Search Results (595)

Radiation resistance presents a significant challenge in the treatment of triple-negative breast cancer (TNBC). To investigate the molecular adaptations associated with radiation therapy resistance, MDA-MB-231 cells were subjected to a repeated radiation (RR) regimen totaling 57 Gy over 11 weeks, followed by clonal selection. The resulting radiation-adapted cells (MDA-MB-231^RR) were analyzed using whole-transcriptome RNA sequencing, revealing substantial dysregulation of pathways related to cell adhesion, mitochondrial function, and epithelial–mesenchymal transition (EMT). These transcriptional changes were corroborated by functional assays. MDA-MB-231^RR cells exhibited reduced expression of adhesion receptors (ITGB1, ITGA2, ITGA6) and extracellular matrix proteins (fibronectin, collagen, laminins), accompanied by significantly impaired cell adhesion to fibronectin, collagen, and laminin substrates. Mitochondrial dysfunction was supported by downregulation of oxidative phosphorylation genes (MTCO1, MTND1) and confirmed by JC-1 dye assays demonstrating a marked reduction in mitochondrial membrane potential. EMT-associated changes included increased mesenchymal markers and loss of epithelial markers (CTNNB1, SNAI2, CK19), consistent with enhanced migratory potential. Taken together, this study delineates key molecular features of radiation adaptation in TNBC, providing a foundation for the development of targeted therapies to overcome treatment resistance. Full article

The reverse circulation drill bit is the key component for the efficient and smooth implementation of the pneumatic hollow-through down-the-hole (DTH) hammer reverse circulation continuous coring (sampling) technology. To obtain the structural form of a reverse circulation drill bit with better reverse circulation performance, revealing its local flow fields by computational fluid dynamics (CFD) simulation is an effective approach. Taking the inner jet holes-type reverse circulation drill bit as the research object, three kinds of symmetrical and asymmetrical structures of inner jet holes were proposed. The CFD simulation results show that increasing the air volume supply and the number of inner jet holes leads to an increase in the velocity of air flow jet within the inner jet holes, an increase in the negative pressure formed in the central through channel below the inner jet holes, an enhancement of the reverse circulation performance and suction capacity formed by the reverse circulation drill bit, and an acceleration of the upward flow velocity of the rock cores (samples) located at the bottom of the borehole. Additionally, the reverse circulation performance formed by the reverse circulation drill bit with staggered arranged inner jet holes is superior to that of the reverse circulation drill bit with uniformly distributed inner jet holes. Under the same simulation conditions, the static pressure (i.e., negative pressure) and the upward flow velocity formed by the JB6 model are 2.34 kPa and 30.778 m/s higher than those formed by the JB3-3 model, while these two values formed by the JC6 model are 0.197 kPa and 3.689 m/s higher than those formed by the JB6 model, respectively. In conclusion, an asymmetric structural design would be more reasonable for the design of the inner jet holes-type reverse circulation drill bit. Full article

Organ transplantation significantly enhances the survival and quality of life for recipients. However, multiple dependent and independent variables can adversely affect life expectancy after transplantation. Cancer is one of the most common causes of morbidity and mortality for long-term organ transplant recipients. The incidence of cancer in transplanted tissues can be twice as high in approximately 32 distinct cancer types. Oncogenic viruses present in graft tissues may contribute to the etiology of various cancers in transplant recipients. Such oncogenic viruses include hepatitis viruses, papillomaviruses, Epstein–Barr virus, Kaposi’s sarcoma, Merkel cell virus, JC virus, BK virus, and human T-lymphotropic virus type 1, all of which have been associated with various malignancies in these patients. To mitigate this risk, a comprehensive viral screening protocol should be integrated into the transplantation process. Depending on the type of graft, diagnostic methods, control strategies, and post-transplantation care may vary considerably. To efficiently implement any strategy to inhibit viral oncogenicity, a comprehensive understanding of viral–host interactions involving oncogenic viruses within graft tissue is essential. The current view of tumor biology is that changes in the tumor microenvironment and immune signaling influence evolutionary selection pressures. Such interactions ultimately promote conditions that favor uncontrolled host–cell proliferation and malignant transformation. This review examines these viral–host interactions and their role in cancer development among transplant recipients. Full article

This study presents a novel multi-objective optimization (MOO) model for the design of an off-grid hybrid renewable energy system (HRES) to support sustainable agriculture and rural development in Sub-Saharan Africa (SSA). Based upon a case study selected in Linia (Chad), three system architectures are compared under different levels of the reliability requirements (LPSP = 1%, 5%, and 10%). A Multi-Objective Particle Swarm Optimization (MOPSO) algorithm is applied to optimize the Levelized Cost of Energy (LCOE), CO₂ emissions mitigation, and social impact, referring to the Human Development Index (HDI) enhancement and the job creation (JC) opportunity, using the MATLAB R2024b environment. The calculation results show that among the three configuration schemes, the PV–Wind–Battery configuration obtains the optimal techno–economic–environmental coordination, with the lowest LCOE (0.0948 $/kWh) and the largest CO₂ emission reduction (9.58 × 10⁸ kg), and the Wind–Battery system gets the most social benefit. The method developed provides users with a decision-support method for renewable energy systems (RES) integration into rural agricultural settings, taking into consideration financial cost, environmental sustainability, and community development. This information is important for policymakers and practitioners advocating for decentralized, socially inclusive clean energy access initiatives in underserved regions. Full article

This study investigated the fracture behavior of high-ductility alkali-activated composites (HDAACs) under thermo-mechanical coupling. Fracture tests were conducted on hybrid polypropylene/polyethylene (PP/PE) fiber-HDAAC with varying PP fiber replacement ratios (0%, 25%, and 50%) and coupled temperatures (0 °C, 30 °C, 70 °C, 100 °C, and 150 °C). The fracture mechanisms were analyzed through failure modes, mode I fracture energy (G_F), and the J-integral method. The results showed that below 100 °C, specimens exhibited ductile failure with a main crack along the notch accompanied by stable matrix cracking, with G_F peaking at 16.47 kJ/m². At 150 °C, fiber melting led to a reduction in G_F to 2.01 kJ/m². Initial cracking energy (J_IC ≈ 0.1 kJ/m²) remained stable, while unstable fracture energy (J_IF) peaked at 70 °C and dropped sharply at 150 °C. The energy consumed by matrix cracking showed (J_m) a similar trend to that consumed by fiber pull-out and fracture (J_b), with J_m/J_C = 0.4–0.5. Higher PP replacement reduced both J_m and J_b. The fracture behavior differences under thermo-mechanical coupling versus post-heating were mainly due to fiber exposure timing. This study highlights the critical influence of thermo-mechanical coupling on HDAAC fracture mechanisms, offering guidance for designing HDAACs for high-temperature applications. Full article

This study analyzed the dynamic behavior of EN C45 structural steel under impulse loading generated by a pressure wave. The experiments were conducted on a special test rig using two load configurations: (I) direct contact of the load with the sample surface and (II) detonation at a distance of 30 mm. Depending on the loading conditions, the specimens were fragmented or developed extensive internal cracks and plastic deformations. To complement the experimental program, hybrid numerical simulations were performed using the finite element method (FEM), smoothed particles hydrodynamics (SPH), and coupled Euler–Lagrange (CEL) approach. A modified Johnson–Cook (JC) model was used to account for dynamic damage and cracks. Computed tomography (CT) and metallographic analyses provided detailed information on the formation of cracks in MnS inclusions, brittle cracks near the sample axis, and shear deformation zones away from the axis. These observations allowed direct correlation with the predicted numerical deformation and damage fields. The innovative nature of this work lies in the combination of three complementary computational techniques with computed tomography analysis and microstructure analysis, providing a comprehensive framework for describing and confirming the mechanisms of damage and fragmentation of structural steels under explosive loading. Full article

In light of a Volatile, Uncertain, Complex and Ambiguous (VUCA) world, the need for employee adaptability is a critical capacity to navigate challenges and facilitate employees thriving in organizations. One important capacity, systems intelligence, captures employees’ ability to think, adapt and act effectively in interactions with systems. In a three-wave longitudinal study, we examine the relationship between systems intelligence (SI), job crafting (JC), and job performance (JP) over time. We employ the job demands-resources model to demonstrate that SI increases JP, hypothesizing that job resources, as manifested in JC, act as mediator between personal resources (SI) and JP. Data were collected from employees in Pakistan working across the banking, telecommunications, information technology, and engineering sectors. In the first wave, 303 participants completed the survey using validated self-report measures, followed by 212 in the second wave, and 99 in the third wave, each two months apart. Our findings show that systems intelligence at Time 1 was positively related to job performance at Time 3 but not Time 2. We found no significant association of SI at Time 1 with JC at Time 2 or Time 3. JC at Time 2 did not mediate the effects of SI at Time 1 on JP at Time 3. However, JC (T1 & T2) had a significant positive effect on JP (T2 & T3). Overall, our findings suggest that the pathways from systems intelligence and job crafting to job performance are independent. This dual pathway to performance has important theoretical implications as well as practical implications for organizations. Organizations can improve team and individual productivity by fostering systems intelligence and promoting job crafting behaviours. This research directs the attention of leaders and HR functions to the value of tailored interventions in developing these abilities and achieving long-term success and adaptive performance in the workforce. Full article

Currently, there is a need to improve the cryopreservation process for male gametes, especially for patients with low cryotolerance during sperm cryopreservation. Methods: The content and size of donor extracellular vesicles (EVs) in seminal plasma (SP) were assessed using nanoparticle tracking analysis (NTA), CD marker analysis, and transmission electron microscopy (TEM). Patient ejaculates were exposed to cryopreservation with or without prior co-culture with SP EVs and were not exposed to cryopreservation. The interaction of SP EVs with spermatozoa was assessed by TEM. Apoptotic, necrotic and late apoptotic cells, and mitochondrial functional activity were detected by flow cytometry. Results: NTA showed the highest concentration of SP EVs with a size of 80 nm, corresponding to small EVs. The binding of SP EVs to spermatozoa occurred along the entire plasma membrane, with an increased concentration of SP EVs at the neck and upper third of the sperm head. A significant increase in sperm motility was observed in the EVs co-culture group after cryopreservation/thawing. Flow cytometry showed a significant difference in the JC-1 Red/JC-1 Green ratio, indicating a higher mitochondrial membrane potential in the EVs exposure group. Conclusions: SP EVs have a protective function during human sperm cryopreservation. Full article

Lung cancer remains a leading cause of cancer-related mortality worldwide, where conventional chemotherapy is often limited by severe side effects and drug resistance. Ginsenosides, the primary bioactive triterpenoid saponins isolated from the root of Panax ginseng C. A. Mey, have demonstrated potential in combating non-small-cell lung cancer (NSCLC). However, their efficacy under nutrient-deficient conditions remains unclear. This study aimed to investigate the effects of ginsenosides on the growth and death of lung cancer cells under low-nutrient conditions and to explore the underlying mechanisms. A549 cells were divided into two groups: one cultured in 10% serum and another under serum-free conditions, followed by treatment with ginsenosides CK, Rh2(S), and Rg3(S) for 24 h. Cell proliferation and apoptosis were evaluated using a CCK-8 assay, Calcein/PI fluorescence staining, Hoechst 33258 staining, and flow cytometry. Potential targets and signaling pathways of ginsenosides were predicted using network pharmacology and bioinformatics analyses. The mRNA expression of key genes was measured by qRT-PCR, and mitochondrial membrane potential was assessed using JC-1 staining. The results showed that ginsenosides induced dose-dependent apoptosis in serum-starved A549 cells. Bioinformatics analysis suggested the involvement of the PI3K/Akt/FoxO signaling pathway, which was supported by decreased Akt mRNA levels and increased FoxO mRNA expression. Furthermore, mRNA levels of Bim, Caspase-3, Caspase-8, and Caspase-9 were significantly upregulated, accompanied by a loss of mitochondrial membrane potential. These findings indicate that under serum deprivation, ginsenosides enhance apoptosis in A549 cells, likely through the regulation of the PI3K/Akt/FoxO pathway. Full article

Background: p16 immunohistochemistry (IHC) serves as a surrogate marker for high-risk human papillomavirus (hrHPV) and is widely used in gynecologic pathology. However, few studies have directly compared the staining performance and reproducibility of different p16 antibody clones in this context. Methods: We retrospectively evaluated 176 gynecologic tumor specimens including 42 whole slide sections and 134 tissue microarray cores from the cervix, endometrium, vulva, and ovary using three fully automated p16 IHC assays: E6H4 (Ventana/Roche), JC8 (Agilent/Dako), and 6H12 (Leica). Two pathologists independently reviewed each case, and concordance and interobserver agreement were analyzed. Sensitivity, specificity, and Cohen’s κ statistics were calculated, with E6H4 serving as the reference. Results: All three antibody clones demonstrated excellent staining performance with preserved tissue morphology and minimal background artifacts. Concordance for p16 positivity/negativity was 100% across all clone pairings (95% CI: 97.9–100%). Interobserver reproducibility was also perfect, with a κ coefficient of 1.00 (95% CI: 0.94–1.00). Minor non-block staining patterns did not impair interpretability. Conclusions: Our findings indicate that E6H4, JC8, and 6H12 clones yield comparable staining results when used in conjunction with standardized automated protocols. These results support the practical interchangeability of these clones in clinical and research settings, particularly when cost, availability, or risk management require substitution. Laboratories should continue to perform internal validation and utilize external quality assurance programs when implementing p16 IHC. Full article

Neuroinflammation plays a central role in the pathogenesis of Alzheimer’s disease (AD), with amyloid-β (Aβ) deposition and neurofibrillary tangles driving both central and peripheral inflammatory responses. This study investigated the neuroprotective and anti-inflammatory effects of Vitex trifolia (VT), Plantago major (PM), Apocyni Veneti Folium (AVF), and Eucommiae folium (EF) using network pharmacology and a co-culture model of PC12 neuronal and Caco-2 intestinal epithelial cells. Bioactive compounds were identified via high-performance liquid chromatography (HPLC) and screened with network pharmacology analysis, yielding 27 for VT, 10 for PM, 6 for AVF, and 3 for EF. Molecular docking confirmed strong binding affinities between the key bioactive compounds and AD-related targets. A co-culture system of PC12 neuronal and Caco-2 intestinal epithelial cells was established to evaluate the effects of VT, PM, AVF, and EF extracts (at concentrations of 10 µg/mL, 20 µg/mL, and 50 µg/mL) and donepezil hydrochloride (positive-control) on Aβ_25–35-induced neurotoxicity and lipopolysaccharide (LPS)-induced intestinal inflammation, to assess cell viability, and effects on oxidative stress, mitochondrial function, and inflammatory markers. The VT, PM, AVF, and EF extracts activated phosphoinositide 3-kinase (PI3K)-Akt-glycogen synthase kinase-3β (GSK-3β) signaling, enhanced phosphorylation of AMP kinase, suggesting inhibition of Aβ accumulation and tau hyperphosphorylation (p < 0.05). However, donepezil hydrochloride only enhanced AMPK phosphorylation. The extracts reduced lipid peroxidation and acetylcholinesterase by about 5-fold. JC-1 staining confirmed preserved mitochondrial membrane potential, while hematoxylin and eosin staining indicated improved intestinal barrier integrity (p < 0.05). PM and AVF reduced the number of mast cells (p < 0.05). In conclusion, these findings highlight the multi-target potential of VT, PM, AVF, and EF in mitigating both neuronal and intestinal inflammation. Their dual regulatory effects on the gut–brain axis suggest promising therapeutic applications in AD through the modulation of central and peripheral immune responses. Full article

Bare soil expansion in urban forests, driven by persistent high-intensity trampling, degrades both macro-scale natural resources and micro ecological conditions. Targeted interventions are therefore essential. In this study, trampled bare ground in forest parks and artificially cultivated Ophiopogon japonicus were used as experimental models We employed trampled bare ground in forest parks as well as artificially cultivated O. japonicus as experimental models. Five treatments were implemented: enclosure control (CK), ploughing (F), Bacillus thuringiensis NL-11 application (J), biochar addition (C), and co-application of B. thuringiensis NL-11 with biochar (JC). Our results indicate that, compared with CK, biochar treatments reduced soil bulk density by 30%, increased soil porosity by 89%, and improved water-holding capacity. The soil nitrate nitrogen content in the NL-11 treatment was increased by 113.8% compared with CK, while the co-application of NL-11 with biochar exhibited the highest sucrase and urease activities. Notably, the co-application of B. thuringiensis NL-11 with biochar exhibited the most pronounced effects on aboveground biomass, plant height, and root development, followed by the B. thuringiensis NL-11 treatment. Microbial β-diversity shifts under co-application of B. thuringiensis NL-11 with biochar treatment strongly correlated with soil enzyme activation and plant growth enhancement (Mantel test, p < 0.05). Correlation analysis confirmed that exogenous nutrient inputs significantly influenced enzyme activities, thereby promoting plant development. These results highlight the effectiveness of integrating microbial inoculation with biochar to restore trampled urban forest soils. Full article

Background/Objectives: Aristolochia ringens, a medicinal plant widely used in traditional medicine, has shown potential therapeutic applications. This study aimed to investigate the anticancer mechanism of action of its crude extract against human colorectal adenocarcinoma cells (Caco-2 and HT-29). Methods: Cell viability was assessed using the MTT assay to determine IC₅₀ values. Immunofluorescence microscopy was used to examine nuclear morphology and microtubule integrity. Flow cytometry with PI staining was used for cell cycle analysis and Annexin V-FITC/PI staining for apoptosis detection. Mitochondrial membrane potential was evaluated using JC-1 dye. Bioactivity-guided fractionation was performed via HPLC, and GC–MS was used to profile active constituents. Results: The extract exhibited dose-dependent cytotoxicity with IC₅₀ values below 30 µg/mL in colon adenocarcinoma cell lines. Treated Caco-2 cells showed nuclear shrinkage and disrupted microtubules. PI-based flow cytometry revealed G₁ phase arrest, and Annexin V-FITC/PI staining indicated enhanced late apoptosis. JC-1 staining demonstrated mitochondrial depolarization. HPLC fractionation identified fractions 2 and 3 as active, and preliminary GC–MS analysis tentatively annotated the presence of alkaloids, sesquiterpenes/diterpenes, and steroidal compounds. Conclusions: A. ringens exerts anticancer effects through a mitochondria-mediated apoptotic pathway, involving G₁ checkpoint arrest and cytoskeletal disruption. These findings provide the first integrated cellular and mechanistic evidence of its anticancer potential in colorectal cancer, supporting its promise as a source of novel therapeutic lead compounds. Full article

To accurately assess the effect of different plate thicknesses on the residual stress field of laser shock peened GH3039 superalloy, residual stress measurements were performed on GH3039 alloy plates with thicknesses of 2 mm and 5 mm after laser shock peening (LSP) treatment. Both quasi-static and high strain rate mechanical tests of GH3039 were conducted, and the Johnson-Cook (J-C) constitutive equation for GH3039 alloy at specific strain rates was fitted based on the experimental results. To obtain the parameter C in the J-C constitutive equation of GH3039 alloy under ultra-high strain rates, a modified method was proposed based on LSP experiment and finite element simulation results. Using the modified GH3039 alloy J-C constitutive equation, numerical simulations and comparative analyses of the residual stress field of GH3039 alloy plates of different thicknesses under LSP were carried out using ABAQUS software. The simulated residual stress fields of laser-shocked GH3039 alloy plates of different thicknesses were in good agreement with the experimental measurements, indicating that the modified GH3039 alloy J-C constitutive equation can accurately predict the mechanical behavior of GH3039 alloy under ultra-high strain rates. Based on the modified GH3039 alloy J-C constitutive equation, the effect of different plate thicknesses on the residual stress distribution of laser-shocked GH3039 alloy was studied, along with the underlying mechanisms. The unique distribution characteristics of residual stresses in laser-shocked GH3039 plates with varying thicknesses are primarily attributed to differences in plate bending stiffness and the detrimental coupling effects of reflected tensile waves. Full article

Background/Objectives: The prolonged M1-like pro-inflammatory polarization of macrophages is a key factor in the delayed healing of diabetic ulcers (DU). SIRT3, a primary mitochondrial deacetylase, has been identified as a regulator of inflammation and represents a promising new therapeutic target for DU treatment. Nonetheless, the efficacy of existing SIRT3 agonists remains suboptimal. Methods: Here, we introduce a novel compound, SZC-6, demonstrating promising activity levels. Results: SZC-6 treatment down-regulated the expression of inflammatory factors in LPS-treated RAW264.7 cells and reduced the proportion of M1 macrophages. Mitosox, IF, and JC-1 staining revealed that SZC-6 preserved cellular mitochondrial homeostasis and reduced the accumulation of reactive oxygen species. In vivo experiments demonstrated that SZC-6 treatment accelerated wound healing in diabetic mice. Furthermore, HE and Masson staining revealed increased neovascularization at the wound site with SZC-6 treatment. Tissue immunofluorescence results indicated that SZC-6 effectively decreased the proportion of M1-like cells and increased the proportion of M2-like cells at the wound site. We also found that SZC-6 significantly reduced MyD88, p-IκBα, and NF-χB p65 protein levels and inhibited the nuclear translocation of P65 in LPS-treated cells. Conclusions: The study concluded that SZC-6 inhibited the activation of the NF-χB pathway, thereby reducing the inflammatory response and promoting skin healing in diabetic ulcers. SZC-6 shows promise as a small-molecule compound for promoting diabetic wound healing. Full article