Search Results (17,718)

With the rising integration of high-performance GPUs, localized hotspots induced by discrete heat sources present severe thermal challenges. Traditional single-inlet–single-outlet liquid cold plates can scarcely meet the heat dissipation requirements of inhomogeneous high heat fluxes. This study systematically investigates the effects of nine multiple-inlet–multiple-outlet (MIMO) configurations, ranging from single-inlet–single-outlet to three-inlet–three-outlet, on cold plate hydrothermal performance. An innovative stepwise optimization strategy, topology optimization (TO)-driven channel layout combined with fin-enhancement (FE)-based fine regulation, is proposed and verified to precisely regulate surface temperature distribution of discrete heat sources. The results show that the three-inlet–three-outlet configuration C-3 exhibits the optimal comprehensive performance among the nine configurations. Compared with the worst configuration A-2, C-3 reduces the pressure drop by 58.37% to only 147.18 Pa and yields the highest PEC, striking the optimum trade-off between heat transfer enhancement and fluid flow resistance. Through multi-inlet flow distribution and multi-outlet heat extraction, C-3 accurately suppresses heat accumulation in high heat flux regions, limiting the maximum temperature to merely 29.82 °C and drastically narrowing the substrate temperature difference from 8.69 °C to 2.12 °C. In comparison with the traditional cold plate (TCP), the optimized cold plate (OCP) realizes a 17.42% increase in performance evaluation criterion (PEC). Furthermore, the fin-enhanced optimized cold plate (FEOCP) reduces the temperature standard deviation by 54.15% relative to TCP, significantly enhancing temperature uniformity with only an additional pressure drop penalty of 5.43%. This study reveals the regulation mechanism of MIMO configurations on the flow field distribution of liquid cold plates and verifies the effectiveness of the TO-FE optimization framework, thus providing highly valuable engineering solutions for the high-efficiency, uniform-temperature and low-resistance heat dissipation of high-power electronic devices. Full article

High-performance thermal protection materials are urgently required in harsh thermal environments, such as hypersonic vehicles, the thermal runaway of energy batteries and high-temperature equipment. Conventional aerogels only exhibit passive thermal insulation and fail to resist instantaneous high-temperature attack. Herein, a cooling material of ammonium oxalate (AO) was introduced to achieve efficient, active endothermic protection. A cellular isolation effect induced by graphene nanosheets combined with anti-solvent crystallization was adopted to significantly decrease the size of AO crystals by over 93%. Based on superfine morphology and the constructed conduction network, the decomposition rate and heat absorption capacity of obtained graphene-doped AO powders (GdAPs) are improved by 41.2% and 30.4%, respectively. The mechanisms of morphology regulation and enhanced heat absorption are explored specifically in this study. Furthermore, GdAPs are embedded in phenolic resin to prepare thermal protection composite materials. Benefiting from their nearly complete thermal decomposition, GdAPs serve as a sacrificial template to generate discrete micropores in pyrolyzed resin. So, the as-prepared carbon aerogels (CAs) with a regulable microstructure exhibit an extremely low thermal conductivity of 0.056 W/(m·K), which is lower than those of reported CAs with the same density. Based on the above advantages, a synergistic endothermic-insulating thermal protection material is reported for the first time, and its heating rate is only 28.6% of that of commercial silica aerogel under identical high-temperature shock. Therefore, a new accessible strategy is demonstrated to provide high-efficiency thermal protection for resisting both abrupt and prolonged high temperature. Full article

Background/Objectives: Microtubule-targeting agents represent a pillar of cancer chemotherapy; however, their clinical utility is constrained by significant toxicity, pharmacokinetic instability, and susceptibility to multidrug resistance transporters. This study aimed to explore the impact of replacing substituted phenyl rings with a naphthalene moiety in sulfonamide-based colchicine-site ligands, with the goal of identifying new antiproliferative candidates with improved profiles. Methods: We designed, synthesized, and evaluated a library of 35 naphthalene sulfonamides bearing varied aryl groups and sulfonamide nitrogen substituents. We assessed the antiproliferative activity against multiple cancer cell lines. Mechanistic studies, including fluorescence microscopy, cell cycle analysis, and cell death assays, were performed to evaluate the effect of these compounds on microtubule polymerization dynamics and cell fate. Molecular docking and in silico pharmacokinetic profiling were carried out to support the proposed binding mode at the colchicine site and to assess drug-likeness. Results: Exclusively, compounds bearing a trimethoxyphenyl group showed antiproliferative activity in the submicromolar range, thus identifying it as a structural requirement. The most potent compound (2) reached double-digit nanomolar IC₅₀ values (67–104 nM) across multiple cancer cell lines. Microscopy confirmed intracellular disruption of microtubule polymerization. Unlike colchicine, these compounds did not induce canonical mitotic arrest but instead triggered apoptotic cell death. In silico analyses supported binding at the colchicine site and revealed favorable predicted pharmacokinetic properties. Conclusions: The naphthalene sulfonamides described herein demonstrate potent antiproliferative activity through a distinct mechanism compared to colchicine, and their favorable in silico profiles position them as promising candidates for further development as antitumor agents. Full article

High sound pressure level (SPL) acoustic sensing requires miniaturized microphones that can operate under large acoustic loading while maintaining mechanical linearity, sufficient sensing response, and broadband audio frequency behavior. This work targets high-SPL operation and numerically investigates a graphene piezoresistive MEMS microphone based on a membrane-supported beam–island diaphragm. The proposed structure retains a continuous membrane for acoustic load bearing, while the upper beam–island topology redirects deformation-induced strain toward beam root regions where graphene piezoresistors are placed. This design is intended to increase the local strain available for piezoresistive readout without simply relying on larger global diaphragm deflection. Finite-element analysis was used to optimize the diaphragm geometry and evaluate strain enhancement, pressure response linearity, modal behavior, and harmonic response. Under the 170 dB SPL reference condition, the optimized structure increases the peak structural strain from 47.83 με in a thickness-equivalent solid diaphragm to 562.53 με, achieving an approximately 11.8-fold enhancement in local sensing strain while maintaining a highly linear pressure response (R2 > 0.9999). Additionally, the results also show that the sensor exhibits a high first natural frequency of 64.07 kHz and a small response variation of approximately 0.94 dB within the 0–20 kHz target frequency range, indicating excellent dynamic stability and high-fidelity signal transduction characteristics. To connect the structural response with piezoresistive readout, first-order electromechanical output estimation was further performed using representative graphene gauge factors, quarter-bridge readout assumptions, contact resistance correction, and Johnson-noise-limited signal-to-noise ratio estimation. A ±5% geometric tolerance check further indicates that the membrane side length is the most fabrication-sensitive parameter, while the selected design remains generally robust except for reduced linearity margin under positive membrane side-length deviation. These results demonstrate the potential of the proposed graphene-based MEMS microphone for high-SPL broadband acoustic sensing applications in harsh and high-intensity acoustic environments. Full article

Ultra-High Molecular Weight Polyethylene (UHMWPE), the standard base material in ski manufacturing, offers excellent gliding performance but exhibits limited mechanical and scratch resistance on hard and icy snow conditions. In this work, stainless steel is proposed as a mechanically robust alternative, and its inherently higher friction against snow is addressed through surface engineering. The snow friction behavior of 301H stainless steel surfaces decorated with fishbone-like microstructures combined with Laser-Induced Periodic Surface Structures (LIPSSs) was investigated using a custom-built snow tribometer. Several pattern designs, with different pitch distances and depths, were engraved using femtosecond laser pulse irradiation. We conducted morphological, physical, and chemical investigations through microscopy, static contact angle measurements, and X-ray Photoelectron Spectroscopy analyses. Results indicate that the gliding performance is not directly related to the modifications in surface chemistry and wetting behavior of the samples but is affected by the geometry and orientation with respect to the sliding direction of the specific micro- and nano-features. Overall, we achieved friction coefficient values comparable to those found in UHMWPE with a fast and economically sustainable single-step laser-texturing process. This approach allows the industrial up-scaling of the fishbone-texture design to real-size alpine ski prototypes. Full article

Motoneurons are under strong pressure to maintain stable motor output throughout an individual life, through homeostatic regulation of their electrical properties. Dysregulated spinal motoneuron excitability has long been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Recent work in SOD1^G93A mice suggests that the homeostatic response of motoneurons becomes dysregulated as cellular processes are disrupted by the disease, causing fluctuations in motoneuron electrical properties. Yet, few studies directly test whether ALS motoneurons respond differently than wild-type motoneurons to a common chronic perturbation. Here, we used in vivo electrophysiology to test whether motoneurons from pre-symptomatic SOD1^G93A mice modulate excitability differently than wild-type motoneurons in response to the same homeostatic perturbation: chronic inhibition exerted by the benzodiazepine diazepam. Using linear mixed-effects statistical models, we assessed whether diazepam treatment differentially modulated passive properties, firing behavior, spike properties, and/or synaptic inputs in SOD1^G93A versus wild-type motoneurons. We identified a significant genotype × treatment interaction effect selectively for properties related to passive membrane integration and spike initiation, including membrane time constant, peak input resistance, and recruitment current. In contrast, firing gain, spike waveform characteristics, and synaptic inputs were largely unaffected. These findings indicate that sustained inhibitory perturbation selectively triggered overactive intrinsic compensatory mechanisms in SOD1^G93A motoneurons rather than inducing widespread changes in firing or synaptic transmission. Together, our results provide direct evidence for over-active homeostatic control of motoneuron excitability and support a view of motoneuron dysfunction in ALS as a problem of altered feedback regulation rather than simply hyper- or hypo-excitability. Full article

Lactylation is an emerging lactate-derived post-translational modification that may link tumour metabolic reprogramming, epigenetic regulation and DNA damage repair. Enhanced glycolysis and lactate accumulation are common in many tumours, and lactate has been reported to induce histone and non-histone lactylation in specific experimental contexts. Recent studies suggest that lactylation is associated with several DNA repair pathways, including base excision repair/single-strand break repair, nucleotide excision repair, homologous recombination and non-homologous end joining, and may contribute to therapy resistance in selected cancer models. Specifically, XRCC1 lactylation has been reported to promote nuclear translocation and repair activity in glioblastoma models; H4K12 lactylation has been linked to PARP inhibitor resistance through RAD23A activation in ovarian cancer models; and BLM lactylation has been associated with enhanced homologous recombination repair in bladder cancer models. Lactylation of NBS1, RAD51 and XLF has also been implicated in DNA repair regulation in specific experimental systems, although some mechanistic links are inferred from pathway activation or functional rescue experiments rather than directly demonstrated across multiple tumour types. These findings suggest that lactylation may modulate DNA repair and therapeutic response in a context-dependent manner. Targeting lactate metabolism, transport and lactylation regulators, including LDHA, MCT1/4, ACAT1, AARS1 and GCN5, or using site-specific lactylation-inhibiting peptides may improve chemotherapy and PARP inhibitor efficacy, but clinical translation remains limited by heterogeneity, metabolic plasticity, toxicity and insufficient validation. Full article

Background/Objectives: The toxic side effects and resistance-associated limitations of conventional chemotherapeutic agents necessitate the development of more effective and selective combination strategies incorporating naturally derived compounds. In this study, the cytotoxic, apoptotic, oxidative stress-associated, and immunomodulatory effects of thymoquinone (TQ), a bioactive compound derived from Nigella sativa, and docetaxel (Dos), a taxane-based chemotherapeutic agent, were investigated alone and in combination in OVCAR3 ovarian cancer cells using integrated two-dimensional (2D) and three-dimensional (3D) experimental models. Materials and Methods: Cell viability was evaluated following treatment with TQ (10–500 µM), Dos (1–500 nM), and the TQ + Dos combination, and synergistic interactions were assessed by IC₅₀⁻ and combination index-based analyses. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Cytokine levels were determined using ELISA, whereas apoptosis- and cell cycle-associated gene expression profiles were evaluated by RT-qPCR. Active caspase-3 expression was assessed by immunocytochemistry. Intracellular reactive oxygen species (ROS) accumulation was examined using DCFH-DA-based fluorescence imaging and antioxidant rescue experiments using N-acetyl-L-cysteine (NAC). In addition, the antitumor activity of the combination was further evaluated in OVCAR3-derived 3D tumor spheroid models using spheroid morphology, ATP-based viability, and live/dead fluorescence imaging analyses. Results: The TQ + Dos combination demonstrated enhanced cytotoxic and apoptotic activity in OVCAR3 cells compared with single-agent treatments and induced marked G2/M cell cycle arrest. Combination treatment increased pro-apoptotic gene expression and was associated with reduced expression of anti-apoptotic markers and modulated inflammatory cytokine profiles. Fluorescence-based analyses demonstrated marked intracellular ROS accumulation following TQ + Dos treatment, whereas NAC pretreatment partially attenuated oxidative stress and restored viability, suggesting partial involvement of ROS-associated mechanisms in treatment-induced cytotoxicity. Importantly, the combination maintained stronger cytotoxic and growth-inhibitory effects than either monotherapy in 3D ovarian cancer spheroids, where combination treatment induced pronounced spheroid shrinkage, viability loss, and structural disruption. Relatively lower toxicity observed in HaCaT cells suggested partial selectivity toward cancer cells. Conclusions: Collectively, these in vitro findings suggest that the TQ + Dos combination produces greater cytotoxic, apoptotic, and growth-inhibitory effects than either agent alone in ovarian cancer models and is associated with alterations in apoptosis-, cell cycle-, and oxidative stress-related responses. The observation of these effects in 3D spheroid models supports further investigation of this combination in more advanced preclinical systems. Full article

Freeze–thaw durability of 3D-printed engineered cementitious composites (3DP-ECC) is strongly affected by print-induced interlayer defects and anisotropy, particularly in cold regions. This study investigated Cast-ECC and Z-direction 3DP-ECC incorporating Yellow River sediment (YRS) as an equal-mass replacement for quartz sand at 0–100%. Compressive, three-point bending, and four-point bending tests, relative dynamic elastic modulus (RDME), XCT, MIP, SEM–EDS, and Weibull damage modeling were used to evaluate degradation up to 150 freshwater freeze–thaw cycles. Moderate YRS replacement (25–50%) improved particle packing, reduced visible defects, and refined the pore structure, thereby enhancing frost resistance. The R50 mixture showed the best residual performance: after 150 cycles, compressive strength decreased from 55 to 46 MPa in Cast-ECC and from 54 to 44 MPa in 3DP-ECC, corresponding to retention rates of 83.6% and 81.5%, respectively. The residual peak load in four-point bending of 3DP-ECC-R50 was 15.4% lower than that of Cast-ECC-R50, confirming the detrimental role of interlayer defects under loading perpendicular to the layers. RDME-based Weibull fitting described the overall damage evolution (R² = 0.876–0.994), while XCT, MIP, and SEM–EDS indicated that interlayer discontinuities, pore-structure evolution, and local microstructural degradation governed anisotropic deterioration. The results support durability-oriented design of YRS-based 3DP-ECC in cold regions. Full article

Laser powder bed fusion (LPBF) of high-strength aluminum alloy 7075 (AA7075) is severely limited by hot cracking. However, the underlying mechanisms, particularly the coupling between thermal fields, solidification microstructure, and cracking behavior, remain insufficiently clarified. This study elucidates these mechanisms by integrating experimental characterization with thermal simulation to investigate the temperature field, microstructure, and cracking relationships in both AA7075 and a crack-resistant 7075-Er-Zr alloy. Results show that coarse hot crack morphology is highly dependent on linear energy density E_L. In AA7075, E_L < 450 J/m promotes laterally inclined cracks (short, narrow cracks extending from the melt pool boundary toward the track center), whereas E_L higher than that value leads to the continuous centerline cracks (long, wide cracks along the track center). Fine microcracks are also observed at melt pool boundaries. The 7075-Er-Zr alloy demonstrates superior crack resistance. At E_L = 600 J/m, longitudinal centerline cracks still penetrate along the track, but the alloy achieves crack-free tracks at 200 W with scanning speeds above 1000 mm/s, otherwise exhibiting only short discontinuous cracks. Microcracks at melt pool boundaries are markedly suppressed in the modified alloy. The enhanced crack resistance is attributed to Er/Zr-induced grain refinement and a transition to an equiaxed grain structure, which disrupts intergranular gaps. Critically, thermal simulations identify an annular region with a peak temperature gradient. In AA7075, this region develops aligned columnar grains that facilitate both microcracks and centerline cracks. In the 7075-Er-Zr alloy, microcracks are fully eliminated within this region. However, a residual crystallographic texture persists in the annular region, which promotes the continued occurrence of centerline cracks under high energy density (e.g., E_L = 600 J/m). The annular region remains a critical weak link, and its microstructural control determines the prevailing crack type. This work provides a fundamental understanding of the thermal-microstructural origins of cracking and offers a theoretical foundation for developing crack-resistant aluminum alloys via LPBF. Full article

Lipid peroxidation (LPO) is a process where polyunsaturated fatty acids (PUFA) in cellular membranes are oxidized. This process is mediated by reactive oxygen species (ROS) and leads to the formation of reactive products, including 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and oxidized phospholipids. At low concentrations these products act as second messengers in adaptive redox signalling and metabolic homeostasis, whereas at higher concentrations they compromise membrane integrity and promote cell death. Lipid peroxidation plays a crucial role in anticancer therapies. Here we focus on three mechanistically complementary drugs—sorafenib, cisplatin, and olaparib—because each converges, directly or indirectly, on the redox/LPO axis (system xc−/GPX4 modulation, mitochondrial ROS, and SLC7A11 regulation, respectively), modulating tumor cell responses by inducing PUFA oxidation, mitochondrial dysfunction, and membrane damage. However, tumor cells have several protective pathways against oxidative stress, such as increased expression of glutathione peroxidase 4 (GPX4), the SLC7A11 system Xc, and detoxification of reactive aldehydes. Enrichment of membranes with PUFA increases susceptibility to lipid peroxidation and ferroptosis, thereby sensitizing tumor cells to therapy, whereas enrichment with monounsaturated fatty acids (MUFA), driven by the SREBP1–SCD1 axis, limits peroxidation and confers resistance. Among regulated cell death modalities, ferroptosis is strictly dependent on lipid peroxidation, whereas apoptosis, necrosis, necroptosis, pyroptosis, and immunogenic cell death can be modulated by lipid peroxidation but do not universally require it. Collectively, these mechanisms indicate that lipid peroxidation is an important—though not exclusive—determinant of anticancer drug sensitivity and resistance, and that its dual, context-dependent role (tumor-suppressive at high flux, tumor-promoting under chronic, sub-lethal exposure) must be considered when designing LPO-based therapeutic strategies. Full article

Red clay in humid-hot environments suffers from severe water sensitivity and rainfall-induced slope instability, while traditional cement/lime stabilization faces high carbon emission challenges. Existing studies on plant ash-modified red clay mainly focus on basic mechanical properties, while systematic research on water retention characteristics and slope stability under extreme rainfall in humid-hot climates remains insufficient. To address this gap, this study proposes a sustainable stabilization method using agricultural waste-derived plant ash for red clay modification in humid-hot regions. Red clay exhibits distinct engineering behaviors owing to its unique physicochemical properties, leading to compromised slope stability and reduced resistance to rainwater infiltration. In this study, red clay was stabilized with 5%, 10%, 15%, and 20% plant ash. Laboratory tests evaluated compaction characteristics, shear strength, and water retention, supported by microstructural analysis via scanning electron microscopy (SEM). Slope stability under rainfall conditions was further simulated using ABAQUS 2022 software. Key findings include: (1) The addition of plant ash significantly altered the compaction properties. As the plant ash content increased from 0% to 20%, the maximum dry density of the modified red clay decreased linearly from 1.68 g/cm³ (unmodified soil) to 1.53 g/cm³, while the optimum moisture content rose from 21.86% to 23.85%. (2) The mechanical properties exhibited a non-linear response, peaking at 10% ash content. At this optimum dosage, the unconfined compressive strength, cohesion, and internal friction angle increased by 70.4%, 83.0%, and 37.1%, respectively, compared to untreated soil. (3) Plant ash enhanced water retention capacity, shifting the soil-water characteristic curve (SWCC). The modified soil demonstrated faster dehydration at low suction but improved water retention at high suction. The permeability coefficient decreased by an order of magnitude. Microstructural analysis revealed reduced porosity and fracture infilling by cementitious gels. (4) Numerical simulations confirmed that 10% plant ash reduced maximum slope displacement from 0.96 m to 0.61 m under heavy rainfall (90 mm total precipitation over 36 h, peak intensity 90 mm/day), elevating the safety factor from 0.85 to 1.45. Failure modes transitioned from deep-seated slip to localized shallow erosion. These results demonstrate that plant ash is a sustainable and effective additive for red clay slope stabilization in tropical climates. Full article

The thermo-mechanical degradation of the base–subgrade interface in airport pavements was investigated using a three-dimensional sequentially coupled finite element framework in ABAQUS 2023, in which progressive interfacial debonding was described by a bilinear cohesive-zone model through the damage variable CSDMG. The results show that thermal loading markedly accelerates interface degradation when combined with moving wheel loads. Compared with the wheel-loading-only condition, thermo-mechanical coupling advances the first damage initiation from 0.04993 h to 0.00254 h and shortens the severe-degradation stage from 1.000 h to 0.00927 h. This acceleration is attributed to a thermal stress pre-weakening effect, whereby constrained thermal deformation partially consumes the available cohesive resistance and shifts the interface closer to the softening threshold before external loading is applied. A decomposition of the mixed-mode initiation criterion further indicates that the first damage event is governed by synergistic normal–shear interaction, with the normalized contribution ratio (t_n/t_n⁰)²:(t_s/t_s⁰)² = 0.38:0.62, showing that wheel-induced shear is the dominant trigger while tensile opening induced by thermal curling provides substantial preconditioning assistance. In addition, a representative normalized comparison between simulated average CSDMG and cumulative AE hit count demonstrates a consistent stage evolution from distributed deformation to accelerated localization and residual stabilization. These findings indicate that the base–subgrade interface should be treated as a temperature-sensitive weak layer in airport pavement assessment, particularly near joints and other discontinuity-controlled regions. Full article

Seawater zinc–air batteries (SZABs) stand out as promising candidates for marine and offshore energy supply. However, their practical implementation is greatly restricted by tardy oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) kinetics at the air cathode, severe chloride ion-induced catalyst corrosion, and structural deterioration of traditional binder-containing electrodes in seawater media. Herein, we design and fabricate a binder-free integrated electrode consisting of carbon-supported iron phthalocyanine- modified star-like cobalt sulfide arrays directly grown on nickel foam. The optimal catalyst (0.3FePc-C/CoS) integrates the respective advantages of Fe single atoms and cobalt sulfide, exhibiting excellent ORR and OER activity, delivering a prominent half-wave potential of 0.89 V versus RHE, and exhibiting a low OER overpotential of 160 mV at 50 mA cm⁻² and robust stability in seawater. As a self-supported air cathode, the 0.3FePc-C/CoS-based battery attains a favorable open-circuit voltage reaching 1.48 V, prominent peak power density (126.4 mW cm⁻²), small charge–discharge potential polarization (0.52 V), excellent energy efficiency (68.8%) and extraordinary long-term cycling durability (>360 h). This work not only discloses a feasible synergistic modulation strategy for constructing high-performance bifunctional electrocatalysts but also provides a valuable reference for developing corrosion-resistant integrated air electrodes toward practical marine energy storage applications. Full article

Malassezia are commensal lipid dependent yeasts which can cause opportunistic skin infection. Topical imidazole antifungals such as clotrimazole and ketoconazole are the frontline treatment. However, the tendency of fungal infections to recur, combined with the emergence of multi-azole-resistant Malassezia isolates means that many patients have used these antifungal treatments repeatedly or for extended durations with limited efficacy. While the impact of single azole treatments has been studied, the ability of specific azoles to induce cross-resistance is unclear. Understanding the effect of prior exposure of one treatment on susceptibility to other antifungals is important in the selection of the appropriate treatment to avoid driving the evolution of greater resistance. We previously identified drug transporters from the ATP-Binding Cassette (ABC) and Major Facilitator Superfamily (MFS) to be upregulated on extended exposure to clotrimazole. In this study, we investigated the effect of extended clotrimazole, ketoconazole and fluconazole exposure on antifungal cross-resistance profiles and examined the expression of the MFS transporters OPT1 and FLR1 in resistance emergence. We observed that treatment with clotrimazole was associated with increased cross-resistance to other antifungals. Ketoconazole treatment caused elevated MICs in all tested antifungals that did not decrease after drug removal. These findings advance our understanding of fungal adaptive resistance mechanisms and inform improved antifungal strategies to mitigate resistance development. Full article