Search Results (215)

Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) (PNIPAm), hydrophilic poly(ethylene glycol) (PEG) grafts, and a polycationic poly(L-lysine) (PLL) block of varying lengths ((PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)_z, z = 10–65)—were investigated. Plasmid DNA complexation with the copolymers was achieved through temperature-modulated methods. The resulting polyplexes were characterized by evaluating complex strength, particle size, zeta potential, plasmid DNA loading capacity, resistance to anionic stress, stability in serum, and lysosomal membrane destabilization assay. The copolymers’ potential for plasmid DNA delivery was assessed through cytotoxicity and transfection studies in cancer cell lines. Results. Across all complexation methods, the copolymers effectively condensed plasmid DNA into stable polyplexes. Particle sizes (60–90 nm) ranged with no apparent correlation to copolymer type, complexation method, or N/P ratio, whereas zeta potentials (+10–+20 mV) and resistance to polyanionic stress were dependent on the PLL length and N/P ratio. Cytotoxicity analysis revealed a direct correlation between PLL chain length and cell viability, with all copolymers demonstrating minimal cytotoxicity at concentrations required for efficient transfection. PNL-20 ((PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)₂₀) exhibited the highest transfection efficiency among the tested formulations while maintaining low cytotoxicity. Conclusions. The study highlights the promising potential of (PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)_z copolymers for effective plasmid DNA delivery to cancer cells. It reveals the importance of attaining the right balance between polyplex tightness and plasmid release to achieve improved biocompatibility and transfection efficiency. Full article

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article

Breeding programs often overlook the use of root traits. Therefore, we investigated the relevance of sorghum root traits in explaining its adaptation to combined drought and heat stress (CDHS). Six (i.e., three pre-release lines + three checks) sorghum genotypes were established at two low-altitude (i.e., <600 masl) locations with a long-term history of averagely very high temperatures in the beginning of the summer season, under two management (i.e., CDHS and well-watered (WW)) regimes. At each location, the genotypes were laid out in the field using a randomized complete block design (RCBD) replicated two times. Root trait data, namely root diameter (RD), number of roots (NR), number of root tips (NRT), total root length (TRL), root depth (RDP), root width (RW), width–depth ratio (WDR), root network area (RNA), root solidity (RS), lower root area (LRA), root perimeter (RP), root volume (RV), surface area (SA), root holes (RH) and root angle (RA) were gathered using the RhizoVision Explorer software during the pre- and post-flowering stage of growth. RSA traits differentially showed significant (p < 0.05) correlations with grain yield (GY) at pre- and post-flowering growth stages and under CDHS and WW conditions also revealing genotypic variation estimates exceeding 50% for all the traits. Regression models varied between pre-flowering (p = 0.013, R² = 47.15%, R² Predicted = 29.32%) and post-flowering (p = 0.000, R² = 85.64%, R² Predicted = 73.30%) growth stages, indicating post-flowering as the optimal stage to relate root traits to yield performance. RD contributed most to the regression model at post-flowering, explaining 51.79% of the 85.64% total variation. The Smith–Hazel index identified ICSV111IN and ASAREACA12-3-1 as superior pre-release lines, suitable for commercialization as new varieties. The study demonstrated that root traits (in particular, RD, RW, and RP) are linked to crop performance under CDHS conditions and should be incorporated in breeding programs. This approach may accelerate genetic gains not only in sorghum breeding programs, but for other crops, while offering a nature-based breeding strategy for stress adaptation in crops. Full article

Ectomycorrhizal symbiosis is a cornerstone of ecosystem health, facilitating nutrient uptake, stress tolerance, and biodiversity maintenance in trees. Optimizing Pinus armandii–Tuber indicum mycorrhizal synthesis enhances the ecological stability of coniferous forests while supporting high-value truffle cultivation. This study conducted a pot experiment to compare the effects of three root nutrient regulations—Aolu 318S (containing N-P₂O₅-K₂O in a ratio of 15-9-11 (w/w%)), Aolu 328S (11-11-18), and Youguduo (19-19-19)—on the mycorrhizal synthesis of P. armandii–T. indicum. The results showed that root nutrient supplementation significantly improved the seedling crown, plant height, ground diameter, biomass dry weight, and mycorrhizal infection rate of both the control and mycorrhizal seedlings, with the slow-release fertilizers Aolu 318S and 328S outperforming the quick-release fertilizer Youguduo. The suitable substrate composition in this experiment was as follows: pH 6.53–6.86, organic matter content 43.25–43.49 g/kg, alkali-hydrolyzable nitrogen 89.25–90.3 mg/kg, available phosphorus 83.69–87.32 mg/kg, available potassium 361.5–364.65 mg/kg, exchangeable magnesium 1.17–1.57 mg/kg, and available iron 33.06–37.3 mg/kg. It is recommended to mix the Aolu 318S and 328S solid fertilizers evenly into the substrate, with a recommended dosage of 2 g per plant. These results shed light on the pivotal role of a precise N-P-K ratio regulation in fostering sustainable ectomycorrhizal symbiosis, offering a novel paradigm for integrating nutrient management with mycorrhizal biotechnology to enhance forest restoration efficiency in arid ecosystems. Full article

Oxidative stress overwhelms cellular antioxidant defenses, causing DNA damage and pro-tumorigenic signaling that accelerate cancer initiation and progression. Electron shuttles (ESs) from phytocompounds offer precise redox control but lack quantitative benchmarks. This study aims to give a clearer definition to electron shuttles by characterizing mulberry’s electrochemical capabilities via the three defined ES criteria and deciphering its mechanism against oxidative stress-related cancer. Using double-chambered microbial-fuel-cell power metrics, cyclic voltammetry, and compartmental fermentation modeling, we show that anthocyanin shows a significant difference (p < 0.05) in power density at ≥500 µg/mL (maximum of 2.06-fold power-density increase) and reversible redox cycling (ratio = 1.65), retaining >90% activity over four fermentation cycles. Molecular docking implicates meta-dihydroxyl motifs within the core scaffold in receptor binding, overturning the view that only ortho- and para-substituents participate in bioactivity. In vitro, anthocyanins both inhibit nitric oxide release and reduce DU-145 cell viability dose-dependently. Overall, our findings establish mulberry anthocyanins as robust electron shuttles with potential for integration into large-scale bio-electrochemical platforms and targeted redox-based cancer therapies. Full article

Ocean acidification, caused by increased atmospheric CO₂, threatens marine organisms that depend on calcium-based structures such as jellyfish statoliths. This study investigated the effects of low pH on the morphology and statolith formation of ephyrae in Aurelia coerulea, comparing two developmental pathways to form ephyra: polyp-strobilation and planula-strobilation. Under the pH 6.8 condition, polyps failed to produce viable ephyrae, whereas planula-strobilation succeeded in releasing ephyrae with normal morphology, though statoliths were absent. Under the pH 7.8 condition, both strobilation types produced normal-shaped ephyrae with reduced statolith size but increased statolith number compared with the control (pH 8.1), suggesting a compensatory response to acidification. Statolith morphology differed between pathways: planula-strobilated ephyrae had needle-shaped statoliths with high aspect ratios, indicating a rapid, early-stage crystallization process. Despite their minimal body size and statolith development, planula-strobilated ephyrae maintained the functional mass of statoliths necessary for survival. This rapid, morphologically minimized development suggests that planula-strobilation is an adaptive reproductive strategy in response to environmental stress. Our findings suggest that A. coerulea possesses a flexible life history strategy that may facilitate its resilience to ongoing ocean acidification scenarios. Full article

Ferulic acid (FA) exhibits beneficial properties in ulcerative colitis (UC) pathogenesis, while sensitivity to the environment and enzymes limits its use in UC therapy. Therefore, this study aims to develop a colon-targeted nanocomplex delivery system using FA and investigate its protective effects and underlying regulatory mechanisms in UC mice. A novel Zein/FA–pectin (PEC)/chitosan (CS) nanocomplex was successfully fabricated in this study. Through systematic adjustment of the PEC/CS-to-Zein/FA ratio, optimal encapsulation efficiency (60.1%) and loading capacity (26.2%) were achieved. The characterized data indicated that hydrogen bonds, electrostatic interactions, and hydrophobic forces were the main driving forces maintaining the formation of the nanocomplexes, accompanied by alterations in the secondary structure of Zein. The Zein/FA–PEC/CS nanocomplexes demonstrated excellent thermal/storage particle size stability and exhibited both protective and sustained-release effects of FA during simulated gastrointestinal digestion. Furthermore, the results demonstrated that the nanocomplexes potentially alleviate UC by regulating inflammatory cytokines, oxidative stress, and gut microbiota. Compared to unencapsulated FA, the nanocomplexes have a better effect on alleviating UC symptoms. In summary, Zein/FA–PEC/CS nanocomplexes have promising prospects in alleviating colitis in UC mice. Full article

In response to the high cost and environmental impact of backfill materials in Xinjiang mines, an eco-friendly, large-volume composite was developed by bonding desert-sand mortar to waste concrete. A rock-filled concrete process produced a highly flowable mortar from desert sand, cement, and fly ash. Waste concrete blocks served as coarse aggregate. Specimens were cured for 28 days, then subjected to uniaxial compression tests on a mining rock-mechanics system using water-to-binder ratios of 0.30, 0.35, and 0.40 and aggregate sizes of 30–40 mm, 40–50 mm, and 50–60 mm. Mechanical performance—failure modes, stress–strain response, and related properties—was systematically evaluated. Crack propagation was tracked via digital image correlation (DIC) and acoustic emission (AE) techniques. Failure patterns indicated that the pure-mortar specimens exhibited classic brittle fractures with through-going cracks. Aggregate-containing specimens showed mixed-mode failure, with cracks flowing around aggregates and secondary branches forming non-through-going damage networks. Optimization identified a 0.30 water-to-binder ratio (Groups 3 and 6) as optimal, yielding an average strength of 25 MPa. Among the aggregate sizes, 40–50 mm (Group 7) performed best, with 22.58 MPa. The AE data revealed a three-stage evolution—linear-elastic, nonlinear crack growth, and critical failure—with signal density positively correlating to fracture energy. DIC maps showed unidirectional energy release in pure-mortar specimens, whereas aggregate-containing specimens displayed chaotic energy patterns. This confirms that aggregates alter stress fields at crack tips and redirect energy-dissipation paths, shifting failure from single-crack propagation to a multi-scale damage network. These results provide a theoretical basis and technical support for the resource-efficient use of mining waste and advance green backfill technology, thereby contributing to the sustainable development of mining operations. Full article

Background: Renal injury is a critical health issue in pet dogs, often exacerbated by drug-induced nephrotoxicity such as gentamicin (GM). This study investigated the protective effects of ergosterol (Erg), a natural compound from edible mushrooms, against GM-induced damage in Madin–Darby canine kidney (MDCK) cells. Methods: MDCK cells were treated with GM (0.5–3 mmol/L) for 12 h to establish injury. Erg (1 to 32 μg/mL) was pretreated for 12 h before GM exposure (2 mmol/L). Cell viability, nitric oxide (NO), lactate dehydrogenase (LDH), oxidative stress markers (SOD, GSH, CAT, MDA), inflammatory cytokines (IL-1β, IL-6, TNF-α), renal function indicators (Scr, BUN), and autophagy/apoptosis-related proteins (ATG5, Beclin1, P62, BAX, BCL-2) were assessed via CCK-8, ELISA, fluorescence staining, and Western blot. Statistical significance (p < 0.05) was determined by ANOVA and LSD post hoc tests. Results: GM (2 mmol/L) significantly reduced cell viability (p < 0.01) and elevated NO and LDH levels (p < 0.01). Erg pretreatment (4–8 μg/mL) restored cell viability (p < 0.01), suppressed NO (p < 0.01) and LDH release (p < 0.01), and enhanced antioxidant enzyme activities (SOD, GSH, CAT; p < 0.01). Erg attenuated GM-induced reactive oxygen species (ROS) overproduction (p < 0.01) and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α; p < 0.01). Renal markers Scr and BUN were reduced (p < 0.01). Mechanistically, Erg upregulated autophagy proteins ATG5 and Beclin1 (p < 0.01), reduced P62 accumulation (p < 0.01), and lowered the BAX/BCL-2 ratio (p < 0.01). Conclusions: Erg protects MDCK cells from GM-induced nephrotoxicity by restoring autophagy flux, suppressing mitochondrial apoptosis, and mitigating oxidative stress and inflammation. These findings highlight Erg’s potential as a natural therapeutic agent for canine renal injury. Further in vivo studies are needed to validate its clinical efficacy. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder defined clinically by progressive cognitive decline and memory impairment and pathologically by the accumulation of amyloid-beta plaques, tau neurofibrillary tangles, neuroinflammation, and immune system dysregulation. Peripheral biomarkers are gaining attention as valuable tools for elucidating neuroinflammatory mechanisms in the AD continuum, with potential implications for diagnosis and prognosis. Among these, the neutrophil-to-lymphocyte ratio (NLR) has emerged as a promising systemic inflammatory marker. NLR, a readily available and cost-effective parameter derived from routine blood tests, reflects the balance between innate and adaptive immune responses. Elevated NLR has been associated with AD and mild cognitive impairment (MCI), showing correlations with disease severity, amyloid burden, and neuroinflammation. Increased neutrophil counts may contribute to neurodegeneration through oxidative stress and pro-inflammatory cytokine release, while decreased lymphocyte levels suggest impaired adaptive immunity. However, despite growing evidence, the clinical utility of NLR in AD remains debated due to heterogeneity in study populations and confounding factors, such as comorbidities and medication effects. This review provides a comprehensive analysis of the association between NLR and AD throughout the disease continuum. Future research should prioritize longitudinal studies and integrative approaches that combine NLR with other inflammatory and neurodegenerative markers to enhance early diagnosis and personalized therapeutic strategies. Full article

Rainfall-induced landslide mitigation remains a critical research focus in geotechnical engineering, particularly for safeguarding buildings and infrastructure in unstable terrain. This study investigates the stabilizing performance of slopes reinforced with negative Poisson’s ratio (NPR) anchor cables under rainfall conditions through physical model tests. A scaled geological model of a heavily weathered rock slope is constructed using similarity-based materials, building a comprehensive experimental setup that integrates an artificial rainfall simulation system, a model-scale NPR anchor cable reinforcement system, and a multi-parameter data monitoring system. Real-time measurements of NPR anchor cable axial forces and slope internal stresses were obtained during simulated rainfall events. The experimental results reveal distinct response times and force distributions between upper and lower NPR anchor cables in reaction to rainfall-induced slope deformation, reflecting the temporal and spatial evolution of the slope’s internal sliding surface—including its generation, expansion, and full penetration. Monitoring data on volumetric water content, earth pressure, and pore water pressure within the slope further elucidate the evolution of effective stress in the rock–soil mass under saturation. Comparative analysis of NPR cable forces and effective stress trends demonstrates that NPR anchor cables provide adaptive stress compensation, dynamically counteracting internal stress redistribution in the slope. In addition, the structural characteristics of NPR anchor cables can effectively absorb the energy released by landslides, mitigating large deformations that could endanger adjacent buildings. These findings highlight the potential of NPR anchor cables as an innovative reinforcement strategy for rainfall-triggered landslide prevention, offering practical solutions for slope stabilization near buildings and enhancing the resilience of building-related infrastructure. Full article

Titanium (Ti) and its alloys have attracted more interest, as they are widely employed as biomaterials due to their great biocompatibility, excellent strength ratio, and lightweight. However, corrosion occurs slowly due to an electrochemical reaction once the Ti material has been placed in the human body, contributing to infection and failure of implants in medical applications. Thus, the corrosion phenomenon has caused great concern in the biomedical field. It is desirable to make the surface modification to provide better corrosion resistance. The fabrication techniques of the coatings fabricated onto Ti and/or Ti alloy surfaces have been reported, including sol–gel, annealing, plasma spraying, plasma immersion ion implantation, physical vapor deposition, chemical vapor deposition, anodization, and micro-arc oxidation. This review first describes the corrosion types, including localized corrosion (both pitting and crevice corrosion), galvanic corrosion, selective leaching, stress corrosion cracking (SCC), corrosion fatigue (CF), and fretting corrosion. In the second part, the effects of corrosion on the human body were discussed, and the primary cause for clinical failure and allergies has been identified as the excessive release of poisonous and dangerous metal ions (Co, Ni, and Ti) from corroded implants into bodily fluids. The inclusion and exclusion criteria during the selection of literature are described in the third section. In the last section, we emphasized the current research progress of Ti alloy (particularly Ti6Al4V alloy) coatings in biomaterials for medical applications involving dental, orthopedic, and cardiovascular implants for anticorrosive applications. However, there are also several problems to explore and address in future studies, such as the release of excessive metal ions, etc. This review will draw attention to both researchers and clinicians, which could help to increase the coatings fabricated onto Ti and/or Ti alloy surfaces for anticorrosive applications in biomaterials for medical applications. Full article

On 23 January 2024, a M_S7.1 earthquake struck Wushi County, Xinjiang Uygur Autonomous Region, marking the largest seismic event in the Southern Tianshan (STS) region in the past century. This study investigates the relationship between hydrothermal fluid circulation and seismic activity by analyzing the chemical composition and origin of fluids in natural hot springs along the Maidan Fracture (MDF). Results reveal two distinct hydrochemical water types (Ca-HCO₃ and Ca-Mg-Cl). The δD and δ¹⁸O values indicating spring water are influenced by atmospheric precipitation input and altitude. Circulation depths (621–3492 m) and thermal reservoir temperatures (18–90 °C) were estimated. Notably, the high ³He/⁴He ratios (3.71 Ra) and mantle-derived ³He content reached 46.48%, confirming that complex gas–water–rock interactions occur at fracture intersections. Continuous monitoring at site S13 (144 km from the epicenter of the Wushi M_S7.1 earthquake) captured pre-and post-seismic hydrogeochemical fingerprints linked to the Wushi MS7.1 earthquake. Stress accumulation along the MDF induced permeability changes, perturbing hydrogeochemical equilibrium. At 42 days pre-Wushi M_S7.1 earthquake, δ¹³C DIC exceeded +2σ thresholds (−2.12‰), signaling deep fracture expansion and CO₂ release. By 38 days pre-Wushi M_S7.1 earthquake, Na⁺, SO₄²⁻, and δ¹⁸O surpassed 2σ levels, reflecting hydraulic connection between deep-seated and shallow fracture networks. Ion concentrations and isotope values showed dynamic shifts during the earthquake, which revealed episodic stress transfer along fault asperities. Post-Wushi M_S7.1 earthquake, fracture closure reduced deep fluid input, causing δ¹³C DIC to drop to −4.89‰, with ion concentrations returning to baseline within 34 days. Trace elements such as Be and Sr exhibited anomalies 12 days before the Wushi M_S7.1 earthquake, while elements like Li, B, and Rb showed anomalies 24 days after the Wushi M_S7.1 earthquake. Hydrochemical monitoring of hot springs captures such critical stress-induced signals, offering vital insights for earthquake forecasting in tectonically active regions. Full article

Background: Oxidative stress is a key therapeutic target in neurological disorders. As processing wastes from the peanut industry, peanut skins are great sources of antioxidants and possess potential in neuroprotection. Methods: We prepared a peanut skin extract (PSE) and investigated its protective effects against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in HT-22 neuronal cells. Results: PSE was rich in phenolic compounds (123.90 ± 0.46 mg GAE/g), comprising flavonoids (75.97 ± 0.23 mg RE/g) and proanthocyanidins (53.34 ± 1.58 mg PE/g), and displayed potent radical scavenging activities in chemical-based assays. In HT-22 cells, PSE pretreatment restored oxidative balance and endogenous antioxidant defense disrupted by t-BHP, as evidenced by significant reductions in ROS generation and lipid peroxidation levels, along with enhanced endogenous antioxidants. Specifically, 25 μg/mL PSE pretreatment reduced ROS levels by 53.03%, decreased MDA content by 78.82%, enhanced superoxide dismutase (SOD) activity by 12.42%, and improved the ratio of glutathione (GSH) to oxidized glutathione (GSSG) by 80.34% compared to the t-BHP group. Furthermore, PSE rescued mitochondrial membrane potential collapse, inhibited cytochrome c (Cyt.c) release, and prevented subsequent apoptotic death. Notably, the neuroprotective efficacy of PSE was comparable to that of edaravone, an approved neuroprotective drug. Mechanistic investigations combining network pharmacology and experimental validation revealed that the PI3K/Akt/Nrf2 signaling pathway played a pivotal role in mediating the neuroprotective effects of PSE. Compared to t-BHP-treated cells, 25 µg/mL PSE pretreatment significantly upregulated PI3K/Akt phosphorylation, the expression of Nrf2, and its downstream antioxidant proteins heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1). Conclusions: Collectively, these findings demonstrate the potential of PSE as a natural protective agent against oxidative-related neurological disorders. Full article

The internal force state in concrete components is a crucial factor in evaluating the safety performance of existing buildings, bridges, and other concrete structures, while theoretical and numerical analysis of an ideal model may not accurately capture the actual internal forces within concrete components. This study introduces the basic principles of stress release technology for identifying internal forces in existing reinforced concrete components and provides a detailed derivation of normal and shear strains of component sections under each internal force component. It demonstrates that the internal forces of reinforced concrete sections can be accurately identified by testing the strain on the midpoint of three surface sides. A finite element model is established to investigate the relationship between groove depth and groove side length when normal or shear stress is released to zero, as well as the impact of reinforcement ratio on the stress release level. Experimental research is conducted using the grooving method to identify internal forces in reinforced concrete components under different external loads. The test results exhibit strong agreement with numerical simulation results. Additionally, the identification errors for axial forces and bending moments are within 10%, underscoring the feasibility of measuring internal forces in existing reinforced concrete components through the stress release method. Full article