The relationship between openness and social anxiety: the chain mediating roles of social networking site use and self-evaluation.

BACKGROUND: As social networking sites (SNSs) with diverse functions gradually become an important social place for modern people, openness, as a personality trait that represents the willingness to consider diverse things, will be more likely to affect people's cognitive and emotional experience (e.g., social anxiety) in social interactions. This study examined the relationship between openness and social anxiety and the underlying psychological mechanism in the internet age based on the cognitive-behavioral model of social anxiety. METHODS: This cross­sectional survey study conducted a questionnaire survey of 522 college students from two provinces in China (191 male; age range 18-25; M = 20.76, SD = 1.34). RESULTS: The results showed that openness is negatively related to social anxiety. Self-evaluation and passive SNS use independently mediate the relationship between openness and social anxiety, respectively. Moreover, openness is associated with social anxiety both through the chain mediating roles of active SNS use and self-evaluation and through the chain mediating roles of passive SNS use and self-evaluation. CONCLUSIONS: Openness is negatively associated with social anxiety, and the different ways of SNS use and self-evaluation are the underlying mechanisms. These results provide insights into the clinical treatment of social anxiety and how to benefit from online interactions.

Hepatic Stellate Cell- and Liver Microbiome-Specific Delivery System for Dihydrotanshinone I to Ameliorate Liver Fibrosis.

Liver fibrosis is a major contributor to the morbidity and mortality associated with liver diseases, yet effective treatment options remain limited. Hepatic stellate cells (HSCs) are a promising target for hepatic fibrogenesis due to their pivotal role in disease progression. Our previous research has demonstrated the potential of Dihydrotanshinone I (DHI), a lipophilic component derived from the natural herb Salvia miltiorrhiza Bunge, in treating liver fibrosis by inhibiting the YAP/TEAD2 interaction in HSCs. However, the clinical application of DHI faces challenges due to its poor aqueous solubility and lack of specificity for HSCs. Additionally, recent studies have implicated the impact of liver microbiota, distinct from gut microbiota, on the pathogenesis of liver diseases. In this study, we have developed an HSC- and microbiome-specific delivery system for DHI by conjugating prebiotic-like cyclodextrin (CD) with vitamin A, utilizing PEG2000 as a linker (VAP2000@CD). Our results demonstrate that VAP2000@CD markedly enhances the cellular uptake in human HSC line LX-2 and enhances the deposition of DHI in the fibrotic liver in vivo. Subsequently, intervention with DHI-VAP2000@CD has shown a notable reduction in bile duct-like structure proliferation, collagen accumulation, and the expression of fibrogenesis-associated genes in rats subjected to bile duct ligation. These effects may be attributed to the regulation of the YAP/TEAD2 interaction. Importantly, the DHI-VAP2000@CD intervention has also restored microbial homeostasis in the liver, promoting the amelioration of liver inflammation. Overall, our findings indicate that DHI-VAP2000@CD represents a promising therapeutic approach for liver fibrosis by specifically targeting HSCs and restoring the liver microbial balance.

Role of Guanxi (interpersonal relationship) in bribe-taking behaviors: evidence from China.

Bribery, an illegal conspiracy between two transactional parties, has a wide range of destructive effects on society. From an interpersonal interaction perspective, we explored how Guanxi (interpersonal relationships, including direct and indirect ones) influences individuals, especially government officials' bribe-taking probability, using behavioral experiments and questionnaires. The findings suggested that direct Guanxi promoted individuals' acceptance of bribes (Study 1a), and indirect Guanxi had the same role and effect sizes (Study 1b). However, the mechanisms were slightly different. Government officials were more likely to accept bribes from family members and friends (direct Guanxi) (than strangers) because they had more trust and felt more responsible and obligated to help them (Study 2). However, accepting bribes from those who contacted them through their family or friends (indirect Guanxi) (vs. strangers) was only driven by trust (Study 3). The present study explores the lubricant role of Guanxi in corruption, extends the literature on why bribery occurs from a new perspective, and provides suggestions for fighting corruption.

Neural correlates of bribe-taking decision dilemma: An fNIRS study.

Bribe-taking decision is a social dilemma for individuals: the pursuit of economic self-interest vs. compliance with social norms. Despite the well-known existence of the conflict in deciding whether to accept bribes, little is known about its neural responses. Using functional near-infrared imaging (fNIRS) technology and the bribe-taking decision game (economic gambling game as a control condition), the current study dissociated the neural correlates of the different motivations in the bribery dilemma, as well as the inhibitory effect of social norms on bribery and its underlying brain mechanisms in supra-cortical regions. Findings revealed that if individuals are more motivated by economic interest, rejecting money (vs. accepting money) accompanies higher activity in the dorsolateral prefrontal cortex (DLPFC) and frontopolar cortex (FPC), which reflects impulse inhibition and decision evaluation; whereas, if individuals are more consider social norms, their DLPFC is more active when they accept bribes (vs. reject bribes), which reflects their fear of punishment. Additionally, the key brain region where social norms inhibit bribery involves the left DLPFC. The current findings contribute to the literature on the neural manifestations of corrupt decisions and provide some insights into the anti-corruption movement.

New IMB16-4 Nanoparticles Improved Oral Bioavailability and Enhanced Anti-Hepatic Fibrosis on Rats.

Liver fibrosis is challenging to treat because of the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamido) benzamide referred to as IMB16-4. However, its poor aqueous solubility and poor oral bioavailability obstruct the drug discovery programs. To increase the dissolution, improve the oral bioavailability and enhance the antifibrotic activity of IMB16-4, PVPK30 was selected to establish the IMB16-4 nanoparticles. Drug release behavior, oral bioavailability, and anti-hepatic fibrosis effects of IMB16-4 nanoparticles were evaluated. The results showed that IMB16-4 nanoparticles greatly increased the dissolution rate of IMB16-4. The oral bioavailability of IMB16-4 nanoparticles was improved 26-fold compared with that of pure IMB16-4. In bile duct ligation rats, IMB16-4 nanoparticles significantly repressed hepatic fibrogenesis and improved the liver function. These findings indicate that IMB16-4 nanoparticles will provide information to expand a novel anti-hepatic fibrosis agent.

Gene expression in human umbilical vein endothelial cells exposed to fine particulate matter: RNA sequencing analysis.

Exposure to airborne particulate matter (PM2.5) is associated with cardiovascular diseases. In order to investigate the molecular mechanisms of air pollution-induced CVDs toxicity, human umbilical vein endothelial cells (HUVECs) were exposed to PM2.5 collected from January, 2016 winter in Beijing, China. We performed RNA sequencing to elucidate key molecular mechanism of PM 2.5-mediated toxicity in HUVECs. A total of 1753 genes, 864 up-regulated and 889 down-regulated, were observed to be differentially expressed genes (DEGs). Among these, genes involved in metabolic response, oxidative stress, inflammatory response, and vascular dysfunction were significantly differentially expressed (log2 FC > 4). The results were validated by quantitative real-time PCR (qPCR) and Western blot for CYP1B1, HMOX1, IL8, and GJA4. Pathway analysis revealed that DEGs were involved in the biological processes related to metabolism, inflammation, and host defense against environmental insults. This research is providing a further understanding of the mechanisms underlying PM2.5-induced cardiovascular diseases (CVDs).

Costunolide Loaded in pH-Responsive Mesoporous Silica Nanoparticles for Increased Stability and an Enhanced Anti-Fibrotic Effect.

Liver fibrosis remains a significant public health problem. However, few drugs have yet been validated. Costunolide (COS), as a monomeric component of the traditional Chinese medicinal herb Saussurea Lappa, has shown excellent anti-fibrotic efficacy. However, COS displays very poor aqueous solubility and poor stability in gastric juice, which greatly limits its application via an oral administration. To increase the stability, improve the dissolution rate and enhance the anti-liver fibrosis of COS, pH-responsive mesoporous silica nanoparticles (MSNs) were selected as a drug carrier. Methacrylic acid copolymer (MAC) as a pH-sensitive material was used to coat the surface of MSNs. The drug release behavior and anti-liver fibrosis effects of MSNs-COS-MAC were evaluated. The results showed that MSNs-COS-MAC prevented a release in the gastric fluid and enhanced the dissolution rate of COS in the intestinal juice. At half the dose of COS, MSNs-COS-MAC still effectively ameliorated parenchymal necrosis, bile duct proliferation and excessive collagen. MSNs-COS-MAC significantly repressed hepatic fibrogenesis by decreasing the expression of hepatic fibrogenic markers in LX-2 cells and liver tissue. These results suggest that MSNs-COS-MAC shows great promise for anti-liver fibrosis treatment.

Faecal bile acids and colonic bile acid membrane receptor correlate with symptom severity of diarrhoea-predominant irritable bowel syndrome: A pilot study.

AIMS: To compare both the faecal bile acids (BAs) and the levels of two bile acid receptors, Takeda G protein-coupled receptor 5 (TGR5) and vitamin D receptor (VDR), in the colonic mucosa between patients with irritable bowel syndrome with predominant diarrhea (IBS-D) and healthy controls, and explore the correlations among clinical characteristics, bile acid receptors expression, and BAs. METHODS: The severity of abdominal pain and diarrhoea was assessed in IBS-D patients using validated questionnaires, faecal BAs were measured by ultraperformance liquid chromatography coupled to tandem mass spectrometry, and rectosigmoid biopsies were taken for the analyses of TGR5 and VDR expression using immunohistochemistry. RESULTS: The level of TGR5 immunoreactivity in rectosigmoid mucosal biopsies was significantly higher in IBS-D patients than in controls, while the VDR immunoreactivity displayed no significant difference between patients and controls. The patients with more severe or more frequent abdominal pain had significantly higher TGR5 level. Faecal primary BAs were significantly increased in IBS-D patients and were positively correlated with the severity of diarrhoea. The level of TGR5 was positively associated with primary BAs and negatively associated with secondary BAs among all participants providing both mucosal and stool samples. CONCLUSIONS: Colonic mucosal TGR5 protein expression and faecal bile acids were correlated with the symptom severity of IBS-D patients.

Novel IMB16-4 Compound Loaded into Silica Nanoparticles Exhibits Enhanced Oral Bioavailability and Increased Anti-Liver Fibrosis In Vitro.

BACKGROUND: Liver fibrosis, as a common and refractory disease, is challenging to treat due to the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamide) benzamide (IMB16-4), which is expected to have good potential effects against liver fibrosis. However, IMB16-4 is water-insoluble and has very low bioavailability. METHODS: Mesoporous silica nanoparticles (MSNs) were selected as drug carriers for the purpose of increasing the dissolution of IMB16-4, as well as improving its oral bioavailability and inhibiting liver fibrosis. The physical states of IMB16-4 and IMB16-4-MSNs were investigated using nitrogen adsorption, thermogravimetric analysis (TGA), HPLC, UV-Vis, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). RESULTS: The results show that MSNs enhanced the dissolution rate of IMB16-4 significantly. IMB16-4-MSNs reduced cytotoxicity at high concentrations of IMB16-4 on human hepatic stellate cells LX-2 cells and improved oral bioavailability up to 530% compared with raw IMB16-4 on Sprague-Dawley (SD) rats. In addition, IMB16-4-MSNs repressed hepatic fibrogenesis by decreasing the expression of hepatic fibrogenic markers, including α-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-ß1) and matrix metalloproteinase-2 (MMP2) in LX-2 cells. CONCLUSIONS: These results provided powerful information on the use of IMB16-4-MSNs for the treatment of liver fibrosis in the future.

Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Bile acids (BAs) have attracted attention in the research of irritable bowel syndrome with predominant diarrhea (IBS-D) due to their ability to modulate bowel function and their tight connection with the gut microbiota. The composition of the fecal BA pool in IBS-D patients is reportedly different from that in healthy populations. We hypothesized that BAs may participate in the pathogenesis of IBS-D and the altered BA profile may be correlated with the gut microbiome. AIM: To investigate the role of BAs in the pathogenesis of IBS-D and the correlation between fecal BAs and gut microbiota. METHODS: Fifty-five IBS-D patients diagnosed according to the Rome IV criteria and twenty-eight age-, sex-, and body mass index-matched healthy controls (HCs) were enrolled in this study at the gastroenterology department of China-Japan Friendship Hospital. First, clinical manifestations were assessed with standardized questionnaires, and visceral sensitivity was evaluated via the rectal distension test using a high-resolution manometry system. Fecal primary BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA), secondary BAs including deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) as well as the corresponding tauro- and glyco-BAs were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry. The gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between fecal BAs with clinical features and gut microbiota were explored. RESULTS: Fecal CA (IBS-D: 3037.66 [282.82, 6917.47] nmol/g, HC: 20.19 [5.03, 1304.28] nmol/g; P < 0.001) and CDCA (IBS-D: 1721.86 [352.80, 2613.83] nmol/g, HC: 57.16 [13.76, 1639.92] nmol/g; P < 0.001) were significantly increased, while LCA (IBS-D: 1621.65 [58.99, 2396.49] nmol/g, HC: 2339.24 [1737.09, 2782.40]; P = 0.002] and UDCA (IBS-D: 8.92 [2.33, 23.93] nmol/g, HC: 17.21 [8.76, 33.48] nmol/g; P = 0.025) were significantly decreased in IBS-D patients compared to HCs. Defecation frequency was positively associated with CA (r = 0.294, P = 0.030) and CDCA (r = 0.290, P = 0.032) and negatively associated with DCA (r = -0.332, P = 0.013) and LCA (r = -0.326, P = 0.015) in IBS-D patients. In total, 23 of 55 IBS-D patients and 15 of 28 HCs participated in the visceral sensitivity test. The first sensation threshold was negatively correlated with CDCA (r = -0.459, P = 0.028) in IBS-D patients. Furthermore, the relative abundance of the family Ruminococcaceae was significantly decreased in IBS-D patients (P < 0.001), and 12 genera were significantly lower in IBS-D patients than in HCs (P < 0.05), with 6 belonging to Ruminococcaceae. Eleven of these genera were negatively correlated with primary BAs and positively correlated with secondary BAs in all subjects. CONCLUSION: The altered metabolism of BAs in the gut of IBS-D patients was associated with diarrhea and visceral hypersensitivity and might be ascribed to dysbiosis, especially the reduction of genera in Ruminococcaceae.

Effects of DNA Damage and Oxidative Stress in Human Bronchial Epithelial Cells Exposed to PM2.5 from Beijing, China, in Winter.

Epidemiological studies have corroborated that respiratory diseases, including lung cancer, are related to fine particulate matter (<2.5 µm) (PM2.5) exposure. The toxic responses of PM2.5 are greatly influenced by the source of PM2.5. However, the effects of PM2.5 from Beijing on bronchial genotoxicity are scarce. In the present study, PM2.5 from Beijing was sampled and applied in vitro to investigate its genotoxicity and the mechanisms behind it. Human bronchial epithelial cells 16HBE were used as a model for exposure. Low (67.5 µg/mL), medium (116.9 µg/mL), and high (202.5 µg/mL) doses of PM2.5 were used for cell exposure. After PM2.5 exposure, cell viability, oxidative stress markers, DNA (deoxyribonucleic acid) strand breaks, 8-OH-dG levels, micronuclei formation, and DNA repair gene expression were measured. The results showed that PM2.5 significantly induced cytotoxicity in 16HBE. Moreover, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and cellular heme oxygenase (HO-1) were increased, and the level of glutathione (GSH) was decreased, which represented the occurrence of severe oxidative stress in 16HBE. The micronucleus rate was elevated, and DNA damage occurred as indicators of the comet assay, γ-H2AX and 8-OH-dG, were markedly enhanced by PM2.5, accompanied by the influence of 8-oxoguanine DNA glycosylase (OGG1), X-ray repair cross-complementing gene 1 (XRCC1), and poly (ADP-ribose) polymerase-1 (PARP1) expression. These results support the significant role of PM2.5 genotoxicity in 16HBE cells, which may occur through the combined effect on oxidative stress and the influence of DNA repair genes.

Mitochondrial dysfunction in endothelial cells induced by airborne fine particulate matter (<2.5 µm).

Exposure to ambient fine particulate matter (<2.5 µm; PM2.5 ) increases the risk of the physiopathology of vascular diseases. However, the underlying mechanism, particularly the mitochondrial damage mechanism, of PM2.5 -induced vascular dysfunction is still unclear. In this study, we examined PM2.5 -induced alterations of mitochondrial morphology, and further demonstrated the adverse effects on mitochondrial dynamics and function in vascular endothelial cells. Consequently, cultured EA.hy926 cells were subjected to PM2.5 collected from Beijing. A Cell Counting Assay Kit-8 demonstrated that PM2.5 exposure decreased the proliferation of EA.hy926 cells in a dose-dependent manner. The exposure caused an increment of abnormal mitochondria coupled with the decrease of fusion protein MFN2 and the increase of fission protein FIS1, suggesting that PM2.5 inhibits mitochondrial fusion. Further analyses revealed PM2.5 decreased the mitochondrial membrane potential (ΔΨm) and increased the mitochondrial permeability transport pore opening, eventually resulting in impairments in adenosine triphosphate synthesis. Therefore, it is clearly shown that PM2.5 triggered endothelial toxicity through mitochondria as the target, including the damage of mitochondrial homeostasis.