group(Ctrl group),model group(NEC group)and treatment group(MG group).The NEC model was induced by hypoxia,cold stimulation,deep formula milk and LPS intragastric administration in 7-day-old rats for four days.They were killed after five days of treatment with MG(20 mg·kg-1).HE staining was used to observe the intestinal pathological injury.Western blot was used to detect the expressions of IL-1 β,TNF-α,NL-RP3,ASC,caspase-1 and tight junction protein in the distal ileum of rats.Colon contents were collected for 16S rDNA sequencing to understand the gut microbio-ta.Results MG improved the body mass and intesti-nal injury of NEC neonatal rats.The expressions of in-testinal IL-1β,TNF-α,NLRP3,ASC and caspase-1 proteins were down-regulated,and the expressions of Claudin,Occludin and ZO-1 proteins were up-regula-ted.16S rDNA showed that MG increased the diversity of intestinal flora,and at the phylum level,MG in-creased the abundance of firmicutes and bacteroides in NEC model,and decreased the abundance of pro-teobacteria.At the genus level,MG treatment in-creased the abundance of Lactobacillus,unclassified_Muribaculaceae,Racteroides,but decreased the abun-dance of Escherichia_Shigella,Rodentibacter and Fuso-bacterium.Conclusion MG intervention can protect the intestinal tract of NEC rats by potentially improving barrier function,and regulating the intestinal microbiota through the NLRP3/ASC/caspase-1 signaling pathway.

Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.