Inhalable Polymeric Microparticles for Phage and Photothermal Synergistic Therapy of Methicillin-Resistant Staphylococcus aureus Pneumonia.

Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.

How denitrifiers defense ciprofloxacin: Insights from intracellular and extracellular stress response.

Overuse of antibiotics has led to their existence in nitrogen-containing water. The impacts of antibiotics on bio-denitrification and the metabolic response of denitrifiers to antibiotics are unclear. We systematically analyzed the effect of ciprofloxacin (CIP) on bio-denitrification and found that 5 mg/L CIP greatly inhibited denitrification with a model denitrifier (Paracoccus denitrificans). Nitrate reduction decreased by 32.89 % and nitrous oxide emission increased by 75.53 %. The balance analysis of carbon and nitrogen metabolism during denitrification showed that CIP exposure blocked electron transfer and reduced the flow of substrate metabolism used for denitrification. Proteomics results showed that CIP exposure induced denitrifiers to use the pentose phosphate pathway more for substrate metabolism. This caused a substrate preference to generate NADPH to prevent cellular damage rather than NADH for denitrification. Notably, despite denitrifiers having antioxidant defenses, they could not completely prevent oxidative damage caused by CIP exposure. The effect of CIP exposure on denitrifiers after removal of extracellular polymeric substances (EPS) demonstrated that EPS around denitrifiers formed a barrier against CIP. Fluorescence and infrared spectroscopy revealed that the binding effect of proteins in EPS to CIP prevented damage. This study shows that denitrifiers resist antibiotic stress through different intracellular and extracellular defense strategies.

Feedback of chain elongation microorganisms on iron-based conductive materials: Enhanced microbial functions and biotoxicity adaptation mechanisms.

Despite the increased research efforts aimed at understanding iron-based conductive materials (CMs) for facilitating chain elongation (CE) to produce medium chain fatty acids (MCFAs), the impact of these materials on microbial community functions and the adaptation mechanisms to their biotoxicity remain unclear. This study found that the supply of zero-valent iron (ZVI) and magnetite enhanced the MCFAs carbon-flow distribution by 26 % and 52 %, respectively. Metagenomic analysis revealed the upregulation of fatty acid metabolism, pyruvate metabolism and ABC transporters with ZVI and magnetite. The predominant functional microorganisms were Massilibacterium and Tidjanibacter with ZVI, and were Petrimonas and Candidatus_Microthrix with magnetite. Furthermore, it was demonstrated that CE microorganisms respond and adapt to the biotoxicity of iron-based CMs by adjusting Two-component system and Quorum sensing for the first time. In summary, this study provided a new deep-insight on the feedback mechanisms of CE microorganisms on iron-based CMs.

Upgrading soybean dreg to caproate via intermediate of lactate and mediator of biochar.

To address the environmental hazards posed by high-yield soybean dreg (SD), a high-value strategy is firstly proposed by synthesizing caproate through chain elongation (CE). Optimized conditions for lactate-rich broth as intermediate, utilizing 50 % inoculum ratio, 40 g/L substrate concentration, and pH 5, resulting in 2.05 g/L caproate from direct fermentation. Leveraging lactate-rich broth supplemented with ethanol, caproate was optimized to 2.76 g/L under a refined electron donor to acceptor of 2:1. Furthermore, incorporating 20 g/L biochar elevated caproate production to 3.05 g/L and significantly shortened the lag phase. Mechanistic insights revealed that biochar's surface-existed quinone and hydroquinone groups exhibit potent redox characteristics, thereby facilitating electron transfer. Moreover, biochar up-regulated the abundance of key genes involved in CE process (especially fatty acids biosynthesis pathway), also enriching Lysinibacillus and Pseudomonas as an unrecognized cooperation to CE. This study paves a way for sustainable development of SD by upgrading to caproate.

Sequential bio-treatment of ammonia-rich wastewater from Chinese medicine residue utilization: Regulation of dissolved oxygen.

To effectively treat actual ammonia-rich Chinese medicine residue (CMR) resource utilization wastewater, we optimized an anaerobic-microaerobic two-stage expanded granular sludge bed (EGSB) and moving bed sequencing batch reactor (MBSBR) combined process. By controlling dissolved oxygen (DO) levels, impressive removal efficiencies were achieved. Microaeration, contrasting with anaerobic conditions, bolstered dehydrogenase activity, enhanced electron transfer, and enriched the functional microorganism community. The increased relative abundance of Synergistetes and Proteobacteria facilitated hydrolytic acidification and fostered nitrogen and phosphorus removal. Furthermore, we examined the impact of DO concentration in MBSBR on pollutant removal and microbial metabolic activity, pinpointing 2.5 mg/L as the optimal DO concentration for superior removal performance and energy conservation.

CT-determined low skeletal muscle index predicts poor prognosis in patients with colorectal cancer.

BACKGROUND: Sarcopenia is highly prevalent among patients with colorectal cancer (CRC). Computed tomography (CT)-based assessment of low skeletal muscle index (SMI) is widely used for diagnosing sarcopenia. However, there are conflicting findings on the association between low SMI and overall survival (OS) in CRC patients. The objective of this study was to investigate whether CT-determined low SMI can serve as a valuable prognostic factor in CRC. METHODS: We collected data from patients with CRC who underwent radical surgery at our institution between June 2020 and November 2021. The SMI at the third lumbar vertebra was calculated using CT scans, and the cutoff values for defining low SMI were determined using receiver operating characteristic curves. Univariate and multivariate analyses were performed to assess the associations between clinical characteristics and postoperative major complications. RESULTS: A total of 464 patients were included in the study, 229 patients (46.7%) were classified as having low SMI. Patients with low SMI were older and had a lower body mass index (BMI), a higher neutrophil to lymphocyte ratio (NLR), and higher nutritional risk screening 2002 (NRS2002) scores compared to those with normal SMI. Furthermore, patients with sarcopenia had a higher rate of major complications (10.9% vs. 1.3%; p < 0.001) and longer length of stay (9.09 ± 4.86 days vs. 8.25 ± 3.12 days; p = 0.03). Low SMI and coronary heart disease were identified as independent risk factors for postoperative major complications. Moreover, CRC patients with low SMI had significantly worse OS. Furthermore, the combination of low SMI with older age or TNM stage II + III resulted in the worst OS in each subgroup analysis. CONCLUSIONS: CT-determined low SMI is associated with poor prognosis in patients with CRC, especially when combined with older age or advanced TNM stage.

A case report of IgG4-related hepatic inflammatory pseudotumor in a 3-year old boy.

Background: Hepatic Inflammatory Pseudotumor (IPT) is an infrequent condition often masquerading as a malignant tumor, resulting in misdiagnosis and unnecessary surgical resection. The emerging concept of IgG4-related diseases (IgG4-RD) has gained widespread recognition, encompassing entities like IgG4-related hepatic IPT. Clinically and radiologically, corticosteroids and immunosuppressive therapies have proven effective in managing this condition. Case Presentation: A 3-year-old Chinese boy presented to the clinic with an 11-month history of anemia, fever of unknown origin, and a tender hepatic mass. Blood examinations revealed chronic anemia (Hb: 6.4 g/L, MCV: 68.6 fl, MCH: 19.5 pg, reticulocytes: 1.7%) accompanied by an inflammatory reaction and an elevated serum IgG4 level (1542.2 mg/L). Abdominal contrast-enhanced computed tomography unveiled a 7.6 cm low-density mass in the right lateral lobe, while magnetic resonance imaging demonstrated slight hypointensity on T1-weighted images and slight hyperintensity on T2-weighted images, prompting suspicion of hepatic malignancy. A subsequent liver biopsy revealed a mass characterized by fibrous stroma and dense lymphoplasmacytic infiltration. Immunohistochemical analysis confirmed the presence of IgG4-positive plasma cells, leading to the diagnosis of IgG4-related hepatic IPT. Swift resolution occurred upon initiation of corticosteroid and mycophenolate mofetil therapies. Conclusion: This study underscores the diagnostic approach to hepatic IPT, utilizing histopathology, immunostaining, imaging, serology, organ involvement, and therapeutic response. Early histological examination plays a pivotal role in clinical guidance, averting misdiagnosis as a liver tumor and unnecessary surgical interventions.

Exploring the Link Between Autophagy-Lysosomal Dysfunction and Early Heterotopic Ossification in Tendons.

Heterotopic ossification (HO), the pathological formation of bone within soft tissues such as tendon and muscle, is a notable complication resulting from severe injury. While soft tissue injury is necessary for HO development, the specific molecular pathology responsible for trauma-induced HO remains a mystery. The previous study detected abnormal autophagy function in the early stages of tendon HO. Nevertheless, it remains to be determined whether autophagy governs the process of HO generation. Here, trauma-induced tendon HO model is used to investigate the relationship between autophagy and tendon calcification. In the early stages of tenotomy, it is observed that autophagic flux is significantly impaired and that blocking autophagic flux promoted the development of more rampant calcification. Moreover, Gt(ROSA)26sor transgenic mouse model experiments disclosed lysosomal acid dysfunction as chief reason behind impaired autophagic flux. Stimulating V-ATPase activity reinstated both lysosomal acid functioning and autophagic flux, thereby reversing tendon HO. This present study demonstrates that autophagy-lysosomal dysfunction triggers HO in the stages of tendon injury, with potential therapeutic targeting implications for HO.

Identification of a novel ANK1 gene variant c.1504-9G>A and its mechanism of intron retention in hereditary spherocytosis.

Objective: The objective of this study was to pinpoint pathogenic genes and assess the mutagenic pathogenicity in two pediatric patients with hereditary spherocytosis. Methods: We utilized whole-exome sequencing (WES) for individual analysis (case 1) and family-based trio analysis (case 2). The significance of the intronic mutation was validated through a Minigene splicing assay and supported by subsequent in vitro experiments. Results: Both probands received a diagnosis of hereditary spherocytosis. WES identified a novel ANK1 c.1504-9G>A mutation in both patients, causing the retention of seven nucleotides at the 5' end of intron 13, as substantiated by the Minigene assay. This variant results in a premature stop codon and the production of a truncated protein. In vitro studies indicated a reduced expression of the ANK1 gene. Conclusion: The novel ANK1 c.1504-9G>A variant is established as the causative factor for hereditary spherocytosis, with the c.1504-9G site functioning as a splicing receptor.

Enhancing simultaneous nitrogen and phosphorus availability through biochar addition during Chinese medicinal herbal residues composting: Synergism of microbes and humus.

The disposal of Chinese medicinal herbal residues (CMHRs) derived from Chinese medicine extraction poses a significant environmental challenge. Aerobic composting presents a sustainable treatment method, yet optimizing nutrient conversion remains a critical concern. This study investigated the effect and mechanism of biochar addition on nitrogen and phosphorus transformation to enhance the efficacy and quality of compost products. The findings reveal that incorporating biochar considerably enhanced the process of nutrient conversion. Specifically, biochar addition promoted the retention of bioavailable organic nitrogen and reduced nitrogen loss by 28.1 %. Meanwhile, adding biochar inhibited the conversion of available phosphorus to non-available phosphorus while enhancing its conversion to moderately available phosphorus, thereby preserving phosphorus availability post-composting. Furthermore, the inclusion of biochar altered microbial community structure and fostered organic matter retention and humus formation, ultimately affecting the modification of nitrogen and phosphorus forms. Structural equation modeling revealed that microbial community had a more pronounced impact on bioavailable organic nitrogen, while humic acid exerted a more significant effect on phosphorus availability. This research provides a viable approach and foundation for regulating the levels of nitrogen and phosphorus nutrients during composting, serving as a valuable reference for the development of sustainable utilization technologies pertaining to CMHRs.

Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma.

The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy and immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC treatment remains limited, and the underlying mechanisms are still uncertain. Therefore, this study aimed to characterize the effects and mechanisms of ATO in HCC. By evaluating the susceptibilities of human and murine HCC cell lines to ATO treatment, we discovered that HCC cells exhibited a range of sensitivity to ATO treatment, highlighting their inherent heterogeneity. A gene signature comprising 265 genes was identified to distinguish ATO-sensitive from ATO-insensitive cells. According to this signature, HCC patients have also been classified and exhibited differential features of ATO response. Our results showed that ATO treatment induced reactive oxygen species (ROS) accumulation and the activation of multiple cell death modalities, including necroptosis and ferroptosis, in ATO-sensitive HCC cells. Meanwhile, elevated tumoral immunogenicity was also observed in ATO-sensitive HCC cells. Similar effects were not observed in ATO-insensitive cells. We reported that ATO treatment induced mitochondrial injury and mtDNA release into the cytoplasm in ATO-sensitive HCC tumors. This subsequently activated the cGAS-STING-IFN axis, facilitating CD8+ T cell infiltration and activation. However, we found that the IFN pathway also induced tumoral PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted the anti-tumor response of ATO in ATO-sensitive HCC tumors. In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.

Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi.

Dental calculi can cause gingival bleeding and periodontitis, yet the mechanism underlying the formation of such mineral build-ups, and in particular the role of the local microenvironment, are unclear. Here we show that the formation of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps (NETs) from being degradable by the enzyme DNase I to being degradation resistant, promoting the nucleation and growth of apatite. DNase I inhibited NET-induced mineralization in vitro and ex vivo, yet plasma DNases were ineffective at inhibiting ectopic mineralization in the oral cavity in rodents. The topical application of the DNA-intercalating agent chloroquine in rodents fed with a dental calculogenic diet reverted NET DNA to its degradable form, inhibiting the formation of calculi. Our findings may motivate therapeutic strategies for the reduction of the prevalence of the deposition of bacteria-driven calculi in the oral cavity.

How hetero-single-atom dispersion reconstructed electronic structure of carbon materials and regulated Fenton-like oxidation pathways.

Single-atom catalysts (SACs) have emerged as competitive candidates for Fenton-like oxidation of micro-pollutants in water. However, the impact of metal insertion on the intrinsic catalytic activity of carrier materials has been commonly overlooked, and the environmental risk due to metal leaching still requires attention. In contrast to previous reports, where metal sites were conventionally considered as catalytic centers, our study investigates, for the first time, the crucial catalytic role of the carbon carrier modulated through hetero-single-atom dispersion and the regulation of Fenton-like oxidation pathways. The inherent differences in electronic properties between Fe and Co can effectively trigger long-range electron rearrangement in the sp2-carbon-conjugated structure, creating more electron-rich regions for peroxymonosulfate (PMS) complexation and initiating the electron transfer process (ETP) for pollutant degradation, which imparts the synthesized catalyst (FeCo-NCB) with exceptional catalytic efficiency despite its relatively low metal content. Moreover, the FeCo-NCB/PMS system exhibits enduring decontamination efficiency in complex water matrices, satisfactory catalytic stability, and low metal leaching, signifying promising practical applications. More impressively, the spatial relationship between metal sites and electron density clouds is revealed to determine whether high-valent metal-oxo species (HVMO) are involved during the decomposition of surface complexes. Unlike single-type single-atom dispersion, where metal sites are situated within electron-rich regions, hetero-single-atom dispersion can cause the deviation of electron density clouds from the metal sites, thus hindering the in-situ oxidation of metal within the complexes and minimizing the contribution of HVMO. These findings provide new insights into the development of carbon-based SACs and advance the understanding of nonradical mechanisms underpinning Fenton-like treatments.

Impulsive consensus algorithms for vector second-order Lipschitz nonlinear multi-agent systems using only velocity regulation.

The existing impulsive consensus algorithms for second-order Lipschitz nonlinear multi-agent systems require to apply the impulsive control to both position and velocity vectors at the same time. Such a requirement cannot be met in most of the real-world applications. To overcome the limitations of these impulsive algorithms, two kinds of new second-order impulsive consensus algorithms using only velocity regulation are proposed. Through developing a weighted discontinuous Lyapunov function-based approach that is able to leverage the spectral property of Laplacian matrix, impulse-dwell-time-dependent sufficient conditions for solving second-order impulsive consensus are derived in the form of linear matrix inequalities. Further, it is shown that if the impulsively controlled velocity subsystems are globally exponentially stable, the impulsive static consensus algorithm is able to ensure that all agents tend to an agreed position. Based on the consensus conditions, two convex optimization problems are formulated, by which the impulsive gain matrices for ensuring a prescribed exponential convergence rate can be designed. Finally, the effectiveness of the proposed distributed impulsive consensus algorithms is certified through numerical simulations.

Ability of dynamic gadoxetic acid-enhanced magnetic resonance imaging combined with water-specific T1 mapping to reflect inflammation in a rat model of early-stage nonalcoholic steatohepatitis.

Background: Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) has shown potential in reflecting the hepatic function alterations in nonalcoholic steatohepatitis (NASH). The purpose of this study was to evaluate whether Gd-EOB-DTPA combined with water-specific T1 (wT1) mapping can be used to detect liver inflammation in the early-stage of NASH in rats. Methods: In this study, 54 rats with methionine- and choline-deficient (MCD) diet-induced NASH and 10 normal control rats were examined. A multiecho variable flip angle gradient echo (VFA-GRE) sequence was performed and repeated 40 times after the injection of Gd-EOB-DTPA. The wT1 of the liver and the reduction rate of wT1 (rrT1) were calculated. All rats were histologically evaluated and grouped according to the NASH Clinical Research Network scoring system. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of Gd-EOB-DTPA transport genes. Analysis of variance and least significant difference tests were used for multiple comparisons of quantitative results between all groups. Multiple regression analysis was applied to identify variables associated with precontrast wT1 (wT1pre), and receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance. Results: The rats were grouped according to inflammatory stage (G0 =4, G1 =15, G2 =12, G3 =23) and fibrosis stage (F0 =26, F1 =19, F2 =9). After the infusion of Gd-EOB-DTPA, the rrT1 showed significant differences between the control and NASH groups (P<0.05) but no difference between the different inflammation and fibrosis groups at any time points. The areas under curve (AUCs) of rrT1 at 10, 20, and 30 minutes were only 0.53, 0.58, and 0.61, respectively, for differentiating between low inflammation grade (G0 + G1) and high inflammation grade (G2 + G3). The MRI findings were verified by qRT-PCR examination, in which the Gd-EOB-DTPA transporter expressions showed no significant differences between any inflammation groups. Conclusions: The wT1 mapping quantitative method combined with Gd-EOB-DTPA was not capable of discerning the inflammation grade in a rat model of early-stage NASH.

Biomimetic Self-Maturation Mineralization System for Enamel Repair.

Enamel repair is crucial for restoring tooth function and halting dental caries. However, contemporary research often overlooks the retention of organic residues within the repair layer, which hinders the growth of dense crystals and compromises the properties of the repaired enamel. During the maturation of natural enamel, the organic matrix undergoes enzymatic processing to facilitate further crystal growth, resulting in a highly mineralized tissue. Inspired by this process, a biomimetic self-maturation mineralization system is developed, comprising ribonucleic acid-stabilized amorphous calcium phosphate (RNA-ACP) and ribonuclease (RNase). The RNA-ACP induces initial mineralization in the form of epitaxial crystal growth, while the RNase present in saliva automatically triggers a biomimetic self-maturation process. The mechanistic study further indicates that RNA degradation prompts conformational rearrangement of the RNA-ACP, effectively excluding the organic matter introduced earlier. This exclusion process promotes lateral crystal growth, resulting in the generation of denser enamel-like apatite crystals that are devoid of organic residues. This strategy of eliminating organic residues from enamel crystals enhances the mechanical and physiochemical properties of the repaired enamel. The present study introduces a conceptual biomimetic mineralization strategy for effective enamel repair in clinical practice and offers potential insights into the mechanisms of biomineral formation.

Automatic segmentation of the interscapular brown adipose tissue in rats based on deep learning using the dynamic magnetic resonance fat fraction images.

OBJECTIVE: The study aims to propose an accurate labelling method of interscapular BAT (iBAT) in rats using dynamic MR fat fraction (FF) images with noradrenaline (NE) stimulation and then develop an automatic iBAT segmentation method using a U-Net model. MATERIALS AND METHODS: Thirty-four rats fed different diets or housed at different temperatures underwent successive MR scans before and after NE injection. The iBAT were labelled automatically by identifying the regions with obvious FF change in response to the NE stimulation. Further, these FF images along with the recognized iBAT mask images were used to develop a deep learning network to accomplish the robust segmentation of iBAT in various rat models, even without NE stimulation. The trained model was then validated in rats fed with high-fat diet (HFD) in comparison with normal diet (ND). RESULT: A total of 6510 FF images were collected using a clinical 3.0 T MR scanner. The dice similarity coefficient (DSC) between the automatic and manual labelled results was 0.895 ± 0.022. For the network training, the DSC, precision rate, and recall rate were found to be 0.897 ± 0.061, 0.901 ± 0.068 and 0.899 ± 0.086, respectively. The volumes and FF values of iBAT in HFD rats were higher than ND rats, while the FF decrease was larger in ND rats after NE injection. CONCLUSION: An automatic iBAT segmentation method for rats was successfully developed using the dynamic labelled FF images of activated BAT and deep learning network.

Screening and identification of hub genes of scar physique via weighted gene co-expression network analysis.

Scar physique refers to the abnormal repair of skin injury in some people, which may easily lead to keloid or hypertrophic scar. However, the mechanism of scar physique is still unclear. GSE108110 was obtained from the gene expression omnibus database. Differently expression genes (DEGs) between normal skin tissue of non-scar physique individuals and normal skin tissue of scar physique individuals were screened by R package "limma". Weighted gene co-expression network analysis was performed to find highly relevant gene modules. Functional annotation of DEGs was made. Protein-protein interaction network was constructed, and the identification and analysis of hub DEGs were performed, including identification of hub DEGs associated with scar diseases, MiRNA of hub DEGs prediction, and functional annotation of miRNA. A total of 1389 up-regulate DEGs and 1672 down-regulate DEGs were screened. weighted gene co-expression network analysis analysis showed that the dendrogram and heatmap were used to quantify module similarity by correlation. The associations between clinic traits and the modules were identified based on the correlation between module and scar physique. Eight common hub genes were obtained. The comparative toxicogenomics database shows common hub genes associated with scar tissue. Gene ontology and Kyoto encyclopedia of genes and genomes analysis were significantly enriched in "fibroblast growth factor receptor signaling pathway", "epidermal growth factor receptor signaling pathway", "G1/S transition of mitotic cell cycle", protein polyubiquitination", and others. The 8 hub genes might be involved in the development of scarring and used as early diagnosis, prevention and treatment of scar physique.

Enhanced Oxidation of Organic Compounds by the Ferrihydrite-Ferrate System: The Role of Intramolecular Electron Transfer and Intermediate Iron Species.

Previous studies mostly held that the oxidation capacity of ferrate depends on the involvement of intermediate iron species (i.e., FeIV/FeV), however, the potential role of the metastable complex was disregarded in ferrate-based heterogeneous catalytic oxidation processes. Herein, we reported a complexation-mediated electron transfer mechanism in the ferrihydrite-ferrate system toward sulfamethoxazole (SMX) degradation. A synergy between intermediate FeIV/FeV oxidation and the intramolecular electron transfer step was proposed. Specifically, the conversion of phenyl methyl sulfoxide (PMSO) to methyl phenyl sulfone (PMSO2) suggested that FeIV/FeV was involved in the oxidation of SMX. Moreover, based on the in situ Raman test and chronopotentiometry analysis, the formation of the metastable complex of ferrihydrite/ferrate was found, which possesses higher oxidation potential than free ferrate and could achieve the preliminary oxidation of organics via the electron transfer step. In addition, the amino group of SMX could complex with ferrate, and the resulting metastable complex of ferrihydrite/ferrate would combine further with SMX molecules, leading to intramolecular electron transfer and SMX degradation. The ferrate loss experiments suggested that ferrihydrite could accelerate the decomposition of ferrate. Finally, the effects of pH value, anions, humic acid, and actual water on the degradation of SMX by ferrihydrite-ferrate were also revealed. Overall, ferrihydrite demonstrated high catalytic capacity, good reusability, and nontoxic performance for ferrate activation. The ferrihydrite-ferrate process may be a green and promising method for organic removal in wastewater treatment.