Syndromic immune disorder caused by a viable hypomorphic allele of spliceosome component Snrnp40.

We report a new immunodeficiency disorder in mice caused by a viable hypomorphic mutation of Snrnp40, an essential gene encoding a subunit of the U5 small nuclear ribonucleoprotein (snRNP) complex of the spliceosome. Snrnp40 is ubiquitous but strongly expressed in lymphoid tissue. Homozygous mutant mice showed hypersusceptibility to infection by murine cytomegalovirus and multiple defects of lymphoid development, stability and function. Cell-intrinsic defects of hematopoietic stem cell differentiation also affected homozygous mutants. SNRNP40 deficiency in primary hematopoietic stem cells or T cells or the EL4 cell line increased the frequency of splicing errors, mostly intron retention, in several hundred messenger RNAs. Altered expression of proteins associated with immune cell function was also observed in Snrnp40-mutant cells. The immunological consequences of SNRNP40 deficiency presumably result from cumulative, moderate effects on processing of many different mRNA molecules and secondary reductions in the expression of critical immune proteins, yielding a syndromic immune disorder.

Thousands of induced germline mutations affecting immune cells identified by automated meiotic mapping coupled with machine learning.

Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation-phenotype association. At this time, CE has evaluated putative mutation-phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

Probing the Roles of Indium Oxides on Copper Catalysts for Enhanced Selectivity during CO2-to-CO Electrochemical Reduction.

The electrochemical CO2 reduction reaction (CO2RR) provides an alternative protocol to producing industrial chemicals with renewable electricity sources, and the highly selective, durable, and economic catalysts should expedite CO2RR applications. Here, we demonstrate a composite Cu-In2O3 catalyst in which a trace amount of In2O3 decorated on Cu surface greatly improves the selectivity and stability for CO2-to-CO reduction as compared to the counterparts (Cu or In2O3), realizing a CO faradaic efficiency (FECO) of 95% at -0.7 V (vs RHE) and no obvious degradation within 7 h. In situ X-ray absorption spectroscopy reveals that In2O3 undergoes the redox reaction and preserves the metallic state of Cu during the CO2RR process. Strong electronic interaction and coupling occur at the Cu/In2O3 interface which serves as the active site for selective CO2RR. Theoretical calculation confirms the roles of In2O3 in preventing oxidation and altering the electronic structure of Cu to assist COOH* formation and demote CO* adsorption at the Cu/In2O3 interface.

Stable Pd-Cu Hydride Catalyst for Efficient Hydrogen Evolution.

Pd has been regarded as one of the alternatives to Pt as a promising hydrogen evolution reaction (HER) catalyst. Strategies including Pd-metal alloys (Pd-M) and Pd hydrides (PdHx) have been proposed to boost HER performances. However, the stability issues, e.g., the dissolution in Pd-M and the hydrogen releasing in PdHx, restrict the industrial application of Pd-based HER catalysts. We here design and synthesize a stable Pd-Cu hydride (PdCu0.2H0.43) catalyst, combining the advantages of both Pd-M and PdHx structures and improving the HER durability simultaneously. The hydrogen intercalation is realized under atmospheric pressure (1.0 atm) following our synthetic approach that imparts high stability to the Pd-Cu hydride structure. The obtained PdCu0.2H0.43 catalyst exhibits a small overpotential of 28 mV at 10 mA/cm2, a low Tafel slope of 23 mV/dec, and excellent HER durability due to its appropriate hydrogen adsorption free energy and alleviated metal dissolution rate.

Enhanced susceptibility to chemically induced colitis caused by excessive endosomal TLR signaling in LRBA-deficient mice.

LPS-responsive beige-like anchor (LRBA) protein deficiency in humans causes immune dysregulation resulting in autoimmunity, inflammatory bowel disease (IBD), hypogammaglobulinemia, regulatory T (Treg) cell defects, and B cell functional defects, but the cellular and molecular mechanisms responsible are incompletely understood. In an ongoing forward genetic screen for N-ethyl-N-nitrosourea (ENU)-induced mutations that increase susceptibility to dextran sodium sulfate (DSS)-induced colitis in mice, we identified two nonsense mutations in Lrba Although Treg cells have been a main focus in LRBA research to date, we found that dendritic cells (DCs) contribute significantly to DSS-induced intestinal inflammation in LRBA-deficient mice. Lrba-/- DCs exhibited excessive IRF3/7- and PI3K/mTORC1-dependent signaling and type I IFN production in response to the stimulation of the Toll-like receptors (TLRs) 3, TLR7, and TLR9. Substantial reductions in cytokine expression and sensitivity to DSS in LRBA-deficient mice were caused by knockout of Unc93b1, a chaperone necessary for trafficking of TLR3, TLR7, and TLR9 to endosomes. Our data support a function for LRBA in limiting endosomal TLR signaling and consequent intestinal inflammation.

Enhanced CO2 Electrochemical Reduction Performance over Cu@AuCu Catalysts at High Noble Metal Utilization Efficiency.

The electrochemical CO2 reduction reaction (CO2RR) represents a viable alternative to help close the anthropogenic carbon cycle and convert intermittent electricity from renewable energy sources to chemical energy in the form of value-added chemicals. The development of economic catalysts possessing high faradaic efficiency (FE) and mass activity (MA) toward CO2RR is critical in accelerating CO2 utilization technology. Herein, an elaborate Au-Cu catalyst where an alloyed AuCu shell caps on a Cu core (Cu@AuCu) is developed and evaluated for CO2-to-CO electrochemical conversion. Specific roles of Cu and Au for CO2RR are revealed in the alloyed core-shell structure, respectively, and a compositional-dependent volcano-plot is disclosed for the Cu@AuCu catalysts toward selective CO production. As a result, the Au2-Cu8 alloyed core-shell catalyst (only 17% Au content) achieves an FECO value as high as 94% and an MACO of 439 mA/mgAu at -0.8 V (vs RHE), superior to the values for pure Au, reflecting its high noble metal utilization efficiency.

Bariatric interventions in obesity treatment and prevention in pediatric acute lymphoblastic leukemia: a systematic review and meta-analysis.

Most children are surviving acute lymphoblastic leukemia (ALL) today. Yet, the emergence of cardiometabolic comorbidities in this population may impact long-term outcomes including the quality of life and lifespan. Obesity is a major driver of cardiometabolic disorders in the general population, and in ALL patients it is associated with increased risk of hypertension, dysglycemia, and febrile neutropenia when compared with lean ALL patients undergoing therapy. This systematic review aims to assess the current evidence for bariatric interventions to manage obesity in children with ALL. The primary outcome for this systematic review was the change in BMI z-score with implementation of the interventions studied. Literature searches were conducted in several databases. Ten publications addressing the study question were included in this review, and five studies were used in the meta-analysis to assess the impact of the bariatric interventions on obesity. The BMI z-score did not change significantly with the interventions. However, the quality of evidence was low, which precluded the recommendation of their use. In conclusion, prospective, rigorous, adequately powered, and high-quality longitudinal studies are urgently needed to deliver effective lifestyle interventions to children with ALL to treat and prevent obesity. These interventions, if successful, may improves cardiometabolic health outcomes and enhance the quality of life and life expectancy in children with ALL.

Dominant atopy risk mutations identified by mouse forward genetic analysis.

BACKGROUND: Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice. METHODS: We screened mice carrying homozygous and heterozygous N-ethyl-N-nitrosourea (ENU)-induced germline mutations for aberrant antigen-specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation. RESULTS: Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain-specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B-cell receptor signaling. The precise roles of the five remaining genes (Flcn, Map1lc3b, Me2, Prkd2, and Scarb2) remain to be determined. Loss-of-function mutations in nine of the 12 genes limiting the IgE response were dominant or semi-dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations. CONCLUSIONS: Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.

Tri-atomic Pt clusters induce effective pathways in a Cocore-Pdshell nanocatalyst surface for a high-performance oxygen reduction reaction.

The crux of the hot topic concerning the widespread replacement of fuel cells (FCs) with traditional petrochemical energy is to balance improving the oxygen reduction reaction (ORR) and reducing the cost. The present study employs density functional theory (DFT) to investigate the effect of Pt ensemble size regulation from a single atom to full coverage on the physio-chemical properties, oxygen adsorption energies and overall ORR efficiency of bimetallic nanocatalysts (NCs) with a Cocore-Pdshell structure. Our results reveal that the electronegativity difference and lattice strain between neighboring heteroatoms are enhanced to trigger a synergetic effect in local domains, with the Pt cluster size reduced from nanometers to subnanometers. They induce a directed and tunable charge relocation mechanism from deep Co to topmost Pt to optimize the adsorption energies of O2/O* and achieve excellent ORR kinetics performance with minimum Pt usage but maximum Pt atom utilization (i.e., Pt1 to Pt3) compared with benchmark Pt(111). Such a dependency between the cluster size and corresponding ORR performance for the established Co@Pd-Ptn system can be applied to accurately guide the experimental synthesis of ordered heterogeneous catalysts (e.g., other core@shell-clusters structures) toward low Pt, high efficiency and green economy.

Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in mice.

Successful cancer immunotherapy entails activation of innate immune receptors to promote dendritic cell (DC) maturation, antigen presentation, up-regulation of costimulatory molecules, and cytokine secretion, leading to activation of tumor antigen-specific cytotoxic T lymphocytes (CTLs). Here we screened a synthetic library of 100,000 compounds for innate immune activators using TNF production by THP-1 cells as a readout. We identified and optimized a potent human and mouse Toll-like receptor (TLR)1/TLR2 agonist, Diprovocim, which exhibited an EC50 of 110 pM in human THP-1 cells and 1.3 nM in primary mouse peritoneal macrophages. In mice, Diprovocim-adjuvanted ovalbumin immunization promoted antigen-specific humoral and CTL responses and synergized with anti-PD-L1 treatment to inhibit tumor growth, generating long-term antitumor memory, curing or prolonging survival of mice engrafted with the murine melanoma B16-OVA. Diprovocim induced greater frequencies of tumor-infiltrating leukocytes than alum, of which CD8 T cells were necessary for the antitumor effect of immunization plus anti-PD-L1 treatment.

Excessive endosomal TLR signaling causes inflammatory disease in mice with defective SMCR8-WDR41-C9ORF72 complex function.

The SMCR8-WDR41-C9ORF72 complex is a regulator of autophagy and lysosomal function. Autoimmunity and inflammatory disease have been ascribed to loss-of-function mutations of Smcr8 or C9orf72 in mice. In humans, autoimmunity has been reported to precede amyotrophic lateral sclerosis caused by mutations of C9ORF72 However, the cellular and molecular mechanisms underlying autoimmunity and inflammation caused by C9ORF72 or SMCR8 deficiencies remain unknown. Here, we show that splenomegaly, lymphadenopathy, and activated circulating T cells observed in Smcr8-/- mice were rescued by triple knockout of the endosomal Toll-like receptors (TLRs) TLR3, TLR7, and TLR9. Myeloid cells from Smcr8-/- mice produced excessive inflammatory cytokines in response to endocytosed TLR3, TLR7, or TLR9 ligands administered in the growth medium and in response to TLR2 or TLR4 ligands internalized by phagocytosis. These defects likely stem from prolonged TLR signaling caused by accumulation of LysoTracker-positive vesicles and by delayed phagosome maturation, both of which were observed in Smcr8-/- macrophages. Smcr8-/- mice also showed elevated susceptibility to dextran sodium sulfate-induced colitis, which was not associated with increased TLR3, TLR7, or TLR9 signaling. Deficiency of WDR41 phenocopied loss of SMCR8. Our findings provide evidence that excessive endosomal TLR signaling resulting from prolonged ligand-receptor contact causes inflammatory disease in SMCR8-deficient mice.

Creatine maintains intestinal homeostasis and protects against colitis.

Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted (Gatmc/c ) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatmc/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatmc/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury.

Skin-specific regulation of SREBP processing and lipid biosynthesis by glycerol kinase 5.

The recessive N-ethyl-N-nitrosourea-induced phenotype toku is characterized by delayed hair growth, progressive hair loss, and excessive accumulation of dermal cholesterol, triglycerides, and ceramides. The toku phenotype was attributed to a null allele of Gk5, encoding glycerol kinase 5 (GK5), a skin-specific kinase expressed predominantly in sebaceous glands. GK5 formed a complex with the sterol regulatory element-binding proteins (SREBPs) through their C-terminal regulatory domains, inhibiting SREBP processing and activation. In Gk5toku/toku mice, transcriptionally active SREBPs accumulated in the skin, but not in the liver; they were localized to the nucleus and led to elevated lipid synthesis and subsequent hair growth defects. Similar defective hair growth was observed in kinase-inactive GK5 mutant mice. Hair growth defects of homozygous toku mice were partially rescued by treatment with the HMG-CoA reductase inhibitor simvastatin. GK5 exists as part of a skin-specific regulatory mechanism for cholesterol biosynthesis, independent of cholesterol regulation elsewhere in the body.

IgD class switching is initiated by microbiota and limited to mucosa-associated lymphoid tissue in mice.

Class-switch recombination (CSR) alters the Ig isotype to diversify antibody effector functions. IgD CSR is a rare event, and its regulation is poorly understood. We report that deficiency of 53BP1, a DNA damage-response protein, caused age-dependent overproduction of secreted IgD resulting from increased IgD CSR exclusively within B cells of mucosa-associated lymphoid tissues. IgD overproduction was dependent on activation-induced cytidine deaminase, hematopoietic MyD88 expression, and an intact microbiome, against which circulating IgD, but not IgM, was reactive. IgD CSR occurred via both alternative nonhomologous end-joining and homologous recombination pathways. Microbiota-dependent IgD CSR also was detected in nasal-associated lymphoid tissue of WT mice. These results identify a pathway, present in WT mice and hyperactivated in 53BP1-deficient mice, by which microbiota signal via Toll-like receptors to elicit IgD CSR.

TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS.

Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-dependent signaling. The crystal structure mTLR4/MD-2/Neoseptin-3 at 2.57-Å resolution reveals that Neoseptin-3 binds as an asymmetrical dimer within the hydrophobic pocket of MD-2, inducing an active receptor complex similar to that induced by lipid A. However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS.

Real-time resolution of point mutations that cause phenovariance in mice.

With the wide availability of massively parallel sequencing technologies, genetic mapping has become the rate limiting step in mammalian forward genetics. Here we introduce a method for real-time identification of N-ethyl-N-nitrosourea-induced mutations that cause phenotypes in mice. All mutations are identified by whole exome G1 progenitor sequencing and their zygosity is established in G2/G3 mice before phenotypic assessment. Quantitative and qualitative traits, including lethal effects, in single or multiple combined pedigrees are then analyzed with Linkage Analyzer, a software program that detects significant linkage between individual mutations and aberrant phenotypic scores and presents processed data as Manhattan plots. As multiple alleles of genes are acquired through mutagenesis, pooled "superpedigrees" are created to analyze the effects. Our method is distinguished from conventional forward genetic methods because it permits (1) unbiased declaration of mappable phenotypes, including those that are incompletely penetrant (2), automated identification of causative mutations concurrent with phenotypic screening, without the need to outcross mutant mice to another strain and backcross them, and (3) exclusion of genes not involved in phenotypes of interest. We validated our approach and Linkage Analyzer for the identification of 47 mutations in 45 previously known genes causative for adaptive immune phenotypes; our analysis also implicated 474 genes not previously associated with immune function. The method described here permits forward genetic analysis in mice, limited only by the rates of mutant production and screening.

Near-infrared light-responsive composite microneedles for on-demand transdermal drug delivery.

This study presents near-infrared (NIR) light-responsive polymer-nanostructure composite microneedles used for on-demand transdermal drug delivery. Silica-coated lanthanum hexaboride (LaB6@SiO2) nanostructures were incorporated into polycaprolactone microneedles, serving as an NIR absorber. When the microneedles were irradiated with NIR light, light-to-heat transduction mediated by the LaB6@SiO2 nanostructures caused the microneedle melting at 50 °C. This increased the mobility of the polymer chains, enabling drug release from the matrix. Drug release from the microneedles was evaluated for four laser on/off cycles. In each cycle, the samples were irradiated until the temperature reached 50 °C for 3 min (laser on); the laser was then turned off for 30 min (laser off). The results showed that light-induced phase transition in the polymer triggered drug release from the melted microneedles. A stepwise drug-release behavior was observed after multiple cycles of NIR light exposure. No notable drug leakage was found in the off state. This NIR-light-triggerable device exhibits excellent reproducibility, low off-state leakage, and noninvasive triggerability and, thus, represents an advance in transdermal delivery technology.

High Entropy Spinel Oxide (AlCrCoNiFe2)O as Highly Active Oxygen Evolution Reaction Catalysts.

The advancement of water electrolyzer technologies and the production of sustainable hydrogen fuel heavily rely on the development of efficient and cost-effective electrocatalysts for the oxygen evolution reaction (OER). High entropy ceramics, characterized by their unique properties, such as lattice distortion and high configurational entropy, hold significant promise for catalytic applications. In this study, we utilized the sol-gel autocombustion method to synthesize high entropy ceramics containing a combination of 3d transition metals and aluminum ((AlCrCoNiFe2)O). We then compared their electrocatalytic performance with other series of synthesized multimetal and monometallic oxides for the OER under alkaline conditions. Our electrochemical analysis revealed that the high entropy ceramics exhibited excellent performance and the lowest charge transfer resistance, Tafel slope (29 mV·dec-1), and overpotential (η10 = 230 mV). These remarkable results can be primarily attributed to the high entropy effect induced by the addition of Al, Cr, Co, Ni, and Fe, which introduces increased disorder and complexity into the material's structure. This, in turn, facilitates more efficient OER catalysis by providing diverse active sites and promoting optimal electronic configurations for the reaction. Furthermore, the strong electronic interactions among the constituent elements in the metallic spinels further enhance their catalytic activity in the initiation of the OER process. Combined with the reduced charge transfer resistance, these factors collectively play pivotal roles in enhancing the OER performance of the electrocatalysts. Overall, our study provides valuable insights into the design and development of high-performance electrocatalysts for sustainable energy applications. By harnessing the high entropy effect and leveraging strong electronic interactions, electrocatalytic materials can be tailored to improve efficiency and stability, thus advancing the progress of clean energy technologies.

Highly Nanoporous Nickel Foam as Current Collectors in 3D All-Solid-State Microsupercapacitors.

This study reports a streamlined method for producing a highly nanoporous current collector with a substantial specific surface area, serving as an electrode for microsupercapacitors (MSCs). Initially, commercial Ni foams are patterned into an interdigitated structure by laser cutting. Subsequently, the Ni foams are infused with NiO nanopowders through dip coating, sintering, and reduction in an H2 atmosphere, followed by the growth of MnO2 through a redox reaction. The incorporation of NiO within this three-dimensional Ni current collector results in notable porosity within the range of approximately 200-600 nm. Such a 3D, highly nanoporous electrode dramatically increases the specific surface area by 30 times and substantially boosts the amount of active material deposition, surpassing those of commercially available Ni foams. Performance evaluations of this highly nanoporous electrode in a 1 M KOH solution demonstrate an areal capacity of 19.3 F/cm2, retaining more than 95% capacitance at 5 mA/cm2, and exhibiting an energy density of 671 µW h/cm2, 25 times greater than commercial Ni foams. Moreover, in the realm of solid-state applications for MSCs, the remarkably high porous electrode achieves a commendable areal capacity of 7.22 F/cm2 and an energy density of 263.9 µW h/cm2, rendering it exceptionally suitable for use in MSC applications.

Solvent-Free Synthesis Enables Encapsulation of Subnanometric FeOx Clusters in Pure Siliceous Zeolites for Efficient Catalytic Oxidation Reactions.

Metal/metal oxide clusters possess a higher count of unsaturated coordination sites than nanoparticles, providing multiatomic sites that single atoms do not. Encapsulating metal/metal oxide clusters within zeolites is a promising approach for synthesizing and stabilizing these clusters. The unique feature endows the metal clusters with an exceptional catalytic performance in a broad range of catalytic reactions. However, the encapsulation of stable FeOx clusters in zeolite is still challenging, which limits the application of zeolite-encapsulated FeOx clusters in catalysis. Herein, we design a modified solvent-free method to encapsulate FeOx clusters in pure siliceous MFI zeolites (Fe@MFI). It is revealed that the 0.3-0.4 nm subnanometric FeOx clusters are stably encapsulated in the 5/6-membered rings intersectional voids of the pure siliceous MFI zeolites. The encapsulated Fe@MFI catalyst with a Fe loading of 1.4 wt % demonstrates remarkable catalytic activity and recycle stability in the direct oxidation of methane, while also promoting the direct oxidation of cyclohexane, surpassing the performance of conventional zeolite-supported Fe catalysts.