Search Results (608)

Expression of major histocompatibility complex I (MHC-I) on tumor cells is extremely important for the antitumor immune response for its essential role in activating various immune cells, including tumor-specific CD8+ T cells. Cancers of lower MHC-I expression commonly exhibit less immune cell infiltration and worse prognosis in clinic. In this study, we conducted bioinformatic-experimental screening to identify potential gene targets to enhance MHC-I expression in breast cancer (BRCA). Through a combination of MHC-I scoring, gene expression correlation analysis, survival prognostication, and Cibersort tumor-infiltrated lymphocytes (TILs) scoring, we identify 144 genes negatively correlated with both MHC-I expression and TILs in breast cancer. Furthermore, we verified partially according to KEGG functional enrichment or gene-dependency analysis and figured out multiple genes, including PIP5K1A, NCKAP1, CYFIP1, DIS3, TBP, and EXOC1, as effective gene targets for increasing MHC-I expression in breast cancer. Mechanistically, knockout of each of these genes activated the intrinsic interferon response in breast cancer cells, which not only promoted MHC-I expression but also caused immunogenic cell death of breast cancer. Finally, the scRNA-seq confirmed the negative correlation of PIP5K1A et al. with TILs in breast cancer patients. Collectively, we identified multiple gene targets for an increase in MHC-I expression in breast cancer in this study. Full article

Stress resistance is highly associated with longer and healthier lifespans in various model organisms, including nematodes, fruit flies, and mice. However, we lack a complete understanding of stress resistance in humans; therefore, we investigated how stress resistance and longevity are interlinked in humans. Using more than 180 databases, we identified 541 human genes associated with stress resistance. The curated gene set is highly enriched with genes involved in the cellular response to stress. The Reactome analysis identified 398 biological pathways, narrowed down to 172 pathways using a medium threshold (p-value < 1 × 10⁻⁴). We further summarized these pathways into 14 pathway categories, e.g., cellular response to stimuli/stress, DNA repair, gene expression, and immune system. There were overlapping categories between stress resistance and longevity, including gene expression, signal transduction, immune system, and cellular responses to stimuli/stress. The categories include the PIP3-AKT-FOXO and mTOR pathways, known to specify lifespans in the model systems. They also include the accelerated aging syndrome genes (WRN and HGPS/LMNA), while the genes were also involved in non-overlapped categories. Notably, nuclear pore proteins are enriched among the stress-resistance pathways and overlap with diverse metabolic pathways. This study fills the knowledge gap in humans, suggesting that stress resistance is closely linked to longevity pathways but not entirely identical. While most longevity categories intersect with stress-resistance categories, some do not, particularly those related to cell proliferation and beta-cell development. We also note inconsistencies in pathway terminologies with aging hallmarks reported previously, and propose them to be more unified and integral. Full article

Enterococcal bacteremia (EB) is on the rise both in Sweden and globally. While Enterococcus faecalis (E. faecalis) is susceptible to ampicillin and piperacillin/tazobactam (pip/taz), Enterococcus faecium (E. faecium) is not. Historically, most enterococcal infections have been caused by E. faecalis, but the epidemiology is changing with increasing recognition of enterococci as nosocomial pathogens and the emergence of resistance to commonly used antimicrobial agents. The use of pip/taz has increased dramatically in Sweden, but it is unknown if this has affected the relative incidence of E. faecalis/E. faecium bacteremia. Here, we investigate whether the number and proportion of E. faecium bacteremia (EfmB) cases have increased. Additionally, risk factors associated with EfmB with a focus on prior antibiotic exposure are analyzed. Medical journals of 360 patients with EB admitted to Sahlgrenska University Hospital are reviewed. The proportion of EfmB cases increased from 41% in 2015 to 51% in 2021. Hospital-acquired infection, previous exposure to pip/taz, and carbapenems are identified as independent risk factors for EfmB. There are considerable patient-related differences between the EfmB and EfsB groups, but there is no difference in mortality rates. In conclusion, the increasing proportion of EfmB cases is concerning and is seen parallel to the expanding use of pip/taz, one possible contributing factor. Our findings suggest that a cautious approach to antibiotic use is essential to prevent the spread of antibiotic-resistant bacteria. Full article

Aquaporins (AQPs) play an essential role in membrane water transport during plant responses to water stresses centered on conventional upstream signals. Phytohormones (PHs) regulate plant growth and yield, working with transcription factors to help plants withstand environmental challenges and regulate physiological and chemical processes. The AQP gene family is important, so researchers have studied its function and regulatory system in numerous species. Yet, there is a critical gap the understanding of many of their molecular features, thus our full knowledge of AQPs is far-off. In this study, we undertook a broad examination of the AQP family gene in Populus euphratica via bioinformatics tools and analyzed the expression patterns of certain members in response to drought, salt, and hormone stress. A total of 22 AQP genes were examined in P. euphratica, and were categorized into four main groups, including TIPs, PIPs, SIPs, and NIPs based on phylogenetic analysis. Comparable exon–intron gene structures were found by gene structure examination, and similarities in motif number and pattern within the same subgroup was determined by motif analysis. The PeuAQP gene family has numerous duplications, and there is a distinct disparity in how the members of the PeuAQP family react to post-translational modifications. Abiotic stress and hormone responses may be mediated by AQPs, as indicated by the abundance of stress response elements found in 22 AQP genes, as revealed by the promoter’s cis-elements prediction. Expression pattern analysis reveals that selected six AQP genes from the PIP subgroup were all expressed in the leaves, stem, and roots with varying expression levels. Moreover, qRT-PCR analysis discovered that the majority of the selected AQP members were up- or down-regulated in response to hormone treatment and abiotic stress. Remarkably, PeuAQP14 and PeuAQP15 appeared to be highly responsive to drought stress and PeuAQP15 exhibited a high response to salt stress. The foliar application of the phytohormones (SA, IAA, GA3, MeJA, and ABA) were found to either activate or inhibit PeuAQP, suggesting that they may mitigate the effects of water shortage of poplar water stress. The present work enhances our knowledge of the practical roles of AQPs in stress reactions and offers fundamental information for the AQP genes in poplar species. It also highlights a direction for producing new varieties of poplar species with drought, salt, and hormone tolerance and holds substantial scientific and ecological importance, offering a potential contribution to the conservation of poplar species in arid regions. Full article

Compelling evidence supports the foundational importance of early self-regulation (SR). It also supports parents in the home environment as having the foremost influence on early development. Yet, prevailing approaches to support early SR growth have tended to leverage early education and clinical settings. Partners in Play (PiP) was developed as a sustainable approach for parents to learn how and when to support children through experiences of self-regulation challenges in the home learning environment. This study reports the first randomised control trial evaluation of the PiP program, with 21 parent–child dyads (consisting of twelve girl–mother dyads, eight boy–mother dyads, and one boy–father dyad; mean child age = 4.12 years, SD = 0.65). Dyads were randomised to a PiP intervention group (n = 10), which entailed four online parent information sessions and four out-of-home guided practice dyadic play sessions across 8 weeks, or an active control group (n = 11). The primary outcome was parent autonomy support, and the secondary outcome was child SR. Results indicated a significant increase in parents’ use of autonomy support and a non-significant but moderate-sized effect on child SR. This innovative proof-of-concept program and evaluation provides a roadmap for effecting change in parental support during children’s play, to the prospective benefit of important abilities such as child SR. Analyses show promise for a parent-based model toward parent behaviour change and child SR improvement. Full article

To solve complex multi-attribute decision-making (MADM) problems within a triangular dual hesitant fuzzy (TDHF) environment where the attribute weights (Aws) are either fully or partially known, a novel bidirectional projection method is proposed, named multi-attribute decision-making and based on the consistent bidirectional projection measures of triangular dual hesitant fuzzy sets (TDHFSs). First, some notions are developed, such as the operation laws, score and accuracy functions, negative ideal points (NIPs), and positive ideal points (PIPs) of TDHFSs. The correlation coefficients and the cosine of the angle between the vectors of each alternative and the triangular dual hesitant fuzzy (TDHF) points are introduced. Then, the consistent bidirectional projection decision-making method based on the TDHFSs’ correlation coefficients is proposed. Additionally, an optimization model is established via maximizing the consistent coefficient to determine the Aws. Furthermore, some approaches are investigated based on the proposed approaches concerning the MADM issues with attribute values represented by triangular dual hesitant fuzzy elements (TDHFEs). Finally, a supply chain management (SCM) problem is illustrated, and comparative analyses are implemented to demonstrate the presented approach’s feasibility and efficiency. Full article

The mosquito Culex pipiens occurs in two ecotypes differing in their mating and overwintering behavior: pipiens mate in open environments and diapause, and molestus also mate in small spaces and is active throughout the year. Cx. pipiens carry Wolbachia endosymbionts of the wPip strain, but the frequency of infection differs between studied populations. Wolbachia infection affects the host reproductive success through cytoplasmic incompatibility. wPip Wolbachia is divided into five types, wPip I–V. The type of wPip carried varies among Cx. pipiens populations. In northern European locations different wPip types are found in the two ecotypes, whereas in southern locations, they often carry the same type, indicating differences in hybridization between ecotypes. In this study, Cx. pipiens specimens of both ecotypes were collected from Sweden and compared to specimens from Norway, England, Italy, and the Netherlands, as well as Cx. quinquefasciatus from Mali and Thailand. The abundance varied, but all specimens were infected by Wolbachia, while the tested specimens of other mosquito species were often uninfected. The wPip strains were determined through the sequence analysis of Wolbachia genes ank2 and pk1, showing that Cx. pipiens ecotypes in Scandinavia carry different wPip strains. The observed differences in wPip strains indicate that hybridization is not frequent and may contribute to barriers against hybridization of the ecotypes in Sweden and Norway. Full article

Considering the practical conditions, it has been observed that the support structures of wind turbines inevitably experience bending and axial compression, both during the installation phase and throughout their operational lifespan. The monopile is the most commonly utilized support structure for offshore applications and a reliable method for creating a detachable section within these structures is using a Pile-in-Pile (PIP) slip joint. Consequently, the behavior of PIP slip joints, under combined axial compression and bending, has been meticulously investigated. To facilitate a thorough analysis, overlapping lengths proportional to the pile diameters have been used, encompassing three distinct variations. This approach allows for a comprehensive understanding of structural integrity and performance under varying stress conditions, which are comprehensively understood and accounted for in design considerations. The current study builds upon assessing the pure bending characteristics of slip joints in cylindrical hollow section (CHS) structures. Additionally, two ring stoppers have been strategically employed inside the piles to withstand the axial load. Furthermore, the complexity of the pressure acting in the overlapping length, attributed to the frictional coefficient in that region, has been carefully addressed. The current research also encompasses a comprehensive overview of the P-M envelopes for the existing arrangements, with a particular focus on non-linear buckling, which is known to significantly influence the performance of tubular structures. Finally, a design equation was introduced to concisely describe the behavior of the components and compare it with other design equations provided by an established code. Full article

(1) Background: This mixed-method study aims to identify and describe factors associated with acute and long-term parenting stressors and coping strategies in caregivers of children with intraluminal pulmonary vein stenosis (PVS). (2) Methods: Parents of children with severe PVS were recruited from a large quaternary hospital to complete a survey that included demographics, the Pediatric Inventory for Parents (PIP), and the Coping Health Inventory for Parents (CHIP). We determined the Social Vulnerability Index (SVI) based on self-reported home address. A subset of caregivers completed a 60 min semi-structured interview via Zoom exploring the impact their child’s diagnosis had on their family; experience managing stress in the hospital and at home; current resources and processes for coping; and potential recommendations for hospitals to build resilience and coping. We used multivariable linear regression to examine the association between SVI and parental stress and coping while adjusting for possible confounders. Thematic analysis identified themes related to stress and coping. Finally, we assessed instances of convergence and difference between the qualitative and quantitative results. (3) Results: Participants included 32 caregivers who were 91% female with a mean age of 39 years. The children of participants were 66% female, with a mean age of five years. The parents reported a high amount of stress with an average PIP score of 120, nearly 46 points higher than similar studies in the congenital heart community. We observed no significant associations between SVI and either parental stress or coping in adjusted models. We identified 13 themes, including medical care, hospital, family, support systems, and home medical routine or support. (4) Conclusions: Our study found high levels of illness-related parental stress among caregivers of children with PVS. Stress evolved over time from what caregivers described as ‘survival mode’ to a future-oriented outlook. Currently, caregivers rely heavily on support networks that are not available to all caregivers or may experience strain over time. Caregivers indicated that communication and parental role functioning were coping strategies that could be better supported by providers and health systems. Full article

(1) Background: This study aimed to evaluate how laser-activated irrigation (LAI) influences the retention of a fiber post when used before an endodontic filling, as well as after post space preparation. (2) Materials and Methods: Sixty freshly extracted human incisors were selected. The teeth were randomly assigned to three groups—CONVENTIONAL (CONV), PIPS or SWEEPS—and treated endodontically. Each group received irrigation with 1 × 5 mL EDTA (17%) and 3 × 5 mL NaOCl (5.25%). In the first group, the irrigants were not activated, while in the second and third group, LAI was adopted using PIPS and SWEEPS protocols (Lightwalker from Fotona, Ljubliana, Slovenia). After post space preparation, each group received the same irrigation protocol initially established. Sticky posts (everStick Post, GC AUSTRIA GmbH Swiss) were individually adapted to the corresponding post spaces and cemented using dual cure resin cement (Gradia Core, GC Austria GmbH Swiss). All specimens were vertically embedded into self-curing acrylate (Duracryl plus, Spofa Dent, Europe), and each was sectioned into three segments of type A and type B samples for debonding through push-out and pull-out tests. The results were statistically analyzed. (3) Results: The pull-out test showed the superiority of the SWEEPS group, with a mean fracture force of 133.0 ± 50.7 N, followed by the PIPS group, with 102 N, with a lower standard deviation of ± 34.5 N. The CONV group registered the lowest fracture force. Concerning the push-out test, the SWEEPS group showed superior shear stress in comparison to the other two groups (13.45 ± 4.29 MPa); the CONV group was inferior, with shear tension values of 8.31 ± 4.67 MPa. (4) Conclusions: It can be stated that the SWEEPS and PIPS protocols resulted in considerably higher fiber post retention than the conventional method, whereas the SWEEPS protocol was superior to the PIPS protocol. Full article

In the last three decades, the development of new electricity-generation strategies based on renewable energy has been promoted, which has made it possible to offset the increase in electricity consumption, reduce production costs, and positively impact climate change. These new-generation strategies are based on distributed generation (DG) at different points of the electrical power system, which has economic, social, and environmental impacts by reducing greenhouse gas emissions. The new concept of an electric microgrid, which is an integrated energy generation and management system with autonomous capacity, allows efficient production and consumption, with alternating current (AC) and direct current (DC) microgrids being available. This work presents a topology of direct current microgrids for island mode operation, which aims to supply electricity to variable and constant power loads (CPLs), as well as for the autonomous charging and discharging of batteries. To achieve this objective, a microgrid model is developed, current and voltage control loop controllers are designed, and their performance in different types of operation is analyzed. As a contribution to this work, the parasitic elements in the microgrid model are considered, and the design of the controller in the voltage loop is presented for the power supply to the local linear and non-linear loads, in addition to managing the energy coming from CPLs and controls the charge and discharge of the battery. To validate the performance of the controllers, three microgrid operation tests are carried out, which are presented in the Simulations section. In these tests, it is observed that with the PI controller in the voltage loop, the DC_Link signal presents transients with an amplitude of 5 V below and above the 200 V reference, which shows the poor performance of the controller. However, in all three tests with the modified PI-P controller, the DC_Link voltage remains constant at 200 V, with a negligible transient amplitude of almost 0 V, showing better performance. Full article

Purpose: Effective antimicrobial use enhances care quality and combats antibiotic resistance. Yet, non-guideline factors influence potentially inappropriate prescribing. This study explores psycho-socio-organisational factors in antimicrobial prescribing as perceived by physicians across primary, secondary, and tertiary care. Methods: Adhering to PRISMA guidelines, a systematic review was conducted using PubMed and Scopus databases from 1 January 2000, to 8 March 2023, with an update search until 30 January 2024. Inclusion criteria focused on studies in Europe exploring psycho-socio-organisational factors for antibiotic prescribing from physicians’ perspectives in hospital, inpatient, or primary care settings. Exclusion criteria targeted out-of-office prescriptions or low-quality studies. To evaluate the latter, several quality and risk-of-bias checklists were used. Data were extracted on study characteristics, study design, and methods and identified determinants of antibiotic prescribing. Data was analysed using a narrative synthesis method. Results: Among 8370 articles, 58 met inclusion criteria, yielding 35 articles from 23 countries. Three main themes emerged: personal, psychological, and organisational factors, encompassing seven determinants including work experience, knowledge, guideline adherence, uncertainty management, perceived pressure, time constraints, and diagnostic resource availability. Uncertainty management was key, with work experience and knowledge mitigating it. No additional factors emerged in the updated search. Conclusion: Enhanced uncertainty management decreases perceived patient and/or parental pressure to prescribe antibiotics, contributing to reducing potentially inappropriate prescribing (PIP). Therefore, it is imperative to educate physicians on effectively managing uncertainty. Interventions to improve antibiotic prescribing should be tailored to the specific needs and preferences of the different prescribing physicians. Full article

Spider mite infestation has a severe impact on tea growth and quality. In this study, we conducted a deep exploration of the functions and regulations of the CsPIP5K gene family using chromosomal localization and collinearity analysis. Additionally, we carefully examined the cis elements within these genes. To fully understand the metabolic response of CsPIP5K under spider mite infection, we integrated previously published metabolomic and transcriptomic data. Our analysis revealed that multiple CsPIP5K genes are associated with phospholipid metabolism, with CsPIP5K06 showing the strongest correlation. Therefore, we employed qPCR and subcellular localization techniques to determine the expression pattern of this gene and its functional location within the cell. Overall, this study not only comprehensively elucidated the characteristics, structure, and evolution of the CsPIP5K gene family but also identified several candidate CsPIP5K genes related to phospholipid biosynthesis and associated with spider mites based on previously published data. This research makes a significant contribution to enhancing the resistance of tea to spider mite and maintaining optimal tea quality. Full article

In order to screen candidate aquaporin genes involved in resisting osmotic stress, we analyzed the physiological responses and the expression levels of aquaporin genes in garlic under drought and salt stress with ‘Er Shuizao’ as plant material. Different physiological indicators were detected under drought and salt stress treatments. RT-qPCR was used to detect the expression levels of the candidate aquaporin genes in specific tissues. Finally, we screened AsPIP1-3 as a candidate gene and analyzed its function. The results showed that the relative water content and chlorophyll content of leaves decreased, the O₂⁻ production rate increased, and H₂O₂ accumulated in garlic under drought and salt stress. The activities of SOD, POD, and CAT enzymes first increased and then decreased in garlic. The content of soluble sugar and proline increased to maintain cell osmotic balance, and the content of MDA and relative conductivity continued to increase. Most aquaporin gene expression first increased and then decreased in garlic under drought and salt stress. AsPIP1-3 gene expression is up-regulated under drought and salt stress in garlic. The relative expression was the highest on the 6th day of stress, being related to antioxidant enzyme activity and osmotic regulation. The consistent changes in gene expressions and physiological responses indicated that AsPIP1-3 played a role in resisting garlic osmotic stress. AsPIP1-3 was located on the cell membrane, being consistent with the predicted results of subcellular localization. The germination rate and root length of transgenic Arabidopsis under drought stress were significantly different from the wild type. Drought stress reduced the ROS accumulation of transgenic Arabidopsis, and the antioxidant enzyme activity was significantly higher than the wild type. The relative conductivity and MDA content significantly decreased, and the proline content increased under drought stress. The expression level of the genes related to drought stress response (AtRD22, AtP5CS, AtABF3, and AtLEA) significantly increased. The overexpression of AsPIP1-3 genes improved the drought tolerance of transgenic Arabidopsis plants, showing that AsPIP1-3 proteins enhanced drought tolerance. Our study laid a foundation for exploring the regulatory mechanism of garlic to abiotic stress. Full article

The grapevine was one of the earliest domesticated fruit crops and has been cultivated since ancient times. It is considered one of the most important fruit crops worldwide for wine and table grape production. The current grape varieties are the outcome of prolonged selection initiated during the domestication process of their wild relative. Recent genetic studies have shed light on the origins of the modern domestic grapevine in western Europe, suggesting that its origin stems from the introgression between eastern domestic grapes and western wild grapes. However, the origin of ancient grapevines remains largely unexplored. In this study, we conducted an extensive analysis of 2228 well-preserved waterlogged archaeological grape pips from two sites in Sardinia (Italy), dated to the Late Bronze Age (ca. 1300–1100 BC) and the Iron Age (4th and 3rd centuries BC). Using morphometrics and linear discriminant analyses, we compared the archaeological grape pips with modern reference collections to differentiate between wild and domestic grape types and to investigate similarities with 330 modern cultivars. Grape pips from the Late Bronze Age displayed a high percentage of similarity with domesticated grapevines, with a small percentage assigned to wild ones, while the majority of grape pips from the Iron Age were classified as domestic. Discriminant analyses revealed that both white and red grape varieties were cultivated during the Late Bronze and Iron Ages, suggesting a high level of diversification in grape cultivation. Furthermore, a high percentage of archaeological grape pips from both periods showed strong similarities with modern cultivars from the Caucasus and Balkans. This suggests that the great diversity of grapevines present in Sardinia could result from interbreeding between western Asian cultivars and local grapevines that began in the Late Bronze Age. Additionally, a substantial proportion of archaeological grape pips exhibited similar morphometric characteristics to two important Mediterranean grape cultivars: “Muscat à petits grains blancs” and “Garnacha”. Full article