Search Results (19,210)

Due to post-cementing hydraulic fracturing and other operational stresses, inadequate mechanical properties or suboptimal design of the cement sheath can lead to tensile failure and microcrack development, compromising both hydrocarbon recovery and well integrity. In this study, three field-deployed cement slurry systems were compared on the basis of their basic mechanical properties such as compressive and tensile strength. Laboratory-scale physical simulations of hydraulic fracturing during shale oil production were conducted, using dynamic permeability as a quantitative indicator of integrity loss. The experimental results show that evaluating only basic mechanical properties is insufficient for cement slurry system design. A more comprehensive mechanical assessment is re-quired. Incorporation of an expansive agent into the cement slurry system can alleviate the damage caused by the microannulus to the interfacial sealing performance of the cement sheath, while adding a toughening agent can alleviate the damage caused by tensile cracks to the sealing performance of the cement sheath matrix. Through this research, a microexpansive and toughened cement slurry system, modified with both expansive and toughening agents, was optimized. The expansive agent and toughening agent can significantly enhance the shear strength, the flexural strength, and the interfacial hydraulic isolation strength of cement stone. Moreover, the expansion agents mitigate the detrimental effects of microannulus generation on the interfacial sealing, while the toughening agents alleviate the damage caused by tensile cracking to the bulk sealing performance of the cement sheath matrix. This system has been successfully implemented in over 100 wells in the GL block of Daqing Oilfield. Field application results show that the proportion of high-quality well sections in the horizontal section reached 88.63%, indicating the system’s high performance in enhancing zonal isolation and cementing quality. Full article

L-type Ca²⁺ channels, particularly Ca_V1.2, play a crucial role in cardiac excitation-contraction coupling and are known to exhibit mechanosensitivity. However, the mechanisms regulating their response to mechanical stress remain poorly understood. To investigate the mechanosensitivity and nitric oxide (NO)-dependent regulation of L-type Ca²⁺ channels in rat ventricular cardiomyocytes, we used RNA sequencing to assess isoform expression and whole-cell patch-clamp recordings to measure L-type Ca²⁺ current (I_Ca,L) under controlled mechanical and pharmacological conditions. RNA sequencing revealed predominant expression of Ca_V1.2 (TPM: 0.1170 ± 0.0075) compared to Ca_V1.3 (0.0021 ± 0.0002) and Ca_V1.1 (0.0002 ± 0.0002). Local axial stretch (6–10 μm) consistently reduced I_Ca,L in proportion to stretch magnitude. The NO donor SNAP (200 μM) had variable effects on basal I_Ca,L in unstretched cells (stimulatory, inhibitory, or biphasic) but consistently restored stretch-reduced I_Ca,L to control levels. Ascorbic acid (10 μM), which reduces S-nitrosylation, increased basal I_Ca,L and partially restored the reduction caused by stretch, implicating S-nitrosylation in channel regulation. The sGC inhibitor ODQ (5 μM) decreased I_Ca,L in both stretched and unstretched cells, indicating involvement of the NO–cGMP pathway. Mechanical stress modulates L-type Ca²⁺ channels through a complex interplay between S-nitrosylation and NO–cGMP signaling, with S-nitrosylation playing a predominant role in stretch-induced effects. This mechanism may represent a key component of cardiac mechanotransduction and could be relevant for therapeutic targeting in cardiac pathologies involving mechanically induced dysfunction. Full article

Cardiovascular disease (CVD) remains Europe’s leading cause of mortality, responsible for >45% of deaths. Beyond established risk factors (hypertension, diabetes, dyslipidaemia, smoking, obesity), psychosocial elements—depression, anxiety, financial stress, personality traits, and trauma—significantly influence CVD development and progression. Behavioural Cardiology addresses this connection by systematically incorporating psychosocial factors into prevention and rehabilitation protocols. This review examines the HEARTBEAT model, developed by Greece’s first Behavioural Cardiology Unit, which aligns with current European guidelines. The model serves dual purposes: primary prevention (targeting at-risk individuals) and secondary prevention (treating established CVD patients). It is a personalised medicine approach that integrates psychosocial profiling with traditional risk assessment, utilising tailored evaluation tools, caregiver input, and multidisciplinary collaboration to address personality traits, emotional states, socioeconomic circumstances, and cultural contexts. The model emphasises three critical implementation aspects: (1) digital health integration, (2) cost-effectiveness analysis, and (3) healthcare system adaptability. Compared to international approaches, it highlights research gaps in psychosocial interventions and advocates for culturally sensitive adaptations, particularly in resource-limited settings. Special consideration is given to older populations requiring tailored care strategies. Ultimately, Behavioural Cardiology represents a transformative systems-based approach bridging psychology, lifestyle medicine, and cardiovascular treatment. This integration may prove pivotal for optimising chronic disease management through personalised interventions that address both biological and psychosocial determinants of cardiovascular health. Full article

Background: Burnout syndrome (BS) is an occupational phenomenon resulting from chronic workplace stress that has not been successfully managed. Although there are underlying causes associated with personal attributes, it is generally linked to external factors within the work environment. The aim of the present study was to investigate the impact of lifestyle factors on BS and its dimensions, as well as on suicidal ideation among Spanish professionals dedicated to implant dentistry. Methods: A cross-sectional observational study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. An electronic survey based on the Maslach Burnout Inventory—Human Services Survey (MBI–HSS) was distributed to members of the Spanish Society of Implants. The data were analysed using descriptive statistical methods. Results: A total of 305 participants (20.9%) responded to the questionnaire. Notably, 10.8% of the professionals reported experiencing suicidal thoughts, a factor significantly associated with the presence of BS. The lifestyle factors associated with BS included the following: not engaging in aerobic exercise for at least 30 min per day (p < 0.05), not having hobbies that facilitate mental disconnection from work (p < 0.001), not following a balanced diet (p < 0.0001), having an insufficient social life (p < 0.0001), and experiencing suicidal ideation (p < 0.01). Conclusions: The surveyed dentists generally reported having healthy lifestyle habits. Nevertheless, one in ten professionals acknowledged having experienced suicidal ideation at some point, highlighting a concerning association with BS. Full article

Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article

Fungicides are compounds with potentially toxic effects on the human body, but the molecular mechanisms of their action have not yet been explained. The effect of cyprodinil on cell viability, apoptosis level, cell membrane function, cell morphology and expression of antioxidant enzyme genes in the A-375 and DLD-1 cell lines was examined. The cell lines were selected because they can be an excellent in vitro model of neoplastic changes occurring in the skin and large intestine after exposure to a fungicide. The fungicide selected for the study is commonly used in Poland to protect crops against fungi. Our results showed that the tested compound increased cell viability and proliferation, probably activated by mechanisms related to oxidative stress. Cyprodinil caused an increase in glutathione level (in A-375 by about 37% and in DLD-1 by about 28%) and oxidative stress enzymes activity, but not in apoptosis level. Its membrane interactions and its penetration into cells was concentration dependent. It is worth emphasizing that the novelty of our work lies in the use of non-traditional toxicological methods based on molecular analyses using human cell lines. This allowed us to demonstrate not only the toxicity of a single substance but also its behavior within cellular structures. Our findings suggest that cyprodinil may have tumor-promoting properties in skin and colorectal cancer cells. Full article

Diabetes mellitus (DM) is one of the leading causes of death and disability worldwide and its prevalence continues to rise. Chronic hyperglycemia exposes patients to severe complications. Among these, diabetic vascular lesions are the most destructive. Their primary driver is the synergistic interaction between hyperglycemia-induced oxidative stress and chronic inflammation. This review systematically elucidates how multiple pathological pathways—namely, metabolic dysregulation, mitochondrial dysfunction, endoplasmic reticulum stress, and epigenetic reprogramming—cooperate to drive oxidative stress and inflammatory cascades. Confronting this complex pathological network, natural products, unlike conventional single-target synthetic drugs, exert multi-target synergistic effects, simultaneously modulating several key pathogenic networks. This enables the restoration of redox homeostasis and the suppression of inflammatory responses, thereby improving vascular function and delaying both microvascular and macrovascular disease progression. However, the clinical translation of natural products still faces multiple challenges and requires comprehensive mechanistic studies and rigorous validation to fully realize their therapeutic potential. Full article

This literature-based review draws on studies of thirty-four fish species; most are from northern temperate regions. Fish have flexible and indeterminate growth, and often they do not reach their growth and size potential. They may become stunted with impaired growth and early maturity, chiefly as a phenotypically plastic reaction. The main causes of stunted growth are negatively density-dependent food availability and keen intraspecific competition leading to environmental stress. Typically, their growth levels off early in life as energy consumptions approach energy costs of maintenance. Females typically attain maturity soon after the energy surplus from feeding starts to decrease. Males are often more variable in size at maturity owing to alternative mating strategies, and their size at maturity depends on both species-specific mating behaviours and environmental opportunities. In polyphenic/polymorphic populations, one phenotype may be stunted and the other phenotype non-stunted; stunted individuals do not perform the required ontogenetic niche shift needed to grow larger. The adult morphology of stunted fish is typically like the morphology of juveniles. Their secondary sexual characters are less pronounced, and they phenotypically retain adaptation to their early feeding niche, which is different from that of large-growing individuals. There are open questions regarding to what extent genetics and epigenetics regulate the life histories of stunted phenotypes. Full article

The conventional manufacturing of refractory complex concentrated alloys (RCCAs) for high-temperature applications is complicated, particularly when material costs and high melting points of the materials processed are considered. Additive manufacturing (AM) could provide an effective alternative. However, the extreme temperatures involved represent significant challenges for manufacturing defect-free alloys using this approach. To address this issue, we investigated the preparation of a CrNbTiZr quaternary complex concentrated alloy from an equimolar blend of elemental powders using commercially available powder-blown L-DED technology. Initially, the alloys exhibited some defects owing to the internal stress caused by the temperature gradients. This was subsequently resolved by optimizing the deposition strategy. SEM, XRD and EDS were used to analyze the alloy in the as-deposited condition, revealing a BCC phase and a secondary Laves phase. Furthermore, Vickers hardness testing demonstrated a correlation between the hardness and the volume fraction of the Laves phase. Finally, successfully performed compression tests confirmed that the prepared material exhibits high-temperature strength and therefore is promising for high-temperature application under extreme conditions. Full article

Late-spring frost events severely damage low-chill peach blossoms, causing significant yield losses. Although 5-aminolevulinic acid (ALA) enhances cold tolerance through the PpC3H37-PpWRKY18 module, the regulatory mechanism of ALA on PpC3H37 remains to be elucidated. Using yeast one-hybrid screening with the PpC3H37 promoter as bait, we identified PpDof9 as a key interacting transcription factor. A genome-wide analysis revealed 25 PpDof genes in peaches (Prunus persica). These genes exhibited variable physicochemical properties, with most proteins predicted as nuclear-localized. Subcellular localization experiments in tobacco revealed that PpDof9 was localized to the nucleus, consistent with predictions. A synteny analysis indicated nine segmental duplication pairs and tandem duplications on chromosomes 5 and 6, suggesting duplication events drove family expansion. A conserved motif analysis confirmed universal presence of the Dof domain (Motif 1). Promoter cis-element screening identified low-temperature responsive (LTR) elements in 12 PpDofs, including PpDof1, PpDof8, PpDof9, and PpDof25. The quantitative real-time PCR (qRT-PCR) results showed that PpDof1, PpDof8, PpDof9, PpDof15, PpDof16, and PpDof25 were significantly upregulated under low-temperature stress, and this upregulation was further enhanced by ALA pretreatment. Our findings demonstrate ALA-mediated modulation of specific PpDof TFs in cold response and provide candidates (PpDof1, PpDof9, PpDof8, PpDof25) for enhancing floral frost tolerance in peaches. Full article

In recent years, the majority of countries have focused on the development of earth-penetrating weapons and the construction of deep underground fortifications. It is therefore necessary to assess the damage to underground structures under the attacks of earth-penetrating weapons. In this paper, fluid–solid coupling and restarting methods are used to simulate the damage processes of a granite chamber subjected to the combined action of penetration and explosion with the commercial software of LS-DYNA R11. The applicability of the penetration model and the blasting model is verified by the previous penetration and blasting tests. The verified models are used to simulate the complete process of the underground granite chamber attacked by the earth-penetrating weapons. Based on peak particle velocity (PPV) damage criteria, the numerical results show that the hypervelocity impact of the earth penetrating weapons only causes local damage to the granite rock mass, and more serious damage is caused by the subsequent explosion. During the subsequent explosion, part of the detonation products and energy can escape along the penetration trajectory with the blast loading, resulting in the attenuation of blast stress waves. Subsequently, the relationship between the overlay thickness and the vibration attenuation in granite is also studied, which provides a fast method to determine the threshold damage level for an underground chamber to collapse under the attacks of earth-penetrating weapons. Full article

Drought and water scarcity are some of the most important challenges facing agricultural producers in dry environments. This study aimed to evaluate the effect of algae extract and zeolite in terms of their biostimulant action on water stress tolerance to obtain better growth and production of tomato Lycopersicum esculentum L. grown in an open field under suboptimum and deficient soil moisture content. Large plots had a suboptimum soil moisture content (SSMC) of 25% ± 2 [28% below field capacity (FC)] and deficient soil moisture content (DSMC) of 20% ± 2 [11% above permanent wilting point (PWP)]; both soil moisture ranges were based on field capacity FC (32%) and PWP (18%). Small plots had four treatments: algae extract (AE) 50 L ha⁻¹ and zeolite (Z) 20 t ha⁻¹, a combination of both products (AE + Z) 25 L ha⁻¹ and 10 t h⁻¹, and a control (without application of either product). By applying AE, Z, and AE + Z, plant height, plant vigor, and chlorophyll index were significantly higher compared to the control by 20.3%, 10.5%, and 22.3%, respectively. The effect on relative water content was moderate—only 2.6% higher than the control applying AE, while the best treatment for the photosynthesis variable was applying Z, with a value of 20.9 μmol CO₂ m⁻² s⁻¹, which was 18% higher than the control. Consequently, tomato yield was also higher compared to the control by 333% and 425% when applying AE and Z, respectively, with suboptimum soil moisture content. The application of the biostimulants did not show any mitigating effect on water stress under soil water deficit conditions close to permanent wilting. These findings are relevant to water-scarce agricultural areas, where more efficient irrigation water use is imperative. Plant biostimulation through organic and inorganic extracts plays an important role in mitigating environmental stresses such as those caused by water shortages, leading to improved production in vulnerable agricultural areas with extreme climates. Full article

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article

Status epilepticus occurs when a seizure lasts more than five minutes or when multiple seizures occur with incomplete return to baseline. SE induces a myriad of pathological changes involving synaptic and extra-synaptic factors. The transition from a self-limiting seizure to a self-sustaining one is established by maladaptive receptor trafficking, whereby GABA_A receptors are progressively endocytosed while glutamatergic receptors (NMDA and AMPA) are transported to the synaptic membrane, causing excitotoxicity and alteration in glutamate-dependent downstream signaling. The subsequent influx of Ca²⁺ exposes neurons to increased levels of [Ca²⁺]i, which overwhelms mitochondrial buffering, resulting in irreversible mitochondrial membrane depolarization and mitochondrial injury. Oxidative stress resulting from mitochondrial leakage and increased production of reactive oxygen species activates the inflammasome and induces a damage-associated molecular pattern. Neuroinflammation perpetuates oxidative stress and exacerbates mitochondrial injury, thereby jeopardizing mitochondrial energy supply in a state of accelerated ATP consumption. Additionally, Ca²⁺ overload can directly damage neurons by activating enzymes involved in the breakdown of proteins, phospholipids, and nucleic acids. The cumulative effect of these effector pathways is neuronal injury and neuronal death. Surviving neurons undergo long-term alterations that serve as a substrate for epileptogenesis. This review highlights the multifaceted mechanisms underlying SE self-sustainability, pharmacoresistance, and subsequent epileptogenesis. Full article

The stability of the intermediate rock wall in the blasting construction of bifurcated small-spacing tunnels directly affects the construction safety of the tunnel structure. Clarifying the damage characteristics of the intermediate rock wall has significant engineering value for ensuring the safe and efficient construction of bifurcated tunnels. Based on the Tashan North Road Expressway Tunnel Project, this paper investigated the damage characteristics of the intermediate rock wall in bifurcated tunnels under different blasting construction schemes, using numerical simulation methods to account for the combined effects of in situ stress and blasting loads. The results were validated using comparisons with the measured damage depth of the surrounding rock in the ramp tunnels. The results indicate that the closer the location is to the starting point of the bifurcated tunnel, the thinner the intermediate rock wall and the more severe the damage to the surrounding rock. When the thickness of the intermediate rock wall exceeds 4.2 m, the damage zone does not penetrate through the wall. The damage to the intermediate rock wall exhibits an asymmetric “U”-shaped distribution, with greater damage on the side of the trailing tunnel at the section of the haunch and sidewall, while the opposite is true at the section of the springing. During each excavation step of the ramp and main-line tunnels, the damage to the intermediate rock wall is primarily induced by blasting loads. As construction progresses, the damage to the rock wall increases progressively under the combined effects of blasting loads and the excavation space effect. In the construction of bifurcated tunnels, the greater the distance between the headings of the leading and trailing tunnels is, the less damage will be inflicted on the intermediate rock wall. Constructing the tunnel with a larger cross-sectional area first will cause more damage to the intermediate rock wall. When the bench method is employed, an increase in the bench length leads to a reduction in the damage to the intermediate rock wall. The findings provide valuable insights for the selection of construction schemes and the protection of the intermediate rock wall when applying the bench method in the construction of bifurcated small-spacing tunnels. Full article