Snake fang-inspired stamping patch for transdermal delivery of liquid formulations

A flexible microneedle patch that can transdermally deliver liquid-phase therapeutics would enable direct use of existing, approved drugs and vaccines, which are mostly in liquid form, without the need for additional drug solidification, efficacy verification, and subsequent approval. Specialized dissolving or coated microneedle patches that deliver reformulated, solidified therapeutics have made considerable advances; however, microneedles that can deliver liquid drugs and vaccines still remain elusive because of technical limitations. Here, we present a snake fang-inspired microneedle patch that can administer existing liquid formulations to patients in an ultrafast manner (< 15 s). Rear-fanged snakes have an intriguing molar with a groove on the surface, which enables rapid and efficient infusion of venom or saliva into prey. Liquid delivery is based on surface tension and capillary action. The microneedle patch uses multiple open groove architectures that emulate the grooved fangs of rear-fanged snakes: Similar to snake fangs, the microneedles can rapidly and efficiently deliver diverse liquid-phase drugs and vaccines in seconds under capillary action with only gentle thumb pressure, without requiring a complex pumping system. Hydrodynamic simulations show that the snake fang-inspired open groove architectures enable rapid capillary force-driven delivery of liquid formulations with varied surface tensions and viscosities. We demonstrate that administration of ovalbumin and influenza virus with the snake fang-inspired microneedle patch induces robust antibody production and protective immune response in guinea pigs and mice

Syndecan transmembrane domain specifically regulates downstream signaling events of the transmembrane receptor cytoplasmic domain

Despite the known importance of the transmembrane domain (TMD) of syndecan receptors in cell adhesion and signaling, the molecular basis for syndecan TMD function remains un-known. Using in vivo invertebrate models, we found that mammalian syndecan-2 rescued both the guidance defects in C. elegans hermaphrodite-specific neurons and the impaired development of the midline axons of Drosophila caused by the loss of endogenous syndecan. These compensatory ef-fects, however, were reduced significantly when syndecan-2 dimerization-defective TMD mutants were introduced. To further investigate the role of the TMD, we generated a chimera, 2eTPC, com-prising the TMD of syndecan-2 linked to the cytoplasmic domain of platelet-derived growth factor receptor (PDGFR). This chimera exhibited SDS-resistant dimer formation that was lost in the corre-sponding dimerization-defective syndecan-2 TMD mutant, 2eT(GL)PC. Moreover, 2eTPC specifically enhanced Tyr 579 and Tyr 857 phosphorylation in the PDGFR cytoplasmic domain, while the TMD mutant failed to support such phosphorylation. Finally, 2eTPC, but not 2eT(GL)PC, induced phosphorylation of Src and PI3 kinase (known downstream effectors of Tyr 579 phosphorylation) and promoted Src-mediated migration of NIH3T3 cells. Taken together, these data suggest that the TMD of a syndecan-2 specifically regulates receptor cytoplasmic domain function and subsequent downstream signaling events controlling cell behavior. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.1

Defective Localization With Impaired Tumor Cytotoxicity Contributes to the Immune Escape of NK Cells in Pancreatic Cancer Patients

Tumor-infiltrating lymphocytes (TILs), found in patients with advanced pancreatic ductal adenocarcinoma (PDAC), are shown to correlate with overall survival (OS) rate. Although majority of TILs consist of CD8+/CD4+ T cells, the presence of NK cells and their role in the pathogenesis of PDAC remains elusive. We performed comprehensive analyses of TIL, PBMC, and autologous tumor cells from 80 enrolled resectable PDAC patients to comprehend the NK cell defects within PDAC. Extremely low frequencies of NK cells (<0.5%) were found within PDAC tumors, which was attributable not to the low expression of tumor chemokines, but to the lack of chemokine receptor, CXCR2. Forced expression of CXCR2 in patients' NK cells rendered them capable of trafficking into PDAC. Furthermore, NK cells exhibited impaired cell-mediated killing of autologous PDAC cells, primarily due to insufficient ligation of NKG2D and DNAM-1, and failed to proliferate within the hypoxic tumor microenvironment. Importantly, these defects could be overcome by ex-vivo stimulation of NK cells from such patients. Importantly, when the proliferative capacity of NK cells in vitro was used to stratify patients on the basis of cell expansion, patients whose NK cells proliferated <250-fold experienced significantly lower DFS and OS than those with ≥250-fold. Ex-vivo activation of NK cells restored tumor trafficking and reactivity, hence provided a therapeutic modality while their fold expansion could be a potentially significant prognostic indicator of OS and DFS in such patients

The Role of Cultural Heterogeneity in Strengthening the Link Between Family Relationships and Life Satisfaction in 50 Societies

We argue that the importance of family relationships for individual well-being varies across societies as a function of a society’s degree of cultural heterogeneity. To examine the role of family relationships, we analyzed the responses from 13,009 participants in 50 societies on their life satisfaction across societies varying in their levels of historical and contemporary cultural heterogeneity. Such heterogeneity creates differences in the frequency of interacting with unfamiliar groups, which leads families to become more central to their members’ satisfaction with life. Multi-level analyses showed that historical and contemporary cultural heterogeneity moderated the pattern such that greater historical or contemporary cultural heterogeneity of society promoted a stronger positive relation between family relationship satisfaction and individual life satisfaction. Our results also revealed that the moderating role of historical cultural heterogeneity was more reliable than that of contemporary cultural heterogeneity. These findings demonstrate the importance of societal demography in shaping people’s psychological processes in different historical periods, suggesting a universal, trans-historical cultural process

The role of cultural heterogeneity in strengthening the link between family relationships and life satisfaction in 50 societies

We argue that the importance of family relationships for individual well-being varies across societies as a function of a society’s degree of cultural heterogeneity. To examine the role of family relationships, we analyzed the responses from 13,009 participants in 50 societies on their life satisfaction across societies varying in their levels of historical and contemporary cultural heterogeneity. Such heterogeneity creates differences in the frequency of interacting with unfamiliar groups, which leads families to become more central to their members’ satisfaction with life. Multi-level analyses showed that historical and contemporary cultural heterogeneity moderated the pattern such that greater historical or contemporary cultural heterogeneity of society promoted a stronger positive relation between family relationship satisfaction and individual life satisfaction. Our results also revealed that the moderating role of historical cultural heterogeneity was more reliable than that of contemporary cultural heterogeneity. These findings demonstrate the importance of societal demography in shaping people’s psychological processes in different historical periods, suggesting a universal, trans-historical cultural process.info:eu-repo/semantics/publishedVersio

Personal Relative Deprivation and Locus of Control

We investigated the relationship between personal relative deprivation (PRD)—resentment from the belief that one is worse off than people who are similar to oneself—and locus of control. Research has yet to comprehensively investigate whether PRD is associated with a tendency to favor external (vs.internal) explanations for self- and other-relevant outcomes. Eight studies (Ntotal = 6729) employed cross-sectional, experimental, and (micro)longitudinal designs and used established trait and state measures of PRD and loci of control. Participants higher in PRD adopted more external (vs. internal) explanations for others' outcomes while controlling for socio- demographics (e.g., socioeconomic status; Studies 1–4). This relationship was mediated by a lowered sense of personal control (Study 1) and evident in a cross-national sample of participants in Asia (Study 2). PRD is more robustly associated with external than internal explanations for self and other-relevant outcomes (Studies 5–8), and within-person changes in PRD are positively associated with within-person changes in external explanations (month-to-month and day-to-day; Studies 7–8). Findings indicate that PRD is positively associated with external locus of control independent of socioeconomic status, within and between people, and across cultures. This research highlights the implications of PRD for people's construal of the causal forces that govern their lives

The misasandry myth: An inaccurate stereotype about feminists' attitudes toward men

In six studies, we examined the accuracy and underpinnings of the damaging stereotype that feminists harbor negative attitudes toward men. In Study 1 (n = 1,664), feminist and nonfeminist women displayed similarly positive attitudes toward men. Study 2 (n = 3,892) replicated these results in non-WEIRD countries and among male participants. Study 3 (n = 198) extended them to implicit attitudes. Investigating the mechanisms underlying feminists’ actual and perceived attitudes, Studies 4 (n = 2,092) and 5 (nationally representative UK sample, n = 1,953) showed that feminists (vs. nonfeminists) perceived men as more threatening, but also more similar, to women. Participants also underestimated feminists’ warmth toward men, an error associated with hostile sexism and a misperception that feminists see men and women as dissimilar. Random-effects meta-analyses of all data (Study 6, n = 9,799) showed that feminists’ attitudes toward men were positive in absolute terms and did not differ significantly from nonfeminists'. An important comparative benchmark was established in Study 6, which showed that feminist women's attitudes toward men were no more negative than men's attitudes toward men. We term the focal stereotype the misandry myth in light of the evidence that it is false and widespread, and discuss its implications for the movement

Societal emotional environments and cross-cultural differences in life satisfaction: A forty-nine country study.

In this paper, we introduce the concept of ‘societal emotional environment’: the emotional climate of a society (operationalized as the degree to which positive and negative emotions are expressed in a society). Using data collected from 12,888 participants across 49 countries, we show how societal emotional environments vary across countries and cultural clusters, and we consider the potential importance of these differences for well-being. Multilevel analyses supported a ‘double-edged sword’ model of negative emotion expression, where expression of negative emotions predicted higher life satisfaction for the expresser but lower life satisfaction for society. In contrast, partial support was found for higher societal life satisfaction in positive societal emotional environments. Our study highlights the potential utility and importance of distinguishing between positive and negative emotion expression, and adopting both individual and societal perspectives in well-being research. Individual pathways to happiness may not necessarily promote the happiness of others

Family first: Evidence of consistency and variation in the value of family versus personal happiness across 49 different cultures

People care about their own well-being, but also about the well-being of their families. It is currently however unknown how much people tend to value their own and their family’s well-being. A recent study documented that people value family happiness over personal happiness across four cultures. In this study, we sought to replicate this finding across a larger sample size (N = 12,819) and a greater number of countries (N = 49), We found that the strength of the idealization of family over personal happiness preference was small (average Cohen’s ds = .20 with country levels varying from -.02 to almost .48), but ubiquitous, i.e., direction presented in 98% of the studied countries, 73-75% with statistical significance and .40 and .30). Importantly, we did not find strong support for traditional theories in cross-cultural psychology that associate collectivism with greater prioritization of the family versus the individual; country level individualism-collectivism was not associated with variation in the idealization of family versus individual happiness. Our findings indicate that no matter how much various populists abuse the argument of “protecting family life” to disrupt emancipation, family happiness seems to be a pan-culturally phenomenon. Family well-being is a key ingredient of social fabric across the world, and should be acknowledged by psychology and well-being researchers, and by progressive movements too

Personal life satisfaction as a measure of societal happiness is an individualistic presumption: Evidence from fifty countries

Numerous studies document that societal happiness is correlated with individualism, but the nature of this phenomenon remains understudied. In the current paper, we address this gap and test the reasoning that individualism correlates with societal happiness because the most common measure of societal happiness (i.e., country-level aggregates of personal life satisfaction) is individualism-themed. With the data collected from 13,009 participants across fifty countries, we compare associations of four types of happiness (out of which three are more collectivism-themed than personal life satisfaction) with two different measures of individualism. We replicated previous findings by demonstrating that societal happiness measured as country-level aggregate of personal life satisfaction is correlated with individualism. Importantly though, we also found that the country-level aggregates of the collectivism-themed measures of happiness do not tend to be significantly correlated with individualism. Implications for happiness studies and for policy makers are signaled