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.

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.

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.

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.

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).

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.

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.

Propofol alleviates postoperative cognitive dysfunction by inhibiting inflammation via up-regulating miR-223-3p in aged rats.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) affects 15-25% of surgical patients and causes significant morbidity and mortality. This study aims to investigate the mechanism of propofol reducing POCD in aged rats. METHOD: Rats in Operate group and Propofol group were anesthetized with isoflurane and propofol, respectively, and then underwent cardiac surgery. Rats in Antagomir group were anesthetized with propofol and underwent cardiac surgery with preoperative injection of miR-223-3p antagomir. Barnes maze and Morris water maze (MWM) were used to test spatial learning and memory of rats. Immunofluorescence was used to detect the level of microglial cell marker IBA1. In addition, qRT-PCR was performed to measure the expression of miR-223-3p and inflammatory factors TNF-α, IL-1ß and IL-6. Western blotting was conducted to detect the protein expression of Foxo1, TNF-α, IL-1ß and IL-6. RESULT: Isoflurane-anesthetized rats undergoing cardiac surgery showed significantly reduced spatial learning and memory, promoted microglia activation, decreased miR-223-3p expression and increased inflammatory response in the hippocampus, while isoflurane-anesthetized rats without surgery showed insignificant changes in these indices. Compared to isoflurane anesthesia, propofol anesthesia exhibited less effect on spatial learning and memory of rats with cardiac surgery and contributed to a relative reduction in activated microglia in the hippocampus, a notable increase in miR-223-3p expression, and a decrease in inflammation. The results were reversed after miR-223-3p antagomir was injected into propofol-anesthetized surgical rats. miR-223-3p negatively regulated Foxo1 to suppress the expression of inflammatory factors. CONCLUSION: Propofol reduced inflammation by up-regulating miR-223-3p, thereby reducing POCD in aged rats.

Nanomaterial Biointerfacing via Mitochondrial Membrane Coating for Targeted Detoxification and Molecular Detection.

Natural cell membranes derived from various cell sources have been successfully utilized to coat nanomaterials for functionalization. However, intracellular membranes from the organelles of eukaryotes remain unexplored. Herein, we choose mitochondrion as a representative cell organelle and coat outer mitochondrial membrane (OMM) from mouse livers onto nanoparticles and field-effect transistors (FETs) through a membrane vesicle-substrate fusion process. Polymeric nanoparticles coated with OMM (OMM-NPs) can bind with ABT-263, a B-cell lymphoma protein 2 (Bcl-2) inhibitor that targets the OMM. As a result, OMM-NPs effectively protect the cells from ABT-263 induced cell death and apoptosis in vitro and attenuated ABT-263-induced thrombocytopenia in vivo. Meanwhile, FET sensors coated with OMM (OMM-FETs) can detect and distinguish anti-Bcl-2 antibody and small molecule agonists. Overall, these results show that OMM can be coated onto the surfaces of both nanoparticles and functional devices, suggesting that intracellular membranes can be used as coating materials for novel biointerfacing.

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.

Identification, characterization, and comparison of n-alkanols and anesthetics binding to the C1b subdomain of protein kinase cα: similar function with different binding sites.

Protein kinase C (PKC) is a family of lipid-activated enzymes involved in anesthetic preconditioning signaling pathways. Previously, n-alkanols and general anesthetics have been found to activate PKC by binding to the kinase C1B subdomain. In the present study, we attempt to ascertain the molecular mechanism and interaction mode of human PKCα C1B subdomain with a variety of exogenous n-alkanols and volatile general anesthetics as well as endogenous activator phorbol ester (PE) and co-activator diacylglycerol (DG). Systematic bioinformatics analysis identifies three spatially vicinal sites on the subdomain surface to potentially accommodate small-molecule ligands, where the site 1 is a narrow, amphipathic pocket, the site 2 is a wide, flat and hydrophobic pocket, and the site 3 is a rugged, polar pocket. Further interaction modeling reveals that site 1 is the cognate binding region of natural PE activator, which can moderately simulate the kinase activity in an independent manner. The short-chain n-alkanols are speculated to also bind at the site to competitively inhibit PE-induced kinase activation. The long-chain n-alkanols and co-activator DG are found to target site 2 in a nonspecific manner, while the volatile anesthetics prefer to interact with site 3 in a specific manner. Since the site 1 is composed of two protein loops that are also shared by sites 2 and 3, binding of n-alkanols, DG and anesthetics to sites 2 and 3 can trigger a conformational displacement on the two loops, which enlarges the pocket size and changes the pocket configuration of site 1 through an allosteric mechanism, consequently enhancing kinase activation by improving PE affinity to the site.

Marinomonas piezotolerans sp. nov., isolated from deep-sea sediment of the Yap Trench, Pacific Ocean.

A Gram-stain-negative, aerobic and rod-shaped strain, YLB-05T, was isolated from a sample of deep-sea sediment (depth, 6796 m) from the Yap Trench. It was motile, oxidase-positive and catalase-positive. Growth was observed at salinities of 1-12 % (NaCl, w/v), with the optimum at 5 %. The strain was able to thrive at low (4 °C) temperatures, with the optimum at 37 °C, but did not grow at 50 °C. The optimum pressure for growth was 0.1 MPa with tolerance up to 50 MPa. The 16S rRNA gene sequencing analysis showed that YLB-05T was most closely related to Marinomonas communis LMG 2864T (97.8 %). Phylogenetic analysis placed strain YLB-05T within the genus Marinomonas. The average nucleotide identity and the DNA-DNA hybridization values between strain YLB-05T and closely related type strains were below the respective thresholds for species differentiation. The principal fatty acids were C16 : 0, summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and summed feature 3 (C16 : 1ω7c/C16 : 1 ω6c). The DNA G+C content was 45.7 mol%. The respiratory quinone was determined to be Q-8. The polar lipids were an unidentified phospholipid and an unidentified aminophospholipid. The combined genotypic and phenotypic data showed that strain YLB-05T represents a novel species within the genus Marinomonas, for which the name Marinomonaspiezotolerans sp. nov. is proposed, with the type strain YLB-05T (=MCCC 1A12712T=KCTC 62812T).

Inhibition of Pathogen Adhesion by Bacterial Outer Membrane-Coated Nanoparticles.

Anti-adhesion therapies interfere with the bacterial adhesion to the host and thus avoid direct disruption of bacterial cycles for killing, which may alleviate resistance development. Herein, an anti-adhesion nanomedicine platform is made by wrapping synthetic polymeric cores with bacterial outer membranes. The resulting bacterium-mimicking nanoparticles (denoted "OM-NPs") compete with source bacteria for binding to the host. The "top-down" fabrication of OM-NPs avoids the identification of the adhesins and bypasses the design of agonists targeting these adhesins. In this study, OM-NPs are made with the membrane of Helicobacter pylori and shown to bind with gastric epithelial cells (AGS cells). Treatment of AGS cells with OM-NPs reduces H. pylori adhesion and such anti-adhesion efficacy is dependent on OM-NP concentration and its dosing sequence.

Krüppel-like factor 4 regulates the expression of inducible nitric oxide synthase induced by TNF-α in human fibroblast-like synoviocyte MH7A cells.

Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, has been implicated in the inflammation mediated by macrophages and endothelial cells by regulating the expression of inflammatory mediators. Here, we investigated whether KLF4 affects the expression of inducible nitric oxide synthase (iNOS), an important inflammatory mediator, in the human RA fibroblast-like synovial cell line MH7A. A pcDNA3.1-KLF4 plasmid or short interfering RNA KLF4 was transfected into MH7A cells, and the iNOS expression and nitric oxide (NO) production were analyzed by quantitative PCR, immunoblotting, and nitrite measurement. The iNOS promoter activity was determined by luciferase assay. The results showed overexpression of KLF4 increased iNOS expression and NO production in the presence or absence of TNF-α. Conversely, KLF4 knockdown markedly reduced iNOS expression and NO production induced by TNF-α. KLF4 activated the transcription activity of iNOS promoter in MH7A cells stimulated by TNF-α. This study indicates that KLF4 is important for regulating the expression of iNOS by TNF-α in human synoviocytes.

Varied pathological and therapeutic response effects associated with CHCHD2 mutant and risk variants.

Mutations and polymorphic risk variant of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) have been associated with late-onset Parkinson disease. In vivo pathological evidence of CHCHD2 mutations is currently lacking. Utilizing transgenic Drosophila model, we examined the relative pathophysiologic effect of the pathogenic (c.182C>T, p.Thr61Ile and c.434G>A, p.Arg145Gln) and the risk (c.5C>T, p.Pro2Leu) CHCHD2 variants. All the transgenic models exhibited locomotor dysfunction that could be exacerbated by rotenone exposure, dopaminergic neuron degeneration, reduction in lifespan, mitochondrial dysfunction, oxidative stress, and impairment in synaptic transmission. However, both mutants showed more severe early motor dysfunction, dopaminergic neuronal loss, and higher hydrogen peroxide production compared with the risk variant. p.Thr61Ile (co-segregated in three independent PD families) displayed the most severe phenotype followed by p.Arg145Gln (present only in index patient). We treated the transgenic flies with Ebselen, a mitochondrial hydrogen peroxide scavenger compound; Ebselen appears to be more effective in ameliorating motor function in the mutant than the risk variant models. We provide the first in vivo evidence of the pathological effects associated with CHCHD2 mutations. There was a difference in the pathological and drug response effects between the pathogenic and the risk variants. Ebselen may be a useful neuroprotective drug for carriers of CHCHD2 mutations.

Differential impacts of polyethylene microplastic and additives on soil nitrogen cycling: A deeper dive into microbial interactions and transformation mechanisms.

The impact of microplastics and their additives on soil nutrient cycling, particularly through microbial mechanisms, remains underexplored. This study investigated the effects of polyethylene microplastics, polyethylene resin, and plastic additives on soil nitrogen content, physicochemical properties, nitrogen cycling functional genes, microbial composition, and nitrogen transformation rates. Results showed that all amendments increased total nitrogen but decreased dissolved total nitrogen. Polyethylene microplastics and additives increased dissolved organic nitrogen, while polyethylene resin reduced it and exhibited higher microbial biomass. Amendments reduced or did not change inorganic nitrogen levels, with additives showing the lowest values. Polyethylene resin favored microbial nitrogen immobilization, while additives were more inhibitory. Amendment type and content significantly interacted with nitrogen cycling genes and microbial composition. Distinct functional microbial biomarkers and network structures were identified for different amendments. Polyethylene microplastics had higher gross ammonification, nitrification, and immobilization rates, followed by polyethylene resin and additives. Nitrogen transformation was driven by multiple functional genes, with Proteobacteria playing a significant role. Soil physicochemical properties affected nitrogen content through transformation rates, with C/N ratio having an indirect effect and water holding capacity directly impacting it. In summary, plastic additives, compared to polyethylene microplastics and resin, are less conducive to nitrogen degradation and microbial immobilization, exert significant effects on microbial community structure, inhibit transformation rates, and ultimately impact nitrogen cycling.

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.

Macrophage-Mimicking Cellular Nanoparticles Scavenge Proinflammatory Cytokines in Specimens of Patients with Inflammatory Disorders.

Effectively neutralizing inflammatory cytokines is crucial for managing a variety of inflammatory disorders. Current techniques that target only a subset of cytokines often fall short due to the intricate nature of redundant and compensatory cytokine networks. A promising solution to this challenge is using cell membrane-coated nanoparticles (CNPs). These nanoparticles replicate the complex interactions between cells and cytokines observed in disease pathology, providing a potential avenue for multiplex cytokine scavenging. While the development of CNPs using experimental animal models has shown great promise, their effectiveness in scavenging multiple cytokines in human diseases has yet to be demonstrated. To bridge this gap, this study selected macrophage membrane-coated CNPs (MФ-CNPs) and assessed their ability to scavenge inflammatory cytokines in serum samples from patients with COVID-19, sepsis, acute pancreatitis, or type-1 diabetes, along with synovial fluid samples from patients with rheumatoid arthritis. The results show that MФ-CNPs effectively scavenge critical inflammatory cytokines, including interleukin (IL)-6, IL-8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, in a dose-dependent manner. Overall, this study demonstrates MФ-CNPs as a multiplex cytokine scavenging formulation with promising applications in clinical settings to treat a range of inflammatory disorders.