A novel variation in DEPDC5 causing familial focal epilepsy with variable foci.

Background: Disheveled, EGL-10, and pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a component of GTPase-activating protein (GAP) activity toward the RAG complex 1 (GATOR1) protein, which is an inhibitor of the amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. GATOR1 complex variations were reported to correlate with familial focal epilepsy with variable foci (FFEVF). With the wide application of whole exome sequencing (WES), more and more variations in DEPDC5 were uncovered in FFEVF families. Methods: A family with a proband diagnosed with familial focal epilepsy with variable foci (FFEVF) was involved in this study. Whole exome sequencing (WES) was performed in the proband, and Sanger sequencing was used to confirm the variation carrying status of the family members. Mini-gene splicing assay was performed to validate the effect on the alternative splicing of the variation. Results: A novel variant, c.1217 + 2T>A, in DEPDC5 was identified by WES in the proband. This splicing variant that occurred at the 5' end of intron 17 was confirmed by mini-gene splicing assays, which impacted alternative splicing and led to the inclusion of an intron fragment. The analysis of the transcribed mRNA sequence indicates that the translation of the protein is terminated prematurely, which is very likely to result in the loss of function of the protein and lead to the occurrence of FFEVF. Conclusion: The results suggest that c.1217 + 2T>A variations in DEPDC5 might be the genetic etiology for FFEVF in this pedigree. This finding expands the genotype spectrum of FFEVF and provides new etiological information for FFEVF.

Mediating roles of activities of daily living and depression on the relationship between sleep quality and health-related quality of life.

This study aimed to explore the mediating effects of ADL and depression on the relationship between sleep quality and HRQOL among older people in rural China, while also exploring the moderating impact of loneliness. The study gathered data from a household survey conducted among 1587 Chinese rural older adults (mean age = 73.63 years). The collected data was analyzed using SPSS version 23.0 software (IBM, New York, USA) and the PROCESS macro version 4.0 program. The findings indicated a significant correlation between sleep quality, ADL, depression, loneliness and HRQOL. ADL and depression exhibited a chain mediation effect on the relationship between sleep quality and HRQOL. Notably, the association between sleep quality and HRQOL was entirely mediated by ADL and depression. Additionally, loneliness acted as a moderator in the relationship between ADL and HRQOL. The findings of this study suggest that interventions focusing on sleep quality should prioritize strategies for enhancing older adults' ADL and depression as integral components of promoting older adults' HRQOL.

PARP1 interacts with WDR5 to enhance target gene recognition and facilitate tumorigenesis.

Poly (ADP-ribose) polymerase-1 (PARP1) is a nuclear protein that attaches negatively charged poly (ADP-ribose) (PAR) to itself and other target proteins. While its function in DNA damage repair is well established, its role in target chromatin recognition and regulation of gene expression remains to be better understood. This study showed that PARP1 interacts with SET1/MLL complexes by binding directly to WDR5. Notably, although PARP1 does not modulate WDR5 PARylation or the global level of H3K4 methylation, it exerts locus-specific effects on WDR5 binding and H3K4 methylation. Interestingly, PARP1 and WDR5 show extensive co-localization on chromatin, with WDR5 facilitating the recognition and expression of target genes regulated by PARP1. Furthermore, we demonstrated that inhibition of the WDR5 Win site impedes the interaction between PARP1 and WDR5, thereby inhibiting PARP1 from binding to target genes. Finally, the combined inhibition of the WDR5 Win site and PARP shows a profound inhibitory effect on the proliferation of cancer cells. These findings illuminate intricate mechanisms underlying chromatin recognition, gene transcription, and tumorigenesis, shedding light on previously unrecognized roles of PARP1 and WDR5 in these processes.

Exosomal PD-L1 in cancer and other fields: recent advances and perspectives.

PD-1/PD-L1 signaling is a key factor of local immunosuppression in the tumor microenvironment. Immune checkpoint inhibitors targeting PD-1/PD-L1 signaling have achieved tremendous success in clinic. However, several types of cancer are particularly refractory to the anti-PD-1/PD-L1 treatment. Recently, a series of studies reported that IFN-γ can stimulate cancer cells to release exosomal PD-L1 (exoPD-L1), which possesses the ability to suppress anticancer immune responses and is associated with anti-PD-1 response. In this review, we introduce the PD-1/PD-L1 signaling, including the so-called 'reverse signaling'. Furthermore, we summarize the immune treatments of cancers and pay more attention to immune checkpoint inhibitors targeting PD-1/PD-L1 signaling. Additionally, we review the action mechanisms and regulation of exoPD-L1. We also introduce the function of exoPD-L1 as biomarkers. Finally, we review the methods for analyzing and quantifying exoPD-L1, the therapeutic strategies targeting exoPD-L1 to enhance immunotherapy and the roles of exoPD-L1 beyond cancer. This comprehensive review delves into recent advances of exoPD-L1 and all these findings suggest that exoPD-L1 plays an important role in both cancer and other fields.

Use of ozone oxidation in combination with deacetylation for improving the structure and gelation properties of konjac glucomannan.

In this study, oxidized deacetylated konjac glucomannans with different degrees of oxidation were prepared by a combination of deacetylation and ozone oxidation. Carboxyl groups were found to be introduced into the modified konjac glucomannan while acetyl groups were removed. The backbone, branched chains, and crystal structure of modified konjac glucomannan were not significantly affected. The whiteness was enhanced to 97-99 % and the thermal degradation temperature was up to 250 °C after modification. The solubility of the modified konjac glucomannan (oxidized for 60 min) was significantly increased to 84.56 % (p < 0.05), while its viscosity and swelling power were notably decreased owing to the changes in molecular weight (from 106 to 104) and functional groups. Rheological analysis showed that oxidized deacetylated konjac glucomannan has the ability to form soft-textured gels and the potential to develop dysphagia foods. Future studies should focus on the gelation mechanisms of oxidized deacetylated konjac glucomannan.

How does ultrasound contribute to the migration of extractives inside Ailanthus altissima wood?

Extractives have an impact on the processing and commercial value of wood. Ultrasound is an environmentally friendly technology commonly employed to reduce the extractive content and thus enhance the permeability of wood. This study aimed to understand the migration mechanism of extractives inside wood during ultrasonic treatment, which may help to obtain the desired wood properties. The extractive distribution of Ailanthus altissima was observed by using stereo microscopy, optical microscopy, and scanning electron microscopy, the extractive content was determined, and the relationship between the concentration of water-soluble extractives and absorbance was measured using a UV/Vis spectrophotometer, and the migration model of extractives was studied using layered extraction by innovatively combining the weight and the absorbance methods. The results revealed that the extractives were predominantly distributed in the vessels and diminished after ultrasonic treatment. The extractive content gradually decreased over time (0 ∼ 5 h), with a rapid decline observed within the first 2 h. The concentration of the water-soluble extractives exhibited a proportional relationship with the absorbance. Through the comparison of the layered-extractive concentration, accumulating evidence suggested that the migration of the extractives was a dynamic process, which included the extractives migrating towards easy-extracted area, moving along the direction of ultrasound propagation inside the wood, and leaching out of wood during ultrasonic treatment.

Neoantigen-targeted TCR-engineered T cell immunotherapy: current advances and challenges.

Adoptive cell therapy using T cell receptor-engineered T cells (TCR-T) is a promising approach for cancer therapy with an expectation of no significant side effects. In the human body, mature T cells are armed with an incredible diversity of T cell receptors (TCRs) that theoretically react to the variety of random mutations generated by tumor cells. The outcomes, however, of current clinical trials using TCR-T cell therapies are not very successful especially involving solid tumors. The therapy still faces numerous challenges in the efficient screening of tumor-specific antigens and their cognate TCRs. In this review, we first introduce TCR structure-based antigen recognition and signaling, then describe recent advances in neoantigens and their specific TCR screening technologies, and finally summarize ongoing clinical trials of TCR-T therapies against neoantigens. More importantly, we also present the current challenges of TCR-T cell-based immunotherapies, e.g., the safety of viral vectors, the mismatch of T cell receptor, the impediment of suppressive tumor microenvironment. Finally, we highlight new insights and directions for personalized TCR-T therapy.

The Increasing Burden of Cancer Among Women and in Rural Areas: A Retrospective Population-Based Study.

The retrospective study aimed to describe the epidemiological characteristics and trends of cancer in Anhui Province, China between 2010 and 2018. Cancer registry data were analyzed using the Joinpoint regression model to calculate trends in cancer incidence and mortality. Age-standardized incidence rate, calculated based on the world Segi's population (ASIRW) was higher in males (239.34 per 100 000) than in females (157.13 per 100 000), and higher in rural areas (203.98 per 100 000) compared to urban areas (189.93 per 100 000). The ASIRW for males decreased with an AAPC of -3.0%, while that of females showed an upward trend with an AAPC of 2.1%. At the same time, the ASIRW in urban areas decreased with an AAPC of -2.4%, whereas it remained relatively stable in rural areas. Among males, lung cancer was the most prevalent type of cancer, while breast cancer was the most frequent cancer among women. The age-standardized mortality rate according to the world Segi's population (ASMRW) was 115.32 per 100 000. The ASMRW was higher in males (156.70 per 100 000) than in females (75.51 per 100 000), and higher in rural areas (122.18 per 100 000) than urban areas (109.21 per 100 000). Lung cancer accounted for the majority of cancer-associated mortalities in the province. Attention needs to be focused on women and rural areas due to rapidly increasing incidence and mortality rates for cancer. Furthermore, an effective public health response is imperative, encompassing early screening, diagnosis, and treatment of prevalent cancers in high-risk populations and regions. It's crucial to promote healthy lifestyles among the public through health education.

Cu-MOF derived CuO@g-C3N4 nanozyme for cascade catalytic colorimetric sensing.

The use of peroxidase mimics has great potential for various real applications due to their strong catalytic activity. Herein, a facile strategy was proposed to directly prepare CuO@g-C3N4 by Cu-MOF derivatization and demonstrated its efficacy in constructing a multiple enzymatic cascade system by loading protein enzymes onto it. The resulting CuO@g-C3N4 possessed high peroxidase-like activity, with a Michaelis constant (Km) of 0.25 and 0.16 mM for H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB), respectively. Additionally, the high surface area of CuO@g-C3N4 facilitated the loading of protein enzymes and maintained their activity over an extended period, expanding the potential applications of CuO@g-C3N4. To test its feasibility, CuO@g-C3N4/protein oxidase complex was prepared and used to sense the ripeness and freshness of fruits and meat, respectively. The mechanism relied on the fact that the ripeness of fruits increased and freshness of food decreased with the release of marked targets, such as glucose and xanthine, which could produce H2O2 when digested by the corresponding oxidase. The peroxidase mimics of CuO@g-C3N4 could then sensitively colorimetric detect H2O2 in present of TMB. The obtained CuO@g-C3N4/oxidase complex exhibited an excellent linear response to glucose or xanthine in the range of 1.0-120 µmol/L or 8.0-350 µmol/L, respectively. Furthermore, accurate quantification of glucose and xanthine in real samples is achieved with spiked recoveries ranging from 80.2% to 120.0% and from 94.2% to 112.0%, respectively. Overall, this work demonstrates the potential of CuO@g-C3N4 in various practical applications, such as food freshness detection.

Genome-Wide Identification of the PP2C Gene Family and Analyses with Their Expression Profiling in Response to Cold Stress in Wild Sugarcane.

Type 2C protein phosphatases (PP2Cs) represent a major group of protein phosphatases in plants, some of which have already been confirmed to play important roles in diverse plant processes. In this study, analyses of the phylogenetics, gene structure, protein domain, chromosome localization, and collinearity, as well as an identification of the expression profile, protein-protein interaction, and subcellular location, were carried out on the PP2C family in wild sugarcane (Saccharum spontaneum). The results showed that 145 PP2C proteins were classified into 13 clades. Phylogenetic analysis suggested that SsPP2Cs are evolutionarily closer to those of sorghum, and the number of SsPP2Cs is the highest. There were 124 pairs of SsPP2C genes expanding via segmental duplications. Half of the SsPP2C proteins were predicted to be localized in the chloroplast (73), with the next most common predicted localizations being in the cytoplasm (37) and nucleus (17). Analysis of the promoter revealed that SsPP2Cs might be photosensitive, responsive to abiotic stresses, and hormone-stimulated. A total of 27 SsPP2Cs showed cold-stress-induced expressions, and SsPP2C27 (Sspon.01G0007840-2D) and SsPP2C64 (Sspon.03G0002800-3D) were the potential hubs involved in ABA signal transduction. Our study presents a comprehensive analysis of the SsPP2C gene family, which can play a vital role in the further study of phosphatases in wild sugarcane. The results suggest that the PP2C family is evolutionarily conserved, and that it functions in various developmental processes in wild sugarcane.

iTCep: a deep learning framework for identification of T cell epitopes by harnessing fusion features.

Neoantigens recognized by cytotoxic T cells are effective targets for tumor-specific immune responses for personalized cancer immunotherapy. Quite a few neoantigen identification pipelines and computational strategies have been developed to improve the accuracy of the peptide selection process. However, these methods mainly consider the neoantigen end and ignore the interaction between peptide-TCR and the preference of each residue in TCRs, resulting in the filtered peptides often fail to truly elicit an immune response. Here, we propose a novel encoding approach for peptide-TCR representation. Subsequently, a deep learning framework, namely iTCep, was developed to predict the interactions between peptides and TCRs using fusion features derived from a feature-level fusion strategy. The iTCep achieved high predictive performance with AUC up to 0.96 on the testing dataset and above 0.86 on independent datasets, presenting better prediction performance compared with other predictors. Our results provided strong evidence that model iTCep can be a reliable and robust method for predicting TCR binding specificities of given antigen peptides. One can access the iTCep through a user-friendly web server at http://biostatistics.online/iTCep/, which supports prediction modes of peptide-TCR pairs and peptide-only. A stand-alone software program for T cell epitope prediction is also available for convenient installing at https://github.com/kbvstmd/iTCep/.

Mn-Doped Spinel for Removing Cr(VI) from Aqueous Solutions: Adsorption Characteristics and Mechanisms.

In this study, the manganese (Mn) was doped in the MnFe2O4 crystal by the solid-phase synthesis method. Under the optimum conditions (pH = 3), the max removal rate and adsorption quantity of Cr(VI) on MnFe2O4 adsorbent obtain under pH = 3 were 92.54% and 5.813 mg/g, respectively. The DFT calculation results indicated that the adsorption energy (Eads) between HCrO4- and MnFe2O4 is -215.2 KJ/mol. The Cr(VI) is mainly adsorbed on the Mn atoms via chemical bonds in the form of HCrO4-. The adsorption of Mn on the MnFe2O4 surface belonged to chemisorption and conformed to the Pseudo-second-order equation. The mechanism investigation indicated that the Mn in MnFe2O4 has an excellent enhancement effect on the Cr(VI) removal process. The roles of Mn in the Cr(VI) removal process included two parts, providing adsorbing sites and being reductant. Firstly, the Cr(VI) is adsorbed onto the MnFe2O4 via chemisorption. The Mn in MnFe2O4 can form ionic bonds with the O atoms of HCrO4-/CrO42-, thus providing the firm adsorbing sites for the Cr(VI). Subsequently, the dissolved Mn(II) can reduce Cr(VI) to Cr(III). The disproportionation of oxidized Mn(III) produced Mn(II), causing Mn(II) to continue to participate in the Cr(VI) reduction. Finally, the reduced Cr(III) is deposited on the MnFe2O4 surface in the form of Cr(OH)3 colloids, which can be separated by magnetic separation.

CoV2-TCR: A web server for screening TCR CDR3 from TCR immune repertoire of COVID-19 patients and their recognized SARS-CoV-2 epitopes.

Although multiple vaccines have been developed and widely administered, several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been reported to evade immune responses and spread diffusely. Here, 108 RNA-seq files from coronavirus disease 2019 (COVID-19) patients and healthy donors (HD) were downloaded to extract their TCR immune repertoire by MiXCR. Those extracted TCR repertoire were compared and it was found that disease progression was related negatively with diversity and positively with clonality. Specifically, greater proportions of high-abundance clonotypes were observed in active and severe COVID-19 samples, probably resulting from strong stimulation of SARS-CoV-2 epitopes and a continued immune response in host. To investigate the specific recognition between TCR CDR3 and SARS-CoV-2 epitopes, we constructed an accurate classifier CoV2-TCR with an AUC of 0.967 in an independent dataset, which outperformed several similar tools. Based on this model, we observed a huge range in the number of those TCR CDR3 recognizing those different peptides, including 28 MHC-I epitopes from SARS-CoV-2 and 22 immunogenic peptides from SARS-CoV-2 variants. Interestingly, their proportions of high-abundance, low-abundance and rare clonotypes were close for each peptide. To expand the potential application of this model, we established the webserver, CoV2-TCR, in which users can obtain those recognizing CDR3 sequences from the TCR repertoire of COVID-19 patients based on the 9-mer peptides containing mutation site(s) on the four main proteins of SARS-CoV-2 variants. Overall, this study provides preliminary screening for candidate antigen epitopes and the TCR CDR3 that recognizes them, and should be helpful for vaccine design on SARS-CoV-2 variants.

Isl1 promotes gene transcription through physical interaction with Set1/Mll complexes.

Histone H3 lysine 4 (H3K4) methylation is generally recognized as a prominent marker of gene activation. While Set1/Mll complexes are major methyltransferases that are responsible for H3K4 methylation, the mechanism of how these complexes are recruited into the target gene promotor is still unclear. Here, starting with an affinity purification-mass spectrometry approach, we have found that Isl1, a highly tissue-specific expressed LIM/homeodomain transcription factor, is physically associated with Set1/Mll complexes. We then show that Wdr5 directly binds to Isl1. And this binding is likely mediated by the homeodomain of Isl1. Functionally, using mouse ß-cell and human neuroblastoma tumor cell lines, we show that both Wdr5 binding and H3K4 methylation level at promoters of some Isl1 target genes are significantly reduced upon depletion of Isl1, suggesting Isl1 is required for efficient locus-specific H3K4 methylation. Taken together, our results establish a critical role of Set1/Mll complexes in regulating the target gene expression of Isl1.

Dietary Methionine Restriction Alleviates Choline-Induced Tri-Methylamine-N-Oxide (TMAO) Elevation by Manipulating Gut Microbiota in Mice.

Dietary methionine restriction (MR) has been shown to decrease plasma trimethylamine-N-oxide (TMAO) levels in high-fat diet mice; however, the specific mechanism used is unknown. We speculated that the underlying mechanism is related with the gut microbiota, and this study aimed to confirm the hypothesis. In this study, we initially carried out an in vitro fermentation experiment and found that MR could reduce the ability of gut microbiota found in the contents of healthy mice and the feces of healthy humans to produce trimethylamine (TMA). Subsequently, mice were fed a normal diet (CON, 0.20% choline + 0.86% methionine), high-choline diet (H-CHO, 1.20% choline + 0.86% methionine), or high-choline + methionine-restricted diet (H-CHO+MR, 1.20% choline + 0.17% methionine) for 3 months. Our results revealed that MR decreased plasma TMA and TMAO levels in H-CHO-diet-fed mice without changing hepatic FMO3 gene expression and enzyme activity, significantly decreased TMA levels and expression of choline TMA-lyase (CutC) and its activator CutD, and decreased CutC activity in the intestine. Moreover, MR significantly decreased the abundance of TMA-producing bacteria, including Escherichia-Shigella (Proteobacteria phylum) and Anaerococcus (Firmicutes phylum), and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria and SCFA levels. Furthermore, both MR and sodium butyrate supplementation significantly inhibited bacterial growth, down-regulated CutC gene expression levels in TMA-producing bacteria, including Escherichia fergusonii ATCC 35469 and Anaerococcus hydrogenalis DSM 7454 and decreased TMA production from bacterial growth under in vitro anaerobic fermentation conditions. In conclusion, dietary MR alleviates choline-induced TMAO elevation by manipulating gut microbiota in mice and may be a promising approach to reducing circulating TMAO levels and TMAO-induced atherosclerosis.

Dietary Methionine Restriction Promotes Fat Browning and Attenuates Hepatic Lipid Accumulation in High-Choline-Fed Mice Associated with the Improvement of Thyroid Function.

This study aims to explore the influences of a methionine-restricted diet (MRD) on fat browning and hepatic lipid accumulation in mice fed with a high-choline diet (HCD) and their possible mechanisms. ICR mice were randomly divided into three groups and fed with a normal diet (0.86% methionine + 0.20% choline, ND), HCD (0.86% methionine + 1.20% choline), or MRD (0.17% methionine + 1.20% choline) for 90 consecutive days. We found that MRD reduced body weight and fat mass; increased heat production and ambulatory locomotor activity; reduced hepatic and plasma lipid levels, hepatic fatty infiltration area, and adipocyte volume in white and brown adipose tissue; promoted fat browning, especially upregulated gene and protein expression levels of uncoupling protein 1 (UCP1); and promoted fat catabolism and inhibited fat anabolism in the liver and adipose tissue. Moreover, MRD increased antioxidant defenses and reduced inflammatory cytokine levels in the thyroid, blood, and liver. Furthermore, MRD improved thyroid morphological structure, promoted the synthesis and secretion of thyroid hormones, and enhanced the actions of thyroid hormones on its receptor organs (liver and adipose tissue). These findings suggested that MRD promoted fat browning and attenuated hepatic lipid accumulation in HCD mice associated with the improvement of thyroid function.

Echo feedback mediates noise-induced vocal modifications in flying bats.

Diverse animal taxa are capable of rapidly modifying vocalizations to mitigate interference from environmental noise. Echolocating bats, for example, must frequently perform sonar tasks in the presence of interfering sounds. Numerous studies have documented sound production flexibility in echolocating bats; however, it remains unknown whether noise-induced vocal modifications (NIVMs) mitigate interference effects on echoes or calls. In this study, we leverage echo level compensation behavior of echolocating bats to answer this question. Using a microphone array, we recorded echolocation calls of Hipposideros pratti trained to approach and land on a perch in the laboratory under quiet and noise conditions. We found that H. pratti exhibited echo level compensation behavior during approaching flights, which depended critically on distance to the landing perch. Broadcast noise delayed and affected the rate of echo level compensation in H. pratti. Moreover, H. pratti increased vocalization amplitude, i.e., exhibited the Lombard effect, while also adjusting call duration and bandwidth with increasing noise levels. Quantitative analyses of the data show that H. pratti relies on echo feedback, not vocal feedback, to adjust signals in the presence of noise. These findings provide compelling evidence that NIVMs in echolocating animals and non-echolocating animals operate through different mechanisms.

FMR1 promotes the progression of colorectal cancer cell by stabilizing EGFR mRNA in an m6A-dependent manner.

FMR1, a new m6A reader, is known to be involved in the regulation of cancer progression. However, its role, regulatory mechanism, and clinical significance in colorectal cancer (CRC) are elusive. Here, we showed that FMR1 was upregulated in CRC, and it promoted proliferation and metastasis of CRC cells in vitro and in vivo. Mechanically, FMR1 recognized the m6A-modification site in EGFR mRNA, a key molecule in cancer occurrence and targeted therapy, sustained its stability and maintained its expression in an m6A-dependent manner, thereby promoting the tumorigenesis and metastasis of CRC. And the effect of FMR1 knockdown in CRC cells could be abolished by METTL3. Furthermore, FMR1 shRNA plasmid carried by attenuated Salmonella has an effective anti-tumor effect in vivo. Collectively, we identified the METTL3/FMR1/EGFR axis in the progression of CRC. This novel mechanism indicated that the METTL3/FMR1/EGFR axis is a potential target for early therapeutic intervention in CRC progression.

Dietary Methionine via Dose-Dependent Inhibition of Short-Chain Fatty Acid Production Capacity Contributed to a Potential Risk of Cognitive Dysfunction in Mice.

High-methionine diets induce impaired learning and memory function, dementia-like neurodegeneration, and Alzheimer's disease, while low-methionine diets improve learning and memory function. We speculated that variations in intestinal microbiota may mediate these diametrically opposed effects; thus, this study aimed to verify this hypothesis. The ICR mice were fed either a low-methionine diet (LM, 0.17% methionine), normal methionine diet (NM, 0.86% methionine), or high-methionine diet (HM, 2.58% methionine) for 11 weeks. We found that HM diets damaged nonspatial recognition memory, working memory, and hippocampus-dependent spatial memory and induced anxiety-like behaviors in mice. LM diets improved nonspatial recognition memory and hippocampus-dependent spatial memory and ameliorated anxiety-like behavior, but the differences did not reach a significant level. Moreover, HM diets significantly decreased the abundance of putative short-chain fatty acid (SCFA)-producing bacteria (Roseburia, Blautia, Faecalibaculum, and Bifidobacterium) and serotonin-producing bacteria (Turicibacter) and significantly increased the abundance of proinflammatory bacteria Escherichia-Shigella. Of note, LM diets reversed the results. Consequently, the SCFA and serotonin levels were significantly decreased with HM diets and significantly increased with LM diets. Furthermore, HM diets induced hippocampal oxidative stress and inflammation and selectively downregulated the hippocampus-dependent memory-related gene expression, whereas LM diets selectively upregulated the hippocampus-dependent memory-related gene expression. In conclusion, dietary methionine via dose-dependent inhibition of SCFA production capacity contributed to a potential risk of cognitive dysfunction in mice.