Cytoophidia Influence Cell Cycle and Size in Schizosaccharomyces pombe.

Cytidine triphosphate synthase (CTPS) forms cytoophidia in all three domains of life. Here we focus on the function of cytoophidia in cell proliferation using Schizosaccharomyces pombe as a model system. We find that converting His359 of CTPS into Ala359 leads to cytoophidium disassembly. By reducing the level of CTPS protein or specific mutation, the loss of cytoophidia prolongs the G2 phase and expands cell size. In addition, the loss-filament mutant of CTPS leads to a decrease in the expression of genes related to G2/M transition and cell growth, including histone chaperone slm9. The overexpression of slm9 alleviates the G2 phase elongation and cell size enlargement induced by CTPS loss-filament mutants. Overall, our results connect cytoophidia with cell cycle and cell size control in Schizosaccharomyces pombe.

Intolerance of uncertainty across stress, anxiety, and depression among university students in Pakistan: A descriptive cross-sectional study.

Background: The mental health issues due to COVID-19, such as intolerance of uncertainty (IOU), anxiety, stress, and depression, have attracted extensive attention from researchers. The challenges for Pakistani university students could be worse than developed countries due to the lack of online courses/programs and online mental health support provided by academic institutions. Therefore, the current study aims to assess the intolerance of uncertainty, depression, anxiety, and stress of Pakistani university students after the second wave of COVID-19 and the relationship among these constructs. Methods: A convenience cross-sectional sampling method was used to collect data from university students in Pakistan between January 2021 and April 2022 via a structured online questionnaire. The Descriptive analysis focused on frequencies, percentages, mean, and standard deviation (SD) were calculated on IOU-12 and DASS-21. Covariance for the research model and confirmatory factor analyses fit indices for the IOU-12 and DASS-21 were analyzed by AMOS statistical packages. Results: As expected, anxiety, depression, and stress persist among Pakistani university students. On average, they report mild to moderate mental health problems regarding anxiety, depression, stress, and intolerance of uncertainty. Our results indicate a strong positive relationship among the three emotional distress components - anxiety, depression, and stress. However, our results suggest no significant relationship between IOU and the three subcomponents of emotional distress (anxiety, depression, and stress). Limitations: First, the cross-sectional survey design means we cannot conclude on the causal relations. Second, the self-report questionnaire embeds subjectivity issues. Last, the generalizability of the sample to the whole student population in Pakistan is limited, considering the sampling method. Conclusion: This study expanded the current knowledge in the psychological health domain (intolerance of uncertainty, anxiety, depression, and stress) due to the COVID-19 pandemic. In practice, higher education institutions should further mitigate university students' mental health issues. For researchers, our findings inspire future studies to delve into the relationship between IOU and mental health issues due to COVID-19 since our findings display contrary evidence for various reasons.

Utopian or dystopian? The portrayal of the metaverse in popular news on social media.

The metaverse has sparked lots of interest worldwide as many giant tech companies are pursuing this futuristic idea. However, it has not been properly studied empirically by social science scholars yet. Considering the vital role played by media frames in affecting people's attitudes and behaviors towards the technology, this study examined the framing of the metaverse in popular news across Social Network Sites (SNSs) by cluster analyzing Entman's four operational frame elements. It identified five frames: economic prospect frame, unwanted future frame, consumer prospect frame, threatening future frame, and probable future frame. Overall, findings suggest a polarized framing of the metaverse on social media. While the majority of voices about the metaverse are optimistic, there is also a strong negative and dystopian perspective in more than one third of the SNS news. This positive or negative one-sided framing of the metaverse on SNSs may therefore fragmentize and polarize the audience, rather than informing in a balanced way. Implications for future research are discussed.

A Moderated Mediation Model of Perceived Effect of Fitspiration Images on Self: The Influence of Media Literacy and BMI.

The present study investigated the relationship between internal locus of control and the perceived impact of Instagram fitspiration images on the self with media literacy as the mediating role in this relationship. This study also examined the importance of body mass index (BMI) as a moderating factor in the mediated model, where higher BMIs could weaken the relationship between internal locus of control and the perceived effect of fitspiration images mediated through media literacy. A sample of 321 Malaysian university students who were fitspiration viewers filled out a self-report questionnaire assessing internal locus of control, media literacy, perceived effect of fitspiration images on self, body satisfaction and BMI. The data analysis was performed using SPSS PROCESS macro. Results show that internal locus of control is negatively associated with the perceived impact of fitspiration images on self, mediated by media literacy. However, BMI moderates the mediated relationship such that the negative relationship between internal locus of control and the perceived effect of fitspiration images through media literacy does not exert an effect on those with high BMI. These results accentuate the value of incorporating a potential mediator and moderator into the direct relationship between internal locus of control and perceived effect of media ideals on self to provide an enhanced understanding of this process and offer practical insights about the protective role of media literacy and negative effects of high BMI.

Assessing the Workplace Cyberloafing Behavior among Pharmacists in Pakistan.

Objective: After the commencement of the Internet and the popularity of various electronic devices, cyberloafing has become prevalent in the workplace regardless of professional type, demographic characteristics, and country. Individuals use the Internet for work-irrelevant purposes during work hours, which is believed to have a controversial role in work productivity. However, rare studies have paid attention to the prevalence of cyberloafing behavior among Pakistan pharmacists. Considering pharmacists' essential role in the health sector, this study investigates the prevalence of cyberloafing activities among workplace pharmacists in Pakistan. Methods: This cross-sectional survey was conducted among 242 registered pharmacists in Pakistan between October 2021 and February 2022 with a structured self-administered online questionnaire. The final sample consisted of 200 valid responses after screening. Data were processed through exploratory factor analysis and confirmatory factor analyses. Pearson Chi-square analysis was also used to test the correlation between factors. Findings: Descriptive analysis shows that pharmacists spend more time on sharing-related activities and least on gambling/gaming-related activities in the workplace. All the items' Cronbach's alpha values range from 0.923 to 0.927. The analysis indicates that (60%) pharmacists have intermediate Internet skills. The results also suggest that age, Internet usage, and work area have a strong relationship with cyberloafing behaviors which also, in turn, are linked with their perceived Internet skills. This study has important practical implications for pharmacy management in Pakistan. Conclusion: Cyberloafing behavior is prevalent among Pakistan pharmacists. Our findings could inspire how managers and all other relevant stakeholders could improve the pharmacy system in Pakistan.

The Mediating Influence of the Unified Theory of Acceptance and Use of Technology on the Relationship Between Internal Health Locus of Control and Mobile Health Adoption: Cross-sectional Study.

BACKGROUND: Mobile health (mHealth) as an innovative form of information and communications technology can efficiently deliver high-quality health care by enhancing communication and health management, reducing costs, and increasing access to health services. An individual's internal health locus of control (HLOC) is found to be associated with the behavioral intent to adopt mHealth. However, little is known about the underlying mechanism of this association. OBJECTIVE: The primary objective of this study was to test the mediation influence of the Unified Theory of Acceptance and Use of Technology (UTAUT) on the relationship between internal HLOC and the behavioral intention to use mHealth. METHODS: A total of 374 responses were collected from Malaysian adult users of mHealth, using convenience and snowball sampling methods. Partial least squares structural equation modeling was used to analyze the data. Data were collected for variables, including demographics, internal HLOC, and modified UTAUT constructs (ie, performance expectancy, effort expectancy, and social influence). RESULTS: The results showed that there was no direct relationship between internal HLOC and the behavioral intention to use mHealth (ß=-0.039, P=.32). The indirect relationship between internal HLOC and the intent to adopt mHealth was supported, indicating that the UTAUT constructs performance expectancy (ß=0.104, P<.001), effort expectancy (ß=0.056, P=.02), and social influence (ß=0.057, P=.002) mediated this relationship. The results showed full mediation, with total variance explained at 47.2%. CONCLUSIONS: This study developed an integrative model, where a health-related disposition (internal HLOC), mHealth-related beliefs (performance expectancy and effort expectancy), and normative pressure (social influence) were combined to explain the underlying mechanism of the behavioral intent to adopt mHealth. The results showed that the intention to adopt mHealth is mediated by the influence of UTAUT factors, while HLOC has no direct effect on adoption intention. The findings provide insights into augmenting mHealth adoption among the public by enhancing the perceived benefits of mHealth, helping design more effective and user-friendly mHealth tools, and capitalizing on social normative influence to adopt mHealth. This study utilized the constructs of the UTAUT model to determine the intention to use mHealth. Future research should focus on other health- and technology-related theories to ascertain other possible factors influencing the behavioral intent of mHealth adoption.

3D in vitro culture system to study collective migration in mammary organoid epithelium.

We recently established an in vitro culture system in which mammary gland organoid undergoes directional migration in response to an FGF10 concentration gradient. Here, we describe a step-by-step protocol for preparing organoids, the setup of the 3D culture system, and the image acquisition approach. The technical difficulties in conducting the 3D migration assay are choosing epithelial organoids of appropriate sizes and manually paring organoids and beads pre-soaked in FGF10 within a desirable distance (∼100 µm). For complete details on the use and execution of this protocol, please refer to Lu et al. (2020).

Private Self-Consciousness and Self-Monitoring on Instagram: The Mediating Effect of Internal Locus of Control and Self-Concept.

Past studies examining the direct relationship between private self-consciousness and online self-presentation behavior have not met with much success. The aim of this study was to examine the direct relationship between private self-consciousness and self-monitoring as well as the indirect relationship between these two variables through the mediation of locus of control and self-concept among Instagram users. Besides investigating locus of control and self-concept independently, serial mediation of locus of control and self-concept in the relationship between private self-consciousness and self-monitoring was also examined. A sample of 309 university students was conveniently drawn from three private universities in Kuala Lumpur, Malaysia. Participants completed a survey that collected data on private self-consciousness, internal locus of control, self-concept, self-monitoring on Instagram and relevant demographic data. Results of this study showed that there is no direct relationship between private self-consciousness and self-monitoring on Instagram. Independently, locus of control was found to mediate the relationship between private self-consciousness and self-monitoring while self-concept did not. The serial-multiple mediation test supported the mediating role of locus of control and self-concept on this relationship. These indirect relationships contribute to our understanding of the underlying mechanism through which private self-consciousness influences self-monitoring on Instagram.

Asymmetric Stratification-Induced Polarity Loss and Coordinated Individual Cell Movements Drive Directional Migration of Vertebrate Epithelium.

Collective migration is essential for development, wound repair, and cancer metastasis. For most collective systems, "leader cells" determine both the direction and the power of the migration. It has remained unclear, however, how the highly polarized vertebrate epithelium migrates directionally during branching morphogenesis. We show here that, unlike in other systems, front-rear polarity of the mammary epithelium is set up by preferential cell proliferation in the front in response to the FGF10 gradient. This leads to frontal stratification, loss of apicobasal polarity, and leader cell formation. Leader cells are a dynamic population and move faster and more directionally toward the FGF10 signal than do follower cells, partly because of their intraepithelial protrusions toward the signal. Together, our data show that directional migration of the mammary epithelium is a unique multistep process and that, despite sharing remarkable cellular and molecular similarities, vertebrate and invertebrate epithelial branching are fundamentally distinct processes.

NEP1-40-modified human serum albumin nanoparticles enhance the therapeutic effect of methylprednisolone against spinal cord injury.

BACKGROUND: Frequent injection of high-dose methylprednisolone (MP) is used to treat spinal cord injury (SCI), but free MP is associated with various side effects and its water solubility is low, limiting potential dosing regimes and administration routes. Albumin-based nanoparticles, which can encapsulate therapeutic drugs and release cargo in a controlled pattern, show high biocompatibility and low toxicity. The Nogo protein, expressed on the surface of oligodendrocytes, can inhibit axonal growth by binding with the axonal Nogo receptor (NgR). Peptide NEP1-40, an NgR antagonist, can bind specifically to Nogo, significantly improving functional recovery and axon growth in the corticospinal tract. Therefore, we hypothesized that delivering MP within nanoparticles decorated with NEP1-40 could avoid the disadvantages of free MP and enhance its therapeutic efficacy against SCI. RESULTS: We used human serum albumin to prepare MP-loaded NPs (MP-NPs), to whose surface we conjugated NEP1-40 to form NEP1-40-MP-NPs. Transmission electron microscopy indicated successful formation of nanoparticles. NEP1-40-MP-NPs were taken up significantly better than MP-NPs by the Nogo-positive cell line RSC-96 and were associated with significantly higher Basso-Beattie-Bresnahan locomotor scores in rats recovering from SCI. Micro-computed tomography assay showed that NEP1-40-MP-NPs mitigated SCI-associated loss of bone mineral density and accelerated spinal cord repair. CONCLUSIONS: NEP1-40-MP-NPs can enhance the therapeutic effects of MP against SCI. This novel platform may also be useful for delivering other types of drugs.

Characterization of aptamer-mediated gene delivery system for liver cancer therapy.

Liver cancer is a fatal disease with limited therapy options. The recombinant adenovirus expressing tumor-suppressor gene of PTEN (Ad5-PTEN) showed effective antitumor activity against liver cancer. However, its disadvantages produced great limitation on its application, especially its nonspecific and toxicity to normal cells and tissues. The epithelial cell adhesion molecule (EpCAM) is over-expressed in some liver cancer cells and an RNA aptamer EpDT3 could specially target to EpCAM-positive cells. Based on this founding, we aimed to design a kind of gene delivery system of EpDT3-mediated Ad5-PTEN (EpDT3-PEG-Ad5-PTEN, EPAP) in which polyethylene glycol was used to be a linker to conjugate EpDT3 with Ad5-PTEN. This strategy may overcome the disadvantages of naked Ad5-PTEN and enhance the antitumor effect on liver cancer. The SDS-PAGE electrophoresis, TBE-PAGE electrophoresis and fluorescence detection were conducted to confirm the successful preparation of EPAP. Compared with the naked Ad5-PTEN, EPAP showed significant anti-proliferative and anti-migratory activities against HepG2 cells. EPAP also showed selective and precise target ability to EpCAM-positive HepG2 cells in vivo. Therefore, EPAP may be further explored as a novel effective anticancer drug for malignant liver cancer.

Aptamer-mediated gene therapy enhanced antitumor activity against human hepatocellular carcinoma in vitro and in vivo.

A recombinant adenovirus carrying the tumor suppressor gene PTEN (Ad5-PTEN) is an effective antitumor agent against liver cancer. But the application of Ad5-PTEN has been greatly hindered by its auto-immunogenicity, non-specific toxicity to normal tissues, as well as poor stability in blood stream because of neutralizing antibody. Epithelial cell adhesion molecule (EpCAM) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in liver cancer. An RNA aptamer EpDT3 could specially bind with EpCAM and target EpCAM-positive cells. Therefore, we hypothesized that developing a novel gene delivery system of EpDT3-modified Ad5-PTEN could overcome the disadvantages of naked Ad5-PTEN and enhance the antitumor effect on hepatocellular carcinoma. We took polyethylene glycol (PEG) as a linker to conjugate EpDT3 with Ad5-PTEN to prepare EpDT3-PEG-Ad5-PTEN (EPAP) by simple chemical synthesis method. We found that the stability of this novel gene delivery system in human blood serum increased about 16-fold compared to the naked adenovirus. Meanwhile, EPAP enhanced gene expression and cellular uptake in HepG2 cells, and showed significant inhibition in cell proliferation and cell migration against hepatocellular carcinoma cells HepG2 while showing no cytotoxicity to normal liver cells L-02, compared with Ad5-PTEN. Importantly, EPAP could induce cell apoptosis and presented superior antitumor activity against aggressive HepG2 xenograft in nude mice but showed no obvious toxicity to the tested mice at the therapy concentration. In conclusion, EpCAM aptamer EpDT3 could significantly enhance the antitumor effect of Ad5-PTEN with high binding ability to EpCAM-positive cells HepG2.