A Medicago truncatula HD-ZIP gene MtHB2 is involved in modulation of root development by regulating auxin response.

HD-Zip proteins are plant-specific transcription factors known for their diverse functions in regulating plant growth, development, and responses to environmental stresses. Among the Medicago truncatula HD-Zip II genes, MtHB2 has been previously linked to abiotic stress responses. In this study, we conducted a functional characterization of MtHB2 in the regulation of root growth and development. Upon auxin stimulation, expression of MtHB2 was promptly up-regulated. Overexpression of MtHB2 in Arabidopsis thaliana led to reduced primary root growth and inhibited lateral root formation. Interestingly, the transgenic plants expressing MtHB2 exhibited differential responses to three types of auxins (IAA, NAA, and 2,4-D) in terms of root growth and development compared to the wild-type plants. Specifically, primary root growth was less affected, and lateral root formation was enhanced in the transgenic plants when exposed to auxins. This differential response suggests a potential role for MtHB2 in modulating auxin transport and accumulation, as evidenced by the reduced sensitivity of the transgenic plants to the auxin transport inhibitor NPA and lower expression levels of auxin-related reporters such as PIN-FORMED (PIN1)::PIN1-GFP, PIN3::PIN3-GFP, PIN7::PIN7-GFP, and DR5::GFP compared to wild-type plants. Additionally, microarray analysis of the root tissues revealed down-regulation of several auxin-responsive genes in transgenic seedlings compared to wild-type plants. These findings collectively indicate that MtHB2 plays a critical regulatory role in root growth and development by modulating auxin accumulation and response in the roots.

Chlorquinaldol Alleviates Lung Fibrosis in Mice by Inhibiting Fibroblast Activation through Targeting Methionine Synthase Reductase.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited treatment options. Thus, it is essential to investigate potential druggable targets to improve IPF treatment outcomes. By screening a curated library of 201 small molecules, we have identified chlorquinaldol, a known antimicrobial drug, as a potential antifibrotic agent. Functional analyses have demonstrated that chlorquinaldol effectively inhibits the transition of fibroblasts to myofibroblasts in vitro and mitigates bleomycin-induced pulmonary fibrosis in mice. Using a mass spectrometry-based drug affinity responsive target stability strategy, we revealed that chlorquinaldol inhibited fibroblast activation by directly targeting methionine synthase reductase (MTRR). Decreased MTRR expression was associated with IPF patients, and its reduced expression in vitro promoted extracellular matrix deposition. Mechanistically, chlorquinaldol bound to the valine residue (Val-467) in MTRR, activating the MTRR-mediated methionine cycle. This led to increased production of methionine and s-adenosylmethionine, counteracting the fibrotic effect. In conclusion, our findings suggest that chlorquinaldol may serve as a novel antifibrotic medication, with MTRR-mediated methionine metabolism playing a critical role in IPF development. Therefore, targeting MTRR holds promise as a therapeutic strategy for pulmonary fibrosis.

Insights into the tolerant function of VWA proteins in terms of expression analysis and RGLG5-VWA crystal structure.

The VWA domain commonly functions as a crucial component of multiprotein complexes, facilitating protein-protein interactions. However, limited studies have focused on the systemic study of VWA proteins in plants. Here, we identified 28 VWA protein genes in Arabidopsis thaliana, categorized into three clades, with one tandem duplication event and four paralogous genes within collinearity blocks. Then, we determined their expression patterns under abiotic stresses by transcriptomic analysis. All five RGLG genes were found to be responsive to at least one kind of abiotic stress, and RGLG5 was identified as a multiple stress-responsive gene, coding an E3 ubiquitin ligase with a VWA domain and a C-terminal RING domain. Subsequently, we explored tolerant function of RGLG5 by determining the crystal structure of its VWA domain. The structural comparison revealed the allosteric regulation mechanism of RGLG5-VWA, wherein the deflection of α7 led to displacement of key residue binding metal ion within MIDAS motif. Our findings provide full-scale knowledge on VWA proteins, and insights into tolerant function of RGLG5-VWA in terms of crystal structure.

Synthesis of copper/carbon nanofibers by electrostatic spinning toward persulfate activation for treatment of antibiotic wastewater.

Antibiotics in water will cause serious harm to human health and ecosystem. Carbon-based materials and transition metals activated peroxodisulfate (PDS) to produce active species, which can degrade residual antibiotics in water. In this paper, Cu/CNF (carbon nanofibers) composites were first prepared by introducing Cu into CNF using electrostatic spinning technology, which was used to activate PDS to degrade tetracycline (TC). The degradation efficiency of Cu/CNF/PDS was 36.23% higher than that of CNF/PDS. The reason is that introducing Cu can increase the number of surface functional groups and specific surface area of CNF, and then improve the catalytic performance. The functional groups and Cu species are the active sites for catalytic PDS. Moreover, the main ways to degrade TC in the Cu/CNF/PDS system are singlet oxygen (1O2) and electron transfer. Based on the above analysis, we modified CNF with transition metal salts, prepared efficient environmental functional materials, and used them for PDS activation, providing a theoretical basis and technical support for the degradation of antibiotic pollutants and creating new ideas for other research.

TabHLH27 orchestrates root growth and drought tolerance to enhance water use efficiency in wheat.

Cultivating high-yield wheat under limited water resources is crucial for sustainable agriculture in semiarid regions. Amid water scarcity, plants activate drought response signaling, yet the delicate balance between drought tolerance and development remains unclear. Through genome-wide association studies and transcriptome profiling, we identified a wheat atypical basic helix-loop-helix (bHLH) transcription factor (TF), TabHLH27-A1, as a promising quantitative trait locus candidate for both relative root dry weight and spikelet number per spike in wheat. TabHLH27-A1/B1/D1 knock-out reduced wheat drought tolerance, yield, and water use efficiency (WUE). TabHLH27-A1 exhibited rapid induction with polyethylene glycol (PEG) treatment, gradually declining over days. It activated stress response genes such as TaCBL8-B1 and TaCPI2-A1 while inhibiting root growth genes like TaSH15-B1 and TaWRKY70-B1 under short-term PEG stimulus. The distinct transcriptional regulation of TabHLH27-A1 involved diverse interacting factors such as TaABI3-D1 and TabZIP62-D1. Natural variations of TabHLH27-A1 influence its transcriptional responses to drought stress, with TabHLH27-A1Hap-II associated with stronger drought tolerance, larger root system, more spikelets, and higher WUE in wheat. Significantly, the excellent TabHLH27-A1Hap-II was selected during the breeding process in China, and introgression of TabHLH27-A1Hap-II allele improved drought tolerance and grain yield, especially under water-limited conditions. Our study highlights TabHLH27-A1's role in balancing root growth and drought tolerance, providing a genetic manipulation locus for enhancing WUE in wheat.

Ultrasound modification on milk fat globule membrane and soy lecithin to improve the physicochemical properties, microstructure and stability of mimicking human milk fat emulsions.

Starting from the consideration of the structure of human milk fat globule (MFG), this study aimed to investigate the effects of ultrasonic treatment on milk fat globule membrane (MFGM) and soy lecithin (SL) complexes and their role in mimicking human MFG emulsions. Ultrasonic power significantly affected the structure of the MFGM-SL complex, further promoting the unfolding of the molecular structure of the protein, and then increased solubility and surface hydrophobicity. Furthermore, the microstructure of mimicking MFG emulsions without sonication was unevenly distributed, and the average droplet diameter was large. After ultrasonic treatment, the droplets of the emulsion were more uniformly dispersed, the particle size was smaller, and the emulsification properties and stability were improved to varying degrees. Especially when the ultrasonic power was 300 W, the mimicking MFG emulsion had the highest encapsulation rate and emulsion activity index and emulsion stability index were increased by 60.88 % and 117.74 %, respectively. From the microstructure, it was observed that the spherical droplets of the mimicking MFG emulsion after appropriate ultrasonic treatment remain well separated without obvious flocculation. This study can provide a reference for the screening of milk fat globules mimicking membrane materials and the further utilization and development of ultrasound in infant formula.

Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. METHODS: Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. RESULTS: The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. CONCLUSIONS: A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell-cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

Effects of different chemical modifications on physicochemical and antioxidation properties of Lycium barbarum seed dreg polysaccharides.

Recent studies have witnessed that chemical modification can improve the physicochemical and functional properties of plants' polysaccharides. Herein, we modified the natural Lycium barbarum seed dreg polysaccharides (LBSDPs) by sulfation (S-LBSDPs), phosphorylation (P-LBSDPs), and carboxymethylation (C-LBSDPs), and evaluated the chemical composition and antioxidant activity of their derivatives. Natural polysaccharides and their derivatives exhibited typical polysaccharide absorption peaks and characteristic group absorption peaks in FT-IR spectra along with maximum UV absorption. After modification, the total sugar and protein contents of the derivatives were decreased, whereas the uronic acid content was increased. Among the three derivatives, sulfated polysaccharides displayed excellent thermal stability. S-LBSDP and P-LBSDP showed the highest ABTS radical scavenging and reducing power while S-LBSDPs and C-LBSDPs showed better DPPH radical scavenging effect, and P-LBSDPs showed considerable Fe2+ chelating ability. Our data indicate that chemical modifications can impart a positive effect on the antioxidant potential of plant-derived polysaccharides.

One-step biofabrication of liquid core-GelMa shell microbeads for in situ hollow cell ball self-assembly.

There are many instances of hollow-structure morphogenesis in the development of tissues. Thus, the fabrication of hollow structures in a simple, high-throughput and homogeneous manner with proper natural biomaterial combination is valuable for developmental studies and tissue engineering, while it is a significant challenge in biofabrication field. We present a novel method for the fabrication of a hollow cell module using a coaxial co-flow capillary microfluidic device. Sacrificial gelatin laden with cells in the inner layer and GelMa in the outer layer are used via a coaxial co-flow capillary microfluidic device to produce homogenous micro-beads. The overall and core sizes of core-shell microbeads were well controlled. When using human vein vascular endothelial cells to demonstrate how cells line the inner surface of core-shell beads, as the core liquifies, a hollow cell ball with asymmetric features is fabricated. After release from the GelMa shell, individual cell balls are obtained and deformed cell balls can self-recover. This platform paves way for complex hollow tissue modeling in vitro, and further modulation of matrix stiffness, curvature and biochemical composition to mimic in vivo microenvironments.

Research advances on production and application of algal biochar in environmental remediation.

Algae, comprising microalgae and macroalgae, have emerged as a promising feedstock for the production of functional biochar. Recently, the application of algal biochar in environmental remediation gains increasing attention. This review summarizes research advancements in the synthesis and application of algal biochar, a versatile and sustainable material for environmental remediation ranging from wastewater treatment to soil improvement. Algal biochar can be prepared by pyrolysis, microwave-assisted pyrolysis, and hydrothermal carbonization. Physical and chemical modifications have proven to be effective for improving biochar properties. Algal biochar is promising for removing diverse pollutants including heavy metals, organic pollutants, and microplastics. The role in soil improvement signifies a sustainable approach to enhancing soil structure, nutrient retention, and microbial activity. Research gaps are identified based on current understanding, necessitating further exploration into variations in biochar characteristics, the performance improvement, large-scale applications, and the long-term evaluation for environmental application. This review provides a better understanding of algal biochar as a sustainable and effective tool in environmental remediation.

Ultrasound-induced structural changes of different milk fat globule membrane protein-phospholipids complexes and their effects on physicochemical and functional properties of emulsions.

Ultrasonic technology is a non-isothermal processing technology that can be used to modify the physicochemical properties of food ingredients. This study investigated the effects of ultrasonic time (5 min, 10 min, 15 min) and power (150 W,300 W,500 W) on the structural properties of three types of phospholipids composed of different fatty acids (milk fat globule membrane phospholipid (MPL), egg yolk lecithin (EYL), soybean lecithin (SL)) and milk fat globule membrane protein (MFGMP). We found that the ultrasound treatment changed the conformation of the protein, and the emulsions prepared by the pretreatment showed better emulsification and stability, the lipid droplets were also more evenly distributed. Meanwhile, the flocculation phenomenon of the lipid droplets was significantly improved compared with the non-ultrasonic emulsions. Compared with the three complexes, it was found that ultrasound had the most significant effect on the properties of MPL-MFGMP, and its emulsion state was the most stable. When the ultrasonic condition was 300 W, the particle size of the emulsion decreased significantly (from 441.50 ±â€¯4.79 nm to 321.77 ±â€¯9.91 nm) at 15 min, and the physical stability constants KE decreased from 14.49 ±â€¯0.702 % to 9.4 ±â€¯0.261 %. It can be seen that proper ultrasonic pretreatment can effectively improve the stability of the system. At the same time, the emulsification performance of the emulsion had also been significantly improved. While the accumulation phenomenon occurred when the ultrasonic power was 150 W and 500 W. These results showed that ultrasonic pretreatment had great potential to improve the properties of emulsions, and this study would provide a theoretical basis for the application of emulsifier in the emulsions.

Discovery of a dual-acting inhibitor of interleukin-1ß and STATs for the treatment of inflammatory bowel disease.

Currently, a significant proportion of inflammatory bowel disease (IBD) patients fail to respond to conventional drug therapy such as immunosuppressants and biologic agents. Interference with the JAK/STAT pathway and blocking of IL-1 signaling are two promising therapeutic strategies for these unresponsive IBD patients. This work describes the discovery of an inhibitor 10v that not only blocks NLRP3 and AIM-2 inflammasome-mediated IL-1ß signaling, but also reduces the expression of STAT1 and STAT5 in the JAK/STAT pathway. Importantly, 10v exhibits a significant anti-IL-1ß effect and decreases the levels of STAT1 and STAT5 in a mouse model of colitis. As a result, a novel small molecule is identified with a dual inhibitory capacity towards both inflammasomes/IL-1ß and STAT pathways, which supports further exploration of the therapeutic potential for IBD patients that do not respond to current drug therapy.

Engineering High-Spin State Cobalt Cations in Sulfide Spinel for Enhancing Water Oxidation.

The spin states of active sites have a significant impact on the adsorption/desorption ability of the reaction intermediates during the oxygen evolution reaction (OER). Sulfide spinel is not generally considered a highly efficient OER catalyst owing to the low spin state of Co3+ and the lack of unpaired electrons available for adsorption of reaction intermediates. Herein, it is proposed a novel Nd-evoked valence electronic adjustment strategy to engineer the spin state of Co ions. The unique f-p-d orbital electronic coupling effect stimulates the rearrangement of Co d orbital electrons and increases the eg electron filling to achieve high-spin state Co ions, which promotes charge transport by propagating a spin channel and generates a high number of active sites for intermediate adsorption. The optimized CuCo1.75 Nd0.25 S4 catalyst exhibits outstanding electrocatalytic properties with a low overpotential of 320 mV at 500 mA cm-2 and a 48 h stability at 300 mA cm-2 . In situ synchrotron radiation infrared spectra confirm the quick accumulation of key *OOH and *O intermediates. This work deepens the comprehensive understanding of the relationship between OER activity and spin configurations of Co ions and offers a new design strategy for spinel compound catalysts.

N/S Co-Doped Graphene Aerogels as Superior Anode Materials for High-Rate Lithium-Ion Batteries.

The nitrogen and sulfur co-doped graphene aerogel (SNGA) was synthesized by a one-pot hydrothermal route using graphene oxide as the starting material and thiourea as the S and N source. The obtained SNGA with a three-dimensionally hierarchical structure, providing more available pathways for the transport of lithium ions. The existing form of S and N was regulated by changing the calcination temperature and thiourea doping amount. The results revealed that high temperature could decompose -SOX- functional groups and promote the transformation of C-S-C to C-S, ensuring the cyclic stability of electrode materials, and increasing the thiourea dosage amount introduced more pyridine nitrogen, improving the multiplicative performance of electrode materials. Benefiting from the synergistic effect of sulfur and nitrogen atoms, the prepared SNGA showed superior rate capability (107.8 mAh g-1 at 5 A g-1), twice more than that of GA (52.8 mAh g-1), and excellent stability (232.1 mAh g-1 at 1 A g-1 after 300 cycles), 1.85 times more than that of GA (125.6 mAh g-1). The present study provides a detailed report on thiourea as a dopant to provide a sufficient basis for SNGA and a theoretical guide for further modifying.

The ceRNA Mechanism of lncRNA MEG3/miR-21-5p/SPRY2 in Cell Proliferation and Apoptosis in Bladder Cancer.

Bladder cancer (BC) is the second most common genitourinary malignancy. Long noncoding RNA (lncRNA) is implicated in BC progression. This study delved into the underlying mechanism of lncRNA MEG3 in BC. Bioinformatics analysis predicted the expression of lncRNA MEG3, its association with the survival of BC patients, its subcellular localization, and its binding sites with miR-21-5p. Differentially expressed genes (DEGs) in the GSE13507 chip were analyzed using GEOexplorer, downstream targets of miR-21-5p were predicted from databases, and the overlapping genes were analyzed by the website Venny2.1 (https://bioinfogp.cnb.csic.es/tools/venny/index.html); their impacts on patient survival were analyzed by the Starbase database. The expression of SPRY2 and TGFBI associated with patient survival was analyzed in TCGA. RT-qPCR and western blot were performed to detect levels of MEG3, miR-21-5p, and SPRY2 in BC/SV-HUC-1 cells. Malignant biological behaviors of BC cells were detected using CCK8, flow cytometry, and Transwell assays. RNA pull-down and dual-luciferase assays were employed to verify the binding relationship of miR-21-5p with MEG3 and SPRY2. MEG3 was found to be lowly expressed in BC cells and mainly distributed in the cytoplasm. Over-expression of MEG3 was found to inhibit BC cell activity, promote apoptosis, and reduce invasion and migration. miR-21-5p was found to be highly expressed in BC cells, and its down-regulation was found to inhibit the malignant behavior of BC cells. Over-expression of miR-21-5p was found to reverse the effect of pcDNA3.1-MEG3 on BC cells. MEG3 was found to competitively bind to miR-21-5p as a ceRNA to promote SPRY2 levels. LncRNA MEG3 promotes SPRY2 expression by competitively binding to miR-21-5p, thereby inhibiting proliferation and promoting apoptosis of BC cells.

Novel trends and challenges in fat modification of next-generation infant formula: Considering the structure of milk fat globules to improve lipid digestion and metabolism of infants.

Differences in the composition and structure of lipid droplets in infant formula (IF) and human milk (HM) can affect the fat digestion of infants, leading to high risk of metabolic diseases during later stages of growth. Recently, interest in simulating HM fat (HMF) has gradually increased due to its beneficial functions for infants. Much research focuses on the simulation of fatty acids and triacylglycerols. Enzymatic combined with new technologies such as carbodiimide coupling immobilization enzymes, solvent-free synthesis, and microbial fermentation can improve the yield of simulated HMF. Furthermore, fat modification in next-generation IF requires attention to the impact on the structure and function of milk fat globules (MFG). This review also summarizes the latest reports on MFG structure simulation, mainly related to the addition method and sequence of membrane components, and other milk processing steps. Although some of the simulated HMF technologies and products have been applied to currently commercially available IF, the cost is still high. Furthermore, understanding the fat decomposition of simulated HMF during digestion and assessing its nutritional effects on infants later in life is also a huge challenge. New process development and more clinical studies are needed to construct and evaluate simulated HMF in the future.

Robustness of Trion State in Gated Monolayer MoSe2 under Pressure.

Quasiparticles consisting of correlated electron(s) and hole(s), such as excitons and trions, play important roles in the optical phenomena of van der Waals semiconductors and serve as unique platforms for studies of many-body physics. Herein, we report a gate-tunable exciton-to-trion transition in pressurized monolayer MoSe2, in which the electronic band structures are modulated continuously within a diamond anvil cell. The emission energies of both the exciton and trion undergo large blueshifts over 90 meV with increasing pressure. Surprisingly, the trion binding energy remains constant at 30 meV, regardless of the applied pressure. Combining ab initio density functional theory calculations and quantum Monte Carlo simulations, we find that the remarkable robustness of the trion binding energy originates from the spatially diffused nature of the trion wave function and the weak correlation between its constituent electron-hole pairs. Our findings shed light on the optical properties of correlated excitonic quasiparticles in low-dimensional materials.

Preparation and Characterization of Eugenol Incorporated Pullulan-Gelatin Based Edible Film of Pickering Emulsion and Its Application in Chilled Beef Preservation.

The purpose of this study was to develop a composite film composed of eugenol Pickering emulsion and pullulan-gelatin, and to evaluate its preservation effect on chilled beef. The prepared composite film was comprehensively evaluated in terms of the stability of emulsion, the physical properties of the film, and an analysis of freshness preservation for chilled beef. The emulsion size (296.0 ± 10.2 nm), polydispersity index (0.457 ± 0.039), and potential (20.1 ± 0.9 mV) proved the success of emulsion. At the same time, the films displayed good mechanical and barrier properties. The index of beef preservation also indicated that eugenol was a better active ingredient than clove essence oil, which led to the rise of potential of hydrogen, chroma and water content, and effectively inhibited microbial propagation, protein degradation and lipid oxidation. These results suggest that the prepared composites can be used as promising materials for chilled beef preservation.

Platelet-Rich Plasma for Androgenetic Alopecia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Platelet-rich plasma (PRP) contains a variety of growth factors and has been widely used in maxillofacial surgery, orthopedics, plastic surgery, ophthalmology, and other fields. In recent years, with the increasing morbidity of androgenetic alopecia (AGA), the use of PRP has also increased. The objective of this article was to evaluate the efficacy and safety of PRP for AGA. We searched PubMed, Embase, Web of Science, and Cochrane Library, covering the databases from their earliest records until March 2022. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to explore the effects of PRP for hair density, hair count, and hair diameter in AGA. Nine trials involving 238 patients were included. The meta-analysis showed that PRP for AGA increased hair density at 3 and 6 months with statistically significant differences compared with the placebo (P < .05). PRP also increased hair count and hair diameter compared with the baseline, but there was no significant difference compared with the placebo (P > .05). Two of the 7 studies reported adverse reactions. No serious adverse reactions were found. In conclusion, PRP is an effective and safe treatment for increasing the hair density in AGA. Trial registration: The systematic review was registered with PROSPERO (CRD42022362432).

Engineering Unsymmetrically Coordinated Fe Sites via Heteroatom Pairs Synergetic Contribution for Efficient Oxygen Reduction.

Single-atom Fe catalysts are considered as the promising catalysts for oxygen reduction reaction (ORR). However, the high electronegativity of the symmetrical coordination N atoms around Fe site generally results in too strong adsorption of *OOH intermediates on the active site, severely limiting the catalytic performance. Herein, a "heteroatom pair synergetic modulation" strategy is proposed to tailor the coordination environment and spin state of Fe sites, enabling breaking the shackles of unsuitable adsorption of intermediate products on the active centers toward a more efficient ORR pathway. The unsymmetrically Co and B heteroatomic coordinated Fe single sites supported on an N-doped carbon (Fe─B─Co/NC) catalyst perform excellent ORR activity with high half-wave potential (E1/2 ) of 0.891 V and a large kinetic current density (Jk ) of 60.6 mA cm-2 , which is several times better than those of commercial Pt/C catalysts. By virtue of in situ electrochemical impedance and synchrotron infrared spectroscopy, it is observed that the optimized Fe sites can effectively accelerate the evolution of O2 into the *O intermediate, overcoming the sluggish O─O bond cleavage of the *OOH intermediate, which is responsible for fast four-electron reaction kinetics.