Search Results (32,587)

Progressive immune damage associated with Human Immunodeficiency Virus (HIV) alters mucosal homeostasis, favouring oral microbial imbalance and the development of opportunistic infections. The aim of this study was to characterize the composition and structure of the oral microbiota in different clinical conditions of HIV infection. A cross-sectional study was conducted in 99 Mexican men divided into five groups: HIV-negative controls, newly diagnosed without antiretroviral treatment, virally suppressed, with oral candidiasis, and with HPV infection. Metagenomic DNA was obtained from salivary samples, and the V1–V3 region of the 16S rRNA gene was massively sequenced. Taxonomic profiles, alpha/beta diversity, differential abundance, microbial co-occurrence networks and degree of dysbiosis were analysed. The results showed distinctive profiles between the groups. Alpha and beta diversity was significantly higher in the groups with oral Candida and HPV lesions, reflecting a disturbance of microbial balance. Differential abundance analysis revealed an increase in Streptococcus, Veillonella, Lactobacillus and Actinomyces genera in HIV patients, while healthy subjects showed higher abundance of Neisseria, Treponema, and Rothia, associated with a eubiotico state. The group of patients with HPV lesions had the highest number of taxa with differential abundance, suggesting an ecological environment altered by the lesion. Analysis of co-occurrence networks revealed a progressive pattern of microbial complexity: controls presented simple networks with weak positive correlations, while HIV groups showed increased connection density and appearance of structured nuclei. The group of patients with HPV lesions presented the highest connectivity, with multiple strongly correlated cores and core nodes such as Prevotella melaninogenica and Shuttleworthia. The dysbiosis score increased progressively from healthy subjects to those with HPV lesions, indicating a gradient of oral microbial disruption. These findings suggest that HIV immunosuppression and the presence of oral lesions are associated with enhanced dysbiosis, although their individual contributions could not be independently assessed due to the absence of non-HIV lesion controls. The integration of microbial networks and dysbiosis scores could be useful for assessing mucosal and immune health in people with HIV and used as biomarkers of clinical progression. Full article

Somatic cell nuclear transfer (SCNT) holds promise for animal cloning but remains limited by low efficiency and phenotypic abnormalities, often attributed to incomplete nuclear reprogramming. This study presents an integrative genomic and epigenomic analysis of cloned buffaloes and their respective donors using long-read Oxford Nanopore sequencing. Our results showed a high degree of genomic similarity between clones and donors, with most variations located in non-coding regions and structural variants (SV) distributions highly correlated at the chromosomal level. Gene and protein level overlap of SV-affected loci revealed 70.9–73.3% gene-level and 69.7–72.5% protein-level similarity. Despite this genetic similarity, DNA methylation analysis identified differentially methylated regions (DMRs), particularly in intergenic and promoter regions. Clones exhibited slightly lower CpG methylation than the donors. The DMRs in donor vs. clone comparisons indicated higher hypomethylated regions than hypermethylated regions. Functional enrichment of DMR-associated genes highlighted pathways linked to mitochondrial function, oxidative phosphorylation, and reproductive processes. Although clones showed moderate genome-wide methylation correlation with donors, key differences in methylation suggest incomplete epigenetic reprogramming. Despite these epigenetic differences, all clones were phenotypically normal and healthy into adulthood. This study offers the first comprehensive SV and methylome profile of SCNT-derived buffaloes and emphasizes the role of epigenetic mechanisms in clone development and health, providing valuable insights to enhance cloning efficiency. Full article

The terahertz (THz) frequency range holds critical importance for next-generation, wireless communications and biomedical sensing applications. However, conventional metamaterial design approaches suffer from computationally intensive simulations and optimization processes that can extend over several months. This work presents an intelligent inverse design framework integrating deep neural network (DNN) surrogate modeling with success-history-based adaptive differential evolution (SHADE) for tunable graphene-based THz metasurfaces. Our DNN surrogate model achieves an exceptional coefficient of determination (R² = 0.9984) while providing a four-order-of-magnitude acceleration compared with conventional electromagnetic solvers. The SHADE-integrated framework demonstrates 96.7% accuracy in inverse design tasks with an average convergence time of 10.2 s. The optimized configurations exhibit significant tunability through graphene Fermi level modulation, as validated by comprehensive electromagnetic field analysis. This framework represents a significant advancement in automated electromagnetic design and establishes a robust foundation for intelligent photonic systems across diverse frequency regimes. Full article

Fragaria pentaphylla, a unique wild strawberry species in China, is rich in various fruit colors and a valuable resource for studying color genes. Fruits of different colors from F. pentaphylla were selected as the experimental material. Liquid chromatography-mass spectrometry (LC-MS) and high-throughput RNA sequencing (RNA-seq) were employed to identify key genes responsible for the development of different fruit colors. Metabolite analysis revealed that 3249 metabolites were detected, including nine differential metabolites related to anthocyanin synthesis and five biological pathways. Additionally, an analysis combining transcriptome and metabolome data showed that the structural genes FpDFR, FpCHS, FpCHI, and FpUFGT were upregulated in red fruit, with significantly higher expression levels compared to pink and white fruits, actively promoting anthocyanin production in red fruit. Conversely, genes FpANR and FpLAR were upregulated in white fruit, enhancing catechin synthesis and inhibiting anthocyanin formation. The gene FpPAL was upregulated in pink fruit. Transcription factors FpbHLH18, FpMYB1, FpMYB24, and FpMYB114 collaborate with structural genes to enhance the synthesis of anthocyanins in red fruit. The findings improve our understanding of the molecular mechanisms that control anthocyanin production in F. pentaphylla. The identified key candidate genes may be utilized in the molecular breeding of strawberries. Full article

The theory of integral inequalities has a wide range of applications in physics and numerical computation, and plays a fundamental role in mathematical analysis. The present study delves into the attractive domain of Hermite–Hadamard–Mercer (H-H-M)-type inequalities having a special emphasis on Wright’s general functions, referred to as Raina’s functions in the scientific literature. The main goal of our progressive study is to use Raina’s Fractional Integrals to derive two useful lemmas for second-differentiable functions. Using the derived lemmas, we proved a large number of fractional integral inequalities related to trapezoidal and midpoint-type inequalities where those that are twice differentiable in absolute values are convex. Some of these results also generalize findings from previous research. Next, we provide applications to error estimates for trapezoidal and midpoint quadrature formulas and to analytical evaluations involving modified Bessel functions of the first kind and q-digamma functions, and we show the validity of the proposed inequalities in numerical integration and analysis of special functions. Finally, the results are well-supported by numerous examples, including graphical representations and numerical tables, which collectively highlight their accuracy and computational significance. Full article

Traditional analyses of ship roll damping and added moment of inertia rely on free roll decay and forced roll tests, but acquiring linear (small angles) and nonlinear (large angles) relationships demands extensive computational cases and parameter fitting, limiting efficiency. To address this, this study couples Support Vector Machine (SVM) and Neural Ordinary Differential Equation (NODE) networks: SVM solves for added moment of inertia, linear damping, and nonlinear damping, while NODE constructs a complete model for the roll motion equation. Using the DTMB5415 hull form, Computational Fluid Dynamics (CFD) simulations of forced roll build a “time-angle-moment” sample space, and the coupled model learns and predicts free roll decay under different initial angles. The results show that SVM effectively determines roll damping and added moment of inertia from constant-amplitude variable-frequency and constant-frequency variable-amplitude data, reducing required cases significantly. NODE’s simulation of free roll decay validates coefficient accuracy. Within a certain angle range, the SVM-NODE model meets rapid roll motion analysis needs, providing an innovative method for ship roll research and engineering. Full article

In human cells, the biogenesis of membrane proteins, which account for one quarter of polypeptides and sixty percent of human drug targets, is initiated at the membrane of the endoplasmic reticulum (ER). This process involves N-terminal signal peptides or transmembrane helices in the membrane protein precursors. Over one hundred proteins enable membrane-targeting and -insertion of the precursors as well as their folding and covalent modifications. Four targeting pathways to the Sec61 channel in the ER membrane with their effectors and three cooperating or independent membrane protein–insertases have been identified. We combined knock-down of individual components of these pathways and insertases in HeLa cells with label-free quantitative mass spectrometric analysis of the proteomes. Differential protein abundance analysis in comparison to control cells was employed to identify clients of components involved in the targeting or membrane insertion of precursors. Alternatively, knock-out cells or relevant patient fibroblasts were employed. The features of the client polypeptides were characterized to identify the client types of the different components and, ideally, their rules of engagement. In this review/article-hybrid, the focus is on global lessons from and limitations of the proteomic approach in answering the cell biological question, as well as on new aspects, such as N-terminal acetylation of membrane protein precursors. Full article

Background/Objectives: The objectives of this study were to determine whether the early initiation of cardiac rehabilitation (CR) within 6 weeks of discharge improves long-term outcomes in patients hospitalized for acute heart failure (HF) and to evaluate whether baseline lysyl oxidase-like 2 (LOXL2) levels affect the response to CR. Methods: We prospectively enrolled patients with acute HF who completed a structured Heart Failure Disease Management Program between January 2019 and July 2022. Participants were categorized into an early-CR group (initiating supervised CR within 6 weeks post-discharge and continuing a home-based program) or a non-CR group. The primary outcome was all-cause mortality. The secondary outcomes included HF rehospitalization and changes in scores on the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) at 6 and 12 months. A post hoc analysis was conducted to stratify patients by baseline LOXL2 levels in order to assess differential CR effects in relation to the severity of cardiac fibrosis. Results: Out of 162 patients, 34 participated in early CR. After 1:1 propensity score matching, each group contained 33 patients. Over a median follow-up of 2.85 years, the early-CR group experienced lower all-cause mortality (0 vs. 87.2 events per 1000 patient-years; rate difference: −0.087). A subgroup analysis revealed the greatest benefit among patients with LOXL2 levels > 200 pg/mL (0 vs. 172.3 events per 1000 patient-years; rate difference: −0.172). Conclusions: Early post-discharge CR was associated with improved survival in patients with acute HF. The survival benefit was more pronounced in patients with an elevated level of LOXL2, suggesting its potential role as a biomarker for fibrosis-guided CR strategies. Health systems seeking scalability may consider embedding exercise-based and biomarker-guided CR programs within clinical networks early on to improve access while advancing patient-centered care. Further randomized trials are warranted to confirm these findings. Full article

As urban-living heritage sites, mountainous historic districts face the dual challenges of authenticity preservation and living development and the diverse and complex needs of different user groups. To address these challenges, this study systematically examines the cognitive differences between residents and merchants in mountainous historic districts and their implications for sustainable heritage management, using the Ciqikou Historic District in Chongqing as a case study. Through grounded theory methodology, we investigate residents and merchants via questionnaires and semi-structured interviews. Using coding analysis, the study reveals the cognitive similarities and differences of different users toward mountainous historic districts and explores their formation mechanisms, focusing on the spatial differentiation of cognition influenced by topographical and locational factors. Results indicate that both user groups share common cognitive concerns regarding building safety, transportation, policies, and infrastructure. Residents prioritise aspects related to daily convenience, whereas merchants focus more on economic benefits, leading to differences in their cognitive classifications and evaluations. Location plays a significant role in shaping user cognition, with notable cognitive differences observed between residents and merchants across different locations, and intra-group variation exists within the same user group at different locations. Based on a living–authenticity theoretical framework, this study constructs a living development–authentic preservation strategic framework and a multidimensional synergistic implementation framework encompassing integrity–locality–user, providing effective pathways for the preservation and sustainable development of mountainous historic districts. Full article

In this study, we explore the neuroprotective and modulatory potential of graphenic materials (GMs) in terms of the maturation of dopaminergic neurons and their capacity to counteract the cellular stress induced by toxins such as MPP⁺ (1-methyl-4-phenylpyridinium) and Tunicamycin. We found that GMs promote significant morphological changes in neuronal cells after prolonged exposure, enhancing both differentiation and cellular adhesion. Through structural analysis, we unveiled a complex organization of GMs and a marked upregulation of tyrosine hydroxylase (TH), a key marker of mature dopaminergic neurons. Under oxidative stress induced by MPP⁺, GMs significantly reduced the release of lactate dehydrogenase (LDH), indicating protection against mitochondrial damage. Moreover, GMs substantially decreased the levels of α-synuclein (α-Syn), a protein closely associated with neurodegenerative disorders such as Parkinson’s disease. Notably, partially reduced graphene oxide (PRGO) and fully reduced graphene oxide (FRGO) films were particularly effective at reducing α-Syn-associated toxicity compared to positive controls. Under conditions of endoplasmic reticulum (ER) stress triggered by Tunicamycin, GMs—especially PRGO microflakes—modulated the unfolded protein response (UPR) pathway. This effect was evidenced by the increased expression of BIP/GRP78 and the decreased phosphorylation of stress sensors such as PERK and eIF2α; this suggests that a protective role is played against ER stress. Additionally, GMs enhanced the synthesis of Torsin 1A, a chaperone protein involved in correcting protein folding defects, with PRGO microflakes showing up to a fivefold increase relative to the controls. Through the cFos analysis, we further revealed a pre-adaptive cellular response in GM-treated cells exposed to MPP⁺, with PRGO microflakes inducing a significant twofold increase in cFos expression compared to the positive control, indicating partial protection against oxidative stress. In conclusion, these results underscore GMs’ capacity to modulate the critical cellular pathways involved in oxidative, mitochondrial, and ER stress responses, positioning them as promising candidates for future neuroprotective and therapeutic strategies. Full article

Background: Inflammatory bowel disease (IBDs) are chronic, immune-mediated disorders of the gastrointestinal tract, encompassing ulcerative colitis (UC) and Crohn’s disease (CD), and primarily affecting individuals with genetic susceptibility. IBDs are characterized by dysregulated mucosal immune responses to intestinal microbiota, leading to sustained inflammation and tissue damage. These conditions not only pose a significant burden on healthcare systems but are also frequently associated with distinct comorbidities. Rationale: Given the immunological nature of both IBDs and type 2 diabetes (T2D)—each involving a complex interplay between genetic predisposition and environmental triggers—an increasing number of studies have suggested a pathophysiological link between the two. Both diseases involve chronic low-grade inflammation and alterations in immune signaling pathways, such as cytokine dysregulation, T-cell imbalance, and aberrant innate immune activation. Methods: To investigate this association more robustly, we conducted a cohort study involving 49 consecutive patients diagnosed with both IBD and T2D. Results: Our findings revealed a strong correlation between the two conditions, with UC emerging as the predominant IBD subtype linked to T2D. Notably, the highest prevalence was observed in patients aged 65–74 years, suggesting age-related immune modulation may play a role. In a matched case-control analysis (48 cases vs. 96 controls), 70.8% of the IBD–T2D cases were diagnosed with UC, 25.0% with CD, and 4.2% with indeterminate colitis. Similarly, in the cohort study, UC accounted for 73.81% of cases, CD for 21.43%, and non-determined colitis for 4.76%. Conclusions: These data support the hypothesis that UC, more so than CD, exhibits a stronger immunological and clinical association with T2D. Interestingly, CD was absent in the 55–64 age group, potentially indicating age-specific immunological trajectories or differential environmental exposures. The observed patterns reinforce the concept that immune dysregulation is a shared underpinning of both IBD and T2D, and that UC may serve as an immunological bridge linking gastrointestinal and metabolic inflammation. Full article

This study assesses decarbonization progress in the European Union manufacturing sector between 2015 and 2023, using harmonized Eurostat indicators. The dataset covers emission intensity, energy intensity, renewable energy use, and structural markers of value added. After standardization, variables are reduced through principal component analysis (PCA). The resulting scores are then clustered with k-means, with the number of clusters chosen using elbow and silhouette diagnostics and validated through hierarchical clustering, representing a methodological innovation over existing typological studies. The results highlight persistent heterogeneities across member states. A group of frontrunners combines low intensities with a high share of RES; efficiency-centric groups advance mainly through energy intensity reductions but lag in fuel-switching, while structurally constrained groups remain hindered by energy mix limitations and outdated capital stocks. Dynamically, moderate convergence is observed along the main transition dimension, but persistent divergence remains in structural composition. These patterns justify differentiated policy approaches: accelerating fuel substitution where efficiency gains have already been achieved and integrated packages of modernization and infrastructure in structurally constrained economies. The novelty of this study lies in providing a harmonized, EU-wide, and reproducible typology of industrial decarbonization trajectories, enabling systematic cross-country comparison. Policy relevance is reinforced by linking the typology to current EU instruments such as the Emissions Trading System (ETS), the Carbon Border Adjustment Mechanism (CBAM), the Innovation Fund, and the Net-Zero Industry Act. The integration of PCA with clustering provides an evidence-based that is valuable for prioritizing European industrial policies in line with the Green Deal. Full article

Nitrogen is an essential mineral nutrient for plant growth and development. However, the molecular response mechanisms of sugarcane under varying nitrogen regimes remain unclear. This study investigated the dynamic responses of sugarcane (GT42) leaves to nitrogen treatment using hydroponic systems. Leaf samples were collected under low nitrogen (LN, 0.2 mM NH₄NO₃) and normal nitrogen (NN, 2 mM NH₄NO₃) treatments at 1, 3, 6, 12, 24, 48, and 72 h, as well as under high nitrogen (HN, 6 mM NH₄NO₃) treatment at 3, 6, and 24 h. RNA-Seq analysis identified differentially expressed genes (DEGs) between LN/NN and HN/NN treatments at corresponding time points. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs from both LN/NN and HN/NN comparisons revealed significant enrichment in nitrogen metabolism and zeatin biosynthesis pathways. These findings aligned with our Weighted Gene Co-Expression Network Analysis (WGCNA) results from LN-treated samples. Through detailed reconstruction of the nitrogen metabolic pathway and zeatin biosynthesis co-expression networks, we established their pivotal regulatory roles in sugarcane’s adaptation to varying nitrogen availability. Our results demonstrate a dynamic, concentration-dependent regulatory network in sugarcane leaves under nitrogen treatment. These findings provide potential targets for improving nitrogen use efficiency (NUE) in sugarcane breeding programs. The study offers new insights into the molecular mechanisms underlying sugarcane’s response to nitrogen fluctuations, with implications for developing nitrogen-efficient cultivars. Full article

This study explores the chemical and sensory differentiation of Greek white wines produced from five indigenous grape varieties—Savvatiano, Vidiano, Moschofilero, Assyrtiko, and Malagouzia—across diverse terroirs in Greece. A targeted analytical approach was employed to quantify 12 key volatile aroma compounds derived primarily from amino acid metabolism and lipid degradation, using GC-MS and GC-FID. The selected volatiles, including isoamyl alcohol, phenylethyl alcohol, tyrosol, and hexanoic acid ethyl ester, were chosen for their sensory relevance and their biosynthetic linkage to nitrogenous precursors. Principal Component Analysis (PCA) of wines from the 2019 and 2020 vintages revealed clear varietal clustering, under standardized winemaking conditions. Malagouzia wines were characterized by rich and diverse volatile profiles, particularly long-chain fatty acids and esters, while Vidiano exhibited a consistently restrained aromatic expression. Sensory analysis using sorting and ultra-flash profiling confirmed the chemical clustering, with Moschofilero, Vidiano and Malagouzia wines forming distinct sensory groups. The findings demonstrate that key amino acid-derived volatiles can serve as biochemical markers of varietal typicity and support the use of volatile profiling as a tool for terroir-driven wine classification and quality assessment in Greek white wines. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal type of neurodegenerative disease marked by progressive and selective degeneration of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. However, the intricate molecular mechanisms underlying primary cell death pathways, including ferroptosis-related genes (FRGs) mediating MN dysfunction in ALS, remain elusive. Ferroptosis, a novel type of iron-dependent cell death with the accumulation of lipid peroxidation products, stands distinct from apoptotic-related stress and other cell death mechanisms. Although growing advances have highlighted the role of iron deposition, apoptosis and alteration of antioxidant systems in ALS pathogenesis, there is little data at the systems biology level. Therefore, we performed a comprehensive bioinformatic analysis of bulk RNA-sequencing (RNA-seq) data by systematically comparing the gene expression profiles from iPSC-derived MNs of ALS patients and healthy controls using our datasets as well as from the GEO database to reveal the role of ferroptosis-related gene alterations in ALS, especially in selective MN vulnerability of FUSED IN SARCOMA (FUS) mutations. In this study, we first identified differentially expressed genes (DEGs) between FUS mutant and healthy controls. Subsequently, the crossover genes between DEGs and FRGs were selected as differentially expressed ferroptosis-related genes (DEFRGs). Functional enrichment and protein–protein interaction (PPI) analysis of DEFRGs identified that DNA damage, stress response and extra cellular matrix (ECM) were the most significantly dysregulated functions/pathways in FUS-ALS causing mutations compared to healthy controls. While GSEA analysis showed enrichment of genes associated with apoptosis, the degree of ferroptosis and iron ion homeostasis/response to iron of FUS MNs was lower. Altogether, our findings may contribute to a better understanding of the relevant role of cell death pathways underlying selective vulnerability of MNs to neurodegeneration in FUS-ALS pathophysiology. Full article