Search Results (2,187)

Pulmonary carcinoma remains a highly aggressive malignancy driven by complex signaling and epigenetic dysregulation. This study investigates a novel oncogenic pathway involving the Mg^2+/Mn²⁺-dependent protein phosphatase 1B PPM1B/myosin phosphatase (MP)/protein arginine methyltransferase 5 (PRMT5) axis, which promotes carcinogenesis by symmetrically dimethylating histone H2A and suppressing tumor suppressor genes. We hypothesized that loss of PPM1B would activate this pathway and drive tumorigenesis. Western blotting, PCR, and immunohistochemistry revealed a significant reduction in PPM1B expression in both squamous cell carcinoma (SCC) and human lung adenocarcinoma (ADC) compared to normal lung tissues, which correlated with worse patient survival. Despite an increase in total MYPT1, the regulatory subunit of MP, its inhibitory phosphorylation at Thr853 was significantly elevated in both tumor types. The inactivation of MP corresponded with a significant increase in the activating phosphorylation of PRMT5 at Thr80, especially in SCC, which was linked to a particularly poor prognosis. Downstream, this resulted in a dramatic elevation in the symmetric dimethylation of histone H2A, leading to decreased expression of retinoblastoma protein. Our findings demonstrate that decreased PPM1B expression drives the oncogenic activation of the MP/PRMT5 axis. This mechanism contributes to the aggressive nature of SCC, establishing PPM1B as a promising prognostic marker in lung cancer. Full article

In deep coal mines characterized by high temperature, high humidity, high-salinity water, and elevated ground stress, stress corrosion cracking (SCC) of bolts is widespread, causing frequent instability of roadway surrounding rock and hindering long-term stability. This study systematically examines the failure characteristics of anchorage materials in highly corrosive roadways and clarifies the effects of deep-mine temperature and humidity on material corrosion. Long-term corrosion tests on bolts reveal changes in mechanical properties and macroscopic morphology and elucidate the intrinsic mechanisms of SCC. The results show that with the increase in corrosion time, the yield strength, ultimate load and elongation of the anchor rod decrease by up to 11.8%, 13.6%, and 7.08%, respectively. Under high stress, localized corrosion pits form on bolt surfaces, rupturing the oxide film and initiating rapid anodic dissolution and cathodic hydrogen evolution. Interaction between corroded surfaces and microcracks produced by internal impurities leads to progressive damage accumulation and ultimate fracture of the bolts. These findings provide guidance for corrosion protection of coal mine roadway support materials and for improving the long-term performance of roadway supports. Full article

We evaluated four candidate SNPs (GC-NPFFR2 rs137147462, GC-NPFFR2 rs109452259, BRCA1 rs134817801, and DGAT1 p.K232A) previously reported in relation to mastitis or milk production traits, using 10,729 test-day phenotypic records collected over 10 years from 269 Japanese Holstein cows (Bos taurus) enrolled in the national Dairy Herd Improvement (DHI) program. Linear mixed models were used to estimate genotypic effects on somatic cell score (SCS) and to test multiple inheritance models. To assess clinical relevance, mastitis severity was further analyzed using categories defined by somatic cell counts (SCC). Among the SNPs tested, GC-NPFFR2 rs137147462 showed the clearest and most consistent association with SCS under a recessive model, with GG cows exhibiting higher SCS throughout lactation. Ordinal logistic regression confirmed a higher probability of progression to severe mastitis in GG cows. DGAT1 p.K232A showed additive effects, with the A allele increasing milk yield while lowering fat and protein percentages. AA cows also showed higher SCS under a modest recessive effect. BRCA1 rs134817801 and GC-NPFFR2 rs109452259 had minimal effects. These findings support GC-NPFFR2 rs137147462 as a promising marker for mastitis resistance and indicate the importance of considering not only additive but also recessive genetic models in genomic selection strategies. Full article

The curative management of localized esophageal and esophagogastric junction (EGJ) cancers has undergone major changes over the past decade, shaped by multimodal strategies integrating chemotherapy, chemoradiotherapy, surgery, and more recently, immunotherapy. For esophageal squamous cell carcinoma (SCC), neoadjuvant or definitive chemoradiotherapy remains the standard of care in Western countries. In contrast, for adenocarcinoma (AC) of the esophagus and EGJ, perioperative chemotherapy has emerged as the preferred strategy. Despite these advances, long-term outcomes remain suboptimal, and recurrence continues to pose a major challenge, highlighting the need to optimize patient selection and treatment sequencing. The integration of immunotherapy in the perioperative or adjuvant setting has recently led to improvements in surrogate endpoints yet overall survival benefit remains under investigation. For patients with tumors harboring microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), checkpoint inhibitors show exceptional activity, and non-operative management may be feasible in select cases. Conversely, human epidermal growth receptor 2 (HER2)-targeted strategies, although effective in metastatic disease, have not yet translated into practice-changing benefit in the curative setting. The role of circulating tumor deoxyribo nucleic acid (DNA) and functional imaging as real-time tools to assess response and guide treatment adaptation is also being actively explored. This review provides a comprehensive overview of current standards, ongoing developments, and future directions for the treatment of localized esophageal and EGJ cancers, with a focus on emerging personalization strategies and biomarker-driven approaches aimed at improving cure rates and minimizing treatment-related morbidity. Full article

Natural plant fibres have gained growing research interest as a construction material due to efforts to reduce the negative environmental impacts caused by construction activities. Many researchers have investigated the suitability of utilising plant fibres as reinforcement in self-compacting concrete (SCC) as a substitute for synthetic fibres, recognising that the production of synthetic fibres generates significant amounts of CO₂. In this study a bibliometric analysis was conducted to investigate the current research achievements and map the scientific studies where plant fibres were used in SCC. A detailed discussion on the effects of various plant fibres and their underlying mechanisms on the properties of SCC is also provided. The findings indicated that using plant fibres typically reduces the flowability, filling ability, and passing ability of SCC due to the high water absorption of plant fibres, fibre and aggregate interlocking, and the fibre agglomeration effect. Incorporating plant fibres increases the viscosity and enhances the segregation resistance of SCC due to the strong cohesion between plant fibres and the cement matrix. The inclusion of plant fibres usually improves the mechanical properties of SCC because of the synergetic effects of plant fibres on crack-bridging and strain redistribution across the cross-section of SCC. Adding plant fibres to SCC also reduces drying shrinkage and cracking due to the fibre bridging effect, while generally lowering the resistance to sulphate attack, acid attack, and freeze–thaw cycles and increasing the water absorption rate of SCC due to the increased porosity of the mix. A comprehensive overview of research gaps and future perspectives for further investigations is also provided in this study. Full article

Background/Objectives: Apathy is an independent risk factor for dementia and motoric–cognitive risk syndrome (MCR), a predementia syndrome characterized by slow gait and subjective cognitive complaints (SCCs). Our objective is to assess the cross-sectional association of apathy with gait velocity, SCC, and MCR in a community-based cohort of older adults. Methods: A cross-sectional survey of N = 746 community-dwelling older adults (≥60 years of age) enrolled in the Kerala Einstein Study. Apathy was measured using the Apathy Evaluation Scale (AES). Participants were stratified by AES tertile to evaluate bivariate associations, and multivariate linear and logistic regression models were used to assess the relationship of apathy with gait velocity, SCC, and MCR. Results: Compared with participants in the lowest apathy tertile, those in the highest tertile were significantly older, less physically active, and had slower gait. High-apathy participants also had lower Addenbrooke’s Cognitive Examination scores (79.4 vs. 84.5, p < 0.001) and higher depression scores (9.3 vs. 5.4, p < 0.001). Apathy was associated with slower gait velocity (β = −3.465, p ≤ 0.002), but this relationship was no longer significant after adjusting for ACE score. Apathy and SCC were significantly associated in adjusted models (p < 0.001). Although participants with MCR had higher levels of apathy compared to those without MCR (34.6 vs. 31.4, p < 0.01), prevalent MCR and apathy were not significantly associated in regression models. Conclusions: Among community-dwelling older adults in Kerala, apathy is associated with slower gait and more severe subjective cognitive complaints but not cross-sectional MCR prevalence. These findings suggest that apathy may serve as an early risk factor in dementia pathogenesis across diverse patient populations, warranting further longitudinal investigation. Full article

Infertility is a major health problem affecting about 15% of couples worldwide. Male etiology is found in almost one-third of cases. This study identified the nature of the relationship between sperm DNA fragmentation (SDF), sperm chromatin condensation (SCC) and sperm parameters. In this study, 80 samples were analyzed using two methods: the TUNEL technique to assess sperm DNA quality and aniline blue coloration to determine the level of chromatic condensation of spermatozoa. In addition, to specify the standard sperm parameters, the spermogram and the spermocytogram were analyzed. The main results revealed a significant difference between SDF and motility and, similarly, between SCC, motility, and teratozoospermia macrocephaly types (p < 0.0001, p < 0.0001, respectively), but no differences between SCC, SDF, and the other sperm parameters (p > 0.99). Full article

Background/Objectives: Functional p53 is critical for anti-tumor activity of mitomycin-C. In wild-type TP53 human papillomavirus (HPV)-positive squamous cell carcinoma (SCC) cell lines, mitomycin-C repressed E6 oncoprotein expression and induced p53, p21, and Bax, resulting in apoptosis. In mutant TP53 HPV-negative SCC cell lines, mitomycin-C was inactive. The primary aim of this trial was to determine the objective response rate (ORR) with mitomycin-C among patients with HPV-positive (cohort A) and HPV-negative (cohort B) platinum-refractory, recurrent or metastatic head and neck SCC (RM-HNSCC). Methods: Patients with platinum-refractory RM-HNSCC received mitomycin-C (10 mg/m² on day one every five weeks) until discontinuation criteria were met. Tumor response was assessed by RECIST1.1. We hypothesized an ORR of ≥30% (H₁) with mitomycin-C (vs. H₀ ORR of ≤10%). Using a two-stage Simon phase 2 design for each cohort, 2 or more responses among 12 evaluable patients were required to enroll 23 additional patients. H₁ was accepted if 6 or more responses occurred among 35 evaluable patients (power 0.90; one-sided α = 0.10). Results: Forty-seven patients were treated with mitomycin-C: 34 in cohort A and 13 in cohort B. Tumor response occurred in 3 of 33 evaluable patients in cohort A (ORR 9.1%, 95%CI: 0–19.4) and in 0 of 12 evaluable patients in cohort B. The duration of tumor responses in cohort A was 2.3, 2.5, and 4.5 months. The most common treatment-related AEs of any grade were anemia (96%), fatigue (62%), and thrombocytopenia (40%). No treatment-related deaths occurred. Conclusions: Mitomycin-C had limited activity in HPV-positive, and no activity in HPV-negative, platinum-refractory RM-HNSCC. Full article

Background: ADAR1 (ADAR), ADAR2 (ADARB1), and ADAR3 (ADARB2) are deaminase adenosine RNA-specific enzymes that play a significant role in RNA metabolism. ADAR1 (ADAR) and ADAR2 (ADARB1) catalyze A-to-I editing and ADAR3 (ADARB2) plays a regulatory role. The role of these three genes still remains unknown in head and neck cancers (HNSCC). The aim of this study is to reveal the role of deaminase adenosine RNA-specific enzymes in pathomechanisms of HNSCC and to investigate their potential utility as diagnostic and/or prognostic biomarkers. Methods: The quantitative PCR analysis was conducted using RNA isolated from 22 pairs of matched tumor and adjacent normal tissues, 76 formalin-fixed paraffin-embedded (FFPE) tumor samples, and a panel of HNSCC cell lines (DOK, SCC-25, SCC-40, FaDu, and CAL-27). In parallel, transcriptomic and clinical data from the Cancer Genome Atlas HNSCC cohort were analyzed. Patients were stratified into high- and low-expression groups, and statistical assessments included overall survival and progression-free interval analyses, evaluation of gene expression in relation to clinicopathological parameters, correlation with other genes, and functional pathway exploration using gene set enrichment analysis. Results: ADARB2 was significantly downregulated in HNSCC tumor tissues compared to adjacent normal mucosa (p = 0.044), with discriminatory potential to distinguish malignant from non-malignant tissues (AUC = 0.692, p = 0.029). TCGA data confirmed ADAR (p < 0.0001) and ADARB1 (p < 0.0001) upregulation in tumors, while ADARB2 was markedly reduced (p = 0.04). Patients with high ADARB2 expression showed significantly longer overall survival (pa = 0.0121; pb = 0.0098), with a trend toward improved progression-free survival (pb = 0.0681). Subsite analysis revealed high ADAR expression correlated with poor OS in pharyngeal tumors (p < 0.05), whereas high ADARB2 expression was linked to improved DFS (pa = 0.0023, pb = 0.0047). GSEA indicated that low ADARB2 expression was enriched in oncogenic pathways, including Wnt/β-catenin (p = 0.006), MYC targets (p = 0.009), and TGF-β1 (p = 0.009). Conclusions: ADARB2 expression was significantly reduced in HNSCC tumor tissues compared to normal mucosa and demonstrated strong discriminatory power for distinguishing malignant from non-malignant samples. High ADARB2 expression was associated with markedly improved overall survival, whereas low expression correlated with enrichment of oncogenic pathways, including Wnt/β-catenin, Notch, and Hedgehog, consistent with a poorer clinical prognosis. These findings highlight ADARB2 as a promising diagnostic biomarker and independent prognostic factor in HNSCC. Full article

Oral squamous cell carcinoma (OSCC) is marked by profound differences in survival between the localized and disseminated disease, estimated to result in a 70% and less than a 40% five-year survival rate with surgical and/or radiation approaches (in localized cases) and chemotherapy (in metastatic cases), respectively. Given the suboptimal efficacy of current management options, new therapeutic approaches are needed to supplement existing chemotherapies and improve outcomes. One emerging therapeutic option is naltrexone (NTX), an opioid antagonist that has shown promising outcomes at low doses in other forms of cancer. This study sought to determine the effectiveness of intermittent dosing of naltrexone on oral cancer cell survival, either as a single agent or in combination with traditional chemotherapy. Two human OSCC lines (locally invasive SCC-25 and metastatic Detroit 562) were cultured. Cells were exposed to 1 µM and 10 µM NTX alone, using intermittent (5 h once, 5 h daily, 5 h every other day) or constant 72 h exposure. Cells were exposed to combination therapy with cisplatin or docetaxel under three NTX regimens (5 h, 24 h, and continuous). Cell viability was determined using Sulphorhodamine B (SRB) assay and Cell Counting Kit-8 (CCK-8). Differences across treatments were assessed using ANOVA (p < 0.05). The effect of low-dose NTX alone, across varying treatment regimens, did not yield significant, consistent changes in OSCC cell survival. Combination with cytotoxic drugs reduced cell viability more efficiently than chemotherapy alone at select doses, particularly through intermittent short-term pretreatment schedules, but the full dose response demonstrated antagonism between NTX and chemotherapy, independent of the dosing schedule. These results contrast with previous findings in other cancers, and, thus, further study and optimization will be needed to determine the clinical benefit and reproducibility of these findings. Full article

The present study assessed the efficacy of selective dry cow therapy (SDCT) on two commercial Holstein-Friesian farms in the Czech Republic, involving 572 quarter milk samples from 74 cows collected over a two-year period. Quarter samples were taken both at dry-off (n = 296) and post-calving (n = 276) to assess somatic cell count (SCC), cultured microbial results (counts), milk composition, and mastitis incidence. The average SCC at dry-off was 264,000 cells/mL (SD = 650,000) in Farm 1 and 224,000 cells/mL in Farm 2. Mastitis incidence averaged 24.42% and 18.75% in Farms 1 and 2, respectively. Correlation analysis revealed significant associations between pre-dry-off milk parameters and post-calving udder health indicators, including negative correlations between SCC prior to drying-off and lactose content after calving (r = −0.161, p < 0.01). Statistical analyses showed a significant farm effect on cultured microbial occurrence and mastitis occurrence after calving (p < 0.05), as well as a significant influence of lactation number on postpartum mastitis and SCC (p < 0.05). Also, mastitis incidence was significantly higher (9.43%, p < 0.05) in treated quarters. The use of selective non-antibiotic dry cow therapy does not impair udder health and milk quality but helps reduce the risk of antibiotic resistance. Further refinement of diagnostic criteria is needed to optimize treatment decisions and improve herd-level outcomes. Full article

At present, the construction of China’s shared manufacturing platform is developing rapidly. However, it is still in the stage of practical exploration, facing numerous challenges, such as difficulties in resource integration, immature business models, and a weak digital foundation. This paper takes Changzhou Zhiyun Tiangong’s “Super Virtual Factory” as an example, utilizing the grounded theory to conduct a case study on this shared manufacturing platform. Using a ‘condition-action-result’ framework, this paper explores the value co-creation (VCC) mechanism in a shared manufacturing ecosystem. We analyze how digital intelligence convergence (DIC) and supply chain collaboration (SCC) facilitate the digital intelligence transformation of consumption, production capacity, and products. The study finds that consumer insight, technological drive, government support, enterprise challenges, and the Changzhou home appliance industry cluster are the internal driving forces for the shared manufacturing ecosystem to carry out industrial ecological VCC; DIC and SCC are the two key elements for digital intelligence technology empowerment. Digital intelligence technology is empowered from three aspects—technology, resources, and structure—enabling organizational members with capability and authority while achieving “decentralization” of industrial chains. Finally, digital intelligence empowerment enables the shared manufacturing ecosystem to achieve VCC of the industrial ecosystem, thereby establishing a VCC model for the digital intelligence empowerment shared manufacturing ecosystem. The results of the study not only help enrich the theory of VCC in shared manufacturing platforms but also provide practical insights for the digital intelligence transformation of traditional manufacturing enterprises. Full article

Several studies have demonstrated an association between impaired innate immunity and metabolic parameters, particularly during the periparturient period. However, to our knowledge, no study has been conducted under field conditions investigating the link between low milk polymorphonuclear neutrophil (PMN) levels and increased disease frequency. In an attempt to address this knowledge gap, this study examined 6209 cows from 20 dairy herds in Lombardy that were enrolled in a monthly individual dairy herd improvement milk testing program. Analyses of milk test record samples (MTR) included somatic cell count (SCC) and differential cell count (DSCC). A third variable, PLCC (polymorphonuclear neutrophil leukocyte cell count), was calculated by multiplying SCC × DSCC, thus representing PMN cells/mL. A database including compulsory records of all antimicrobial treatments applied in each herd was used as a proxy for disease frequency. In total, 58,090 valid MTR and 12,014 antimicrobial treatments (AMT) were considered for this study. Statistical analyses showed a significant association between the prevalence of cows with a low number of milk PMN and the prevalence of AMT. These results allow routine identification of whether the number of cows with low PLCC exceeds an alarm level within a herd. This threshold was calculated using an ROC curve with a cut-off point of 6% for AMT. This threshold was estimated at 2%, providing 78% accuracy in identifying herds at risk of an increasing treatment rate. This study confirms that cellular markers measured within MTR systems are useful in identifying herds at risk of impaired cellular immunity, thus paving the way for further studies assessing herd and cow immune status with routine milk sampling. Full article

Background: Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive imaging technique providing high-resolution en-face and cross-sectional views of the epidermis and superficial dermis for in vivo characterisation of actinic keratosis (AK), Bowen’s disease (BD) and squamous cell carcinoma (SCC). Despite its promise, standardised imaging protocols are lacking. Objective: This systematic review aims to assess the utility of LC-OCT for diagnosing AK, BD and SCC, with particular emphasis on workflow optimisation and protocol standardisation. Methods: A systematic literature search was performed using PubMed, Embase, and Scopus databases (January 2018–October 2024). Two reviewers independently screened the records, extracted data and applied the Confidence in the Evidence from Reviews of Qualitative research (CERQual) framework to assess confidence in key findings. Results: Eleven studies met the inclusion criteria. LC-OCT reliably identified key histopathological correlates. Across studies, LC-OCT consistently visualised hyperkeratosis, keratinocytic atypia, parakeratosis, and acanthosis, as well as characteristic vascular alterations and dermal remodeling. LC-OCT also demonstrated its capacity to detect invasive features by revealing disruptions in the dermo-epidermal junction and the presence of tumour strands infiltrating the dermis. Multimodal imaging combined with technical optimisations such as minimal probe pressure, paraffin oil coupling, and dermoscopy-guided localisation, substantially improved image resolution and interobserver concordance. Conclusions: This systematic review provides a basis for establishing standardised LC-OCT imaging protocols in keratinocytic tumours. While LC-OCT shows promise as a non-invasive diagnostic tool, further multicenter studies are needed to refine imaging workflows and evaluate the integration of artificial intelligence-based analysis to improve diagnostic accuracy and reproducibility. Full article

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy in the world, representing approximately 20% of all skin cancers. Immunosuppression is a well-established risk factor, contributing not only to the development of new cSCC lesions but also to more aggressive disease and increased mortality. Despite the National Comprehensive Cancer Network (NCCN) and the American Joint Committee on Cancer (AJCC) 8th edition updates recognizing immunosuppression as a risk factor for cSCC, standardized management protocols for these high-risk patients remain limited. As a result, treatment of this already high-risk group remains a significant challenge and highlights the need for dedicated research and attention to improve outcomes in this patient population. This review explores the current knowledge regarding cSCC in IS patients, outlines key gaps in the knowledge, and highlights recent clinical trials to further guide the evaluation and management of these patients. Full article