Unraveling brain aging through the lens of oral microbiota.

The oral cavity is a complex physiological community encompassing a wide range of microorganisms. Dysbiosis of oral microbiota can lead to various oral infectious diseases, such as periodontitis and tooth decay, and even affect systemic health, including brain aging and neurodegenerative diseases. Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration, indicating potential avenues for intervention strategies. In this review, we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases, and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration. We also highlight advances in therapeutic development grounded in the realm of oral microbes, with the goal of advancing brain health and promoting healthy aging.

Improving diffusion kinetics of zinc ions/stabilizing zinc anode by molecular slip mechanism and anchoring effect in supramolecular zwitterionic hydrogels.

The severe hydrogen evolution reaction and parasitic side reaction on Zn anode are the key issues which hinder the development of aqueous Zn-based energy storage devices. Herein, a polyacrylamide/carboxylated cellulose nanofibers/betaine citrate supramolecular zwitterionic hydrogels with molecular slip effects are proposed for enhancing Zn2+ diffusion and protecting Zn anodes. Non-covalent interactions within supramolecular hydrogels forms the skeleton for molecular slip and the strong coordination of carboxyl and amino groups with Zn2+ further facilitates the rapid Zn2+ transfer. Additionally, anchoring carboxyl and amino groups at the anode promotes the uniform deposition of Zn2+and protects Zn anode. On the basis of molecular slip mechanism and anchoring effect in the supramolecular zwitterionic hydrogels, Zn||Zn symmetric batteries undergo 800 h of stable electroplating stripping at a depth of discharge of 80 %. Zn||Cu asymmetric batteries exhibit an impressive average coulombic efficiency of 99.4 % over a remarkable span of 900 cycles at a current density of 15 mA cm-2. Furthermore, Zn||NH4V4O10 batteries successfully undergo over 1,000 cycles at a current density of 0.5 A g-1. Intrinsic ion diffusion mechanism of supramolecular hydrogel electrolytes provides an original strategy for the application of high-performance Zn-based energy storage devices.

Association of cognitive performance with overall, dosage, intensity, and domain physical activity in aging: NHANES 2011-2014.

BACKGROUND: The specific relationship between PA in detailed types and cognition is still unclear due to limited evidence. Our study aimed to investigate the relationship between cognitive performance and various aspects of physical activity, including overall activity, dosage, intensity levels [moderate physical activity (MPA), vigorous PA], and different domains of activity [occupational PA (OPA), transportation PA (TPA), and leisure-time PA (LTPA)] in older adults using data from the NHANES database. METHODS: This cross-sectional analysis used data from 2 cycles of NHANES (2011-2014). PA was determined through participants' self-reports using the Global Physical Activity Questionnaire (GPAQ). Cognitive performance was evaluated by the presence of psychometric mild cognitive impairment (p-MCI), identified based on a composite measure derived from three cognitive tests including the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency test, and the Digit Symbol Substitution test (DSST). Logistic regression models were used to evaluate the association. RESULTS: A total of 2588 participants aged 60 years or older were included, with an average age of 69.4 years and 48% being male. In the fully adjusted model, compared to no PA, performing 300 min of PA, and MPA were associated with 44%, and 33% reductions in the prevalence of p-MCI, respectively. Additionally, engaging in 1-149 min/week [OR 0.56, 95% CI (0.33-0.92)] and ≥ 300 min/week [OR 0.66, 95% CI (0.44-0.96)] of OPA, as well as ≥ 300 min/week [OR 0.56, 95% CI (0.36-0.86)] of LTPA, were also associated with a lower prevalence of p-MCI. Additionally, engaging in a diverse range of PA had better outcomes. CONCLUSIONS: Our results suggested a positive association between higher levels of PA and enhanced cognitive performance. Different intensities and domains of PA have varying impacts on cognition. Future exploration, such as objectively measured PA and longitudinal studies were needed to validate our conclusion.

Association between serum albumin and pulmonary function in adolescents: analyses of NHANES 2007-2012.

BACKGROUND: Pulmonary function tests (PFTs) are an important tool for assessing pulmonary diseases, although clinicians often find it challenging to accurately evaluate the pulmonary function of children. METHODS: We intend to investigate the association between serum albumin (SA) and lung function among U.S. adolescents. This cross-sectional study included 3,072 adolescents (aged 12 to 19) from 2007 to 2012National Health and Nutrition Examination Survey (NHANES). PFTs, including forced vital capacity (FVC)%predicted, forced expiratory volume in 1 s (FEV1)%predicted, FEV1/FVC%predicted, and maximum mid-expiratory flow (FEF25-75) % predicted, were utilized to assess the association between serum albumin levels and lung function. To explore the potential associations between SA and pulmonary function, we employed multivariate linear regression, subgroup analysis, smoothing curve fitting and threshold effect. RESULTS: A positive correlation was observed between serum albumin levels and pulmonary function. In the model with a fully adjusted, each 1 g/dL serum albumin increase in SA corresponded to an increase of 2.69% in FVC%pred, 5.8% in FEV1%pred, 10.99% in FEF25-75%pred and 2.98% in FEV1/FVC%pred. This association between SA and FEV1%pred differed across gender subgroups. A non-linear relationship was observed between SA and FEV1/FVC%pred. CONCLUSION: Our results demonstrated a positive correlation between SA and lung function, suggesting a novel modality for evaluating pulmonary function, specifically in children. CLINICAL TRIAL NUMBER: Not applicable.

Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging.

To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging. Furthermore, we observed that IgG could induce a pro-senescent state in macrophages and microglia, thereby exacerbating tissue aging, and that targeted reduction of IgG mitigated aging across various tissues in male mice. This study provides a high-resolution spatial depiction of aging and indicates the pivotal role of immunoglobulin-associated senescence during the aging process.

Mediating role of inflammatory indicators in the association between sleep status and blood pressure in centenarians: evidence from China Hainan Centenarian Cohort Study.

Objectives: To conduct a comprehensive analysis in Hainan centenarians on the link between sleep status and their blood pressure status. Furthermore, the study also aims to explore how inflammatory indicators may mediate the relationship. Methods: The China Hainan Centenarians Cohort Study (CHCCS) collected baseline data on sleep status, inflammatory indicators, and blood pressure data. The study used a mediation model to investigate how inflammatory indicators mediate the relationship between sleep status and blood pressure status. Result: In this study, a total of 967 centenarians were included. The prevalence of hypertension among the centenarians was 71.4%. The analysis showed that centenarians with poor sleep quality had a 43% higher risk of hypertension compared to those with normal sleep quality (OR = 1.43, 95% CI: 1.03-1.97). Additionally, centenarians with nighttime sleep durations of ≤ 6 h or > 9 h had higher proportions of high pulse pressure (PP), with OR values of 1.76 (95% CI: 1.18-2.63) and 2.07 (95% CI: 1.34-3.19), respectively. Mediation analysis illustrated that complement C3 played a mediating role in the relationship between sleep quality and hypertension, with an effect ratio of 2.4%. Similarly, lymphocyte count, the neutrophil-to-lymphocyte ratio (NLR), and the systemic immune-inflammation index (SII) were identified as mediating factors in the association between nighttime sleep duration and high PP, with effect ratios of 91.22%, 36.93%, and 0.20%, respectively. Conclusion: In centenarians, poor sleep quality raises the risk of hypertension, with complement C3 as a mediator. Additionally, nighttime sleep durations of ≤ 6 h or > 9 h increases the risk of high PP, mediated by lymphocyte count, NLR, and SII.

Characterization of GABAergic marker expression in prefrontal cortex in dexamethasone induced depression/anxiety model.

Background: The pivotal responsibility of GABAergic interneurons is inhibitory neurotransmission; in this way, their significance lies in regulating the maintenance of excitation/inhibition (E/I) balance in cortical circuits. An abundance of glucocorticoids (GCs) exposure results in a disorder of GABAergic interneurons in the prefrontal cortex (PFC); the relationship between this status and an enhanced vulnerability to neuropsychiatric ailments, like depression and anxiety, has been identified, but this connection is still poorly understood because systematic and comprehensive research is lacking. Here, we aim to investigate the impact of dexamethasone (DEX, a GC receptor agonist) on GABAergic interneurons in the PFC of eight-week-old adult male mice. Methods: A double-blind study was conducted where thirty-two mice were treated subcutaneously either saline or DEX (0.2 mg/10 ml per kg of body weight) dissolved in saline daily for 21 days. Weight measurements were taken at five-day intervals to assess the emotional changes in mice as well as the response to DEX treatment. Following the 21-day regimen of DEX injections, mice underwent examinations for depression/anxiety-like behaviours and GABAergic marker expression in PFC. Results: In a depression/anxiety model generated by chronic DEX treatment, we found that our DEX procedure did trigger depression/anxiety-like behaviors in mice. Furthermore, DEX treatment reduced the expression levels of a GABA-synthesizing enzyme (GAD67), Reelin, calcium-binding proteins (parvalbumin and calretinin) and neuropeptides co-expressed in GABAergic neurons (somatostatin, neuropeptide Y and vasoactive intestinal peptide) in the PFC were reduced after 21 days of DEX treatment; these reductions were accompanied by decreases in brain size and cerebral cortex thickness. Conclusion: Our results indicate that a reduction in the number of GABAergic interneurons may result in deficiencies in cortical inhibitory neurotransmission, potentially causing an E/I imbalance in the PFC; this insight suggests a potential breakthrough strategy for the treatment of depression and anxiety.

Exploring the Crystal Structure and Electronic Properties of γ-Al2O3: Machine Learning Drives Future Material Innovations.

For decades, researchers have struggled to determine the precise crystal structure of γ-Al2O3 due to its atomic-level disorder and the challenges associated with obtaining high-purity, high-crystallinity γ-Al2O3 in laboratory settings. This study investigates the crystal structure and electronic properties of γ-Al2O3 coatings under the influence of an external electric field, integrating machine learning with density functional theory (DFT). A potential 160-atom supercell structure was identified from over 600,000 γ-Al2O3 configurations and confirmed through high-resolution transmission electron microscopy and selected area electron diffraction. The findings indicate that γ-Al2O3 deviates from the conventional spinel structure, suggesting that octahedral vacancies can reduce the system's energy. Under an external electric field, the material's band structure and density of states (DOS) undergo significant changes: the bandgap narrows from 3.996 to 0 eV, resulting in metallic behavior, while the projected density of states (PDOS) exhibits peak broadening and splitting of oxygen atom PDOS below the Fermi level. These alterations elucidate the variations in the electrical conductivity of alumina coatings under an electric field. These findings clarify the mechanisms of γ-Al2O3's electronic property modulation and offer insights into its covalent and ionic mixed bonding as a wide-bandgap semiconductor. This discovery is essential for understanding dielectric breakdown in insulating materials.

Optimized carbonylation treatment of Litopenaeus vannamei matrix decreased its immunoreactivity and improved edible quality, simultaneously.

The study aimed to investigate how carbonylation affects the immunoreactivity and edible quality of the Litopenaeus vannamei matrix. The carbonylation treatment conditions of the shrimp matrix were optimized. Firstly, the treatment condition is optimized with 1.0 mmol/L malonaldehyde at 37 °C, 12 h. The optimized carbonylated shrimp showed lower immunoreactivity, carbonyl group, and free amino acids. Then the edible quality was evaluated, optimized carbonylated shrimp matrix presented better digestibility and the continuous digestion products showed lower immunoreactivity. Optimized carbonylated shrimp for the other sensory indicators showed better texture properties and an inviting appearance. Looser microstructure by scanning electron microscopy contributed to the higher digestibility, lower immunoreactivity, and better edible quality for optimized carbonylated shrimp matrix. Besides, more potentially modified amino acid residues exposed on the allergen surface may be the other reason. In conclusion, optimized carbonylation treatment reduced the immunoreactivity and improved the edible quality of shrimp.

Multi-Omics Analysis Reveals Molecular Responses of Alkaloid Content Variations in Lycoris aurea Across Different Locations.

Lycoris aurea, celebrated for its visually striking flowers and significant medicinal value due to the presence of alkaloids such as lycorine and galanthamine, has intricate yet poorly understood regulatory mechanisms. This study provides a detailed examination of the transcriptomic, metabolomic and ecological dynamics of L. aurea, aiming to elucidate the underlying molecular mechanisms of alkaloid biosynthesis. Our comparative analysis across different ecological settings highlighted key genes involved in alkaloid biosynthesis, such as genes encoding aldehyde dehydrogenase and norbelladine 4'-O-methyltransferase, which were distinctively increased in the high alkaloids-producing group. We identified a total of 6871 differentially expressed genes and 915 metabolites involved in pathways like terpenoid backbone biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis. Protein interaction network analysis revealed significant upregulation of photosynthesis, photosystem and photosynthetic membrane pathways in the alkaloids-producing region. Furthermore, our research delineated the interactions among soil microbial communities, genes and plant and soil biochemical properties, noting that bacterial populations correlate with soil properties that favour the activation of metabolic pathways essential for alkaloid production. Collectively, this study advances our understanding of the genetic and metabolic alkaloid biosynthesis pathways in L. aurea, shedding light on the complex interactions that govern alkaloid production.

Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases.

Ageing is a complex biological process in which a gradual decline in physiological fitness increases susceptibility to diseases such as neurodegenerative disorders and cancer. Cellular senescence, a state of irreversible cell-growth arrest accompanied by functional deterioration, has emerged as a pivotal driver of ageing. In this Review, we discuss how heterochromatin loss, telomere attrition and DNA damage contribute to cellular senescence, ageing and age-related diseases by eliciting genome instability, innate immunity and inflammation. We also discuss how emerging therapeutic strategies could restore heterochromatin stability, maintain telomere integrity and boost the DNA repair capacity, and thus counteract cellular senescence and ageing-associated pathologies. Finally, we outline current research challenges and future directions aimed at better comprehending and delaying ageing.

Intensive chemotherapy versus standard chemotherapy among patients with high risk, operable, triple negative breast cancer based on integrated mRNA-lncRNA signature (BCTOP-T-A01): randomised, multicentre, phase 3 trial.

OBJECTIVE: To evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer. DESIGN: Randomised, multicentre, open label, phase 3 trial. SETTING: 7 cancer centres in China between 3 January 2016 and 17 July 2023. PARTICIPANTS: Female patients aged 18-70 years with early triple negative breast cancer after definitive surgery. INTERVENTIONS: After risk stratification using the integrated signature, patients at high risk were randomised (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (arm A; n=166) or a standard treatment of four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (arm B; n=170). Patients at low risk received the same adjuvant chemotherapy as arm B (arm C; n=168). MAIN OUTCOME MEASURES: The primary endpoint was disease-free survival in the intention-to-treat analysis for arm A versus arm B. Secondary endpoints included disease-free survival for arm C versus arm B, recurrence-free survival, overall survival, and safety. RESULTS: Among the 504 enrolled patients, 498 received study treatment. At a median follow-up of 45.1 months, the three year disease-free survival rate was 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio 0.51, 95% confidence interval (CI) 0.28 to 0.95; P=0.03). The three year recurrence-free survival rate was 92.6% in arm A and 83.2% in arm B (hazard ratio 0.50, 95% CI 0.25 to 0.98; P=0.04). The three year overall survival rate was 98.2% in arm A and 91.3% in arm B (hazard ratio 0.58, 95% CI 0.22 to 1.54; P=0.27). The rates of disease-free survival (three year disease-free survival 90.1% v 80.6%; hazard ratio 0.57, 95% CI 0.33 to 0.98; P=0.04), recurrence-free survival (three year recurrence-free survival 94.5% v 83.2%; 0.42, 0.22 to 0.81; P=0.007), and overall survival (three year overall survival 100% v 91.3%; 0.14, 0.03 to 0.61; P=0.002) were significantly higher in patients in arm C than in those in arm B with the same chemotherapy regimen. The incidence of grade 3-4 treatment related adverse events were 64% (105/163), 51% (86/169), and 54% (90/166) for arms A, B, and C, respectively. No treatment related deaths occurred. CONCLUSIONS: The multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable triple negative breast cancer. Intensive regimens incorporating gemcitabine and cisplatin into anthracycline/taxane based therapy significantly improved disease-free survival with manageable toxicity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02641847.

MicroRNA-451 from Human Umbilical Cord-Derived Mesenchymal Stem Cell Exosomes Inhibits Alveolar Macrophage Autophagy via Tuberous Sclerosis Complex 1/Mammalian Target of Rapamycin Pathway to Attenuate Burn-Induced Acute Lung Injury in Rats.

Objective: Our previous studies established that microRNA (miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-Exos) alleviates acute lung injury (ALI). This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy. Methods: Exosomes were isolated from hUC-MSCs. Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor. Hematoxylin-eosin staining evaluated inflammatory injury. Enzyme-linked immunosorbnent assay measured lipopolysaccharide (LPS), tumor necrosis factor-α, and interleukin-1ß levels. qRT-PCR detected miR-451 and tuberous sclerosis complex 1 (TSC1) expressions. The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system. Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin (mTOR) pathway and autophagy. Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level. Results: hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy. MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1. Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages. Silencing TSC1 activated mTOR signaling and inhibited autophagy, while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced. Conclusion: miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway, providing a potential therapeutic strategy for ALI.

Study on the Effect of Electron/Hole Injection on the Energy-Storage Properties of Polymer Dielectrics.

As a critical component of electrostatic capacitors, the polymer dielectric directly affects the performance of the capacitor. In this work, Polycarbonate (PC)/Polyvinylidene fluoride (PVDF) asymmetric bilayer polymer dielectrics were prepared, and the influence of different polymer materials' barrier characteristics on various electrical properties of composite dielectrics was studied by changing the direction of applied electric fields. Research has found that the dielectric constant of a composite dielectric is between PVDF and PC (approximately 4.8 at 10 Hz) and is independent of the relative position of PVDF and PC in the dielectric. However, the relative position of PC and PVDF has a significant impact on the energy-storage characteristics of composite dielectrics. When PVDF comes into contact with the negative electrode, even though PC has a higher hole barrier, the composite dielectric can only withstand a maximum electric-field strength of 400 MV/m, which is much lower than the maximum electric-field strength that pure PC can withstand (520 MV/m), and it only achieves an energy-storage density of 3.7 J/cm3. When the PC comes into contact with the negative electrode, the high electron barrier of the PC effectively suppresses the injection of electrons at the electrode. It can withstand the same electric-field strength as PC (520 MV/m), achieving an energy-storage density of 5.48 J/cm3, which is 1.46 times that of pure PC and 1.64 times that of PVDF. This experiment effectively combined the advantages of PC and PVDF by utilizing the electron/hole barrier of polymer materials to obtain a fully organic dielectric with excellent energy-storage performance.

Supramolecular deep eutectic solvents: Current advances and critical evaluation of cyclodextrins from solute to solvent in emerging functional food.

The acceptance of nonconventional solvents as viable substitutes for traditional organic solvents has been widely recognized in order to comply with food-safety and sustainability regulations. Cyclodextrins (CDs), derived from starch, are cyclic oligosaccharides with the ability to form inclusion complexes with a variety of functional substances as the result of their distinctive structure, which enables them to effectively encapsulate bioactive compounds, rendering them highly sought after for use in food applications. In the implementing plan to achieve carbon-neutral emissions by 2050, the novel generation of supramolecular deep eutectic solvents (SUPRADES) has garnered increased attention and interest. The approach of utilizing SUPRADES as emerging solvents was just beginning to be applied to food studies. This review summarizes a revision of the current advances and critical evaluation of cyclodextrin-based SUPRADES (CD-based SUPRADES) as promising solvents for the enhancement of the extraction efficiency, solubilization and stability of bioactive compounds, adsorption and separation of food components, packaging materials, and modification of biopolymers. To meet the sustainable processing needs of the food industry, the emerging categories of CD-based SUPRADES need to be further fabricated. Herein, our review will sort out the potential application of CD-based SUPRADES in the food industry, aiming to provide a better understanding of CD-based SUPRADES within the viewpoint of food science. Formulation intricacies and scalability issues in real functional foods using CD-based SUPRADES as media need more efforts.

Optimizing the stability of NiFeOOH via oxyanion intercalation for water oxidation at large current densities.

In alkaline water splitting, transition metals (Ni, Fe) have received extensive attention, and NiFe-oxyhydroxide (NiFeOOH) is regarded as an exceptionally active electrocatalysts for oxygen evolution reaction (OER). However, maintaining the long-term stability of NiFeOOH at high current densities is challenging due to Fe segregation and catalyst degradation. Herein, this study proposes an approach to enhancing the stability of the Ni/Fe-O covalent bond by intercalating oxyanions (NO3-, PO43-, SO42-, and SeO42-) into the NiFeOOH substrate, improving its resistance to bond breakage. And the NiFeOOH-NO3- electrocatalyst was found to be optimal, achieving an overpotential of 311 mV and stable performance at 1 A cm-2 for several hundred hours. Consequently, NiFeOOH-NO3- exhibited a significantly improved OER stability, with a mere 3.33 % stability attenuation after 100 h, compared to 13.19 % for pristine NiFeOOH. Notably, the presence of NO3- in NiFeOOH effectively mitigates Fe segregation, leading to a fourfold enhancement in long-term stability relative to that of NiFeOOH without NO3- modification. Theoretical calculations show that the introduction of NO3- effectively shifts metal 3d band centers of NiFeOOH closer to the Fermi level. It is suggested that the oxyanions lead to increased strength of the Ni/Fe-O bonds, thereby inhibiting the dissolution of Fe and enhancing the stability of NiFeOOH phase. This research represents a significant advance in controlling Fe segregation to stabilize NiFe-based electrocatalysts for high-current-density water oxidation.

Two Thiophene-Functionalized Co-MOFs as Green Heterogeneous Catalysts for the Biginelli Reaction.

Two Co(II) metal-organic frameworks (Co-MOFs), namely, [Co(DMTDC)(bimb)]n (Co-MOF-1) and {[Co(DPTDC)(bimb)(H2O)]·2DMF}n (Co-MOF-2) (H2DMTDC = 3,4-dimethylthieno[2,3-b]thiophene-2,5-dicarboxylic acid, H2DPTDC = 3,4-diphenylthieno[2,3-b]thiophene-2,5-dicarboxylic acid, bimb = 1,4-bis((1H-imidazol-1-yl)methyl)benzene), were obtained by the reaction of flexible N-containing ligand bimb and two structurally related thiophene-containing ligands H2DMTDC and H2DPTDC, respectively. These Co-MOFs displayed a 3D framework and porous structure, respectively. Co-MOF-1 and the activated sample Co-MOF-2' could act as green heterogeneous catalysts for the one-pot multicomponent Biginelli reaction, specifically the dehydration condensation process involving aldehydes, acetoacetates, and urea to yield dihydropyrimidin-2(1H)-ones. The reaction has advantages such as solvent-free conditions, water as only byproduct, readily accessible starting materials, excellent functional group compatibility, and simple operation. Both catalysts exhibited a wide substrate scope and maintained significant catalytic activity over five cycles. The special catalytic performance may be ascribed to functional groups within the ligand.

Protein degradation of antizyme depends on the N-terminal degrons.

Antizyme (AZ) is a regulatory protein that plays a crucial role in modulating the activity of ornithine decarboxylase (ODC), which is the initial and rate-limiting enzyme in the complex pathway of polyamine biosynthesis. AZ facilitates the swift degradation of ODC, thereby modulating the levels of cellular polyamines. This study unveils a new ubiquitin-independent mechanism for AZ degradation, emphasizing the essential role of N-terminal degrons. Contrary to traditional ubiquitin-dependent degradation, our findings reveal that AZ degradation is significantly influenced by its N-terminal region. By conducting a series of experiments, including in vitro degradation assays, cycloheximide chase experiments, differential scanning calorimetry, and measurement of cellular concentrations of polyamines, we demonstrate that N-terminal truncation significantly enhances AZ's stability and facilitates the reduction of polyamine levels by accelerating ODC degradation. The removal of the N-terminal portion of AZ results in a reduced degradation rate and enhanced thermal stability of the protein, leading to a more efficient inhibition of polyamine synthesis. These findings are corroborated by the analysis of AZ isoforms, AZ1, AZ2, and AZ3, which display differential degradation patterns based on the specific N-terminal segments. This substantiates a degradation mechanism driven by an intrinsically disordered N-terminal region acting as a degron, independent of lysine ubiquitination. These results underscore the significant regulatory function of the N-terminal domain in the activity of AZ and the maintenance of polyamine homeostasis.

A colorimetric platform using highly active Prussian blue composite nanocubes for the rapid determination of ascorbic acid and acid phosphatase.

Cobalt-doped Prussian blue composite nanocubes (Co-PB NCs) were synthesized, which can quickly convert O2 to O2•- and 1O2. Due to the presence of cobalt and iron transition metal redox electron pairs, Co-PB NCs with high oxidase mimetic activity can rapidly oxidize the substrate 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue products (ox-TMB) without the assistance of unstable H2O2. Using ascorbic acid-2-phosphate trisodium salt (AAP) as a substrate, it can be converted to reduced ascorbic acid (AA) under acid phosphatase (ACP) hydrolysis, resulting in suppression of TMB oxidation. Therefore, an enzyme cascade signal amplification strategy for rapid colorimetric detection of AA/ACP was developed based on the high-efficiency oxidase-like activity of Co-PB NCs combined with the hydrolysis effect of ACP. The color changes at low concentrations of AA and ACP could be observed by the naked eye, and the detection limits of AA and ACP were 1.67 µM and 0.0266 U/L, respectively. The developed colorimetric method was applied to the determination of AA in beverages and ACP in human serum, and the RSDs were less than 3%, showing good reproducibility. This work provides a promising strategy for the use of metal-doped Prussian blue composite material for the construction of rapid colorimetric sensing platforms that avoid the use of unstable hydrogen peroxide.

Lipid-lowering effects of gefarnate in statin-treated patients with residual hypertriglyceridemia: a randomized controlled study.

BACKGROUND: The prevention of coronary artery disease (CAD) faces dual challenges: the aspirin-induced gastrointestinal injury, and the residual cardiovascular risk after statin treatment. Geraniol acetate (Gefarnate) is an anti-ulcer drug. It was reported that geraniol might participate in lipid metabolism through a variety of pathways. The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia. METHODS: In this prospective, open-label, randomized, controlled trial, 69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group, received gefarnate (100 mg/3 times a day) combined with statin and statin alone, respectively. At baseline and after one-month treatment, the levels of plasma triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol were tested. RESULTS: After one-month gefarnate treatment, triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L (P = 0.0018), LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L (P = 0.0004), HDL-C level increased from 0.97 mmol/L to 1.17 mmol/L (P = 0.0228). Based on statin therapy, gefarnate could significantly reduce the plasma triglyceride level (P = 0.0148) and increase the plasma HDL-C level (P = 0.0307). Although the LDL-C and total cholesterol levels tended to decrease, there was no statistically significant difference. CONCLUSIONS: The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia. This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.