Search Results (24)

Today, the development of ion exchange membranes has increased considerably in various applications, such as water treatment, energy conversion and storage, as well as environmental applications. In this study, several ion exchange membranes based on cellulose acetate propionate (CAP) and ionic liquids (ILs) were fabricated using the phase inversion method, aiming to develop more sustainable membrane materials for environmental and energy applications. Three different ILs with a similar cation and different anions (1-(4-sulfobutyl)-3-methylimidazolium trifluoromethanesulfonate [SMIM][TFS], 1-(4-sulfobutyl)-3-methylimidazolium hydrogen sulfate [SMIM][HS], and 1-(4-sulfobutyl)-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [SMIM][TFSI]) were used in three concentrations (i.e., 9, 17, and 23 wt.%). The main objective of this work is to evaluate the influence of the anion structure on the membrane’s physical, morphological, hydrophilic, thermal, mechanical, and electrochemical properties. Water contact angle measurements demonstrated the weaker hydrophilicity of composite membranes containing [SMIM][TFS] (81–106°) and [SMIM][TFSI] (87–94°) in comparison with pure CAP (~79°) and CAP/[SMIM][HS] (79–83°) membranes. The CAP/[SMIM][HS] membrane showed higher elongation at break (~36%) compared with the pure CAP membrane (~24%), confirming the plasticization behavior of [SMIM][HS]. The CAP/[SMIM][TFS] membrane containing 23 wt.% of IL showed promising membrane potential, permselectivity, transport number and ion flux ratio values of 53.2 mV, 74.7%, 0.85, and 5.5, respectively, indicating its potential as a candidate for further evaluation in electrochemical membrane processes such as electrodialysis and fuel cells. Full article

Background/Objectives: A central question in molecular genetics concerns how transcriptional regulatory sequences and de novo genes originate and reach evolutionary fixation. In this study, we utilize the human bicistronic gene SMIM45 as a model to analyze the evolutionary trajectories of gene development. This locus comprises several functional units: three enhancers (one featuring an embedded silencer), an exonic silencer that partially overlaps an ORF, a highly conserved ancestral sequence encoding a 68 aa microprotein, and a human-specific de novo gene encoding a 107 aa protein expressed spatiotemporally in embryonic brain tissues. Methods: The alignment of gene sequences from different species was used to determine the evolutionary development of enhancers and silencers, and the development of the exonic silencer was determined through application of the cultivator model and assessment of nearest-neighbor bases. Results: We identify significant disparities in formation mechanisms; for example, the LOC127896430 NANOG hESC enhancer originated simply via two Alu insertions that constitute the enhancer. In contrast, the exonic silencer (a segment of the LOC130067579 ATAC-STARR-seq lymphoblastoid silent region 13815)—a distinct, novel type of silencer—originated from a combination of diverse mechanisms, including a “cultivator gene” process of base pair fixation, consistent with the cultivator model proposed by Li Zhao and coworkers. Conclusions: SMIM45 exemplifies novel development mechanisms occurring over hundreds of millions of years, culminating in the birth of a human-specific, de novo 107 aa cistron. The associated complex of enhancers and silencers suggests intricate regulation of the 107 aa protein in fetal brain tissues. Full article

Bovine Viral Diarrhea Virus (BVDV) poses a significant threat to the global cattle industry, causing substantial economic losses. Long non-coding RNAs (lncRNAs) play crucial regulatory roles in various biological processes, including viral infections. However, the specific lncRNAs influencing BVDV replication remain poorly characterized. This study identified lncSMIM14 as a key host factor upregulated during BVDV infection in MDBK cells. Functional analyses demonstrated that lncSMIM14 overexpression significantly enhanced BVDV replication, evidenced by increased viral mRNA levels, progeny virus titers, cytopathic effects, and dsRNA abundance, while its knockdown exerted the opposite effect. Mechanistically, we revealed that lncSMIM14 specifically targets and positively regulates the expression of the endocytosis-related GTPase Rab3a. Importantly, Rab3a itself was shown to be essential for efficient BVDV replication, as its overexpression promoted viral replication, and its knockdown inhibited it. Furthermore, Rab3a co-localized with key endocytic regulators Rab5a and Rab7a, and both lncSMIM14 overexpression and Rab3a overexpression promoted the formation of endocytic vesicles, particularly post-BVDV infection. Our findings unveil a novel mechanism wherein BVDV exploits the host lncRNA lncSMIM14 to hijack Rab3a-mediated endocytosis, facilitating its own replication. This study identifies the lncSMIM14-Rab3a axis as a critical host pathway subverted by BVDV, providing new potential targets for antiviral intervention. Full article

Microproteins are small polypeptides translated from short open reading frames (sORFs) that typically encode < 100 amino acids. Advances in ribosome profiling, mass spectrometry, and computational prediction have revealed a growing number of microproteins that play important roles in cellular metabolism, organelle function, and stress adaptation; however, these were considered non-coding or functionally insignificant. At the mitochondrial level, microproteins, such as MTLN (also known as mitoregulin/MOXI) and BRAWNIN, contribute to lipid oxidation, oxidative phosphorylation efficiency, and respiratory chain assembly. Other microproteins at the endoplasmic reticulum–mitochondria interface, including PIGBOS and several muscle-resident regulators of calcium cycling, show diverse biological contexts in which these microproteins act. A subset of microproteins responds to nutrient availability. For example, SMIM26 modulates mitochondrial complex I translation under serine limitation, and non-coding RNA expressed in mesoderm-inducing cells encoded with peptides facilitates glucose uptake during differentiation, indicating that some microproteins can affect metabolic adaptation through localized translational- or organelle-level mechanisms. Rather than functioning as primary nutrient sensors, these microproteins complement classical nutrient-responsive pathways such as AMP-activated protein kinase-, peroxisome proliferator-activated receptor-, and carbohydrate response element binding protein-mediated signaling. As the catalog of microproteins continues to expand, integrating proteogenomics, nutrient biology, and functional studies will be central to defining their physiological relevance; these integrative approaches will also help reveal their potential applications in metabolic health. Full article

Background/Objectives: Psoriasis is currently treated with biologics targeting the IL-17A signaling, which plays a major role in immune response and keratinocyte hyperproliferation. These include inhibitors of IL-17A and/or its heterodimer with IL-17F (Secukinumab, Ixekinumab and Bimekizumab) and the receptor IL17-RA (Brodalumab). Although these drugs are safe and highly effective, there is significant variability in response among patients. This can be partly attributed to the patients’ genetic background, thus pointing to the need to identify pharmacogenetic markers for treatment response. Methods: The study involved 88 Greek patients who were treated with inhibitors of the IL-17A signaling for at least 6 months. Patients were classified as responders and non-responders according to the change in Psoriasis Area Severity Index. A total of 730,000 variants were genotyped and analyzed for association with the 3-month and 6-month responses to treatment. Results: The analysis identified 21 variants which were associated with the response, showing statistical significance after Bonferroni correction. These include variants located in protein coding genes (TP63, NRG1, SCN8A, TAF9, TMEM9, SMIM36, SYT14, BPIFC, SEZ6L2, PCARE), as well as intergenic and long non-coding RNA intronic variants. The functional significance of the variants was assessed using in silico analysis and for several variants, a link with immune processes was proposed. Notably, rs11649499 status, which was associated with complete clinical remission at 3 months, may influence key lipid mediators involved in psoriasis. Conclusions: This GWAS identified novel variants that could be utilized upon validation in larger populations as predictive markers regarding patient response to drugs targeting the IL-17A pathway. Full article

This study explores how Instagram fashion influencers build brand loyalty through customer engagement within the framework of sustainable consumption. Grounded in the stimulus–organism–response (SOR) theory, influencer marketing is conceptualized as a stimulus that activates customer engagement (organism), which in turn enhances brand loyalty (response). A cross-sectional survey was conducted with 279 Instagram users in Palestine who actively follow fashion influencers, and the model was tested using partial least squares structural equation modeling (PLS-SEM). The findings confirm that social media influencer marketing (SMIM) significantly improves both engagement and loyalty. Customer engagement was found to be both a partial mediator and a significant moderator, such that highly engaged consumers exhibited stronger loyalty responses—suggesting intensified value alignment and emotional resonance in sustainability contexts. This study extends the prior literature by integrating the creation–consumption–contribution (C–C–C) model into the SOR framework and conceptualizing engagement as both a psychological state and a boundary condition. It contributes to sustainable consumption research by illustrating how participatory digital behaviors can foster ethical brand relationships, particularly in emerging economies. Practically, it offers strategic guidance for fashion brands and influencers to design campaigns that promote co-creation, authenticity, and eco-conscious narratives. It also emphasizes the importance of aligning influencer values with those of sustainability-minded consumers to foster long-term loyalty. By contextualizing the findings within the Palestinian market, the study highlights how cultural factors may shape engagement and sustainability perceptions, paving the way for future cross-cultural investigations. Full article

Hepatocellular carcinoma (HCC) is a malignancy that is notorious for its dismal prognosis. Dysregulation of the tumor microenvironment (TME) in HCC has emerged as a key hallmark in determining disease progression and the response to immunotherapy. The aim of this study was to identify novel TME regulators that contribute to therapeutic resistance, thus providing mechanistic insights for targeted interventions. The expression of SMIM25 was evaluated in the the Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC) and Guangxi HCC cohorts, and its clinicopathological significance was assessed. RNA sequencing and bioinformatics analyses were performed to elucidate the potential impact of elevated SMIM25 levels. Immunohistochemistry (IHC) and single-cell mass cytometry (CyTOF) were employed to examine the cellular composition of the tumor microenvironment. The biological effects of SMIM25 on cell proliferation and migration were studied in vitro using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide(MTT) and wound healing assays, while its impact on tumor growth was evaluated in vivo in a nude mouse model. Transcriptomic and single-cell proteomic analyses were integrated to explore the mechanism by which SMIM25 affects the progression of HCC. The expression of SMIM25 was significantly up-regulated in both HCC tissues and cell lines (p < 0.05). RNA sequencing analyses revealed a significant positive correlation between SMIM25 expression and immunosuppression, and between SMIM25 expression and extracellular matrix(ECM)-related molecular features. Single-cell mass cytometry revealed two immunosuppressive cell clusters that were enriched in HCC patients with high SMIM25 expression. Moreover, SMIM25 was associated with immune exclusion and ECM remodeling signals in the TME of HCC. SMIM25 overexpression was associated with the expression of the tumor inflammatory marker cyclooxygenase-2(COX-2), and a COX-2 inhibitor could partially reverse the biological phenotype associated with SMIM25 expression in HCC cells (p < 0.05). Further transcriptome analysis in immunotherapy cohorts suggested the SMIM25-COX-2 axis might have predictive value for the response to immunotherapy. Our results suggest that SMIM25 may serve as a biomarker for the prognosis of HCC patients and may also be a predictive biomarker for the response to immunotherapy, enabling more precise and personalized HCC treatment. Full article

Aggressive B-cell lymphoma encompasses Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and, as per the 2016 WHO classification, high-grade B-cell lymphoma (HGBL) not otherwise specified (NOS) and HGBL double/triple hit (DH/TH). However, the diagnostic distinction of HGBL from BL and DLBCL is difficult by means of histology/immunostaining in a substantial number of patients. This study aimed to improve subtyping by the identification of molecular features of aggressive B-cell lymphomas, with a specific focus on HGBL. To this end, we performed a comprehensive gene expression and mutational pattern analysis as well as the detection of B-cell clonality of 34 cases diagnosed with BL (n = 4), DLBCL (n = 16), HGBL DH (n = 8), and HGBL NOS (n = 6). Three distinct molecular subgroups were identified based on gene expression, primarily influenced by MYC expression/translocation and cell proliferation. In HGBL, compared to BL, there was an upregulation of PRKAR2B and TERT. HGBL DH exhibited elevated expression of GAMT and SMIM14, while HGBL NOS showed increased expression of MIR155HG and LZTS1. Our gene mutation analysis revealed MYC, ARID1A, BCL2, KMT2D, and PIM1 as the most affected genes in B-cell lymphoma, with BCL2 and CREBBP predominant in HGBL DH, and MYC and PIM1 in HGBL NOS. Clonality analysis of immunoglobulin heavy and light chain rearrangements did not show distinguishable V- or J-usage between the diagnostic subgroups. Full article

Dendritic cells (DCs) serve as key regulators in tumor immunity, with activated DCs potentiating antitumor responses through the secretion of pro-inflammatory cytokines and the expression of co-stimulatory molecules. Most current studies focus on the relationship between DC subgroups and clear-cell renal-cell carcinoma (ccRCC), but there is limited research on the connection between DCs and ccRCC from the perspective of immune activation. In this study, activated DC genes were identified in both bulk and single-cell RNA-seq data. A prognostic model related to activated DCs was constructed using univariate, multivariate Cox regression and LASSO regression. The prognostic model was validated in three external validation sets: GSE167573, ICGC, and E-MTAB-1980. The prognostic model consists of five genes, PLCB2, XCR1, IFNG, HLA-DQB2, and SMIM24. The expression of these genes was validated in tissue samples using qRT-PCR. Stratified analysis revealed that the prognostic model was able to better predict outcomes in advanced ccRCC patients. The risk scores were associated with tumor progression, tumor mutation burden, immune cell infiltration, and adverse outcomes of immunotherapy. Notably, there was a strong correlation between the expression of the five genes and the sensitivity to JQ1, a BET inhibitor. Molecular docking indicated high-affinity binding of the proteins encoded by these genes with JQ1. In conclusion, our study reveals the crucial role of activated DCs in ccRCC, offering new insights into predicting immune response, targeted therapy effectiveness, and prognosis for ccRCC patients. Full article

High-radio-frequency (RF) conductivity is required in advanced electronic materials to reduce the electromagnetic loss and power dissipation of electronic devices. Graphene/copper (Gr/Cu) multilayers possess higher conductivity than silver under direct current conditions. However, their RF conductivity and detailed mechanisms have rarely been evaluated at the micro scale. In this work, the RF conductivity of copper–copper (P-Cu), monolayer-graphene/copper (S-Gr/Cu), and multilayer-graphene/copper (M-Gr/Cu) multilayer structures were evaluated using scanning microwave impedance microscopy (SMIM) and dielectric resonator technique. The results indicated that the order of RF conductivity was M-Gr/Cu < P-Cu < S-Gr/Cu at 3 GHz, contrasting with P-Cu < M-Gr/Cu < S-Gr/Cu at DC condition. Meanwhile, the same trend of M-Gr/Cu < P-Cu < S-Gr/Cu was also observed using the dielectric resonator technique. Based on the conductivity-related Drude model and scattering theory, we believe that the microwave radiation can induce a thermal effect at S-Gr/Cu interfaces, leading to an increasing carrier concentration in S-Gr. In contrast, the intrinsic defects in M-Gr introduce additional carrier scattering, thereby reducing the RF conductivity in M-Gr/Cu. Our research offers a practical foundation for investigating conductive materials under RF conditions. Full article

In the human genome, two short open reading frames (ORFs) separated by a transcriptional silencer and a small intervening sequence stem from the gene SMIM45. The two ORFs show different translational characteristics, and they also show divergent patterns of evolutionary development. The studies presented here describe the evolution of the components of SMIM45. One ORF consists of an ultra-conserved 68 amino acid (aa) sequence, whose origins can be traced beyond the evolutionary age of divergence of the elephant shark, ~462 MYA. The silencer also has ancient origins, but it has a complex and divergent pattern of evolutionary formation, as it overlaps both at the 68 aa ORF and the intervening sequence. The other ORF consists of 107 aa. It develops during primate evolution but is found to originate de novo from an ancestral non-coding genomic region with root origins within the Afrothere clade of placental mammals, whose evolutionary age of divergence is ~99 MYA. The formation of the complete 107 aa ORF during primate evolution is outlined, whereby sequence development is found to occur through biased mutations, with disruptive random mutations that also occur but lead to a dead-end. The 107 aa ORF is of particular significance, as there is evidence to suggest it is a protein that may function in human brain development. Its evolutionary formation presents a view of a human-specific ORF and its linked silencer that were predetermined in non-primate ancestral species. The genomic position of the silencer offers interesting possibilities for the regulation of transcription of the 107 aa ORF. A hypothesis is presented with respect to possible spatiotemporal expression of the 107 aa ORF in embryonic tissues. Full article

The regulation of food intake occurs at multiple levels, and two of the components of this process are orexigenic and anorexigenic peptides, which stimulate or inhibit appetite, respectively. The study of the function of these compounds in domestic cattle is essential for production efficiency, animal welfare, and health, as well as for economic benefits, environmental protection, and the contribution to a better understanding of physiological aspects that can be applied to other species. In this study, the real-time PCR method was utilized to determine the expression levels of GHRL, GHSR, SMIM20, GPR173, LEP, LEPR, and NUCB2 (which encode ghrelin, its receptor, phoenixin-14, its receptor, leptin, its receptor, and nesfatin-1, respectively) in the gastrointestinal tract (GIT) of Polish Holstein–Friesian breed cattle. In all analyzed GIT segments, mRNA for all the genes was present in both age groups, confirming their significance in these tissues. Gene expression levels varied distinctly across different GIT segments and between young and mature subjects. The differences between calves and adults were particularly pronounced in areas such as the forestomachs, ileum, and jejunum, indicating potential changes in peptides regulating food intake based on the developmental phase. In mature individuals, the forestomachs predominantly displayed an increase in GHRL expression, while the intestines had elevated levels of GHSR, GPR173, LEP, and NUCB2. In contrast, the forestomachs in calves showed upregulated expressions of LEP, LEPR, and NUCB2, highlighting the potential importance of peptides from these genes in bovine forestomach development. Full article

Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total N = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the β-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (p-values < 3.09 × 10⁻⁶; CDH17, TAS2R43, SMIM10L1, TAS2R14). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by TAS2R14, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, Streptococcus mutans and Staphylococcus aureus. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes. Full article

The liver is considered the major target organ affected by oral exposure to titanium dioxide nanoparticles (TiO₂ NPs), but the mechanism of hepatotoxicity is not fully understood. This study investigated the effect of TiO₂ NPs on the expression profile of long non-coding RNA (lncRNA) in hepatocytes and tried to understand the potential mechanism of hepatotoxicity through bioinformatics analysis. The human hepatocellular carcinoma cells (HepG2) were treated with TiO₂ NPs at doses of 0–200 μg/mL for 48 h and then RNA sequencing was implemented. The differential lncRNAs between the control and TiO₂ NPs-treated groups were screened, then the lncRNA–mRNA network and enrichment pathways were analyzed via multivariate statistics. As a result, 46,759 lncRNAs were identified and 129 differential lncRNAs were screened out. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the targeted mRNAs of those differential lncRNAs were enriched in the Hedgehog signaling pathway, Vasopressin-regulated water reabsorption, and Glutamatergic synapse. Moreover, two lncRNA–mRNA networks, including lncRNA NONHSAT256380.1-JRK and lncRNA NONHSAT173563.1-SMIM22, were verified by mRNA detection. This study demonstrated that an alteration in the lncRNA expression profile could be induced by TiO₂ NPs and epigenetics may play an important role in the mechanism of hepatotoxicity. Full article

Several corresponding regions of human and mammalian genomes have been shown to affect sensitivity to the manifestation of metabolic syndrome via nutrigenetic interactions. In this study, we assessed the effect of sucrose administration in a newly established congenic strain BN.SHR20, in which a limited segment of rat chromosome 20 from a metabolic syndrome model, spontaneously hypertensive rat (SHR), was introgressed into Brown Norway (BN) genomic background. We mapped the extent of the differential segment and compared the genomic sequences of BN vs. SHR within the segment in silico. The differential segment of SHR origin in BN.SHR20 spans about 9 Mb of the telomeric portion of the short arm of chromosome 20. We identified non-synonymous mutations e.g., in ApoM, Notch4, Slc39a7, Smim29 genes and other variations in or near genes associated with metabolic syndrome in human genome-wide association studies. Male rats of BN and BN.SHR20 strains were fed a standard diet for 18 weeks (control groups) or 16 weeks of standard diet followed by 14 days of high-sucrose diet (HSD). We assessed the morphometric and metabolic profiles of all groups. Adiposity significantly increased only in BN.SHR20 after HSD. Fasting glycemia and the glucose levels during the oral glucose tolerance test were higher in BN.SHR20 than in BN groups, while insulin levels were comparable. The fasting levels of triacylglycerols were the highest in sucrose-fed BN.SHR20, both compared to the sucrose-fed BN and the control BN.SHR20. The non-esterified fatty acids and total cholesterol concentrations were higher in BN.SHR20 compared to their respective BN groups, and the HSD elicited an increase in non-esterified fatty acids only in BN.SHR20. In a new genetically defined model, we have isolated a limited genomic region involved in nutrigenetic sensitization to sucrose-induced metabolic disturbances. Full article