Plasmonic nanoparticles exhibit unique optical and thermal properties that make them ideal for next-generation diagnostic technologies. Among them, gold nanoprisms (AuNPrs) are especially powerful due to their anisotropic geometry, tunable surface plasmon resonance in the near-infrared (NIR) region, and high photothermal conversion efficiency. These features transform them from passive labels into active nanotransducers capable of amplifying diagnostic signals. Building on these advantages, we developed two AuNPr-based sensing platforms: Thermo Lateral Flow Immunoassay (ThermoLFIA) and Thermo Oligonucleotide-based Lateral Flow Assay (ThermoOLFA). By coupling AuNPrs with thermoresponsive substrates, both systems use localized heat generation to boost analytical sensitivity, enabling visual enhancement far beyond that of conventional gold spheres. ThermoLFIA demonstrated clinically relevant detection of gastrointestinal cancer biomarkers (CEA, CA19-9, VEGF), outperforming standard ELISA tests. In parallel, functionalization of AuNPrs with DNA probes enabled ThermoOLFA to detect SARS-CoV-2 RNA with sensitivity comparable to RT-qPCR, but without amplification steps and within 25 min. This proof-of-concept confirms that plasmonic nanoprisms can drive rapid, portable, and ultrasensitive diagnostics, opening a path toward point-of-care platforms with strong clinical and translational potential.
Ca2+ signals play a crucial role in heat stress (HS) resistance. However, how Ca2+ signals are decoded and regulate the downstream targets of HS signaling remains unclear in plants. Cool-season grasses are sensitive to high-temperature conditions and should evolve distinctive heat stress response mechanisms. Here, we identified the calcium-dependent protein kinase 19 (FaCPK19), which decoded the unique Ca2+ signal triggered by HS in cool-season grass tall fescue (Festuca arundinacea Schreb.). The FaCPK19 was activated upon HS and positively regulated thermotolerance in tall fescue. FaCPK19 interacted with the thermo-tolerance 1 (FaTT1), which encodes an α2 subunit of the 26S proteasome, and phosphorylated its Thr172 (T172) residue. Under HS, overexpressing FaTT1T172A (FaTT1T172A-OE, phospho-deficient) grasses resulted in significantly lower 20S and 26S proteasome activity and reduced expression of downstream HS-responsive genes compared to gain-function transgenic grasses (FaTT1-OE). The Facpk19 mutant was weakened in 20S and 26S proteasome activity under HS. Loss of T172 phosphorylation in FaTT1T172A-OE showed a weakened heat-tolerance phenotype than FaTT1-OE. T172 residue at TT1 is evolutionarily conserved from plants to animals, indicating it could be widely used for thermotolerance breeding in grasses and crops. Our findings reveal a Ca2+-FaCPK19-FaTT1 axis by which an HS-induced Ca2+ signal is decoded with enhanced thermotolerance in tall fescue.
The rising growth of agricultural waste poses significant challenges to environmental sustainability, community health, and commercial stability. However, the development of multifunctional bio-based additives that simultaneously provide reinforcement and antioxidant performance in natural rubber (NR) composites remains limited. This study examines the potential of an aluminum (lignin/silica/fatty acid) hybrid (Al(LSF)), derived from rice straw black liquor, as a dual-functional additive with reinforcing and antioxidant properties in natural rubber (NR) composites. The Al(LSF) hybrid was analyzed by XRF, SEM-EDX, TEM, particle size analysis, and zeta potential measurements. Morphology, curing behavior, mechanical properties, and thermo-oxidative aging resistance of Al(LSF) in NR matrices were also investigated. Results showed that Al(LSF) exhibited nanoscale characteristics enabling uniform dispersion in the NR matrix. The incorporation of Al(LSF) (1-4 phr) improved curing properties, as evident by the decreased optimum curing time by approximately 18.3% as compared to TMQ/NR composites. Tensile strength of NR composites increased by approximately 45.4%, and elongation at break reduced by approximately 26.4% at 1 phr loading of Al(LSF) hybrid. The improvement in thermo-oxidative aging resistance of NR composites with Al(LSF) could be observed from th increased aging coefficient from 0.43 to 0.55 (approximately 27.9%). NR composites reinforced with Al(LSF) displayed better mechanical strength and aging properties than those filled with conventional fillers such as silica and sodium bentonite, depending on hybrid loading. Al(LSF)/NR composites can be explored for applications requiring improved long-term thermo-oxidative aging resistance and mechanical strength, such as tires, conveyor belts, gaskets, shoe soles, and other rubber products used outdoors exposed to extreme environmental conditions. Therefore, Al(LSF) hybrid could be considered as a potential multifunctional bio-additive to enhance mechanical strength and thermo-oxidative stability of NR while valorizing agricultural waste.
Waste heat sources are potentially useful for component separation in fluid mixtures. To better understand how thermal driving forces can contribute to separation, we have investigated the Soret balances of forces for thermodiffusion and thermo-osmosis. A set of two-component fluid isotope mixtures with mass ratio m 2 / m 1 has been investigated in membranes with molecular-sized pores. Numerical support generated by molecular dynamics simulations is achieved for two models; one for the Soret coefficient, S = a m ( m 2 - m 1 ) / ( m 2 + m 1 ) + b ε ( ε 2 m - 1 ) , and one for the thermo-osmotic coefficient, D p = a ( Δ H / Δ T ) + b , where ε 2 m is a parameter for the fluid-membrane interactions, Δ refers to a difference across the membrane, H is the bulk fluid enthalpy, and T is the temperature. In these formulas a m , b ε , a , b are system-specific constants. The results apply to Lennard-Jones/spline isotope mixtures of mass ratios 0.1 < ( m 2 / m 1 ) < 10 , with thermally insulating membrane materials, and component-specific fluid-pore interactions. The results give information about how the Soret balances depend on membrane properties, which potentially can be used to tailor membranes for efficient separation.
Tumor recurrence and metastasis are important factors affecting the efficacy of transhepatic arterial chemoembolization. To prolong the survival of patients, comprehensive interventional therapy and antitumor drugs that can control their release need to be developed. Poly(N-isopropylacrylamide-co-acrylic acid) nanogels are firstly self-assembled with doxorubicin, the constructed doxorubicin-loaded nanogels were then emulsified with iodized oil under high-shear conditions to form doxorubicin-iodized oil nanogel suspensions (Dox-TIPE). The structural characteristics, thermosensitive properties and rheological properties were evaluated. The in vitro biocompatibility and drug release behavior of Dox-TIPE were assayed and in vivo interventional therapy was examined in a VX2 rabbit liver cancer model. Dox-TIPE can effectively exert the dual advantages of chemoembolization therapy, achieving a superior therapeutic effect on inhibiting rabbit liver tumor growth. It promotes TUNEL expression in the tumor boundary region while reducing Ki67 expression, which results in decreased tumor cell proliferation and increased apoptosis rates. Furthermore, Dox-TIPE effectively suppresses the expressions of HIF-1α, VEGF, and CD31 in tumor target areas, thereby preventing the formation of tumor neovascularization and collateral circulation. We successfully produced Dox-TIPE which offers a multifunctional platform combining embolization, chemotherapy, imaging, and immunomodulation. This novel embolic material shows strong potential to address current limitations of TACE in liver cancer treatment and may serve as a promising candidate for next-generation embolization therapies.
Elevated temperature disrupts spikelet development and threatens rice yields; however, the underlying molecular mechanisms are not completely elucidated. Although the core jasmonic acid (JA) signalling transcription factor OsMYC2 is essential for spikelet development, it remains unclear whether and how OsMYC2 mediates temperature-responsive regulation of this process. Here, we identified a thermo-sensitive panicle defect mutant tspd4, which exhibits various spikelet abnormalities under high temperature (HT) that are largely reversed under low temperature (LT). Genetic analysis revealed that tspd4 carries a weak allele of OsMYC2, encoding a protein with a single amino acid deletion (OsMYC2ΔI128). We demonstrated that HT triggers the proteasome-mediated degradation of OsMYC2ΔI128, significantly reducing its abundance. This temperature-dependent instability impairs the interaction between OsMYC2ΔI128 and JA signalling repressors (OsJAZs), thereby disrupting downstream transcriptional programmes. We further identified the key floral regulator OsMADS1 as a transcriptional target of OsMYC2ΔI128. The OsMADS1 expression is significantly downregulated in tspd4 under HT. Genetic experiments confirm that OsMADS1 functions downstream of OsMYC2ΔI128 to mediate the thermo-sensitive spikelet phenotype. Our study uncovers a temperature-responsive post-translational mechanism linking a core JA signalling transcription factor to spikelet development in rice, and provides a framework for understanding how ambient temperature reshapes reproductive development through protein stability control.
Tidal wetland aquaculture reclamation is a widespread anthropogenic land-use practice that profoundly alters ecological functions, yet its effects on sediment dark carbon fixation (DCF) and temperature response remain unclear. We investigated how converting natural bare tidal flats to moderate- (<60 individuals m-2) and high-intensity (>100 individuals m-2) aquaculture ponds alters sediment DCF, its thermal sensitivity, and associated microbial communities. Converting natural tidal flats to flooded aquaculture ponds significantly increased sediment potential DCF rates, sulfide, ferrous ion, and ammonium and organic matter, while reducing sediment ferric ion and overlying water dissolved oxygen. DCF rates in natural tidal flats were 1.35 ± 0.49 μg C g-1 d-1, which respectively substantially increased by 102% and 271% in moderate- and high-intensity aquaculture ponds, establishing them as potent estuarine DCF hotspots. Aquaculture reclamation enriched carbon-fixing microorganisms, and shifted their compositions from a "generalist" (characterized by aerobic and versatile taxa) to a "specialist" (dominated by strictly anaerobic taxa) type. This shift indicated a fundamental ecological change driven by habitat anaerobiosis, triggering a microbial energy reallocation from growth to maintenance. The proposed "aquaculture reclamation-induced thermo-carbon pump" concept describes how anthropogenic inputs enhance coastal carbon sequestration and its thermal sensitivity, representing a positive feedback mechanism in carbon-climate interactions.
Horizontal Slinky-type geothermal heat exchangers (GHEs) are widely used in ground-source heat pump systems due to their compact layout and low installation cost, yet their performance is often constrained by shallow burial depth and weak internal flow mixing. This study presents a three-dimensional CFD analysis of a horizontal Slinky GHE enhanced with Twisted-tape inserts. The effects of Twisted-tape pitch (100, 250, and 350 mm), burial depth (0.5-1.5 m), and water mass flow rate (0.30-1.0 kg/s) are investigated under turbulent flow conditions using ANSYS Fluent with the realizable k-ε model. The novelty of this work lies in the combined optimization of Twisted-tape geometry and burial depth, evaluated through both first-law (Nusselt number, pressure drop) and second-law (entropy generation, exergy destruction) performance metrics. Twisted-tape inserts significantly enhance convective heat transfer: compared with the plain tube, the average Nusselt number increases by up to 28-35% for the 100 mm pitch and 22-30% for the 250 mm pitch. Although the 100 mm pitch provides the highest thermal enhancement, it also results in a 40-52% pressure-drop increase. The 250 mm pitch yields the maximum thermo-hydraulic performance criterion (PEC), improving PEC by 12-18%, indicating the optimal balance between heat-transfer augmentation and hydraulic penalty. Increasing burial depth improves thermal stability and heat extraction, enhancing the heat-transfer coefficient by approximately 15-21%. The optimal configuration is identified as a 250 mm pitch at a burial depth of 1.0-1.5 m. These findings provide practical design guidance for improving the efficiency of horizontal Slinky geothermal heat exchangers. The findings offer practical design guidance for horizontal Slinky geothermal systems, indicating that careful optimization of coil pitch, burial depth, and operating mass flow rate can substantially improve heat extraction performance while keeping hydraulic losses within acceptable limits under realistic ground and ambient conditions.
暂无摘要（点击查看详情）
Photothermal ammonia synthesis has emerged as a promising route to couple nitrogen fixation with solar energy, yet the mechanistic origin of light-assisted activity remains difficult to establish because illumination can contribute through heat generation, photoexcited carriers, or both simultaneously. This Review examines recent photothermal NH3 synthesis systems from a diagnostic perspective. Representative Ru- and Fe-based materials are discussed within four photothermal regimes: photo-driven thermocatalysis, photo-assisted thermocatalysis, photothermal co-catalysis, and thermally assisted photocatalysis; and are evaluated according to two complementary questions: what is the most likely dominant photothermal regime under the reported reaction conditions, and how strong is the mechanistic evidence supporting that assignment? Particular attention is given to temperature-normalized light/dark comparisons, apparent activation energy and reaction-order analysis, wavelength- and intensity-dependent activity, isotopic validation, operando spectroscopy, and methods for constraining local thermal gradients. Across the strongest cases, the clearest mechanistic effects emerge when light-responsive functionality overlaps with the kinetically relevant elementary step at a catalytically active interface. The analysis also shows that photothermal co-catalysis should be assigned more restrictively than the other regimes and only when simultaneous and cooperative thermo-photochemical contributions are supported by sufficiently robust mechanistic evidence. By comparing Ru- and Fe-based systems through this evidence-based framework, this Review identifies structure-, interface-, and kinetic-constraint-dependent trends, proposes practical criteria for mechanistic assignment, and outlines priorities for catalyst design, reporting standards, and reactor development in photothermal ammonia synthesis.
We present a compact induction heating system for time-resolved in situ X-ray diffraction imaging, enabling contact-free volumetric heating of samples up to approximately 1600°C with flexible operation in different working modes. Real-time, spatially resolved thermography is achieved using an integrated near-infrared camera. A three-dimensional finite-element model of electromagnetic heating, steady-state heat transfer and thermo-elastic stress predicts Joule heating, temperature fields and resolved shear stresses, and guides experimental design. The system has been demonstrated at a synchrotron topography station using simultaneous X-ray white-beam topography and infrared thermography during controlled heating of an indented Si(001) wafer. Dislocation activity is observed starting at local temperatures above 1000°C, increasing at higher temperatures. The experimentally observed number of dislocations on individual {111}〈110〉 glide systems correlates with the simulated resolved shear stresses. This integrated approach enables quantitative, time-resolved studies of dislocation dynamics under well defined thermal conditions and offers a simulation-guided route to tailoring temperature gradients and stress fields for future materials and in situ experiments.
In this study, two fully conjugated microporous polymers (ICTO-CMP1 and ICTO-CMP2) were synthesized via aldol condensation, and they hold broad light absorption properties, excellent photothermal conversion efficiency, and superior stability. Under 660 nm laser irradiation at 100 mW cm-2, the surface temperature of ICTO-CMP1 rapidly increased from room temperature to 140°C within 1 min. Moreover, the interfacial solar evaporation system based on ICTO-CMP1 achieves a high water evaporation rate of 3.67 kg m-2 h-1 with a solar-to-vapor efficiency of 96.3% under simulated sunlight irradiation, and the corresponding thermoelectric device delivers an output voltage of 290 mV. Furthermore, ICTO-CMP1 enables simultaneous water desalination and electricity generation. This study offers a viable route for developing conjugated porous polymer-based solar absorbers for photo-thermo-electric conversion applications.
The structure of phospholipid headgroups and chains are well-established drivers of membrane elastic properties, but functions for different chemistries that join these moieties together are poorly understood. While canonical phospholipids feature ester linkages, alkyl ether- and plasmenyl-linked species emerged in prokaryotes, are highly abundant in metazoans, and have been implicated in neurodegeneration and aging. Ether phospholipid chemistry, and plasmenyl linkages in particular, arose independently several times in evolution, suggesting conserved functions in the structure of cell membranes. Here we combine experiments and molecular simulations to determine how backbone linkage chemistry modulates membrane mechanics. We find that ether linkages additively promote negative intrinsic curvature, destabilizing bilayers and enhancing membrane fusion. They also decouple membrane stiffness from viscosity, softening membranes while maintaining packing in the hydrophobic core. The plasmenyl linkage uniquely stabilizes the inverted hexagonal phase by lowering the energetic cost of chain stretching, providing a rationale for the evolution of its biosynthesis. These results explain the fusogenicity of ether lipids and show how they regulate membrane topology through multiple physical mechanisms. We propose that phospholipid backbone linkage chemistry constitutes a modular control element for membrane mechanics and topology. The structure and dynamics of cell membranes can be sensitive to small chemical changes in their phospholipid building blocks. Phospholipids with ether bonds connecting their glycerol backbone and hydrocarbon chains have long been proposed to impart chemical stability to thermo- and acidophile microbial membranes, but have more recently been identified as major components of mammalian tissues. We show that ether linkages promote membrane dynamics through imposition of a canonical molecular geometry and by decoupling of bending stiffness from chain ordering. Plasmalogen lipids, in which the ether linkage is modified with a vicinal double bond, further promote non-lamellar topologies through a chain-stretching mechanism. These biophysical features suggest a basis for the repeated emergence of ether phospholipids in evolution and their observed functions in membrane trafficking. The thermodynamic and structural bases of plasmalogen function are especially notable as these lipids have been increasingly implicated in neurodegenerative and cardiovascular disease.
Stimuli-responsive nanogels have been utilized as perfect nanocarriers for anticancer drug delivery because of their on-demand, controlled, and site-specific drug-releasing chemistry. These HNP are cross-linked hydrophilic polymer nanoparticles with a high-water content, biocompatibility, and adjustable reactivity to chemical or physical stimuli (such as pH, temperature, and redox potential, which are among the most extensively studied triggers in cancer-targeted nanogel systems). Because of their structural flexibility, these nanocarriers can react intelligently and passively to the tumor microenvironment's high glutathione content, acid pH, and overexpressed enzymes, ensuring increased intracellular release and reduced systemic toxicity. Cross-linking strategies, top-down and bottom-up production processes, and core characterization methods concerning size, charge, morphology, and release kinetics are the main topics of this article. Anticancer medications like doxorubicin, paclitaxel, camptothecin, and docetaxel have been shown to be well accommodated in a variety of nanogels, including pH-responsive, thermo-responsive, redox-responsive, magnetic-based, and multi-responsive ones for increased bioavailability and anti-tumor activity. In addition, receptor-mediated endocytosis mediated by targeting ligands such as folic acid, hyaluronic acid, aptamers and monoclonal antibodies improves the cellular uptake and uptake in tumor of drug-loaded nanogels. Collectively, intelligence-triggered nanogels stated above possess outstanding benefits in combination therapy, controlled drug release, and theranostic application and so illustrate these as state-of-the-art intelligent delivery systems for tumor treatment. Future goals include optimizing biocompatibility, removing tumor penetration obstacles using techniques including surface charge modification, PEGylation, and enzyme-sensitive cross-linkers, and guaranteeing scalability and therapeutically transferable formulations.
The highly polymorphic nature of mitochondrial DNA (mtDNA) poses a significant challenge for primer design in PCR-based assays, because mismatches under primer binding sites can lead to reduced amplification and thus lower sequencing read depth or even complete amplicon dropout. While manufacturers aim to prevent this by adding variant-specific combinations to the primer pools (also known as degenerate primers), it cannot be entirely avoided that some samples are still affected, particularly when rare variants appear in the primer target region. In this study, we evaluated the impact of such variants on the amplification efficiency using two widely implemented Massively Parallel Sequencing kits, the Precision ID MtDNA Control Region / Whole Genome Panels (Thermo Fisher Scientific) and the ForenSeq mtDNA Whole Genome Kit (Verogen). The samples used in this study came from routine casework applications (analysed in the Control Region) and from a study of population genetics and phylogeography (encompassing the entire mitogenome). The observed instances of drop-out or reduced read depth were examined for their phylogenetic background and for their expected abundance and relevance in forensic casework. We discuss possible solutions to mitigate these issues, including the use of overlapping amplicons and an increased number of degenerate primers.
Slab tearing, the lateral detachment of subducting oceanic slab from continental lithosphere, is widely inferred from seismic tomography, yet its surface expressions in mountain belts and adjacent foreland basins remain ambiguous and often contradictory. Existing geodynamic models predict that slab tearing propagates at unrealistically high velocities, implying its transient signatures unlikely to be preserved in surface or stratigraphic records. In contrast, geological observations, such as lateral migration of foreland basin depocenters and systematic basin thickening in the direction of tear propagation, indicate more persistent surface responses, highlighting a long-standing disconnect between models and field evidence. Here we resolve this paradox by showing that lateral variations in passive-margin strength fundamentally control the initiation, propagation, and surface imprint of slab tearing. Using fully coupled three-dimensional thermo-mechanical and surface-process simulations, we demonstrate that accounting for passive-margin heterogeneity significantly slows tear propagation and produces long-lived tectonostratigraphic signatures consistent with natural examples from the Alps, Carpathians, Zagros, and other orogenic belts. These results bridge deep-mantle dynamics and surface geological records, providing a unified framework to identify and interpret slab tearing in orogenic systems worldwide.
The parabrachial (PB) nucleus participates in neural coding for diverse sensory modalities, including nociception and taste. Recent neurophysiological studies identified a subpopulation of PB neurons that responds to both gustatory and oral nociceptive (trigeminal) stimuli. These taste-integrative neurons populate PB subnuclei that receive somatosensory input from bodily skin supplied by spinal afferents. Yet whether spinal sensory input can excite these cells was unexplored. Here, we applied electrophysiological and optogenetic techniques in anesthetized TRPV1;Ai32 mice, which support transdermal photoexcitation of cutaneous TRPV1-lineage thermo-nociceptive fibers, to study if spinal sensory stimulation could engage taste-active PB cells. Action potentials were monitored in isolated PB neurons during oral application of diverse taste and chemesthetic stimuli, oral thermal stimulation using temperature-controlled water, and pinch of the hindpaw and tail. In some cases, photostimulation was applied to pinch-sensitive receptive fields to optogenetically excite bodily TRPV1-lineage fibers. Analysis of 94 PB neurons identified 35 cells (37.2%) that responded to more than one stimulus modality, including 10 taste-excited neurons that also fired impulses to noxious oral chemesthetic (trigeminal) stimuli, oral thermal input, and hindpaw/tail pinch. Such neurons could also respond to photoexcitation of TRPV1-lineage afferents innervating body extremities and frequently displayed bitter-oriented (aversive) taste response profiles. These data suggest that spinal afferent input, including pain-related neural messages from skin, converges onto taste-active PB neurons. These neurons would be misclassified as unimodal "taste" cells under traditional methods but display multisensory response repertoires that agree with involvement of PB circuits in sensory-affective processing.
A mathematical approach is introduced to achieve pseudoenhanced peak efficiency in liquid chromatography-high resolution mass spectrometry (LC-HRMS1), utilizing second-derivative transformations with respect to time and Gaussian smoothing cycles. The pipeline involved interpolating all MS scans, recorded as profile scans, onto a common m/z axis, allowing for second-derivative transformations for each m/z increment with respect to time across the entire data set. Validation using a public study (comprising 1100 compounds analyzed on a Thermo Q Exactive) demonstrates substantial improvements in feature detection and resolution, with qualitative and quantitative benefits. The transformation enables increased peak efficiency by up to 2 orders of magnitude in multicycle implementations without requiring physical hardware enhancements. The approach provides enhanced separation of complex mixtures, reduced background contributions, and increased reliability in untargeted metabolomics and related analyses.
Glycosylation is a critical post-translational modification (PTM) in biotherapeutics that influences protein structure, stability, pharmacokinetics, biological activity, and immunogenicity. Comprehensive characterization of glycosylation and other PTMs is therefore important for biopharmaceutical development and quality assessment. Aflibercept is a recombinant fusion protein containing five N-glycosylation sites and multiple potential O-glycosylation sites. Although site-specific N-glycosylation of aflibercept has been previously investigated, integrated characterization of glycosylation heterogeneity and aspartic acid (Asp) isomerization using an electron-transfer/higher-energy collision dissociation (EThcD) based workflow remains limited. In this study, EThcD data-dependent MS2 (ddMS2) peptide mapping was performed on a Thermo Scientific Orbitrap Excedion Pro mass spectrometer equipped with the EASY-ETD option for detailed characterization of aflibercept. Site-specific N-glycosylation profiles at all five glycosylation sites were identified and relatively quantified. In addition, an O-glycopeptide localized at S12 was detected, providing direct experimental evidence supporting site-specific O-glycosylation in aflibercept. The EThcD fragmentation approach also enabled differentiation and localization of isoAsp residues through characteristic diagnostic fragment ions, including low-abundance peptides containing multiple Asp residues. Several additional PTMs, including deamidation and oxidation, were simultaneously characterized within the same analytical workflow. The results also indicate that EThcD peptide mapping can support the integrated multi-attribute method (MAM) concept for complex glycoproteins by combining glycosylation analysis, Asp/isoAsp differentiation, and PTM profiling in a single experiment. This workflow may be useful for detailed structural characterization and analytical comparability assessment of therapeutic glycoproteins and biosimilars.
Protonic ceramic electrolysis cells (PCECs) are regarded as a promising technology for producing green hydrogen due to the lower operational temperatures, higher conversion efficiencies, enhanced durability/safety, no requirement of hydrogen drying system and simplified water management over the traditional oxygen-ion-conducting solid oxide electrolysis cells. Nevertheless, the overall performance of PCECs is hindered by the slow kinetics of oxygen evolution reaction (OER) and insufficient triple conductivities (H+/O2-/e-) of air electrodes (e.g., perovskite oxides) at lower temperatures. Although remarkable advancements have been achieved about the development of cobalt-based perovskite air electrodes (highly active but instable), designing optimal and highly efficient/durable air electrodes for PCECs remains challenging. Herein, an in-time and critical review about the advances in designing cobalt-free air electrodes for PCECs is presented by highlighting the fundamental mechanisms, performance-influencing factors, and the superiority of cobalt-free perovskite oxides over cobalt-based counterparts. Several distinct design strategies to boost the OER activity/durability and thermo-mechanical compatibility of cobalt-free air electrodes for PCECs are also proposed. Finally, current limitations/contradictions, existed challenges/controversies and future directions are presented. This review aims to provide critical insights for the rational design of high-efficiency and long-lasting air electrodes for PCECs to realize widespread applications.