Search Results (1,995)

Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea (Thunb.) DC.—long used in Thai and East Asian medicine, contains atractylodin (ATD), a potent bioactive compound with anticancer potential. Here, we developed ATD-loaded poly(lactic co-glycolic acid) nanoparticles (ATD PLGA NPs) and evaluated their antitumor efficacy against CCA. The formulated nanoparticles had a mean diameter of 229.8 nm, an encapsulation efficiency of 83%, and exhibited biphasic, sustained release, reaching a cumulative release of 92% within seven days. In vitro, ATD-PLGA NPs selectively reduced the viability of CL-6 and HuCCT-1 CCA cell lines, with selectivity indices (SI) of 3.53 and 2.61, respectively, outperforming free ATD and 5-fluorouracil (5-FU). They suppressed CL-6 cell migration and invasion by up to 90% within 12 h and induced apoptosis in 83% of cells through caspase-3/7 activation. Micronucleus assays showed lower mutagenic potential than the positive control. In vivo, ATD-PLGA NPs dose-dependently inhibited tumor growth and prolonged survival in CCA-xenografted nude mice; the high-dose regimen matched or exceeded the efficacy of 5-FU. Gene expression analysis revealed significant downregulation of pro-tumorigenic factors (VEGF, MMP-9, TGF-β, TNF-α, COX-2, PGE₂, and IL-6) and upregulation of the anti-inflammatory cytokine IL-10. Collectively, these results indicate that ATD-PLGA NPs are a promising nanotherapeutic platform for targeted CCA treatment, offering improved anticancer potency, selectivity, and safety compared to conventional therapies. Full article

The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, thus providing abundant resources for the discovery of antiviral candidates. While many candidates have been suggested to have antiviral activity against SARS-CoV-2 infection, few have been validated for their mechanisms, including possible effects on viral entry. This study aimed to identify SARS-CoV-2 entry inhibitors from medicinal herbs and herbal formulas that are known for heat-clearing and detoxifying properties and/or antiviral activities. A SARS-CoV-2 pseudoparticle (SARS-CoV-2pp) system was used to assess mechanism-specific entry inhibition. Our results showed that the methanol extract of Anemarrhena asphodeloides rhizome, as well as the water extracts of Cimicifuga foetida rhizome, Xiao Chai Hu Tang (XCHT), and Sheng Ma Ge Gen Tang (SMGGT), have substantial inhibitory effects on the entry of SARS-CoV-2pps into host cells. Given the observation that Cimicifuga foetida exhibited the most potent inhibition and is a constituent of SMGGT, we further investigated the major compounds of the herb and identified caffeic acid as a bioactive component for blocking SARS-CoV-2pp entry. Entry inhibition of Cimicifuga foetida and caffeic acid was validated on both wild-type and the currently dominant JN.1 strain SARS-CoV-2pp systems. Moreover, caffeic acid was able to both inactivate the pseudoparticles and prevent their entry into pretreated host cells. The results support the traditional use of these herbal medicines and underscore their potential as valuable resources for identifying active compounds and developing therapeutic entry inhibitors for the management of COVID-19. Full article

Hyperspectral image (HSI) classification is an important task in the field of remote sensing, with far-reaching practical significance. Most Convolutional Neural Networks (CNNs) only focus on local spatial features and ignore global spectral dependencies, making it difficult to completely extract spectral information in HSI. In contrast, Vision Transformers (ViTs) are widely used in HSI due to their superior feature extraction capabilities. However, existing Transformer models have challenges in achieving spectral–spatial feature fusion and maintaining local structural consistency, making it difficult to strike a balance between global modeling capabilities and local representation. To this end, we propose a Prompt-Gated Transformer with a Spatial–Spectral Enhancement (PGTSEFormer) network, which includes a Channel Hybrid Positional Attention Module (CHPA) and Prompt Cross-Former (PCFormer). The CHPA module adopts a dual-branch architecture to concurrently capture spectral and spatial positional attention, thereby enhancing the model’s discriminative capacity for complex feature categories through adaptive weight fusion. PCFormer introduces a Prompt-Gated mechanism and grouping strategy to effectively model cross-regional contextual information, while maintaining local consistency, which significantly enhances the ability for long-distance dependent modeling. Experiments were conducted on five HSI datasets and the results showed that overall accuracies of 97.91%, 98.74%, 99.48%, 99.18%, and 92.57% were obtained on the Indian pines, Salians, Botswana, WHU-Hi-LongKou, and WHU-Hi-HongHu datasets. The experimental results show the effectiveness of our proposed approach. Full article

Cancer is a major global health issue, with rising incidence rates highlighting the urgent need for more effective treatments. Despite advances in cancer therapy, challenges such as adverse effects and limitations of existing treatments remain. Immunotherapy, which harnesses the body’s immune system to target cancer cells, offers promising solutions. Gamma delta (γδ) T cells are noteworthy due to their potent ability to kill various cancer cells without needing conventional antigen presentation. Recent studies have focused on the role of γδ T cells in α-galactosylceramide (α-GalCer)-mediated immunity, opening new possibilities for cancer immunotherapy. We engineered humanized T cell receptor (HuTCR)-T1 γδ mice by replacing mouse sequences with human counterparts. This study investigates the cytotoxic activity of humanized γδ T cells against several human cancer cell lines (A431, HT-29, K562, and Daudi) in vitro, aiming to elucidate mechanisms underlying their anticancer efficacy. Human cancer cells were co-cultured with humanized γδ T cells, with and without α-GalCer, for 24 h. The humanized γδ T cells showed enhanced cytotoxicity across all tested cancer cell lines compared to wild-type γδ T cells. Additionally, γδ T cells from HuTCR-T1 mice exhibited higher levels of anticancer cytokines (IFN-γ, TNF-α, and IL-17) and Granzyme B, indicating their potential as potent mediators of anticancer immune responses. Blocking γδ T cells’ cytotoxicity confirmed their γδ-mediated function. These findings represent a significant step in preclinical development of γδ T cell-based cancer immunotherapies, providing insights into their mechanisms of action, optimization of therapeutic strategies, and identification of predictive biomarkers for clinical application. Full article

Background/Objectives: Cannabinoid use is rising among patients undergoing spinal fusion, yet its influence on bone healing is poorly defined. The endocannabinoid system (ECS)—through cannabinoid receptors 1 (CB1) and 2 (CB2)—modulates skeletal metabolism. We reviewed preclinical, mechanistic and clinical evidence to clarify how individual cannabinoids affect fracture repair and spinal arthrodesis. Methods: PubMed, Web of Science and Scopus were searched from inception to 31 May 2025 with the terms “cannabinoid”, “CB1”, “CB2”, “spinal fusion”, “fracture”, “osteoblast” and “osteoclast”. Animal studies, in vitro experiments and clinical reports that reported bone outcomes were eligible. Results: CB2 signaling was uniformly osteogenic. CB2-knockout mice developed high-turnover osteoporosis, whereas CB2 agonists (HU-308, JWH-133, HU-433, JWH-015) restored trabecular volume, enhanced osteoblast activity and strengthened fracture callus. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with CB2 bias, accelerated early posterolateral fusion in rats and reduced the RANKL/OPG ratio without compromising final union. In contrast, sustained or high-dose Δ⁹-tetrahydrocannabinol (THC) activation of CB1 slowed chondrocyte hypertrophy, decreased mesenchymal-stromal-cell mineralization and correlated clinically with 6–10% lower bone-mineral density and a 1.8–3.6-fold higher pseudarthrosis or revision risk. Short-course or low-dose THC appeared skeletal neutral. Responses varied with sex, age and genetic background; no prospective trials defined safe perioperative dosing thresholds. Conclusions: CB2 activation and CBD consistently favor bone repair, whereas chronic high-THC exposure poses a modifiable risk for nonunion in spine surgery. Prospective, receptor-specific trials stratified by THC/CBD ratio, patient sex and ECS genotype are needed to establish evidence-based cannabinoid use in spinal fusion. Full article

Control charts (CCs) are one of the most important techniques in statistical process control (SPC) used to monitor the behavior of critical variables. SPC is based on the averages of the samples taken. In this way, not every measurement is observed, and errors in measurements or out-of-control behaviors that are not shown graphically can be hidden. This research proposes a novel segmented control chart (SCC) that considers each measurement of the samples, expressed in matrix form. The vision system technique is used to segment measurements by shading and segmenting into binary values based on the control limits of SPC. Once the matrix is segmented, the seven main features of the matrix are extracted using the translation-, scale-, and rotation-invariant Hu moments of the segmented matrices. Finally, a grouping is made to classify the samples in clear and simple language as excellent, good, or regular using the k-means algorithm. The results visually display the total pattern behavior of the samples and their interpretation when they are classified intelligently. The proposal can be replicated in any production sector and strengthen the control of the sampling process. Full article

Objective: This study aimed to evaluate whether modifying the post-processing algorithm of Twin-Spiral Dual-Energy computed tomography (DECT) improves infarct detection compared to conventional Dual-Energy CT (DECT) and Single-Energy CT (SECT) following endovascular therapy (EVT) for large vessel occlusion (LVO). Methods: We retrospectively analyzed 52 patients who underwent Twin-Spiral DECT after endovascular stroke therapy. Ten patients were used to generate a device-specific parameter (“y”) using an AI-based neural network (SynthSR). This parameter was integrated into the post-processing algorithm for edema map generation. Quantitative Hounsfield unit (HU) measurements were used to assess density differences in ischemic brain tissue across conventional virtual non-contrast (VNC) images and edema maps. Results: The median HU of infarcted tissue in conventional mixed DECT was 33.73 ± 4.58, compared to 22.96 ± 3.81 in default VNC images. Edema maps with different smoothing filter settings showed values of 14.39 ± 4.96, 14.50 ± 3.75, and 15.05 ± 2.65, respectively. All edema maps demonstrated statistically significant HU differences of infarcted tissue compared to conventional VNC images ($p<0.001$) while maintaining the density values of non-infarcted brain tissue. Conclusions: Enhancing the post-processing algorithm of conventional virtual non-contrast imaging improves infarct detection compared to standard mixed or virtual non-contrast reconstructions in Dual-Energy CT. Full article

Background: Complete environmental adaptation requires both survival and reproductive success. The hypoxic Qinghai-Tibet Plateau (>3000 m) challenges reproduction in indigenous species. Tibetan sheep, a key plateau-adapted breed, possess remarkable hypoxic tolerance, yet the genetic basis of their reproductive success remains poorly understood. Methods: We integrated transcriptomic and genomic data from Tibetan sheep and two lowland breeds (Small-tailed Han sheep and Hu sheep) to identify Tibetan sheep reproduction-associated genes (TSRGs). Results: We identified 165 TSRGs: four genes were differentially expressed (DEGs) versus Small-tailed Han sheep, 77 DEGs versus Hu sheep were found, and 73 genes were annotated in reproductive pathways. Functional analyses revealed enrichment for spermatogenesis, embryonic development, and transcriptional regulation. Notably, three top-ranked selection signals (VEPH1, HBB, and MEIKIN) showed differential expression. Murine Gene Informatics (MGI) confirmed that knockout orthologs exhibit significant phenotypes including male infertility, abnormal meiosis (male/female), oligozoospermia, and reduced neonatal weight. Conclusions: Tibetan sheep utilize an evolved suite of genes underpinning gametogenesis and embryogenesis under chronic hypoxia, ensuring high reproductive fitness—a vital component of their adaptation to plateaus. These genes provide valuable genetic markers for the selection, breeding, and conservation of Tibetan sheep as a critical genetic resource. Full article

Background/Objectives: Pathological vertebral fragility (path-VF) increases the risk of osteoporotic fractures and pedicle screw loosening (PSL) after posterior instrumented spinal fusion (PISF). While WHO body mass index (BMI) categories broadly identify risks related to underweight and obesity, fixed thresholds may inadequately reflect vertebral fragility risks among elderly patients, especially within the normal-weight range. This study investigates whether current BMI classifications sufficiently capture the risk of path-VF in older adults. Methods: This retrospective study included 225 patients who underwent kyphoplasty or PISF (2022–2023). Path-VF was defined by non-tumorous fractures, screw reinforcement, or PSL within six months without prior reinforcement. Patients were grouped into the path-VF (n = 94) and control (n = 131) groups. HU and BMI values, BMI-related ORs, and age trends were analysed, and a logistic regression was performed. Results: Mean HU values were significantly lower in the path-VF group (71.37 ± 30.50) than in controls (130.35 ± 52.53, p < 0.001). Path-VF females (26.26 ± 5.38) had a lower BMI than the control females (29.33 ± 5.98, p = 0.002); no difference was found in males. Normal-weight females showed a borderline risk for path-VF (OR 2.03, p = 0.0495). Obesity (OR_male 0.31/OR_female 0.37) and being male and overweight (OR 0.21) were protective (all p < 0.05). BMI declined with age in path-VF males (p = 0.001) but increased in the controls (p = 0.023). A logistic regression identified a BMI < 22.5 kg/m² and age > 67.5 years as significant risk thresholds. Notably, 20.2% of path-VF patients over 67.5 had a normal weight, suggesting a potentially overlooked subgroup. Conclusions: The current WHO lower limit for normal BMI (18.5 kg/m²) may underestimate the risk of path-VF in patients older than 67.5 years, potentially overlooking 24.7% of cases. The results offer a new approach for clinicians to interpret BMI values at the lower end of the normal range (<22.5 kg/m²) with caution in elderly patients undergoing spinal surgery. Full article

Heat stress (HS) is a major environmental factor negatively impacting the reproductive performance of livestock. This study investigates the molecular mechanisms of heat stress on the hypothalamic–pituitary–ovarian (HPO) axis in Hu sheep. A heat-stressed animal model was established, and high-throughput RNA sequencing (RNA-seq) was employed to analyze gene expression in the hypothalamus, pituitary, and ovarian tissues of both control and heat-stressed groups. The results revealed significant changes in estrus behavior, hormone secretion, and reproductive health in heat-stressed sheep, with a shortened estrus duration, prolonged estrous cycles, and decreased levels of FSH, LH, E₂, and P4. A total of 520, 649, and 482 differentially expressed genes (DEGs) were identified in the hypothalamus, pituitary, and ovary, respectively. The DEGs were enriched in pathways related to hormone secretion, neurotransmission, cell proliferation, and immune response, with significant involvement of the p53 and cAMP signaling pathways. Tissue-specific responses to heat stress were observed, with distinct regulatory roles in each organ, including GPCR activity and cytokine signaling in the hypothalamus, calcium-regulated exocytosis in the pituitary, and cilium assembly and ATP binding in the ovary. Key genes such as SYN3, RPH3A, and IGFBP2 were identified as central to the coordinated regulation of the HPO axis. These findings provide new insights into the molecular basis of heat stress-induced impairments in reproductive function—manifested by altered estrous behavior, reduced hormone secretion (FSH, LH, E₂, and P4), and disrupted gene expression in the hypothalamic–pituitary–ovarian (HPO) axis—and offer potential targets for improving heat tolerance and reproductive regulation in sheep. Full article

Background: We have previously shown the remarkable impact of a single infusion of supercharged NK cells (sNK) in preventing and eliminating oral, pancreatic, and uterine cancers implanted in humanized BLT (hu-BLT) mice. Objective: In this report, we extended the studies to melanoma tumors to observe whether there were differences in response to sNK cells. Methods: We investigated the safety and tissue biodistribution profile of sNK cells in hu-BLT mice. This included the effect of sNK cell therapy on the peripheral blood-derived PBMCs, bone marrow, and spleen of hu-BLT mice. Results: Our investigation showed promising outcomes, as sNK cell infusions effectively inhibited melanoma tumor growth in hu-BLT mice. These potent cells not only traversed through the peripheral blood, spleen, and bone marrow but also infiltrated the tumor site, triggering in vivo differentiation of melanoma tumors. Moreover, the infusion of sNK cells increased the percentages of NK cells in the peripheral blood of hu-BLT mice, restoring cytotoxicity and IFN-γ secretion within the peripheral blood, spleen, and bone marrow of melanoma-bearing mice. Conclusions: This therapeutic approach not only reversed tumor progression but also revitalized the functionality of endogenous NK cells, potentially reversing the immunosuppressive effects induced by tumor cells in cancer patients. Full article

Background/Objectives: The aim of this study was to determine whether extracellular volume (ECV) fraction as determined by contrast-enhanced computed tomography (CECT) can help distinguish between autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC). Methods: Participants comprised 101 patients, including 20 diagnosed with AIP (AIP group), 42 with histologically confirmed PDAC (PDAC group), and 39 without pancreatic disease (healthy group). Contrast enhancement (CE) was calculated as CT attenuation in Hounsfield units [HU] on equilibrium-phase CECT–CT attenuation on pre-contrast CT. The ECV fraction was calculated by measuring the region of interest within the pancreatic region and aorta on pre-contrast and equilibrium-phase CECT. CT measurements were compared among groups. CE and ECV fractions were also compared for diffuse (n = 12) and focal or segmental types (n = 8). Focal- or segmental-type AIP was defined as the involvement of one or two pancreas segments. Diagnostic efficacy was evaluated through receiver operating characteristic (ROC) analyses. Results: CE and ECV fractions differed significantly between the groups (p < 0.001 each). CE was significantly higher in the AIP group (56.8 ± 7.9 HU) than in the PDAC group (42.3 ± 17.0 HU, p < 0.001) or healthy group (32.2 ± 6.1 HU, p < 0.001). ECV fraction was significantly higher in the AIP group (47.2 ± 7.3%) than in the PDAC group (31.7 ± 12.0%, p < 0.001) or healthy group (27.5 ± 5.4%, p < 0.001). In the AIP group, no significant differences in CE (56.7 ± 8.2 HU vs. 56.9 ± 8.1 HU; p = 1.000) or ECV fraction (48.0 ± 5.6% vs. 46.6 ± 8.4%; p = 0.970) were seen between diffuse and focal or segmental types. Areas under the ROC curve for differentiating AIP from PDAC were 0.78 for CE and 0.86 for ECV fraction, showing no significant difference (p = 0.083). Conclusions: ECV fraction might be clinically useful in differentiating AIP from PDAC. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the leading cause of chronic liver disease worldwide, affecting approximately 25–30% of the global adult population and highlighting the urgent need for effective therapeutics and prevention strategies. MASLD is characterized by excessive hepatic lipid accumulation and can progress, in a subset of patients, to metabolic dysfunction-associated steatohepatitis (MASH), a pro-inflammatory and pro-fibrotic condition associated with increased risk of liver cirrhosis and hepatocellular carcinoma. Although the molecular drivers of MASLD progression remain incompletely understood, several key metabolic pathways—such as triglyceride handling, cholesterol catabolism, bile acid metabolism, mitochondrial function, and autophagy—are consistently dysregulated in MASLD livers. This narrative review summarizes primary literature and highlights insights from recent reviews on the multifaceted role of the mRNA-binding protein Human antigen R (HuR) in the post-transcriptional regulation of critical cellular processes, including nutrient metabolism, cell survival, and stress responses. Emerging evidence underscores HuR’s essential role in maintaining liver homeostasis, particularly under metabolic stress conditions characteristic of MASLD, with hepatocyte-specific HuR depletion associated with exacerbated disease severity. Moreover, comorbid conditions such as obesity, type 2 diabetes mellitus, and cardiovascular disease not only exacerbate MASLD progression but also involve HuR dysregulation in extrahepatic tissues, further contributing to liver dysfunction. A deeper understanding of HuR-regulated post-transcriptional networks across metabolic organs may enable the development of targeted therapies aimed at halting or reversing MASLD progression. Full article

Optimizing the metabolizable protein level in ruminant diets represents a promising strategy to increase nitrogen use efficiency and mitigate environmental pollution. This study explored the impacts of varying metabolizable protein (MP) levels on amino acid (AA) balance, nitrogen (N) utilization, and the ruminal microbiota in Hu lambs. Fifty-four female Hu lambs of 60 d old, with an average body weight (BW) of 18.7 ± 2.37 kg, were randomly allocated to three dietary MP groups: (1) low MP (LMP, 7.38% of DM), (2) moderate MP (MMP, 8.66% of DM), and (3) high MP (HMP, 9.93% of DM). Three lambs with similar BW within each group were housed together in a single pen, serving as one experimental replicate (n = 6). The feeding trial lasted for 60 days with 10 days for adaptation. The final BW of lambs in the MMP and HMP groups increased (p < 0.05) by 5.64% and 5.26%, respectively, compared to the LMP group. Additionally, lambs fed the MMP diet exhibited an 11.6% higher (p < 0.05) average daily gain than those in the LMP group. Increasing dietary MP levels enhanced (p < 0.05) N intake, urinary N, retained N, and percent N retained, but decreased apparent N digestibility (p < 0.05). Urinary uric acid, total purine derivatives, intestinally absorbable dietary protein, microbial crude protein, intestinally absorbable microbial crude protein, and actual MP supply all increased (p < 0.05) with higher MP values in the diet. The plasma concentrations of arginine, lysine, methionine, phenylalanine, threonine, aspartic acid, proline, total essential AAs, and total nonessential AAs were the lowest (p < 0.05) in the LMP group. In the rumen, elevated MP levels led to a significant increase (p < 0.05) in the ammonia N content. The relative abundances of Candidatus_Saccharimonas, Ruminococcus, and Oscillospira were the lowest (p < 0.05), whereas the relative abundances of Terrisporobacter and the Christensenellaceae_R-7_group were the highest (p < 0.05) in the MMP group. In conclusion, the moderate dietary metabolizable protein level could enhance growth performance, balance the plasma amino acid profiles, and increase nitrogen utilization efficiency in Hu lambs, while also altering the rumen bacterial community by increasing beneficial probiotics like the Christensenellaceae_R-7_group. Full article

Synthetic biology has fundamentally advanced cell engineering and helped to develop effective therapeutics such as chimeric antigen receptor (CAR)-T cells. For these applications, the detection, localization, and quantification of heterologous fusion proteins assembled from interchangeable building blocks is of high importance. The V5 tag, a 14-residue epitope tag, offers promising characteristics for these applications but has only rarely been used in this context. Thus, we have systematically evaluated the murine anti-V5 tag antibody mu_SV5-Pk1 as well as its humanized version, hu_SV5-Pk1, to analyze cells expressing V5-tagged receptors in samples from various in vitro and in vivo experiments. We found that the V5 tag signal on cells is affected by certain fixation and detachment reagents. Immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) mouse tissue samples was performed to sensitively detect cells in tissue. We improved IHC by applying the hu_SV5-Pk1 monoclonal antibody (mAb) to avoid cross-reactivity within and unspecific background signals arising on fixed mouse tissue. Conversely, the absence of unspecific binding by the mu_SV5-Pk1 mAb was evaluated on 46 human normal or cancer tissues. Our findings present a robust toolbox for utilizing the V5 tag and cognate antibodies in synthetic biology applications. Full article