Search Results (188)

Background: Non-syndromic cleft lip/palate (NCL/P) is a prevalent congenital anomaly. Despite an unclear epidemiological link between orofacial clefts and dental caries, genetic studies suggest that polymorphisms in taste receptor genes may influence caries risk. Objectives: This study had two primary objectives: (1) to compare SNPs in NCL/P-associated genes (IRF6, FOXE1) between Kuwaiti NCL/P cases and controls, and (2) to explore whether variants in caries-associated (KLK4, DSPP) and taste receptor (TAS1R2, TAS2R38) genes are associated with dental caries susceptibility in individuals with NCL/P, independent of overall caries prevalence. Methods: A case–control design was employed, with 25 NCL/P cases and 25 unaffected controls recruited from a Dental Craniofacial Clinic in Kuwait. Genomic DNA was extracted from buccal swabs, and SNP genotyping was performed using real-time PCR for genes related to NCL/P, dental caries, and taste perception. Caries status was assessed using the dmft/DMFT scoring system. The genotyped genes included NCL/P-related (IRF6, FOXE1), caries-related (KLK4, DSPP), and taste receptor genes (TAS1R2, TAS2R38). Results: At nominal significance, KLK4, DSPP, and TAS1R2 showed associations with NCL/P status, while IRF6 and FOXE1 did not. After applying Benjamini–Hochberg FDR correction across 10 SNPs, no allele- or genotype-level association remained significant (q < 0.05). The strongest signal was KLK4 rs2235091 (allele-level p = 0.016; q = 0.159). An exploratory age- and sex-adjusted logistic model for KLK4 suggested a possible effect (aOR 0.40; 95% CI 0.18–0.87; p = 0.021). Within-group analyses of caries burden revealed no associations that survived FDR control (lowest q = 0.056 for FOXE1 in controls). Conclusions: After controlling for multiple testing, no SNP showed a statistically significant association with NCL/P or caries burden. Nominal signals for KLK4, DSPP, and TAS1R2 did not survive FDR correction; an exploratory adjusted model suggested a possible KLK4 effect, but this requires cautious interpretation. The small sample size is a key limitation, and the findings highlight the need for larger, well-powered studies to clarify genetic contributions to NCL/P and caries risk. Full article

Background/Objectives: Rapid cellular proliferation, a hallmark of malignancy, requires sustained and elevated protein synthesis, which in turn requires efficient ribosome biogenesis. The aim of this study was to evaluate the expression levels of TP53, C-MYC, FBL, and NCL in pre-B ALL and neuroblastoma tissues compared to healthy bone marrow samples—factors that may carry prognostic significance in pediatric malignancies. Materials and methods: The cohort included 45 pre-B ALL patients, 19 neuroblastoma patients, and 12 healthy bone marrow donors as controls. Total RNA was extracted from bone marrow or tumor samples and cDNA synthesis was performed with the Bio-Rad iScript kit. Quantitative PCR was conducted using SYBR Green chemistry, with GAPDH as the reference gene. Primers targeted TP53, C-MYC, FBL, and NCL, and gene expression was calculated using the 2^−ΔCt method. Results: The expression of C-MYC and FBL was found to be significantly decreased in patients with pre-B ALL in comparison to the healthy control group. NCL expression was highest in healthy donors, intermediate in pre-B ALL, and lowest in neuroblastoma. In addition to intergroup comparisons, correlations between gene expression levels were assessed within each diagnostic group. In the pre-B ALL group, a positive correlation was observed between TP53 and C-MYC expression, as well as between TP53 and both FBL and NCL. Furthermore, a significant positive correlation was found between FBL and NCL. In the neuroblastoma group, a statistically significant positive correlation was identified between C-MYC and FBL expression. In the control group, TP53 expression was positively correlated with NCL, and FBL expression showed a significant positive correlation with NCL. Conclusions: This study suggests the altered expression of ribosome biogenesis-related genes in pediatric pre-B acute lymphoblastic leukemia and neuroblastoma. The reported dysregulation suggests a disease-associated disruption in nucleolar function and translational regulation and may contribute to oncogenesis through altered ribosomal assembly, protein synthesis, or proliferative signaling. Full article

In recent years, with changes in dietary structure, beef has become the third most consumed meat in China after pork and chicken, with its consumption increasing by approximately 50%. The quality and commercial value of beef vary considerably across different muscles. However, due to the high similarity in the appearance of beef cuts and strong background interference, traditional image features are often insufficient for accurate classification. In this study, an improved convolutional neural network based on YOLOv11 was proposed. Four beef muscles were categorized: sirloin (longissimus dorsi), fillet/tenderloin (psoas major), oyster blade (infraspinatus), and ribeye (longissimus thoracis). A dataset comprising 3598 images was established to support model training and validation. We divided the dataset into training, testing, and validation sets in a 6:2:2 ratio. To enhance model performance, wavelet convolution (WTConv) was employed to effectively expand the receptive field and improve image understanding, while a large separable kernel attention (LSKA) module was introduced to strengthen local feature representation and reduce background interference. Comparative experiments were conducted with other deep learning models as well as ablation tests to validate the proposed model’s effectiveness. Experimental results demonstrated that the proposed model achieved a classification accuracy of 98.50%, with Macro-Precision and Macro-Recall reaching 97.38% and 97.38%, respectively, and a detection speed of 147.66 FPS. These findings confirm the potential of the YOLOv11n-cls model for accurate beef classification and its practical application in intelligent meat recognition and processing within the Chinese beef industry. Full article

Background: High expression of nucleolin (NCL) on the surface of tumor cells is closely associated with disease progression and poor prognosis. The aptamer–PROTAC conjugate (APC) technology provides a novel molecular design strategy for the targeted degradation of NCL. Methods: Based on the principles of PROTAC technology and chemical modification techniques, in this study, a series of AS1411-lenalidomide chimeras featuring different linker structures were designed and synthesized for the specific purpose of targeted degradation of NCL. Four AS1411-PROTACs (C1–C4) were successfully constructed via a click chemistry strategy, and their structures were validated. Results: In vitro experimental results showed that C4 exhibited the most optimal activity, significantly downregulating NCL expression and inhibiting the proliferation of breast cancer cells (MCF-7). Notably, the activity of C4 remained unaltered regardless of the annealing process. Mechanistic studies demonstrated that C4 induced NCL degradation through the ubiquitin–proteasome pathway while also promoting apoptosis and cell cycle arrest. In a nude mouse tumor model, C4 displayed potent antitumor efficacy, with no discernible signs of obvious systemic toxicity. Conclusions: This study provides compelling evidence demonstrating that C4 is a highly promising anticancer compound. It also provides important evidence for the development of novel nucleic acid aptamer–PROTAC conjugate drugs for more clinical applications. Full article

04Cr13Ni5Mo martensitic stainless steel is extremely sensitive to forging temperature and is prone to generating extremely large cracks, which leads to the failure of forging. Therefore, high-temperature tensile tests were performed on 04Cr13Ni5Mo martensitic stainless steel using a Gleeble-1500D thermo-mechanical simulator to investigate its damage mechanisms. The tests covered a temperature range of 950–1200 °C and strain rates of 0.001–1 s⁻¹. The high-temperature damage behavior and tissue evolution law at high temperatures were studied by means of EBSD, TEM, etc. Secondly, two high-temperature damage models of 04Cr13Ni5Mo, namely Normalized Cockcroft and Latham (NCL) and Oyane, were established by combining optimization algorithm and finite element simulation. Then, the two high-temperature damage models were integrated into the Forge^®NxT 3.2 finite element software. Simulated thermal tensile tests were conducted on 04Cr13Ni5Mo at temperatures from 950 to 1200 °C, strain rates from 0.001 to 1 s⁻¹. A comparison was made between the predicted and experimentally measured fracture displacements of the tensile specimens. The calculated correlation coefficients (R) were 0.995 and 0.991, respectively. It was determined that the NCL model has better simulation accuracy for predicting the forging cracks of 04Cr13Ni5Mo. The reliability of the finite element method for predicting forging crack defects in 04Cr13Ni5Mo forgings was established. Full article

This study investigates the effects of transportation, specifically public transit, the built environment, and sociodemographic factors on community quality of life (QOL) and individuals’ overall life satisfaction (OLS) in the United States. Using data from the 2017 National Community Livability Survey (NCLS), which includes responses from 994 adults across all 50 states, structural equation modeling (SEM) was applied to examine four latent constructs: the built environment, access to amenities, transportation quality, and support for transit funding. Additional observed variables included perceived importance of public transit, public transit need, ease of travel, and key sociodemographic indicators. Results show that the built environment and transportation quality significantly enhance community QOL but do not have a direct effect on individual OLS. In contrast, support for transit funding has a significant positive effect on individual OLS but not on community QOL. Public transit and walking access to amenities such as parks and recreation facilities, grocery stores, healthcare services, etc., improve both the built environment’s perceptions and community QOL. Interestingly, the perceived importance of public transit negatively influences community QOL, while perceived transit need negatively impacts individual OLS. Ease of travel is the only factor with a significant positive effect on both outcomes. Sociodemographic factors such as gender, age, income, health, education, and race are also found to significantly influence individual life satisfaction. These findings suggest that enhancing perceptions of the built environment, improving transportation quality—particularly public and active transit—and ensuring ease of travel can contribute to improved quality of life. Policies that integrate transportation planning with broader livability and well-being goals may offer more inclusive benefits at both the community and individual levels. Full article

Swimming is one of the most popular forms of recreational sport worldwide, recommended for people of all ages as a healthy activity. While numerous studies have focused on the impact of indoor air quality on the health of pool users, relatively few have addressed how specific airborne parameters in indoor swimming facilities affect the durability of construction materials. This article analyzes the current state of knowledge on the influence of the pool indoor environment on structural reliability, with trichloramine (NCl₃) emphasized as a degradation factor. Indoor pool environments are classified as chemically aggressive, due to elevated air temperature (~30 °C), high humidity (often exceeding 60%), and the presence of volatile chlorine compounds released from disinfected water. Our case study demonstrates that during swimming competitions, the average concentration of airborne NCl₃ reached a value of 900 µg/m³, with peaks up to 1200 µg/m³, i.e., about ten times higher than on typical usage days. The median trichloramine concertation during the competition was 1071 µg/m³. Such exposure conditions accelerate corrosion processes in stainless steels and other building materials, reducing service life and requiring targeted monitoring and preventive maintenance. Based on the findings, recommendations are provided regarding material selection, highlighting the importance of surface texture, ventilation strategies, and protective measures tailored to periods of intensive facility use. Full article

Background/Objectives: A Petit Bleu de Gascogne (PBDG) dog presented with a progressive neurological disorder characterized by hind-limb weakness, anxiety and hallucinatory episodes, lip smacking, progressive vision loss, muscle atrophy, and ataxia. Magnetic resonance imaging revealed diffuse brain atrophy. The dog was euthanized at approximately 23 months of age due to the progression of neurological signs. A study was undertaken to identify the molecular genetic basis of the disorder in this dog. Methods: Microscopic analyses were performed to characterize the disease pathology and whole-genome sequencing was performed to identify the molecular genetic basis of the disorder. Results: The proband exhibited pronounced accumulations of autofluorescent intracellular inclusions in the brain, retina, and heart with ultrastructural appearances similar to those of lysosomal storage bodies that accumulate in the neuronal ceroid lipofuscinosis (NCLs), a group of progressive neurodegenerative disorders. Whole-genome sequence analysis of DNA from the proband identified homozygous missense variants in AP3B1 and TRAPPC9 that encode proteins involved in sorting and transport of proteins through the Golgi apparatus to lysosomes. Screening of unaffected PBDGs for these variants identified dogs that were homozygous for either variant, but no other dogs that were homozygous for both. Conclusions: These findings raise the possibility that the disease involves the combined influence of the two variants, and that the proteins encoded by these genes interact within the Golgi apparatus to mediate protein sorting and transport to lysosomes. An alteration in this interaction could underlie the NCL-like lysosomal storage disorder observed in the proband. Full article

The gold(III) starting material [Au(damp-κC¹,N)Cl₂] (Hdamp = 2-(dimethylaminomethyl)benzene) reacts with the thiourea-type ligands 3,3-diethyl-1-benzoylthiourea (HL1) or N-(3,3-diethylamino-thiocarbonyl)-N′-(2-hydroxyphenyl)benzamidine (H₂L2) under formation of the gold(III) cations [Au(damp-κC¹,N)(L1-κS,O)]⁺ (1) and [Au(Hdamp-κC¹)(L2-κS,N,O)]⁺ (2). The products have been isolated in crystalline form as their PF₆⁻ salts and studied by X-ray diffraction and spectroscopic methods. The preservation of the gold(III) oxidation state and the square-planar coordination spheres in the products is most probably due to the formation of chelate rings by the incoming ligands and the presence of the Au–C bond to the phenyl rings of the damp⁻ or Hdamp ligands. Full article

Nucleic acid aptamers leverage defined tertiary structures for precise molecular recognition, positioning them as transformative biomedical tools. We engineered AP1-F, a G-quadruplex (G4)-structured aptamer that selectively binds membrane-anchored nucleolin (NCL) non-permeabilizing, overcoming a key limitation of conventional probes. Microscale thermophoresis confirmed nanomolar affinity to NCL. By means of rigorous optimization, AP1-F attained a greater than ten-fold fluorescence signal ratio between malignant and normal cells in co-cultures, exceeding the extensively researched AS1411. Dual-channel flow cytometry demonstrated over 98.78% specificity at single-cell resolution within heterogeneous cell populations, owing to AP1-F’s unique membrane localization—unlike AS1411’s intracellular uptake, which elicited erroneous signals from cytoplasmic NCL. Competitive binding experiments and Laser Confocal Imaging confirmed that AP1-F specifically identifies cancer cells by binding to the NCL recognition site on the membrane. In pathological sections, AP1-F exhibited a 40.5-fold fluorescence intensity ratio between tumor and normal tissue, facilitating accurate tissue-level differentiation. Significantly, it delineated molecular subtypes by associating membrane NCL patterns with morphometric analysis: luminal-like MCF-7 displayed consistent staining in cohesive clusters, whereas basal-like MDA-MB-468 revealed sporadic NCL with irregular outlines—characteristics imperceptible to intracellular-targeted antibodies, thus offering subtype-specific diagnostic insights. This combination biochemical–morphological approach accomplished subtype differentiation with a single-step, non-permeabilized process that maintained lower cytotoxicity and tissue integrity. AP1-F enhances diagnostic accuracy by utilizing spatial confinement to eradicate intracellular interference, connecting molecular specificity to intraoperative margin evaluation or biopsy categorization. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is a progressive condition whose heterogeneous endotypes, clinical manifestations, and recovery pathways complicate the identification of reliable predictors of rehabilitation outcomes. Several respiratory and functional assessments are available with no consensus on the most predictive ones. While univariate markers may miss multifactorial interactions essential for prognosis, data-driven unsupervised clustering methods can integrate complex information from different sources. This study aimed to apply unsupervised clustering to identify pre-rehabilitation characteristics predictive of discharge outcomes for COPD patients undergoing pulmonary rehabilitation. Methods: A total of 126 COPD patients undergoing pulmonary rehabilitation were included in the analysis. Three assessments were performed at admission, namely the forced oscillation technique, spirometry, and the six-minute walk test (6MWT). The outcome was the change in 6MWT distance between admission and discharge. Unsupervised clustering methods were applied to admission variables to identify subgroups associated with outcomes. Results: Among the clustering algorithms tested, k-means (with N_cl = 2) provided the optimal solution. The resulting respiratory rehabilitation index (R2I) was significantly associated with the outcome dichotomized via the minimal clinically important difference of 30 m. Patients with R2I = 1, indicating severe functional and respiratory impairments, were associated with higher post-rehabilitation functional improvement (p = 0.032). While few functional parameters of 6MWT were statistically different between the groups identified by outcome, nearly all variables in the analysis exhibited significant distribution differences among the R2I clusters. Conclusions: These findings highlight the heterogeneity of COPD and the potential of unsupervised clustering to identify distinct patient subgroups, enabling more personalized rehabilitation strategies. Full article

A scalable synthesis of two-dimensional titanium nitride chloride (TiNCl) via flash Joule heating (FJH) using titanium tetrachloride (TiCl₄) precursor has been developed. This single-step method overcomes traditional synthesis challenges, including high energy consumption, multi-step procedures, and hazardous reagent requirements. The structural and chemical properties of the synthesized TiNCl were characterized through multiple analytical techniques. X-ray diffraction (XRD) patterns confirmed the presence of TiNCl phase, while Raman spectroscopy data showed no detectable oxide impurities. Fourier transform infrared spectroscopy (FTIR) analysis revealed characteristic Ti–N stretching vibrations, further confirming successful titanium nitride synthesis. Transmission electron microscopy (TEM) imaging revealed thin, plate-like nanostructures with high electron transparency. These analyses confirmed the formation of highly crystalline TiNCl flakes with nanoscale dimensions and minimal structural defects. The material exhibits excellent structural integrity and phase purity, demonstrating potential for applications in photocatalysis, electronics, and energy storage. This work establishes FJH as a sustainable and scalable approach for producing MXenes with controlled properties, facilitating their integration into emerging technologies. Unlike conventional methods, FJH enables rapid, energy-efficient synthesis while maintaining material quality, providing a viable route for industrial-scale production of two-dimensional materials. Full article

Neuronal ceroid lipofuscinoses (NCLs) are paediatric neurodegenerative disorders that primarily affect the central nervous system (CNS). The high prevalence of gastrointestinal (GI) symptoms has prompted researchers and clinicians to move beyond an exclusively “brain-centric” perspective. At the molecular level, mutations in CLN genes lead to lysosomal dysfunction and impaired autophagy, resulting in intracellular accumulation of storage material that disrupts both central and enteric neuronal homeostasis. To systematically examine current clinical and preclinical knowledge on gut involvement in NCLs, with a focus on recent findings related to the enteric nervous system and gut microbiota. We conducted a systematic review following the PRISMA guidelines using PubMed as the sole database. Both clinical (human) and preclinical (animal) studies were included. A total of 18 studies met the inclusion criteria, focusing on gastrointestinal dysfunction, nervous system involvement, and gut microbiota. We found that the nature of GI symptoms was multifactorial in NCLs, involving not only the CNS but also the autonomic and enteric nervous systems, which were affected early by lysosomal deposits and enteric neuron degeneration. Of note, preclinical studies showed that gene therapy could improve not only CNS manifestations but also GI ones, which may have beneficial implications for patient care. While the role of the ENS seems to be clearer, that of gut microbiota needs to be further clarified. Current evidence from preclinical models highlighted alterations in the composition of the microbiota and suggested a possible influence on the progression and modulation of neurological symptoms. However, these results need to be confirmed by further studies demonstrating the causality of this relationship. GI involvement is a key feature of NCLs, with early impact on the enteric nervous system and possible links to gut microbiota. Although preclinical findings—particularly on gene therapy—are encouraging due to their dual impact on both CNS and GI manifestations, the causal role of the gut microbiota remains to be fully elucidated. In this context, the development of sensitive and specific outcome measures to assess GI symptoms in clinical trials is crucial for evaluating the efficacy of future therapeutic interventions. Full article

Nucleolin (NCL), an RNA-binding protein which regulates critical cellular processes, is frequently dysregulated in human cancers, including breast cancer, making it an attractive therapeutic target. However, molecular details of the RNA-NCL interaction have not been investigated yet. A tRNA fragment named tRF3E, displaying tumor suppressor roles in breast cancer, was found to bind NCL with high affinity displacing NCL-controlled transcripts. Here, we investigated the determinants and cooperativity of tRF3E-NCL interaction by Electrophoretic Mobility Shift Assays and in silico docking analysis, using wild-type or mutated tRF3E. We found that NCL, through its RNA-binding domains (RBD1–2 and RBD3–4), binds simultaneously two tRF3E molecules, giving rise to an energetically favored complex. Instead, a mutant form of tRF3E (M19–24), in which the NCL recognition element in position 19–24 has been disrupted, contacts NCL exclusively at RBD3–4, causing the loss of cooperativity among RBDs. Importantly, when expressed in MCF7 breast cancer cells, tRF3E significantly reduced cell proliferation and colony formation, confirming its role as tumor suppressor, but tRF3E functional properties were lost when the 19–24 motif was mutated, suggesting that cooperativity among multiple domains is required for the NCL-mediated tRF3E antitumor function. This study sheds light on the dynamic of RNA-NCL interaction and lays the foundations for using tRF3E as a promising NCL-targeted biodrug candidate. Full article

Background: This study aimed to evaluate the influence of a screw coating on the screw preload and removal torque value (RTV) with and without the application of a cyclic load (CL) to make screws with greater untightening resistance to prevent screw loosening. Methods: Ninety complexes composed of implants, abutments, and prosthetic screws were examined and tested under CL oral conditions (n = 45) and non-CL conditions (nCL, n = 45). Each group was divided into three subgroups (n = 15): a control group (CG) without a screw coating, a GapSeal^®-coated screw group (GG), and a polytetrafluoroethylene (PTFE) tape-wrapped screw group (PG). All screws were tightened at 30 Ncm, and the preload was recorded. In the nCL group, the screws were untightened to record the RTV. In the CL group, the screws were tightened, subjected to a CL in distillated water at a temperature of 37 °C, and then untightened to record the RTV. Micro-Ct analysis was conducted on two samples from each group before CL. SEM analyses of two samples per subgroup before and after CL were also performed. Results: The preload in the PG was significantly lower under nCL (29.92 Ncm) compared with CG (30.95 Ncm) and GG (31.19 Ncm) and also under a CL (PG: 30.92 Ncm) compared with CG (31.72 Ncm) and GG (31.42 Ncm). The RTVs of the PG were significantly lower under nCL (15.30 Ncm) compared with CG (27.98 Ncm) and GG (28.46 Ncm). Under CL, the RTVs of the PG were significantly higher (31.50 Ncm) compared with CG (26.00 Ncm) and GG (27.44 Ncm). Conclusions: Wrapping the screw with PTFE tape significantly reduced the preload but resulted in a significantly greater RTV under CL conditions in the simulated oral environment, suggesting that this could be a solution to decrease the risk of screw loosening. Full article