Search Results (695)

Traumatic brain injury (TBI) disrupts the blood–brain barrier (BBB), resulting in increased permeability, neuronal loss, and cognitive dysfunction. This study investigates the therapeutic potential of thyroid hormone (T4) to reduce BBB dysfunction following moderate fluid percussion injury. T4 injection (intraperitoneal) after TBI restores the levels of pericytes and endothelial cells vital for BBB integrity, reduces edema by downregulating AQP-4 gene expression, and enhances levels of the tight junction protein ZO-1. T4 counteracts the TBI-related increase in MMP-9 and TLR-4, significantly reducing BBB permeability. Furthermore, T4 enhances the neuroprotective functions of astrocytes by promoting the activity of A2 astrocytes. Additionally, T4 treatment increases DHA levels (important for membrane integrity and function), stimulates mitochondrial biogenesis, and leads to a notable improvement in spatial learning and memory retention. These findings suggest that T4 has significant potential to reduce vascular leakage and inflammation after TBI, thereby improving cognitive function and maintaining BBB integrity. Full article

Background: Multilevel posterior spinal fusion to T10 often encounters complications such as screw loosening and proximal junctional kyphosis. Cement augmentation or prophylactic vertebroplasty is used to prevent these, but their biomechanical effects remain unclear. Methods: A validated finite element model (T8–pelvis) from CT data of a 57-year-old male was tested in five configurations: fusion only, fusion with cement augmentation at T10, T10–T11, T10–T11 plus T9 vertebroplasty, and T10–T11 plus T8–T9 vertebroplasty. Range of motion (ROM), intradiscal pressure (IDP), posterior ligament/facet stress, and cement–bone interface stresses were analyzed under a 400 N follower load and 10 N·m moments. Results: Cement augmentation at the upper instrumented vertebra produced <5% changes in ROM, IDP, and posterior ligament/facet stresses compared with fusion only, indicating preserved stability. Prophylactic vertebroplasty redistributed stress proximally, with elevated cement–bone interface stresses localized at T9 when vertebroplasty was performed at a single adjacent level (T9) and distributed to both T8 and T9 when performed at two adjacent levels (T8–9)—with T9 stressed mainly during lateral bending and extension, and T8 during flexion and lateral bending. Conclusion: Cement augmentation alone did not compromise adjacent-level biomechanics, but prophylactic vertebroplasty created abnormal stress concentrations at adjacent interfaces, potentially increasing fracture risk. These findings highlight the need for careful patient selection and further studies in osteoporotic populations. Full article

Background: Orthodontically driven osteogenesis (ODO) is a surgical tunnel modification of periodontally accelerated osteogenic orthodontics (PAOO), combining selective corticotomy with bone grafting in sequential and/or segmental fashion. This is a minimally invasive approach that enhances periodontal health and allows orthodontic tooth movement beyond the original alveolar envelope. Considering the lack of long-term three-dimensional data on orthodontically driven osteogenesis (ODO), this study aims to quantitatively assess the long-term stability of alveolar bone and buccal cortical thickness following ODO, using CBCT imaging. The null hypothesis is that ODO does not result in significant changes in alveolar bone volume or cortical thickness over a seven-year follow-up period. Methods: Twenty patients (13 females, 7 males; mean age 27.4 ± 5.3 years) who had undergone orthodontically driven osteogenesis (ODO) using a minimally invasive tunnel approach and segmental corticotomy protocol followed by clear aligner therapy were retrospectively evaluated. The mean follow-up period after treatment was 7 years (range: 5–15 years). Cone beam computed tomography (CBCT) scans were obtained at one year postoperatively (T1) and again at the long-term follow-up visit (T2). Buccal bone thickness measurements were taken at standardized levels (3 mm, 5 mm, and 7 mm apical to the cementoenamel junction) and compared between T1 and T2 to evaluate bone stability over time. In addition, histologic evaluation of the previously grafted area was performed in two patients: one sample was collected during an alveolar ridge augmentation procedure six months after ODO, and the other during orthognathic surgery eight months after ODO. The samples were analyzed to assess new bone formation and integration of graft material. Results: Radiographic analysis showed long term stability of the new bone support. Histologic examination showed newly formed lamellar and reticular bone. Bone marrow showed no inflammatory infiltration, and bone particles were still detectable but incorporated in the newly created bone. Conclusions: Based on these findings, ODO appears to be a promising technique that could induce stable bone osteogenesis. A larger cohort study can enhance the evidence of these promising results to popularize this technique. Full article

Background: The human gut microbiome—a diverse ecosystem of trillions of microorganisms—plays an essential role in metabolic, immune, and neurological regulation. However, modern lifestyle factors such as antibiotic overuse, cesarean delivery, reduced breastfeeding, processed and high-sodium diets, alcohol intake, smoking, and exposure to environmental toxins (e.g., glyphosate) significantly reduce microbial diversity. Loss of keystone species like Bifidobacterium infantis (B. infantis) and Lactobacillus reuteri (L. reuteri) contributes to gut dysbiosis, which has been implicated in chronic metabolic, autoimmune, cardiovascular, and neurodegenerative conditions. Materials and Methods: This Qualitative Systematic Review (QualSR) synthesized data from over 547 studies involving human participants and standardized microbiome analysis techniques, including 16S rRNA sequencing and metagenomics. Studies were reviewed for microbial composition, immune and metabolic biomarkers, and clinical outcomes related to microbiome restoration strategies. Results: Multiple cohort studies have consistently reported a 40–60% reduction in microbial diversity among Western populations compared to traditional societies, particularly affecting short-chain fatty acid (SCFA)-producing bacteria. Supplementation with B. infantis is associated with a significant reduction in systemic inflammation—including a 50% decrease in C-reactive protein (CRP) and reduced tumor necrosis factor-alpha (TNF-α) levels—alongside increases in regulatory T cells and anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-β1). L. reuteri demonstrates immunomodulatory and neurobehavioral benefits in preclinical models, while both probiotics enhance epithelial barrier integrity in a strain- and context-specific manner. In murine colitis, B. infantis increases ZO-1 expression by ~35%, and L. reuteri improves occludin and claudin-1 localization, suggesting that keystone restoration strengthens barrier function through tight-junction modulation. Conclusions: Together, these findings support keystone species restoration with B. infantis and L. reuteri as a promising adjunctive strategy to reduce systemic inflammation, reinforce gut barrier integrity, and modulate gut–brain axis (GBA) signaling, indicating translational potential in metabolic and neuroimmune disorders. Future research should emphasize personalized microbiome profiling, long-term outcomes, and transgenerational effects of early-life microbial disruption. Full article

Cancer metastasis is responsible for most cancer-related deaths. Migration and invasion, key steps in the metastatic cascade, require nuclear pliability to traverse the physical barriers of the extracellular matrix and cell–cell junctions. The nuclear envelope (NE) contains LINC complex proteins, including nesprin-4, which regulate nuclear integrity, stiffness, and cell movement. We report that nesprin-4 expression is generally upregulated in breast cancer samples but is reduced in triple-negative breast cancer (TNBC) samples compared to other subtypes. A nesprin-4 expression analysis in 62 breast cancer cell lines showed that nesprin-4 expression correlates positively with cell lines representing less aggressive tumors, while TNBC cell lines have low or no nesprin-4 expression. To determine the role of nesprin-4, we modulated nesprin-4 expression levels in three breast cancer cell lines: MCF7, T47D (luminal A and nesprin-4-positive), and MDA-MB-231 (TNBC and nesprin-4-negative). We found that nesprin-4 promotes migration and invasion by driving cell polarization. However, we also found that nesprin-4 impedes intravasation into endothelial microvessels. Thus, we propose that nesprin-4 plays a dual role in breast cancer, promoting efficient migration and invasion, but blocking intravasation. Full article

Power metal-oxide-semiconductor field-effect transistors (MOSFETs) provide numerous advantages and are widely utilized in various power circuits. The junction temperature plays a critical role in determining the reliability, performance, and operational lifetime of power MOSFETs. Therefore, accurate monitoring of the junction temperature of power MOSFETs is essential to ensure the safe operation of power circuit systems. In bridge or motor drive circuits, MOSFETs often operate in a freewheeling state via the body diode, where the freewheeling current is typically variable. The proposed method for junction temperature measurement utilizes the body diode and is designed to accommodate varying forward currents. It also accounts for the temperature-dependent ideality factor to improve measurement accuracy. By integrating the forward voltage and forward current of the body diode, this approach reduces the required sampling frequency. To validate the method’s effectiveness, three representative types of power MOSFETs, a Si MOSFET (IRF520), a SiC MOSFET (C2M0080120D), and an aerospace-grade radiation-hardened MOSFET (RSCS25045T1RH), were used to measure junction temperatures before and after irradiation. Following ideality factor correction, the maximum absolute error compared to reference measurements from thermocouples and a thermal imager remained within 2 K across the temperature range of 300 K to 420 K. Experimental results confirm the feasibility of the proposed method. Full article

Droplet-based microfluidics has rapidly advanced applications in chemistry, biology, materials science, medicine, food science, and cosmetics. Using this technology, various oils have been employed for fluid encapsulation. This study is the first to investigate the use of an animal-based unsaturated fatty acid oil—emu oil—for microdroplet formation. We characterized droplet generation in the presence and absence of a non-fluorinated surfactant at a defined concentration and examined the influence of geometrical parameters using T-junction microchannels with two different central channel widths. The results were compared with those obtained from a plant-based oil (olive oil) under parallel experimental conditions. Given the growing concerns regarding the environmental and health risks of fluorocarbon oils combined with fluorinated surfactants, which are widely used in microfluidics, emu oil represents a potentially safer alternative for microdroplet-based technologies across multiple fields. Full article

Type 2 diabetes mellitus (T2DM), a metabolic disorder defined by glucose and lipid metabolism dysregulation, has become a major global health issue. Hence, effective measures to prevent T2DM are urgently required. Lophatherum gracile Brongn (LGB) has been used in managing diabetes-related systemic diseases. However, the hypoglycemic bioactive components in LGB and the mechanisms underlying their hypoglycemic activity remain elusive. The current study sought to characterize the bioactive components of LGB and elucidate its mechanism of action against T2DM. Six common characteristic peaks were identified from six batches of LGB, with 39 characteristic chemical components preliminarily identified. Through component–activity correlation analysis, three functional components—namely isoorientin, orientin, and isovitexin—were selected as key candidates. In T2DM mice, LGB effectively improved glucose and lipid metabolic dysfunction. Untargeted metabolomics analysis revealed that LGB modulated pathways related to lipid and carbon metabolism. 16S rRNA gene sequencing and targeted metabolomics analysis revealed that LGB decreased the ratio of Firmicutes to Bacteroidetes and increased the abundance of bacterial groups such as Lactobacillales and Bacteroides. Additionally, LGB elevated the levels of SCFAs, specifically acetic and butyric acid. Moreover, LGB alleviated intestinal inflammation and upregulated the expression of tight junction proteins by inhibiting the LPS/TLR4/NF-κB signaling pathway. This study demonstrated that LGB treated T2DM, with isoorientin, orientin, and isovitexin identified as the main contributing components. The hypoglycemic mechanism is linked to the “gut microbiota−SCFAs−inflammatory response” signaling axis. Full article

In recent years, graphitic carbon nitride (g-C₃N₄) has gained considerable ground in the field of heterogeneous photocatalysis for the abatement of emerging contaminants from aqueous environments. Nonetheless, certain limitations, including a small surface area and a high recombination rate, limit its photocatalytic efficacy. In this study, g-C₃N₄ was synthesized from urea and then underwent thermal exfoliation. A portion of the exfoliated material was subsequently subjected to protonation via acid treatment, and both protonated and non-protonated variants of exfoliated g-C₃N₄ were combined with small amounts of Ti₃C₂T_x MXene. The morphology, chemical structure, and optical properties of the synthesized materials were examined using various characterization techniques. Additionally, their photocatalytic performance was evaluated through laboratory tests using the commonly detected anti-hypertensive drug valsartan as a model pollutant. The degradation kinetics of valsartan revealed that combining 1% Ti₃C₂T_x MXene with exfoliated g-C₃N₄ (both protonated and non-protonated) achieves optimal removal. Notably, the composite material 1%-pCNMX (protonated variant) displayed a 20% higher removal kinetic rate than unmodified exfoliated g-C₃N₄, removing a higher quantity of valsartan within the same time frame. Furthermore, all protonated composites proved more effective in degrading valsartan than their non-protonated counterparts, demonstrating the positive impact of acid treatment. The improved photocatalytic activity was attributed to the successful formation of Schottky junctions between g-C₃N₄ and Ti₃C₂T_x, which reduced the recombination rate of photogenerated charge carriers. Full article

Severe pressure pulsations caused by complex flow fields in pumped-storage power stations significantly threaten operational safety and stability. With advances in computational technology, fully three-dimensional simulations coupling pipelines and pump-turbine units have become feasible. In this study, a fully three-dimensional analysis model was developed, coupling the water conveyance system and a finely modeled prototype-scale pump-turbine with splitter blades, to numerically simulate the compressible flow field under the maximum head pump mode. The study reveals a strong bidirectional coupling between the flow in the long outlet pipe and the internal flow within the pump-turbine unit. Influenced by structural features such as bifurcations and flow impingement at the T-junction, complex three-dimensional vortices arise and cannot be neglected. Based on the flow field, the study further investigates the time-domain, frequency-domain, and spatial characteristics of pressure pulsations at various downstream hydraulic components, ranging from the vaneless space to the outlet of the long outlet pipe. The pressure pulsation frequencies are shown to be affected by both rotor–stator interactions and the complex vortical structures in the flow. These findings clearly demonstrate the necessity of fully three-dimensional simulations that incorporate both the water conveyance system and the pump-turbine unit. Full article

Background and Objectives: The systemic immune-inflammation index (SII), derived from peripheral blood parameters, has emerged as a novel marker reflecting the balance between host immunity and tumor-related inflammatory burden. This study aimed to investigate the prognostic impact of baseline SII on survival outcomes in patients with gastric or gastroesophageal junction (GEJ) cancer undergoing perioperative FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy. Materials and Methods: In this retrospective study, 168 patients with histologically confirmed gastric or GEJ cancer who received perioperative FLOT therapy were included. SII was calculated using the formula: SII = (Platelets × Neutrophils)/Lymphocytes. ROC curve analysis determined the optimal SII cutoff for predicting mortality. Patients were categorized into low (SII ≤685) and high (SII >685) groups. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan–Meier analysis and compared via the log-rank test. Cox proportional hazards regression models were used for univariate and multivariate analysis. Results: The optimal cutoff value for SII was determined to be 685 (AUC: 0.652, 95% CI: 0.558–0.747, p = 0.003). High SII was significantly shorter OS (17.4 vs. 28.2 months, p = 0.001) Multivariate analysis identified high SII (HR = 1.88, 95% CI: 1.36–2.89, p = 0.039), advanced T stage (HR = 3.693, p < 0.001), poor treatment response (HR = 0.36, p < 0.001), and ECOG-PS ≥1 (HR = 3.297, p < 0.001) as independent predictors of mortality. Conclusions: Elevated baseline SII is an independent predictor of worse OS and DFS in gastric and GEJ cancer patients receiving perioperative FLOT chemotherapy. SII may serve as a practical and inexpensive biomarker to support risk stratification and personalized treatment decisions. Full article

The present study investigates passive microdroplet generation in a T-junction microchannel using microscopic observations, microscale particle image velocimetry (Micro-PIV) visualization, and lattice Boltzmann simulations. The key flow regimes, i.e., dripping, threading, and parallel flow, are characterized by analyzing the balance between hydrodynamic forces and surface tension, revealing the critical role of the flow rate ratio of the continuous to dispersed fluids in regime transitions. Micro-PIV visualizes velocity fields and vortex structures during droplet formation, while a lattice Boltzmann model with wetting boundary conditions captures interface deformation and flow dynamics, showing good agreement with experiments in the dripping and threading regimes but discrepancies in the parallel flow regime due to neglected surface roughness. The present experimental results highlight non-monotonic trends in the maximum head interface and breakup positions of the dispersed fluid under various flow rates, reflecting the competition between the squeezing and shearing forces of the continuous fluid and the hydrodynamic and surface tension forces of the dispersed fluid. Quantitative analysis shows that the droplet size increases with the flow rate of continuous fluid but decreases with the flow rate of dispersed fluid, while generation frequency rises monotonically with the flow rate of dispersed fluid. The dimensionless droplet length correlates with the flow rate ratio, enabling tunable control over droplet size and flow regimes. This work enhances understanding of T-junction microdroplet generation mechanisms, offering insights for applications in precision biology, material fabrication, and drug delivery. Full article

SLC35A2-CDG is a congenital disorder of glycosylation caused by mutations in the SLC35A2 gene encoding a Golgi-localized UDP-galactose transporter. This transporter plays an essential role in glycan synthesis by transporting UDP-galactose from the cytoplasm into the Golgi lumen. Its dysfunction leads to impaired galactose-containing glycans and various neurological symptoms, although the underlying mechanisms remain largely unknown. We identified a novel SLC35A2-CDG patient carrying a pathogenic variant (c.617_620del, p.(Gln206ArgfsTer45)) who exhibited neurological abnormalities including bilateral ventriculomegaly. To investigate the disease mechanism, we established the first Drosophila model of SLC35A2-CDG. Knockout of Ugalt, the fly ortholog of SLC35A2, resulted in embryonic lethality, indicating its essential role. Knockdown of Ugalt reduced mucin-type O-glycans on muscles and neuromuscular junctions (NMJs), without affecting N-glycans. Ugalt knockdown larvae exhibited mislocalized NMJ boutons accompanied by a deficiency in basement membrane components on muscles. This phenotype resembles that of mutants of dC1GalT1 and dGlcAT-P, both involved in mucin-type O-glycosylation. Genetic interaction between Ugalt and dC1GalT1 was confirmed through double knockdown and double heterozygous analyses. Given that Drosophila NMJs are widely used as a model for mammalian central synapses, our findings suggest that Ugalt regulates NMJ architecture via mucin-type O-glycosylation and provide insights into the molecular basis of neurological abnormalities in SLC35A2-CDG. Full article

Background: Collabieae is a medium-sized group within the orchid subfamily Epidendroideae that is distributed primarily across tropical Asia. Most Collabieae species are known for their considerable ornamental and medicinal merits. However, habitat destruction and overharvesting have led to severe decline in their wild populations. Chloroplast (cp) genomes are highly valued in evolutionary studies, due to comparative conservation and accumulation of genomic variations. Elucidating the structure of chloroplast genome is instrumental in conserving genetic diversity within the Collabieae. Methods: we explored the chloroplast genome characteristics of Collabieae. We incorporated three newly sequenced genomes from species (Acanthophippium sylhetense, Eriodes barbata, and Spathoglottis plicata), along with seven related species. Results: all analyzed cp genomes displayed a typical quadripartite circular structure. The total lengths ranged from 157,036 bp to 158,321 bp. Each genome contained 136 genes: 88 protein-coding genes, 38 tRNA genes, eight rRNA genes, and two pseudogenes. Across the ten Collabieae species, gene number, order, orientation, GC content, and codon usage bias were highly consistent, indicative of strong sequence conservation. However, notable structural divergence was observed at the plastome junctions, alongside variations in SSR and repetitive element frequencies. Moreover, six hypervariable regions were identified. Noncoding regions exhibited higher variability compared to protein-coding regions. Phylogenetic analysis indicated that E. barbata forms a distinct, small branch sister to the rest of the Collabieae members. Genera Acanthophippium and Spathoglottis were sister to the remaining groups within the tribe. Conclusions: this overall phylogenetic framework aligns well with previous findings. Our study provides valuable cp genomic resources and advances evolutionary research in Collabieae. Full article

Hippophae neurocarpa S. W. Liu & T. N. Ho exhibits established medicinal characteristics, valuable dietary attributes, and remarkable adaptability, displaying strong resistance to cold, drought, and to acidic and alkaline soils. These traits and others make it a valuable species for soil erosion control and a distinctive economic forest tree in western China. However, research on its geographic distribution remains limited. To address this gap, we employed the MaxEnt model to map its current distribution and to predict the future geographic distribution of suitable habitats for this species under SSP1-2.6, SSP2-4.5, and SSP5-8.5 climate scenarios. Collectively, these data suggest that the species’ current and future suitable habitats are predominantly concentrated at the junction of the northeastern Qinghai-Tibet Plateau and the Loess Plateau. Under present climatic conditions, highly suitable habitats are primarily located in the northeastern Qinghai-Tibet Plateau, with smaller patches in the Hengduan and Himalaya mountains. The AUC value of this model reached 0.954; projections under three future emission scenarios indicate an overall expansion trend in suitable habitat area. Notably, by the 2070s under the SSP2-4.5 scenario, the total suitable habitat area is projected to increase by 11.64%—the highest among all scenarios. Additionally, climate change is expected to drive a slight northward shift in the species’ distribution center toward higher latitudes. Key environmental factors influencing its projected distribution include elevation (elev), temperature seasonality (bio04), mean temperature of the coldest quarter (bio11), and precipitation of the warmest quarter (bio18). These insights are critical for conserving H. neurocarpa’s genetic resources and guiding future biodiversity conservation strategies. Full article