Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Objective To explore the protective effect and mechanism of Xinkang Granules-containing serum in adriamycin-induced injury of cardiomyocytes H9C2 based on cGAS-STING signaling axis.Methods Adriamycin was used to induce the H9C2 cells injury model.The cells were divided into normal group,model group,Xinkang Granules group and inhibitor group.After 24 hours of intervention,the CCK-8 method was used to detect cell survival rate,the DCFH-DA fluorescent probe was used to detect the content of cell reactive oxygen species(ROS),cell apoptosis rate was detected by flow cytometry,ELISA was used to detect the content of tumor necrosis factor-α(TNF-α)in cell supernatant,colorimetry was used to detect lactate dehydrogenase(LDH)in cells,RT-qPCR was used to detect the expression of mitochondrial transcription factor A(TFAM),cyclic guanosine-adenylate synthetase(cGAS),stimulator of interferon genes(STING)and TNF-α mRNA,Western blot and immunofluorescence were used to detect the protein expressions of cGAS and STING.Results Compared with the normal group,cell survival rate in the model group was significantly reduced(P<0.01),the ROS content was significantly increased(P<0.01),the apoptosis rate significantly increased(P<0.01),the content of TNF-α in the supernatant significantly increased(P<0.01),the activity of LDH significantly increased(P<0.01),the expression of TFAM mRNA significantly decreased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expression of cGAS and STING significantly increased(P<0.01).Compared with the model group,cell survival rate in Xinkang Granules group and inhibitor group significantly increased(P<0.01),the ROS content significantly decreased(P<0.01),the apoptosis rate significantly decreased(P<0.01),the content of TNF-α in supernatant significantly decreased(P<0.01),the activity of LDH significantly decreased(P<0.01),the expression of TFAM mRNA significantly increased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expressions of cGAS and STING significantly decreased(P<0.05,P<0.01).Conclusion Xinkang Granules have a protective effect on adriamycin-induced H9C2 cardiomyocytes,which may be related to the inhibition of cGAS/STING axis activation and the secretion of inflammatory factors.

The immunosuppressive tumor micro-environment significantly limits the efficacy of im-munotherapy.Tumor-associated macrophages(TAMs),the most abundant immune cells in the tu-mor microenvironment,often exhibit an immuno-suppressive M2 phenotype,contributing to this im-munosuppressive landscape.Modulating TAMs to adopt anti-tumor phenotypes can enhance immu-notherapy outcomes and inhibit tumor progression.In recent years,tumor immunotherapy leveraging engineered bacteria has garnered considerable at-tention.Bacteria possess the ability to target tu-mors,preferentially colonizing tumor regions,and contain abundant pathogen-associated molecular patterns that effectively activate TAMs within the immunosuppressive tumor environment.This acti-vation enhances the tumoricidal and clearance ca-pabilities of TAMs.With the rapid advancements in synthetic biology,engineered bacteria have emerged as a potent therapeutic modality for im-munotherapy,leading to increased focus on the regulation of TAMs by engineered bacteria.This pa-per first outlines clinical studies on targeted TAMs therapy and engineered bacteria-based tumor ther-apy.It then reviews recent advancements in bacte-rial regulation of TAMs,detailing how engineered bacteria enhance TAM recruitment,improve TAM phagocytosis,and remodel TAM phenotypes.Mod-ulating TAMs with engineered bacteria presents a promising therapeutic strategy and introduces a novel approach in tumor immunotherapy.

Objective This study aims to investigate the effects of acupuncture on the spatial learning and memory capacities,the morphological characteristics of hippocampal neurons,the components of extracellular matrix,as well as the structure of the blood-brain barrier in SAMP8 mice.Moreover,it endeavors to explore the underlying mechanism through which the"Tongdu Qishen"(activating governor vessel and awakening spirit)acupuncture method ameliorates the cognitive function and modulates cerebral blood flow in SAMP8 mice.Methods Twenty 6-month-old male SAMP8 mice were randomly allocated into a model group and an electroacupuncture group,with ten mice in each group.Additionally,ten homologous 6-month-old male SAMR1 mice were designated as the normal control group.In the electroacupuncture group,the acupoint"Renzhong"(GV 26)was punctured using a quick insertion technique,while"Baihui"(GV 20)and"Yintang"(EX-HN 3)were punctured via a transverse insertion method.Subsequently,the needle handles were connected to an electroacupuncture apparatus,which was set to operate with a dense-sparse wave at a frequency of 100 Hz/2 Hz and an electric current of 2 mA.Each session of acupuncture lasted for 20 minutes and was conducted once a day for a consecutive period of 28 days.The normal group,the model group,and the electroacupuncture group all underwent identical fixation and restraint procedures to ensure consistent experimental conditions.The Morris water maze was employed to evaluate the spatial learning and memory abilities of the mice.The Nissl staining technique was utilized to assess the alterations in hippocampal neurons of SAMP8 mice.The laser speckle imaging system was adopted to measure the cerebral blood flow of the mice in each group.Transmission electron microscopy was applied to observe the ultrastructure of the blood-brain barrier within the frontal cortex tissue of the SAMP8 mice's brains.The Western blotting method was used to detect the expressions of Collagen-Ⅳ and Fibronectin in the brain tissues of SAMP8 mice.Results In comparison with the model group,the"Tongdu Qishen"acupuncture method demonstrated a significant efficacy in improving the spatial learning and memory abilities of SAMP8 mice(P<0.05).It also effectively alleviated the degeneration of hippocampal neurons,remarkably increased the cerebral blood flow perfusion volume of SAMP8 mice(P<0.05),ameliorated the damage to the blood-brain barrier structure,significantly upregulated the content of Collagen-Ⅳ(P<0.05),and significantly downregulated the content of Fibronectin(P<0.0001).Conclusion The"Tongdu Qishen"acupuncture method is capable of favorably regulating the extracellular matrix of SAMP8 mice,thereby improving cerebral blood flow and ultimately enhancing their learning and memory abilities.

Objective To investigate the in vitro antibacterial effect of Radix Sophorae Flavescentis on tigecycline-resistant carbapenem-resistant Klebsiella pneumonia(CRKP)and elucidate how Radix Sophorae Flavescentis restores the sensitivity of CRKP to tigecycline through the efflux pump pathway.Methods The CRKP standard strain BAA1705 was induced to be tigecycline-resistant using the microdilution broth method,and the expression of efflux pumps was verified by efflux pump inhibitors.The fractional inhibitory concentration index(FIC)was calculated using the microdilution checkerboard method to determine the minimum inhibitory concertration(MIC)of the two drugs in combination.Fluorescent real-time quantitative PCR(qRT-PCR)was used to analyze the expression of the AcrB gene before and after Radix Sophorae Flavescentis treatment,and the e?ux pump activity was validated by the Rhodamine 6G e?ux assay.Results The e?ux pump inhibition experiment on the artificially induced T-BAA1705 strain showed overexpression of e?ux pumps.The combined antibacterial test results indicated synergy between Radix Sophorae Flavescentis and tigecycline(FIC=0.375 2).The qRT-PCR results showed that the AcrB levels in the Radix Sophorae Flavescentis monotherapy group were lower than in the untreated group(0.018±0.002 vs 0.040±0.001),and the AcrB levels(0.009±0.001),RamA levels(0.184±0.003)and MarA(0.013±0.001)levels in the combination therapy group were all lower than in the untreated group(0.040±0.001,0.387±0.016,0.125±0.007),while the AcrR level was higher than in the untreated group(0.388±0.001 vs 0.288±0.001),and the differences were statistical significance(t=12.28～47.12,all P<0.05);the e?ux pump activity in the Radix Sophorae Flavescentis monotherapy group and the combination therapy group was lower than in the untreated T-BAA1705(60.667±0.448,60.267±0.376,65.133±0.296),and the differences were statistical significance(t=8.31,10.17,all P<0.05).Conclusion Radix Sophorae Flavescentis can restore the sensitivity of tigecycline-resistant CRKP to tigecycline and effectively inhibit bacterial growth when used in combination with tigecycline.The mechanism may involve Radix Sophorae Flavescentis inhibiting the expression of the AcrAB-TolC e?ux pump.

The immunosuppressive tumor micro-environment significantly limits the efficacy of im-munotherapy.Tumor-associated macrophages(TAMs),the most abundant immune cells in the tu-mor microenvironment,often exhibit an immuno-suppressive M2 phenotype,contributing to this im-munosuppressive landscape.Modulating TAMs to adopt anti-tumor phenotypes can enhance immu-notherapy outcomes and inhibit tumor progression.In recent years,tumor immunotherapy leveraging engineered bacteria has garnered considerable at-tention.Bacteria possess the ability to target tu-mors,preferentially colonizing tumor regions,and contain abundant pathogen-associated molecular patterns that effectively activate TAMs within the immunosuppressive tumor environment.This acti-vation enhances the tumoricidal and clearance ca-pabilities of TAMs.With the rapid advancements in synthetic biology,engineered bacteria have emerged as a potent therapeutic modality for im-munotherapy,leading to increased focus on the regulation of TAMs by engineered bacteria.This pa-per first outlines clinical studies on targeted TAMs therapy and engineered bacteria-based tumor ther-apy.It then reviews recent advancements in bacte-rial regulation of TAMs,detailing how engineered bacteria enhance TAM recruitment,improve TAM phagocytosis,and remodel TAM phenotypes.Mod-ulating TAMs with engineered bacteria presents a promising therapeutic strategy and introduces a novel approach in tumor immunotherapy.

Objective To investigate the in vitro antibacterial effect of Radix Sophorae Flavescentis on tigecycline-resistant carbapenem-resistant Klebsiella pneumonia(CRKP)and elucidate how Radix Sophorae Flavescentis restores the sensitivity of CRKP to tigecycline through the efflux pump pathway.Methods The CRKP standard strain BAA1705 was induced to be tigecycline-resistant using the microdilution broth method,and the expression of efflux pumps was verified by efflux pump inhibitors.The fractional inhibitory concentration index(FIC)was calculated using the microdilution checkerboard method to determine the minimum inhibitory concertration(MIC)of the two drugs in combination.Fluorescent real-time quantitative PCR(qRT-PCR)was used to analyze the expression of the AcrB gene before and after Radix Sophorae Flavescentis treatment,and the e?ux pump activity was validated by the Rhodamine 6G e?ux assay.Results The e?ux pump inhibition experiment on the artificially induced T-BAA1705 strain showed overexpression of e?ux pumps.The combined antibacterial test results indicated synergy between Radix Sophorae Flavescentis and tigecycline(FIC=0.375 2).The qRT-PCR results showed that the AcrB levels in the Radix Sophorae Flavescentis monotherapy group were lower than in the untreated group(0.018±0.002 vs 0.040±0.001),and the AcrB levels(0.009±0.001),RamA levels(0.184±0.003)and MarA(0.013±0.001)levels in the combination therapy group were all lower than in the untreated group(0.040±0.001,0.387±0.016,0.125±0.007),while the AcrR level was higher than in the untreated group(0.388±0.001 vs 0.288±0.001),and the differences were statistical significance(t=12.28～47.12,all P<0.05);the e?ux pump activity in the Radix Sophorae Flavescentis monotherapy group and the combination therapy group was lower than in the untreated T-BAA1705(60.667±0.448,60.267±0.376,65.133±0.296),and the differences were statistical significance(t=8.31,10.17,all P<0.05).Conclusion Radix Sophorae Flavescentis can restore the sensitivity of tigecycline-resistant CRKP to tigecycline and effectively inhibit bacterial growth when used in combination with tigecycline.The mechanism may involve Radix Sophorae Flavescentis inhibiting the expression of the AcrAB-TolC e?ux pump.

Objective:To explore the aperiodic components(1/f slopes)and their associations with cognitive impairment in patients with schizophrenia.Methods:Nineteen patients with schizophrenia according to the Interna-tional Statistical Classification of Diseases and Related Health Problem,Tenth Revision(ICD-10)and 21 normal controls were administrated the total Brief Assessment of Cognition in Schizophrenia(BACS)to measure the cogni-tive performance.The 5-minute eyes-closed and eyes-open resting EEG signals were collected and parameterized in-to aperiodic components(1/f slope).Finally,Pearson correlation was used to examine the relationships between the 1/f slope and cognition assessment scores.Results:The patients with schizophrenia had higher 1/f slope compared to HC on central location of scalp(P＜0.05).The vocal memory scores showed a significantly positive relation with 1/f slopes in patients with schizophrenia(anterior location:r=-0.68,P＜0.05;central location:r=-0.44,P＜0.05),but a significantly negative relation in normal controls(anterior location:r=0.57,P＜0.05;posterior lo-cation:r=0.54,P＜0.05).Conclusion:The 1/f slopes of EEG in schizophrenia were steeper than normal control,suggesting its strong cognitive functional significance and complex mechanisms in schizophrenia.

Objective Exploring the behavioral changes induced by quinpirole in obsessive-compulsive disorder(OCD)mouse,investigating the activation of neurons in different brain regions,and identifying differentially expressed genes(DEGs)and enriched biological pathways through transcriptome sequencing technology to elucidate the pathogenesis of OCD.Methods Randomly assign 32 male C57BL/6J mice,aged two months,to an OCD group and a control group(n=16).Administering quinpirole(0.75 mg/kg)via subcutaneous injection to the OCD group mice every other day for a total of 19 injections,while the control group mice received an equivalent volume of saline solution.Following the completion of the model construction,open field testing,elevated plus maze testing,and marble burying tests were conducted.After the completion of behavioral studies,tissue samples were collected.Neuronal damage was assessed using Nissl staining,while the expression of c-Fos and Iba1 proteins was examined through immunofluorescence staining.Transcriptome sequencing technology was utilized to screen for differentially expressed genes and to enrich relevant signaling pathways.The expression of inflammatory cytokines,including TNF-α,NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65),and IL-6,was detected using Western Blot analysis.Results Mouse induced with OCD by quinpirole exhibit anxiety-like behaviors and compulsive-like behaviors.Neurons in the hippocampal and hypothalamic regions exhibit signs of damage.The expression of c-Fos and Iba1 proteins is increased in the cortex,striatum,hypothalamus,and other brain regions.Western Blot result indicate a significant increase in the expression of pro-inflammatory cytokines such as TNF-α,p-NF-κB p65,and IL-6.Conclusions In OCD mouse,neurons in multiple brain regions are abnormally activated,microglia exhibit dysfunction,and neuroinflammation induced by the activation of the NF-κB signaling pathway accompanies the development of OCD.