Causal Relationships between Gut Microbiotas, Blood Metabolites, and Neuroendocrine Tumors: A Mediated Mendelian Randomization Study.

Introduction Neuroendocrine tumors (NETs) are a heterogeneous group of epithelial tumors originating from different anatomical sites, identifying the gut microbiota and metabolic mechanisms involved in the onset of NETs may help to develop appropriate disease prevention and monitoring strategies. Methods We employed a mediated two-sample Mendelian Randomization (MR) approach, analyzing gut microbiota from German studies and NET datasets from the 10th round of the FinnGen project. Mediation analyses were conducted using the metabolites dataset from the Canadian Longitudinal Study of Aging (CLSA) and the TwinsUK study. Instrumental variables (IVs) chosen according to established MR criteria and analyzed using the Wald ratio, inverse-variance weighted (IVW), MR-Egger, and weighted median methods. To ensure robustness, sensitivity analyses were performed using Cochrane's Q, Egger's intercept, MR-PRESSO, and leave-one-out (LOO) methods. Results Causal relationships were identified between the genetic determinants of 6, 5, 2, 1, 2, 3 gut microbiotas and the risk of colorectal, lung, pancreatic, rectum, small intestine and stomach NETs. Similarly, the genetic determinants of 4, 6, 1, 5, 10 and 7 metabolites were found to be causally related to the risk of colorectal, lung, pancreatic, rectum, small intestine and stomach NETs, respectively. Through Wald ratio and IVW methods, we preliminarily identified 957 microbiota-metabolite pairs with significant causal associations, and formed 13 mediated relationships between the impact of gut microbiotas on NETs. Conclusion Our study suggests that gut microbiotas and its derived metabolites may contribute to the onset of NET, offering a novel insight into the disease's pathogenesis.

Enhanced recovery after surgery speeds up healing for hip fracture patients.

OBJECTIVE: To investigate the effects of enhanced recovery after surgery (ERAS) on the perioperative healing and stress response in patients with hip fractures. METHODS: A retrospective analysis was conducted on the medical records of 86 patients with hip fractures admitted to the Affiliated Hospital of Southwest Medical University between January 2022 and August 2023. Among them, 48 patients in the research group received ERAS, while 38 patients in the control group received conventional nursing. Hip joint function, pain levels, stress response, fracture healing time, incidence of complications, and nursing satisfaction were compared between the two groups. RESULTS: After nursing, the Harris scores notably increased in both groups, with the research group showing notably higher scores compared to the control group (P<0.05). The levels of cortisol and epinephrine, as well as the visual analog scale scores significantly decreased in both groups, with the research group showing significantly lower levels (P<0.05). In addition, the research group experienced significantly shorter fracture healing time (P<0.05), higher nursing satisfaction (P=0.014), and lower incidence of complications (P=0.028). Logistic regression analysis revealed that age, underlying diseases, nursing method, emotional disorders, and timing of surgery were independent factors influencing the post-nursing outcomes. CONCLUSION: The ERAS mode can effectively alleviate pain, improve hip joint function, reduce fracture healing time and complications, mitigate stress response, and accelerate postoperative recovery in patients with hip fractures. It is worthy of application and promotion in clinical practice.

Conduction system pacing upgrade versus biventricular pacing on pacemaker-induced cardiomyopathy: a retrospective observational study.

Objective: The feasibility of the conduction system pacing (CSP) upgrade as an alternative modality to the traditional biventricular pacing (BiVP) upgrade in patients with pacemaker-induced cardiomyopathy (PICM) remains uncertain. This study sought to compare two modalities of CSP (His bundle pacing (HBP) and left bundle branch pacing (LBBP)) with BiVP and no upgrades in patients with pacing-induced cardiomyopathy. Methods: This retrospective analysis comprised consecutive patients who underwent either BiVP or CSP upgrade for PICM at the cardiac department from 2017 to 2021. Patients with a follow-up period exceeding 12 months were considered for the final analysis. Results: The final group of patients who underwent upgrades included 48 individuals: 11 with BiVP upgrades, 24 with HBP upgrades, and 13 with LBBP upgrades. Compared to the baseline data, there were significant improvements in cardiac performance at the last follow-up. After the upgrade, the QRS duration (127.81 ± 31.89 vs 177.08 ± 34.35 ms, p < 0.001), NYHA class (2.28 ± 0.70 vs 3.04 ± 0.54, p < 0.05), left ventricular end-diastolic diameter (LVEDD) (54.08 ± 4.80 vs 57.50 ± 4.85 mm, p < 0.05), and left ventricular ejection fraction (LVEF) (44.46% ± 6.39% vs 33.15% ± 5.25%, p < 0.001) were improved. There was a noticeable improvement in LVEF in the CSP group (32.15% ± 3.22% vs 44.95% ± 3.99% (p < 0.001)) and the BiVP group (33.90% ± 3.09% vs 40.83% ± 2.99% (p < 0.001)). The changes in QRS duration were more evident in CSP than in BiVP (56.65 ± 11.71 vs 34.67 ± 13.32, p < 0.001). Similarly, the changes in LVEF (12.8 ± 3.66 vs 6.93 ± 3.04, p < 0.001) and LVEDD (5.80 ± 1.71 vs 3.16 ± 1.35, p < 0.001) were greater in CSP than in BiVP. The changes in LVEDD (p = 0.549) and LVEF (p = 0.570) were similar in the LBBP and HBP groups. The threshold in LBBP was also lower than that in HBP (1.01 ± 0.43 vs 1.33 ± 0.32 V, p = 0.019). Conclusion: The improvement of clinical outcomes in CSP was more significant than in BiVP. CSP may be an alternative therapy to CRT for patients with PICM. LBBP would be a better choice than HBP due to its lower thresholds.

Muti-dimensional High-entropy Materials for Energy Conversion Reactions: Current State and Future Trends.

The high-entropy materials (HEMs), composed of five or more elements, have attracted significant attention in electrocatalysis due to their unique physicochemical properties arising from the existence of multi-elements compositions. Beyond chemical composition, microstructure significantly influences the catalytic performance and even the catalytic mechanism towards energy conversion reactions. Given the rapid proliferation of research on HEMs and the critical roles of microstructure in their catalytic performance, a timely and comprehensive review of recent advancements is imperative. This review meticulously examines the synthesis methods and physicochemical characteristics of HEMs with distinct one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) morphologies. By highlighting representative examples from the past five years, we elucidate the unique properties of HEMs with 1D, 2D and 3D microstructures, detailing their intricate influence on electrocatalytic performance, aiming to spur further advancements in this promising research area.

Associations between immune cell traits and autoimmune thyroid diseases: a bidirectional two-sample mendelian randomization study.

Autoimmune thyroid diseases (AITDs), mainly including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common autoimmune disorders characterized by abnormal immune responses targeting the thyroid gland. We conducted a bidirectional two-sample MR analysis using the largest dataset of peripheral immune cell phenotypes from Sardinia, and the AITD dataset from the 10th round of the FinnGen and the UK Biobank project. Instrumental variables (IVs) were rigorously selected based on the three assumptions of MR and analyzed using the Wald ratio, inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were performed using Cochrane's Q, the Egger intercept, the MR-PRESSO, and the leave-one-out (LOO) method to ensure the robustness of the results. The Steiger test was utilized to identify and exclude potential reverse causation. The results showed that 3, 3, and 11 immune cell phenotypes were significantly associated with the risk of AITD. In GD, the proportion of naive CD4-CD8- (DN) T cells in T cells and the proportion of terminally differentiated CD4+T cells in T cells showed the strongest inducing and protective effects, respectively. In HT, lymphocyte count and CD45 on CD4+T cells showed the strongest inducing and protective effects, respectively. In autoimmune hypothyroidism, CD127 CD8+T cell count and terminally differentiated DN T cell count exhibited the strongest inducing and protective effects, respectively. Through MR analysis, our study provides direct genetic evidence of the impact of immune cell traits on AITD risk and lays the groundwork for potential therapeutic and diagnostic target discovery.

Integrated metabolomic and transcriptomic analysis of triterpenoid accumulation in the roots of Codonopsis pilosula var. modesta (Nannf.) L.T.Shen at different altitudes.

INTRODUCTION: Codonopsis Radix is a beneficial traditional Chinese medicine, and triterpenoid are the major bioactive constituents. Codonopsis pilosula var. modesta (Nannf.) L.T.Shen (CPM) is a precious variety of Codonopsis Radix, which is distributed at high mountain areas. The environment plays an important role in the synthesis and metabolism of active ingredients in medicinal plants, but there is no report elaborating on the effect of altitude on terpenoid metabolites accumulation in CPM. OBJECTIVES: This study aims to analyse the effects of altitude on triterpenoid biosynthetic pathways and secondary metabolite accumulation in CPM. MATERIAL AND METHODS: The untargeted metabolomics based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and 10 triterpenoids based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method were analysed at the low-altitude (1480 m) and high-altitude (2300 m) CPM fresh roots. The transcriptome based on high-throughput sequencing technology were combined to analyse the different altitude CPM triterpenoid biosynthetic pathways. RESULTS: A total of 17,351 differentially expressed genes (DEGs) and 55 differentially accumulated metabolites (DAMs) were detected from the different altitude CPM, and there are significant differences in the content of the 10 triterpenoids. The results of transcriptome study showed that CPM could significantly up-regulate the gene expression levels of seven key enzymes in the triterpenoid biosynthetic pathway. CONCLUSIONS: The CPM at high altitude is more likely to accumulate triterpenes than those at low altitude, which was related to the up-regulation of the gene expression levels of seven key enzymes. These results expand our understanding of how altitude affects plant metabolite biosynthesis.

CuCl2/FeCl3 Bimetallic Photocatalyst for Sustainable Ethylene Production from Ethanol via Recoverable Redox Cycles.

Photocatalytic conversions of ethanol to valuable chemicals are significant organic synthesis reactions. Herein, we developed a CuCl2/FeCl3 bimetallic photocatalyst for sustainable dehydration of ethanol to ethylene by recoverable redox cycles. The selectivity of ethylene was 98.3% for CuCl2/FeCl3, which is much higher than that of CuCl2 (34.5%) and FeCl3 (86.5%). Due to the ligand-to-metal charge transfer (LMCT) process involved in generating the liquid products, the CuCl2/FeCl3 catalyst will be reduced to CuCl/FeCl2. Oxygen (O2) is required for the recovery of CuCl2/FeCl3 to avoid exhaustion. The soluble Fe3+/Fe2+ redox species deliver catalyst regeneration properties more efficiently than single metal couples, making a series of redox reactions (Cu2+/Cu+, Fe3+/Fe2+, and O2/ethanol couples) recyclable with synergistic effects. A flow reactor was designed to facilitate the continuous production of ethylene. The understanding of bimetallic synergism and consecutive reactions promotes the industrial application process of photocatalytic organic reactions.

Tuning charge transport by manipulating concentration dependent single-molecule absorption configurations.

Understanding and tuning charge transport in molecular junctions is pivotal for crafting molecular devices with tailored functionalities. Here, we report a novel approach to manipulate the absorption configuration within a 4,4'-bipyridine (4,4'-BPY) molecular junction, utilizing the scanning tunneling microscope break junction technique in a concentration-dependent manner. Single-molecule conductance measurements demonstrate that the molecular junctions exhibit a significant concentration dependence, with a transition from high conductance (HC) to low conductance (LC) states as the concentration decreases. Moreover, we identified an additional conductance state in the molecular junctions besides already known HC and LC states. Flicker noise analysis and theoretical calculations provided valuable insights into the underlying charge transport mechanisms and single-molecule absorption configurations concerning varying concentrations. These findings contribute to a fundamental comprehension of charge transport in concentration-dependent molecular junctions. Furthermore, they offer promising prospects for controlling single-molecule adsorption configurations, thereby paving the way for future molecular devices.

High-speed centrifugation rather than Lipoclear reagent can be used for removing the interference of lipemia on serological tests of infectious diseases: AIDS, hepatitis B, hepatitis C, and syphilis by chemiluminescent microparticle immunoassay.

The aim of this study was to investigate the interference of lipemia on measurement of HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HCV, HIV Ag/Ab, and anti-TP in serum by chemiluminescent microparticle immunoassay (CMIA) and compare lipemia removing performance between high-speed centrifugation and Lipoclear reagent. Mixed native serum samples (NSs) and hyperlipemia serum samples (HLS) were prepared for the investigated parameters. The levels of these parameters in NS and HLS were determined by CMIA on an Abbott ARCHITECT i2000SR immunoassay analyzer. HBsAg, anti-HBs, and anti-TP were affected with relative bias >12.5% (acceptable limit) when the level of triacylglycerol (TG) was higher than 27.12 mmol/L in HLS. Clinically unacceptable bias were observed for HBeAg and anti-HBe in HLS with TG higher than 40.52 mmol/L. However, anti-HCV and HIV Ag/Ab were not interfered in severe lipemia with TG < 52.03 mmol/L. In addition, the Lipoclear reagent did not reduce the interference of lipemia with relative bias from -62.50% to -18.02%. The high-speed centrifugation under the optimized condition of 12 000g for 10 min successfully removed the interference of lipemia with relative bias from -5.93% to 0% for HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and anti-TP. To conclude, high-speed centrifugation can be used for removing the interference of lipemia to measure HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and anti-TP. Accordingly, a standardized sample preanalytical preparation of the patients and other screening participants as well as a specimen examination procedure for removing lipemia interference on the serological tests was recommended.

Recent Progress on Perovskite-Based Electrocatalysts for Efficient CO2 Reduction.

An efficient carbon dioxide reduction reaction (CO2RR), which reduces CO2 to low-carbon fuels and high-value chemicals, is a promising approach for realizing the goal of carbon neutrality, for which effective but low-cost catalysts are critically important. Recently, many inorganic perovskite-based materials with tunable chemical compositions have been applied in the electrochemical CO2RR, which exhibited advanced catalytic performance. Therefore, a timely review of this progress, which has not been reported to date, is imperative. Herein, the physicochemical characteristics, fabrication methods and applications of inorganic perovskites and their derivatives in electrochemical CO2RR are systematically reviewed, with emphasis on the structural evolution and product selectivity of these electrocatalysts. What is more, the current challenges and future directions of perovskite-based materials regarding efficient CO2RR are proposed, to shed light on the further development of this prospective research area.

Allyl methyl disulfide (AMDS) prevents N,N-dimethyl formamide-induced liver damage by suppressing oxidative stress and NLRP3 inflammasome activation.

N,N-dimethylformamide (DMF), a widely consumed industrial solvent with persistent characteristics, can induce occupational liver damage and pose threats to the general population due to the enormous DMF-containing industrial efflux and emission from indoor facilities. This study was performed to explore the roles of allyl methyl disulfide (AMDS) in liver damage induced by DMF and the underlying mechanisms. AMDS was found to effectively suppress the elevation in the liver weight/body weight ratio and serum aminotransferase activities, and reduce the mortality of mice induced by DMF. In addition, AMDS abrogated DMF-elicited increases in malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels and decreases in glutathione (GSH) levels in mouse livers. The increase in macrophage number, mRNA expression of M1 macrophage biomarkers, and protein expression of key components in the NF-κB pathway and NLRP3 inflammasome induced by DMF exposure were all suppressed by AMDS in mouse livers. Furthermore, AMDS inhibited DMF-induced cell damage and NF-κB activation in cocultured AML12 hepatocytes and J774A.1 macrophages. However, AMDS per se did not significantly affect the protein level and activity of CYP2E1. Collectively, these results demonstrate that AMDS effectively ameliorates DMF-induced acute liver damage possibly by suppressing oxidative stress and inactivating the NF-κB pathway and NLRP3 inflammasome.

Conduction system pacing for ventricular pacing requirement is feasible and effective on patients with hypertrophic cardiomyopathy and cardiac dysfunction.

Objective: We aimed to evaluate the feasibility and safety of his-bundle pacing (HBP) and left bundle branch pacing (LBBP) in patients with hypertrophic cardiomyopathy (HCM) and heart failure (HF). Methods: Patients with HF and interventricular septal thickness (IVST) ≥ 13 mm resulted from HCM, who accepted conduction system pacing (CSP) with a percentage of ventricular pacing > 40% from May 2018 to April 2022 were consecutively enrolled in our center. LBBP was preferred and HBP was the alternative therapy unless IVST ≥ 16 mm or LBBP failed, whereas LBBP would be the alternative therapy if HBP failed in patients with IVST ≥ 16 mm. All patients were followed up for at least one year. Data including clinical, echocardiographic parameters and electrocardiogram measurements, were collected and evaluated in patients with and without left ventricular ejection fraction (LVEF) < 50%. Results: A total of 27 patients (65.93 ± 9.09 years old) were enrolled and only 3 patients failed in CSP (11.11%) via LBBP (6/13) and HBP (18/21) procedures. LVEF (P = 0.521), left ventricular end-diastolic diameter (LVEDD) (P = 0.816), and QRS duration (P = 0.928) did not worsen after CSP, and left atrial diameter (LAD) (49.58 ± 8.99 mm vs.47.04 ± 9.82 mm, P = 0.045) tended to improve slightly after 19.19 ± 7.71 months follow-up. Of note, LVEF (39.22%±7.51% vs. 45.22%±9.59%, P = 0.015), LVEDD (52.11 ± 10.10 mm vs. 48.33 ± 9.07 mm, P = 0.037), LAD (50.33 ± 8.93 mm vs. 46.11 ± 5.97 mm, P = 0.013) and New York Heart Association (NYHA) grade (2.67 ± 0.5 vs. 1.38 ± 1.02, P = 0.029) improved in 9 patients with LVEF < 50%, whereas LVEF (P = 0.372), LVEDD (P = 0.665), LAD (P = 0.093) and NYHA grade (P = 0.452) did not deteriorate in patients with preserved ejection fraction. Conclusion: CSP was safe and feasible in patients with HCM and cardiac dysfunction, and did not worsen cardiac performance especially in patients with LVEF < 50%. HBP might be an effective alternative to LBBP in patients with significantly thickened interventricular septum.

A Network Meta-Analysis of Randomized Clinical Trials to Assess the Efficacy and Safety of Antiviral Agents for Immunocompetent Patients with Herpes Zoster-Associated Pain.

BACKGROUND: The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to reduce pain across all stages of the disease. Although many antiviral agents via oral or intravenous administration were recommended by clinical practice, the best approach to prevent HZ-associated pain remains uncertain. OBJECTIVES: The purpose of this study was to compare the efficacy and adverse events of various antiviral agents used for the treatment of HZ-associated pain through a network meta-analysis. STUDY DESIGN: A systematic review and meta-analysis. SETTING: The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to Feb 2020. METHODS: Randomized clinical trials evaluating antiviral agents currently available for treating HZ-associated pain were included. We extracted data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted network meta-analyses with random-effects models. The primary outcome was the presence of acute pain at the end of anti-virus treatment, and the secondary outcomes included the presence of pain at 28-30 days after the onset of the acute herpetic rash, the presence of postherpetic neuralgia (PHN), and any other adverse events. RESULTS: A total of 17 randomized control trials with 5,579 participants were included in this study. According to the results of the network meta-analysis, for the treatment of acute pain, there was no significant difference between oral acyclovir and intravenous acyclovir. Furthermore, oral famciclovir was the most effective treatment concerning both the odds ratio (OR) (superior to placebo OR = 0.25; 95% CI: 0.13~0.48) and the surface under the cumulative ranking curve (SUCRA) values of 0.84 for the treatment of acute pain among all the oral antiviral agents. For the presence of pain at 28-30 days, no significant difference was observed in efficacy between all antiviral treatments and placebo concerning the OR; however, oral valaciclovir ranked first (SUCRA values of 0.96). For the presence of NPH, oral famciclovir was determined to be the most effective (SUCRA values of 0.77) treatment with an efficacy of 0.42 (95% CI: 0.18~0.99) versus placebo. For adverse events, there was no significant difference between oral antivirals and placebo; however, intravenous acyclovir ranked last with a score of OR 4.31 (95% CI: 1.26~14.75) versus placebo. LIMITATIONS: The distribution of severity of pain was different in various studies; then, the lack of availability of individual data prevented us from analyzing the effects of the risk factors. CONCLUSIONS: For the treatment of acute pain and PHN, oral famciclovir was the most effective treatment among all the oral antiviral agents. For alleviating pain after 28-30 days, oral valaciclovir appeared to be the most effective among all antiviral agents. Additionally, all oral antiviral agents were well tolerated. CLINICAL TRIAL REGISTRATION INFORMATION: PROSPERO under the identification CRD42020212834.

Tuning magnetocrystalline anisotropy by controlling the orbital electronic configuration of two-dimensional magnetic materials.

A suitable magnetic anisotropy energy (MAE) is a key factor for magnetic materials. However, an effective MAE control method has not yet been achieved. In this study, we propose a novel strategy to manipulate MAE by rearranging the d-orbitals of metal atoms with oxygen functionalized metallophthalocyanine (MPc) by first-principles calculations. By the dual regulation of electric field and atomic adsorption, we have achieved a substantial amplification of the single regulation method. The use of O atoms to modify the metallophthalocyanine (MPc) sheets effectively adjusts the orbital arrangement of the electronic configuration in the d-orbitals of the transition metal near the Fermi level, thereby modulating the MAE of the structure. More importantly, the electric field amplifies the effect of electric-field regulation by adjusting the distance between the O atom and metal atom. Our results demonstrate a new approach to modulating the MAE of two-dimensional magnetic films for practical application in information storage.

[Response of Soil Organic Carbon Accumulation in Paddy Fields in Fujian Province to Future Temperature Increases].

Understanding the effect of the soil carbon "source-sink" in cropland in China under future warming scenarios is the basis for making reasonable carbon neutralization policies. This study focused on the paddy soil in Fujian Province, a typical subtropical region in China including 84 counties (cities and districts). We employed the 1:50000 soil database and biogeochemical process model (DNDC) to simulate the dynamic changes in paddy soil organic carbon under different warming scenarios for the period of 2017-2053. The results indicated that in the context of normal temperature (control run) and 2, 4, and 6℃ of warming, the total amounts of carbon sequestration of paddy soil in Fujian Province were 11.56,9.44, 7.08, and 4.91 Tg, respectively; accordingly, the average annual carbon sequestration rates (expressed by C) were 173, 141, 106, and 74 kg·(hm2·a)-1, indicating that the rate of carbon sequestration was decreasing with the increase in future temperature. However, overall, the paddy field soil in the province was still a "carbon sink" under the warming of 6 (C. We also found that the gleyed paddy soil was mostly affected by the increase in temperature, and the decrease in carbon sequestration rate ranged from 20% to 69% using different treatments. In contrast, the salinized paddy soil was slightly affected, with a 14%-43% decrease in carbon sequestration rates. As for the different administrative regions, Sanming City was the most affected by temperature increase, with the rate of carbon sequestration decreasing by 27%-83% using different treatments. However, it was reduced by only 10%-41% and 14%-42% in Quanzhou and Putian (coastal areas), respectively. Overall, due to different soil properties, fertilization management, and climatic environment, there was a strong variability in the carbon sequestration rates of paddy soil for different soil subtypes and administrative regions in Fujian in response to future climatic warming.

Fe(III) Docking-Activated Sites in Layered Birnessite for Efficient Water Oxidation.

Non-noble metal catalysts for promoting the sluggish kinetics of oxygen evolution reaction (OER) are essential to efficient water splitting for sustainable hydrogen production. Birnessite has a local atomic structure similar to that of an oxygen-evolving complex in photosystem II, while the catalytic activity of birnessite is far from satisfactory. Herein, we report a novel Fe-Birnessite (Fe-Bir) catalyst obtained by controlled Fe(III) intercalation- and docking-induced layer reconstruction. The reconstruction dramatically lowers the OER overpotential to 240 mV at 10 mA/cm2 and the Tafel slope to 33 mV/dec, making Fe-Bir the best of all the reported Bir-based catalysts, even on par with the best transition-metal-based OER catalysts. Experimental characterizations and molecular dynamics simulations elucidate that the catalyst features active Fe(III)-O-Mn(III) centers interfaced with ordered water molecules between neighboring layers, which lower reorganization energy and accelerate electron transfer. DFT calculations and kinetic measurements show non-concerted PCET steps conforming to a new OER mechanism, wherein the neighboring Fe(III) and Mn(III) synergistically co-adsorb OH* and O* intermediates with a substantially reduced O-O coupling activation energy. This work highlights the importance of elaborately engineering the confined interlayer environment of birnessite and more generally, layered materials, for efficient energy conversion catalysis.