Formation and Trend of Guanxi Practice and Guanxi Phenomenon

Abstract: With the increase of interactions between Chinese and international communities, guanxi, a Chinese term, has catching more and more attentions from non-Chinese speaking people. Guanxi, from a sociological perspective, is formed on the ascribed, social or third party bases through the mechanism of ganqing and renqing. Different from other scholars, the authors consider guanxi phenomenon is an outcome of co-impacts from Confucianism and institutionalization of material factors and structural factors. It is argued that guanxi phenomenon will decline in future China gradually because of rationalization required by capitalism but will not disappear completely due to human nature and cultural nature

Brief Report: Evidence of Ingroup Bias on the Shooter Task in a Saudi Sample

When predominantly White participants in Western countries are asked to shoot individuals in a computer game who may carry weapons, they show a greater bias to shoot at outgroup members and people stereotyped as dangerous. The goal was to determine the extent to which shooter biases in the Middle East would vary as a function of target ethnicity and culturally appropriate or inappropriate headgear. Within a sample of 37 male Saudi Arabian residents, we examined shooter biases outside of Western nations for the first time. Targets in this task were either White or Middle Eastern in appearance, and wore either American style baseball caps or a Saudi Arabian style shemagh and igal. Our results replicated the bias to shoot racial outgroup members observed in Western samples; we found a bias to shoot White over Middle Eastern targets. Unexpectedly, we also found a bias for Saudi participants to shoot at people wearing culturally appropriate traditional Saudi headgear over Western style baseball caps. To explain this latter finding, we cautiously speculate that relative perceptions of dangerousness in the Middle East may be influenced by media exposure and changing social conditions in the region

Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.

PurposeTumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL).Patients and methodsTavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.v.) was administered every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST, secondary endpoints included duration of response, overall survival and progression-free survival. Toxicity was evaluated by the CTCAE v4. Extensive correlative analysis was done.ResultsThe combination of tavo and pembrolizumab was well tolerated with adverse events similar to those previously reported with pembrolizumab alone. Patients had a 41% ORR (n = 22, RECIST 1.1) with 36% complete responses. Correlative analysis showed that the combination enhanced immune infiltration and sustained the IL-12/IFNγ feed-forward cycle, driving intratumoral cross-presenting dendritic cell subsets with increased TILs, emerging T cell receptor clones and, ultimately, systemic cellular immune responses.ConclusionsThe combination of tavo and pembrolizumab was associated with a higher than expected response rate in this poorly immunogenic population. No new or unexpected toxicities were observed. Correlative analysis showed T cell infiltration with enhanced immunity paralleling the clinical activity in low cpCTL tumors

Defective sphingosine-1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation

Sphingosine-1-phosphate (S1P) signaling regulates lymphocyte egress from lymphoid organs into systemic circulation. Sphingosine phosphate receptor 1 (S1P1) agonist, FTY-720 (Gilenya™) arrests immune trafficking and prevents multiple sclerosis (MS) relapses. However, alternative mechanisms of S1P-S1P1 signaling have been reported. Phosphoproteomic analysis of MS brain lesions revealed S1P1 phosphorylation on S351, a residue crucial for receptor internalization. Mutant mice harboring a S1pr1 gene encoding phosphorylation-deficient receptors [S1P1(S5A)] developed severe experimental autoimmune encephalomyelitis (EAE) due to T helper (TH) 17-mediated autoimmunity in the peripheral immune and nervous system. S1P1 directly activated Janus-like kinase–signal transducer and activator of transcription 3 (JAK-STAT3) pathway via interleukin 6 (IL-6). Impaired S1P1 phosphorylation enhances TH17 polarization and exacerbates autoimmune neuroinflammation. These mechanisms may be pathogenic in MS

Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy

Checkpoint blockade immunotherapies can be extraordinarily effective, but might benefit only the minority of patients whose tumors are pre-infiltrated by T cells. Here, using lung adenocarcinoma mouse models, including genetic models, we show that autochthonous tumors that lacked T cell infiltration and resisted current treatment options could be successfully sensitized to host antitumor T cell immunity when appropriately selected immunogenic drugs (e.g., oxaliplatin combined with cyclophosphamide for treatment against tumors expressing oncogenic Kras and lacking Trp53) were used. The antitumor response was triggered by direct drug actions on tumor cells, relied on innate immune sensing through toll-like receptor 4 signaling, and ultimately depended on CD8 + T cell antitumor immunity. Furthermore, instigating tumor infiltration by T cells sensitized tumors to checkpoint inhibition and controlled cancer durably. These findings indicate that the proportion of cancers responding to checkpoint therapy can be feasibly and substantially expanded by combining checkpoint blockade with immunogenic drugs

Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3–8.9 μM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity–dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.Charles A. Dana Foundation. Brain and Immuno-ImagingRaymond and Beverley Sackler FoundationNational Institutes of Health (U.S.) (grant R01-DA28299)National Institutes of Health (U.S.) (grant DP2-OD2441)National Institutes of Health (U.S.) (grant R01-GM068664)Jacobs Institute for Molecular Engineering for Medicine. Jacobs Institute for Molecular Engineering for MedicineNational Institutes of Health (U.S.) (grant R01-DE013023

Exploring Loneliness: The Effects of Self-consciousness and Other Intrapersonal Factors

Loneliness is a feeling of deprivation and dissatisfaction produced by a discrepancy between the kind of social relations we want and the kind or social relations we have, and it affects millions of people. The literature suggests relationships between loneliness and interpersonal factors associated with poor quality relationships, such as social skills deficits; however, little research attention has been focused on the intrapersonal factors associated with loneliness. The current study is an exploratory investigation of the factors. It was specifically hypothesized that loneliness would be associated with various forms of self-consciousness. Additionally, because previous research on gender differences in relationships suggests that women invest more of themselves in social thinking, we predicted these relationships to be stronger for females. A sample of 122 college students (25 males, 97 females) was used. Participants completed basic demographic questions as well as several measures of loneliness and self-consciousness, including: the UCLA Loneliness Scale (revised version), The Self-Consciousness Scale, and the Imaginary Audience Scale. Correlational analyses were conducted separately for males and females. For females, the results showed significant relationships between loneliness and public and private self-consciousness, social anxiety and the imaginary audience phenomenon. For males, loneliness was related to social anxiety and aspects of the imaginary audience phenomenon, but not to private or public self-consciousness

ER stress in dendritic cells promotes cancer

XBP1 is part of the ER stress response, and when activated in cancer cells, it fosters tumor growth. In this issue of Cell, Cubillos-Ruiz et al. demonstrate that XBP1 in tumor-infiltrating dendritic cells blunts anti-tumor immunity. These findings further imply XBP1 as a relevant target for cancer therapy

Common TLR5 mutations control cancer progression

The mechanisms regulating tumor-associated inflammation are incompletely understood. In this issue of Cancer Cell, Rutkowski and colleagues indicate that TLR5 signaling deficiency, which occurs in ∼10% of the population, changes interactions with commensal microbiota and deregulates a cascade of inflammatory events that can suppress or accelerate extraintestinal cancers

Mental and Physical Health Predictors After Romantic Betrayal

Participants were 123 victims of romantic betrayal (55 males/68 females, mean age = 34.8 years) who volunteered to be in the study in exchange for monetary compenation. Each completed a questionnaire that asked participants to describe their worst experience as a victim of romantic betrayal, and to complete a widely used measure of adult attachment (Hazan & Shaver, 1987) and a checklist of mental/physical health symptoms experienced within the first month after betrayal. Participants were divided into three groups based on the attachment measure, yielding groups of avoidantly attached (those who feel very uncomfortable with intimacy and lack basic trust in others), anxious-ambivalently attached (those who are nervous about intimacy but seek it anyway to quell their doubts), and securely attached individuals (those who are comfortable with intimacy and trusting of their partners). Using a multivariate analysis of variance (MANOVA) technique, the three groups were compared to determine if attachment style was related to the number of mental and physical health symptoms reported by victims. Results indicated that securely attached individuals reported significantly fewer symptoms of major depression and serious anxiety reactions after betrayal, as well as fewer physical health symptoms, than those who were avoidantly attached. Implications for identification and treatment of individuals who are at risk for mental and physical health problems after betrayal will be discussed