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18 pages, 4523 KB  
Article
Terahertz Waves Trigger Apoptosis in Cutaneous Squamous Cell Carcinoma via Apoptosis-Inducing Factor Mediated Mitochondrial Pathway
by Liu Sun, Wenxia Wang, Shuocheng She, Lei Wang, Jinwu Zhao, Pandeng Hou and Mingxia He
Cells 2026, 15(9), 810; https://doi.org/10.3390/cells15090810 - 29 Apr 2026
Abstract
Background: Terahertz (THz) waves exhibit both photon-like and electron-like properties, showing emerging potential in biomedical applications. Cutaneous squamous cell carcinoma (CSCC) is one of the most common skin tumors. Studies have reported that THz waves can induce apoptosis in cancer cells or ablate [...] Read more.
Background: Terahertz (THz) waves exhibit both photon-like and electron-like properties, showing emerging potential in biomedical applications. Cutaneous squamous cell carcinoma (CSCC) is one of the most common skin tumors. Studies have reported that THz waves can induce apoptosis in cancer cells or ablate tumor tissues. Our previous studies also confirmed that 0.1 THz radiation could significantly promote apoptosis in cutaneous melanoma cells, while it had no apparent effect on fibroblast viability, proliferation, migration, and apoptosis. However, the effects of 0.1 THz radiation on CSCC cells have not yet been explored. Furthermore, there remains a lack of investigation into the structural and functional effects on fibroblasts. Therefore, it is necessary to conduct a systematic study to evaluate the influence of 0.1 THz radiation on both CSCC cells and fibroblasts in order to better understand its potential therapeutic applications in the treatment of skin cancer. Purpose: This study aims to explore the biological effects of 0.1 THz radiation on SCC-7 cells and to uncover the molecular mechanisms underlying THz-induced apoptosis, as well as its potential effect on L-929 cells. Methods: Cell viability was evaluated through the CCK-8 assay, while cell cycle distribution was analyzed with the DNA content detection kit. Wound healing assays were performed to assess cell migration, and Annexin V-FITC staining was used to detect apoptosis. Caspase-3 activity was measured using the caspase-3 activity assay kit. Cell morphology was observed using the Atomic Force Microscope (AFM) and the Transmission Electron Microscopy (TEM). Alterations in membrane potential were detected with the M09 membrane potential probe kit, and intracellular Ca2+ levels were quantified using the Fluo-8 AM fluorescent probe. Mitochondrial permeability transition pore (mPTP) opening was assessed with the MPTP detection kit, mitochondrial membrane potential changes were measured using the JC-1 probe kit, and cellular ATP levels were measured with the enhanced ATP assay kit. Subsequently, proteomic analysis was performed. Intracellular reactive oxygen species (ROS) levels were quantified with the ROS detection kit, and cytochrome c (Cyt c) release was quantified using the mouse Cyt c ELISA kit. Apoptosis-inducing factor (AIF) expression was analyzed at both mRNA and protein levels by quantitative real-time PCR (qPCR) and Western blot. AIF expression in CSCC tissues was further evaluated based on the GSE42677 and GSE45164 databases. Finally, cyclosporin A (CsA) was used to inhibit mPTP, and in combination with the iMAC inhibitor, the Aifm1 expression and Cyt c release were examined. Results: Our results showed that THz waves significantly disrupted the membrane integrity of SCC-7 cells and induced mitochondrial structural and functional damage. This resulted in a significant increase in ROS levels and the activation of mPTP and the mitochondrial apoptosis channel (MAC). THz radiation promoted the release of Cyt c and AIF from mitochondria, triggering a noncanonical caspase-3-dependent apoptosis pathway. Notably, L-929 cells did not show significant phenotypic or apoptotic changes under the same irradiation conditions. Bioinformatics analysis of the Gene Expression Omnibus (GEO) database revealed that AIF expression was significantly altered in CSCC tissues compared to normal skin tissues. Conclusions: These findings indicated that 0.1 THz radiation effectively induced apoptosis in SCC-7 cells by triggering mitochondrial dysfunction and ROS generation, which led to the release of AIF. Furthermore, the dysregulation of AIF in CSCC tissues suggested its potential as a promising biomarker. These results provided important molecular insights into the therapeutic potential of THz radiation, particularly for the treatment of cutaneous squamous cell carcinoma. Full article
(This article belongs to the Section Cellular Biophysics)
21 pages, 12356 KB  
Article
Sarcomatoid Squamous Cell Carcinoma and Its Mimics: A Meta-Analysis of Institutional Cases and Published Reports
by Salin Kiratikanon, Yuqing Xiong, Jakob M. T. Moran and Mai P. Hoang
Cancers 2026, 18(9), 1411; https://doi.org/10.3390/cancers18091411 - 29 Apr 2026
Abstract
Background/Objective: Sarcomatoid squamous cell carcinoma (sSCC) is a rare tumor that resembles atypical fibroxanthoma/pleomorphic dermal sarcoma (AFX/PDS) and spindle cell/dedifferentiated melanoma histologically. Methods: Immunohistochemistry was performed on 51 sSCCs from 46 patients, 26 AFX/PDS from 24 patients, and 15 spindle cell/dedifferentiated [...] Read more.
Background/Objective: Sarcomatoid squamous cell carcinoma (sSCC) is a rare tumor that resembles atypical fibroxanthoma/pleomorphic dermal sarcoma (AFX/PDS) and spindle cell/dedifferentiated melanoma histologically. Methods: Immunohistochemistry was performed on 51 sSCCs from 46 patients, 26 AFX/PDS from 24 patients, and 15 spindle cell/dedifferentiated melanoma from 15 patients. Twenty-nine studies comprising 307 sSCCs, 636 AFX/PDS, and 168 spindle cell/dedifferentiated melanomas were included in the pooled analysis. Results: p63 showed the highest pooled sensitivity for sSCC (0.89), followed by keratin AE1/AE3 (0.87), keratin MNF116 (0.87), keratin 903 (0.85), p40 (0.82), and keratin 5/6 (0.72). Evidence regarding pooled diagnostic performance was limited for several markers. Among the best-supported markers for sSCC, p63 demonstrated a pooled OR of 42.36 (95% CI 13.95–128.61), sensitivity of 0.82, and specificity of 0.94; p40 showed a pooled OR of 50.27 (95% CI 13.91–181.70), sensitivity of 0.90, and specificity of 0.85; and keratin 5/6 had a pooled OR of 108.60 (95% CI 27.10–435.20), sensitivity of 0.94, and specificity of 0.93. For AFX/PDS, CD10 showed a pooled OR of 10.64 (95% CI 2.96–38.19), sensitivity of 0.73, and specificity of 0.80. For spindle cell/dedifferentiated melanoma, S100 showed a pooled OR of 161.23 (95% CI 24.55–1058.69), sensitivity of 0.95, and specificity of 0.94 (95% CI 0.85–0.97), while SOX10 yielded a pooled OR of 121.27 (95% CI 6.33–2323.34). Conclusions: A panel comprising p63 or p40, keratin 5/6, CD10, CD163 or CD68, and SOX10 or S100 may aid in distinguishing sSCC from AFX/PDS and spindle cell/dedifferentiated melanoma. Full article
(This article belongs to the Special Issue Cancers in Dermatology—from Diagnosis to Treatment)
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22 pages, 2402 KB  
Article
Macro–Micro Properties and Damage Model of Calcareous Sand Stabilized by Sulfoaluminate and Ferroaluminate Cements Under Different Water Environments
by Minghao Gu, Liang Cao, Peng Cao, Zhifei Tan, Ziyu Wang and Jingwei Ma
Materials 2026, 19(9), 1793; https://doi.org/10.3390/ma19091793 - 28 Apr 2026
Abstract
Island reef road construction faces a complex marine service environment characterized by high salinity and high humidity. Meanwhile, rapid construction and prompt subgrade repair are urgently required, creating a strong demand for novel calcareous-sand-based stabilization materials that combine excellent mechanical performance with resistance [...] Read more.
Island reef road construction faces a complex marine service environment characterized by high salinity and high humidity. Meanwhile, rapid construction and prompt subgrade repair are urgently required, creating a strong demand for novel calcareous-sand-based stabilization materials that combine excellent mechanical performance with resistance to seawater erosion. To this end, this study developed an early-strength cemented calcareous-sand reinforcement material for road base construction. Sulfoaluminate cement (SAC) and ferrite-aluminate cement (FAC), both featuring rapid setting/early strength development and superior corrosion resistance, were used to cement calcareous sand (CS) and to investigate its mechanical and microstructural characteristics under different water environments. Unconfined compressive strength tests (UCS) showed that SC-CS and FC-CS could meet subgrade requirements at 1 d and 7 d, with SC-CS and FC-CS reaching 3.12 MPa and 3.44 MPa at 1 d, and 3.26 MPa and 3.67 MPa at 7 d, respectively, under seawater SS conditions. Seawater mixing and immersion were found to promote the early strength and stiffness development of both SC-CS and FC-CS, with a more pronounced effect observed for FC-CS. Based on experimental results, a damage model for the stabilized specimens was established with a fitting accuracy of R2 > 0.97. This constitutive model accurately describes the stress–strain relationship of the material and quantitatively characterizes its damage evolution. Microscopic XRD and SEM analyses indicated that the main hydration product in freshwater-cured specimens was ettringite, and the interparticle connection of CS was dominated by bridging through rod-like ettringite. In contrast, under seawater conditions, the ettringite content decreased, while hydrotalcite and calcium aluminate hydrate increased, forming massive and lamellar bridging products. Compared with SC-CS, the bridging structure in FC-CS was denser. Moreover, the compactness of the bridging structure not only affected its mechanical properties but also governed the movement mode of CS particles, thereby influencing the damage evolution and failure mode of the specimens. The findings provide theoretical support for the construction needs of island road. Full article
(This article belongs to the Section Construction and Building Materials)
9 pages, 506 KB  
Communication
POU6F1 Expression Predicts Favorable Prognosis in Lung Adenocarcinoma: Validation Using Patient Cohort and TCGA Data
by Mincheol Chae, Jae-Ho Lee, Hyowon Hong, Dong Yoon Keum and Deok Heon Lee
Curr. Issues Mol. Biol. 2026, 48(5), 456; https://doi.org/10.3390/cimb48050456 - 28 Apr 2026
Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains a leading cause of cancer-related mortality worldwide. Lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) represent the two major histological subtypes with distinct molecular characteristics. POU domain [...] Read more.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains a leading cause of cancer-related mortality worldwide. Lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) represent the two major histological subtypes with distinct molecular characteristics. POU domain class 6 transcription factor 1 (POU6F1) is involved in gene regulation and cellular differentiation, but its clinical significance in NSCLC remains unclear. This study investigated the clinicopathologic and prognostic significance of POU6F1 expression in NSCLC. POU6F1 mRNA expression was analyzed in tumor tissues obtained from 153 patients with NSCLC using quantitative real-time polymerase chain reaction. The associations between POU6F1 expression and clinicopathological characteristics were evaluated, and survival analysis was performed to determine its prognostic value. In addition, publicly available datasets from The Cancer Genome Atlas (TCGA) were analyzed to validate the clinical significance of POU6F1 expression. High POU6F1 expression was observed in 48 patients (31.4%), whereas 105 patients (68.6%) showed low expression. High POU6F1 expression was significantly associated with younger age (p = 0.027), female sex (p = 0.041), non-smoking status (p = 0.002), adenocarcinoma histology (p = 0.021), and the presence of EGFR mutations (p = 0.038). Survival analysis demonstrated that high POU6F1 expression was associated with improved overall survival in patients with NSCLC (p = 0.015). When stratified by histological subtype, higher POU6F1 expression was associated with better survival outcomes in AD but not in SCC. Analysis of TCGA datasets confirmed that elevated POU6F1 expression was significantly associated with favorable survival in AD, whereas no significant prognostic value was observed in SCC. POU6F1 expression is significantly associated with clinicopathological characteristics and improved survival in patients with lung AD. Multivariate Cox regression analysis further confirmed that POU6F1 expression was an independent prognostic factor for overall survival. These findings suggest that POU6F1 may serve as a potential prognostic biomarker based on mRNA expression in NSCLC, particularly in AD. Further studies are warranted to validate these findings at the protein level and to elucidate the underlying biological mechanisms. Full article
(This article belongs to the Section Molecular Medicine)
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21 pages, 1215 KB  
Article
Effect of Somatic Cell Count on Milk Production, Composition, Colour, Coagulation Properties and Cheese-Making Ability Traits in Manchega Dairy Sheep
by Imen Heddi, Javier Caballero-Villalobos, Nicolò Amalfitano, Fernando Martínez, Miguel Ángel Cantarero-Aparicio, Alessio Cecchinato, Manuel Ramón, Ana Garzón and Ramón Arias
Foods 2026, 15(9), 1527; https://doi.org/10.3390/foods15091527 - 28 Apr 2026
Abstract
Somatic cell count (SCC) in milk is widely used as an indicator of intramammary infections in dairy sheep and is routinely monitored by the dairy industry as a marker of milk quality. This study aimed to evaluate the effect of SCC levels on [...] Read more.
Somatic cell count (SCC) in milk is widely used as an indicator of intramammary infections in dairy sheep and is routinely monitored by the dairy industry as a marker of milk quality. This study aimed to evaluate the effect of SCC levels on milk production, composition, colour, coagulation properties, and cheese-making ability in Manchega dairy sheep. A total of 752 individual milk samples were analysed. To normalise SCC distribution, the somatic cell score (SCS) was calculated and samples were classified into SCS classes. Increasing SCS significantly reduced daily milk yield and lactose content, increased milk pH, and decreased lightness (L*). Higher SCS was also associated with impaired coagulation properties, including longer rennet clotting time (RCT) and curd firming rate (k20), as well as reduced curd firmness (A30, A60). Similar effects were observed for modelled coagulation parameters, with delayed RCTeq and reduced kCF and CFp. Regarding cheese-making ability, SCS significantly affected curd humidity and protein recovery, whereas no significant effects were detected for dry curd yield or fat recovery. Overall, elevated somatic cell counts were associated with a reduction in the technological quality of Manchega sheep milk, particularly affecting coagulation behaviour and curd characteristics. These results underline the importance of controlling SCC levels in dairy sheep systems for both udder health monitoring and maintaining milk suitability for cheese-making. Full article
(This article belongs to the Section Dairy)
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19 pages, 1029 KB  
Review
Perineural Spread and Base of Skull Involvement in Cutaneous Squamous Cell Carcinoma—A Critical Review from an Endemic Region
by Charles Y. Lin, Rahul Ladwa and Ryan Sommerville
Curr. Oncol. 2026, 33(5), 250; https://doi.org/10.3390/curroncol33050250 - 27 Apr 2026
Viewed by 4
Abstract
Perineural spread (PNS) from cutaneous squamous cell carcinoma (cSCC) to the skull base is increasingly recognised as a route of cancer spread. Management historically involved definitive radiotherapy to treat PNS at the skull base. In the endemic region with modern magnetic resonance neurogram [...] Read more.
Perineural spread (PNS) from cutaneous squamous cell carcinoma (cSCC) to the skull base is increasingly recognised as a route of cancer spread. Management historically involved definitive radiotherapy to treat PNS at the skull base. In the endemic region with modern magnetic resonance neurogram (MRN) and skull base surgical expertise, the outcome has improved over the years. With the advent of immunotherapy, the outcome may be maintained while preserving critical organs in the head and neck region. We conducted a critical review of the literature to establish the treatment outcomes and pattern of failure as practice evolved. Furthermore, we described our skull base surgical and radiotherapy management guideline and outlined the emerging paradigm shift in the immunotherapy era. Full article
(This article belongs to the Special Issue The Role of Targeted Therapy in Head and Neck Cancers)
14 pages, 1348 KB  
Article
Integrating LASSO and Extreme Gradient Boosting for Optimal Multiple Linear Regression Modeling of Milk Color Traits in Relation to Somatic Cell Count and Milk Composition in Dairy Cows
by Atalay Ergül, Celile Aylin Oluk, Çiğdem Takma, Serap Göncü and Mervan Bayraktar
Dairy 2026, 7(3), 32; https://doi.org/10.3390/dairy7030032 - 27 Apr 2026
Viewed by 117
Abstract
Milk color reflects the optical output of a complex colloidal system governed by protein micelles, fat globules, and serum phase interactions. In this study, we evaluated whether CIE Lab* color parameters can explain variation in milk composition and somatic cell count (SCC) using [...] Read more.
Milk color reflects the optical output of a complex colloidal system governed by protein micelles, fat globules, and serum phase interactions. In this study, we evaluated whether CIE Lab* color parameters can explain variation in milk composition and somatic cell count (SCC) using Lasso-based multiple linear regression and Extreme Gradient Boosting (XGBoost). A total of 119 Holstein milk samples were analyzed for fat, protein, lactose, dry matter, electrical conductivity, freezing point, and SCC, and five color indices (L*, a*, b*, Hue, and Chroma) were used as predictors. Model robustness was evaluated using 10-fold cross-validation and an independent 80/20 train–test split. In regression analyses, Lasso explained 32.7% of protein variation (R2 = 0.327), 26.3% of dry matter (R2 = 0.263), 22.8% of lactose (R2 = 0.228), and 19.1% of fat (R2 = 0.191). Spectral tone parameters (a*, Hue, and Chroma) were consistently retained as key predictors, whereas L* showed a limited contribution. SCC exhibited weak direct associations with color traits but was significantly related to electrical conductivity (p < 0.05), indicating inflammation-driven ionic changes rather than pigment effects. In classification analysis (SCC ≥ 200,000 cells/mL), the XGBoost model achieved 74% accuracy and an AUC of 0.69 in the independent test set, with Chroma and electrical conductivity identified as the most influential features. These findings suggest that, among the evaluated color variables, Chroma provided the most relevant information for discriminating SCC status, whereas the overall contribution of milk color traits to compositional prediction remained moderate. Therefore, color-derived measurements should be interpreted as instrument-based optical indicators that may complement, but not replace, conventional milk quality assessments. Full article
(This article belongs to the Section Milk Processing)
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16 pages, 1470 KB  
Article
YAP-TEAD Inhibition Impairs Interferon Tau-Induced Gene Expression and Reduces Integrin β1 Abundance in Primary Bovine Luteal Cells
by Suzana Rossato Feltrin, Karine de Vargas Aires, Amanda Luiza Prante, Ana Paula da Silva, Carlos Miguel Staudt, Manuela Brauner Freitas, Carolina dos Santos Amaral, Luis Fernando Schütz, Valério Marques Portela and Alfredo Quites Antoniazzi
Ruminants 2026, 6(2), 28; https://doi.org/10.3390/ruminants6020028 - 27 Apr 2026
Viewed by 78
Abstract
The Hippo pathway effector Yes-associated protein (YAP), acting through TEA domain (TEAD) transcription factors, regulates transcriptional programs in ovarian tissues; however, its role in interferon tau (IFNT) signaling within bovine luteal cells has not been investigated. This study aimed to determine whether YAP-TEAD [...] Read more.
The Hippo pathway effector Yes-associated protein (YAP), acting through TEA domain (TEAD) transcription factors, regulates transcriptional programs in ovarian tissues; however, its role in interferon tau (IFNT) signaling within bovine luteal cells has not been investigated. This study aimed to determine whether YAP-TEAD interaction is required for IFNT-induced interferon-stimulated gene (ISG) expression in primary bovine luteal cells and to perform an exploratory assessment of selected receptor genes (ITGB1, GRP78, VEGFR2). Primary luteal cells were treated with recombinant ovine IFNT (roIFNT; 1 ng/mL) in the presence or absence of verteporfin (VP; 0.1, 0.5, or 1.0 µM), a pharmacological YAP-TEAD inhibitor, and mRNA expression was quantified by RT-qPCR. VP dose-dependently suppressed YAP target genes (YAP1, CTGF, ANKRD1) and reduced roIFNT-induced expression of MX1, MX2, and OAS1, whereas ISG15 was unaffected. Steroidogenic gene expression (3β-HSD, P450scc, StAR) remained unchanged across treatments, indicating preserved cell viability. Among the exploratory receptor endpoints, VP decreased ITGB1 and increased GRP78 at the highest concentration, while VEGFR2 was unaffected. These findings indicate that YAP-TEAD activity contributes to IFNT-induced ISG responsiveness in bovine luteal cells, with preliminary evidence of effects on integrin-mediated signaling pathways. Full article
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21 pages, 3970 KB  
Article
Andrographis paniculata Inhibits Tongue Squamous Cell Carcinoma via Regulating Wnt/β-Catenin Signaling and Epithelial-Mesenchymal Transition
by Grace Gar-Lee Yue, Jingyi Huang, Xiaotong Lu, Julia Kin-Ming Lee, Si Gao, Jason Ying Kuen Chan and Clara Bik-San Lau
Int. J. Mol. Sci. 2026, 27(9), 3772; https://doi.org/10.3390/ijms27093772 - 23 Apr 2026
Viewed by 142
Abstract
Tongue squamous cell carcinoma (TSCC) is an aggressive malignancy with poor prognosis and limited therapeutic options. Herbal medicines with multitarget activities and low toxicity have attracted increasing attention in cancer adjuvant therapy. This study aimed to investigate the anti-tumor effects and underlying mechanisms [...] Read more.
Tongue squamous cell carcinoma (TSCC) is an aggressive malignancy with poor prognosis and limited therapeutic options. Herbal medicines with multitarget activities and low toxicity have attracted increasing attention in cancer adjuvant therapy. This study aimed to investigate the anti-tumor effects and underlying mechanisms of the water extract of Andrographis paniculata (APW) in TSCC in vitro and in vivo. Two TSCC cell lines, Cal-27 and SCC25, were used for cell-based functional and mechanistic studies, while a Cal-27 xenograft-bearing mouse model was established for evaluating the in vivo effect of APW treatment. Our results showed that APW could significantly inhibit the proliferation of Cal-27 and SCC25 cells and induce apoptosis in a concentration-dependent manner. APW could promote mitochondrial-mediated apoptosis by upregulating Bax and cleaved caspase proteins but downregulating Bcl-2 in TSCC cells. It also suppressed the Wnt/β-catenin signaling pathway, reducing β-catenin expression and its downstream targets, CCND1, MYC, and JUN. Furthermore, APW disrupted mitochondrial integrity, induced cytochrome c release, and reduced mitochondrial membrane potential. APW also inhibited epithelial–mesenchymal transition, increasing E-cadherin and decreasing N-cadherin and vimentin expressions, thereby suppressing cell migration of TSCC cells. Furthermore, the 5-week APW treatment significantly reduced tumor growth and angiogenesis without evident hepatic or renal toxicity in Cal-27 xenograft-bearing mice. In conclusion, APW exerted potent anti-tumor effects by targeting both the Wnt/β-catenin pathway and mitochondrial apoptotic machinery, suggesting the great potential of APW as an adjuvant therapeutic candidate for TSCC treatment. Full article
(This article belongs to the Section Molecular Pharmacology)
12 pages, 830 KB  
Article
Immunohistological Characterization of Actinic Keratoses with Varying Degrees of Proliferation
by Vasileios Dervenis, Conrad Falkenberg, Alexandra Knebel, Lutz Schmitz and Thomas Dirschka
Cancers 2026, 18(9), 1340; https://doi.org/10.3390/cancers18091340 - 23 Apr 2026
Viewed by 306
Abstract
Background: Actinic keratoses (AKs) are considered early in situ forms of cutaneous squamous cell carcinoma (cSCC). However reliable histopathological or molecular markers for predicting the risk of progression are still lacking. The aim of this study was to investigate the relationship between immunohistochemical [...] Read more.
Background: Actinic keratoses (AKs) are considered early in situ forms of cutaneous squamous cell carcinoma (cSCC). However reliable histopathological or molecular markers for predicting the risk of progression are still lacking. The aim of this study was to investigate the relationship between immunohistochemical markers and basal proliferation patterns of AKs in order to identify histopathological associations that may be relevant for malignant transformation. Methods: A total of 97 AK samples from facial and scalp areas were retrospectively analyzed and classified according to their basal proliferation pattern (Pro I: non-proliferative and Pro III: proliferative). Immunohistochemical staining was performed for Ki-67, p53, p16 and podoplanin. In addition, histopathological parameters such as Röwert-Huber grade, inflammatory infiltrate, parakeratosis, elastosis and the presence of acantholysis were evaluated. Results: Pro III lesions were significantly more frequently associated with higher Röwert-Huber grades (AK III: 47.9% vs. 14.3%; p = 0.0004) and with acantholysis (p = 0.0004). No significant differences between the groups were found for Ki-67, p53 and p16. Podoplanin expression, however, was significantly higher in Pro III lesions (93.7% vs. 57.1%, p < 0.0001) and was predominantly localized basally. The combination of a PRO III pattern and podoplanin positivity identified a distinct histopathological subgroup associated with features linked to progression. Conclusions: Podoplanin expression, especially in combination with PRO III pattern and acantholysis, characterizes a histologically and biologically distinct AK subgroup. In contrast, Ki-67, p53 and p16 showed no additional discriminative value in this cohort. Podoplanin could therefore be a useful addition to existing classification systems and in the future support risk-adapted treatment decision. However, prospective longitudinal studies are required to determine its prognostic value. Full article
(This article belongs to the Special Issue Risk of Skin Cancer: Non-Melanoma/Melanoma)
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16 pages, 5454 KB  
Case Report
De Novo Primary Squamous Cell Carcinoma of the Prostate: Substantial Tumor Regression After Definitive Radiotherapy in a Medically Inoperable Patient
by Sang Jun Byun, Misun Choe, Jin Young Kim, Byung Hoon Kim, Hyun Chan Jang, Seung Gyu Park, Euncheol Choi, Sang Hee Youn, Myeongsoo Kim, Byungyong Kim and Byungwook Choi
Life 2026, 16(5), 702; https://doi.org/10.3390/life16050702 - 22 Apr 2026
Viewed by 215
Abstract
Primary squamous cell carcinoma (SCC) of the prostate is a rare and biologically aggressive malignancy lacking a standardized management strategy. De novo primary SCC arising without prior androgen deprivation therapy or radiotherapy is uncommon and presents significant diagnostic and therapeutic challenges. We present [...] Read more.
Primary squamous cell carcinoma (SCC) of the prostate is a rare and biologically aggressive malignancy lacking a standardized management strategy. De novo primary SCC arising without prior androgen deprivation therapy or radiotherapy is uncommon and presents significant diagnostic and therapeutic challenges. We present the clinical presentation, diagnostic evaluation, treatment strategy, and early therapeutic response of de novo primary SCC of the prostate in a 56-year-old male with end-stage renal disease on maintenance hemodialysis. The patient presented with gross hematuria and a bulky prostate mass invading the bladder with bilateral pelvic lymphadenopathy despite low prostate-specific antigen (PSA) levels. Histopathological and immunohistochemical analyses confirmed pure SCC, staged as cT4N1M0. Because systemic chemotherapy was contraindicated and surgery was not feasible, definitive whole-pelvis radiotherapy with a simultaneous integrated boost was administered. Marked tumor regression was observed one month after treatment. Subsequent imaging demonstrated extensive tumor necrosis with fistulous communication in the context of locally invasive disease. Because long-term oncologic durability could not be assessed owing to non-oncologic clinical deterioration, these findings suggest that definitive radiotherapy may provide meaningful locoregional tumor control in selected medically inoperable patients with de novo prostatic SCC. Full article
(This article belongs to the Special Issue Diagnosis, Treatment and Prognosis of Prostate Cancer—2nd Edition)
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28 pages, 6141 KB  
Article
The Evolution of the Mental Health–Acute Coronary Syndrome Intersection: A 50-Year Bibliometric Mapping and Changepoint Analysis (1975–2025)
by Alexandra Herlaș-Pop, Andrei-Flavius Radu, Ada Radu, Gabriela S. Bungau, Delia Mirela Tit, Cristiana Bustea and Elena Emilia Babes
Healthcare 2026, 14(8), 1115; https://doi.org/10.3390/healthcare14081115 - 21 Apr 2026
Viewed by 270
Abstract
Background/Objectives: The intersection of mental health and acute coronary syndromes has become an increasingly prominent area of cardiovascular and psychosomatic research, yet its temporal dynamics and intellectual structure remain incompletely characterized. Methods: This study analyzed 13,646 peer-reviewed documents spanning five decades, [...] Read more.
Background/Objectives: The intersection of mental health and acute coronary syndromes has become an increasingly prominent area of cardiovascular and psychosomatic research, yet its temporal dynamics and intellectual structure remain incompletely characterized. Methods: This study analyzed 13,646 peer-reviewed documents spanning five decades, employing advanced changepoint detection (PELT) algorithms, network visualization (VOSviewer), and bibliometric performance metrics (Bibliometrix) to quantify the evolution of the mental health–ACS intersection. Results: Statistical analysis identified two robust inflection points at 1990 and 2005 that demarcate distinct developmental periods. The 1990 breakpoint marked an important transition, although additional metadata-completeness analysis indicated that part of the increase from 72 to 142 publications may reflect improved availability of non-title Topic-field metadata in WoSCC around 1990–1991. The 2005 breakpoint represented the most critical transition (Cohen’s d = 4.05, p < 0.000001), initiating exponential growth from 349 to over 600 annual publications by 2022 and coinciding with growing research attention to psychiatric comorbidity within ACS literature. Keyword co-occurrence networks revealed a shift in research focus: early publications predominantly addressed mental health as a psychological reaction to cardiac events, whereas more recent publications increasingly frame depression, anxiety, and PTSD alongside mechanistic constructs such as inflammatory pathways, autonomic dysfunction, and platelet reactivity. Although seminal intervention trials (i.e., ENRICHD, SADHART) established pharmacological safety and symptom improvement, keyword analyses indicate that following these trials, research attention increasingly shifted toward precision psychiatry concepts and mechanistic pathway elucidation. Conclusions: These findings provide a quantitative map of how publication activity at the mental health–ACS intersection has evolved, offering a structured basis for identifying under-researched areas and informing future research agendas. Full article
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29 pages, 524 KB  
Article
Unlocking Sustainable Supply Chains Through Blockchain Traceability: The Strategic Roles of Transparency, Collaboration, and Environmental Orientation
by Alhassian Abobassier, Amir Khadem, Hasan Yousef Aljuhmani and Ahmad Bassam Alzubi
Sustainability 2026, 18(8), 4138; https://doi.org/10.3390/su18084138 - 21 Apr 2026
Viewed by 408
Abstract
This study investigates the influence of blockchain-enabled supply chain traceability (BESCT) on sustainable supply chain practices (SSCP) in the context of small and medium-sized enterprises (SMEs) in the Turkish manufacturing sector. Grounded in the Resource-Based View (RBV), the research further examines the mediating [...] Read more.
This study investigates the influence of blockchain-enabled supply chain traceability (BESCT) on sustainable supply chain practices (SSCP) in the context of small and medium-sized enterprises (SMEs) in the Turkish manufacturing sector. Grounded in the Resource-Based View (RBV), the research further examines the mediating roles of perceived information transparency (PIT) and supply chain collaboration (SCC) and the moderating effect of environmental orientation (EO). The study employs a quantitative research design using data collected from 652 managers representing various manufacturing SMEs. Structural equation modeling via SmartPLS 4.0 is applied to test a moderated mediation model and assess the relationships among the constructs. The results indicate that BESCT is positively associated with SSCP both directly and through PIT and SCC as mediating mechanisms. PIT is linked to improved visibility and information integrity, while SCC is associated with joint sustainability efforts across supply chain partners. Moreover, EO strengthens the positive associations between BESCT and PIT with SSCP, while its effect on collaboration is more nuanced. Given the cross-sectional design, these findings should be interpreted as associative rather than causal. In addition, the use of a non-probability convenience sampling approach may limit generalizability, and the results should be interpreted with caution. This study contributes to the RBV literature by conceptualizing blockchain as a traceability-enabled dynamic capability that supports sustainability-oriented practices in SMEs. Full article
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17 pages, 1540 KB  
Article
Gas Injection Optimization and Shrinkage Control for Salt Cavern CO2 Storage (SCCS) Based on Creep-Shrinkage Sensitivity Analysis
by Tingting Jiang, Yiyun Zhang, Youqiang Liao, Dongzhou Xie and Tao He
Energies 2026, 19(8), 1970; https://doi.org/10.3390/en19081970 - 18 Apr 2026
Viewed by 169
Abstract
Salt cavern CO2 storage (SCCS) technology represents a crucial pathway for achieving large-scale carbon sequestration. However, its long-term operation faces the challenge of cavern shrinkage due to surrounding rock creep, which directly impacts storage safety and stability. Despite its importance, there is [...] Read more.
Salt cavern CO2 storage (SCCS) technology represents a crucial pathway for achieving large-scale carbon sequestration. However, its long-term operation faces the challenge of cavern shrinkage due to surrounding rock creep, which directly impacts storage safety and stability. Despite its importance, there is currently a lack of research focusing on the proactive control of SCCS cavern shrinkage and its collaborative optimization with operational economy. To fill this gap, this paper first investigated the effects of the stress state (f1), height-to-diameter ratio (f2), symmetry factor (f3), and cavern volume (f4) on the volumetric shrinkage rate through numerical simulations of regular caverns and univariate sensitivity analysis. The sensitivity ranking and quantitative relationships of these factors were clarified as f1(2.31)>f4(0.309)>f2(0.166)>f3(0). Subsequently, a multi-objective nonlinear optimization model was established, and the primal-dual interior-point method was adopted as the solution algorithm. Using actual cavern data as a case study for the solution, the results demonstrate that the optimization model converges stably in approximately 1.1 s. The resulting optimal gas injection allocation scheme achieves a 14.77% improvement in the comprehensive score compared to the baseline scheme. This study provides a theoretical basis and a practical tool for the rapid generation of SCCS gas injection allocation schemes. Full article
(This article belongs to the Topic CO2 Capture and Renewable Energy, 2nd Edition)
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28 pages, 626 KB  
Review
The Epigenetic Landscape and Exposome of Non-Melanoma Skin Cancer: Mechanisms, Biomarkers, and Therapeutic Perspectives
by Adrian Albulescu, Alina Fudulu, Iulia Virginia Constantin (Iancu), Adriana Plesa, Irina Huica and Anca Botezatu
Genes 2026, 17(4), 477; https://doi.org/10.3390/genes17040477 - 17 Apr 2026
Viewed by 195
Abstract
Accounting for over 1.2 million new diagnoses worldwide in 2022, non-melanoma skin cancer (NMSC) represents the most common human cancer, predominantly manifesting as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). NMSC serves as a powerful natural model for studying how environmental [...] Read more.
Accounting for over 1.2 million new diagnoses worldwide in 2022, non-melanoma skin cancer (NMSC) represents the most common human cancer, predominantly manifesting as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). NMSC serves as a powerful natural model for studying how environmental exposure, the exposome, reprograms the epigenome to drive carcinogenesis. Chronic ultraviolet radiation (UVR), the dominant risk factor, induces DNA damage and inflammation that dysregulate epigenetic enzymes (e.g., DNMTs, HDACs). These effects are layered with perturbations from β-HPV infection and cutaneous dysbiosis, altering DNA methylation, histone modifications, and non-coding RNA and miRNA expression in a multistep carcinogenic process. This review synthesizes the central role of epigenetic regulation as the critical interface between genetic susceptibility and cumulative exposome factors in NMSC pathogenesis. We integrate how UVR, HPV, and inflammation converge to remodel the keratinocyte epigenome. Finally, we evaluate the translational potential of this knowledge for refined risk stratification through epigenetic biomarkers and discuss emerging therapeutic strategies, including epidrugs, that target these dysregulated pathways for advanced NMSC management. Full article
(This article belongs to the Special Issue Epigenetic Regulation in Tumors)
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