Search Results (300)

In lace textile manufacturing, the dyeing process in parallel machine environments faces challenges from sequence-dependent setup times due to color family transitions, machine eligibility constraints based on weight capacities, and probabilistic re-dyeing operations arising from quality inspection failures, which often lead to increased tardiness. To tackle this multi-constrained problem, a stochastic integer programming model is formulated to minimize total estimated tardiness. A novel symmetry-driven two-population collaborative differential evolution (TCDE) algorithm is then proposed. It features two symmetrically complementary subpopulations that achieve a balance between global exploration and local exploitation. One subpopulation employs chaotic parameter adaptation through a logistic map for symmetrically enhanced exploration, while the other adjusts parameters based on population diversity and convergence speed to facilitate symmetry-aware exploitation. Moreover, it also incorporates a symmetrical collaborative mechanism that includes the periodic migration of top individuals between subpopulations, along with elite-set guidance, to enhance both population diversity and convergence efficiency. Extensive computational experiments were conducted on 21 small-scale (optimally validated via CVX) and 15 large-scale synthetic datasets, as well as 21 small-scale (similarly validated) and 20 large-scale industrial datasets. These experiments demonstrate that TCDE significantly outperforms state-of-the-art comparative methods. Ablation studies also further verify the critical role of its symmetry-based components, with computational results confirming its superiority in solving the considered problem. 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

Alzheimer’s disease (AD) is a neurodegenerative disease with a multifaceted pathogenesis, which remains elusive, seriously affecting the quality of life of elderly patients and placing a heavy burden on affected individuals, their families, and society. As third-party synapses in brain networks, astrocytes play an important role in maintaining the normal function of neural networks, which contribute to the abnormal function of networks in AD. In recent years, numerous studies have shown that clusterin, a protein expressed by astrocytes, can participate in the progression of AD. Clusterin plays a significant role in many pathological processes of AD, such as lipid metabolism, AD pathological features, the imbalance in neural circuit excitatory inhibition, and neuroinflammation. Therefore, delving deeper into the association between clusterin and AD will help us to understand the mechanisms of disease better and provide a theoretical basis for early diagnosis and the development of treatment strategies for AD. 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

In farmed animals, body color is not only an ecological trait but also an important trait that influences the commercial value of the animals. Melanin plays an important role in the formation of body color in animals, while the tyrosinase (TYR) gene family is a group of key enzymes that regulate melanogenesis. The Chinese soft-shelled turtle (Pelodiscus sinensis) is one of the most important reptiles in freshwater aquaculture. However, the potential role of the TYR gene family in the body color formation of P. sinensis remains unclear. This study aimed to investigate the expression and conservation of the TYR gene family in relation to body color variation in P. sinensis. Three core members of this gene family were identified from the P. sinensis genome. Following identification, the genomic features were analyzed. They shared similar physicochemical properties and conserved domains. Chromosome mapping showed that the three genes of P. sinensis were all located on the autosomes, while phylogenetic and collinearity analysis suggested that the protein functions of the three genes in the studied species were highly conserved. Amino acid sequence alignment indicated high conservation among the three TYR gene family proteins (TYR, TYRP1, and DCT) in multiple critical regions, particularly in their hydrophobic N-/C-terminal regions and cysteine/histidine-rich conserved domains. The qRT-PCR revealed that the TYR and DCT genes were highly expressed in the eyes of individuals with different body colors. The expression levels of TYR and TYRP1 genes in the skin were significantly higher in dark-colored individuals than in light-colored ones (p < 0.05). These results will lay the groundwork for functional studies and breeding programs targeting color traits in aquaculture. Full article

Objectives: This study aims to describe the clinical features and genetic findings of nine Vietnamese patients with autosomal recessive bestrophinopathy. Methods: This retrospective and cross-sectional study included individuals diagnosed with autosomal recessive bestrophinopathy at the Eye Clinic, Vietnam National Geriatric Hospital between May 2024 and April 2025. The patients underwent a visual acuity assessment, retinal multimodal imaging, and molecular testing through BEST1 gene sequencing. Results: Nine patients from seven unrelated families were included. The mean age was 38.6 years (range: 14.1–79.6). Visual acuity ranged from 20/20 to 20/125. All patients showed vitelliform lesions, subretinal deposits, and both intraretinal and subretinal fluid. Other main features included diffuse macular hyperfluorescence and hyperopia. Less common clinical features encompassed glaucoma, retinoschisis, outer retinal thinning, serous retinal detachment, retinal thickening, and thinning of the retinal pigment epithelium. Compound heterozygous or homozygous variants were detected in all patients. Among the five identified BEST1 variants, the most frequent were p.(A195V) and p.(R200*). One novel variant, p.(K289*), was detected. Conclusions: The main clinical retinal features of nine Vietnamese patients with autosomal recessive bestrophinopathy included vitelliform lesions, subretinal deposits, retinal fluid, and diffuse macular hyperfluorescence. The most common variants were p.(A195V) and p.(R200*). Additionally, the identification of various compound heterozygotes and a novel BEST1 variant expands the mutation spectrum of the disease. Full article

Background and Objectives: Essential tremor (ET) is a common neurological disorder, typically presenting as bilateral, rhythmic, and symmetric kinetic or postural tremors. In contrast, Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by resting tremor, rigidity, bradykinesia, and postural instability. Although both disorders involve tremor, ET and PD differ in clinical presentation and pathophysiology: ET generally involves action tremor and has a strong familial component, while PD more commonly presents with resting tremor and a weaker family history. A subset of ET patients may develop Parkinsonian features over time, although the relationship between ET and subsequent PD remains unclear. Genetic studies have identified only a few pathogenic variants in ET, suggesting it develops as a result of multifactorial genetic and environmental influences rather than simple Mendelian inheritance. ET is also recognized as a risk factor for developing PD, although the underlying mechanisms remain poorly understood. This study aimed to clarify potential genetic overlaps and distinctions in patients diagnosed with both ET and PD. Materials and Methods: We retrospectively analyzed 40 patients with a family history of ET or PD who were initially diagnosed with ET and later developed PD. Genetic screening and clinical assessments were conducted to investigate associated variants and clinical features. Results: Among these 40 patients, 17 different mutations were detected in 16 individuals. Three pathogenic or likely pathogenic variants were identified. The clinical characteristics and treatment responses of these patients were reviewed in relation to their genetic findings. Notably, none of the identified variants had previously been reported in association with PD following ET. Conclusions: A comprehensive clinical and genetic evaluation of ET patients who develop PD may offer insights into the underlying pathophysiology and inform future therapeutic strategies. Our findings support the need for further studies to explore the genetic landscape of patients with overlapping ET and PD features. Full article

Background: Syndromic inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders, involving the retina and additional organs. Over 80 forms of syndromic IRD have been described. Methods: We aimed to phenotypically and genotypically characterize a cohort of 171 individuals from 140 Israeli families with syndromic IRD. Ophthalmic examination included best corrected visual acuity, fundus examination, visual field testing, retinal imaging and electrophysiological evaluation. Most participants were also evaluated by specialists in fields relevant to their extra-retinal symptoms. Genetic analyses included haplotype analysis, homozygosity mapping, Sanger sequencing and next-generation sequencing. Results: In total, 51% of the families in the cohort were consanguineous. The largest ethnic group was Muslim Arabs. The most common phenotype was Usher syndrome (USH). The most common causative gene was USH2A. In 29% of the families, genetic analysis led to a revised or modified clinical diagnosis. This included confirmation of an atypical USH diagnosis for individuals with late-onset retinitis pigmentosa (RP) and/or hearing loss (HL); diagnosis of Heimler syndrome in individuals with biallelic pathogenic variants in PEX6 and an original diagnosis of USH or nonsyndromic RP; and diagnosis of a mild form of Leber congenital amaurosis with early-onset deafness (LCAEOD) in an individual with a heterozygous pathogenic variant in TUBB4B and an original diagnosis of USH. Novel genotype–phenotype correlations included biallelic pathogenic variants in KATNIP, previously associated with Joubert syndrome (JBTS), in an individual who presented with kidney disease and IRD, but no other features of JBTS. Conclusions: Syndromic IRDs are a highly heterogeneous group of disorders. The rarity of some of these syndromes on one hand, and the co-occurrence of several syndromic and nonsyndromic conditions in some individuals, on the other hand, complicates the diagnostic process. Genetic analysis is the ultimate way to obtain an accurate clinical diagnosis in these individuals. Full article

Cutaneous manifestations can serve as early and sometimes the first clinical indicators in various hereditary cancer predisposition syndromes. This review provides a comprehensive overview of the dermatological signs associated with these syndromes, aiming to facilitate their recognition in clinical practice. Hereditary Breast and Ovarian Cancer syndrome is notably linked to an increased risk of melanoma. BAP1 tumor predisposition syndrome is characterized by BAP1-inactivated melanocytic tumors. Muir–Torre syndrome, a variant of Lynch syndrome, presents with distinctive cutaneous neoplasms such as sebaceous carcinomas, sebaceous adenomas, and keratoacanthomas. PTEN hamartoma tumor syndrome commonly features hamartomatous growths, trichilemmomas, acral keratoses, oral papillomas, and genital lentiginosis. Gorlin syndrome is marked by basal cell carcinomas and palmoplantar pits, while Peutz–Jeghers syndrome is identified by mucocutaneous pigmentation. In familial adenomatous polyposis, the cutaneous findings include epidermoid cysts, fibromas, desmoid tumors, and lipomas. Additionally, we examined monogenic disorders associated with cancer risk and skin involvement, such as xeroderma pigmentosum, neurofibromatosis type 1, familial atypical multiple-mole melanoma syndrome, and Fanconi anemia. The early recognition of these dermatologic features is essential for a timely diagnosis and the implementation of appropriate surveillance strategies in individuals with hereditary cancer syndromes. Full article

Kiwifruit allergy was first described over 40 years ago and is becoming increasingly common worldwide. This is most likely related to the fact that kiwifruit production and consumption increased by almost two orders of magnitude during the last 50 years. Currently, there are thirteen officially registered allergens belonging to the species Actinidia deliciosa (green kiwifruit), and three officially registered allergens belonging to the species Actinidia chinensis (golden kiwifruit). The molecular properties of the kiwifruit allergens are summarized, and their features are discussed, considering the protein families to which they belong. At present, kiwifruit allergens are found to belong to 13 protein families. Allergic reactions caused by these molecules can be local, for example, related to the oral cavity, but in some cases systemic responses, such as anaphylaxis, are also observed. Generally, kiwifruit allergy should not be considered as a homogenous disorder, as it was noted that there are distinct groups of patients with different sensitization profiles. Therefore, the diagnostic process may be challenging, as in many cases other food allergies must be considered. Frequently cross-reactivity between kiwifruit allergens and their homologs originating from other organisms has a significant impact on the wellbeing of the affected individuals. Full article

Xyloglucan endotransglucosylase/hydrolase (XTH) is a crucial enzyme in plant cell wall remodeling, which contributes to plant growth, development, and stress response. Based on the transcriptome data of Larix kaempferi, this study identified and analyzed 16 XTH genes. Sequence alignment and phylogenetic analysis indicated that the LkXTH gene family can be divided into three subfamilies, namely the Early Diverging Group, Group I/II, and Group III, all of which share highly conserved motifs and structural features. Expression profiling demonstrated that LkXTH genes are actively expressed in the roots, stems, and leaves of L. kaempferi. Under drought stress, the expression of LkXTH1, LkXTH2, LkXTH3, LkXTH4, LkXTH6, LkXTH14, LkXTH15, LkXTH17, and LkXTH18 increased rapidly in roots. Meanwhile, the expression levels of LkXTH5, LkXTH7, LkXTH8, and LkXTH13 exhibited significant upregulation in leaves. Notably, LkXTH11 and LkXTH16 significantly increased in both roots and leaves, with a more pronounced increase in leaves, but LkXTH10 displayed significant upregulation in the stems. Furthermore, the heterologous expression of LkXTH1 and LkXTH17 in yeast significantly enhances drought tolerance. These findings indicate that individual LkXTH genes exhibit distinct organ-specific responses to drought stress, thereby advancing our understanding of their functional roles in larch drought response. Full article

Plastic waste accumulation presents critical environmental challenges demanding innovative circular economy solutions. This study developed a comprehensive machine learning framework to systematically identify optimal enzyme combinations for polyester depolymerization. We integrated kinetic parameters from the BRENDA database with sequence-derived features and network topology metrics to train ensemble classifiers predicting enzyme-substrate relationships. A multi-objective optimization algorithm evaluated enzyme combinations across four criteria: prediction confidence, substrate coverage, operational compatibility, and functional diversity. The ensemble classifier achieved 86.3% accuracy across six polymer families, significantly outperforming individual models. Network analysis revealed a modular organization with hub enzymes exhibiting broad substrate specificity. Multi-objective optimization identified 156 Pareto-optimal enzyme combinations, with top-ranked pairs achieving composite scores exceeding 0.89. The Cutinase–PETase combination demonstrated exceptional complementarity (score: $0.875\pm 0.008$), combining complete substrate coverage with high catalytic efficiency. Validation against experimental benchmarks confirmed enhanced depolymerization rates for recommended enzyme cocktails. This framework provides a systematic approach for enzyme prioritization in plastic valorization, advancing biological recycling technologies through data-driven biocatalyst selection while identifying key economic barriers requiring technological innovation. Full article

Background: Huntington’s disease (HD) is a progressive, autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. Despite advances in understanding its molecular basis, epidemiological data in many countries, including Bulgaria, remain limited. This study aims to present clinical and genetic findings from a 20-year single-centre cohort. Methods: A retrospective review was conducted of patients evaluated for HD at the University Hospital “St. Marina” in Varna between 2004 and 2024. Data included demographics, CAG repeat length, clinical features, imaging, and psychiatric assessments. Statistical analysis focused on correlations between variables, with significance set at p < 0.05. Results: Out of 79 referred individuals, 43 were molecularly confirmed. The mean age of onset was 43 years, with a four-year diagnostic delay. The average CAG repeat length was 44.6, though two symptomatic patients had reduced penetrance alleles (38 and 39 repeats). Cognitive and psychiatric symptoms were each present in 72% of cases. Depression was significantly more prevalent in women (p = 0.011). Most patients had a positive family history, predominantly maternal. Conclusions: Our findings highlight diagnostic delays, gender-specific psychiatric vulnerabilities, and the importance of personalized care. Improved access to genetic counselling and early diagnosis are essential for optimizing outcomes. Full article

We report on the preparation and characterization of a new family of hydrogen-bonded nematogenic liquid crystalline dimers. The dimers are supramolecular complexes that consist of a benzoic acid derivative, acting as the proton donor, featuring a spacer with seven methylene groups and a terminal decyloxy chain, paired with an azopyridine derivative as the proton acceptor. The latter was either fluorinated or nonfluorinated with variable alkoxy chain length. The formation of a hydrogen bond between the individual components was confirmed using FTIR and ¹H NMR spectroscopy. All supramolecules were investigated for their liquid crystalline behaviour via a polarized optical microscope (POM) and differential scanning calorimetry (DSC). All materials exhibit enantiotropic nematic phases as confirmed by X-ray diffraction (XRD) and POM investigations. The nematic phase range depends strongly on the degree and position of fluorine atoms. Additionally, the supramolecules demonstrated a rapid and reversible transition between the liquid crystal phase and the isotropic liquid state because of trans-cis photoisomerization upon light irradiation. Therefore, this study presents a straightforward approach to design photo-responsive nematic materials, which could be of interest for nonlinear optics applications. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental impairment that occurs due to mutations related to the formation of the nervous system, combined with the impact of various epigenetic and environmental factors. This necessitates the identification of the genetic variations involved in ASD pathogenesis. We performed whole exome sequencing (WES) in a cohort of 22 Bulgarian male and female individuals showing ASD features alongside segregation analyses of their families. A targeted panel of genes was chosen and analyzed for each case, based on a detailed examination of clinical data. Gene analyses revealed that specific variants concern key neurobiological processes involving neuronal architecture, development, and function. These variants occur in a number of genes, including SHANK3, DLG3, NALCN, and PACS2 which are critical for synaptic signaling imbalance, CEP120 and BBS5 for ciliopathies, SPTAN1 for spectrins structure, SPATA5, TRAK1, and VPS13B for neuronal organelles trafficking and integrity, TAF6, SMARCB1, DDX3X, MECP2, and SETD1A for gene expression, CDK13 for cell cycle control, ALDH5A1, DPYD, FH, and PDHX for mitochondrial function, and PQBP1, HUWE1, and WDR45 for neuron homeostasis. Novel single nucleotide variants in the SPATA5, CEP120, BBS5, SETD1A, TRAK1, VPS13B, and DDX3X genes have been identified and proposed for use in ASD diagnostics. Our data contribute to a better understanding of the complex neurobiological features of autism and are applicable in the diagnosis and development of personalized therapeutic approaches. Full article