ABSTRACT The study analysed methods for reducing anthropogenic pressure on the environment through modular construction technology. It used data analysis, environmental performance assessment, and examination of practical applications. The findings showed that modular construction reduces construction waste, energy consumption, carbon emissions, and project duration compared with traditional methods. Shorter construction periods also lower noise, dust, traffic, and disruption to local communities and ecosystems. Factory-based module production improves labour conditions by reducing physical strain and occupational risks, while increasing demand for skilled and technologically competent workers. It also decreases emissions from construction equipment and transport and supports more efficient logistics. The use of energy-efficient and environmentally friendly materials helps reduce building heat loss, while automated production improves compliance with design standards and limits rework. Overall, modular construction demonstrates environmental and economic advantages, confirming its potential to reduce anthropogenic load, improve resource efficiency, and support sustainable development without compromising construction quality.

Against the background of the restructuring of the global energy landscape, intensified geopolitical conflicts and accelerated low-carbon transformation, the Arctic is becoming a key region for international energy cooperation. The purpose of this work is to identify sustainable mechanisms of international cooperation in large-scale Arctic projects using Yamal LNG and Arctic LNG 2 as examples. The materials and methods include analysis of open operational data (2017–2025), ownership structure, investment volumes, production capacities, export flows, technical solutions, as well as comparative and systemic approaches. The results show that Yamal LNG implemented an effective Russia–China–Europe trilateral cooperation model, with a 76% share of European exports in 2025. In turn, Arctic LNG 2, under the influence of sanctions, accelerated its reorientation to the Eastern market (about 90% of exports to Asia) and the Eastern supply chain. It is established that the key success factors are: global modular construction (85% of modules produced in China), the Arc7 ice-class fleet ensuring year-round navigation along the Northern Sea Route, long-term take-or-pay contracts, as well as financing and logistics substitution under external pressure. Conclusion: the proposed cooperation models and technical solutions (including GBS platforms) have proven their efficiency, reproducibility, and resilience to external shocks. The practical significance of the work lies in forming an empirical basis for risk management, optimization of cross-border interaction, and further development of the «Polar Silk Road» under changing geopolitical conditions.

A Pd-catalyzed addition/cyclization cascade of di- and trialkynylphosphine oxides with (2-hydroxyaryl)boronic acids affords phosphacoumarins bearing P-C(sp), P-C(sp2), or P-C(sp3) linkages in high yields. The reaction proceeds via an unconventional P-C/O exchange in which an alkynyl group serves as the leaving group and the alkyne acts as both the addition site and the leaving group. This single-scaffold approach to three distinct P-C bond types is attractive for the modular synthesis of phosphorus heterocycles.

Systemic delivery of nucleic acid therapeutics to tissues outside the liver remains difficult because of rapid clearance, off-target accumulation and inefficient cellular uptake. Here we developed a multifunctional construct that assembles circular nucleic acids for targeted delivery, termed circular functional molecular flare. These constructs are produced by ligase-mediated, DNA-templated polymerization: short codons encoding aptamers, oncogene-silencing oligonucleotides, CpG motifs and drug conjugates are hybridized onto circular templates and covalently linked to form stable structures with defined composition and valence. The resulting molecules enable co-delivery of immunostimulatory agonists and cytotoxins to remodel the tumour microenvironment and activate antigen-presenting cells, eliciting potent antitumour immune responses in mouse models. Aptamer-antisense chimeras achieve selective knockdown of the oncogenic Kirsten rat sarcoma viral oncogene homologue transcript in pancreatic cancer through RNase H-mediated degradation of its messenger RNA, suppressing tumour growth without transfection reagents. These findings establish circular functional molecular flare as a chemically programmable approach for engineering targeted nucleic acid therapeutics with improved stability, specificity and efficacy in extrahepatic disease models.

The asymmetric functionalization of nonactivated alkylboronic pinacol esters (APEs) represents a longstanding challenge, owing to their intrinsic inertness toward conventional two-electron transmetalation pathways and the difficulty in achieving precise stereochemical control over carbon-centered radicals. Herein, we report a copper-catalyzed asymmetric deborylative radical coupling enabled by amino radical transfer (ART). By employing aminobenzoates as dual-function reagents, acting both as aminyl radical precursors to trigger ART-mediated homolytic C(sp3)-B bond cleavage and as oxygen nucleophiles, this three-component transformation enables enantioselective coupling of APEs with conjugated dienes. The method delivers structurally diverse chiral allylic esters with excellent enantioselectivities (up to 99% ee). Furthermore, this protocol enables the concise formal synthesis of natural products and the modular construction of chiral ionizable lipids with precise three-dimensional architectures. These lipids achieve enhanced organ-selective mRNA delivery, exhibiting extrahepatic targeting with an improved preference for the spleen. Notably, this work establishes a versatile catalytic platform for transforming bench-stable APEs feedstocks into oxygen-containing chiral molecules, facilitating the development of tissue-specific genetic medicines.

Extracellular vesicles (EVs) carry molecular signatures of their originating cells and have thus emerged as promising biomarkers. However, their clinical utility remains limited due to their low abundance and the modest sensitivity of current EV detection methods in complex biological environments. Here, we present a quantum well defect functionalized carbon nanotube sensor coupled with integrin-recognition RGD tripeptide for EV detection in human plasma. Leveraging the abundance of integrins on EV surfaces, we targeted α5β1, αVβ1, and αVβ3 subtypes. The nanosensor exhibited robust hypsochromic shifts in defect emission upon integrin binding, achieving sub-picomolar detection limits for integrin subunits and quantifying EVs at concentrations as low as 10 4 EVs·mL -1 for glioblastoma, ovarian cancer, and fibroblast cell-derived EV types. Molecular dynamics simulation indicated that integrin docking at the RGD-coupled quantum defect can substantially reshape the interfacial environments of the quantum defects, explaining the high sensitivity in EV detection in complex biological media. Finally, transmembrane protein analysis validated the expression of surface integrins across the tested EV types. The modular nanosensor construct can be targeted to detect disease-associated EV subpopulations, advancing EV-based diagnostics.

The growing demand for sustainable and adaptable construction has increased interest in modular building systems; however, conventional modular solutions often face limitations in transport efficiency and reusability. Foldable modular buildings (FMBs) provide a compact, deployable alternative that enhances delivery efficiency and on-site constructability. This study classifies four FMB types based on their deployment mechanisms, namely midcolumn fold, Z-fold, expandable fold, and 2D panelized systems. It evaluates their constructability using a weighted decision matrix derived from established modular construction decision-making criteria. The results indicate that vertically deployed systems (Z-fold and midcolumn fold) achieve the highest constructability scores due to reduced assembly complexity and lower labor demands. In contrast, 2D panelized systems offer greater design flexibility. A sensitivity analysis demonstrates that constructability preferences depend on application context, with panelized systems favored for residential use and foldable modular systems better suited to emergency and temporary buildings. Finite-element modeling of glass fiber–reinforced polymer (GFRP)-framed modules shows adequate global structural performance, although midcolumn joints reduce lateral stiffness and midbeam joints increase gravity-induced deflections. A fatigue-based serviceability assessment incorporating stiffness degradation of GFRP bolted joints indicates that fatigue effects under wind loading do not govern performance within the design life. Overall, FMBs exhibit high constructability and sufficient structural reliability, highlighting their potential for efficient, adaptable modular construction.

Neurological injuries and neurodegenerative disorders, including spinal cord injury, traumatic brain injury, stroke, and Parkinson's disease remain largely incurable. In the central nervous system (CNS), a self-reinforcing cascade of neuroinflammation, oxidative stress, blood-brain barrier breakdown, and glial fibrotic scarring restricts long-distance axonal regrowth and graft survival. The peripheral nervous system (PNS) exhibits greater intrinsic regenerative potential, yet critical-length defects remain challenging and have driven the development of clinically relevant conduit designs. This review provides an overview of the microenvironment following CNS injury and summarizes the key design requirements for engineered repair matrices, while highlighting lessons from advanced peripheral nerve guidance conduits. Injectable extracellular matrix (ECM)-mimetic and smart hydrogels can conformally fill CNS cavities, modulate immune and redox cascades, restore vascular function, and provide permissive niches for neural stem/progenitor and endothelial cells. CNS-compatible bioinks and 3D bioprinting enable the fabrication of neurovascular architectures and multicellular constructs with controlled mechanics, topology, and circuit geometry. Advances in nerve guidance conduits inform translation of PNS principles to the brain and spinal cord. Organoid-based strategies, including vascularized organoids, biomaterial-supported grafts, and organoid-neuroelectronic interfaces, suggest routes toward modular biohybrid constructs. Integrating pathology-informed biomaterials, biofabrication, and organoid engineering offers a roadmap for neural circuit reconstruction.

Modular construction with precast concrete elements offers significant potential for rapid and resource‐efficient building. This paper presents findings from the scientific coordination project of Priority Program (PP) 2187, addressing key challenges in the design and production chain. Generalized structural models for 1D and 2D modular structures are derived, and load‐bearing capacities of slender reinforced concrete modules are described using M/N interaction charts including geometric scatter. Production‐induced tolerances are systematically quantified and propagated to the structural level via Gaussian error propagation. For multi‐dimensional structures, a sensitivity‐based placement strategy using Elementary Effects is proposed, reducing global deformations by up to 43%. Construction sequences are optimized using Simulated Annealing, ensuring intermediate construction states do not govern final dimensioning. The convertibility of modular structures is assessed through sensitivity analysis of load redistribution. All boundary conditions are integrated into a digital twin based on the Asset Administration Shell. The findings reveal that adaptive modular construction represents a viable pathway toward industrialized, sustainable, and circular concrete construction.

This study evaluates the carbon emission reduction potential of industrialized construction technologies-specifically robotic 3D printing and prefabrication-in lower-star hotels in Hangzhou, China, from 2018 to 2023. A multidimensional ternary spatiotemporal model is developed to quantify the interactions among temporal, spatial, and hotel classification dimensions, enabling a systematic comparison between conventional construction (CC) and prefabricated construction (PC). The results show that prefabricated construction consistently reduces embodied carbon emissions across hotel categories, with the most significant reduction observed in 2-star and 3-star hotels, where carbon emissions can be reduced by approximately 20-35% compared to conventional methods. The findings further indicate that carbon reduction effectiveness varies by hotel classification and spatial distribution, with lower-star hotels benefiting more from standardized modular construction, while high-star hotels exhibit relatively lower reduction efficiency due to structural complexity. Spatiotemporal analysis also reveals heterogeneous decoupling patterns across districts, suggesting that carbon-economic relationships are strongly influenced by regional development conditions and construction intensity. This study advances the integration of carbon accounting and construction technology assessment by providing a quantitative and scalable framework for evaluating embodied carbon reduction in the hospitality sector. The findings offer robust evidence to support targeted low-carbon construction strategies and contribute to carbon-economic decoupling pathways in resource-constrained urban environments, aligning with the scope of carbon balance and management.

“Coil‑Tag bioconjugation represents a powerful shift toward modular, programmable, and supramolecular construction of ADCs with site‑specificity and defined DARs.”As the ADC field matures and demand for greater homogeneity and site-specificity intensifies, new bioconjugation platforms are emerging to address the limitations of classical cysteine-maleimide and lysine-amide chemistries. Grace Yang, Alina Ringaci, and Mark W Grinstaff provide insights into the Coil-Tag platform, a modular, supramolecular conjugation strategy based on the self-assembly of engineered α-helical coiled-coil peptides. They highlight its design principles, its advantages over existing site-specific methods, and its expanding utility across ADC fabrication, CAR-T cell engineering, diagnostics, and biomaterials.

Bridged frameworks are widely recognized as privileged motifs in natural products and pharmaceuticals, and their distinctive three-dimensional architectures often underpin target recognition and bioactivity. However, their preparation remains a formidable challenge, with most strategies relying on either linear multi-step syntheses or structurally specialized substrates. Here we report a bridged scaffold editing strategy for heterocycles and carbocycles, which employs formaldehyde and ureas in a distinct multicomponent reaction, toward modular and efficient construction of diverse bridged polycycles. Notably, this protocol enables concurrent C(sp²)-H and unactivated C(sp³)-H functionalization, for directly assembling bridged polycyclic products from planar or quasi-planar cyclic substrates through regio- and diastereoselective multiple bond formations. Experimental and computational studies collectively elucidate the plausible reaction pathways underlying these transformations. By offering rapid and general access to three-dimensional polycyclic skeletons, this approach expands the molecular editing toolbox and provides a versatile platform for generating structurally unique compounds with potential applications in drug discovery.

Rhamnolipids are glycolipid biosurfactants produced by Pseudomonas aeruginosa, valued for their surface activity, biodegradability, and potential as green alternatives to synthetic surfactants. The first rhamnosylation step, catalyzed by RhlB, is central to the catalytic efficiency of monorhamnolipid formation and subsequent dirhamnolipid biosynthesis. To explore natural diversity and enhance RhlB activity, we established a multilayer DNA-protein mining pipeline to identify polymorphisms influencing catalytic activity. The framework integrated analyses of nucleotide transitions/transversions, mutation patterns, binding-site configurations, stability hotspots, and active-site plasticity. Phylogenetic analysis revealed two hypermutator phylogroups, highlighting evolutionary divergence within RhlB. Three rhlB variants (rhlB1, rhlB2, rhlB3) were experimentally validated in a modular rhlAB genetic construct for monorhamnolipid biosynthesis in Escherichia coli. Using a defined synthetic medium and high-throughput screening platform, monorhamnolipid production was quantified as 20.1 μg mL-1 for the reference rhlAB construct, 22.18 μg mL-1 for rhlAB1, 3.2 μg mL-1 for the dysfunctional rhlAB2, and 55.51 μg mL-1 for rhlAB3, representing a 2.76-fold increase over the reference. Functional analysis suggested that mutation H263R in RhlB2 disrupted catalytic activity, while reversion (R263H) restored activity to 24.63 μg mL-1. Enhanced catalysis in RhlB3 was attributed to loop mutations (I234V and P238R) that improved substrate binding affinity and domain alignment. This study demonstrates that integrating computational mining with experimental validation can reveal naturally optimized enzyme variants, providing a scalable framework for accelerating enzyme engineering and advancing sustainable biosurfactant production.

A general electrosynthetic strategy for the preparation and direct functionalization of 2-oxa-bicyclo[2.1.1]hexanes (i.e. 2-oxa-BCHs) from hydroxymethyl-substituted bicyclo[1.1.0]butanes is reported. The method relies on the anodic generation of electrophilic heteroatom-centred species, including TEMPO-derived oxy-cations, halogen radicals, and thiyl radicals, rendering C(4) functionalized 2-oxa-BCHs selectively in good to excellent yields. The protocol operates under mild conditions, avoids stoichiometric oxidants, and displays broad substrate scope (41 examples). The synthetic utility of the resulting scaffolds is further demonstrated through late-stage functionalization, bio-conjugation, and telescoped synthesis from commercially available precursors. Mechanistic studies (cyclovoltammetry as well as DFT computations) support a pathway involving anodic oxidation for the formation of the electrophilic trigger followed by C–C bond capture and transannular intramolecular cyclization. Overall, this work establishes electrosynthesis as a powerful platform for the modular construction and diversification of 2-oxa-BCHs with potential relevance in drug discovery and expanding the chemical space of benzene bioisosteres.

Densely functionalized 6/5/6 polycycles are prevalent in bioactive natural products, yet their efficient assembly remains a persistent synthetic challenge. Here, we report a palladium-catalyzed autotandem cascade that merges Suzuki-Miyaura coupling with an underexplored oxidative cyclometalation to effect C═C-conserving geminal heterocoupling, thereby enabling rapid construction of fused 6/5/6 scaffolds from readily prepared bicyclic precursors and alkenyl boronates. The transformation proceeds under operationally simple conditions, tolerates broad substrate variation, and is scalable to decagram quantities. Its synthetic utility is demonstrated in a formal synthesis of gracilamine and the total syntheses of GA18 methyl ester and xiamycin E, where the geminal heterocoupling forges the fused tricyclic core and provides advanced intermediates for subsequent target-oriented elaboration. Mechanistic studies support an autotandem pathway involving initial cross-coupling followed by oxidative cyclometalation. Collectively, these studies establish a useful method for the modular construction of fused 6/5/6 polycycles.

Difunctionalization of internal alkynes provides prominent methods for the modular construction of tetrasubstituted alkenes. However, the development of an enantioselective version of such transformation remains elusive. We present herein an enantioselective nickel-catalyzed arylative coupling reaction of simple alkynes with N-sulfonylimines and arylboronic reagents. This asymmetric three-component transformation furnished a wide range of enantioenriched tetrasubstituted allylic amines with excellent regioselectivity and stereoselectivity under mild conditions.

The rapid construction of chiral pharmacophores through stepwise and modular synthesis approaches presents a significant opportunity to accelerate lead compound discovery in drug development. While carbon-based chiral cores currently dominate drug molecule structures, the stepwise functionalization of sp³ carbon centers via C-H or C-X bond manipulations remains challenging. In contrast, silicon atoms offer superior functionalization capabilities with reactive Si-H or Si-X bonds, making them ideal central atoms for the modular and stepwise construction of pharmacophores. In this study, we constructed a total of 64 silicon-containing pharmacophores through efficient modular and stepwise synthesis, starting from Si-H or Si-X bonds. Screening these sila-pharmacophores for their ability to recruit protein degradation systems led to the identification of several potent sila-protein degraders (SiDs). The versatility of these SiDs was demonstrated by their successful conjugation to various small-molecule binders/inhibitors, resulting in efficient degradation of multiple target proteins and thus expanding their potential across diverse drug targets. Notably, we observed significant tumor-suppressive activity of a SiD-conjugated ALK degrader in a xenograft model using the H3122 cell line (ALK-positive), highlighting the therapeutic potential of sila-pharmacophores. These findings underscore that silicon-centered drug motifs not only offer synthetic accessibility and convenience but also enhance drug-like properties. The silicon-carbon switch strategy introduced herein provides an innovative approach to new drug motif development, highlighting its extensive potential in drug discovery and opening new avenues for chemical biology research.

ABSTRACT The development of bioconjugates with high payload loading and defined stoichiometry remains a persistent challenge in medicinal chemistry. In this Account, we present a modular multi‐arm linker platform that decouples payload loading from site‐specific antibody conjugation. This platform utilizes a central peptide core with multiple linking arms for attaching effector/targeting molecules and a single coupling arm (e.g., maleimide) for antibody conjugation. To achieve site‐specificity without the need for enzymatic processing, we employ a bioinorganic strategy: a computationally designed zinc‐binding motif (ACPGHA) fused to the antibody C‐terminus. Density functional theory calculations suggest Zn(II) binds and deprotonates the engineered cysteine to a reactive thiolate for rapid, chemoselective Michael addition to the linker's maleimide. We demonstrate how the modular multi‐arm linker platform, paired with Zn 2+ ‐mediated site‐specific conjugation, enables the modular construction of (i) a theranostic antibody‐radionuclide conjugate for pancreatic cancer and (ii) a potent antibody‐drug conjugate for multiple myeloma. This integration of coordination chemistry, computational design/modeling, and protein engineering provides a robust framework for constructing homogeneous bioconjugates with precise stoichiometry. Beyond cytotoxic payload delivery, the same multi‐arm linker architecture enables pharmacokinetic modulation of a peptide agonist via conjugation of two albumin‐targeting fatty acids.

Bending behavior of self-locking and rapid-unlocking inter-module connection for demountable modular steel construction

Modular construction (MC) is a sustainable construction method; however, its extensive adoption is hindered by challenges in logistics planning and coordination. Recognizing this barrier, many governments are planning the deployment of modular construction hubs (MCHs) to provide contractors with storage buffers near construction sites to alleviate logistics-related challenges. Current MCH planning efforts, however, are largely government-led and focus on evaluating candidate sites, with limited consideration of contractors’ operational perspectives through optimization. To bridge this gap, this paper proposes a novel bilevel programming framework that models the strategic interactions between governments and contractors in MCH planning. The upper level formulates the government’s decisions on MCH site selection, MCH construction and expansion, and service pricing, aiming to maximize MCH utilization and cost efficiency. The lower level captures contractors’ supply chain decisions, aiming to minimize logistics costs following MCH deployment. To solve the model, a decomposition-based biobjective particle swarm optimization algorithm is developed to generate a diverse set of Pareto optimal solutions for trade-off analysis. A nondominated sorting genetic algorithm-II is also implemented as a benchmark for performance comparison. The proposed model and algorithms are validated using data from Hong Kong. Semistructured interviews are conducted to gain industry feedback on the derived planning outcomes. Finally, this research provides governments with an effective tool for designing optimal MCH planning, which can enhance the resilience of MC supply chains and facilitate broader adoption of MC technologies in the construction sector.