Integrated small RNA, transcriptome and physiological approaches provide insight into Taxodium hybrid 'Zhongshanshan' roots in acclimation to prolonged flooding.

Although Taxodium hybrid 'Zhongshanshan' 406 (Taxodium mucronatum Tenore × Taxodium distichum; Taxodium 406) is an extremely flooding-tolerant woody plant, the physiological and molecular mechanisms underlying acclimation of its roots to long-term flooding remain largely unknown. Thus, we exposed saplings of Taxodium 406 to either non-flooding (control) or flooding for 2 months. Flooding resulted in reduced root biomass, which is in line with lower concentrations of citrate, α-ketoglutaric acid, fumaric acid, malic acid and adenosine triphosphate (ATP) in Taxodium 406 roots. Flooding led to elevated activities of pyruvate decarboxylase, alcohol dehydrogenase and lactate dehydrogenase, which is consistent with higher lactate concentration in the roots of Taxodium 406. Flooding brought about stimulated activities of superoxide dismutase and catalase and elevated reduced glutathione (GSH) concentration and GSH/oxidized glutathione, which is in agreement with reduced concentrations of O2- and H2O2 in Taxodium 406 roots. The levels of starch, soluble protein, indole-3-acetic acid, gibberellin A4 and jasmonate were decreased, whereas the concentrations of glucose, total non-structural carbohydrates, most amino acids and 1-aminocyclopropane-1-carboxylate (ACC) were improved in the roots of flooding-treated Taxodium 406. Underlying these changes in growth and physiological characteristics, 12,420 mRNAs and 42 miRNAs were significantly differentially expressed, and 886 miRNA-mRNA pairs were identified in the roots of flooding-exposed Taxodium 406. For instance, 1-aminocyclopropane-1-carboxylate synthase 8 (ACS8) was a target of Th-miR162-3p and 1-aminocyclopropane-1-carboxylate oxidase 4 (ACO4) was a target of Th-miR166i, and the downregulation of Th-miR162-3p and Th-miR166i results in the upregulation of ACS8 and ACO4, probably bringing about higher ACC content in flooding-treated roots. Overall, these results indicate that differentially expressed mRNA and miRNAs are involved in regulating tricarboxylic acid cycle, ATP production, fermentation, and metabolism of carbohydrates, amino acids and phytohormones, as well as reactive oxygen species detoxification of Taxodium 406 roots. These processes play pivotal roles in acclimation to flooding stress. These results will improve our understanding of the molecular and physiological bases underlying woody plant flooding acclimation and provide valuable insights into breeding-flooding tolerant trees.

T cell infiltration mediates neurodegeneration and cognitive decline in Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with pathological features of ß-amyloid (Aß) and hyperphosphorylated tau protein accumulation in the brain, often accompanied by cognitive decline. So far, our understanding of the extent and role of adaptive immune responses in AD has been quite limited. T cells, as essential members of the adaptive immune system, exhibit quantitative and functional abnormalities in the brains of AD patients. Dysfunction of the blood-brain barrier (BBB) in AD is considered one of the factors leading to T cell infiltration. Moreover, the degree of neuronal loss in AD is correlated with the quantity of T cells. We first describe the differentiation and subset functions of peripheral T cells in AD patients and provide an overview of the key findings related to BBB dysfunction and how T cells infiltrate the brain parenchyma through the BBB. Furthermore, we emphasize the risk factors associated with AD, including Aß, Tau protein, microglial cells, apolipoprotein E (ApoE), and neuroinflammation. We discuss their regulation of T cell activation and proliferation, as well as the connection between T cells, neurodegeneration, and cognitive decline. Understanding the innate immune response is crucial for providing comprehensive personalized therapeutic strategies for AD.

Secular trends and urban-rural disparities in height of Chinese adolescents aged 18 years from 1985 to 2019.

OBJECTIVES: To examine the secular trends and urban-rural disparities in height of Chinese adolescents aged 18 years from 1985 to 2019. METHODS: Data were extracted from the Chinese National Surveys on Students' Constitution and Health from 1985 to 2019, and the heights of a total of 76 554 boys and 75 908 girls aged 18 years were measured. The Mann-Kendall trend test was used to analyze the secular trends in height. Changes in different periods and urban-rural disparities were tested by z-tests and calculating the ratios of the coefficient of variation (CV) of height. RESULTS: The height of Chinese boys and girls aged 18 years increased from 168.21 and 157.10 cm in 1985 to 172.15 cm and 160.11 cm in 2019, respectively, with a larger increase in rural areas. The secular trends in height were the largest for boys from 1995 to 2005 and for girls from 2014 to 2019, and the same results were observed in urban and rural areas. The urban-rural disparities for boys and girls decreased by 1.79 and 0.91 cm, respectively, with significant decreases for boys in all regions and for girls in the eastern region. The overall CVs of height increased by 0.13% and 0.25% for boys and girls, respectively, with the largest increase among rural girls. CONCLUSIONS: The height of Chinese adolescents aged 18 years continued to increase between 1985 and 2019. The urban-rural disparities narrowed, and inequalities within rural areas for girls increased.

Study on barrier mechanism and application of silico-alkaline sol-modified bentonite cutoff wall materials to lead pollution in lead-zinc tailings pond.

In this paper, the barrier mechanism of silico-alkaline sol-modified bentonite as cutoff wall materials for lead ions in lead­zinc tailings ponds was investigated. Mechanical property tests, adsorption capacity tests, and permeability tests were conducted to assess the performance of the materials. The results indicated that the addition of silico-alkaline sol at a proportion of 20% by weight of bentonite improved the mechanical strength, anti-seepage ability, and adsorption capacity of the materials towards lead ions. The modification process of bentonite using silico-alkaline sol was confirmed through XED analysis. It was observed that silico-alkaline sol particles adsorbed onto the end face of montmorillonite crystal layer, altering its charge properties. This modification enhanced the adsorption capacity of bentonite towards metal cations. The interaction between the cutoff walls and lead ions was primarily governed by ion exchange. Through the utilization of CT and the finite element method (FEM), demonstrated the exiguity of connected flow lines in the vertical direction within the cutoff walls. Furthermore, column tests revealed that lead ions permeating through the cutoff walls gradually transformed into residuals and were immobilized within the wall. Visual Modflow analysis confirmed the effective application of the cutoff wall in remediating contaminated sites and the potential for practical implementation.

Risk of Suicidal Ideation and Behavior in Individuals With Parkinson Disease: A Systematic Review and Meta-Analysis.

Importance: Suicide risk may be increased in patients with Parkinson disease (PD), a common neurodegenerative condition. Mood disorders, especially depression, are prevalent in patients with PD who report suicidality. Objective: To address inconsistent results from studies of suicidal ideation and behavior in patients with PD. Data Sources: The study team searched MEDLINE and Embase from inception to June 14, 2023, and further screened the bibliographies of relevant studies to ensure a comprehensive search. Study Selection: Original studies, published in English, discussing either suicidal ideation, behavior, or both in adults with PD were included. Accepted study designs included cross-sectional, case-control, and cohort studies. Studies that only included patients with PD after deep brain stimulation were excluded. Data Extraction and Synthesis: This meta-analysis was conducted in line with the PRISMA guidelines. Two authors reviewed each study and extracted the data independently, with discrepancies referred to a third independent author. Main Outcomes and Measures: Outcomes included the prevalence of suicidal ideation and behavior, measured as proportions, and the risk of suicidal behavior in patients with PD relative to controls, measured in both odds ratio (OR) and hazards ratio (HR). Results: A total of 28 studies comprising 505 950 PD patients were included in the final analysis. The prevalence of suicidal ideation was evaluated in 14 studies (22.2%; 95% CI, 14.6-32.3) and suicidal behavior in 21 studies (1.25%; 95% CI, 0.64-2.41). Excluding 4 outliers, prevalence of suicidal behavior was significantly higher in prospective studies (1.75%; 95% CI, 1.03-2.95) than retrospective studies (0.50%; 95% CI, 0.24-1.01). Excluding 1 outlier, OR of suicidal behavior was pooled across 10 studies and significant (OR, 2.15; 95% CI, 1.22-3.78; P = .01). HR of suicidal behavior was assessed in 9 studies (HR, 1.73; 95% CI, 1.40-2.14; P < .001). Conclusions and Relevance: This meta-analysis involving more than 500 000 patients with PD found 22.2% and 1.25% of patients with PD to have suicidal ideation and behavior, respectively. Patients with PD had 2 times the risk of suicidal behavior than controls. Early recognition and management of suicidality in PD can help reduce mortality.

Targeted Elimination of Surface Defects in Carbon Fibers: Formation of a Hybrid Structure Combining Rigidity with Flexibility from Sonochemical-Induced Directional Growth of Nano-ZIF-8 and Subsequent Annealing.

Currently, the mechanical performance of carbon fibers (CFs) has yet to fully realize its theoretical potential. This is predominantly attributed to the significant constraints posed by surface defects, greatly impeding the widespread application of carbon fibers. In order to address this issue, we employed a sonochemical-induced approach in this study to achieve in situ growth of nanoscale zeolitic imidazolate framework-8 (ZIF-8) at the surface defects of carbon fibers. After high-temperature treatment, the structure of ZIF-8 decomposed into ZnO and inorganic carbon, reinforcing the carbon fiber structure from both flexible and rigid aspects. Our research indicates that when the temperature reaches 500 °C, a substantial portion of ZIF-8 undergoes thermal decomposition, giving rise to zinc oxide and inorganic carbon. The flexible inorganic carbon and rigid ZnO form a meshlike structure, which welds to the surface defects of carbon fibers, resulting in strong interactions and contributing to the delay of fiber fracture. Compared to unmodified carbon fibers, the mechanical performance increased by approximately 15.86%. Based on the aforementioned analysis, this method can be considered a direct and effective approach for reinforcing carbon fiber structures, presenting a novel approach for the precise elimination of surface defects on carbon fibers.

Glycan-modified cellular nanosponges for enhanced neutralization of botulinum toxin.

Botulinum toxin (BoNT) is a potent neurotoxin that poses a significant threat as a biowarfare weapon and a potential bioterrorist tool. Currently, there is a lack of effective countermeasures to combat BoNT intoxication in the event of a biological attack. Here, we report on a novel solution by combining cell metabolic engineering with cell membrane coating nanotechnology, resulting in the development of glycan-modified cellular nanosponges that serve as a biomimetic and broad-spectrum BoNT detoxification strategy. Specifically, we increase the expression levels of gangliosides on THP-1 cells through metabolic engineering, and then collect the modified THP-1 cell membrane and coat it onto synthetic polymeric cores, creating cellular nanosponges that closely mimic host cells. Our findings demonstrate that higher levels of gangliosides on the cellular nanosponges result in greater binding capacities with BoNT. The glycan-modified cellular nanosponges exhibit superior efficacy in neutralizing BoNT cytotoxicity in vitro when compared to their unmodified counterparts. In a mouse model of BoNT intoxication, the glycan-modified cellular nanosponges show more pronounced survival benefits when administered both as a treatment and a preventative regimen. These results highlight the potential of cellular nanosponges, especially when modified with glycans, as a promising countermeasure platform against BoNT and related clostridial toxins.

Physiological and transcriptional regulation in Taxodium hybrid 'Zhongshanshan' leaves in acclimation to prolonged partial submergence.

MAIN CONCLUSION: Taxodium 703 leaves activate fermentation, amino acids metabolism and ROS detoxification, and reduce TCA cycle and ABA biosynthesis in acclimation to prolonged partial submergence stress. Taxodium hybrid 'Zhongshanshan 703' (T. mucronatum × T. distichum; Taxodium 703) is a highly flooding-tolerant woody plant. To investigate the physiological and transcriptional regulatory mechanisms underlying its leaves in acclimation to long-term flooding, we exposed cuttings of Taxodium 703 to either non-flooding (control) or partial submergence for 2 months. The leaf tissues above (AL) and below (BL) flooding-water were separately harvested. Partial submergence decreased concentrations of chlorophyll (a + b) and dehydroascorbate (DHA) and lactate dehydrogenase (LDH) activity in AL, and reduced biomass, concentrations of succinic acid, fumaric acid and malic acid, and transcript levels of genes involved in tricarboxylic acid (TCA) cycle in BL. Under partial submergence, concentrations of starch, malondialdehyde and abscisic acid (ABA) decreased, and also mRNA levels of nine-cis-epoxycarotenoid dioxygenases that are involved in ABA biosynthesis in AL and BL of Taxodium 703. Partial submergence increased O2- content in AL, and improved concentrations of pyruvate and soluble sugars and activities of LDH and peroxidase in BL. In addition, partial submergence increased concentrations of ethanol, lactate, alanine, γ-aminobutyric acid, total amino acids and ascorbic acid (ASA), and ASA/DHA, activities of alcohol dehydrogenases (ADH) and ascorbate peroxidase, as well as transcript levels of ADH1A, ADH1B and genes involved in alanine biosynthesis and starch degradation in AL and BL of Taxodium 703. Overall, these results suggest that Taxodium 703 leaves activate fermentation, amino acids metabolism and reactive oxygen species detoxification, and maintain a steady supply of sugars, and reduce TCA cycle and ABA biosynthesis in acclimation to prolonged partial submergence stress.

Extending the In Vivo Residence Time of Macrophage Membrane-Coated Nanoparticles through Genetic Modification.

Nanoparticles coated with natural cell membranes have emerged as a promising class of biomimetic nanomedicine with significant clinical potential. Among them, macrophage membrane-coated nanoparticles hold particular appeal due to their versatility in drug delivery and biological neutralization applications. This study employs a genetic engineering approach to enhance their in vivo residence times, aiming to further improve their performance. Specifically, macrophages are engineered to express proline-alanine-serine (PAS) peptide chains, which provide additional protection against opsonization and phagocytosis. The resulting modified nanoparticles demonstrate prolonged residence times when administered intravenously or introduced intratracheally, surpassing those coated with the wild-type membrane. The longer residence times also contribute to enhanced nanoparticle efficacy in inhibiting inflammatory cytokines in mouse models of lipopolysaccharide-induced lung injury and sublethal endotoxemia, respectively. This study underscores the effectiveness of genetic modification in extending the in vivo residence times of macrophage membrane-coated nanoparticles. This approach can be readily extended to modify other cell membrane-coated nanoparticles toward more favorable biomedical applications.

Secular trends and spatial network effect on the height of Chinese adult adolescents from 1985 to 2019.

OBJECTIVES: To understand the distribution and secular trends of Chinese adult boys and girls and investigate their spatial network effects and determinants of spatial network effects. METHODS: Our study extracted data of 18-year-old boys and 17-year-old girls in China from the national students fitness and health survey reports in 1985, 2000, 2010, and 2019. A total of 89 839 participants were selected. The growth range and growth rate in each period were calculated. A neighborhood relationship network was created to share the common boundary. RESULTS: During the period 1985-2019, the average height of Chinese 18-year-old boys increased from 168.19 to 172.14 cm, and that of 17-year-old girls increased from 156.97 to 160.17 cm (all p trend <.05). Both boys and girls showed significant correlations in first- and second-level neighbors (all p < .05) with the most significant correlations in first-level neighbors (all p < .001). But there were no significant correlations in third-level neighbors. Height of girls and boys in each region was correlated with gross domestic product (GDP) per capita, urbanization rate, population density, longitude, and latitude. After controlling for factors with significance, only the initial regional height of girls in 2000 was positively correlated with first level neighborhood (p < .05). CONCLUSION: Since 1985, the heights of Chinese boys aged 18 and girls aged 17 have been increasing and the increases accelerated. Height is related to nearer neighbors. After controlling GDP per capita, urbanization rate, population density, longitude and latitude, the correlations has almost disappeared.

Vibrio intestinalis sp. nov., isolated from intestine of seahorse.

A novel Gram-stain-negative, catalase- and oxidase-positive, facultatively anaerobic, and rod-shaped motile bacterial strain, designated as YLB-11T, was isolated from seahorse intestine. The 16S rRNA gene sequencing analysis showed that YLB-11T was most closely related Vibrio mytili LMG 19157T (98.9 % nucleotide sequence identity). Phylogenetic analysis placed strain YLB-11T within the genus Vibrio. The major cellular fatty acids were summed feature 3 (C16: 1 ω6c/C16 : 1 ω7c, 36.4 %), C16 : 0 (19.1 %) and summed feature 8 (C18:1 ω6c/C18:1 ω7c, 12.3 %). The DNA G+C content of YLB-11T was 44.7 mol %. The in silico DNA-DNA hybridization and average nucleotide identity values for whole-genome sequence comparisons between YLB-11T and related species were clearly below the thresholds used for the delineation of a novel species. Therefore, YLB-11T is considered to represent novel species of the genus Vibrio, for which the name Vibrio intestinalis sp. nov. is proposed. The type strain is YLB-11T (=MCCC 1A17441T=KCTC 72604T).

Polyethylene microplastic and soil nitrogen dynamics: Unraveling the links between functional genes, microbial communities, and transformation processes.

Microplastics (MPs) have emerged as pollutants of growing concern due to their potential threat to soil ecosystems. While some studies have investigated the effects of MPs on soil nitrogen content, the underlying physicochemical and microbial driving mechanisms still need to be explored. In this study, a six-month incubation experiment was conducted with varying polyethylene MP addition rates: CK (0%, mass ratio), MP0.5 (0.5%), MP1 (1%), MP2 (2%), MP4 (4%), and MP8 (8%). The experiment aimed to examine the effects of MPs on soil nitrogen content, physicochemical properties, nitrogen cycling-related genes, microorganisms, and gross nitrogen transformation rates. The results revealed no significant changes in soil total nitrogen and dissolved total nitrogen. However, dissolved organic nitrogen significantly decreased by 16.00-54.60% following MP addition, while ammonium (NH4+-N, 45.71-271.43%) and nitrate (NO3--N, 43.15-209.54%) nitrogen and microbial biomass nitrogen (46.02-123.70%) significantly increased. Soil pH, bulk density, and soil porosity decreased after MP addition, while soil carbon contents, water-stable macroaggregates, and redox potential increased. The soil microbial community structure changed significantly, and microbial diversity increased under MP treatment. MP addition significantly altered the abundance of soil nitrogen cycling functional genes. The relative abundance of nitrogen fixation and denitrification genes decreased with increasing MP addition rates, while organic degradation and synthesis genes increased. The soil nitrogen cycling functional microbial composition shifted dramatically with increased MP addition. Networks with high addition rates (MP2 +MP4 +MP8) exhibited more total nodes, total links, negative links, node degrees, and modules but shorter average path distances and lower modularity than those with low addition rates (CK +MP0.5 +MP1), reflecting increased network complexity induced by MPs. The gross ammonification rate, NH4+-N consumption and immobilization rates, and NO3--N immobilization rate increased, while the gross nitrification rate and net nitrification rate exhibited an initial increase followed by a decrease with increasing MP addition rates, peaking at MP2. Furthermore, redundancy analysis and structural equation modeling demonstrated that soil physicochemical properties significantly affected soil nitrogen cycling genes and microorganisms, ultimately altering nitrogen content. In conclusion, polyethylene MPs promoted soil nitrogen mineralization and transformation and changed the related functional microorganism community structure, exhibiting a noticeable dose-effect relationship. This study provides deeper insight into the effects of MPs on soil nitrogen cycling.

Emerging nanoparticle designs against bacterial infections.

The rise of antibiotic resistance has caused the prevention and treatment of bacterial infections to be less effective. Therefore, researchers turn to nanomedicine for novel and effective antibacterial therapeutics. The effort resulted in the first-generation antibacterial nanoparticles featuring the ability to improve drug tolerability, circulation half-life, and efficacy. Toward developing the next-generation antibacterial nanoparticles, researchers have integrated design elements that emphasize physical, broad-spectrum, biomimetic, and antivirulence mechanisms. This review highlights four emerging antibacterial nanoparticle designs: inorganic antibacterial nanoparticles, responsive antibacterial nanocarriers, virulence nanoscavengers, and antivirulence nanovaccines. Examples in each design category are selected and reviewed, and their structure-function relationships are discussed. These emerging designs open the door to nontraditional antibacterial nanomedicines that rely on mechano-bactericidal, function-driven, nature-inspired, or virulence-targeting mechanisms to overcome antibiotic resistance for more effective antibacterial therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Afforestation of Taxodium Hybrid Zhongshanshan Influences Soil Bacterial Community Structure by Altering Soil Properties in the Yangtze River Basin, China.

Taxodium hybrid Zhongshanshan has been widely planted in the Yangtze River Basin (YRB) for soil and carbon conservation, with quantities over 50 million. The objective of this study was to determine how T. hybrid Zhongshanshan plantations affected soil physicochemical properties and bacterial community structure in the YRB, and to examine the consistency of changes by afforestation. Soils under T. Zhongshanshan plantations across six sites of the YRB were compared with soils of adjacent non-forested sites. Soil physicochemical properties and bacterial community structure were determined to clarify edaphic driving factors and reveal the effects of afforestation on bacteria. The results indicated that most soil attributes manifested improvements, e.g., total nitrogen in Jiangxi and Shanghai; available phosphorus in Hubei, Chongqing and Yunnan, exhibited the potential to maintain or ameliorate soil quality. A decrease in soil bulk density caused by plantation was also observed at the expense of soil macro-aggregates augment. Afforestation of T. Zhongshanshan plantation has habitually improved Shannon diversity and Chao1 richness, of which dominant phyla were Proteobacteria, Acidobacteria, and Actinobacteria, and increased the relative abundance of the phyla Proteobacteria and Nitrospirae, and the classes Flavobacteriia, Acidobacteria_Gp5, and Bacilli. We concluded that T. Zhongshanshan plantation can be employed to facilitate soil nutrient accumulation in the YRB, but that the degree, rate and direction of changes in soil attributes are sites dependent. It is recommended that afforestation of nutrient-depleted and less productive lands in the YRB should utilize this fast-growing species in combination with proper fertilization.

Effects of black soldier fly larvae as protein or fat sources on apparent nutrient digestibility, fecal microbiota, and metabolic profiles in beagle dogs.

Black soldier fly (Hermetia illucens) larvae (BSFL) act as a biological system converting organic waste into protein and fat with great potential application as pet food. To evaluate the feasibility of BSFL as a protein and fat source, 20 healthy beagle dogs were fed three dietary treatments for 65 days, including (1) a basal diet group (CON group), (2) a basal diet that replaced 20% chicken meal with defatted black soldier fly larvae protein group (DBP group), and (3) a basal diet that replaced 8% mixed oil with black soldier fly larvae fat group (BF group). This study demonstrated that the serum biochemical parameters among the three groups were within the normal range. No difference (p > 0.05) was observed in body weight, body condition score, or antioxidant capacity among the three groups. The mean IFN-γ level in the BF group was lower than that in the CON group, but there was no significant difference (p > 0.05). Compared with the CON group, the DBP group had decreasing (p < 0.05) apparent crude protein and organic matter digestibility. Furthermore, the DBP group had decreasing (p < 0.05) fecal propionate, butyrate, total short-chain fatty acids (SCFAs), isobutyrate, isovalerate, and total branched-chain fatty acids (BCFAs) and increased (p < 0.05) fecal pH. Nevertheless, there was no difference (p > 0.05) in SCFAs or BCFAs between the CON and BF groups. The fecal microbiota revealed that Lachnoclostridium, Clostridioides, Blautia, and Enterococcus were significantly enriched in the DBP group, and Terrisporobacter and Ralstonia were significantly enriched in the BF group. The fecal metabolome showed that the DBP group significantly influenced 18 metabolic pathways. Integrating biological and statistical correlation analysis on differential fecal microbiota and metabolites between the CON and DBP groups found that Lachnoclostridium, Clostridioides, and Enterococcus were positively associated with biotin. In addition, Lachnoclostridium, Clostridioides, Blautia, and Enterococcus were positively associated with niacinamide, phenylalanine acid, fumaric acid, and citrulline and negatively associated with cadavrine, putrescine, saccharopine, and butyrate. In all, 20% DBP restrained the apparent CP and OM digestibility, thereby affecting hindgut microbial metabolism. In contrast, 8% BF in the dog diet showed no adverse effects on body condition, apparent nutrient digestibility, fecal microbiota, or metabolic profiles. Our findings are conducive to opening a new avenue for the exploitation of DBP and BF as protein and fat resources in dog food.

Using Cell Membranes as Recognition Layers to Construct Ultrasensitive and Selective Bioelectronic Affinity Sensors.

Conventional sandwich immunosensors rely on antibody recognition layers to selectively capture and detect target antigen analytes. However, the fabrication of these traditional affinity sensors is typically associated with lengthy and multistep surface modifications of electrodes and faces the challenge of nonspecific adsorption from complex sample matrices. Here, we report on a unique design of bioelectronic affinity sensors by using natural cell membranes as recognition layers for protein detection and prevention of biofouling. Specifically, we employ the human macrophage (MΦ) membrane together with the human red blood cell (RBC) membrane to coat electrochemical transducers through a one-step process. The natural protein receptors on the MΦ membrane are used to capture target antigens, while the RBC membrane effectively prevents nonspecific surface binding. In an attempt to detect tumor necrosis factor alpha (TNF-α) cytokine using the bioelectronic affinity sensor, it demonstrates a remarkable limit of detection of 150 pM. This new sensor design integrates natural cell membranes and electronic transduction, which offers synergistic functionalities toward a broad range of biosensing applications.

The APP intracellular domain promotes LRRK2 expression to enable feed-forward neurodegenerative mechanisms in Parkinson's disease.

Gain-of-function mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are common in familial forms of Parkinson's disease (PD), which is characterized by progressive neurodegeneration that impairs motor and cognitive function. We previously demonstrated that LRRK2-mediated phosphorylation of ß-amyloid precursor protein (APP) triggers the production and nuclear translocation of the APP intracellular domain (AICD). Here, we connected LRRK2 to AICD in a feed-forward cycle that enhanced LRRK2-mediated neurotoxicity. In cooperation with the transcription factor FOXO3a, AICD promoted LRRK2 expression, thus increasing the abundance of LRRK2 that promotes AICD activation. APP deficiency in LRRK2G2019S mice suppressed LRRK2 expression, LRRK2-mediated mitochondrial dysfunction, α-synuclein accumulation, and tyrosine hydroxylase (TH) loss in the brain, phenotypes associated with toxicity and loss of dopaminergic neurons in PD. Conversely, AICD overexpression increased LRRK2 expression and LRRK2-mediated neurotoxicity in LRRK2G2019S mice. In LRRK2G2019S mice or cultured dopaminergic neurons from LRRK2G2019S patients, treatment with itanapraced reduced LRRK2 expression and was neuroprotective. Itanapraced showed similar effects in a neurotoxin-induced PD mouse model, suggesting that inhibiting the AICD may also have therapeutic benefits in idiopathic PD. Our findings reveal a therapeutically targetable, feed-forward mechanism through which AICD promotes LRRK2-mediated neurotoxicity in PD.

QEEG indices are associated with inflammatory and metabolic risk factors in Parkinson's disease dementia: An observational study.

Background: Quantitative electroencephalography (QEEG) is a reliable and non-invasive diagnostic tool to quantify cortical synaptic injury or loss in the clinical assessment of neurodegenerative diseases, and may be able to differentiate various types of dementia. We investigated if QEEG indices can differentiate Parkinson's Disease (PD) with nondementia (PD-ND) from PD with dementia (PDD), and to determine if QEEG indices correlate with inflammation and lipid metabolism markers in PD. Methods: This clinical study collected data between July 1, 2018 and July 1, 2021 in Zhujiang Hospital of Southern Medical University in China and data was analysed. A total of 125 individuals comprising of 31 PDD, 47 patients with PD-ND and 47 healthy controls were included. We calculated the absolute spectral power (ASP) of frequency bands and the slow-to-fast frequency ratios of specific brain regions. Plasma levels of hypersensitive C-reactive protein (Hs-CRP), superoxide dismutase (SOD), and high-density lipoprotein cholesterol (HDL-C) were measured and correlations with QEEG indices were examined. Findings: A significantly higher ASP of delta frequency especially in the frontal region was observed in patients with PDD compared to PD-ND (P=0.004) and controls (P=0.000). Decreased HDL-C (OR=0.186, P=0.030), and increased Hs-CRP (OR =2.856, P=0.015) were associated with PDD. Frontal-delta ASP was negatively correlated with plasma HDL-C (r=-0.353, P=0.000) and SOD (r=-0.322, P=0.001), and positively correlated with Hs-CRP (r=0.342, P=0.000). Interpretation: We highlight novel correlations between QEEG indices and inflammation and lipid metabolism markers in PD-ND and PDD. QEEG indices, HDL-C and Hs-CRP are potentially useful for the evaluation of PDD. Our current findings suggest that peripheral inflammation might contribute to the pathogenesis of cognitive impairment and EEG slowing in PDD. The mechanism underlying frontal-delta ASP and its correlation with neuro-inflammatory and metabolic markers in PDD should be further investigated. Funding: The National Natural Science Foundation of China (NO: 81873777, 82071414); the Scientific Research Foundation of Guangzhou (NO: 202206010005); the Science and Technology Program of Guangdong of China (NO: 2020A0505100037); the High-level Hospital Construction Research Project of Maoming People's Hospital (NO: xz2020009); the Science and Technology Program of Maoming City (NO: 2021S0026). Dr EK Tan is supported by the National Medical Research Council, Singapore.

Bending and Vibration Analysis of Flexoelectric Beam Structure on Linear Elastic Substrates.

With the development of micro-nanotechnology, smart electronic devices are being updated and developed, and more and more flexoelectric sensors, actuators, and energy harvesters attached to elastic substrates have attracted a surge of interest due to unique features at the nano-scale. In this paper, the static bending behavior and vibration characteristics of a flexoelectric beam structure based on a linear elastic substrate under a magnetic field environment are investigated. Based on the electrical Gibbs free energy density, the governing equations and boundary conditions of structures are derived by using the Euler-Bernoulli beam theory and the Hamilton's variational principle. The expressions of the deflection and the induced electric potential of the beam structure are expressed analytically. The natural frequency of the beam under the open-circuit electrical conditions with surface electrodes (OCI) are obtained after further extending the solution. The results show that the flexoelectric effect, the linear elastic substrate, and the magnetic field have significant effects on the static bending and vibration behaviors of the flexoelectric beam which are beneficial for designing and developing flexoelectric devices with elastic substrates.

Membrane Cholesterol Depletion Enhances Enzymatic Activity of Cell-Membrane-Coated Metal-Organic-Framework Nanoparticles.

Metal-organic-framework nanoparticles (MOF NPs) have been increasingly used to encapsulate therapeutic enzymes for delivery. To better interface these MOF NPs with biological systems, researchers have coated them with natural cell membranes, enabling biomimicking properties suitable for innovative biomedical applications. Herein, we report that the enzymatic activity of cell-membrane-coated MOF NPs can be significantly enhanced by reducing membrane cholesterol content. We demonstrate such cholesterol-enzymatic activity correlation using zeolitic imidazolate framework-8 MOF NPs to encapsulate catalase, horseradish peroxidase, and organophosphate hydrolase, respectively. MOF NPs coated with membranes of human red blood cells or macrophages show similar outcomes, illustrating the broad applicability of this finding. The mechanistic investigation further reveals that reducing cholesterol levels effectively enhances membrane permeability likely responsible for the increased enzymatic activity. These results also imply a facile approach to tailoring the enzymatic activity of cell-membrane-coated MOF NPs by simply tuning the membrane cholesterol level.