Search Results (2,720)

Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic, non-communicable spectrum of diseases characterized by lipid accumulation. It is often asymptomatic, and its prevalence varies by region, age, gender, and economic status. It is estimated that 25% of the world’s population currently suffer from MAFLD, and 20 million patients will die from MAFLD-related diseases. In the last 20 years, tea and anti-obesity research have indicated that regularly consuming tea decreases the risk of cardiovascular disease, stroke, obesity, diabetes, and metabolic syndrome (MeS). In this review, we aimed to present studies concerning the influence of matcha extracts and epigallocatechin-3 gallate (EGCG) supplements on metabolic functions in the context of MAFLD in human and animal studies. The published data show promise. In both human and animal studies, the beneficial effects on body weight, cholesterol levels, and liver metabolism and function were noted, even in short-period experiments. The safety levels for EGCG and green tea extract consumption are marked. More experiments are needed to confirm the results observed in animal studies and to show the mechanisms by which green tea exerts its effects. The preliminary data from research concerning microbiota or epigenetic changes observed after polyphenols and green tea consumption need to be expanded. To improve the efficiency and availability of green tea or supplement consumption as a treatment for MAFLD patients, more research with larger groups and longer study durations is needed. Full article

Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific to ASD. While grey matter has been the primary focus, white matter (WM) may be more specific in identifying the particular biological signature of the neurodiversity of ASD. Diffusion tensor imaging (DTI) is the more appropriate tool to investigate WM in ASD. Despite being introduced in 1994, its application to ASD research began in 2001. Studies employing DTI identify altered fractional anisotropy (FA), mean diffusivity, and radial diffusivity (RD) in individuals with ASD compared to typically developing (TD) individuals. Methods: We systematically reviewed literature on 21 May 2025 on PubMed using the following strategy: (“autism spectrum”[ti] OR autistic[ti] OR ASD[ti] OR “high-functioning autism” OR Asperger*[ti] OR Rett*[ti]) AND (DTI[ti] OR “diffusion tensor”[ti] OR multimodal[ti] OR “white matter”[ti] OR tractograph*[ti]). Our search yielded 239 results, of which 26 were adult human studies and eligible. Results: Analysing the evidence, we obtained regionally diverse WM alterations in adult ASD, specifically in FA, MD, RD, axial diffusivity and kurtosis, neurite density, and orientation dispersion index, compared to TD individuals, mostly in frontal and interhemispheric tracts, association fibres, and subcortical projection pathways. These alterations were less prominent than those of children and adolescents, indicating that individuals with ASD may improve during brain maturation. Conclusions: Our findings suggest that white matter alterations in adults with ASD are regionally diverse but generally less pronounced than in younger populations. This may indicate a potential improvement or adaptation of brain structure during maturation. Further research is needed to clarify the neurobiological mechanisms underlying these changes and their implications for clinical outcomes. Full article

Background/Objectives: An important new consideration when studying autism spectrum disorder (ASD) is the bioenergetic mechanisms underlying the relatively recent rapid evolutionary expansion of the human brain, which pose fundamental risks for mitochondrial dysfunction and calcium signaling abnormalities and their potential role in ASD, as recently highlighted by insights from the BTBR mouse model of ASD. The rapid brain expansion taking place as Homo sapiens evolved, particularly in the parietal lobe, led to increased energy demands, making the brain vulnerable to such metabolic disruptions as are seen in ASD. Methods: Mitochondrial dysfunction in ASD is characterized by impaired oxidative phosphorylation, elevated lactate and alanine levels, carnitine deficiency, abnormal reactive oxygen species (ROS), and altered calcium homeostasis. These dysfunctions are primarily functional, rather than being due to mitochondrial DNA mutations. Calcium signaling plays a crucial role in neuronal ATP production, with disruptions in inositol 1,4,5-trisphosphate receptor (ITPR)-mediated endoplasmic reticulum (ER) calcium release being observed in ASD patient-derived cells. Results: This impaired signaling affects the ER–mitochondrial calcium axis, leading to mitochondrial energy deficiency, particularly in high-energy regions of the developing brain. The BTBR mouse model, with its unique Itpr3 gene mutation, exhibits core autism-like behaviors and metabolic syndromes, providing valuable insights into ASD pathophysiology. Conclusions: Various interventions have been tested in BTBR mice, as in ASD, but none have directly targeted the Itpr3 mutation or its calcium signaling pathway. This review presents current genetic, biochemical, and neurological findings in ASD and its model systems, highlighting the need for further research into metabolic resilience and calcium signaling as potential diagnostic and therapeutic targets for ASD. Full article

The wave spectrum, as a key statistical feature describing wave energy distribution, is crucial for understanding wave propagation mechanisms and supporting ocean engineering applications. This study, based on ERA5 reanalysis spectrum data, proposes a model combining CNN and xLSTM for rapid gridded wave spectrum prediction over the Bohai and Yellow Seas domain. It uses 2D gridded spectrum data rather than a spectrum at specific points as input and analyzes the impact of various input factors at different time lags on wave development. The results show that incorporating water depth and mean sea level pressure significantly reduces errors. The model performs well across seasons with the seasonal spatial average root mean square error (SARMSE) of spectral energy remaining below 0.040 m²·s and RMSEs for significant wave height (SWH) and mean wave period (MWP) of 0.138 m and 1.331 s, respectively. At individual points, the spectral density bias is near zero, correlation coefficients range from 0.95 to 0.98, and the peak frequency RMSE is between 0.03 and 0.04 Hz. During a typical cold wave event, the model accurately reproduces the energy evolution and peak frequency shift. Buoy observations confirm that the model effectively tracks significant wave height trends under varying conditions. Moreover, applying a frequency-weighted loss function enhances the model’s ability to capture high-frequency spectral components, further improving prediction accuracy. Overall, the proposed method shows strong performance in spectrum prediction and provides a valuable approach for regional wave spectrum modeling. Full article

Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype–phenotype correlations. Methods: Genetic testing was initially performed for 38 CFTR mutations, and in heterozygous patients or those in whom no mutation was detected, CFTR gene sequencing (NGS) was performed. Results: The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with CFTR class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with CFTR class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. Conclusions: We compared the results obtained with data from the literature and correlated the detected CFTR variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified CFTR variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis. Full article

Background/Objectives: Inborn errors of immunity (IEIs) represent a wide spectrum of diseases characterized by a predisposition to recurrent infections, as well as increased susceptibility to autoimmune, atopic, and autoinflammatory diseases and malignancies. The aim of this study was to report the registry-based frequency and describe the clinical characteristics of IEIs among patients in the Republic of Kazakhstan. Methods: We analyzed data from 269 patients belonging to 204 families who were either self-referred or referred by healthcare providers to the University Medical Center of Nazarbayev University with suspected IEIs. All patients resided in various regions across Kazakhstan. Results: A total of 269 diagnosed cases were identified in the national registry. The estimated prevalence was 1.3 per 100,000 population. The gender ratio was nearly equal, with 139 males and 130 females. The median age at diagnosis was 5 years (range: 1 month to 70 years), while the mean age was 11.3 years. The most common diagnosis was humoral immunodeficiency, observed in 120 individuals (44.6%), followed by complement deficiencies in 83 individuals (30.8%). Combined immunodeficiencies with syndromic features were found in 35 patients (13%), and phagocytic cell defects were identified in 12 patients (4.5%). The predominant clinical manifestations included severe recurrent infections and autoimmune cytopenias, while atopic and autoinflammatory symptoms were reported less frequently. Conclusions: These findings contribute to a better understanding of the registry-based distribution and clinical spectrum of IEIs in Kazakhstan and underscore the importance of early diagnosis and targeted care for affected individuals. Full article

Background: This study aimed to (a) assess the prevalence of multidrug-resistant (MDR) Enterobacteriaceae in the waters of two rivers and wastewater treatment plants (WWTPs) in a region of Catalonia, Spain; (b) genetically characterize the MDR strains; and (c) compare extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolates from environmental and human sources. Methods: A total of 62 samples were collected from the influent and effluent of 31 WWTPs and 29 river water samples from 11 sites. Simultaneously, 382 hospitalized patients were screened for MDR Enterobacteriaceae using rectal swabs. All isolates underwent antibiotic susceptibility testing and whole-genome sequencing. Results: MDR Enterobacteriaceae were detected in 48.4% of WWTP samples, with 18.5% ESBL-producing E. coli and 1.5% (one sample) OXA-48-producing K. pneumoniae in influents, and 12.8% ESBL-producing E. coli in effluents. In river waters, 5.6% of samples contained ESBL-producing E. coli and 1.4% (1 sample) contained VIM-producing Enterobacter cloacae complex strains. Among patients, 10.2% (39/382) carried MDR Gram-negative bacilli, of which 66.7% were ESBL-producing E. coli. In aquatic ecosystems E. coli ST131 (13.3%) and ST162 (13.3%) were the most common strains, while in humans the common were E. coli ST131 (33.3%), ST69 (11.1%) and ST410 (7.4%) in humans. The most frequent environmental antibiotic resistance genes (ARG) were bla_CTX-M-15 (24%) and bla_TEM-1B (20%), while the most common ARGs were bla_TEM-1B (20.4%), bla_CTX-M15 (18.4%) and bla_CTX-M-27 (14.3%). IncF plasmids were predominant in environmental and human strains. Conclusions: ESBL-producing E. coli and carbapenemase-producing Enterobacteriaceae are present in aquatic environments in the region. Phylogenetic similarities between environmental and clinical strains suggest a possible similar origin. Further studies are necessary to clarify transmission routes and environmental impact. Full article

Pyrochlore Bi_1.8Mn_0.5Ni_0.5Ta₂O_9-Δ (sp.gr. Fd-3m, a = 10.5038(9) Å) was synthesized by the solid-phase reaction method and characterized by vibrational and X-ray spectroscopy. According to scanning electron microscopy, the ceramics are characterized by a porous microstructure formed by randomly oriented oblong grains. The average crystallite size determined by X-ray diffraction is 65 nm. The charge state of transition element cations in the pyrochlore was analyzed by soft X-ray spectroscopy using synchrotron radiation. For mixed pyrochlore, a characteristic shift of Bi4f and Ta4f and Ta5p spectra to the region of lower energies by 0.25 and 0.90 eV is observed compared to the binding energy in Bi₂O₃ and Ta₂O₅ oxides. XPS Mn2p spectrum of pyrochlore has an intermediate energy position compared to the binding energy in MnO and Mn₂O₃, which indicates a mixed charge state of manganese (II, III) cations. Judging by the nature of the Ni2p spectrum of the complex oxide, nickel ions are in the charge state of +(2+ζ). The relative permittivity of the sample in a wide temperature (up to 350 °C) and frequency range (25–10⁶ Hz) does not depend on the frequency and exhibits a constant low value of 25. The minimum value of 4 × 10⁻³ dielectric loss tangent is exhibited by the sample at a frequency of 10⁶ Hz. The activation energy of conductivity is 0.7 eV. The electrical behavior of the sample is modeled by an equivalent circuit containing a Warburg diffusion element. Full article

Background: Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), are genetically complex and often linked to structural genomic variations such as copy number variants (CNVs). Current diagnostic strategies face challenges in interpreting the clinical significance of such variants. Methods: We developed a customized, gene-oriented chromosomal microarray (CMA) targeting 6026 genes relevant to neurodevelopment, aiming to improve diagnostic yield and candidate gene prioritization. A total of 39 patients with unexplained developmental delay, intellectual disability, and/or ASD were analyzed using this custom platform. Systems biology approaches were employed for downstream interpretation, including protein–protein interaction networks, centrality measures, and tissue-specific functional module analysis. Results: Pathogenic or likely pathogenic CNVs were identified in 31% of cases (9/29). Network analyses revealed candidate genes with key topological properties, including central “hubs” (e.g., NPEPPS, PSMG1, DOCK8) and regulatory “bottlenecks” (e.g., SLC15A4, GLT1D1, TMEM132C). Tissue- and cell-type-specific network modeling demonstrated widespread gene involvement in both prenatal and postnatal developmental modules, with glial and astrocytic networks showing notable enrichment. Several novel CNV regions with high pathogenic potential were identified and linked to neurodevelopmental phenotypes in individual patient cases. Conclusions: Customized CMA offers enhanced detection of clinically relevant CNVs and provides a framework for prioritizing novel candidate genes based on biological network integration. This approach improves diagnostic accuracy in NDDs and identifies new targets for future functional and translational studies, highlighting the importance of glial involvement and immune-related pathways in neurodevelopmental pathology. Full article

Sporadic colorectal cancer (CRC), the third leading cause of cancer-related death globally, arises through a continuum from normal tissue to adenomas, progressing from low-grade (LGD) to high-grade dysplasia (HGD); yet, the early epigenetic drivers of this transition remain unclear. To investigate these events, we profiled LGD and HGD adenomas using EM-seq, and identified a consensus differential methylation signature (DMS) of 626 regions through two independent bioinformatics pipelines. This signature effectively distinguished LGD from HGD in both tissue and plasma-derived cell-free DNA (cfDNA), highlighting specific methylation patterns. Functional annotation indicated enrichment for regulatory elements associated with transcription factor activity and cell signaling. Applying the DMS to the TCGA CRC dataset revealed three tumor subtypes with increasing hypermethylation and one normal cluster. The most hypermethylated subtype exhibited poor survival, high mutation burden, and disrupted transcriptional networks. While overlapping with classical CpG Island Methylator Phenotype (CIMP) categories, the DMS captured a broader spectrum of methylation alterations. These findings suggest that the DMS captures functionally relevant, antecedent epigenetic alterations in CRC progression, enabling the robust stratification of dysplasia severity and tumor subtypes. This signature holds promise for enhancing preclinical detection and molecular classification, and warrants further evaluation in larger prospective cohorts. Full article

Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-Es) pose a significant global threat with notable increases in prevalence worldwide. Carbapenems are often used as the first line of treatment. However, their overuse accelerates resistance development, highlighting the urgent need for clinically viable carbapenem-sparing strategies. Cefmetazole (CMZ) and flomoxef (FMOX) are parenteral antibiotics that are widely used in Japan and have emerged as potential carbapenem alternatives. Repositioning these agents effectively addresses the clinical need for carbapenem-sparing strategies and outpatient ESBL-E management. This review aims to reposition CMZ and FMOX for real-world clinical practice by synthesizing basic research, clinical studies, and pharmacokinetics/pharmacodynamics (PKs/PDs) analyses, which suggest that these agents may be effective in treating ESBL-E infections—particularly urinary tract infections, as evidenced by their minimum inhibitory concentration (MIC) values. The clinical outcomes of these interventions have been comparable to those of carbapenems, which support their role in antimicrobial stewardship. Their PK/PD characteristics emphasize the importance of dose optimization to ensure therapeutic efficacy, whereas recent insights into resistance mechanisms provide a foundation for appropriate use. As novel antibiotic development takes substantial time, revisiting existing options is increasingly important. Notably, the Infectious Diseases Society of America’s 2024 guidance on antimicrobial resistance has omitted CMZ and FMOX, owing to which clinicians have limited guidance on their use, particularly in regions like Japan where these antibiotics are widely employed. By addressing this knowledge gap, the present review offers a comprehensive evaluation of these drugs and highlights their potential as intravenous agents in ESBL-E management. Furthermore, it highlights the ongoing challenge of ensuring effective oral step-down therapy in an outpatient setting to reinforce the global relevance of CMZ and FMOX in a broader treatment framework, underscoring their potential for outpatient administration where clinically appropriate. Full article

The in situ emulsification synergistic self-profile control system has wide application prospects for efficient development on offshore oil reservoirs. During water flooding in Bohai heavy oil reservoirs, random emulsification occurs with superimposed Jamin effects. Effectively utilizing this phenomenon can enhance the efficient development of offshore oilfields. This study addresses the challenges hindering water flooding development in offshore oilfields by investigating the emulsification mechanism and key influencing factors based on oil–water emulsion characteristics, thereby proposing a novel in situ emulsification flooding method. Based on a fundamental analysis of oil–water properties, key factors affecting emulsion stability were examined. Core flooding experiments clarified the impact of spontaneous oil–water emulsification on water flooding recovery. Two-dimensional T1–T2 NMR spectroscopy was employed to detect pure fluid components, innovating the method for distinguishing oil–water distribution during flooding and revealing the characteristics of in situ emulsification interactions. The results indicate that emulsions formed between crude oil and formation water under varying rheometer rotational speeds (500–2500 r/min), water cuts (30–80%), and emulsification temperatures (40–85 °C) are all water-in-oil (W/O) type. Emulsion viscosity exhibits a positive correlation with shear rate, with droplet sizes primarily ranging between 2 and 7 μm and a viscosity amplification factor up to 25.8. Emulsion stability deteriorates with increasing water cut and temperature. Prolonged shearing initially increases viscosity until stabilization. In low-permeability cores, spontaneous oil–water emulsification occurs, yielding a recovery factor of only 30%. For medium- and high-permeability cores (water cuts of 80% and 50%, respectively), recovery factors increased by 9.7% and 12%. The in situ generation of micron-scale emulsions in porous media achieved a recovery factor of approximately 50%, demonstrating significantly enhanced oil recovery (EOR) potential. During emulsification flooding, the system emulsifies oil at pore walls, intensifying water–wall interactions and stripping wall-adhered oil, leading to increased T2 signal intensity and reduced relaxation time. Oil–wall interactions and collision frequencies are lower than those of water, which appears in high-relaxation regions (T1/T2 > 5). The two-dimensional NMR spectrum clearly distinguishes oil and water distributions. Full article

Spondyloepimetaphyseal dysplasia type Isidor-Toutain (RPL13-SEMD) is an autosomal dominant skeletal dysplasia caused by heterozygous pathogenic variants in the RPL13 gene, encoding the ribosomal protein eL13. To date, 13 pathogenic variants in RPL13 have been reported, all clustering within intron 5 and exon 6, suggesting this hotspot region is critical for the function of ribosomes in skeletal tissues. Here, we present clinical and radiological characteristics of seven individuals, five children and two adults, from four unrelated families with RPL13-SEMD caused by two novel variants (c.477+5G>C and c.539_541del) and two previously reported variants (c.477+1G>C and c.548G>A) in RPL13. RNA analysis demonstrated that c.477+5G>C leads to a 54-nucleotide extension of exon 5, resulting in an 18-amino acid insertion. The phenotypic spectrum ranged from mild manifestations, such as Blount-like tibial deformity without significant short stature or Perthes-like femoral epiphyseal changes, to severe skeletal deformities with disproportionate short stature, accompanied by extraskeletal features (e.g., penoscrotal hypospadias, coccygeal abnormalities). For the first time, we describe Blount-like tibial deformity as a feature of this dysplasia, which resolves with age. Our study provides additional insights into the clinical, radiological, and genotypic features of RPL13-SEMD through detailed analysis of patients and their affected relatives. Full article

With the increasing market demand for spinels of various colors, purple spinel—long regarded as a symbol of nobility—has attracted growing attention. In this study, pinkish-purple to purple spinels from the Mogok region of Myanmar were systematically examined using conventional gemological, spectroscopic, and chemical analytical techniques. Raman analysis reveals that these spinels commonly contain octahedral inclusions composed of calcite, dolomite, magnesite, and graphite. Chemically, the samples are primarily magnesia-alumina spinels. Color variation is influenced by trace elements: increasing Cr and V contents enhance the red hue, while higher Fe concentrations intensify the purple tone. UV–Vis spectra show that Cr³⁺ and V³⁺ jointly contribute to absorptions at 388 nm and 548 nm, with Fe²⁺ and Fe³⁺ responsible for the bands at 371 nm and 457 nm, respectively, together controlling the pink-to-purple color variation. Most samples display four Cr³⁺-related peaks near 700 nm; however, these are absent in deeply purple spinels. In contrast, light pink spinels show weaker absorption at 371 nm and 457 nm, attributed to Fe²⁺ and Fe³⁺. Fluorescence spectra confirm characteristic Cr³⁺ emission bands at 673 nm, 684 nm, 696 nm, 706 nm, and 716 nm, indicating a strong crystal field environment. Raman spectra have peaks mainly around 312 cm⁻¹, 406 cm⁻¹, 665 cm⁻¹, and 768 cm⁻¹. The peaks of the infrared spectrum mainly appear around 840 cm⁻¹, 729 cm⁻¹, 587 cm⁻¹, 545 cm⁻¹, and 473 cm⁻¹. Full article

Feather mites play an important role in bird communities, covering a wide spectrum of associations with their hosts, ranging from parasitic to mutualistic relations. As a result of long co-evolution with their warm-blooded hosts, this diverse group of arthropods can be found in a wide range of environments where their hosts occur, including the high Arctic. The feather mite fauna of Greenland is poorly known. Herein, we present new data on feather mites found on three species of passerine birds, which were captured on Disko Island (Qeqertarsuaq), West Greenland. The feather mite species Analges longispinosus was found on Snow Bunting (Plectrophenax nivalis); Proctophyllodes plectrophenax on Snow Bunting and Lapland Longspur (Calcarius lapponicus); and Proctophyllodes hipposideros on Northern Wheatear (Oenanthe oenanthe). The two Proctophyllodes species represent new records for Greenland. Further studies are needed to reveal the diversity of feather mite species in this remote Arctic region. Full article