Search Results (2,051)

Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. Full article

Multi-objective evolutionary algorithms (MOEAs) have emerged as powerful optimization tools for addressing the complex, often conflicting goals present in modern waste disposal systems. This review explores recent advances and practical applications of MOEAs in key areas, including waste collection routing, waste-to-energy (WTE) systems, and facility location and allocation. Real-world case studies from cities like Braga, Lisbon, Uppsala, and Cyprus demonstrate how MOEAs can enhance operational efficiency, boost energy recovery, and reduce environmental impacts. While these algorithms offer significant advantages, challenges remain in computational complexity, adapting to dynamic environments, and integrating with emerging technologies. Future research directions highlight the potential of combining MOEAs with machine learning and real-time data to create more flexible and responsive waste management strategies. By leveraging these advancements, MOEAs can play a pivotal role in developing sustainable, efficient, and adaptive waste disposal systems capable of meeting the growing demands of urbanization and stricter environmental regulations. Full article

Karst groundwater systems are critical to water supply and ecological sustainability in northern China, yet their heterogeneity poses challenges for flow characterization. The Yuquan Mountain (YM) Spring, historically a major karst spring in western Beijing, has experienced persistent drying, raising concerns about its recharge and flow mechanisms. This study integrates published isotope data, spatial distributions of Na⁺ and Cl⁻ as hydrochemical tracers, groundwater age estimates, and geophysical survey results to assess the recharge sources and flow pathways within the YM Spring catchment area. The analysis identifies two major recharge zones: the Tanzhesi area, primarily recharged by direct infiltration of precipitation through exposed carbonate rocks, and the Junzhuang area, which receives mixed recharge from rainfall and Yongding River seepage. Three potential flow pathways are proposed, including shallow flow along faults and strata, and a deeper, speculative route through the Jiulongshan-Xiangyu syncline. The synthesis of multiple lines of evidence leads to a refined conceptual model that illustrates how geological structures govern recharge, flow, and discharge processes in this karst system. These findings not only enhance the understanding of subsurface hydrodynamics in complex geological settings but also provide a scientific basis for future spring restoration planning and groundwater management strategies in the regions. Full article

Opportunistic Networks (OppNets) lack the capability to maintain consistent end-to-end paths between source and destination nodes, unlike Mobile Ad Hoc Networks (MANETs). This absence of stable routing presents substantial challenges for data transmission in OppNets. Due to node mobility, routing paths are inherently dynamic, requiring the selection of neighboring nodes as intermediate hops to forward data toward the destination. However, frequent node movement can cause considerable delays for senders attempting to identify appropriate next hops, consequently degrading the quality of service (QoS) in OppNets. To mitigate this challenge, this paper proposes an alternative approach for scenarios where senders cannot locate suitable next hops. Specifically, we propose utilizing direct communication via line of sight (LoS) between sender and receiver nodes to satisfy QoS requirements. The proposed scheme is experimented with using the ONE simulator, which is widely used for OppNet experiments and study, and compared against existing schemes such as the history-based routing protocol (HBRP) and AEProphet routing protocol. Full article

As a new generation of mobile communication networks, 6G security faces many new security challenges. Vehicle to Everything (V2X) will be an important part of 6G. In V2X, connected and automated vehicles (CAVs) need to frequently share data with other vehicles and infrastructures. Therefore, identity revocation technology in the authentication is an important way to secure CAVs and other 6G scenario applications. This paper proposes an efficient credential revocation scheme with a four-layer architecture. First, a rapid pre-filtration layer is constructed based on the cuckoo filter, responsible for the initial screening of credentials. Secondly, a directed routing layer and the precision judgement layer are designed based on the consistency hash and the dynamic RSA accumulator. By proposing the dynamic expansion of the RSA accumulator and load-balancing algorithm, a smaller and more stable revocation delay can be achieved when many users and terminal devices access 6G. Finally, a trusted storage layer is built based on the blockchain, and the key revocation parameters are uploaded to the blockchain to achieve a tamper-proof revocation mechanism and trusted data traceability. Based on this architecture, this paper also proposes a detailed identity credential revocation and verification process. Compared to existing solutions, this paper’s solution has a combined average improvement of 59.14% in the performance of the latency of the cancellation of the inspection, and the system has excellent load balancing, with a standard deviation of only 11.62, and the maximum deviation is controlled within the range of ±4%. Full article

The global elimination of hepatitis C virus (HCV) has been prioritized by the World Health Organization (WHO) as a key public health target, with a deadline set for 2030. This initiative aims to significantly reduce both new infection rates and HCV-associated mortality. A major breakthrough in achieving this goal has been the development of direct-acting antiviral agents (DAAs), which offer cure rates exceeding 95%, along with excellent safety and tolerability. Nevertheless, transmission via parenteral routes continues to be the dominant pathway, particularly among high-risk groups, such as individuals who inject drugs, incarcerated populations, those exposed to unsafe medical practices, and healthcare professionals. Identifying, monitoring, and delivering tailored interventions to these groups is crucial to interrupt ongoing transmission and to reduce the burden of chronic liver disease. On a global scale, several nations have demonstrated measurable progress toward HCV elimination, with some nearing the targets set by WHO. These achievements have largely resulted from context-adapted policies that enhanced diagnostic and therapeutic access while emphasizing outreach to vulnerable communities. This review synthesizes current advancements in HCV prevention and control and proposes strategic frameworks to expedite global elimination efforts. Full article

This review surveys recent advances and emerging prospects in phase-transfer catalysis (PTC) for fuel desulfurization. In response to increasingly stringent environmental regulations, the removal of sulfur from transportation fuels has become imperative for curbing SO_x emissions. Conventional hydrodesulfurization (HDS) operates under severe temperature–pressure conditions and displays limited efficacy toward sterically hindered thiophenic compounds, motivating the exploration of non-hydrogen routes such as oxidative desulfurization (ODS). Within ODS, PTC offers distinctive benefits by shuttling reactants across immiscible phases, thereby enhancing reaction rates and selectivity. In particular, PTC enables efficient migration of organosulfur substrates from the hydrocarbon matrix into an aqueous phase where they are oxidized and subsequently extracted. The review first summarizes the deployment of classic PTC systems—quaternary ammonium salts, crown ethers, and related agents—in ODS operations and then delineates the underlying phase-transfer mechanisms, encompassing reaction-controlled, thermally triggered, photo-responsive, and pH-sensitive cycles. Attention is next directed to a new generation of catalysts, including quaternary-ammonium polyoxometalates, imidazolium-substituted polyoxometalates, and ionic-liquid-based hybrids. Their tailored architectures, catalytic performance, and mechanistic attributes are analyzed comprehensively. By incorporating multifunctional supports or rational structural modifications, these systems deliver superior desulfurization efficiency, product selectivity, and recyclability. Despite such progress, commercial deployment is hindered by the following outstanding issues: long-term catalyst durability, continuous-flow reactor design, and full life-cycle cost optimization. Future research should, therefore, focus on elucidating structure–performance relationships, translating batch protocols into robust continuous processes, and performing rigorous environmental and techno-economic assessments to accelerate the industrial adoption of PTC-enabled desulfurization. Full article

This paper proposes a multi-hop peer-to-peer (P2P) video streaming architecture designed to support dynamic, conversation-aware communication. The primary contribution is a decentralized system built on WebRTC that eliminates reliance on a central media server by employing super node aggregation. In this architecture, video streams from multiple peer nodes are dynamically routed through a group of super nodes, enabling real-time reconfiguration of the network topology in response to conversational changes. To support this dynamic behavior, the system leverages WebRTC data channels for control signaling and overlay restructuring, allowing efficient dissemination of topology updates and coordination messages among peers. A key focus of this study is the rapid and efficient reallocation of network resources immediately following conversational events, ensuring that the streaming overlay remains aligned with ongoing interaction patterns. While the automatic detection of such events is beyond the scope of this work, we assume that external triggers are available to initiate topology updates. To validate the effectiveness of the proposed system, we construct a simulation environment using Docker containers and evaluate its streaming performance under dynamic network conditions. The results demonstrate the system’s applicability to adaptive, naturalistic communication scenarios. Finally, we discuss future directions, including the seamless integration of external trigger sources and enhanced support for flexible, context-sensitive interaction frameworks. Full article

Avian influenza viruses (AIVs) pose significant risks to occupational populations engaged in poultry farming, livestock handling, and live poultry market operations due to frequent exposure to infected animals and contaminated environments. This review synthesizes evidence on AIV exposure patterns and risk factors through a comprehensive analysis of viral characteristics, host dynamics, environmental influences, and human behaviors. The main routes of transmission include direct animal contact, respiratory contact during slaughter/milking, and environmental contamination (aerosols, raw milk, shared equipment). Risks increase as the virus adapts between species, survives longer in cold/wet conditions, and spreads through wild bird migration (long-distance transmission) and live bird trade (local transmission). Recommended control measures include integrated animal–human–environment surveillance, stringent biosecurity measures, vaccination, and education. These findings underscore the urgent need for global ‘One Health’ collaboration to assess risk and implement preventive measures against potentially pandemic strains of influenza A viruses, especially in light of undetected mild/asymptomatic cases and incomplete knowledge of viral evolution. Full article

The shikimate pathway is the fundamental metabolic route for aromatic amino acid biosynthesis in bacteria, plants, and fungi, but is absent in mammals. This review explores how multi-enzyme synergy and allosteric regulation coordinate metabolic flux through this pathway by focusing on three key enzymes: 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase, chorismate mutase, and tryptophan synthase. We examine the structural diversity and distribution of these enzymes across evolutionary domains, highlighting conserved catalytic mechanisms alongside species-specific regulatory adaptations. The review covers directed evolution strategies that have transformed naturally regulated enzymes into standalone biocatalysts with enhanced activity and expanded substrate scope, enabling synthesis of non-canonical amino acids and complex organic molecules. Industrial applications demonstrate the pathway’s potential for sustainable production of pharmaceuticals, polymer precursors, and specialty chemicals through engineered microbial platforms. Additionally, we discuss the therapeutic potential of inhibitors targeting pathogenic organisms, particularly their mechanisms of action and antimicrobial efficacy. This comprehensive review establishes the shikimate pathway as a paradigmatic system where understanding allosteric networks enables the rational design of biocatalytic platforms, providing blueprints for biotechnological innovation and demonstrating how evolutionary constraints can be overcome through protein engineering to create superior industrial biocatalysts. Full article

The agents of prion diseases have the capacity to efficiently infect susceptible hosts by peripheral routes and to project to clinical target areas of the central nervous system (CNS) via peripheral nerves. Understanding the process of prion spread from the site of infection to the CNS may allow us to identify novel therapeutic strategies. To investigate the mechanism involved in the intranerval transit of 263K scrapie prions in golden Syrian hamsters (GSHs), we transected the sciatic nerve at increasing times post-footpad injection and recorded the incubation periods as estimates of the efficiency of infection. We calculated that intranerval transit of this strain of scrapie is at least 10 times faster than previously reported and may reach 50 mm/day, similar to other neurotropic viruses. By in vivo exposure/injection of sciatic nerves to 263K infectivity, we have also shown that prion entry likely occurs via nerve terminals rather than by direct contact with the sciatic nerve. Application of this experimental approach in other forms of prion diseases could allow verification of the timing of neuroinvasion, a relevant parameter for the definition of therapeutic interventions. Full article

Canine morbillivirus (CDV), the cause of canine distemper, is a pathogen affecting many hosts. While modified live virus (MLV) vaccines are crucial for controlling the disease in dogs, cases of vaccine-related infections have been found in both domestic and wild animals. Specifically, the America-1 and Rockborn-like vaccine genotypes are concerning due to their spread and ability to transmit between different species. This study conducted a review and analysis of molecular detections of these strains in various carnivores (domestic, captive, synanthropic, and wild species). This study used a conceptual model considering host ecology and the domestic–wild interface to evaluate plausible transmission connections over time using Linear Directional Mean (LDM) and Weighted Mean Centre (WMC) methods. Statistical analyses examined the relationship between how likely a strain is to spread and factors like host type and vaccination status. The findings showed that the America-1 genotype spread in a more organised way, with domestic dogs being the main source and recipient, bridging different environments. Synanthropic mesocarnivores also played this same role, with less intensity. America-1 was most concentrated in the North Atlantic and Western Europe. In contrast, the Rockborn-like strain showed a more unpredictable and restricted spread, residual circulation from past use rather than ongoing spread. Species involved in vaccine-related infections often share characteristics like generalist behaviour, social living, and a preference for areas where domestic animals and wildlife interact. We did not find a general link between a host vaccination status and the likelihood of the strain spreading. The study emphasised the ongoing risk of vaccine-derived strains moving from domestic and synanthropic animals to vulnerable wild species, supporting the need for improved vaccination approaches. Mapping these plausible transmission routes can serve as a basis for targeted surveillance, not only of vaccine-derived strains, but of any other circulating genotype. Full article

The article describes a simple and scalable preparation of 2-monothiacalix[4]arene 7, the simplest representative of the mixed-bridged (CH₂ and S) calix[4]arenes. The synthesis is based on the condensation of linear building blocks (bisphenols), which are relatively readily available, and allows, depending on the conditions, the use of two alternative reaction routes that provide macrocycle 7 in high yield. The dynamic behavior of the basic macrocyclic skeleton was investigated using NMR spectroscopy at variable temperatures. High-temperature measurements showed that compound 7 undergoes a cone–cone equilibrium with activation free energy ΔG^# of the inversion process of 63 kJ·mol⁻¹. Interestingly, the same barrier for the oxidized sulfone derivative 14 shows a value of 60 kJ·mol⁻¹, indicating weakened hydrogen bonds at the lower rim of the calixarene. The same was also confirmed at low temperatures, when barriers to changing the direction of the cyclic hydrogen bond arrays (flip-flop mechanism) were determined (compare ΔG^# = 44 kJ·mol⁻¹ for 7 vs. ΔG^# = 40 kJ·mol⁻¹ for 14). Full article

Ethanol upgrading via catalytic C–C coupling, commonly known as the Guerbet reaction, offers a sustainable route to produce 1-butanol, a high-performance biofuel. To address gaps in the mechanistic understanding of the catalytic reaction, we investigated the process involving a fixed-bed reactor, operated at 275–325 °C, 21 bar, and weight hourly space velocities of 0.25–2.5 g_EtOH/(g_cat·h), using helium as a carrier gas, with a 5:1 He/EtOH molar ratio. The catalyst was a MgO–Al₂O₃ mixed oxide (Mg/Al = 2:1), derived from a hydrotalcite precursor. A detailed kinetic model was developed, encompassing 15 species and 27 reversible steps (10 sorption and 17 reaction steps), within a 1+1D sorption–reaction–transport framework. Four C₄-forming pathways were included: aldol condensation to form crotonaldehyde, semi-direct coupling to form butyraldehyde and crotyl alcohol, and direct coupling to form 1-butanol. To avoid overfitting, Arrhenius parameters were grouped by reaction type, resulting in sixty rate parameters and one active site-specific density parameter. The optimized model achieved high accuracy, with an average prediction error of 1.44 times the experimental standard deviation. The mechanistic analysis revealed aldol condensation as the dominant pathway below 335 °C, with semi-direct coupling to crotyl alcohol prevailing above 340 °C. The resulting model provides a robust framework for understanding and predicting complex reaction networks in ethanol upgrading systems. Full article

The hydrological response of a watershed is strongly influenced by the spatiotemporal dynamics of rainfall. Rainfall events of similar magnitude can produce markedly different flood processes due to variations in the spatiotemporal patterns of rainfall, posing significant challenges for flood forecasting under complex rainfall scenarios. Traditional methods typically rely on high-resolution or synthetic rainfall data to characterize the scale, direction and velocity of rainstorms, in order to analyze their impact on the flood process. These studies have shown that storms traveling along the main river channel tend to exert the greatest impact on flood processes. Therefore, tracking the movement of the rainfall center along the flow direction, especially when only rain gauge data are available, can reduce model complexity while maintaining forecast accuracy and improving model applicability. This study proposes a machine learning-based time-variable instantaneous unit hydrograph that integrates rainfall spatiotemporal dynamics using quantitative spatial indicators. To overcome limitations of traditional variable unit hydrograph methods, a pre-training and fine-tuning strategy is employed to link the unit hydrograph S-curve with rainfall spatial distribution. First, synthetic pre-training data were used to enable the machine learning model to learn the shape of the S-curve and its general pattern of variation with rainfall spatial distribution. Then, real flood data were employed to learn the actual runoff routing characteristics of the study area. The improved model allows the unit hydrograph to adapt dynamically to rainfall evolution during the flood event, effectively capturing hydrological responses under varying spatiotemporal patterns. The case study shows that the improved model exhibits superior performance across all runoff routing metrics under spatiotemporal rainfall variability. The improved model increased the simulation qualified rate for historical flood events, with significant rainfall center movement during the event from 63% to 90%. This study deepens the understanding of how rainfall dynamics influence watershed response and enhances hourly-scale flood forecasting, providing support for disaster early warning with strong theoretical and practical significance. Full article