Search Results (216)

The HIV-1 aspartic protease is an effective target for the treatment of HIV/AIDS. Current therapy utilizes a selection of nine protease inhibitors (PIs) in combination with other classes of antiretroviral drugs. Although PIs were originally developed based on the knowledge of the HIV-1 subtype B protease, the existence of other HIV-1 subtypes and the effects of drug resistance on currently available PIs have become a major challenge in the treatment of HIV/AIDS. Specifically, the HIV-1 subtype C accounts for more than half of the global HIV infections. Considering the importance and relevance of the subtype C virus, in this timely review we discuss the effect of polymorphisms in the HIV-1 subtype C protease on drug resistance, flap flexibility, and hinge region dynamics. We discuss novel paradigms of protease inhibition that attempt to overcome the limitations of currently available inhibitors which fall short considering genetic diversity and resistance mutations. Full article

Ultra-high-performance concrete (UHPC) jackets present a promising solution for enhancing the seismic resilience of seismically deficient reinforced concrete (RC) bridge columns. This study investigates jacket thickness optimization through integrated experimental and numerical analyses. Quasi-static cyclic tests on a control column and a specimen retrofitted with a 30-mm UHPC jacket over the plastic hinge region demonstrated significant performance improvements: delayed damage initiation, controlled cracking, a 24.6% increase in lateral load capacity, 139.5% higher energy dissipation at 3% drift, and mitigated post-peak strength degradation. A validated OpenSees numerical model accurately replicated this behavior and enabled parametric studies of 15-mm, 30-mm, and 45-mm jackets. Results identified the 30-mm thickness as optimal, balancing substantial gains in lateral strength (~12% higher than other thicknesses), ductility, and energy dissipation while avoiding premature failure modes—insufficient confinement in the 15-mm jacket and strain incompatibility-induced brittle failure in the 45-mm jacket. These findings provide quantitative design guidance, establishing 30 mm as the recommended thickness for efficient seismic retrofitting of existing RC bridge columns. Full article

The Southern Lhasa Terrane, as the southernmost tectonic unit of the Eurasian continent, has long been a focal area in global geoscientific research due to its complex evolutionary history. The Yeba Formation exposed in this terrane comprises an Early–Middle Jurassic volcanic–sedimentary sequence that records multiphase tectonic deformation. This study applies structural analysis to identify three distinct phases of tectonic deformation in the Yeba Formation of the Southern Lhasa Terrane. The D₁ deformation is characterized by brittle–ductile shearing, as evidenced by the development of E-W-trending regional shear foliation (S₁). S₁ planes dip northward at angles of 27–87°, accompanied by steeply plunging stretching lineations (85–105°). Both south- and north-directed shear-rotated porphyroclasts are observed in the hanging wall. ⁴⁰Ar-³⁹Ar dating results suggest that the D₁ deformation occurred at ~79 Ma and may represent an extrusion-related structure formed under a back-arc compressional regime induced by the low-angle subduction of the Neo-Tethys Ocean plate. The D₂ deformation is marked by the folding of the pre-existing shear foliation (S₁), generating an axial planar cleavage (S₂). S₂ planes dip north or south with angles of 40–70° and fold hinges plunge westward or NWW. Based on regional tectonic evolution, it is inferred that the deformation may have resulted from sustained north–south compressional stress during the Late Cretaceous (79–70 Ma), which caused the overall upward extrusion of the southern Gangdese back-arc basin, leading to upper crustal shortening and thickening and subsequently initiating folding. The D₃ deformation is dominated by E-W-striking ductile shear zones. The regional shear foliation (S₃) exhibits a preferred orientation of 347°∠75°. Outcrop-scale ductile deformation indicators reveal a top-to-the-NW shear sense. Combined with regional tectonic evolution, the third-phase (D3) deformation is interpreted as a combined product of the transition from compression to lateral extension within the Lhasa terrane, associated with the activation of the Gangdese Central Thrust (GCT) and the uplift of the Gangdese batholith since ~25 Ma. Full article

The tensile strength of loess, a key mechanical parameter for crack-related failures, has not received much attention in previous research, with the literature demonstrating a lack of systematic studies. Therefore, in this study, the variations in the tensile strength, crack distribution, crack number, and internal stress of an undisturbed loess were studied in detail by combining the unconfined penetration test (UPT) and a discrete element method (DEM)-based simulation. The tensile strengths of undisturbed loess samples with different height–diameter ratios (1, 1.5, and 2) were investigated by using the UPT with loading plates of different diameters (12.86 mm, 15.56 mm, and 19.02 mm). DEM simulation was then conducted based on the experimental results. The results showed that (1) the tensile strength of undisturbed loess decreased with increased height–diameter ratio, while it increased with an increase in the diameters of the loading plates; (2) the DEM simulation allowed us to study the tensile characteristics of the undisturbed loess, and the simulated tensile strengths obtained via DEM simulation agreed with those determined via the UPT; (3) the distribution of internal stress and crack number in the DEM model were significantly influenced by the height–diameter ratio and loading plate diameter; (4) the number of cracks in the DEM model increased with an increase in the diameter of the loading plate, while the number of cracks first increased and then decreased with an increase in the height–diameter ratio. This study helps us to understand the variation in the tensile strengths of undisturbed loess samples from both macroscopic and microscopic perspectives. It is expected to serve as a reference for design, construction, and maintenance in engineering projects hinging upon the Loess Plateau region in China. Full article

The global climate crisis necessitates the urgent implementation of sustainable practices and carbon emission reduction strategies across all sectors. Transport, as a major contributor to greenhouse gas emissions, requires transitional technologies to bridge the gap between fossil fuel dependency and renewable energy systems. Natural gas, recognised as the cleanest fossil-derived fuel with approximately half the CO₂ emissions of coal and 75% of oil, presents a potential transitional solution through Natural Gas Vehicles (NGVs). This manuscript presents several distinctive contributions that advance the understanding of Natural Gas Vehicles within the contemporary energy transition landscape while synthesising updated emission performance data. Specifically, the feasibility and sustainability of NGVs are investigated within the energy transition framework by systematically incorporating recent technological developments and environmental, economic, and infrastructure considerations in comparison to conventional vehicles (diesel and petrol) and unconventional alternatives (electric and hydrogen-fuelled). The analysis reveals that NGVs can reduce CO₂ emissions by approximately 25% compared to petrol vehicles on a well-to-wheel basis, with significant reductions in NO_x and particulate matter. However, these environmental benefits depend heavily on the source and type of natural gas used (CNG or LNG), while economic viability hinges largely on governmental policies and infrastructure development. The findings suggest that NGVs can serve as an effective transitional technology in the transport sector’s sustainability pathway, particularly in regions with established natural gas infrastructure, but require supportive policy frameworks to overcome implementation barriers. Full article

The efficacy of water resource management and protection hinges on a profound understanding of the controlling factors and regulatory mechanisms that shape groundwater chemistry within aquifers. Despite this, our comprehension of how groundwater chemistry and ion sources vary across diverse aquifer types remained limited. To bridge this gap, our study conducted a detailed hydrochemical and statistical investigation of porous, fissured, and karst aquifers. By applying multivariate statistical techniques, including principal component analysis (PCA) and hierarchical cluster analysis (HCA), the hydrochemical characteristics and main ion sources of each aquifer type, as well as distinct controlling factors and regulation patterns, were determined. Notably, evaporation predominantly affected the hydrochemistry of porous aquifers, whereas mineral dissolution and rock weathering processes played a pivotal role in shaping the groundwater evolution of fissured and karst aquifers. HCO₃⁻ and SO₄²⁻ are the most common anions of all types, while Na⁺ is dominant in porous and fissured aquifers and Ca²⁺ is dominant in karst aquifers. The most common hydrochemical types identified were HCO₃-Ca·Mg (accounting for approximately 56.84%) and SO₄·Cl-Na (constituting approximately 21.75%). PCA results revealed that lateral recharge from fissured aquifers in hilly regions into the groundwater of porous aquifer, and wastewater discharge and agricultural fertilizer application, significantly impact the groundwater chemistry across all three aquifer types. It is worth noting that the dissolution of carbonate minerals, often influenced by human activities, had a profound effect on the hydrochemistry of each aquifer. Conversely, the dissolution of evaporitic minerals affected groundwater chemistry primarily through cation exchange processes. In summary, the hydrochemical characteristics of these aquifer types were predominantly shaped by a complex interplay of mineral dissolution, cation exchange, evaporation, and anthropogenic activities, with notable contributions from fissured aquifer recharge and pollution. These insights were critical for informing national-level strategies for groundwater resource protection and management. Full article

The transition to a sustainable energy future hinges on the development of reliable large-scale hydrogen storage solutions to balance the intermittency of renewable energy and decarbonize hard-to-abate industries. Underground hydrogen storage (UHS) in salt caverns emerged as a technically and economically viable strategy, leveraging the unique geomechanical properties of salt formations—including low permeability, self-healing capabilities, and chemical inertness—to ensure safe and high-purity hydrogen storage under cyclic loading conditions. This review provides a comprehensive analysis of the advantages of salt cavern hydrogen storage, such as rapid injection and extraction capabilities, cost-effectiveness compared to other storage methods (e.g., hydrogen storage in depleted oil and gas reservoirs, aquifers, and aboveground tanks), and minimal environmental impact. It also addresses critical challenges, including hydrogen embrittlement, microbial activity, and regulatory fragmentation. Through global case studies, best operational practices for risk mitigation in real-world applications are highlighted, such as adaptive solution mining techniques and microbial monitoring. Focusing on China’s regional potential, this study evaluates the hydrogen storage feasibility of stratified salt areas such as Jiangsu Jintan, Hubei Yunying, and Henan Pingdingshan. By integrating technological innovation, policy coordination, and cross-sector collaboration, salt cavern hydrogen storage is poised to play a pivotal role in realizing a resilient hydrogen economy, bridging the gap between renewable energy production and industrial decarbonization. Full article

The accurate identification and protection of the lingual nerve during oral surgery are critical to avoid complications such as a loss of taste or sensation and chronic pain. While numerous studies have described the nerve’s anatomy and injury outcomes, no consensus exists on the optimal method to trace its full course. This narrative review systematically examined the literature from 2010 to 2024, using databases like PubMed, MEDLINE, Embase, and Google Scholar. Keywords included “Lingual nerve,” “Course,” “Anatomy,” and “Clinical implications,” combined with Boolean operators. Studies were selected based on defined criteria, and findings were synthesized to highlight key challenges in diagnosing the nerve’s path. This review identifies difficulties at multiple anatomical sites: the foramen ovale, infratemporal fossa, pterygomandibular space, third molar and retromolar regions, premolar/molar areas, floor of the mouth, and anterior gingiva and tongue. Lingual nerve injury, especially during lower third molar surgeries, remains a major concern, often exacerbated by factors like patient age, unerupted teeth, and lingual surgical approaches. Effective prevention hinges on precise anatomical knowledge and meticulous surgical technique. Microsurgical repair remains the primary treatment but often yields unpredictable outcomes. Emerging regenerative therapies show early promise but require further clinical validation. Imaging tools such as magnetic resonance imaging (MRI) and ultrasound may enhance diagnostic accuracy and surgical planning; however, each has limitations in everyday practice. Ultimately, early identification, careful surgical handling, and appropriate imaging support are vital for improving patient outcomes and minimizing the risks of lingual nerve injury. Full article

The connection zones between precast concrete composite slabs and composite walls commonly experience severe reinforcement conflicts due to protruding rebars, significantly reducing construction efficiency. To address this, a novel slotted concrete composite slab–composite shear wall (SCS-CW) connection without protruding rebars is proposed in this study. In this novel connection, rectangular slots are introduced at the ends of the precast slabs, and lap-spliced reinforcement is placed within the slots to enable force transfer across the joint region. To investigate the static performance of SCS-CW connections, four groups of connection specimens were designed and fabricated. Using the structural detailing of the connection zone as the variable parameter, the mechanical performance of each specimen group was analyzed. The results show that the specimens demonstrated bending failure behavior. The key failure modes were yielding of the longitudinal reinforcement in the post-cast layer, yielding of the lap-spliced reinforcement, and concrete crushing at the precast slab ends within the plastic hinge zone. Compared to composite slab–composite wall connections with protruding rebars, the SCS-CW connections demonstrated superior ductility and a higher load-carrying capacity, satisfying the design requirements. Additionally, it was revealed that the anchorage length of lap-spliced reinforcement significantly affected the ultimate load-carrying capacity and ductility of SCS-CW connections, thus highlighting anchorage length as a critical design parameter for these connections. This study also presents methods for calculating the flexural bearing capacity and flexural stiffness of SCS-CW connections. Finally, finite element modeling was conducted on the connections to further investigate the influences of the lap-spliced reinforcement quantity, diameter, and anchorage length on the mechanical performance of the connections, and corresponding design recommendations are provided. Full article

Global digitalization drives policy-led transformation in the construction industry, yet its effectiveness hinges on localized implementation. However, research on China’s regional digital policies remains insufficient, particularly in systematic evaluation mechanisms. Focusing on Wuhan, this study proposes a progressive “3M” (macro–meso–micro) policy evaluation framework to analyze local policy efficacy under national strategies. Macro-level PESTEL analysis identifies weak legal frameworks as a critical gap. Meso-level PMC index modeling establishes a hierarchical optimization pathway prioritizing incentive measures, followed by policy timeliness, assessment mechanisms, policy focus, and policy nature. Micro-level Spearman’s correlation analysis further pinpoints five implementation drivers: pilot projects, long-term planning, detailed measures, talent cultivation, and regulatory reinforcement. The results indicate that Wuhan’s policies require targeted improvements: (1) synergizing pilot innovation with legal safeguards, (2) integrating green principles into long-term planning, (3) refining technical standards and policy alignment, (4) enhancing multidisciplinary talent development through industry–academia collaboration, and (5) establishing IoT-enabled dynamic monitoring platforms. This hierarchical evaluation system provides empirical evidence for optimizing China’s construction policies while offering a transferable governance framework for global cities navigating digital transitions. Future research should extend the temporal and spatial coverage while incorporating adaptive evaluation tools to address policy dynamism. Full article

Steel slag aggregate (SSA), as a high-performance and sustainable material, has demonstrated significant potential in enhancing the mechanical properties of concrete and improving the bond behavior between reinforcement and the concrete matrix, thereby contributing to the seismic resilience of steel slag concrete columns (SSCCs). Nevertheless, the underlying mechanism through which SSA influences the seismic performance of SSCCs remains insufficiently understood, and current analytical models fail to accurately capture the effects of bond strength on structural behavior. In this study, a comprehensive experimental program comprising central pull-out tests and quasi-static cyclic loading tests was conducted to investigate the influence of SSA on bond strength and the seismic response of SSCCs. Key seismic performance indicators, including the hysteresis curve, equivalent viscous damping ratio, and ductility coefficient, were evaluated. The role of bond strength in governing energy dissipation and ductility characteristics was elucidated in detail. The results indicate that bond strength significantly affects the seismic performance of SSCC components. At an SSA replacement ratio of 40%, the specimens show optimal performance: energy dissipation capacity increases by 11.3%, bond–slip deformation in the plastic hinge region decreases by 10%, and flexural deformation capacity improves by 9% compared to the control group. However, when the SSA replacement exceeds 60%, the performance metrics are similar to those of ordinary concrete, showing no significant advantages. Based on the experimental findings, a modified bond–slip constitutive model for the steel slag concrete–reinforcement interface is proposed. Furthermore, a finite element model incorporating bond–slip effects is developed, and its numerical predictions exhibit strong agreement with the experimental results, effectively capturing the lateral load-carrying capacity and stiffness degradation behavior of SSCCs. Full article

The accuracy of weather forecasting hinges crucially on the availability of comprehensive historical weather data. In remote regions face the challenge of sparse data collection, impacting the accuracy of meteorological predictions. This study delves into the data scarcity issue and its repercussions on weather forecasting in these regions. By evaluating the Meteorological Data Supply Portal of the India Meteorological Department and various climatic classifications, this paper gain insights into the present state of weather data accessibility and identify the regions with substantial gaps. This study investigates the extent to which Machine Learning Techniques can compensate for these deficiencies. By leveraging advanced machine learning and deep learning techniques on available data from well-documented regions, this paper propose a framework for generating reliable weather forecasts for remote territories. This paper not only highlights the current landscape of meteorological data availability in remote areas but also examines the potential of ML to democratize weather forecasting, thereby enabling better-preparedness for adverse weather conditions in these underserved regions. The hypothesis of this paper contends that with sufficient training on diverse datasets, ML can provide a significant predictive advantage, serving as a testament to the ingenuity of modern computational methods in confronting real-world challenges. Here, the deep learning model achieves a notable accuracy of 83%, showcasing a substantial improvement over traditional rule-based system. The integration of ML not only enhanced predictive accuracy but also demonstrated a nuanced understanding of complex weather dynamics through data-driven insights. Full article

The transforming growth factor-β (TGF-β) signaling pathway is involved in various cellular functions, including immunological response, extracellular matrix formation, differentiation, growth and development, and cell cycle regulation. The TGF β receptor type 1 (TGF-βR1) has emerged as a key component of this pathway, exhibiting significant overexpression in diverse malignancies, including hepatocellular carcinoma, gastric cancer, breast cancer, and colon cancer. Multiple therapeutic targets have been identified for the TGF-β signaling pathway, encompassing antibodies, ligand traps, vaccines, antisense oligonucleotides, and small-molecule TGF-βR1 kinase inhibitors. This review delineates the structural and functional characteristics of the small-molecule TGF-βR1 kinase inhibitors. The inhibitors discussed herein are categorized based on shared pharmacophoric features, notably a five-membered heterocyclic ring linked to three distinct features (R1, R2, and R3). These features interact with amino acids within the selectivity pocket, hinge region, or solvent-exposed area, respectively. These insights contribute to a clearer understanding of the structural requirements for selective TGF-βR1 inhibition. The presented findings in this review article offer a valuable foundation for future drug discovery efforts targeting the TGF-β signaling pathway. Full article

Insect flight mechanisms are highly efficient and involve complex hinge structures that facilitate amplified wing movement through thoracic deformation. However, in the field of flapping-wing robots, the replication of thoracic skeletal structures has received little attention. In this study, we propose and compare two different hinge models inspired by insect flight: an elastic hinge model (EHM) and an axle hinge model (AHM). Both models were fabricated using 3D printing technology using PLA material. The EHM incorporates flexible structures in both the hinge and lateral scutum regions, allowing for deformation-driven wing motion. In contrast, the AHM employs metal pins in the hinge region to reproduce joint-like articulation, while still permitting elastic deformation in the lateral scutum. To evaluate their performance, we employed an SMA actuator to generate flapping motion, and measured the wing displacement, flapping frequency, and exoskeletal deformation. The experimental results demonstrate that the EHM achieves wing flapping through overall structural flexibility, whereas the AHM provides more defined hinge motion while maintaining exoskeletal elasticity. These findings contribute to our understanding of the role of hinge mechanics in bioinspired flapping-wing robots. Future research will focus on optimizing these mechanisms for higher frequency operation, weight reduction, and better energy efficiency. Full article

Molecular imaging probes play a pivotal role in assaying molecular events in various physiological systems. In this study, we demonstrate a new genre of bioluminescent probes for imaging protein–protein interactions (PPIs) in mammalian cells, named the molecular association assay (MAA) probe. The MAA probe is designed to be as simple as a full-length marine luciferase fused to a protein of interest with a flexible linker. This simple fusion protein alone surprisingly works by recognizing a specific ligand, interacting with a counterpart protein of the PPI, and developing bioluminescence (BL) in mammalian cells. We made use of an artificial intelligence (AI) tool to simulate the binding modes and working mechanisms. Our AlphaFold-based analysis on the binding mode suggests that the hinge region of the MAA probe is flexible before ligand binding but becomes stiff after ligand binding and protein association. The sensorial properties of representative MAA probes, FRB-ALuc23 and FRB-R86SG, are characterized with respect to the quantitative feature, BL spectrum, and in vivo tumor imaging using xenografted mice. Our AI-based simulation of the working mechanisms reveals that the association of MAA probes with the other proteins works in a way to facilitate the substrate’s access to the active sites of the luciferase (ALuc23 or R86SG). We prove that the concept of MAA is generally applicable to other examples, such as the ALuc16- or R86SG-fused estrogen receptor ligand-binding domain (ER LBD). Considering the versatility of this conceptionally unique and distinctive molecular imaging probe compared to conventional ones, we are expecting the widespread application of these probes as a new imaging repertoire to determine PPIs in living organisms. Full article