Oxygen-functionalized Fe3O4@o-polypyrrole acting as high-efficiency oxidase mimics and their application in glutathione colorimetric sensing.

The enzyme-like properties of nanozymes may be considerably affected by the structure and surface groups, which thus need to be optimized. Here, through a simple NaOH chemical corrosion method, the chemical structure similar to N-Methylpyrrolidone (NMP), which possessed intrinsic oxidase-like activity, was introduced into polypyrrole (PPy), and then this nanomaterial became oxygen-functionalized PPy (o-PPy) with excellent oxidase-like activity from PPy without this property. Furthermore, after compounding magnetic Fe3O4, the obtained nanocomposites Fe3O4@o-PPy nanoparticles (Fe3O4@o-PPy NPs) showed superiorities in separation during synthesis and real-time control of enzyme catalysis. Studies have found that the enzymatic activity of Fe3O4@o-PPy NPs depended on the amount of functionalized oxygen and the conjugation extent of o-PPy. Fe3O4@o-PPy NPs had efficient oxidase-like activity under a wide range of pH and temperature. Based on the oxidase-like activity of Fe3O4@o-PPy NPs, a colorimetric sensor for glutathione (GSH), which presented rich color changes and satisfactory colorimetric resolution by adding the amaranth, was realized. We believe that the functional modification and structural regulation of PPy can not only realize its wider application but also promote the discovery of novel and efficient nanozymes.

Chitosan-coated liposome with lysozyme-responsive properties for on-demand release of levofloxacin.

As an anti-infection antibiotic delivery route, a drug-controlled release system based on a specific condition stimulus response can enhance drug stability and bioavailability, reduce antibiotic resistance, achieve on-demand release and improve targeting and utilization efficiency. In this study, chitosan-coated liposomes containing levofloxacin (Lef@Lip@CS) were prepared with lysozyme in body fluids serving as an intelligent "switch" to enable accurate delivery of antibiotics through the catalytic degradation ability of chitosan. Good liposome encapsulation efficacy (64.89 ± 1.86 %) and loading capacity (5.28 ± 0.18 %) were achieved. The controlled-release behavior and morphological characterization before and after enzymatic hydrolysis confirmed that the levofloxacin release rate depended on the lysozyme concentration and the degrees of deacetylation of chitosan. In vitro bacteriostatic experiments showed significant differences in the effects of Lef@Lip@CS before and after enzyme addition, with 6-h inhibition rate of 72.46 % and 100 %, and biofilm removal rates of 51 % and 71 %, respectively. These findings show that chitosan-coated liposomes are a feasible drug delivery system responsive to lysozyme stimulation.

Construction of human 3D striato-nigral assembloids to recapitulate medium spiny neuronal projection defects in Huntington's disease.

The striato-nigral (Str-SN) circuit is composed of medium spiny neuronal projections that are mainly sent from the striatum to the midbrain substantial nigra (SN), which is essential for regulating motor behaviors. Dysfunction of the Str-SN circuitry may cause a series of motor disabilities that are associated with neurodegenerative disorders, such as Huntington's disease (HD). Although the etiology of HD is known as abnormally expanded CAG repeats of the huntingtin gene, treatment of HD remains tremendously challenging. One possible reason is the lack of effective HD model that resembles Str-SN circuitry deficits for pharmacological studies. Here, we first differentiated striatum-like organoids from human pluripotent stem cells (hPSCs), containing functional medium spiny neurons (MSNs). We then generated 3D Str-SN assembloids by assembling striatum-like organoids with midbrain SN-like organoids. With AAV-hSYN-GFP-mediated viral tracing, extensive MSN projections from the striatum to the SN are established, which formed synaptic connection with GABAergic neurons in SN organoids and showed the optically evoked inhibitory postsynaptic currents and electronic field potentials by labeling the striatum-like organoids with optogenetic virus. Furthermore, these Str-SN assembloids exhibited enhanced calcium activity compared to that of individual striatal organoids. Importantly, we further demonstrated the reciprocal projection defects in HD iPSC-derived assembloids, which could be ameliorated by treatment of brain-derived neurotrophic factor. Taken together, these findings suggest that Str-SN assembloids could be used for identifying MSN projection defects and could be applied as potential drug test platforms for HD.

Smartphone-assisted hydrogel platform based on BSA-CeO2 nanoclusters for dual-mode determination of acetylcholinesterase and organophosphorus pesticides.

A dual-mode sensor was developed for detecting acetylcholinesterase (AChE) and organophosphorus pesticides (OPs) via bifunctional BSA-CeO2 nanoclusters (NCs) with oxidase-mimetic activity and fluorescence property. The dual-mode sensor has the characteristics of self-calibration and self-verification, meeting the needs of different detection conditions and provide more accurate results. The colorimetric sensor and fluorescence sensor have been successfully used for detecting AChE with limit of detection (LOD) of 0.081 mU/mL and 0.056 mU/mL, respectively, while the LOD for OPs were 0.9 ng/mL and 0.78 ng/mL, respectively. The recovery of AChE was 93.9-107.2% and of OPs was 95.8-105.0% in actual samples. A novel strategy was developed to monitor pesticide residues and detect AChE level, which will motivate future work to explore the potential applications of multifunctional nanozymes.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausibility of distinct influences of both sleep duration extremes in cardiovascular health. With several of our loci reflecting specificity towards population background or sex, our discovery sheds light on the importance of embracing granularity when addressing heterogeneity entangled in gene-environment interactions, and in therapeutic design approaches for blood pressure management.

Integration of Magnetic-Field-Directed Self-Assembly-Based Cell Culture and Biosensing Platform for Improving hPSCs-Derived Neurons and Quantitative Detection of Neurotransmitter.

Despite the fact that human neural cell models have played significant roles in both research and cell replacement therapies for neurological diseases, the existing techniques for obtaining neurons from human pluripotent stem cells (hPSCs) are arduous and intricate. Additionally, the evaluation of neuron quality in the natural environment remains deficient. Consequently, we have developed a comprehensive platform utilizing magnetic-field-directed self-assembly (MDSA) of MXenes@Fe3O4 (M/F) nanocomposites. This platform facilitates the cultivation and in situ analysis of differentiated dopaminergic (DA) neurons. Our results showed that the introduction of M/F enhances neurite outgrowth and leads to the development of more intricate ramifications. Moreover, with the increase of magnetic field intensity, neurite outgrowth is further enhanced, and the proportion of differentiated mature neurons from hPSCs increases. This suggests that our platform promotes the maturation of neurons, emphasizing the crucial role of biophysical cues in expediting the differentiation process. The homogenization platform formed by MDSA of M/F nanocomposites exhibits high conductivity, leading to its exceptional performance in the real-time monitoring of the release of dopamine neurotransmitter from hPSC-derived DA neurons. Hence, this platform demonstrates significant potential for monitoring cell quality. In conclusion, our integrated platform, based on MDSA of M/F nanocomposites, offers a reliable and efficient means for the in vitro generation of human neurons with a controllable quality. The as-prepared platform holds potential for enhancing neuronal maturation and ensuring consistent cell quality, showing significant implications for in vitro biological research, disease modeling, and cell replacement therapy.

A review of natural plant extracts in beverages: Extraction process, nutritional function, and safety evaluation.

The demand for foods and beverages with therapeutic and functional features has increased as a result of rising consumer awareness of health and wellness. In natural, plants are abundant, widespread, and inexpensive, in addition to being rich in bioactive components that are beneficial to health. The bioactive substances contained in plants include polyphenols, polysaccharides, flavonoids, aromatics, aliphatics, terpenoids, etc., which have rich active functions and application potential for plant-based beverages. In this review, various existing extraction processes and their advantages and disadvantages are introduced. The antioxidant, anti-inflammatory, intestinal flora regulation, metabolism regulation, and nerve protection effects of plant beverages are described. The biotoxicity and sensory properties of plant-based beverages are also summarized. With the diversification of the food industry and commerce, plant-based beverages may become a promising new category of health functional foods in our daily lives.

A molecularly imprinted ratiometric fluorescence sensor based on blue/red carbon quantum dots for the visual determination of thiamethoxam.

Neonicotinoids such as thiamethoxam (TMX) were widely used in agricultural production and tended to accumulate in the environment, potentially harming human and ecosystem health. To enable widespread monitoring of TMX residues, it was essential to design a reliable and sensitive detection method. Here, we developed a novel smartphone-enablled molecularly imprinted ratiometric fluorescence sensing system for selective on-site detection of TMX. It was based on blue-emission carbon dots (CDs) wrapped with a molecularly imprinted layer (B-CDs@MIPs), which provided the response signal, while red-emission CDs (R-CDs) served as an internal reference. The fluorescence signal ratio of the sensor increased with the TMX concentration, resulting in an obvious fluorescence color change from red to blue. The sensor exhibited a satisfactory limit of detection (LOD) of 13.5 nM in fluorescence analysis while LOD of 70.1 nM in visual determination. In addition, the sensing system was validated using food and environment samples, exhibiting recoveries from 91.40% to 105.7%, indicating excellent reliability for TMX detection in actual samples. Thus, the sensing system developed in this study offered promising prospects for visual detection of pesticide residues in complex environmental samples.

Direct synthesis of hydrogen fluoride-free multilayered Ti3C2/TiO2 composite and its applications in photocatalysis.

Ti3C2/TiO2 hybrids are environment-friendly and exhibit excellent photocatalytic and hydrogen-generating power characteristics. Herein, a novel single-step method is proposed for fabricating multilayer structures in which TiO2, generated from (NH4)2TiF6, wraps the Ti3C2 MXene by etching Ti3AlC2 with (NH4)2TiF6. The optimal reaction conditions for the etching of Ti3AlC2 with (NH4)2TiF6 were systematically studied. The phase composition, morphology, and photophysical properties of the Ti3C2/TiO2 hybrids were investigated using X-ray diffraction, field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and UV-vis spectrophotometry. The thermal stability of the hybrids was investigated using thermogravimetric and differential thermal analyses. Along with the formation of Ti3C2 MXene, Ti3AlC2 reacted with (NH4)2TiF6 at 60 °C for 24 h to form hybrids surrounded by NH4TiOF3 crystals. Subsequent reactions of these hybrids with H3BO3 resulted in the conversion of NH4TiOF3 crystals into TiO2 and eventually into Ti3C2/TiO2 hybrids. Furthermore, the photocatalytic activity of the Ti3C2/TiO2 hybrids was measured by monitoring the photodegradation of methylene blue under ultraviolet light, which showed that the photocatalytic activity of the Ti3C2/TiO2 hybrids was higher than that of the commercial anatase TiO2 nanoparticles.

Underlying mechanisms and molecular targets of genistein in the management of type 2 diabetes mellitus and related complications.

Diabetes mellitus (DM) is a chronic metabolic disease caused by a complex interaction of genetic and environmental factors and is characterized by persistent hyperglycemia. Long-term hyperglycemia can cause macrovascular and microvascular damage, and compromise the heart, brain, kidney, peripheral nerves, eyes and other organs, leading to serious complications. Genistein, a phytoestrogen derived from soybean, is known for its various biological activities and therapeutic properties. Recent studies found that genistein not only has hypoglycemic activity but can also decrease insulin resistance. In addition, genistein has particular activity in the prevention and treatment of diabetic complications, such as nephropathy, cardiovascular disease, osteoarthrosis, encephalopathy and retinopathy. Therefore, the purpose of this review is to summarize the latest medical research and progress of genistein in DM and related complications and highlights its potential molecular mechanisms and therapeutic targets. Meanwhile, evidence is provided for the development and application of genistein as a potential drug or functional food in the prevention and treatment of diabetes and its related complications.

A biosensor based on Fe3O4@MXene-Au nanocomposites with high peroxidase-like activity for colorimetric and smartphone-based detection of glucose.

A novel magnetic nanozyme Fe3O4@MXene-Au nanocomposite, which possessed higher peroxidase-like activity than that of Fe3O4 nanoparticles and Fe3O4@MXene nanocomposites, was developed. The outstanding magnetic properties of the nanozyme endowed it with the ability of simple and rapid separation, achieving great recyclability. Based on Fe3O4@MXene-Au nanocomposites and glucose oxidase (Glu Ox), a highly selective colorimetric biosensor for glucose detection was developed. Fe3O4@MXene-Au nanocomposites can catalyze H2O2 produced from glucose catalyzed by glucose oxidase to ·OH and oxidize colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB) with a significant absorbance at 652 nm. The linear range of glucose was 0-1.4 mM under optimal conditions, with a limit of detection (LOD) of 0.11 mM. Glucose in human whole blood was successfully detected with satisfactory recoveries. Furthermore, a facile agarose hydrogel detection platform was designed. With smartphone software, glucose detection can be realized by the agarose hydrogel platform, demonstrating the potential in on-site and visual detection of glucose.

iPSCs-Derived Neurons and Brain Organoids from Patients.

Induced pluripotent stem cells (iPSCs) can be differentiated into specific neurons and brain organoids by adding induction factors and small molecules in vitro, which carry human genetic information and recapitulate the development process of human brain as well as physiological, pathological, and pharmacological characteristics. Hence, iPSC-derived neurons and organoids hold great promise for studying human brain development and related nervous system diseases in vitro, and provide a platform for drug screening. In this chapter, we summarize the development of the differentiation techniques for neurons and brain organoids from iPSCs, and their applications in studying brain disease, drug screening, and transplantation.

The power of TOPMed imputation for the discovery of Latino-enriched rare variants associated with type 2 diabetes.

AIMS/HYPOTHESIS: The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population. METHODS: We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort. RESULTS: Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10-9). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance. CONCLUSIONS/INTERPRETATION: Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores. DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).

Erratum: Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.

[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.].

IMMerge: merging imputation data at scale.

SUMMARY: Genomic data are often processed in batches and analyzed together to save time. However, it is challenging to combine multiple large VCFs and properly handle imputation quality and missing variants due to the limitations of available tools. To address these concerns, we developed IMMerge, a Python-based tool that takes advantage of multiprocessing to reduce running time. For the first time in a publicly available tool, imputation quality scores are correctly combined with Fisher's z transformation. AVAILABILITY AND IMPLEMENTATION: IMMerge is an open-source project under MIT license. Source code and user manual are available at https://github.com/belowlab/IMMerge.

LDL delivery of microbial small RNAs drives atherosclerosis through macrophage TLR8.

Macrophages present a spectrum of phenotypes that mediate both the pathogenesis and resolution of atherosclerotic lesions. Inflammatory macrophage phenotypes are pro-atherogenic, but the stimulatory factors that promote these phenotypes remain incompletely defined. Here we demonstrate that microbial small RNAs (msRNA) are enriched on low-density lipoprotein (LDL) and drive pro-inflammatory macrophage polarization and cytokine secretion via activation of the RNA sensor toll-like receptor 8 (TLR8). Removal of msRNA cargo during LDL re-constitution yields particles that readily promote sterol loading but fail to stimulate inflammatory activation. Competitive antagonism of TLR8 with non-targeting locked nucleic acids was found to prevent native LDL-induced macrophage polarization in vitro, and re-organize lesion macrophage phenotypes in vivo, as determined by single-cell RNA sequencing. Critically, this was associated with reduced disease burden in distinct mouse models of atherosclerosis. These results identify LDL-msRNA as instigators of atherosclerosis-associated inflammation and support alternative functions of LDL beyond cholesterol transport.

Effects of Purified ß-Glucosidases from Issatchenkia terricola, Pichia kudriavzevii, Metschnikowia pulcherrima on the Flavor Complexity and Typicality of Wines.

The aim of this study was to investigate the effects of purified ß-glucosidases from Issatchenkia terricola SLY-4, Pichia kudriavzevii F2-24, and Metschnikowia pulcherrima HX-13 (named as SLY-4E, F2-24E, and HX-13E, respectively) on the flavor complexity and typicality of wines. Cabernet Sauvignon wines were fermented by Saccharomycescerevisiae with the addition of SLY-4E, F2-24E, and HX-13E; the fermentation process and characteristics of wines were analyzed. The addition of SLY-4E, F2-24E, and HX-13E into must improved the contents of terpenes, higher alcohols, and esters, and decreased the contents of C6 compounds and fatty acids, which enhanced the fruity, floral, and taste aspects, reducing the unpleasant green of wines with no significant difference in their appearance. ß-glucosidases from different yeast species produced different aroma compound profiles which presented different flavor and quality. F2-24EW had the best effect on flavor and quality of wine followed by SLY-4EW and HX-13EW. These research results can provide references for the use of ß-glucosidases from non-Saccharomyces yeasts to improve the flavor complexity, typicality, and quality of wines.

Evaluating the impact of experience value promotes user voice toward social media: Value co-creation perspective.

Experience value is positively associated with user voice toward social media, but existing research lacks an examination of its mechanisms of action. Based on value co-creation theory, this paper explores the relationship between experience value (i.e., social value, entertainment value, information value) and customer voice, and explains the specific influence mechanism through the mediating role of user loyalty. The results of the empirical tests show that social value, entertainment value and information value have significant effects on user loyalty; user loyalty has a significant effect on promotive voice but not on prohibitive voice; user loyalty mediates the relationship between body social value, entertainment value, information value and promotive voice. The findings of this research reveal the important role of experience value on customer voice, which is an important guide for social media to achieve sustainable development.

Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations.

BACKGROUND: Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Given the high level of ancestral diversity in Hispanic American population, genetic studies may reveal variants that are infrequent/monomorphic in more homogeneous populations. METHODS: Using multi-trait Adaptive Sum of Powered Score (aSPU) method, we examined individual and shared genetic effects underlying inflammatory (CRP) and adiposity-related traits (Body Mass Index [BMI]), and central adiposity (Waist to Hip Ratio [WHR]) in HLA participating in the Population Architecture Using Genomics and Epidemiology (PAGE) cohort (N = 35,871) with replication of effects in the Cameron County Hispanic Cohort (CCHC) which consists of Mexican American individuals. RESULTS: Of the > 16 million SNPs tested, variants representing 7 independent loci were found to illustrate significant association with multiple traits. Two out of 7 variants were replicated at statistically significant level in multi-trait analyses in CCHC. The lead variant on APOE (rs439401) and rs11208712 were found to harbor multi-trait associations with adiposity and inflammation. CONCLUSIONS: Results from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development.

Dysfunction of vesicular storage in young-onset Parkinson's patient-derived dopaminergic neurons and organoids revealed by single cell electrochemical cytometry.

Electrochemical cytometry based on nano-tip microelectrodes was used to quantify the vesicular storage at the single-cell level in human neurons and midbrain organoids which acted as disease models of young-onset Parkinson's disease (YOPD). Human dopaminergic (DA) neurons and midbrain organoids were derived from an induced pluripotent stem cell line from one YOPD patient. We show a significant deficiency in vesicular catecholamine storage and a slower pore forming process on the surface of the microelectrode in the DA neurons derived from the YOPD patient. The upregulation of α-synuclein in both neurons and organoids derived from the YOPD patient is associated with vesicular storage dysfunction, revealing a correlation between the pathogenesis of YOPD and vesicular chemical storage deficiency, a novel chemical insight into the potential pathology of YOPD. Notably, efficacy evaluation and drug testing were performed with our platform to demonstrate that both amantadine, a clinical drug for Parkinson's disease (PD), and phorbol 12-myristate 13-acetate, an attractive candidate, ameliorate the dysfunction of vesicular storage in DA neurons derived from the YOPD patient. Our platform offers promising avenues for new drug discovery for PD and other neurodegenerative disorders.