Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Kynurenine pathway (KP) is a major catabolic route of tryptophan, generating a series of bioactive metabolites including kynurenine, kynurenic acid (KA), quinolinic acid, and 3-hydroxykynurenine. Beyond its fundamental role in amino acid metabolism, KP exerts critical regulatory functions in neurodevelopment, synaptic plasticity, and immune modulation. Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with onset in early childhood, characterized by persistent deficits in social communication and restricted, repetitive behaviors. Despite extensive research, the etiological mechanisms underlying ASD remain highly complex and incompletely understood, involving genetic, environmental, and immunological factors. Emerging clinical evidence has consistently revealed a significant imbalance in KP metabolites in individuals with ASD, often accompanied by altered ratios of neuroprotective versus neurotoxic byproducts. However, the primary drivers of this metabolic dysregulation and its causative contribution to ASD pathogenesis are not yet fully elucidated. In this review, we systematically review the enzymatic steps of KP and the principal physiological functions of its major metabolites, with particular emphasis on their dual roles in neuroprotection and neurotoxicity. We then analyze the potential pathogenic mechanisms through which KP dysfunction may contribute to ASD, focusing on two interconnected etiological dimensions. First, KP imbalance can promote oxidative stress, which in turn triggers chronic inflammatory responses via microglial activation and release of pro-inflammatory cytokines, thereby disrupting neuronal homeostasis. Second, aberrant KP metabolism affects neurotransmitter systems, particularly glutamatergic and dopaminergic signaling, leading to impaired neural circuit development and synaptic pruning. By integrating current findings on the KP-ASD association, this review offers a comprehensive etiological framework and a clinically relevant paradigm. Furthermore, we highlight that specific KP metabolites, such as the KA/quinolinic acid ratio, hold promise as peripheral biomarkers for early diagnosis and disease stratification. Finally, we discuss the therapeutic potential of targeting KP enzymes or receptors for personalized intervention strategies, while acknowledging the challenges in translating these findings into clinical practice.

ObjectiveTo explore the mechanism by which aerobic exercise improves hippocampal neuroinflammation and learning and memory ability in brain-aged mice via interferon regulatory factor 7 (IRF7). MethodsA total of 60 male specific pathogen-free (SPF) C57BL/6J mice were enrolled in the experiment, including 30 young mice (2 months old) and 30 naturally aging mice (12 months old). Young mice and old mice were respectively randomly assigned to four groups: young control group (group C, n=15), young exercise group (group CE, n=15), and aging control group (group A, n=15), aging exercise group (group AE, n=15). Mice in the exercise groups received an 8-week continuous treadmill aerobic exercise intervention, while control mice were kept under routine feeding without exercise intervention. After the intervention, Barnes maze and Y-maze behavioral tests were performed to comprehensively assess the learning and memory abilities of each group of mice. Transmission electron microscopy was used to observe the ultrastructural morphological changes of hippocampal synapses. Western blot assay was utilized to detect the protein expression and phosphorylation levels of Janus kinase 1 (JAK1), signal transducer and activator of transcription 1 (STAT1), as well as the expression of postsynaptic density protein 95 (PSD95). Immunofluorescence staining was applied to quantify the fluorescence intensity of ionized calcium-binding adapter molecule 1 (IBA1) in hippocampal tissues. The expression levels of inflammatory cytokines including interferon-α (IFN-α), interferon-β (IFN-β), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA expression level of IRF7, and DNA methylation assay was further conducted to analyze the methylation level of the IRF7 gene in mouse hippocampus. ResultsAt the molecular level, compared with group C, the protein expression levels of JAK1, STAT1, p‑JAK1, and p‑STAT1 in group A were significantly increased (P<0.05), whereas PSD95 expression was decreased (P<0.05). ELISA assays showed that the levels of IFN‑α, IFN‑β, TNF‑α, and IL‑1β were significantly elevated in group A (P<0.001). RT‑PCR analysis revealed that, compared with group C, the mRNA expression of IRF7 in group A was markedly upregulated (P<0.000 1), while the CpG methylation rate of the IRF7 promoter was significantly reduced (P<0.05). In contrast, all the above parameters in the AE group showed improvements relative to those in group A. Immunofluorescence staining indicated positive IBA1 expression in the brain tissues of group A mice. Exercise intervention reversed these abnormal changes. ConclusionIn aged mice, aerobic exercise induces hypermethylation of the IRF7 promoter region, suppresses IRF7 expression and activation of the downstream IFN‑I/JAK1/STAT1 signaling pathway, accompanied by alleviated neuroinflammation, improved learning and memory, and ameliorated brain aging-related phenotypes.

Objective To explore the correlation between gallbladder stones and small intestinal bacterial overgrowth(SIBO).Methods A retrospective analysis was conducted on the clinical data of 393 patients who attended the Department of Gastroenterology of the Sixth Medical Center of Chinese PLA General Hospital from January 2021 to September 2023.They were divided into gallbladder stones group(n=190)and control group(n=203)based on the presence of gallbladder stones.Their general clinical data,laboratory test results,and abdominal symptoms were compared.Multivariate logistic regression was used to analyze the risk factors for gallbladder stones.Additionally,the total population was divided into SIBO-positive group(n=239)and SIBO-negative group(n=154),and their clinical characteristics were analyzed by logistic regression to explore the risk factors for SIBO.Results Univariate analysis revealed that gallbladder stones group had a higher rate of age,body mass index(BMI),fasting plasma glucose(FPG),glutaminase levels,prevalence of hypertension,diabetes,coronary heart disease,non-alcoholic fatty liver disease,gallbladder polyps,and SIBO,as well as a higher prevalence of CH4-positive and H2-positive in SIBO group than control group(P＜0.05).In terms of abdominal symptoms,the incidence of bad breath(48.4%vs.35.5%),dyspepsia(38.4%vs.28.6%),abdominal pain(30.5%vs.14.8%),bloating(42.1%vs.28.6%),diarrhea(20.5%vs.7.4%),and more exhaustion(46.8%vs.34.5%)were significantly higher in gallbladder stones group than those in control group(P＜0.05).Multivariate logistic regression analysis showed that independent positive determinants for incident gallbladder stones were age,BMI,FPG,total bilirubin(TBIL),coronary heart disease,gallbladder polyps,and SIBO.Univariate analysis revealed that age,prevalence of gallbladder stones,proportion of single stones,triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)were significantly higher in SIBO-positive group than those in SIBO-negative group(P＜0.05).Multivariate logistic regression analysis showed that the risk factors for SIBO were age,coronary heart disease,and gallbladder stones,while the protective factor for SIBO was high-density lipoprotein cholesterol(HDL-C).Conclusion There is a significant correlation between gallbladder stones and small SIBO;interventions on related factors of gallbladder stones and small SIBO may help reduce their incidence.

Objective To explore the influencing factors of different types of small intestinal bacterial overgrowth(SIBO).Methods A total of 539 patients who were hospitalized in the Department of Gastroenterology,the Sixth Medical Center of PLA General Hospital from June 2021 to December 2021 and who underwent methane-hydrogen breath test were retrospectively selected.Based on breath test results,patients were divided into SIBO-negative group(n=300)and SIBO-positive group(n=239).The clinical data were compared between two groups.According to the specific values of breath test results,SIBO-positive patients were further divided into hydrogen-producing bacterial overgrowth(hydrogen-positive,n=103),intestinal methanogen overgrowth(methanogen-positive,n=80),and simultaneous methanogen and hydrogen-producing bacterial overgrowth(double positive,n=56)groups.Multivariate logistic regression analysis was employed to identify influencing factors of different SIBO types.Additionally,SIBO-positive patients were categorized by age into<45 years(n=23),45-60 years(n=82),60-75 years(n=124),and≥75 years(n=10)to compare SIBO positivity rates across age groups.Results The patients in SIBO-positive and double positive groups were older and had a lower body mass index(BMI)than those in SIBO-negative group,with statistically significant differences(P<0.05).Compared with the patients in SIBO-negative group,those in hydrogen-positive group showed a higher proportion of history of coronary heart disease,those in methanogen-positive group were older,and higher proportion of statin use,with statistically significant differences(P<0.05).Multivariate logistic regression analysis revealed that,among different SIBO types,a history of coronary heart disease served as an independent risk factor for hydrogen-producing bacterial overgrowth(OR=2.728,95%CI 1.271-5.857,P=0.010).For methanogen overgrowth,increasing age was identified as an independent risk factor(OR=1.040,95%CI 1.009-1.063,P=0.010),while the application of statin played the role of an independent protective factor(OR=0.420,95%CI 0.236-0.754,P=0.003).As for the simultaneous overgrowth of methane-producing and hydrogen-producing bacteria,increased BMI was found to be an independent protective factor(OR=0.870,95%CI 0.786-0.964,P=0.008).In SIBO-positive group,it was found that for patients aged<45 years,both the methane-positive rate and the double-positive rate were significantly lower than the hydrogen positivity rate(P<0.05).Moreover,among patients aged 45-60 years,the double-positive rate was significantly lower than the hydrogen positivity rate(P<0.01).When it comes to the hydrogen-positive rate,it was significantly lower for patients aged 45-60 and 60-75 years compared with that of patients aged<45 years(P<0.05).In contrast,the methane-positive rate and the double-positive rate were significantly higher for patients aged 45-60 and 60-75 years than those of patients aged<45 years(P<0.01).Conclusion A history of coronary heart disease and increasing age are independent risk factors for intestinal hydrogen-producing bacterial overgrowth and methanogen overgrowth,respectively.The application of statins and increased BMI are independent protective factors for intestinal methanogen simultaneous overgrowth of methanogen and hydrogen-producing bacteria,respectively.

Objective To explore the clinical characteristics and influencing factors in type 2 diabetes mellitus(T2DM)patients with metabolic-associated fatty liver disease(MAFLD)who are at moderate-to-high risk of metabolic-associated fatty liver fibrosis.Methods A retrospective analysis was conducted on the clinical data of 495 T2DM patients with MAFLD who were treated in the Department of Endocrinology,the Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,from August 2022 to May 2024.According to the fibrosis-4(FIB-4)index,the patients were divided into two groups:low risk group for metabolic-associated fatty liver fibrosis(n=311)and moderate-to-high risk group for metabolic-associated fatty liver fibrosis(n=184).Differences in clinical characteristics and laboratory test results between the two groups were compared.Univariate and multivariate binary logistic regression analyses were used to screen the influencing factors of moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD.Receiver operating characteristic(ROC)curves and area under the curve(AUC)were employed to evaluate the predictive value of these factors for moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD.Results Compared with low risk group,moderate-to-high risk group had significantly higher age,proportions of patients with a history of hypertension and coronary heart disease,as well as higher levels of aspartate aminotransferase(AST),blood urea nitrogen(BUN),and creatinine(Cr)(P<0.05).In contrast,moderate-to-high group had a lower proportion of male patients,and lower levels of platelet count(PLT),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),glycated hemoglobin(HbA1c),free triiodothyronine(FT3),free thyroxine(FT4),and thyroid feedback quantile-based index(TFQI)(P<0.05).Univariate binary logistic regression analysis showed that male(P=0.020),HbA1c(P=0.014),BUN(P<0.001),Cr(P<0.001),TC(P=0.001),LDL-C(P<0.001),FT3(P<0.001),FT4(P<0.001),and TFQI(P=0.039)were influencing factors for moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD.Multivariate binary logistic regression analysis revealed that BUN(OR=1.165,95%CI 1.006-1.348,P=0.042)and Cr(OR=1.020,95%CI 1.005-1.036,P=0.008)were independent risk factors for moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD,while male(OR=0.574,95%CI 0.339-0.972,P=0.039),LDL-C(OR=0.659,95%CI 0.483-0.898,P=0.008),FT3(OR=0.590,95%CI 0.404-0.864,P=0.007),and FT4(OR=0.863,95%CI 0.762-0.977,P=0.020)were independent protective factors.ROC curve analysis showed that the AUC of the combined 6 influencing factors for predicting moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD was 0.728(95%CI 0.682-0.774),with a sensitivity of 0.620 and a specificity of 0.759.Conclusions Gender,BUN,Cr,LDL-C,FT3,and FT4 are independent influencing factors for moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD.Monitoring and early intervention for the above abnormal biochemical indices are beneficial in delaying the occurrence and development of liver fibrosis in T2DM patients with MAFLD.

Objective To investigate the mechanism of hippocampal neuronal plasticity of newborn neurons in the hippocampus by which exercise improves the fear and anxiety symptoms of post-traumatic stress disorder(PTSD).Methods Totally 40 C57BL/6J male mice were randomly divided into by control group(Ctrl)and PTSD group,the PTSD group was divided into a no-exercise group(PTSD),a low-intensity exercise group(L)and a high-intensity exercise group(H).The PTSD model mice were constructed by combining conditioned plantar-foot shock(CF)and single-session sustained stress(SPS).After the exercise intervention,the fear and anxiety levels of the mice were assessed using the conditioned fear test and the elevated cross maze test;Subsequently,the densities of the newborn mature neurons in dentate gyrus(DG)of hippocampus were detected by immunofluorescent double-labelling staining,and the newborn neuron morphology was marked by injecting retrovirus pRetro-U6-EF1-EGFP-3xFLAG-WPRE in DG of hippocampus to observe its morphology.The morphology of the newborn neurons was labelled to observe their dendritic length and the number of branch points;Meanwhile,the concentration level of adiponctin(APN)in the hippocampal area was determined by ELISA.Results The result showed that both high and low-intensity exercise interventions significantly reduced the freezing time of PTSD mice in the conditioned fear test,and in the elevated cross maze experiment,the residence time and the number of entries in the open arm of the mice in the H group increased significantly compared with those in the PTSD group,while the residence time and the number of entries in the closed arm were significantly reduced.In addition,both high and low-intensity exercise interventions significantly increased the surface density and dendritic length of newborn mature neurons in the hippocampal DG region of PTSD mice,and high-intensity exercise significantly increased the number of dendritic branching points,and the density of newborn mature neurons in the H group was more significantly increased compared with that in the L group.At the same time,the hippocampal APN concentration increased significantly in both L and H groups compared with the PTSD group,and it was more significant in the H group.Conclusion Exercises have an ameliorative effect on anxiety and fear symptoms in PTSD mice,and at the same time,it can increase hippocampal neuroplasticity and adiponctin secretion in PTSD mice,suggesting that the improvement of fear and anxiety symptoms in PTSD by exercise may be related to the increase of hippocampal neuroplasticity and APN secretion,and the improvement effect is better with high-intensity exercise.

Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

Abelmoschi Corolla, the dried corolla of Abelmoschus manihot, has anti-inflammatory, antioxidant, and anti-fibrosis activities. Its chemical constituents mainly include flavonoids, organic acids, steroids, and polysaccharides. This study reviewed the research progress in the chemical constituents and pharmacological activities of Abelmoschi Corolla in recent 20 years. According to the concept of quality marker(Q-marker), the Q-markers of Abelmoschi Corolla were predicted from plant phylogeny, chemical constituent specificity, traditional efficacy, chemical constituent measurability, and absorbed constituents. The primary Q-markers for Abelmoschi Corolla were anticipated to include quercetin-3'-O-β-D-glucopyranoside, gossypetin-8-O-β-D-glucuronide, isoquercetin, myricetin,quercetin, and hyperoside, with the aim of providing reference data for improving the quality evaluation system of Abelmoschi Corolla.
Abelmoschus/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Flowers/chemistry* ; Humans ; Animals ; Quality Control ; Flavonoids/chemistry*