Search Results (5,257)

Cancer progression is closely associated with dysregulation of apoptosis, enabling malignant cells to evade programmed cell death and develop resistance to therapy. Among the key regulators of this process, the tumor suppressor protein p53 and the Bcl-2 family of proteins play central and interconnected roles in controlling cell survival and mitochondrial integrity. In recent years, naturally occurring flavonoids have attracted considerable attention as potential modulators of these pathways due to their diverse biological activities and relatively low toxicity. This review provides a focused and integrative overview of how different subclasses of flavonoids modulate the p53–Bcl-2 signaling axis to regulate apoptosis in cancer cells. Particular emphasis is placed on the mechanistic interplay between p53 stabilization, transcriptional regulation of apoptotic targets, mitochondrial outer membrane permeabilization, and caspase activation. In contrast to previous general reviews on flavonoids and cancer, this work provides an integrated overview of evidence across multiple flavonoid subclasses and experimental cancer models, highlighting both shared and pathway-specific apoptotic responses. Experimental findings from in vitro and in vivo studies are discussed, including the effects of quercetin, kaempferol, myricetin, epigallocatechin gallate, and related compounds on cell-cycle arrest, oxidative stress, mitochondrial dysfunction, and intrinsic apoptotic signaling. Furthermore, the review examines the relationship between flavonoid chemical structure and biological activity, with particular attention to bioavailability, metabolic transformation, and strategies aimed at improving therapeutic efficacy, including structural modification and nanocarrier-based delivery systems. Despite promising preclinical findings, significant translational challenges remain, including poor pharmacokinetic properties, variability among experimental models, and limited clinical validation. Overall, flavonoids represent a promising class of bioactive compounds capable of targeting apoptosis through modulation of the p53–Bcl-2 network, and a deeper mechanistic understanding of their activity may support the development of novel targeted and combination anticancer therapies. Full article

Liquid electrolytes in conventional lithium-ion batteries pose safety risks associated with flammability, leakage, and explosion, whereas solid polymer electrolytes are generally limited by insufficient ionic conductivity at ambient temperature, restricting the development of high-energy lithium batteries. To address these issues, flexible poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP)-based gel polymer electrolyte membranes (GPEs) were prepared via a slit-coating process combined with UV curing. NASICON-type lithium aluminum titanium phosphate (Li_1.3Al_0.3Ti_1.7P₃O₁₂, LATP) and garnet-type tantalum-doped lithium lanthanum zirconate (Li_6.4La₃Zr_1.4Ta_0.6O₁₂, LLZTO) were introduced as inorganic ceramic fillers to improve the ion-transport and interfacial properties of the GPE. Among the investigated samples, the PVDF-HFP-based GPE containing 10 wt% LLZTO exhibited the best overall performance, with an ionic conductivity of 3.40 × 10⁻⁴ S·cm⁻¹ at ambient temperature and a Li⁺ transference number of 0.77. Cyclic voltammetry results showed that the LLZTO-modified electrolyte membrane exhibited sharper and more symmetric redox peaks, higher peak current response, and better curve overlap during repeated cycles, indicating improved electrochemical reversibility and interfacial stability. In addition, LLZTO incorporation enhanced the mechanical strength, broadened the electrochemical stability window, and improved the flame-retardant behavior of the membrane. The LiFePO₄/GPE/Li cell assembled with the optimized membrane delivered an initial discharge capacity of 160 mAh·g⁻¹ at 0.1 C and maintained 80 mAh·g⁻¹ at 1 C, demonstrating good rate capability. Moreover, a capacity retention of 96% was maintained after 100 cycles at 0.1 C, confirming excellent cycling stability. Therefore, this work provides an effective strategy for the structural optimization and scalable preparation of high-performance gel polymer electrolyte membranes for lithium battery applications. Full article

The cell envelope of Gram-positive bacteria is a primary target of host immune defenses and antibiotics, and its stability is influenced by environmental factors, including the availability of the divalent cations Mg²⁺ and Ca²⁺. Alanine also plays a critical role in cell envelope integrity, contributing to peptidoglycan cross-linking, D-alanine modification of teichoic acids, and protein synthesis. However, how these factors functionally interact to maintain envelope stability in S. aureus remains unclear. Here, we demonstrate that growth of S. aureus under Mg²⁺-limited and Ca²⁺-limited conditions requires increased alanine uptake mediated by the transporter AapA. Loss of AapA results in increased cell lysis and impaired growth under cation-limited conditions, and removing alanine from the growth medium phenocopies these aapA mutant defects. Alanine limitation increases susceptibility to the detergent Triton X-100 and the membrane-targeting antibiotic daptomycin, consistent with defects in envelope stability. Furthermore, aapA function contributes to bacterial fitness in insect and murine infection models. Together, these findings indicate that Mg²⁺, Ca²⁺, and alanine play overlapping roles in stabilizing the S. aureus cell envelope, pointing to AapA as a target that may leveraged to enhance antimicrobial efficacy. Full article

Background/Objectives: Cyclotides are plant-derived macrocyclic peptides distinguished by their head-to-tail cyclized backbone and cystine knot motif, which confer remarkable stability against thermal, enzymatic, and chemical degradation. These features, combined with a compact and rigid structure, position cyclotides as promising scaffolds for future antibacterial agents in response to the escalating threat of multidrug-resistant (MDR) pathogens and the stagnation of conventional antibiotic discovery pipelines. This review summarizes the structural features, antibacterial mechanisms, bioengineering strategies, and translational potential of cyclotides against MDR infections. Methods: A narrative review of the literature was conducted using recent original research articles and reviews on cyclotide structure, antibacterial activity, bioengineering, computational modeling, and pharmaceutical applications. Results: Cyclotides exhibit potent antimicrobial activity, primarily through membrane disruption mediated by amphipathic surfaces and affinity for anionic bacterial membranes. Some variants also demonstrate anti-virulence and antibiofilm properties, broadening their therapeutic relevance for difficult-to-treat infections. Bioengineering approaches, including epitope grafting and rational design, have improved selectivity and potency while reducing cytotoxicity. Advances in computational modeling, molecular dynamics, and artificial intelligence have accelerated the prediction and optimization of antimicrobial activity, toxicity, and pharmacokinetic properties. Conclusions: Innovations in synthesis, including recombinant expression and enzymatic ligation, are helping overcome translational barriers related to cost and scalability. Although challenges remain in oral bioavailability and systemic delivery, strategies such as lipidation and scaffold modification support the development of cyclotide-based therapeutics as adaptable platforms for peptide drug discovery. 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

Traditional solid-contact ion-selective electrodes (SC-ISEs) are severely constrained by a long-standing thermodynamic bottleneck, which requires hours of pre-conditioning and stabilization to establish a stable phase-boundary potential. To fundamentally bypass this limitation, we present a paradigm shift in electrochemical ion sensing that exploits dynamic kinetics rather than waiting for thermodynamic equilibrium. In this paper, we report a transient potential profiling method that eliminates the need for equilibration by analyzing the open-circuit voltage decay during the first 60 s of polarization. A discharge step on indicator electrode returns the membrane to a reproducible initial state, allowing for the extraction of a concentration correlated coefficient. Using a calcium ISE with an optimized membrane, the early-stage polarization dynamics were fitted to a single exponential saturation model, predicting the steady state response with an average error of 1.6%. The method achieved high repeatability (intra-day RSD 3.22%), batch to batch reproducibility (4.57%), and recovery rates from 90.7% to 115.0% in real water samples. Validation against ion chromatography showed high agreement (R² = 0.997). This strategy enabled conditioning free, disposable ISEs for point of care and environmental monitoring. Full article

Background: Brucellosis is a global zoonosis caused by Brucella. Histidine biosynthesis is essential for bacterial growth, but its role in Brucella melitensis virulence remains unclear. HisD catalyzes the final two steps of histidine synthesis and is absent in mammals, making it a potential drug target. Results: We constructed a hisD deletion mutant (ΔhisD) and complemented strain (ChisD) via homologous recombination. ΔhisD failed to grow in medium without histidine supplementation. It showed reduced survival under polymyxin B and SDS stress, and impaired outer membrane integrity under polymyxin B challenge, though no defect was observed under non-stressed conditions. Intracellularly, ΔhisD replicated poorly in HeLa and RAW264.7 cells, and this defect was rescued by exogenous histidine. In a mouse model, ΔhisD exhibited lower bacterial loads in liver and spleen, reduced splenomegaly, and attenuated hepatic granuloma formation. Conclusions: Histidine biosynthesis deficiency attenuates Brucella virulence by restricting nutritional acquisition and conditionally compromising outer membrane stability. HisD is a promising target for anti-brucellosis drug development, and ΔhisD holds potential as a live attenuated vaccine candidate. Full article

Engineered nanomaterials are widely used in environmental remediation, agriculture, and industrial applications owing to their large specific surface area, high reactivity, and tunable physicochemical properties. However, their release into aquatic environments has raised increasing concerns regarding potential risks to primary producers. Microalgae are highly sensitive to environmental stressors and play essential roles in photosynthesis, nutrient cycling, carbon fixation, and aquatic food-web stability, making them important model organisms for assessing the toxicity of engineered nanomaterials. This review summarizes the toxic effects and mechanisms of representative engineered nanomaterials, including metal and metal oxide nanoparticles, nanoplastics, and carbon-based nanomaterials, on microalgae. Major toxic pathways include nanoparticle attachment and aggregation on algal surfaces, shading effects, membrane damage, altered permeability, cellular internalization, toxic ion release, reactive oxygen species overproduction, photosynthetic inhibition, and metabolic disturbance. The review further discusses how particle size, morphology, surface coating, dissolution, aging, light, pH, and natural organic matter regulate nanomaterial bioavailability and toxicity. Combined toxicity caused by coexisting nanoparticles or emerging pollutants is also considered, with emphasis on synergistic, antagonistic, and concentration-dependent effects. Finally, recent methodological advances, such as near-native imaging, Raman-based spectroscopy, particle-specific elemental analysis, and multi-omics approaches, are highlighted. This review provides an integrated perspective for understanding nanomaterial toxicity to microalgae and supports future ecological risk assessment in aquatic environments. Full article

Background: Mitochondrial dysfunction is a central event in the pathogenesis of ischemic stroke. The roles of specific mitochondrial complex subunits, such as NDUFA4 and NDUFB3, in cerebral ischemia–reperfusion injury remain poorly defined. This study aims to investigate the dynamic expressions and functional impact of NDUFA4 and NDUFB3 in ischemic stroke. Methods: A transient middle cerebral artery occlusion (MCAO) model was established in male C57BL/6J mice. Label-free quantitative proteomics and Western blotting were employed to analyze protein expression in the ischemic penumbra. Highly differentiated PC12 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) or glutamate excitotoxicity to mimic ischemic injury in vitro. The functional consequences of NDUFB3 knockdown and overexpression were assessed by measuring ATP levels, reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and apoptosis. The involvement of the JNK-mediated mitochondrial apoptotic pathway was also examined. Results: Proteomic analysis revealed a significant upregulation of NDUFA4 and NDUFB3 in the ischemic penumbra of MCAO mice, as verified by western blot. In highly differentiated PC12 cells, both OGD/R and glutamate exposure induced a time-dependent increase in these proteins in mitochondrial fractions. Functional studies demonstrated that NDUFB3 knockdown significantly rescued OGD/R-induced mitochondrial dysfunction, as indicated by restored ATP production, reduced ROS generation, and stabilized ΔΨm. Furthermore, NDUFB3 silencing attenuated apoptosis by inhibiting JNK phosphorylation and decreasing BAX levels. Conversely, overexpression of NDUFB3 alone was sufficient to induce mitochondrial abnormalities, including loss of ΔΨm and elevated oxidative stress in highly differentiated PC12 cells. Conclusions: Ischemic injury triggers the upregulation of mitochondrial complex subunits NDUFA4 and NDUFB3. While this may initially act as a compensatory response, our findings identify NDUFB3 as a critical mediator of ischemic stroke pathology, whose overexpression drives mitochondrial dysfunction and apoptosis. In contrast, the suppression of NDUFB3 provides protection against ischemic injury. Therefore, NDUFB3 may be a potential candidate therapeutic target for reducing mitochondrial damage in ischemic stroke, but this role requires further validation in additional experimental and translational models. Full article

Proton exchange membrane fuel cell–battery hybrid power systems provide an effective solution to overcome the limited endurance of battery-powered multirotor unmanned aerial vehicles. However, the highly transient power demands of quadcopter platforms, combined with balance-of-plant losses and operational constraints, create significant challenges for reliable energy management. This study proposes a degradation-aware stress-mitigation model predictive control-based energy management framework to maximize mission endurance under realistic conditions. A control-oriented, physics-consistent model is developed using manufacturer polarization data from a 500 W Aerostak proton exchange membrane fuel cell. The model captures polarization behavior, balance-of-plant loads, battery dynamics, and direct current-bus power balance. The model predictive control strategy optimally allocates power by maintaining direct current-bus stability, regulating battery state-of-charge within safe limits, and constraining fuel cell power ramp rates to mitigate degradation. High-fidelity simulations are conducted under stochastic wind disturbances and mission-dependent load profiles, including takeoff, climb, cruise, and maneuvering phases. The results show continuous power delivery without unmet load demand. The hybrid system achieves a flight endurance of 220–224 min, consuming a total of 89.99 g of hydrogen at an average rate of 0.398–0.412 g/min, indicating a notable reduction under the considered operating conditions. Additionally, long-term analysis indicates that over 97% of initial endurance is preserved after 100 cycles, demonstrating robustness against fuel cell aging. An analytical real-time feasibility assessment further indicates that the control-oriented formulation is compatible with the computational resources of typical unmanned aerial vehicle-class onboard processors, while the integration of adaptive and robust predictive control techniques is identified as a direction for future work. Full article

Open-cathode Proton Exchange Membrane Fuel Cells (PEMFCs) are a promising technology for increasing the endurance of small Unmanned Aerial Vehicles (UAVs), ground robots, e-bikes, and light electric vehicles. However, their performance under realistic operating conditions is strongly influenced by rapid variations in load, temperature, and ambient pressure, which are often neglected in design-oriented or quasi-steady-state analyses. This study experimentally investigates a 1 kW open-cathode PEMFC system, including its balance of plant and a passive supercapacitor buffer, under a representative UAV flight power profile. Steady-state and dynamic tests were conducted to assess polarization characteristics, thermal behavior, parasitic power consumption, and hydrogen utilization. Results revealed significant thermal inertia and hysteresis effects during load transients, causing voltage deviations from steady-state performance and stabilization times exceeding 90 s. The supercapacitor effectively reduced stack current ramp rates, although some high-frequency oscillations remained. Under flight-representative conditions, the system achieved stable operation with average voltaic efficiency ranging from 55.3% to 60.7% and net efficiency ranging from 50.2% to 54.2%. Auxiliary components had a measurable impact on overall performance: cooling fans accounted for 2–6% of stack power during steady operation and approximately 2.5% of total mission energy, while hydrogen purge losses can significantly reduce vehicle endurance. The findings demonstrate the importance of energy-based performance assessment, including auxiliary loads and purge losses, to obtain realistic estimates of efficiency and endurance in dynamic PEMFC-powered applications. Full article

Marine transportation and storage of liquid hydrogen (LH2) has gained increasing interest, while potential LH2 membrane-type tanks could utilize 316L corrugated austenitic stainless-steel sheets. The corrugation process results in a strain-induced martensitic transformation in the material, introducing rapid diffusion pathways for hydrogen atoms and promoting the formation of hydrogen-trapping sites that alter hydrogen transport and reduce the material’s resistance to hydrogen embrittlement. In this study, 316L sheets were subjected to different levels of uniaxial pre-strain (10, 20, 30, and 40%) with two different strain-rates, to replicate the varying degrees of pre-deformation caused by the corrugation. Microstructural analysis using Electron Backscatter Diffraction (EBSD) (Thermo Fisher Scientific, Waltham, MA, USA) and X-Ray Diffraction (XRD) (Bruker, Billerica, MA, USA) combined with quantitative phase analysis using the Rietveld Method on XRD data, provided valuable insights into the induced phase transformations. Cathodic hydrogen charging method was implemented on as-received and pre-strained material, followed by slow strain rate tensile testing (SSRT) and thermal desorption spectroscopy (TDS) to examine the hydrogen effect on each condition. Experimental results indicated that although 316L exhibits considerable phase stability, it undergoes strain-induced phase transformation resulting in a significant amount of martensite, reaching 5% in the 40% pre-strained condition. Pre-deformation increased hydrogen embrittlement, as evidenced by fractographic analysis which indicated a Relative Reduction of Area (RRA) of 0.83, and by increased hydrogen uptake. These findings contribute to a better understanding of phase transformations and the role of hydrogen in austenitic stainless steels. Full article

The aim of this study was to retrospectively compare modified Del Nido and blood-based St. Thomas cardioplegia in adult patients undergoing isolated aortic valve replacement (AVR). This retrospective study included adult patients undergoing isolated AVR because of aortic valve stenosis between 2024 and 2025. Patients were stratified into blood-based St. Thomas and modified Del Nido groups. The main modification of the Del Nido solution was the adjustment of the crystalloid-to-blood ratio to 1:4. Preoperative and perioperative variables, as well as postoperative biomarkers, including high-sensitivity troponin I, creatine kinase (CK), CK-MB, and lactate, were analyzed. A total of 93 patients were included in the study (blood-based St. Thomas: n = 22; modified Del Nido: n = 71). No significant differences were observed in cardiopulmonary bypass time [98 min (IQR 84–110) vs. 90 min (IQR 74–110); p = 0.184] or aortic cross-clamp time [75 min (IQR 67–86) vs. 73 min (IQR 62–87); p = 0.345]. High-sensitivity troponin I levels at 24 h were numerically, but not statistically significantly, lower in the blood-based St. Thomas group [1961 ng/L (IQR 1367–4423) vs. 2819 ng/L (IQR 1698–5054); p = 0.240]. CK levels at 6 h were comparable between the groups [8.4 μkat/L (IQR 6.5–10.1) vs. 8.5 μkat/L (IQR 6.0–12.7); p = 0.632], as were CK-MB and lactate levels at all evaluated time points. In exploratory multivariable analyses adjusted for age, sex, preoperative LVEF, cardiopulmonary bypass time, and aortic cross-clamp time, cardioplegia type was not independently associated with postoperative biomarker levels. The less frequent dosing and membrane-stabilizing properties of modified Del Nido cardioplegia did not translate into statistically significant clinical or biochemical advantages in the setting of relatively short, isolated AVR procedures. Full article

Polymer electrolyte membranes serving in proton exchange membrane fuel cells (PEMFCs) and direct methanol fuel cells (DMFCs) must possess sufficient mechanical–dimensional stability and excellent proton conducting capacity. Derived from the successful syntheses of two different sulfonated poly(aryl ether ketone)s bearing functional amine groups, two series of novel epoxy-crosslinked and silane-crosslinked sulfonated poly(aryl ether ketone) electrolyte networks are constructed for highly conductive and mechanically stable proton exchange membranes. The designed multi-component architecture, which integrates a moderate-ion-exchange-capacity sulfonated poly(aryl ether ketone) (moderate-IEC SPAEK), a high-IEC SPAEK, and a tailored crosslinker (epoxy or silane), enables a breakthrough in decoupling the traditional trade-off between conductivity and stability. The resulting membranes exhibit an outstanding combination of properties: exceptional proton conductivity exceeding 0.18 S cm⁻¹ at 100 °C, tensile strength above 28.80 MPa, and enhanced chemical resistance, thermo-oxidative stability, and competitive direct methanol fuel cell performance. This work establishes a rational design strategy for crosslinked multi-component membranes as a promising platform for next-generation high-performance fuel cells. Full article

Regulated cell death is essential for tissue homeostasis, immune defense, and disease progression, yet the lipid-based regulatory mechanisms that coordinate cell death signaling remain incompletely understood. Protein palmitoylation is a dynamic and reversible lipid post-translational modification that controls protein membrane association, trafficking, stability, and signaling complex assembly. This review summarizes the regulatory roles of palmitoylation and depalmitoylation in major forms of regulated cell death, including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-related cell death. Particular attention is given to representative palmitoylated substrates, including Fas cell surface death receptor (Fas), receptor-interacting protein kinase 1 (RIPK1), NLR family pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), autophagy-related 16 like 1 (ATG16L1), and Beclin1. These substrates illustrate how palmitoylation links membrane organization, metabolic status, inflammatory signaling, and cell fate decisions. Disease-oriented evidence further indicates that dysregulated palmitoylation contributes to cancer, neurodegenerative diseases, and inflammatory or immune-related disorders by modulating cell death resistance, inflammatory amplification, immune evasion, or impaired proteostasis. Current challenges include limited quantitative information on palmitoylation dynamics, incomplete evidence for some enzyme–substrate relationships, and insufficient distinction between disease-driving and secondary palmitoylation events. Targeting zinc finger Asp-His-His-Cys (zDHHC) palmitoyl acyltransferases, depalmitoylating enzymes, or specific palmitoylated substrates may provide new therapeutic opportunities. Overall, this review positions protein palmitoylation as a dynamic molecular switch linking lipid metabolism, membrane signaling, regulated cell death, and disease remodeling. Full article