Nut consumption, gut microbiota, and body fat distribution: results of a large, community-based population study.

OBJECTIVE: We aimed to investigate the relationships among nut consumption, gut microbiota, and body fat distribution. METHODS: We studied 2255 Chinese adults in the Lanxi Cohort living in urban areas in Lanxi City, China. Fat distribution was assessed by dual-energy x-ray absorptiometry, and nut consumption was assessed using food frequency questionnaires. 16S ribosomal RNA (rRNA) sequencing was performed on stool samples from 1724 participants. Linear regression and Spearman correlation were used in all analyses. A validation study was performed using 1274 participants in the Lanxi Cohort living in rural areas. RESULTS: Nut consumption was beneficially associated with regional fat accumulation. Gut microbial analysis suggested that a high intake of nuts was associated with greater microbial α diversity. Six genera were found to be associated with nut consumption, and the abundance of genera Anaerobutyricum, Anaerotaenia, and Fusobacterium was significantly associated with fat distribution. Favorable relationships between α diversity and fat distribution were also observed. Similar relationships between gut microbiota and fat distribution were obtained in the validation analysis. CONCLUSIONS: We have shown that nut consumption is beneficially associated with body fat distribution and gut microbiota diversity and taxonomy. Furthermore, the microbial features related to high nut intake are associated with a favorable pattern of fat distribution.

Diastereoselective Three-Component 1,3-Dipolar Cycloaddition to Access Functionalized ß-Tetrahydrocarboline- and Tetrahydroisoquinoline-Fused Spirooxindoles.

A chemselective catalyst-free three-component 1,3-dipolar cycloaddition has been described. The unique polycyclic THPI and THIQs were creatively employed as dipolarophiles, which led to the formation of functionalized ß-tetrahydrocarboline- and tetrahydroisoquinoline-fused spirooxindoles in 60-94% of yields with excellent diastereoselectivities (10: 1->99: 1 dr). This reaction not only realizes a concise THPI- or THIQs-based 1,3-dipolar cycloaddition, but also provides a practical strategy for the construction of two distinctive spirooxindole skeletons.

CCNA2 and NEK2 regulate glioblastoma progression by targeting the cell cycle.

Glioblastoma (GBM) is characterized by significant heterogeneity, leading to poor survival outcomes for patients, despite the implementation of comprehensive treatment strategies. The roles of cyclin A2 (CCNA2) and NIMA related kinase 2 (NEK2) have been extensively studied in numerous cancers, but their specific functions in GBM remain to be elucidated. The present study aimed to investigate the potential molecular mechanisms of CCNA2 and NEK2 in GBM. CCNA2 and NEK2 expression and prognosis in glioma were evaluated by bioinformatics methods. In addition, the distribution of CCNA2 and NEK2 expression in GBM subsets was determined using pseudo-time analysis and tricycle position of single-cell sequencing. Gene Expression Omnibus and Kyoto Encyclopedia of Genes and Genome databases were employed and enrichment analyses were conducted to investigate potential signaling pathways in GBM subsets and a nomogram was established to predict 1-, 2- and 3-year overall survival probability in GBM. CCNA2 and NEK2 expression levels were further validated by western blot analysis and immunohistochemical staining in GBM samples. High expression of CCNA2 and NEK2 in glioma indicates poor clinical outcomes. Single-cell sequencing of GBM revealed that these genes were upregulated in a subset of positive neural progenitor cells (P-NPCs), which showed significant proliferation and progression properties and may activate G2M checkpoint pathways. A comprehensive nomogram predicts 1-, 2- and 3-year overall survival probability in GBM by considering P-NPCs, age, chemotherapy and radiotherapy scores. CCNA2 and NEK2 regulate glioblastoma progression by targeting the cell cycle, thus indicating the potential of novel therapy directed to CCNA2 and NEK2 in GBM.

Computational design of an imine reductase: mechanism-guided stereoselectivity reversion and interface stabilization.

Imine reductases (IREDs) are important biocatalysts in the asymmetric synthesis of chiral amines. However, a detailed understanding of the stereocontrol mechanism of IRED remains incomplete, making the design of IRED for producing the desired amine enantiomers challenging. In this study, we investigated the stereoselective catalytic mechanism and designed an (R)-stereoselective IRED from Paenibacillus mucilaginosus (PmIR) using pharmaceutically relevant 2-aryl-substituted pyrrolines as substrates. A putative mechanism for controlling stereoselectivity was proposed based on the crucial role of electrostatic interactions in controlling iminium cation orientation and employed to achieve complete inversion of stereoselectivity in PmIR using computational design. The variant PmIR-Re (Q138M/P140M/Y187E/Q190A/D250M/R251N) exhibited opposite (S)-stereoselectivity, with >96% enantiomeric excess (ee) towards tested 2-aryl-substituted pyrrolines. Computational tools were employed to identify stabilizing mutations at the interface between the two subunits. The variant PmIR-6P (P140A/Q190S/R251N/Q217E/A257R/T277M) showed a nearly 5-fold increase in activity and a 12 °C increase in melting temperature. The PmIR-6P successfully produced (R)-2-(2,5-difluorophenyl)-pyrrolidine, a key chiral pharmaceutical intermediate, at a concentration of 400 mM with an ee exceeding 99%. This study provides insight into the stereocontrol elements of IREDs and demonstrates the potential of computational design for tailored stereoselectivity and thermal stability.

CRYAA and GJA8 promote visual development after whisker tactile deprivation.

Deprivation of one sense can be followed by enhanced development of other senses via cross-modal plasticity mechanisms. To study the effect of whisker tactile deprivation on vision during the early stages of development, we clipped the bilateral whiskers of young mice and found that their vision was impaired but later recovered to normal levels. Our results demonstrate that inhibition of the PI3K/AKT/ERK signaling pathway caused short-term visual impairment during early development, while high expression levels of Crystallin Alpha A (CRYAA) and Gap Junction Protein Alpha 8 (GJA8) in the retina led to the recovery of developmental visual acuity. Interestingly, analysis of single-cell sequencing results from human embryonic retinas at 9-19 gestational weeks (GW) revealed that CRYAA and GJA8 display stage-specific peak expression during human embryonic retinal development, suggesting potential functions in visual development. Our data show that high expression levels of CRYAA and GJA8 in the retina after whisker deprivation rescue impaired visual development, which may provide a foundation for further research on the mechanisms of cross-modal plasticity and in particular, offer new insights into the mechanisms underlying tactile-visual cross-modal development.

Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System.

Synaptic plasticity enhances or reduces connections between neurons, affecting learning and memory. Postsynaptic AMPARs mediate greater than 90% of the rapid excitatory synaptic transmission in glutamatergic neurons. The number and subunit composition of AMPARs are fundamental to synaptic plasticity and the formation of entire neural networks. Accordingly, the insertion and functionalization of AMPARs at the postsynaptic membrane have become a core issue related to neural circuit formation and information processing in the central nervous system. In this review, we summarize current knowledge regarding the related mechanisms of AMPAR expression and trafficking. The proteins related to AMPAR trafficking are discussed in detail, including vesicle-related proteins, cytoskeletal proteins, synaptic proteins, and protein kinases. Furthermore, significant emphasis was placed on the pivotal role of the actin cytoskeleton, which spans throughout the entire transport process in AMPAR transport, indicating that the actin cytoskeleton may serve as a fundamental basis for AMPAR trafficking. Additionally, we summarize the proteases involved in AMPAR post-translational modifications. Moreover, we provide an overview of AMPAR transport and localization to the postsynaptic membrane. Understanding the assembly, trafficking, and dynamic synaptic expression mechanisms of AMPAR may provide valuable insights into the cognitive decline associated with neurodegenerative diseases.

Atp11b Deletion Affects the Gut Microbiota and Accelerates Brain Aging in Mice.

The microbiota-gut-brain axis has attracted significant attention with respect to studying the mechanisms of brain aging; however, the specific connection between gut microbiota and aging remains unclear. The abnormal expression and mutation of proteins belonging to the P4-ATPase family, including Atp11b, results in a variety of neurological diseases. The results of our analysis demonstrate that there was a shift in the abundance of certain gut microbiota in Atp11b-knockout (KO) mice. Specifically, there was an increase in pro-inflammatory bacteria that accelerate aging and a decrease in probiotics that delay aging. Consequently, an enhanced oxidative stress response was observed, which was characterized by a reduction in the superoxide dismutase (SOD) activity and an increase in malondialdehyde (MDA) and reactive oxygen species (ROS) levels. In addition, our data demonstrate that there was a decrease in the number of cells in the dentate gyrus (DG) region of the hippocampus, and aggravation of aging-related pathological features such as senescence ß-galactosidase (SA-ß-Gal), p-HistoneH2AX (Ser139), and p16INK4. Moreover, KO mice show typical aging-associated behavior, such as memory impairment and slow pain perception. Taken together, we demonstrate a possible mechanism of aging induced by gut microbiota in Atp11b-KO mice, which provides a novel perspective for the treatment of aging through the microbiota-gut-brain axis.

Physicochemical property and antioxidant activity of polysaccharide from the seed cakes of Camellia oleifera Abel.

Seed cake refers to the food by-product of Camellia oleifera Abel, and its insufficient utilization can cause serious environment pollution and resource waste. This study aimed to investigate antioxidant activities of the polysaccharide from the seed cakes of Camellia oleifera Abel (COCP) in vitro and in vivo. The physicochemical property of COCP was also determined. COCP was characterized to be an acidic glycoprotein and mainly consisted of rhamnose (Rha), arabinose (Ara), galactose (Gal), glucose (Glc), xylose (Xyl), mannose (Man), and galacturonic acid (Gal-UA). COCP exhibited the polysaccharide's characteristic absorption in the Fourier transform infrared (FT-IR) spectroscopy and showed as sheet-like structures with a smooth surface under the scanning electron microscope (SEM). COCP exerted good scavenging activities on ABTS, DPPH, and OH radicals, with IC50 values of 2.94, 2.24, and 5.09 mg/ml, respectively. COCP treatment improved learning and memory abilities of D-galactose-induced aging mice. Significant decreases were found in the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine (CRE), blood urea nitrogen (BUN), creatine kinase (CK), and lactate dehydrogenase (LDH) in serum, as aging mice were supplemented with COCP. Aging mice showed obviously higher malondialdehyde (MDA) contents and lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in serum, brain, liver, kidney, and heart. The phenomena were noticeably reversed when mice were treated with COCP. Results indicated that COCP exerted excellent antioxidant activities in vitro and in vivo, which support its potential application as a natural antioxidant in food and medicine industries.

Characterization of two infection-induced transcription factors of Magnaporthe oryzae reveals their roles in regulating early infection and effector expression.

The initial stage of rice blast fungus, Magnaporthe oryzae, infection, before 36 h postinoculation, is a critical timespan for deploying pathogen effectors to overcome the host's defences and ultimately cause the disease. However, how this process is regulated at the transcription level remains largely unknown. This study functionally characterized two M. oryzae Early Infection-induced Transcription Factor genes (MOEITF1 and MOEITF2) and analysed their roles in this process. Target gene deletion and mutant phenotype analysis showed that the mutants Δmoeitf1 and Δmoeitf2 were only defective for infection growth but not for vegetative growth, asexual/sexual sporulation, conidial germination, and appressoria formation. Gene expression analysis of 30 putative effectors revealed that most effector genes were down-regulated in mutants, implying a potential regulation by the transcription factors. Artificial overexpression of two severely down-regulated effectors, T1REP and T2REP, in the mutants partially restored the pathogenicity of Δmoeitf1 and Δmoeitf2, respectively, indicating that these are directly regulated. Yeast one-hybrid assay and electrophoretic mobility shift assay indicated that Moeitf1 specifically bound the T1REP promoter and Moeitf2 specifically bound the T2REP promoter. Both T1REP and T2REP were predicted to be secreted during infection, and the mutants of T2REP were severely reduced in pathogenicity. Our results indicate crucial roles for the fungal-specific Moeitf1 and Moeitf2 transcription factors in regulating an essential step in M. oryzae early establishment after penetrating rice epidermal cells, highlighting these as possible targets for disease control.

The role of phosphatidylserine on the membrane in immunity and blood coagulation.

The negatively charged aminophospholipid, phosphatidylserine (PtdSer), is located in the inner leaflet of the plasma membrane in normal cells, and may be exposed to the outer leaflet under some immune and blood coagulation processes. Meanwhile, Ptdser exposed to apoptotic cells can be recognized and eliminated by various immune cells, whereas on the surface of activated platelets Ptdser interacts with coagulation factors prompting enhanced production of thrombin which significantly facilitates blood coagulation. In the case where PtdSer fails in exposure or mistakenly occurs, there are occurrences of certain immunological and haematological diseases, such as the Scott syndrome and Systemic lupus erythematosus. Besides, viruses (e.g., Human Immunodeficiency Virus (HIV), Ebola virus (EBOV)) can invade host cells through binding the exposed PtdSer. Most recently, the Corona Virus Disease 2019 (COVID-19) has been similarly linked to PtdSer or its receptors. Therefore, it is essential to comprehensively understand PtdSer and its functional characteristics. Therefore, this review summarizes Ptdser, its eversion mechanism; interaction mechanism, particularly with its immune receptors and coagulation factors; recognition sites; and its function in immune and blood processes. This review illustrates the potential aspects for the underlying pathogenic mechanism of PtdSer-related diseases, and the discovery of new therapeutic strategies as well.

Vertically Aligned and Interconnected Graphite and Graphene Oxide Networks Leading to Enhanced Thermal Conductivity of Polymer Composites.

Natural graphite flakes possess high theoretical thermal conductivity and can notably enhance the thermal conductive property of polymeric composites. Currently, because of weak interaction between graphite flakes, it is hard to construct a three-dimensional graphite network to achieve efficient heat transfer channels. In this study, vertically aligned and interconnected graphite skeletons were prepared with graphene oxide serving as bridge and support via freeze-casting method. Three freezing temperatures were utilized, and the resulting graphite and graphene oxide network was filled in a polymeric matrix. Benefiting from the ultralow freezing temperature of -196 °C, the network and its composite occupied a more uniform and denser structure, which lead to enhanced thermal conductivity (2.15 W m-1 K-1) with high enhancement efficiency and prominent mechanical properties. It can be significantly attributed to the well oriented graphite and graphene oxide bridges between graphite flakes. This simple and effective strategy may bring opportunities to develop high-performance thermal interface materials with great potential.

Protective Effects of Anthocyanins from Coreopsis tinctoria against Oxidative Stress Induced by Hydrogen Peroxide in MIN6 Cells.

Anthocyanins (AC) from Coreopsis tinctoria possesses strong antioxidant properties, while the effects of AC on cells damage induced by reactive oxygen species (ROS) in diabetes mellitus diseases progression have not been reported. The present study was carried out to evaluate the protective property of AC against cellular oxidative stress with an experimental model, H2 O2 -exposed MIN6 cells. AC could reverse the decrease of cell viability induced by H2 O2 and efficiently suppressed cellular ROS production and cell apoptosis. In addition, Real-time PCR and Western blot analyses indicated that AC could protect MIN6 cells against oxidative injury through increasing the translocation of Nrf2 into nuclear, decreasing the phosphorylation level of p38 and up-regulating the protein expression of antioxidant enzyme (SOD1, SOD2 and CAT). Thus, this study provides evidence to support the beneficial effect of AC in inhibiting MIN6 cells from H2 O2 -induced oxidative injury.