Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting 3D Structure, Cross Talks, and Prognostic Significance of KLF9 in Cervical Cancer

Our study aimed to identify the new blood-based biomarkers for the diagnosis and prognosis of cervical cancer. Moreover, the three-dimensional (3D) structure of Kruppel-like factor 9 (KLF9) was also determined in order to better understand its function, and a signaling pathway was constructed to identity its upstream and downstream targets. In the current study, the co-expressions of tumor protein D52 (TPD52), KLF9, microRNA 223 (miR-223), and protein kinase C epsilon (PKCϵ) were evaluated in cervical cancer patients and a possible relation with disease outcome was revealed. The expressions of TPD52, KLF9, miR-223, and PKCϵ were studied in the blood of 100 cervical cancer patients and 100 healthy controls using real-time PCR. The 3D structure of KLF9 was determined through homology modeling via the SWISS-MODEL and assessed using the Ramachandran plot. The predicted 3D structure of KLF9 had a similarity index of 62% with its template (KLF4) with no bad bonds in it. In order to construct a genetic pathway, depicting the crosstalk between understudied genes, STRING analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and DAVID software were used. The constructed genetic pathway showed that all the understudied genes are linked to each other and involved in the PI3K/Akt signaling pathway. There was a 23-fold increase in TPD52 expression, a 2-fold increase in miR-223 expression, a 0.14-fold decrease in KLF9 expression, and a 0.05-fold decrease of PKCϵ expression in cervical cancer. In the present study, we observed an association of the expressions of TPD52, KLF9, miR-223, and PKCϵ with tumor stage, metastasis, and treatment status of cervical cancer patients. Elevated expressions of TPD52 and miR-223 and reduced expressions of KLF9 and PKCϵ in peripheral blood of cervical cancer patients may serve as predictors of disease diagnosis and prognosis. Nevertheless, further in vitro and tissue-level studies are required to strengthen their role as potential diagnostic and prognostic biomarkers.
Testing the Associations Between Body Image, Social Support, and Physical Activity Among Adolescents and Young Adults Diagnosed With Cancer

Physical activity (PA) is important for managing the side effects and long-term outcomes of cancer treatment, yet many adolescents and young adults diagnosed with cancer (AYAs) are not meeting PA guidelines. Body image and social support are two factors that can influence PA behavior and require further attention in this population. The purpose of this study was to examine the associations between body image, social support, and PA among AYAs. An online cross-sectional survey administered through the Research Electronic Data Capture platform was used to assess self-reported body image (body-related self-conscious emotions of appearance and fitness shame, guilt, authentic pride, and hubristic pride), social support (general and cancer-specific), and PA (mild, moderate-to-vigorous, and resistance exercise) in AYAs (N = 119; Mage = 34.5 ± 5.5 years). Based on findings from path analyses, body image and social support were directly associated with PA (R2 = 0.09–0.33). Social support was also directly associated with body image. However, there were no indirect effects. These findings provide preliminary support for the influential role of appearance and fitness body-related emotions and cancer-specific social support on PA. The results have important implications for the development of targeted strategies aimed at improving body image (e.g., cognitive dissonance and compassion-focused interventions) and social support (e.g., facilitating the provision of cancer-specific support), with the overall goal of increasing AYAs’ PA.
Adenosine A2A Receptor in Bone Marrow-Derived Cells Mediated Macrophages M2 Polarization via PPARγ-P65 Pathway in Chronic Hypoperfusion Situation

Background: The role of adenosine A2A receptor (A2AR) in the ischemic white matter damage induced by chronic cerebral hypoperfusion remains obscure. Here we investigated the role of A2AR in the process of macrophage polarizations in the white matter damage induced by chronic cerebral hypoperfusion and explored the involved signaling pathways. Methods: We combined mouse model and macrophage cell line for our study. White matter lesions were induced in A2AR knockout mice, wild-type mice, and chimeric mice generated by bone marrow cells transplantation through bilateral common carotid artery stenosis. Microglial/macrophage polarization in the corpus callosum was detected by immunofluorescence. For the cell line experiments, RAW264.7 macrophages were treated with the A2AR agonist CHS21680 or A2AR antagonist SCH58261 for 30 min and cultured under low-glucose and hypoxic conditions. Macrophage polarization was examined by immunofluorescence. The expression of peroxisome proliferator activated receptor gamma (PPARγ) and transcription factor P65 was examined by western blotting and real-time polymerase chain reaction (RT-PCR). Inflammatory cytokine factors were assessed by enzyme-linked immunosorbent assay (ELISA) and RT-PCR. Results: Both global A2AR knockout and inactivation of A2AR in bone marrow-derived cells enhanced M1 marker expression in chronic ischemic white matter lesions. Under low-glucose and hypoxic conditions, CGS21680 treatment promoted macrophage M2 polarization, increased the expression of PPARγ, P65, and interleukin-10 (IL-10) and suppressed the expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The CGS21680-induced upregulation of P65 and IL-10 was abolished in macrophages upon PPARγ knockdown. The downregulation of TNF-α and IL-1β by CGS21680 was less affected by PPARγ knockdown. Conclusions: In the cerebral hypoperfusion induced white matter damage, A2AR signaling in bone marrow-derived cells induces macrophage M2 polarization and increases the expression of the anti-inflammatory factor IL-10 via the PPARγ-P65 pathway, both of which might explain its neuroprotective effect.
Resting-State Functional Connectivity Associated With Extraversion and Agreeableness in Adolescence

Although adolescence is a period in which developmental changes occur in brain connectivity, personality formation, and peer interaction, few studies have examined the neural correlates of personality dimensions related to social behavior within adolescent samples. The current study aims to investigate whether adolescents’ brain functional connectivity is associated with extraversion and agreeableness, personality dimensions linked to peer acceptance, social network size, and friendship quality. Considering sex-variant neural maturation in adolescence, we also examined sex-specific associations between personality and functional connectivity. Using resting-state functional magnetic resonance imaging (fMRI) data from a community sample of 70 adolescents aged 12–15, we examined associations between self-reported extraversion and agreeableness and seed-to-whole brain connectivity with the amygdala as a seed region of interest. Then, using 415 brain regions that correspond to 8 major brain networks and subcortex, we explored neural connectivity within brain networks and across the whole-brain. We conducted group-level multiple regression analyses with the regressors of extraversion, agreeableness, and their interactions with sex. Results demonstrated that amygdala connectivity with the postcentral gyrus, middle temporal gyrus, and the temporal pole is positively associated with extraversion in girls and negatively associated with extraversion in boys. Agreeableness was positively associated with amygdala connectivity with the middle occipital cortex and superior parietal cortex, in the same direction for boys and girls. Results of the whole-brain connectivity analysis revealed that the connectivity of the postcentral gyrus, located in the dorsal attention network, with regions in default mode network (DMN), salience/ventral attention network, and control network (CON) was associated with extraversion, with most connections showing positive associations in girls and negative associations in boys. For agreeableness, results of the within-network connectivity analysis showed that connections within the limbic network were positively associated with agreeableness in boys while negatively associated with or not associated with agreeableness in girls. Results suggest that intrinsic functional connectivity may contribute to adolescents’ individual differences in extraversion and agreeableness and highlights sex-specific neural connectivity patterns associated with the two personality dimensions. This study deepens our understanding of the neurobiological correlates of adolescent personality that may lead to different developmental trajectories of social experience.
A Survey on Online Political Participation, Social Capital, and Well-Being in Social Media Users—Based on the Second Phase of the Third (2019) TCS Taiwan Communication Survey Database

This study focused on the frequency of social media use. Through investigating and verifying the correlations between social media use frequency, online political participation, and social capital, we derived two models of socialization that affect citizen well-being and, accordingly, proposed strategic suggestions for democratic society construction and network management. This study drew upon the 2019 Taiwan Communication Survey database and used structural equation modeling (SEM) as a statistical method to explore the causal relationship between these four variables (social media use, online political participation, social capital and well-being). The data analysis yielded an overall good fit with the overall fit indicators: χ2 = 214.417, df = 84, p = 2.293, RMSEA = 0.028, GFI = 0.998, CFI = 0.986, SRMR = 0.066, and CN = 993.411. Future communication scholars who wish to explore issues related to new media users can draw on this model for subsequent research.
HSP110 as a Diagnostic but Not a Prognostic Biomarker in Colorectal Cancer With Microsatellite Instability

Determination of microsatellite instability (MSI) using molecular test and deficient mismatch repair (dMMR) using immunohistochemistry (IHC) has major implications on colorectal cancer (CRC) management. The HSP110 T 17 microsatellite has been reported to be more monomorphic than the common markers used for MSI determination. Large deletion of HSP110 T 17 has been associated with efficacy of adjuvant chemotherapy in dMMR/MSI CRCs. The aim of this study was to evaluate the interest of HSP110 deletion/expression as a diagnostic tool of dMMR/MSI CRCs and a predictive tool of adjuvant chemotherapy efficacy. All patients with MSI CRC classified by molecular testing were included in this multicenter prospective cohort (n = 381). IHC of the 4 MMR proteins was carried out. HSP110 expression was carried out by IHC (n = 343), and the size of HSP110 T 17 deletion was determined by PCR (n = 327). In the 293 MSI CRCs with both tests, a strong correlation was found between the expression of HSP110 protein and the size of HSP110 T 17 deletion. Only 5.8% of MSI CRCs had no HSP110 T 17 deletion (n = 19/327). HSP110 T 17 deletion helped to re-classify 4 of the 9 pMMR/MSI discordance cases as pMMR/MSS cases. We did not observe any correlation between HSP110 expression or HSP110 T 17 deletion size with time to recurrence in patients with stage II and III CRC, treated with or without adjuvant chemotherapy. HSP110 is neither a robust prognosis marker nor a predictor tool of adjuvant chemotherapy efficacy in dMMR/MSI CRC. However, HSP110 T17 is an interesting marker, which may be combined with the other pentaplex markers to identify discordant cases between MMR IHC and MSI.
Numerical Constraints on Folding and Thrusting in Jiudong Basin: Implication for the Northeastward Growth of Qinghai–Tibetan Plateau

Under regional tectonic shortening in the northern margin of Qinghai–Tibetan Plateau, the fold-and-thrust belts composed of four thrust faults (North Qilian-Shan, North Yumu-Shan, South Heli-Shan, and North Jintanan-Shan) formed from southwest to northeast discontinuously sequentially in the Jiudong Basin area during Late Cenozoic. Meanwhile, the North Qilian-Shan, Yumu-Shan, and Heli-Shan ranges were formed successively, as the Earth's local surface was unequally uplifted. In this study, based on geological and geophysical observations, a simple two-dimensional elastic-plastic numerical finite element method model for a southwest-northeast section in Jiudong Basin is successfully established to simulate the spatiotemporal evolution of the local fold-and-thrust belts. Results show that the computed equivalent plastic strain concentration zones and the four observed thrust faults are consistently correlated in spatial position orientation and time sequence. The simulated upper-surface deformation is congruent with the observed topographic peaks and uplift sequences of the North Qilian-Shan, Yumu-Shan, and Heli-Shan ranges. This study provides a geodynamic basis for understanding the growth mechanism of the northern margin of Qinghai–Tibetan Plateau under tectonic horizontal shortening. Also, we provide a thorough sensitivity analysis for the model parameters of this particular geologic setting. Our sensitivity simulations, considering systematic case variations about the regional geometrical-material parameters, suggest the manifestation of three different possible evolution patterns of fold-and-thrust belts for a wedge above a decollement layer, with wedge plastic deformation migrating from 1) thick to thin end (well-known), 2) thin to thick end, and 3) both ends to middle. Finally, our results suggest that in this region, further growth of mountain ranges is expected to continue in the future.
Nanoenviroments of the β-Subunit of L-Type Voltage-Gated Calcium Channels in Adult Cardiomyocytes

In cardiomyocytes, Ca2+ influx through L-type voltage-gated calcium channels (LTCCs) following membrane depolarization regulates crucial Ca2+-dependent processes including duration and amplitude of the action potentials and excitation-contraction coupling. LTCCs are heteromultimeric proteins composed of the Cavα1, Cavβ, Cavα2δ and Cavγ subunits. Here, using ascorbate peroxidase (APEX2)-mediated proximity labeling and quantitative proteomics, we identified 61 proteins in the nanoenvironments of Cavβ2 in cardiomyocytes. These proteins are involved in diverse cellular functions such as cellular trafficking, cardiac contraction, sarcomere organization and excitation-contraction coupling. Moreover, pull-down assays and co-immunoprecipitation analyses revealed that Cavβ2 interacts with the ryanodine receptor 2 (RyR2) in adult cardiomyocytes, probably coupling LTCCs and the RyR2 into a supramolecular complex at the dyads. This interaction is mediated by the Src-homology 3 domain of Cavβ2 and is necessary for an effective pacing frequency-dependent increase of the Ca2+-induced Ca2+ release mechanism in cardiomyocytes.
Altered Topological Organization of Functional Brain Networks in Betel Quid Dependence: A Resting-State Functional MRI Study

Background: Betel quid dependence (BQD) is associated with abnormalities in the widespread inter-regional functional connectivity of the brain. However, no studies focused on the abnormalities in the topological organization of brain functional networks in chewers in Mainland China. Methods: In the current study, resting-state functional magnetic resonance images were acquired from 53 BQD individuals and 37 gender- and age-matched healthy controls (HCs). A functional network was constructed by calculating the Pearson correlation coefficients among 90 subregions in the human Brainnetome Atlas. The topological parameters were compared between BQD individuals and HCs. Results: The results showed that BQD individuals presented a small-world topology, but the normalized characteristic path length (λ) increased compared with HCs (0.563 ± 0.030 vs. 0.550 ± 0.027). Compared to HCs, BQ chewers showed increased betweenness centrality (Be) in the right supplementary motor area, right medial superior frontal gyrus, right paracentral lobule, right insula, left posterior cingulate gyrus, right hippocampus, right post-central gyrus, right superior parietal gyrus, and right supramarginal gyrus, while decreased Be was found in the orbitofrontal area and temporal area, which is associated with reward network, cognitive system, and default mode network. The area under the curve (AUC) value of λ displayed a positive correlation with the duration of BQ chewing (r = 0.410, p = 0.002). Conclusions: The present study revealed the disruption of functional connectome in brain areas of BQD individuals. The findings may improve our understanding of the neural mechanism of BQD from a brain functional network topological organization perspective.
Identification of the Host Substratome of Leishmania-Secreted Casein Kinase 1 Using a SILAC-Based Quantitative Mass Spectrometry Assay

Leishmaniasis is a severe public health problem, caused by the protozoan Leishmania. This parasite has two developmental forms, extracellular promastigote in the insect vector and intracellular amastigote in the mammalian host where it resides inside the phagolysosome of macrophages. Little is known about the virulence factors that regulate host-pathogen interactions and particularly host signalling subversion. All the proteomes of Leishmania extracellular vesicles identified the presence of Leishmania casein kinase 1 (L-CK1.2), a signalling kinase. L-CK1.2 is essential for parasite survival and thus might be essential for host subversion. To get insights into the functions of L-CK1.2 in the macrophage, the systematic identification of its host substrates is crucial, we thus developed an easy method to identify substrates, combining phosphatase treatment, in vitro kinase assay and Stable Isotope Labelling with Amino acids in Cell (SILAC) culture-based mass spectrometry. Implementing this approach, we identified 225 host substrates as well as a potential novel phosphorylation motif for CK1. We confirmed experimentally the enrichment of our substratome in bona fide L-CK1.2 substrates and showed they were also phosphorylated by human CK1δ. L-CK1.2 substratome is enriched in biological processes such as “viral and symbiotic interaction,” “actin cytoskeleton organisation” and “apoptosis,” which are consistent with the host pathways modified by Leishmania upon infection, suggesting that L-CK1.2 might be the missing link. Overall, our results generate important mechanistic insights into the signalling of host subversion by these parasites and other microbial pathogens adapted for intracellular survival.
When Fathers Feel Socially Constrained to Assume a Role: A Negative Predictor of the Coparental Relationship in Switzerland

Role distribution is a central issue for parents in the transition to parenthood, but little is known about the motivations in fathers to assume a specific role. Differences in work-family balance in each parent may be motivated by an individual choice mutually shared by both partners; however, in many couples, the parents may feel forced to adopt a traditional role distribution, either for financial reasons, or to comply with social expectations about what men and women should do when they are parents. This feeling of being socially constrained to adopt a role distribution that is not congruent with intrinsic motivations can generate dissatisfaction and may jeopardize the development of the interparental relationship. Coparenting refers to the emotional and instrumental support parents bring to each other in their parental tasks. It has been shown to be central in family functioning and a powerful predictor of children’s emotional and cognitive development. In this study, we aimed to assess the extent to which different motivations for role distribution in fathers are predictive of the quality of the coparental relationship. A convenience sample of 144 fathers from the French-speaking part of Switzerland completed online questionnaires about their motivations, coparental relationship, and sociodemographic characteristics. Results showed that the reasons for role distribution were mainly economical, practical, and in order to meet personal expectations. Multivariate general linear modeling showed that role distribution that is constrained to meet social expectations and age were predictive of a less cohesive coparental relationship, whereas a deliberate choice in role distribution was linked to a more cohesive coparental relationship.
Mediator Complex Subunit 19 Promotes the Development of Hepatocellular Carcinoma by Regulating the AKT/mTOR Signaling Pathway

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, the pathogenesis of which remains unclear. Mediator complex subunit 19 (MED19), a subunit of the Mediator complex, is a multi-protein co-activator necessary for DNA transcription factors to induce RNA polymerase II transcription. In the current study, we aimed to study the role of MED19 in HCC and elucidate its mechanism. Methods MED19 expression in HCC tissues was determined. The relationship between MED19 and the clinical prognosis was explored. The influence of MED19 on HCC cell viability, migration, invasion, and apoptosis was studied. The expression of AKT/mTOR pathway genes and proteins was detected by qRT-PCR and western blot. The correlation between MED19 and immune infiltration was investigated. Results MED19 was upregulated in HCC tissues compared with tumor-adjacent tissues, and was associated with a poor prognosis. Furthermore, high MED19 expression was correlated with race, gender, etc. Knockdown of MED19 inhibited cell proliferation, migration, invasion, and promoted apoptosis. Knockdown of MED19 decreased p-AKT and p-mTOR protein expression. Additionally, the downstream effectors of the AKT/mTOR pathway, p70S6K1 and 4EBP1, were affected by MED19. Notably, MED19 expression was positively correlated with the infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, etc. Conclusion MED19 is significantly upregulated in HCC tissues and cells. MED19 may promote the progression of HCC in vitro and may be related to immune infiltration. Together, our data show that MED19 could be considered as a new possible biomarker as well as a novel therapeutic target for HCC.