Heterobimetallic NiFe Complex for Photocatalytic CO2 Reduction: United Efforts of NiFe Dual Sites.

Catalytic CO2 reduction poses a significant challenge for the conversion of CO2 into chemicals and fuels. Ni-Fe carbon monoxide dehydrogenase ([NiFe]-CODH) effectively mediates the reversible conversion of CO2 and CO at a nearly thermodynamic equilibrium potential, highlighting the heterobimetallic cooperation for the design of CO2 reduction catalysts. However, numerous NiFe biomimetic model complexes have realized little success in CO2 reduction catalysis, which underscores the crucial role of precise bimetallic configuration and functionality. Herein, we presented a heterobimetallic NiFe complex for the photocatalytic reduction of CO2 to CO, demonstrating significantly enhanced catalytic performance compared to the homonuclear NiNi catalyst. Photocatalytic and mechanistic investigations revealed that with the assistance of a redox-active phenanthroline ligand, NiFe achieves dual-site activation of CO2 through a pivotal intermediate, NiII(µ-CO22--κC:κO)FeII, where the Lewis acidity of the FeII site plays an important role, as corroborated in the homonuclear FeFe system. This study introduces the first heteronuclear NiFe molecular catalyst capable of efficiently catalyzing the reduction of CO2 to CO, deepening insights into heterobimetallic cooperation and offering a novel strategy for designing highly active and selective CO2 reduction catalysts.

Oncogenic KRAS drives immunosuppression of colorectal cancer by impairing DDX60-mediated dsRNA accumulation and viral mimicry.

The interferon (IFN) response is vital for the effectiveness of immune checkpoint inhibition (ICI) therapy. Our previous research showed that KRAS (Kirsten rat sarcoma viral) mutation impairs the IFN response in colorectal cancer (CRC), with an unclear mechanism. Here, we demonstrate that KRAS accelerates double-stranded RNA (dsRNA) degradation, impairing dsRNA sensing and IFN response by down-regulating DExD/H-box helicase 6 (DDX60). DDX60 was identified as a KRAS target here and could bind to dsRNAs to protect against RNA-induced silencing complex (RISC)-mediated degradation. Overexpressing DDX60 induced dsRNA accumulation, reactivated IFN signaling, and increased CRC sensitivity to ICI therapy. Mechanistically, KRAS engaged the AKT (also known as protein kinase B)-GSK3ß (glycogen synthase kinase-3 beta) pathway to suppress STAT3 phosphorylation, thereby inhibiting STAT3-driven DDX60 transcription. Our findings reveal a role for KRAS in dsRNA homeostasis, suggesting potential strategies to convert "cold" tumors to "hot" and to overcome ICI resistance in CRC with KRAS mutations.

Bioinspired Binickel Catalyst for Carbon Dioxide Reduction: The Importance of Metal-ligand Cooperation.

Catalyst design for the efficient CO2 reduction reaction (CO2RR) remains a crucial challenge for the conversion of CO2 to fuels. Natural Ni-Fe carbon monoxide dehydrogenase (NiFe-CODH) achieves reversible conversion of CO2 and CO at nearly thermodynamic equilibrium potential, which provides a template for developing CO2RR catalysts. However, compared with the natural enzyme, most biomimetic synthetic Ni-Fe complexes exhibit negligible CO2RR catalytic activities, which emphasizes the significance of effective bimetallic cooperation for CO2 activation. Enlightened by bimetallic synergy, we herein report a dinickel complex, NiIINiII(bphpp)(AcO)2 (where NiNi(bphpp) is derived from H2bphpp = 2,9-bis(5-tert-butyl-2-hydroxy-3-pyridylphenyl)-1,10-phenanthroline) for electrocatalytic reduction of CO2 to CO, which exhibits a remarkable reactivity approximately 5 times higher than that of the mononuclear Ni catalyst. Electrochemical and computational studies have revealed that the redox-active phenanthroline moiety effectively modulates the electron injection and transfer akin to the [Fe3S4] cluster in NiFe-CODH, and the secondary Ni site facilitates the C-O bond activation and cleavage through electron mediation and Lewis acid characteristics. Our work underscores the significant role of bimetallic cooperation in CO2 reduction catalysis and provides valuable guidance for the rational design of CO2RR catalysts.

Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes: A Meta-Regression of Acupuncture Randomized Controlled Trials.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS: High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.

Genetically modified non-human primate models for research on neurodegenerative diseases.

Neurodegenerative diseases (NDs) are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Currently, there are no therapies available that can delay, stop, or reverse the pathological progression of NDs in clinical settings. As the population ages, NDs are imposing a huge burden on public health systems and affected families. Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments. While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms, the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap. Old World non-human primates (NHPs), such as rhesus, cynomolgus, and vervet monkeys, are phylogenetically, physiologically, biochemically, and behaviorally most relevant to humans. This is particularly evident in the similarity of the structure and function of their central nervous systems, rendering such species uniquely valuable for neuroscience research. Recently, the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms. This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained, as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

Pivotal Role of Geometry Regulation on O-O Bond Formation Mechanism of Bimetallic Water Oxidation Catalysts.

In this study, we highlight the impact of catalyst geometry on the formation of O-O bonds in Cu2 and Fe2 catalysts. A series of Cu2 complexes with diverse linkers are designed as electrocatalysts for water oxidation. Interestingly, the catalytic performance of these Cu2 complexes is enhanced as their molecular skeletons become more rigid, which contrasts with the behavior observed in our previous investigation with Fe2 analogs. Moreover, mechanistic studies reveal that the reactivity of the bridging O atom results in distinct pathways for O-O bond formation in Cu2 and Fe2 catalysts. In Cu2 systems, the coupling takes place between a terminal CuIII -OH and a bridging µ-O⋅ radical. Whereas in Fe2 systems, it involves the coupling of two terminal Fe-oxo entities. Furthermore, an in-depth structure-activity analysis uncovers the spatial geometric prerequisites for the coupling of the terminal OH with the bridging µ-O⋅ radical, ultimately leading to the O-O bond formation. Overall, this study emphasizes the critical role of precisely adjusting the spatial geometry of catalysts to align with the O-O bonding pathway.

Vague-Segment Technique: Automatic Computation of Tumor Stroma Ratio for Breast Cancer on Whole Slides.

The calculation of Tumor Stroma Ratio (TSR) is a challenging medical issue that could improve predictions of neoadjuvant chemotherapy benefits and patient prognoses. Although several studies on breast cancer and deep learning methods have achieved promising results, the drawbacks that pixel-level semantic segmentation processes could not extract core tumor regions containing both tumor pixels and stroma pixels make it difficult to accurately calculate TSR. In this paper, we propose a Vague-Segment Technique (VST) consisting of a designed SwinV2UNet module and a modified Suzuki algorithm. Specifically, the SwinV2UNet identifies tumor pixels and generate pixel-level classification results, based on which the modified Suzuki algorithm extracts the contour of core tumor regions in terms of cosine angle. Through this way, VST obtains vaguely segmentation results of core tumor regions containing both tumor pixels and stroma pixels, where the TSR could be calculated by the formula of Intersection over Union (IOU). For the training and evaluation, we utilize the well-known The Cancer Genome Atlas (TCGA) database to create an annotated dataset, while 150 images with TSR annotations from real cases are also collected. The experimental results illustrate that the proposed VST could generate better tumor identification results compared with state-of-the-art methods, where the extracted core tumor regions lead to more consistencies of calculated TSR with senior experts compared to junior pathologists. The experimental results demonstrate the superiority of our proposed pipeline, which has promise for future clinical application.

Redox-Active Ligand Assisted Multielectron Catalysis: A Case of Electrocatalyzed CO2-to-CO Conversion.

The selective reduction of carbon dioxide remains a significant challenge due to the complex multielectron/proton transfer process, which results in a high kinetic barrier and the production of diverse products. Inspired by the electrostatic and H-bonding interactions observed in the second sphere of the [NiFe]-CODH enzyme, researchers have extensively explored these interactions to regulate proton transfer, stabilize intermediates, and ultimately improve the performance of catalytic CO2 reduction. In this work, a series of cobalt(II) tetraphenylporphyrins with varying numbers of redox-active nitro groups were synthesized and evaluated as CO2 reduction electrocatalysts. Analyses of the redox properties of these complexes revealed a consistent relationship between the number of nitro groups and the corresponding accepted electron number of the ligand at -1.59 V vs. Fc+/0. Among the catalysts tested, TNPPCo with four nitro groups exhibited the most efficient catalytic activity with a turnover frequency of 4.9 × 104 s-1 and a catalytic onset potential 820 mV more positive than that of the parent TPPCo. Furthermore, the turnover frequencies of the catalysts increased with a higher number of nitro groups. These results demonstrate the promising design strategy of incorporating multielectron redox-active ligands into CO2 reduction catalysts to enhance catalytic performance.

Acupuncture for in vitro fertilization-embryo transfer: an overview of systematic reviews. / é’ˆç¸è¾ åŠ©ä½“å¤–å—ç²¾èƒšèƒŽç§»æ¤çš„ç³»ç»Ÿè¯„ä»·å†è¯„ä»·.

OBJECTIVES: To evaluate the report quality, methodological quality and evidence quality of the systematic reviews and meta-analyses (SRs/MAs) of acupuncture for in vitro fertilization-embryo transfer (IVF-ET). METHODS: The SRs/MAs of acupuncture for IVF-ET were searched electronically from databases of CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, from inception of each database to September 27th, 2022. Two reviewers independently screened the literature and extracted the data. Using PRISMA statement, the AMSTAR 2 scale and the GRADE system, the report quality, methodological quality and evidence quality of the included SRs/MAs were assessed. RESULTS: A total of 28 SRs/MAs were included, with PRISMA scores ranging from 8.5 points to 27 points. The problems of report quality focused on protocol and registration, retrieval, risk of bias in studies, additional analysis, limitations and funding. The methodological quality of included studies was generally low, reflecting on items 2, 3, 7, 10, 12 and 16. A total of 85 outcome indexes were included in the GRADE system for evidence grade evaluation. Most of the evidences were low or very low in quality. The reasons for the downgrade were related to study limitations, inconsistency, imprecision and publication bias. CONCLUSIONS: Acupuncture therapy improves the outcomes of IVF-ET, but the methodological quality and evidence quality of related SRs/MAs are low. It is recommended to conduct more high-quality studies in the future to provide more reliable evidences.

Use of Evidence-Based Research Approach in RCTs of Acupuncture-Related Therapies for Primary Dysmenorrhea: A Meta-Research.

OBJECTIVE: To assess the use of evidence-based research (EBR) approach in randomized controlled trials (RCTs) of acupuncture-related therapies for primary dysmenorrhea (PD). METHODS: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Database, and China Science and Technology Journal Database were searched from January 2013 to December 2022 for RCTs of acupuncture on PD. The full text and references of each RCT were read to assess whether systematic reviews (SRs) or other types of studies with similar research questions and end-users' perspectives were cited to justify and design the trial. In addition, the discussion section were analyzed to evaluate whether trials placed the new result in the existing SRs to draw a conclusion. Multivariable logistic regression was used to find variables that associated with 3 aspects of EBR approach: (1) citing clinical studies for justification, (2) citing relevant studies that obtain the perspectives of end users, and (3) citing clinical studies for results discussion. RESULTS: Of 473 RCTs included, 45.67% (216) of the trials cited relevant similar studies, 21.56% (102) referenced to the studies that collected end-users' perspectives, and 10.99% (52) placed result in the context of the previous research. Few RCTs appropriately applied EBR approach. Among all the included studies, 3.17% (15) of the trials used SRs to inform study questions but none of them used updated SRs with acceptable quality; 1.05% (5) of the trials cited SRs of end-user's perspectives in the justification and design of the study, and only 1 trial added results in existing SR to draw a conclusion. Year of publication, language, funding, registration, ethical approval and number of sites were significantly associated with 1 of the 3 aspects of EBR approach. CONCLUSIONS: Few RCTs in acupuncture-related therapies for PD used the EBR approach to minimize research redundancy. Researchers, research institutes, funding agencies, ethics committees, journals and peer reviewers in acupuncture should make efforts to use and promote the EBR approach to ensure the value of new trials.

Selective Four-Electron Reduction of Oxygen by a Nonheme Heterobimetallic CuFe Complex.

We report herein the first nonheme CuFe oxygen reduction catalyst ([CuII (bpbp)(µ-OAc)2 FeIII ]2+ , CuFe-OAc), which serves as a functional model of cytochrome c oxidase and can catalyze oxygen reduction to water with a turnover frequency of 2.4×103  s-1 and selectivity of 96.0 % in the presence of Et3 NH+ . This performance significantly outcompetes its homobimetallic analogues (2.7 s-1 of CuCu-OAc with %H2 O2 selectivity of 98.9 %, and inactive of FeFe-OAc) under the same conditions. Structure-activity relationship studies, in combination with density functional theory calculation, show that the CuFe center efficiently mediates O-O bond cleavage via a CuII (µ-η1 : η2 -O2 )FeIII peroxo intermediate in which the peroxo ligand possesses distinctive coordinating and electronic character. Our work sheds light on the nature of Cu/Fe heterobimetallic cooperation in oxygen reduction catalysis and demonstrates the potential of this synergistic effect in the design of nonheme oxygen reduction catalysts.

Characteristics and risk assessment of chilling injury on Morchella esculenta in Western Sichuan Plateau, China.

The development of precise climate risk zoning for chilling injury of Morchella esculenta can provide scientific basis for agricultural cultivation planning, dynamic assessment of chilling injury, and disaster prevention strategies. Based on meteorological data from 17 counties (cities) that located below the altitude of 3000 m in the Western Sichuan Plateau from 2011 to 2020, we analyzed the critical meteorological conditions for M. esculenta disasters in typical years. With the average yearly cold accumulation and cold injury frequency during the first day when the temperature remained stable between 5 ℃ and 10 ℃ during mushroom emergence as zoning indicators, we established a geographical spatial distribution model of the cold injury index, and then divided the risk level of M. esculenta cold injury in the Western Sichuan Plateau, evaluated the risk of cold injury. The results showed that the temperature index for chilling injury risk of M. esculenta in the study area was the daily minimum temperature ≤2.0 ℃. The daily average temperature <6.0 ℃ would cause slow growth or the cessation of growth, which was set as a warning indicator for chilling injury risk. Along the Dadu River and Minjiang River basins, the frequency of chilling injury on M. esculenta increased from south to north. Wenchuan, Maoxian, and Lixian had the fewest overall chilling injuries during the study period, whereas Jiulong, Yajiang, and Batang had the most. The duration for cold injury was mainly 1-3 d, followed by 4-5 d, and rarely for >5 d. The frequency of chilling injury lasting for more than 5 d in Xiangcheng, Batang, Jiulong, Yajiang, and Xiaojin was more than that lasting for 4-5 d. The annual average days of chilling injury of was 3.0-27.4 d, the daily average minimum temperature was -0.84-1.36 ℃, the extreme lowest temperature was -5.8-0.1 ℃, and the average accumulated cold was 0.16-9.64 ℃·d during the period of chilling injury. With the increases of elevation and latitude, the average days of chilling injury and the average accumulated cold increased. The largest duration of chilling injury was 3-20 d, the maximum accumulated cold was 0.44-13.34 ℃·d. The risk of chilling injury to M. esculenta increased from south to north and from low elevation to high elevation. The suitable planting areas were distributed in strips and branches along the direction of mountains and rivers, mainly in the flat areas of low mountains and valleys below the altitude of 2200 m, including Kangding, Luding, Danba, Wenchuan, Lixian, Maoxian, Jiuzhaigou, and Songpan.

[Fidelity in acupuncture-moxibustion clinical research: application and reflection].

As an indicator that measures the degree of implementation of intervention measures during the implementation process, fidelity could be used for monitoring and quality evaluation of the completion degree of intervention measures, and plays an important role in improving the degree of intervention implementation and clarifying the factors that affect intervention implementation. This article aims to introduce the connotation and significance, measurement, control, and current application status of fidelity, as well as the current application status of fidelity in acupuncture-moxibustion clinical research and its inspiration for future research. Meanwhile, based on the existing evaluation tool development methods of fidelity and the characteristics of acupuncture-moxibustion clinical research, a preliminary fidelity evaluation framework is proposed. Introducing fidelity into acupuncture-moxibustion clinical research could improve the implementation quality and compliance of acupuncture-moxibustion in clinical research, increase the credibility and effectiveness of clinical research results, and promote the transformation of acupuncture-moxibustion experience into easily learnable and promotable treatment plans.

Heterobimetallic NiFe Cooperative Molecular Water Oxidation Catalyst.

We reported herein the development of heterobimetallic NiFe molecular platform to understand NiFe synergistic effect in water oxidation catalysis. Compared to homonuclear bimetallic compounds (NiNi and FeFe), NiFe complex possesses more remarkable catalytic water oxidation performance. Mechanistic studies suggest that this remarkable difference is attributed to the fact that NiFe synergy can effectively promote O-O bond formation. The generated NiIII (µ-O)FeIV =O is the key intermediate and O-O bond was formed via intramolecular oxyl-oxo coupling between bridged O radical and terminal FeIV =O moiety.

Identifying Metal-Oxo/Peroxo Intermediates in Catalytic Water Oxidation by In Situ Electrochemical Mass Spectrometry.

Molecular catalysis of water oxidation has been intensively investigated, but its mechanism is still not yet fully understood. This study aims at capturing and identifying key short-lived intermediates directly during the water oxidation catalyzed by a cobalt-tetraamido macrocyclic ligand complex using a newly developed an in situ electrochemical mass spectrometry (EC-MS) method. Two key ligand-centered-oxidation intermediates, [(L2-)CoIIIOH] and [(L2-)CoIIIOOH], were directly observed for the first time, and further confirmed by 18O-labeling and collision-induced dissociation studies. These experimental results further confirmed the rationality of the water nucleophilic attack mechanism for the single-site water oxidation catalysis. This work also demonstrated that such an in situ EC-MS method is a promising analytical tool for redox catalytic processes, not only limited to water oxidation.

[Variation characteristics of normalized difference vegetation index in Northwestern Sichuan Plateau and its response to extreme climate during 2001-2020]. / 2001­2020å¹´å·è¥¿åŒ—é«˜åŽŸå½’ä¸€åŒ–æ¤è¢«æŒ‡æ•°æ¼”å˜ç‰¹å¾åŠå ¶å¯¹æžç«¯æ°”å€™çš„å“åº”.

The northwestern Sichuan Plateau is a typical eco-climate sensitive area, where vegetation condition is closely related to climate change. We used the MODIS-NDVI and the meteorological data during 2001-2020 to investigate the change trend of normalized difference vegetation index (NDVI) and the mechanism underlying its responses to climate factors in the growing season of northwestern Sichuan Plateau by using the methods of maximum value composite, geodetector model, trend analysis, and correlation analysis. The results showed that vegetation coverage in northwestern Sichuan Plateau was overall good during the study period. 86.8% of the regional vegetation was stable, 12.6% of the regional NDVI was weakly and continuously increasing, and 0.6% of the regional NDVI was decreasing. The ecological environment of the whole region exhibited a steady and good development trend. The vegetation coverage in the study area exhibited apparent spatial variation with a general tendency of increase from southwest to northeast, as well as obvious variation with elevation. The NDVI rose with elevation below 1350 m, varied slightly from 1350 to 3650 m, dropped from 3650 to 5900 m, with a rapid drop between 4750 to 5900 m. There was almost no vegetation above 5900 m. The NDVI of northwestern Sichuan Plateau was affected by the interactions of natural factors. Thermal factors were the dominant climate factors, including monthly maximum value of daily maximum temperature, monthly minimum value of daily minimum temperature, growing season length, annual mean temperature, mean temperature over the growing season. All these factors were positively correlated with NDVI excepted for monthly maximum value of daily maximum temperature. The response of NDVI to temperature index was higher than that of precipitation index. Under the background of climate warming, extreme temperature warming index played a major role in promoting the growth and improvement of vegetation in northwestern Sichuan Plateau, especially in high-altitude areas.

Spectra of Self-Similar Measures.

This paper is devoted to the characterization of spectrum candidates with a new tree structure to be the spectra of a spectral self-similar measure µN,D generated by the finite integer digit set D and the compression ratio N-1. The tree structure is introduced with the language of symbolic space and widens the field of spectrum candidates. The spectrum candidate considered by Laba and Wang is a set with a special tree structure. After showing a new criterion for the spectrum candidate with a tree structure to be a spectrum of µN,D, three sufficient and necessary conditions for the spectrum candidate with a tree structure to be a spectrum of µN,D were obtained. This result extends the conclusion of Laba and Wang. As an application, an example of spectrum candidate Λ(N,B) with the tree structure associated with a self-similar measure is given. By our results, we obtain that Λ(N,B) is a spectrum of the self-similar measure. However, neither the method of Laba and Wang nor that of Strichartz is applicable to the set Λ(N,B).

Proton-Coupled Electron-Transfer Reduction of Dioxygen: The Importance of Precursor Complex Formation between Electron Donor and Proton Donor.

The proton-coupled electron transfer (PCET) reaction has drawn extensive attention for its widespread occurrence in chemistry, biology, and materials science. The mechanistic studies via model systems such as tyrosine and phenol oxidation have gradually deepened the understanding of PCET reactions, which was widely accepted and applied to bond activation and transformation. However, direct PCET activation of nonpolar bonds such as the C-H bond, O2, and N2 has yet to be explored. Herein, we report that the interaction between electron donor and proton donor could overcome the barrier of direct O2 activation via a concerted electron-proton transfer mechanism. This work provides a new strategy for developing direct PCET activation of nonpolar bonds.

Transplantation of Gut Microbiota From High-Fat-Diet-Tolerant Cynomolgus Monkeys Alleviates Hyperlipidemia and Hepatic Steatosis in Rats.

Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of Megasphaera remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of Megasphaera significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of Megasphaera in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype.