Search Results (9,024)

This study investigated into how different current input levels during cold metal transfer (CMT) welding affected the characteristics of the weld bead. For the current variation, three input values were taken: 80 A, 90 A, and 100 A. Weld beads fabricated from all three current inputs were compared by analysing their microstructure, microhardness, tensile strength, and residual stress. The microhardness of the weld bead decreased when the current parameter was increased from 80 A to 100 A. The average tensile strength increased from 80 A to 90 A. The lowest residual stress calculated was −135 MPa with 100 A current. Full article

Triple-negative breast cancer (TNBC) is a clinically and molecularly heterogeneous subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. In this study, tumor specimens from 104 TNBC patients were analyzed to characterize molecular and clinicopathological features and to assess the expression and therapeutic potential of four key surface markers: epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), tissue factor (TF), and trophoblast cell surface antigen (TROP2). Multiplex immunofluorescence (mIF) demonstrated elevated EGFR and TROP2 expression in the majority of samples. Significant positive correlations were observed between EGFR and TF, as well as between TROP2 and both TF and EpCAM. Expression analyses revealed increased EGFR and TF levels with advancing tumor stage, whereas EpCAM expression declined in advanced-stage tumors. TROP2 and TF expression were significantly elevated in higher-grade tumors. Additionally, EGFR and EpCAM levels were significantly higher in patients with elevated Ki-67 indices. Binding specificity assays using single-chain variable fragment (scFv-SNAP) fusion proteins confirmed robust targeting efficacy, particularly for EGFR and TROP2. These findings underscore the therapeutic relevance of EGFR and TROP2 as potential biomarkers and targets in TNBC. Full article

Carbon monoxide (CO) is a major toxic gas emitted from vehicle exhaust, industrial processes, and incomplete fuel combustion, posing serious environmental and health risks. Catalytic oxidation of CO into less harmful CO₂ is an effective strategy to reduce these emissions. In this study, we investigated the catalytic performance of platinum (Pt) single atoms doped on C₃N monolayers with various vacancy defects, including single carbon (C_V) and nitrogen (N_V) vacancies, using density functional theory (DFT) calculations. Our results demonstrate that Pt@N_V-C₃N exhibited the most favorable catalytic properties, with the highest O₂ adsorption energy (−3.07 eV). This performance significantly outperforms Pt atoms doped at other vacancies. It can be attributed to the strong binding between Pt and nitrogen vacancies, which contributes to its excellent resistance to Pt aggregation. CO oxidation on Pt@N_V-C₃N proceeds via the Eley–Rideal (ER2) mechanism with a low activation barrier of 0.41 eV for the rate-determining step, indicating high catalytic efficiency at low temperatures. These findings suggest that Pt@N_V-C₃N is a promising candidate for CO oxidation, contributing to developing cost-effective and environmentally sustainable catalysts. The strong binding of Pt atoms to the nitrogen vacancies prevents aggregation, ensuring the stability and durability of the catalyst. The kinetic modeling further revealed that the ER2 mechanism offers the highest reaction rate constants over a wide temperature range (273–700 K). The low activation energy barrier also facilitates CO oxidation at lower temperatures, addressing critical challenges in automotive and industrial pollution control. This study provides valuable theoretical insights for designing advanced single-atom catalysts for environmental remediation applications. Full article

The Golgi of goblet cells represents a specialized machine for mucin glycosylation. This process occurs in a specialized form of the secretory pathway, which remains poorly examined. Here, using high-resolution three-dimensional electron microscopy (EM), EM tomography, serial block face scanning EM (SBF-SEM) and immune EM we analyzed the secretory pathway in goblet cells and revealed that COPII-coated buds on the endoplasmic reticulum (ER) are extremely rare. The ERES vesicles with dimensions typical for the COPII-dependent vesicles were not found. The Golgi is formed by a single cisterna organized in a spiral with characteristics of the cycloid surface. This ribbon has a shape of a cup with irregular perforations. The Golgi cup is filled with secretory granules (SGs) containing glycosylated mucins. Their diameter is close to 1 µm. The cup is connected with ER exit sites (ERESs) with temporal bead-like connections, which are observed mostly near the craters observed at the externally located cis surface of the cup. The craters represent conus-like cavities formed by aligned holes of gradually decreasing diameters through the first three Golgi cisternae. These craters are localized directly opposite the ERES. Clusters of the 52 nm vesicles are visible between Golgi cisternae and between SGs. The accumulation of mucin, started in the fourth cisternal layer, induces distensions of the cisternal lumen. The thickness of these distensions gradually increases in size through the next cisternal layers. The spherical distensions are observed at the edges of the Golgi cup, where they fuse with SGs and detach from the cisternae. After the fusion of SGs located just below the apical plasma membrane (APM) with APM, mucus is secreted. The content of this SG becomes less osmiophilic and the excessive surface area of the APM is formed. This membrane is eliminated through the detachment of bubbles filled with another SG and surrounded with a double membrane or by collapse of the empty SG and transformation of the double membrane lacking a visible lumen into multilayered organelles, which move to the cell basis and are secreted into the intercellular space where the processes of dendritic cells are localized. These data are evaluated from the point of view of existing models of intracellular transport. Full article

Diacylglycerol-O-acyltransferase 1 (DGAT1, EC 2.3.1.20) is a pivotal enzyme in plant triacylglycerol (TAG) biosynthesis. Previous work identified conserved di-arginine (R) motifs (R-R, R-X-R, and R-X-X-R) in its N-terminal cytoplasmic acyl-CoA binding domain. To elucidate their functional significance, we engineered R-rich sequences in the N-termini of Tropaeolum majus and Zea mays DGAT1s. Comparative analysis with their respective non-mutant constructs showed that deleting or substituting R with glycine in the N-terminal region of DGAT1 markedly reduced lipid accumulation in both Camelina sativa seeds and Saccharomyces cerevisiae cells. Immunofluorescence imaging revealed co-localization of non-mutant and R-substituted DGAT1 with lipid droplets (LDs). However, disruption of an N-terminal di-R motif destabilizes DGAT1, alters LD organization, and impairs recombinant oleosin retention on LDs. Further evidence suggests that the di-R motif mediates DGAT1 retrieval from LDs to the endoplasmic reticulum (ER), implicating its role in dynamic LD–ER protein trafficking. These findings establish the conserved di-R motifs as important regulators of DGAT1 function and LD dynamics, offering insights for the engineering of oil content in diverse biological systems. Full article

Alzheimer’s disease (AD) is increasingly recognized as a multifactorial disorder driven by a combination of disruptions in proteostasis and organelle communication. The 2020 Lancet commission reported that approximately 10 million people worldwide were affected by AD in the mid-20th century. AD is the most prevalent cause of dementia. By early 2030, the global cost of dementia is projected to rise by USD 2 trillion per year, with up to 85% of that cost attributed to daily patient care. Several factors have been implicated in the progression of neurodegeneration, including increased oxidative stress, the accumulation of misfolded proteins, the formation of amyloid plaques and aggregates, the unfolded protein response (UPR), and mitochondrial–endoplasmic reticulum (ER) calcium homeostasis. However, the exact triggers that initiate these pathological processes remain unclear, in part because clinical symptoms often emerge gradually and subtly, complicating early diagnosis. Among the early hallmarks of neurodegeneration, elevated levels of reactive oxygen species (ROS) and the buildup of misfolded proteins are believed to play pivotal roles in disrupting proteostasis, leading to cognitive deficits and neuronal cell death. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles is a characteristic feature of AD. These features contribute to chronic neuroinflammation, which is marked by the release of pro-inflammatory cytokines and chemokines that exacerbate oxidative stress. Given these interconnected mechanisms, targeting stress-related signaling pathways, such as oxidative stress (ROS) generated in the mitochondria and ER, ER stress, UPR, and cytosolic chaperones, represents a promising strategy for therapeutic intervention. This review focuses on the relationship between stress chaperone responses and organelle function, particularly the interaction between mitochondria and the ER, in the development of new therapies for AD and related neurodegenerative disorders. Full article

Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific probes for SPECT would permit imaging-guided therapy in regions with restricted access to PET facilities. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the [^99mTc]Tc-DB8 GRPR-antagonistic peptide. We also addressed the important issue of finding the optimal injected peptide mass. Methods: Fifteen female patients with ER-positive primary breast cancer were enrolled and divided into three cohorts receiving [^99mTc]Tc-DB8 (corresponding to three distinct doses of 40, 80, or 120 µg DB8) comprising five patients each. Additionally, four patients with ER-negative primary tumors were injected with 80 µg [^99mTc]Tc-DB8. The injected activity was 360 ± 70 MBq. Planar scintigraphy was performed after 2, 4, 6, and 24 h, and SPECT/CT scans followed planar imaging 2, 4, and 6 h after injection. Results: No adverse events were associated with [^99mTc]Tc-DB8 injections. The effective dose was 0.009–0.014 mSv/MBq. Primary tumors and all known lymph node metastases were visualized irrespective of injected peptide mass. The highest uptake in the ER-positive tumors was 2 h after injection of [^99mTc]Tc-DB8 at a 80 µg DB8 dose (SUV_max 5.3 ± 1.2). Injection of [^99mTc]Tc-DB8 with 80 µg DB8 provided significantly (p < 0.01) higher uptake in primary ER-positive breast cancer lesions than injection with 40 µg DB8 (SUV_max 2.0 ± 0.3) or 120 µg (SUV_max 3.2 ± 1.4). Tumor-to-contralateral breast ratio after injection of 80 μg was also significantly (p < 0.01, ANOVA test) higher than ratios after injection of other peptide masses. The uptake in ER-negative lesions was significantly lower (SUV_max 2.0 ± 0.3) than in ER-positive tumors. Conclusions: Imaging using [^99mTc]Tc-DB8 is safe, tolerable, and associated with low absorbed doses. The tumor uptake is dependent on the injected peptide mass. The injection of an optimal mass (80 µg) provides the highest uptake in ER-positive tumors. At optimal dosing, the uptake was significantly higher in ER-positive than in ER-negative lesions. Full article

Vibrio parahaemolyticus is a major foodborne pathogen worldwide, responsible for seafood-associated poisoning. Among its toxin genes, tdh2 is the most critical. To investigate the role of tdh2 in V. parahaemolyticus under gastrointestinal conditions, we constructed tdh2 deletion and complementation strains and compared their survival under acid (pH 3 and 4) and bile stress (2%). The results showed that tdh2 expression was significantly upregulated under cold (4 °C) and bile stress (0.9%). Survival assays and PI staining revealed that the tdh2 mutant strain (VP: △tdh2) was more sensitive to acid and bile stress than the wild-type (WT), and this sensitivity was rescued by tdh2 complementation. These findings suggest that tdh2 plays a protective role in enhancing V. parahaemolyticus tolerance to acid and bile stress. In the VP: △tdh2 strain, seven genes were significantly upregulated and six were downregulated as a result of tdh2 deletion. These genes included VPA1332 (vtrA), VPA1348 (vtrB), VP2467 (ompU), VP0301 and VP1995 (ABC transporters), VP0527 (nhaR), and VP2553 (rpoS), among others. Additionally, LC-MS/MS analysis identified 12 differential metabolites between the WT and VP: △tdh2 strains, including phosphatidylserine (PS) (17:2 (9Z,12Z) /0:0 and 20:1 (11Z) /0:0), phosphatidylglycerol (PG) (17:0/0:0), flavin mononucleotide (FMN), and various nucleotides. The protective mechanism of tdh2 may involve preserving cell membrane permeability through regulation of ompU and ABC transporters and enhancing electron transfer efficiency via regulation of nhaR. The resulting reduction in ATP, DNA, and RNA synthesis—along with changes in membrane permeability and electron transfer due to decreased FMN—likely contributed to the reduced survival of the VP: △tdh2 strain. Meanwhile, the cells actively synthesized phospholipids to repair membrane damage, leading to increased levels of PS and PG. This study provides important insights into strategies for preventing and controlling food poisoning caused by tdh⁺ V. parahaemolyticus. 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 β-glucosidase CEL1B has been linked to regulating cellulase expression in Trichoderma reesei, yet its inducer-specific functions and broader regulatory roles remain poorly characterized. In this study, CRISPR-Cas9-mediated gene knockout was applied in the industrial high-producing T. reesei Rut C30 to investigate CEL1B function without the confounding effects of KU70 deletion. Unlike previous studies focused solely on cellulose or lactose induction, transcriptomic analysis of the CEL1B knockout strain revealed its regulatory roles under both lactose- and sophorose-rich conditions, with sophorose representing the most potent natural inducer of cellulase expression. Under lactose induction, CEL1B deletion resulted in a 52.4% increase in cellulase activity (p < 0.05), accompanied by transcriptome-wide upregulation of β-glucosidase genes (CEL3A: 729%, CEL3D: 666.8%, CEL3C: 110.9%), cellulose-sensing receptors (CRT1: 203.0%, CRT2: 105.8%), and key transcription factors (XYR1: 2.7-fold, ACE3: 2.8-fold, VIB1: 2.1-fold). Expression of ER proteostasis genes was significantly upregulated (BIP1: 3.3-fold, HSP70: 6.2-fold), contributing to enhanced enzyme secretion. Conversely, under sophorose induction, CEL1B deletion reduced cellulase activity by 25.7% (p < 0.05), which was associated with transcriptome profiling showing significant downregulation of β-glucosidase CEL3H (66.6%) and cellodextrin transporters (TrireC30_91594: 79.3%, TrireC30_127980: 76.3%), leading to reduced cellobiohydrolase expression (CEL7A: 57.8%, CEL6A: 67.8%). This first transcriptomic characterization of the CEL1B knockout strain reveals its dual opposing roles in modulating cellulase expression in response to lactose versus sophorose, providing new strategies for optimizing inducer-specific enzyme production in T. reesei. Full article

Unsupervised hyperspectral image (HSI) clustering is a fundamental yet challenging task due to high dimensionality and complex spectral–spatial characteristics. In this paper, we propose a novel and efficient clustering framework centered on adaptive and diverse anchor graph modeling. First, we introduce a parameter-free construction strategy that employs Entropy Rate Superpixel (ERS) segmentation to generate multiple anchor graphs of varying sizes from a single HSI, overcoming the limitation of fixed anchor quantities and enhancing structural expressiveness. Second, we propose an anchor-to-pixel label propagation mechanism to transfer anchor-level cluster labels back to the pixel level, reinforcing spatial coherence and spectral discriminability. Third, we perform clustering directly at the anchor level, which substantially reduces computational cost while retaining structure-aware accuracy. Extensive experiments on three benchmark datasets (Trento, Salinas, and Pavia Center) demonstrate the effectiveness and efficiency of our approach. Full article

Detecting pharmaceuticals in environmental matrices, particularly in wastewater, is crucial due to their potential environmental occurrence and unpredictable ecological and health-related consequences. These substances, often present in trace amounts, require highly sensitive and selective analytical methods for effective monitoring. A modified version of the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method was evaluated to evaluate 18 pharmaceuticals and 2 metabolites in wastewater samples using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The method’s performance was assessed using linearity, recovery, precision, limits of quantification (LOQ) and detection (LOD), and the matrix effect (ME). The final method was based on acetonitrile, Na₂EDTA, citrate buffer, and graphene oxide (GO). Finally, the calibration curves prepared in acetonitrile and the matrix extract showed a correlation coefficient of 0.99. Most of the compounds had LOQ values lower than 0.5 μg⋅mL⁻¹. Recoveries were achieved in the 70–98% range, with RSD lower than 13%. GO allowed the elimination of the ME, which occurred in the range of −11% to 15%. The results indicate that a low-cost and straightforward method is suitable for routinely monitoring pharmaceuticals in wastewater, which is crucial for minimizing the impact of pollutants on aquatic ecosystems. Full article

Neuroinflammation is a key feature of Alzheimer’s disease (AD), and stem cell therapies have emerged as promising candidates due to their immunomodulatory properties. Neuro-Cells (NC), a combination of unmodified mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), have demonstrated therapeutic potential in models of central nervous system (CNS) injury and neurodegeneration. Here, we studied the effects of NC in APPswe/PS1dE9 mice, an AD mouse model. Twelve-month-old APPswe/PS1dE9 mice or their wild-type littermates were injected with NC or vehicle into the cisterna magna. Five to six weeks post-injection, cognitive, locomotor, and emotional behaviors were assessed. The brain was stained for amyloid plaque density using Congo red, and for astrogliosis using DAPI and GFAP staining. Gene expression of immune activation markers (Il-1β, Il-6, Cd45, Tnf) and plasticity markers (Tubβ3, Bace1, Trem2, Stat3) was examined in the prefrontal cortex. IL-6 secretion was measured in cultured human monocytes following endotoxin challenge and NC treatment. Untreated APPswe/PS1dE9 mice displayed impaired learning in the conditioned taste aversion test, reduced object exploration, and anxiety-like behavior, which were improved in the NC-treated mutants. NC treatment normalized the expression of several immune and plasticity markers and reduced the density of GFAP-positive cells in the hippocampus and thalamus. NC treatment decreased amyloid plaque density in the hippocampus and thalamus, targeting plaques of <100 μm². Additionally, NC treatment suppressed IL-6 secretion by human monocytes. Thus, NC treatment alleviated behavioral deficits and reduced amyloid plaque formation in APPswe/PS1dE9 mice, likely via anti-inflammatory mechanisms. The reduction in IL-6 production in human monocytes further supports the potential of NC therapy for the treatment of AD. Full article

End-to-end relation extraction (E2ERE) generally performs named entity recognition and relation extraction either simultaneously or sequentially. While numerous studies on E2ERE have centered on enhancing span representations to improve model performance, challenges remain due to the gaps between subtasks (named entity recognition and relation extraction) and the modeling discrepancies between entities and relations. In this paper, we propose a novel Label Annotation Interaction-based representation enhancement method for E2ERE, which institutes a two-phase semantic interaction to augment representations. Specifically, we firstly feed label annotations that are easy to manually annotate into a language model, and conduct the first-round interaction between three types of tokens with a partial attention mechanism; Then we construct a latent multi-view graph to capture various possible links between label and entity (pair) nodes, facilitating the second-round interaction between entities and labels. A series of comparative experiments with methods of various transformer-based architectures currently in use show that LAI-Net can maintain performance on par with the current SOTA in terms of NER task, and achieves significant improvements over existing SOTA models in terms of RE task. Full article

In this position paper, we argue that the conventional understanding of ‘information’ (as generally conceived in science, in a digital fashion) is overly simplistic and not consistently applicable to living systems, which are open systems that cannot be reduced to any kind of ‘portion’ (building block) ascribed to the category of quantity. Instead, it is a matter of relationships and qualities in an indivisible analogical (and ontological) relationship between any presumed ‘software’ and ‘hardware’ (information/matter, psyche/soma). Furthermore, in biological systems, contrary to Shannon’s definition, which is well-suited to telecommunications and informatics, any kind of ‘information’ is the opposite of internal entropy, as it depends directly on order: it is associated with distinction and differentiation, rather than flattening and homogenisation. Moreover, the high degree of structural compartmentalisation of living matter prevents its energetics from being thermodynamically described by using a macroscopic, bulk state function. This requires the Second Principle of Thermodynamics to be redefined in order to make it applicable to living systems. For these reasons, any static, bit-related concept of ‘information’ is inadequate, as it fails to consider the system’s evolution, it being, in essence, the organized coupling to its own environment. From the perspective of quantum field theory (QFT), where many vacuum levels, symmetry breaking, dissipation, coherence and phase transitions can be described, a consistent picture emerges that portrays any living system as a relational process that exists as a flux of context-dependent meanings. This epistemological shift is also associated with a transition away from the ‘particle view’ (first quantisation) characteristic of quantum mechanics (QM) towards the ‘field view’ possible only in QFT (second quantisation). This crucial transition must take place in life sciences, particularly regarding the methodological approaches. Foremost because biological systems cannot be conceived as ‘objects’, but rather as non-confinable processes and relationships. Full article