Search Results (750)

Palindromic antimicrobial peptides (PAMs) constitute versatile scaffolds for the design and optimization of anticancer agents with applications in therapy, diagnosis, and/or monitoring. In the present study, fluorolabeled peptides derived from the palindromic sequence RWQWRWQWR containing fluorescent probes, such as 2-Aminobenzoyl, 5(6)-Carboxyfluorescein, and Rhodamine B, were obtained. RP-HPLC analysis revealed that the palindromic peptide conjugated to Rhodamine B (RhB-RWQWRWQWR) exhibited the presence of isomers, likely corresponding to the open-ring and spiro-lactam forms of the fluorescent probe. This equilibrium is dependent on the peptide sequence, as the RP-HPLC analysis of dimeric peptide (RhB-RRWQWR-hF-KKLG)₂K-Ahx did not reveal the presence of isomers. The antibacterial activity of the fluorescent peptides depends on the probe attached to the sequence and the bacterial strain tested. Notably, some fluorescent peptides showed activity against reference strains as well as sensitive, resistant, and multidrug-resistant clinical isolates of E. coli, S. aureus, and E. faecalis. Fluorolabeled peptides 1-Abz (MIC = 62 µM), RhB-1 (MIC = 62 µM), and Abz-1 (MIC = 31 µM) exhibited significant activity against clinical isolates of E. coli, S. aureus, and E. faecalis, respectively. The RhB-1 (IC₅₀ = 61 µM), Abz-1 (IC₅₀ = 87 µM), and RhB-2 (IC₅₀ = 35 µM) peptides exhibited a rapid, significant, and concentration-dependent cytotoxic effect on HeLa cells, accompanied by morphological changes characteristic of apoptosis. RhB-1 (IC₅₀ = 18 µM) peptide also exhibited significant cytotoxic activity against breast cancer cells MCF-7. These conjugates remain valuable for elucidating the possible mechanisms of action of these novel anticancer peptides. Rhodamine-labeled peptides displayed cytotoxicity comparable to that of their unlabeled analogues, suggesting that cellular internalization constitutes a critical early step in their mechanism of action. These findings suggest that cell death induced by both unlabeled and fluorolabeled peptides proceeds predominantly via apoptosis and is likely contingent upon peptide internalization. Functionalization at the N-terminal end of the palindromic sequence can be evaluated to develop systems for transporting non-protein molecules into cancer cells. Full article

The formation and evolution of haze layers in planetary atmospheres play a critical role in shaping their chemical composition, radiative balance, and optical properties. In the outer solar system, the atmospheres of Titan and the giant planets exhibit a wide range of compositional and seasonal variability, creating environments favorable for the production of complex organic molecules under low-temperature conditions. Among them, Uranus—the smallest of the ice giants—has, since Voyager 2, emerged as a compelling target for future exploration due to unanswered questions regarding the composition and structure of its atmosphere, as well as its ring system and diverse icy moon population (which includes four possible ocean worlds). Titan, as the only moon to harbor a dense atmosphere, presents some of the most complex and unique organics found in the solar system. Central to the production of these organics are chemical processes driven by low-energy photons and electrons (<50 eV), which initiate reaction pathways leading to the formation of organic species and gas phase precursors to high-molecular-weight compounds, including aerosols. These aerosols, in turn, remain susceptible to further processing by low-energy UV radiation as they are transported from the upper atmosphere to the lower stratosphere and troposphere where condensation occurs. In this review, I aim to summarize the current understanding of low-energy (<50 eV) photon- and electron-induced chemistry, drawing on decades of insights from studies of Titan, with the objective of evaluating the relevance and extent of these processes on Uranus in anticipation of future observational and in situ exploration. Full article

Boda boda motorbike taxis are a primary mode of transport in Nairobi, Kenya, and a major source of urban air pollution. This study investigates the environmental and electrical grid impacts of electrifying Nairobi’s boda boda fleet. Using real-world tracking data from 118 motorbikes, we simulated the effects of a full-scale transition from internal combustion engine (ICE) vehicles to electric motorbikes. We analysed various scenarios, including different battery charging strategies (swapping and home charging), motor efficiencies, battery capacities, charging rates, and the potential for solar power offsetting. The results indicate that electrification could reduce daily ${\mathrm{CO}}_2$ emissions by approximately 85% and eliminate tailpipe particulate matter emissions. However, transitioning the entire country’s fleet would increase the national daily energy demand by up to 6.85 GWh and could introduce peak grid loads as high as 2.40 GW, depending on the charging approach and vehicle efficiency. Battery swapping was found to distribute the grid load more evenly and better complement solar power integration compared to home charging, which concentrates demand in the evening. This research provides a scalable, data-driven framework for policymakers to assess the impacts of transport electrification in similar urban contexts, highlighting the critical trade-offs between environmental benefits and grid infrastructure requirements. Full article

Ice accumulation on exposed surfaces presents substantial economic and safety challenges across various industries. To overcome limitations associated with traditional anti-icing methods, such as the use of nanoparticles, this study introduces a novel and facile approach for fabricating superhydrophobic and anti-icing microstructures using cost-effective LCD 3D printing technology. The influence of diverse pillar geometries, including square, cylindrical, hexagonal, and truncated conical forms, was analyzed to assess their effects on the hydrophobic and anti-icing/icephobic performance in terms of wettability, ice adhesion strength, and icing delay time. The role of microstructure topography was further investigated through cylindrical patterns with varying geometric parameters to identify optimal designs for enhancing hydrophobic and icephobic characteristics. Furthermore, the effectiveness of surface functionalization using a low surface energy material was evaluated. Our findings demonstrate that the synergistic combination of tailored microscale geometries and surface functionalization significantly enhances anti-icing performance with reliable repeatability, achieving ice adhesion of 13.9 and 17.9 kPa for square and cylindrical pillars, respectively. Critically, this nanoparticle-free 3D printing and low surface energy treatment method offers a scalable and efficient route for producing high-performance hydrophobic/icephobic surfaces, opening promising avenues for applications in sectors where robust anti-icing capabilities are crucial, such as renewable energy and transportation. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

This review provides the recent advancements in nonlinear sea ice modeling for hydroelastic analysis of ice-covered channels and their interaction with floating structures. It surveys theoretical, experimental, and numerical methodologies used to analyze complex coupled sea ice–structure interactions. The paper discusses governing fluid domain solutions, fluid–ice interaction mechanisms, and ice–structure (ship) contact models, alongside experimental techniques and various numerical models. While significant progress has been made, particularly with coupled approaches validated by experimental data, challenges remain in full-scale validation and accurately representing ice properties and dynamic interactions. Findings highlight the increasing importance of understanding sea ice interactions, particularly in the context of climate change, Arctic transportation, and the development of very large floating structures. This review serves as a crucial resource for advancing safe and sustainable Arctic and offshore engineering. Full article

The presence of sea ice threatens low ice-class vessels’ navigation safety in the Arctic, and traditional Navigation Risk Assessment Models based on sea ice parameters have been widely used to guide safe passages for ships operating in ice regions. However, these models mainly rely on empirical coefficients, and the accuracy of these models in identifying sea ice navigation risk remains insufficiently validated. Therefore, under the binary classification framework, this study used Automatic Identification System (AIS) data along the Northeast Passage (NEP) as positive samples, manual interpretation non-navigable data as negative samples, a total of 10 machine learning (ML) models were employed to capture the complex relationships between ice conditions and navigation risk for Polar Class (PC) 6 and Open Water (OW) vessels. The results showed that compared to traditional Navigation Risk Assessment Models, most of the 10 ML models exhibited significantly improved classification accuracy, which was especially pronounced when classifying samples of PC6 vessel. This study also revealed that the navigability of the East Siberian Sea (ESS) and the Vilkitsky Strait along the NEP is relatively poor, particularly during the month when sea ice melts and reforms, requiring special attention. The navigation risk output by ML models is strongly determined by sea ice thickness. These findings offer valuable insights for enhancing the safety and efficiency of Arctic maritime transport. Full article

The cryopreservation of three-dimensional (3D) biofabricated constructs is a key enabler for their clinical application in regenerative medicine. Unlike two-dimensional (2D) cultures, 3D systems such as encapsulated cell spheroids, molded hydrogels, and bioprinted tissues present specific challenges related to cryoprotectant (CPA) diffusion, thermal gradients, and ice formation during freezing and thawing. This review examines the current strategies for preserving 3D constructs, focusing on the role of biomaterials as cryoprotective matrices. Natural polymers (e.g., hyaluronic acid, alginate, chitosan), protein-based scaffolds (e.g., silk fibroin, sericin), and synthetic polymers (e.g., polyethylene glycol (PEG), polyvinyl alcohol (PVA)) are evaluated for their ability to support cell viability, structural integrity, and CPA transport. Special attention is given to cryoprotectant systems that are free of dimethyl sulfoxide (DMSO), and to the influence of hydrogel architecture on freezing outcomes. We have compared the efficacy and limitations of slow freezing and vitrification protocols and review innovative approaches such as temperature-controlled cryoprinting, nano-warming, and hybrid scaffolds with improved cryocompatibility. Additionally, we address the regulatory and manufacturing challenges associated with developing Good Manufacturing Practice (GMP)-compliant cryopreservation workflows. Overall, this review provides an integrated perspective on material-based strategies for 3D cryopreservation and identifies future directions to enable the long-term storage and clinical translation of engineered tissues. Full article

Ambient PM concentrations are influenced by various emission sources and weather conditions such as temperature, wind speed, and direction. Measurements using optical sensors cannot directly link pollution levels to specific sources. Data from roadside monitoring often show that a significant portion of PM originates from non-traffic sources. Therefore, vehicle-related PM emissions are typically estimated using simulation models based on average emission factors. This study uses the COPERT (Computer Programme to Calculate Emissions from Road Transport) model to estimate emissions from road vehicles under current conditions and future scenarios. These include the introduction of Euro 7 standards and a shift from internal combustion engine (ICE) vehicles to battery electric vehicles (BEVs). The analysis considers exhaust and non-exhaust emissions, as well as indirect emissions from electricity generation for BEV charging. The conducted study showed, among other findings, that replacing internal combustion engine vehicles with electric ones could reduce PM2.5 emissions by approximately 6% (2% when including indirect emissions from electricity generation) and PM10 emissions by about 10% (5% with indirect emissions), compared to the Euro 7 scenario. Full article

Fossil fuels, including coal, are a basis of energy systems in many countries worldwide. However, coal mining is associated with several difficulties, which include high temperatures within the coal mining area. It causes a need for cooling for safety reasons and also for the comfort of miners’ work. Typical cooling systems in mines are based on central systems, in which chilled water is generated in the compressor or absorption coolers on the ground and transported via pipelines to the air coolers in the areas of mining. The progressive mining operation causes a gradual increase in the distance between chilled water generators and air coolers, causing a decrease in the efficiency of the entire system and insufficient cooling capacity. As a result, it is necessary to increase the diameter of the chilled water pipelines and increase the cooling capacity of the chillers, which is associated with additional investment and technical problems. One solution to this problem may be the use of so-called ice slurry instead of chilled water in the existing mine cooling system. This article presents the cooling system, located in the mine LW Bogdanka S.A., based on ice slurry. The structure of the system and its key parameters are presented. The results show that switching from cooling water to ice slurry allowed the cooling capacity of the entire system to increase by 50% while maintaining the existing piping. This demonstrates the very high potential for the use of ice slurry, not only in mines, but wherever further increases in piping diameters to maintain the required cooling capacity are not possible or cost-effective. Full article

Electric vehicles (EVs) have been the most dependable and feasible choice for decarbonizing road transport over the last decade. To ensure the advancement of EVs and establish them as a sustainable alternative to internal combustion engine (ICE) vehicles, the EV sector and technological growth have largely relied on government subsidies. A significant challenge for EVs is their faster depreciation compared to ICE vehicles, primarily owing to swift technological advancements that propel the market while simultaneously rendering older EV models outdated too soon. Another factor that leads to the quicker depreciation of EVs is subsidies. The anticipated cessation of subsidies is expected to provide the required leverage to mitigate the rapid value decline in EVs, given the larger price disparity between new and used EVs. Batteries, which enable EVs to be a viable option, significantly contribute to the depreciation of EVs. In addition to the potential decline in EV battery performance, advancements in technology and reduced prices provide newer models with improved range at a more affordable cost. The used EV market accurately represents the rapid devaluation of EVs; consequently, the two topics are tightly related. Though it might not be immediately apparent, it seems evident that the pace of depreciation of EVs significantly contributes to the small size of the second-hand EV market. Depreciation is a key factor influencing the used EV market. This manuscript outlines the key aspects of depreciation and sustainability in the EV transition, especially those linked to rapid technological advancements, such as batteries, in addition to subsidies and the used EV market. The objective of this manuscript is to expose and analyze the relation between the drivers of the second-hand EV market, such as the cost of ownership, technology, and subsidies, and, on the other hand, present the interplay perspectives and challenges. Full article

Meiyu is a critical component of the summer rainy season over the Yangtze–Huaihe River Basin (YHRB) in China, and the Meiyu onset date (MOD), serving as a key indicator of Meiyu, has garnered substantial attention. This article demonstrates an in-phase relationship between MOD and the preceding spring Barents–Kara Seas ice concentration (BKSIC) during 1979–2023. Specifically, the loss of spring BKSIC promotes an earlier MOD. Further analysis indicates that decreased spring BKSIC reduces the reflection of shortwave radiation, thereby enhancing oceanic solar radiation absorption and warming sea surface temperature (SST) in spring. The warming SST persists into summer and induces significant deep warming in the BKS through enhanced upward longwave radiation. The BKS deep warming triggers a wave train propagating southeastward to the East Asia–Northwest Pacific region, leading to a strengthened East Asian Subtropical Jet and an intensified Western North Pacific Subtropical High in summer. Under these conditions, the transport of warm and humid airflows into the YHRB is enhanced, promoting convective instability through increased low-level warming and humidity, combined with enhanced wind shear, which jointly contribute to an earlier MOD. These results may advance the understanding of MOD variability and provide valuable information for disaster prevention and mitigation. Full article

Understanding the mechanical behavior of frozen clay subgrade soils was essential for ensuring the safe and stable operation of transportation lines. However, the influence of remolding water content w on this behavior remained unclear. To address this gap, this study examined the effect of w through monotonic triaxial testing. Three typical remolding water contents (w = 19%, 27.5% and 35%) and three confining pressures (σ₃ = 200 kPa, 700 kPa and 1200 kPa) were considered. Results showed that the mechanical behavior of frozen clay soils displayed a clear dependence on w, which was controlled by microstructural evolution. As w increased, the shear strength q_max, resilient modulus E₀ and cohesion c increased, which resulted from the progressive development of ice bonding within the shear plane. A threshold w value was found at w_opt = 27.5%, marking a structural transition and separating the variations of q_max, E₀ and c into two regimes. When w ≤ 27.5%, the soil fabric was controlled by clay aggregates. As w increased, the growth in ice cementation was confined within these aggregates, leading to limited increase in q_max, E₀ and c. However, as w exceeded 27.5%, the soil fabric transitioned into a homogeneous matrix of dispersed clay particles. In this case, increasing w greatly promoted the development of an interconnected ice cementation network, thus significantly facilitating the increase in q_max, E₀ and c. The friction angle φ decreased with w increasing, primarily due to the lubrication effect caused by the growing ice. In addition, the enhanced lubrication effect in the clay particle-dominated fabric (w > 27.5%) resulted in a larger reduction rate of φ. Regarding Poisson’s ratio v and dilation angle ψ, the w increase led to growth in both parameters. This phenomenon could be explained by the increased involvement of solid ice into the soil structure. Full article

The transportation sector in South Asia largely depends on internal combustion engine (ICE) vehicles, which are responsible for a large share of greenhouse gas (GHG) emissions, air pollution, and the increase in fuel prices. Although hybrid electric vehicles (HEVs), plug-in hybrid electric vehicles (PHEVs), and fully electric vehicles (EVs) constitute promising alternatives, the rate of their implementation is low due to factors such as the high initial investment, the absence of the required infrastructure, and the reliance on fossil fuel-based electricity. This study is the first of its kind to examine Bangladesh’s drivetrain options in a comprehensive way, with in-depth real-world emission testing and economic analysis as the main tools of investigation into the environmental and economic feasibility of different technologies used in the vehicles available in Bangladesh, including lifecycle costs and infrastructure constraints. The study findings have shown that hybrid and plug-in hybrid vehicles are the best options, since they have moderate emissions and cost efficiency, respectively. Fully electric vehicles, however, face two main challenges: the overall lack of charging infrastructure and the overall high purchase prices. Among the evaluated technologies, PHEVs exhibited the lowest environmental and economic burden. The Toyota Prius PHEV emitted 98% less NOx compared to the diesel-powered Pajero Sport and maintained the lowest per-kilometer cost at BDT 6.39. In contrast, diesel SUVs emitted 178 ppm NOx and cost 22.62 BDT/km, reinforcing the transitional advantage of plug-in hybrid technology in Bangladesh’s context. Full article

Anthracyclines have been clinically well established in cancer chemotherapy for decades. The main limitations of this drug class are the development of resistance and severe side effects. In the present investigation, we analyzed 30 anthracyclines in a panel of 59 cell lines of the National Cancer Institute, USA. The log₁₀IC₅₀ values varied from −10.49 M (3′-deamino-3′-(4″-(3″-cyano)morpholinyl)-doxorubicin, 1) to −4.93 M (N,N-dibenzyldaunorubicin hydrochloride, 30). Multidrug-resistant NCI-ADR-Res ovarian cancer cells revealed a high degree of resistance to established anthracyclines (between 18-fold to idarubicin (4) and 166-fold to doxorubicin (13) compared to parental, drug-sensitive OVCAR8 cells). The resistant cells displayed only low degrees of resistance (1- to 5-fold) to four other anthracyclines (7, 18, 28, 30) and were even hypersensitive (collaterally sensitive) to two compounds (1, 26). Live cell time-lapse microscopy proved the cross-resistance of the three chosen anthracyclines (4, 7, 9) on sensitive CCRF/CEM and multidrug-resistant CEM/ADR5000 cells. Structure–activity relationships showed that the presence of tertiary amino functions is helpful in avoiding resistance, while primary amines rather increased resistance development. An α-aminonitrile function as in compound 1 was favorable. Investigating the mRNA expression of 49 ATP-binding cassette (ABC) transporter genes showed that ABCB1/MDR1 encoding P-glycoprotein was the most important one for acquired and inherent resistance to anthracyclines. Molecular docking demonstrated that all anthracyclines bound to the same binding domain at the inner efflux channel side of P-glycoprotein with high binding affinities. Kaplan–Meier statistics of RNA sequencing data of more than 8000 tumor biopsies of TCGA database revealed that out of 23 tumor entities high ABCB1 expression was significantly correlated with worse survival times for acute myeloid leukemia, multiple myeloma, and hepatocellular carcinoma patients. This indicates that ABCB1 may serve as a prognostic marker in anthracycline-based chemotherapy regimens in these tumor types and a target for the development of novel anthracycline derivatives. Full article